0A4F4F9BD490A749D5437F821CF06DF1
Commission Staff Working Paper Report on Human Embryonic Stem Cell Research (2003)
https://ec.europa.eu/research/press/2003/pdf/sec2003-441report_en.pdf
http://leaux.net/URLS/ConvertAPI Text Files/B0C3A3DEB4FE8814745A3BD4159029F8.en.txt
Examining the file media/Synopses/B0C3A3DEB4FE8814745A3BD4159029F8.html:
This file was generated: 2020-07-15 06:49:08
| Indicators in focus are typically shown highlighted in yellow; |
Peer Indicators (that share the same Vulnerability association) are shown highlighted in pink; |
"Outside" Indicators (those that do NOT share the same Vulnerability association) are shown highlighted in green; |
Trigger Words/Phrases are shown highlighted in gray. |
Link to Orphaned Trigger Words (Appendix (Indicator List, Indicator Peers, Trigger Words, Type/Vulnerability/Indicator Overlay)
Applicable Type / Vulnerability / Indicator Overlay for this Input
Political / Indigenous
Searching for indicator indigenous:
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p.000022: stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023: the use of neural dopamine producing cells derived from aborted foetuses. Clinical trials in patients with Parkinson’s
p.000023: disease have been performed on around 200 patients over the last 10 years especially in Sweden and in USA. They have
p.000023: shown that the transplantation of neural cells derived from the human foetus can have a therapeutic effect, with an
p.000023: important reduction of the symptoms of the disease in the treated patients28. However, the availability of neural
p.000023: foetal tissue is very limited. Efforts are now being made to expand fetal neural stem cells and control their
p.000023: differentiation into dopaminergic neurons.
p.000023:
p.000023: In a recent study, scientists directed mouse embryonic stem cells to differentiate into dopaminergic
p.000023: neurons by treatment with growth factors and by introducing the gene Nurr1. When transplanted into the brains of
p.000023: a rat model of Parkinson’s disease these stem cell- derived dopaminergic neurons re-innervated the brains
p.000023: of the rat, released dopamine and improved motor function.29
p.000023: The possibility to stimulate the patient’s own stem cells in the brain is also being explored. Self-repair could be
p.000023: induced or augmented with neuro-poïetins - small selective growth factors that trigger repair processes by
p.000023: an individual’s own indigenous population of stem cells30.
p.000023: Heart failure
p.000023:
p.000023: When heart muscle cells (cardiomyocytes) are destroyed, e.g. after a heart attack, functional contracting heart muscle
p.000023: is replaced with non-functional scar tissue. It is hoped that healthy heart muscle cells generated in culture in
p.000023: the laboratory and then transplanted into patients could be used to treat patients with e.g. chronic heart
p.000023: disease.
p.000023:
p.000023: Recent research in mice indicates that mouse cardiomyocytes derived from mouse embryonic stem cells, transplanted
p.000023: into a damaged heart, can generate new heart muscle cells and successfully repopulate the heart tissue.
p.000023: These results suggest that cardiomyocytes derived from human embryonic stem cells derived could be developed for
p.000023: cell transplantation therapy in humans suffering from heart failure31.
p.000023: It has also been reported from animal studies that bone marrow stem cells32 have the potential to be used to repair the
p.000023: infarcted heart. The transplantation of autologous bone marrow cells (transplantation of the patient’s own stem cells)
p.000023: into the infected heart has been reported in two small non randomized human studies33.
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: 28 Bjorklund, A. and Lindvall O., “Cell replacement therapies for central nervous system
p.000023: disorders”,
p.000023: Nature Neuroscience, 2000, 3, 537-544.
p.000023: 29 Björklund, L. M. et al. “Embryonic stem cells develop into functional dopaminergic neurons
p.000023: after transplantation in a Parkinson rat model”, Proc. Natl. Acad. Sci. USA , 2002, 99:2344-2349; Kim J-H. et al.,
...
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028: – Current methods for growing human ES cell lines in culture are adequate for research purposes, but the
p.000028: co-culture of human ES cells with animal materials necessary for growth and differentiation would preclude their
p.000028: use in therapy. Scientists are now working on generating stem cell lines, which are grown on human
p.000028: feeder layer or without feeder layer and in completely defined culture media.
p.000028:
p.000028: 2.4.2. Human somatic stem cells
p.000028:
p.000028: Advantages:
p.000028:
p.000028: – The potential of somatic stem cells for therapeutic application is illustrated by the use of haematopoïetic
p.000028: stem cells to treat leukemias and other blood disorders38.
p.000028: – Recent studies suggesting that various somatic stem cells have much greater potential for differentiation
p.000028: than previously suspected have opened up the possibility that other routes to somatic stem cell therapy might be
p.000028: available.
p.000028:
p.000028: – The patient’s own stem cells could be expanded in culture and then reintroduced into the patient which
p.000028: would mean that the cells would not be rejected by the immune system. This represents a significant
p.000028: advantage, as immune rejection is a difficult problem.
p.000028:
p.000028: – In the future it might be possible to stimulate proliferation and fate control of the
p.000028: patient’s own indigenous somatic stem cell population in-situ by systemically- introduced “poïetins”.
p.000028:
p.000028: Limitations:
p.000028: – The isolation, growth and differentiation of adult stem cells have to date proved difficult.
p.000028: Stem cells generally represent a small proportion of cells in adult tissues. It should be recognised that although
p.000028: haematopoïetic stem cells represent a small proportion of cells in the peripheral blood (i.e.
p.000028: haematopoïetic stem cells, 1 out of 100,000 white blood cells), they are now the preferred source of
p.000028: autologous stem cells for transplantation in adults41.
p.000028: – Where a person suffers from a genetic disorder or some types of cancers, somatic stem cells isolated from
p.000028: that individual will retain the damaging genetic alterations underlying the disease and so be of little
p.000028: therapeutic value e.g. in the case of diabetes. However, they could be corrected by gene therapy.
p.000028:
p.000028: – It is not yet known whether somatic stem cells give rise to cells of different tissue types
p.000028: by transdifferentiation, or by dedifferentiation to a less differentiated stem cell, which then differentiates
p.000028: into the new cell types. The control and safety of dedifferentiation is a major challenge and one
p.000028: about which little is yet known.
p.000028:
p.000028: – Adult stem cells may contain more DNA abnormalities caused by sunlight, toxins and errors in making more DNA
p.000028: copies during the course of a lifetime.
p.000028:
p.000028:
p.000028:
...
Political / political affiliation
Searching for indicator political:
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p.000049: have taken the appropriate measures to fulfil all ethical and/or legal requirements at national and European level
p.000049: and finally have respected the ethical framework defined for the 6th Framework programme for Research.
p.000049:
p.000049: – Any research involving the use of human embryos and human embryonic stem cells, following the ethical
p.000049: review mentioned above, will be submitted to a Regulatory Committee.
p.000049:
p.000049: – In specific cases, an ethical review may take place during the implementation of the project.
p.000049:
p.000049:
p.000049:
p.000049: 65 OJ L294 of 29.10.2002, p. 8.
p.000049: 66 Research relating to cancer treatment of the gonads can be financed.
p.000049:
p.000050: 50
p.000050:
p.000050: – As stated in the Council minutes of 30 September 200267 “The Council and the Commission agree
p.000050: that detailed implementing provisions concerning research activities involving the use of human
p.000050: embryos and human embryonic stem cells…shall be established by 31 December 2003”.
p.000050:
p.000050: The Commission will during that period…not propose to fund such research, with the exception of banked or
p.000050: isolated human embryonic stem cells in culture.
p.000050:
p.000050: 3.6. Social scrutiny and dialogue
p.000050: There are significant differences in national attitudes towards specific techniques and areas of research. In
p.000050: particular, human embryonic stem cell research has recently provoked intense public and political debate. As
p.000050: the life sciences and biotechnology develop, they contribute considerably to securing welfare on the personal and
p.000050: societal levels as well as to creating new opportunities for our economies. At the same time, the general
p.000050: public is increasingly concerned about the social and ethical consequences of these advances in knowledge
p.000050: and techniques as well as about the conditions forming the choices made in these fields.
p.000050:
p.000050: The EGE stressed in its opinion regarding “Ethical aspects of human stem cell research and use” there is a need
p.000050: for continuing dialogue and education to promote the participation of citizens, including patients, in
p.000050: scientific governance, namely in social choices created by new scientific developments”.
p.000050:
p.000050: The need for public dialogue on scientific advances and new technologies has also been highlighted in both
p.000050: the Commission’s communication on “Life Sciences and Biotechnology”, published on 27 January 200268 and the
p.000050: Commission’s action plan on “Science and Society” published in December 200169.
p.000050: In this connection, the European Group on Life Sciences70, set up by the European Research Commissioner Philippe
p.000050: Busquin, organised on 18-19 December 2001,a forum entitled “Stem cells: therapies for the future?”. The aim was
p.000050: to offer a platform at European level for a debate between, on one side, scientists and experts
p.000050: concerned with the feasibility and consequences of stem cell research and, on the other side, a wide range of
...
Health / Drug Dependence
Searching for indicator dependence:
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p.000006: opened up the question whether research on human embryonic stem cell is needed and ultimately whether the derivation of
p.000006: new human embryonic stem cell lines may be obsolete at this stage. In spite of the optimism generated by the
p.000006: recent research reports on the pluripotentiality of human somatic stem cells, many scientists, including those who
p.000006: conduct
p.000006:
p.000006:
p.000006:
p.000006:
p.000006: 5 e.g. Jiang, Yuehua et al., “Pluripotency of mesenchymal stem cells derived from adult marrow”, Nature,
p.000006: 2002, 418:41-49.
p.000006:
p.000006:
p.000006:
p.000007: 7
p.000007:
p.000007: somatic stem cell research, support the continuation of human embryonic stem cell research, and do not support the
p.000007: limitation of research to somatic stem cell research only6.
p.000007: The conclusions of many reports7 have highlighted that it is too early to know what important findings will come from
p.000007: embryonic or somatic stem cell research and which stem cells will best meet the needs of basic research and clinical
p.000007: applications.
p.000007:
p.000007: Several arguments have been put forward regarding the needs for derivation of new human embryonic stem cell lines.
p.000007:
p.000007: In particular that human embryonic stem cell research has only just begun and scientists do not yet know if they have
p.000007: developed the best procedures for isolating or maintaining human ES cells in culture. It has also been reported that
p.000007: many of the existing embryonic stem cell lines have been patented in the US. This could create a position of dependence
p.000007: from private industry in other parts of the world8.
p.000007:
p.000007: Governance of human stem cell research
p.000007:
p.000007: Human embryonic stem cell research raises complex ethical questions. The question whether it is ethically defensible to
p.000007: do research on embryonic stem cells can be described as a conflict between different values, between different
p.000007: actors’ rights and obligations, or between the short- and long-term interests of different groups. On the one
p.000007: hand, there is interest in new knowledge that can lead to treatment of hitherto incurable diseases. On the other hand,
p.000007: when this research involves the use of human embryos, it raises the question of ethical values at stake
p.000007: and of the limits and conditions for such research9. Opinions on the legitimacy of experiments using
p.000007: human embryos are divided according to the different ethical, philosophical, and religious traditions
p.000007: in which they are rooted. EU Member States have taken very different positions regarding the regulation of human
p.000007: embryonic stem cell research. It confirms that different views exist throughout the European Union
p.000007: concerning what is and what is not ethically defensible.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: 6 e.g. Dr. Catherine Verfaillie, University of Minnesota Medical School, stated during her presentation at
p.000007: the US President’s Council on Bioethics meeting on 25 April 2002, http://www.bioethics.gov/
...
Health / Drug Usage
Searching for indicator drug:
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p.000005: explored.
p.000005:
p.000005: These novel stem cell based therapies are still at their very early stage of development.
p.000005: In particular regarding the transplantation of differentiated cells derived from stem cells, several
p.000005: scientific and technical hurdles needs to be resolved before clinical application of these therapies, including
p.000005:
p.000005: – Understanding of the mechanisms regulating stem cell growth, fate, differentiation and
p.000005: dedifferentiation.
p.000005:
p.000005: – Eliminating the risk of development of inappropriate differentiated cells and cancerous cells. The
p.000005: risk of tumorigenicity has in particular been highlighted concerning the use of human ES cells as these stem cells
p.000005: develop teratomas.
p.000005:
p.000005: – Ensuring the function and viability of the stem cells or their derivatives during the recipient’s life.
p.000005:
p.000005:
p.000005:
p.000005: 4 A. L. Lennard and G H Jackson, “Science, medicine and the future: Stem cell transplantation”, BMJ, 2000,
p.000005: 321: 433-437.
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006: – Overcoming the problem of immune rejection (which does not arise in the case where the patient’s own stem cells
p.000006: can be used).
p.000006:
p.000006: – For the generation of human cells lines to be used in drug development at pre- clinical stage and in
p.000006: toxicology. Normal human cell types generated from human stem cells can be genetically or
p.000006: pharmacologically manipulated and used for drug discovery. These cell lines may provide more clinically relevant
p.000006: biological systems than animal models for drug testing and are therefore expected to contribute to the development of
p.000006: safer and more effective drugs for human diseases and ultimately to reduce the use of animals. They also offer the
p.000006: possibility to develop better in vitro models to enhance the hazard identification of chemicals. It is
p.000006: possible that these applications will turn out to be the major medical impact of human ES cell research at least in
p.000006: a short-term perspective, as the problems of immune rejection, viability and tumorigenicity do not apply
p.000006: here.
p.000006:
p.000006: – For the understanding of human development. Human ES cells should offer insights into
p.000006: developmental events that cannot be studied directly in the intact human embryo but that have important
p.000006: consequences in clinical areas, including birth defects, infertility, and pregnancy loss.
p.000006:
p.000006: – For the understanding of the basic mechanisms of cell differentiation and proliferation. The
p.000006: understanding of the genes and molecules, such as growth factors and nutrients, that function during development of the
p.000006: embryo may be used to grow stem cells in the laboratory and direct their development into specialized cell types. Some
p.000006: of the most serious medical conditions, such as cancer, are due to abnormal cell division and
p.000006: differentiation. A better understanding of the genetic and molecular controls of these processes may yield information
p.000006: about how such diseases arise and suggest new strategies for therapies.
p.000006:
...
p.000019: 1.3. Potential application of human stem cell research
p.000019: Transplantation of haematopoïetic stem cells (from bone marrow, peripheral blood or umbilical cord blood
p.000019: of healthy donor) has been used for more than a decade to treat e.g. haematological malignancies such as
p.000019: leukemia or congenital immunodeficiencies. Autologous transplantation (transplantation of stem cells from
p.000019: the patient’s own bone marrow or peripheral blood) was introduced to rescue the bone marrow of
p.000019: patients who had received high dose of chemotherapy. It is now increasingly being used as primary treatment for
p.000019: other types of cancer such as breast cancer and neuroblastoma. Autologous transplantation is also used experimentally
p.000019: to treat difficult auto-immune conditions and as a vehicle for gene therapy. Today, over 350 centres in
p.000019: Europe are performing more than 18 000 bone marrow transplants a year24.
p.000019: Human stem cell research is expected to be of interest for several areas of science and medicine25:
p.000019:
p.000019: For the development of novel stem cell based therapies.
p.000019:
p.000019: – Novel stem cell based therapies (often called regenerative medicine or cell based therapies) are
p.000019: also being investigated to develop new methods to repair or replace tissues or cells damaged by injuries or
p.000019: diseases and to treat serious chronic diseases, such as diabetes, Parkinson’s, chronic heart failure or stroke and
p.000019: spinal cord injuries. (See chapter 1.4 for further details)
p.000019:
p.000019: – For the generation of normal human cell lines to be used in drug development at the preclinical stage and in
p.000019: toxicology Stem cells are a source for the generation of normal human cell types that can be genetically or
p.000019: pharmacologically manipulated
p.000019:
p.000019:
p.000019: 22 Wagers A.J. et al., “Little evidence for developmental plasticity of adult haematopoïetic
p.000019: stem cells”, Science, 2002, 297, 2256 2259; De Witt and Knight, “Biologists question adult stem cell
p.000019: versality”, Nature, 2002, 416, 354.
p.000019: 23 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm
p.000019: 24 A. L Lennard and G H Jackson. “Science, medicine and the future: Stem cell transplantation”, BMJ, 2000,
p.000019: 321:433-437.
p.000019: 25 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm Annex
p.000019: E - Opinion n° 15 of the European Group on Ethics http://europa.eu.int/comm/
p.000019: european_group_ethics/docs/avis15_EN.pdf
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: and used for drug discovery. They give scientists the ability to experimentally study - under carefully controlled
p.000020: conditions - the growth and development of many different human cell types that are important to
p.000020: diseases like cancer, diabetes, stroke, heart disease etc. These cell lines may provide more clinically
p.000020: relevant biological systems than animal models for drug testing and are therefore expected to contribute to the
p.000020: development of safer and more effective drugs for major human diseases. For example today, there exists no
p.000020: laboratory model for the human heart, and it is therefore very difficult (impossible) to know exactly what
p.000020: effect medicines have on the heart before performing human studies. The lack of availability of human cells, which
p.000020: express normal function, has so far been the main limiting factor for reducing animal testing in
p.000020: pharmaco-toxicology. It is possible that this application will turn out to be the major medical impact of human
p.000020: ES cell research at least in a short-term perspective. At present insufficient methods exist in some areas of in vitro
p.000020: toxicology predicting target organ toxicity. In other areas such as embryo-toxicity inter-species variation presents
p.000020: major obstacles and humanised systems may enhance the hazard identification of chemicals.
p.000020:
p.000020: – Use of stem cells in gene therapy: Stem cells could be used as vehicles i.e. bearers of genetic information
p.000020: for the therapeutic delivery of genes. A problem for research on gene therapy has been to find safe delivery
p.000020: systems and stem cells may provide a solution here. At present, experiments are being done with gene
p.000020: therapy to treat diseases of the blood system. Their aim is to introduce new healthy genes in the
p.000020: blood-forming stem cells, which can then develop into all types of blood cells and, moreover, are able to renew
...
p.000052: a regulatory environment, the latter largely influenced by ethical issues and public concerns.
p.000052:
p.000052: Regarding the exploitation of results of the stem cell research, many of the collaborations in this area with
p.000052: industry involve small, dedicated firms rather than large pharmaceutical companies. Small firms appear to play
p.000052: a key role in transferring technology from the science base into industry. A number of start-up companies have
p.000052: been created as spin-offs from academia in the sector.
p.000052:
p.000052: In 2001 about 30 public and private biotechnology firms were doing stem cells research and about a dozen are currently
p.000052: investigating the potential of both somatic and embryonic stem cells. Few, if any, companies are investing
p.000052: solely in human embryonic stem cell research. According to the Gilder Biotech report June 2001 the venture
p.000052: capital community is at present giving preference to human somatic stem cells, which are reported to be closer to
p.000052: therapeutic application than human embryonic stem cells72.
p.000052: The companies are concerned with the use of stem cells including human embryonic stem cells for:
p.000052:
p.000052: – Novel stem cell based therapies: direct stem cell transplantation, transplantation of stem cell
p.000052: derived differentiated cells, stimulation of the body’s own stem cells via
p.000052: e.g. growth factors or stem cells in gene therapy.
p.000052:
p.000052: – Drug discovery: use of stem cells for drug screening
p.000052:
p.000052: – Services and technologies: screening, isolation of stem cells, preparation and large scale culture
p.000052: of stem cells, storage of stem cells.
p.000052:
p.000052: One of the current framework conditions affecting stem cell research and commercialisation of stem cells therapies is
p.000052: the patenting of human ES cells and their derivatives. On the one hand patent rights are necessary to protect and
p.000052: secure industry’s huge investments to support innovative research and development. On the other hand academic research
p.000052: is stimulated by having free and open access to these cell lines, as they are essential starting materials for their
p.000052: research. Some scientists consider that human embryonic stem cell lines should not be patented at all. The
p.000052: debate on this issue is intense and includes the ethical dimension of this
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 72 Gilder Biotech report, The American Spectator, June 2001, “Adult cells do
p.000052: it better”; http://www.gilderbiotech.com/ArticlesByScott/Op%20Ed/AdultCells.htm
p.000052:
p.000053: 53
p.000053:
p.000053: research. The European Group on Ethics73 in Science and New Technologies (EGE) recommended in their
p.000053: opinion No.16 on patenting of human stem cells that:
p.000053:
...
Health / HIV/AIDS
Searching for indicator HIV:
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p.000074:
p.000074: • Studies of human diseases on animal models. For example, mouse ES cells can be engineered to
p.000074: incorporate human mutated genes known to be associated with particular diseases and then used to make transgenic mouse
p.000074: strains. If such mice express the pathology of the human disease, this confirms the hypothesis that the
p.000074: gene is involved with the etiology of the disease. This strategy also yields an animal model of the
p.000074: human disease which has in most cases a much better predictability for the human situation than more conventional
p.000074: animal models. One of the most illustrative examples of that method is its use in order to address the potential causes
p.000074: of Alzheimer's disease.
p.000074:
p.000074: • Culturing specific differentiated cell lines to be used for pharmacology studies and toxicology
p.000074: testing. This is the most likely immediate biomedical application, making possible the rapid screening of
p.000074: large numbers of chemicals. By measuring how pure populations of specific differentiated cells respond to potential
p.000074: drugs, it will be possible to sort out medicinal products that may be either useful or on the contrary problematic in
p.000074: human medicine.
p.000074:
p.000074:
p.000074:
p.000074:
p.000074:
p.000074:
p.000075: 75
p.000075:
p.000075: • Use of stem cells in gene therapy. Stem cells could be used as vectors for the delivery of gene therapy. One
p.000075: current application in clinical trials is the use of haematopoietic stem cells genetically modified to make them
p.000075: resistant to the HIV (virus responsible for AIDS).
p.000075:
p.000075: • Production of specific cell lines for therapeutic transplantation. If feasible, this would be the
p.000075: most promising therapeutic application of ES cells. Research is being actively pursued, mostly in the mouse, with the
p.000075: aim of directing the differentiation of pluripotent stem cells to produce pure populations of particular cell types
p.000075: to be used for the repair of diseased or damaged tissues. For instance, the aim would be to produce
p.000075: cardiac muscle cells to be used to alleviate ischaemic heart disease, pancreatic islet cells for
p.000075: treatment of diabetes (juvenile onset diabetes mellitus), liver cells for hepatitis, neural cells for degenerative
p.000075: brain diseases such as Parkinson's disease, and perhaps even cells for treating some forms of cancer. The
p.000075: transplantation of stem cells could also help, for example, to repair spinal cord damage which occurs
p.000075: frequently, mainly following trauma (for instance car accidents) and is responsible for paraplegia. Results of that
p.000075: kind of cell therapy on animals are promising, but are still years away from clinical application. Even more remote
p.000075: (possibly decades away) is the prospect of being able to grow whole organs in vitro, but if tissues for
p.000075: the repair of organs become available, it would greatly relieve the existing unsatisfied demand for donated organs for
p.000075: transplantation. In providing a potentially unlimited source of specific clinically important cells such as bone,
...
Health / Motherhood/Family
Searching for indicator family:
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p.000092: long track record in cross-border cooperation and coordination of nationally financed RTD activities which
p.000092: constitutes a feature of direct relevance to building the European Research Area, while also acknowledging
p.000092: the scope for significant changes to the way COST is organised. Moreover, the Council notes that the Commission
p.000092: will not provide the administrative and scientific secretariat to any COST actions initiated during the
p.000092: Sixth Framework Programme. It notes also that the Commission, recognising that a new COST secretariat may not be fully
p.000092: operational by the end of 2002, is however prepared to continue providing the secretariat to COST actions
p.000092: during a transition period of a few months.
p.000092: The Council and the Commission note that COST is in a process of being reformed and recognise that, following a
p.000092: successful outcome, and given also the recent expansion of COST and the growth in its number of Actions, a substantial
p.000092: grant from the Sixth Framework Programme could be justified.
p.000092: The Council welcomes the Commission's intention to become a partner of COST, with a view to further developing synergy
p.000092: between the Framework Programme and COST. The Council invites the Commission to take appropriate steps in this
p.000092: respect.
p.000092:
p.000092:
p.000092: 4. Specific programme "Structuring the European Research Area" Re: Human resources and mobility
p.000092: The Commission states that in the implementation of the human resources and mobility actions under the
p.000092: present Specific Programme, family-related circumstances, such as maternity or paternity leave, will
p.000092: be inter alia taken into account, according to national legislations, so that potential beneficiaries
p.000092: will not suffer from the abovementioned circumstances.
p.000092:
p.000092:
p.000092: 5. Specific programme "Direct actions by the Joint Research Centre" (EC)
p.000092:
p.000092: The Commission considers that, according to its mission and when requested, the JRC should support the European
p.000092: Parliament in the conception and implementation process of EU policies. Therefore the Commission
p.000092: welcomes the EP's intention to create an ad hoc committee aimed at ensuring an appropriate interface with the
p.000092: JRC.
p.000092:
p.000092: The Commission wishes to confirm that the JRC multiannual work programme will be available on the JRC
p.000092: website: http://www.jrc.org.
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000093: 93
p.000093:
p.000093: 6. Specific programme “Nuclear Energy” (Euratom) Re: Voting rights at the consultative committee
p.000093: The Council and the Commission acknowledge the unanimous agreement of the consultative committee for the fusion
p.000093: programme (CCFP) on the following weighted voting system, which should be applied within the Committee referred to in
p.000093: Article 6(2), when dealing with fusion related aspects. Accordingly, the Commission will take the appropriate steps
p.000093: with a view to amending the Council Decision of 16 December 1980 – as last amended by Council Decision 95/1/EC,
p.000093: Euratom, ECSC of 1 January 1995 – setting up the consultative committee for the fusion programme.
p.000093: Germany 5
p.000093: Austria 2
...
Health / Terminally Ill
Searching for indicator terminally:
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p.000070: Institutes of Health) scientific review in 2001;
p.000070:
p.000070: Having regard to the Round Table organised by the Group on 26 June 2000 in Brussels with members of the European
p.000070: Parliament, jurists, philosophers, scientists, representatives of industries, of religions, of patients' associations,
p.000070: and of international organisations (Council of Europe, UNESCO, WHO);
p.000070:
p.000070: Having regard to the Hearings of scientific experts on 6 June 2000 and on 2 October 2000, and to the Hearings of
p.000070: representatives of religions on 8 September 2000;
p.000070:
p.000070: Having heard the rapporteurs Anne McLaren and Goran Hermerén;
p.000070:
p.000070:
p.000070:
p.000070: 1 - WHEREAS SCIENTIFIC BACKGROUND
p.000070: 1.1. How to define stem cells?
p.000070:
p.000070: Stem cells are cells that can divide to produce either cells like themselves (self-renewal), or cells
p.000070: of one or several specific differentiated types. Stem cells are not yet fully differentiated and therefore can
p.000070: reconstitute one or several types of tissues.
p.000070:
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p.000070:
p.000071: 71
p.000071:
p.000071: 1.2. What are the different kinds of stem cells?
p.000071:
p.000071: Different kinds of stem cells can be distinguished according to their potential to differentiate. They are progenitor,
p.000071: multipotent or pluripotent stem cells.
p.000071:
p.000071: • Progenitor stem cells are those whose terminally differentiated progeny consist of a single cell type
p.000071: only. For instance, epidermal stem cells or spermatogonial stem cells can differentiate respectively into
p.000071: only keratinocytes and spermatozoa.
p.000071:
p.000071: • Multipotent stem cells are those which can give rise to several terminally differentiated cell types constituting
p.000071: a specific tissue or organ. Examples are skin stem cells which give rise to epidermal cells, sebaceous glands and
p.000071: hair follicles or haematopoietic stem cells, which give rise to all the diverse blood cells (erythrocytes,
p.000071: lymphocytes, antibody-producing cells and so on), and neural stem cells, which give rise to all the cell types
p.000071: in the nervous system, including glia (sheath cells), and the many different types of neurons.
p.000071:
p.000071: • Pluripotent stem cells are able to give rise to all different cell types in vitro. Nevertheless, they cannot on
p.000071: their own form an embryo. Pluripotent stem cells, which are isolated from primordial germ cells in the
p.000071: foetus, are called: embryonic germ cells ("EG cells"). Those stem cells which are isolated from the inner cell mass of
p.000071: a blastocyst-stage embryo are called: embryonic stem cells ("ES cells”).
p.000071:
p.000071: It should be noted that scientists do not yet all agree on the terminology concerning these types of stem cells.
p.000071:
p.000071:
p.000071: 1.3. What are the characteristics of the different stem cells?
p.000071:
...
Health / stem cells
Searching for indicator stem cells:
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p.000004: COMMISSION OF THE EUROPEAN COMMUNITIES
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: Brussels, 3.4.2003
p.000004: SEC(2003) 441
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: COMMISSION STAFF WORKING PAPER
p.000004:
p.000004: REPORT ON HUMAN EMBRYONIC STEM CELL RESEARCH
p.000004:
p.000004: TABLE OF CONTENTS
p.000004: Executive summary
p.000004: 4
p.000004: Introduction
p.000015: 15
p.000015: 1. Chapter 1: Origin and characteristics of human stem cells and potential application for stem cell research
p.000017: 17
p.000017: 1.1. Origin and characteristics of human stem cells 17
p.000017: 1.2. Plasticity of human somatic stem cells
p.000019: 19
p.000019: 1.3. Potential application of human stem cell research 20
p.000019: 1.4. Novel stem cell based therapies
p.000022: 22
p.000022: 1.5. Scientific and technical obstacles to overcome before realising the potential clinical uses of novel human
p.000022: stem cell based therapy 22
p.000022: 1.6. Examples of novel stem cell based therapies, which are currently subject to extensive research.
p.000023: 23
p.000023: 2. Chapter 2: Human embryonic stem cell research 26
p.000023: 2.1. Origin and characteristics of human embryonic stem cells 26
p.000023: 2.2. Possible sources for human embryonic stem cells 26
p.000023: 2.3. Growing human embryonic stem cells in the laboratory 27
p.000023: 2.4. The current advantages and limitations of human embryonic stem cells and human somatic stem cells
p.000028: 28
p.000028: 2.5. Examining the need for new human embryonic stem cell lines. 30
p.000028: 2.6. Developments regarding establishment of human stem cell banks and registries. 31
p.000028: 3. Chapter 3: Governance of human embryonic stem cell research 34
p.000028: 3.1. The ethical issues at stake
p.000034: 34
p.000034: 3.2. Regulations in EU Member States regarding human embryonic stem cell research. 38
p.000034: 3.3. New regulations under discussion in EU Member States 44
p.000034: 3.4. Regulations in some non-EU countries regarding human embryonic stem cell research
p.000046: 46
p.000046: 3.5. Governance of stem cell research in the context of FP6 48
p.000046: 3.6. Social scrutiny and dialogue
p.000051: 51
p.000051: 4. Chapter 4: Socio-economic aspects
p.000053: 53
p.000053: GLOSSARY
p.000056: 56
p.000056: ANNEX A: Biology of human development 60
p.000056: ANNEX B: Possibilities to overcome immune rejection responses in stem cell therapy 62
p.000056:
p.000056:
p.000056:
p.000002: 2
p.000002:
p.000002: ANNEX C: Examples of available human embryonic stem cell lines 64
p.000002: ANNEX D: Details regarding provisions in non-EU countries relating to human embryonic stem cell research
p.000066: 66
p.000066: ANNEX E: Opinion No.15 of the European Group on Ethics regarding ethical aspects of human stem cell research and use E
p.000066: - Opinion EGE 70
p.000066: ANNEX F: Statement for the minutes of the Council meeting 30 September 2002 84
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p.000003: 3
p.000003:
p.000003: EXECUTIVE SUMMARY
p.000003:
p.000003: Background:
p.000003: Stem cell research is one of the promising areas of biotechnology, which offers the prospect of developing new
p.000003: methods to repair or replace tissues or cells damaged by injuries or diseases and to treat serious
p.000003: chronic diseases, such as diabetes, Parkinson’s, chronic heart failure as well as stroke and spinal cord
p.000003: injuries. Stem cell research is expected to be equally important for basic science to understand cell differentiation
p.000003: and growth as well as for other specific medical applications such as for the understanding of disease development and
p.000003: for the development of safer and more effective drugs. Scientists are intensively studying the fundamental
p.000003: properties of stem cells.
p.000003:
p.000003: One of the possible sources for stem cells is human pre-implantation embryos. However, when this research
p.000003: involves the use of human embryos it raises the question of ethical values at stake and of the limits and conditions
p.000003: for such research.
p.000003:
p.000003: The complexity of this issue with its ethical implications has been highlighted in the process of adoption of the Sixth
p.000003: Framework Programme for Research (FP6) and its implementing Specific Programmes, where the specific issue of
p.000003: human embryonic stem cell research was subject to debate.
p.000003:
p.000003: In the 6th Framework Programme, Community stem cell research funding is foreseen under Priority 1 « Life
p.000003: Sciences, Genomics and Biotechnology for human health », section i “Application of knowledge and technologies
p.000003: in the fields of genomics and biotechnology for health”. In particular, “research will focus on…development and
p.000003: testing of new preventive and therapeutic tools, such as somatic gene and cell therapies (in particular
p.000003: stem cell therapies)”1.
p.000003: Pending the establishment of detailed implementing provisions by end 2003 at the latest, the Commission agreed
p.000003: however not to fund during this period research projects involving the use of human embryos and human
p.000003: embryonic stem cells with the exception of projects involving banked or isolated human embryonic stem cells in
p.000003: culture. The Commission stated its intention of presenting to Council and European Parliament a report on human
p.000003: embryonic stem cells, which would form the basis for discussion at an inter-institutional seminar on
p.000003: bioethics2.
p.000003: The present report is the result of this commitment, and aims to provide a description of the state of play of the
p.000003: scientific, ethical, legal, social and economic issues related to human stem cell research and human embryonic stem
p.000003: cell research.
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003: 1 OJ L 294 of 29.10.2002, p. 10.
p.000003: 2 See annex F.
p.000003:
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000004: The purpose of the report is to provide a basis for an open and informed debate at the above- mentioned
p.000004: inter-institutional seminar3.
p.000004: Taking into account the seminar’s outcome, the Commission will submit a proposal establishing
p.000004: further guidelines on principles for deciding on the Community funding of research projects involving the use
p.000004: of human embryos and human embryonic stem cells.
p.000004:
p.000004:
p.000004: The content of the report
p.000004:
p.000004: Characteristics of human stem cells
p.000004:
p.000004: Stem cells have three characteristics that distinguish them from other types of cells:
p.000004:
p.000004: – they are non-differentiated (unspecialised) cells,
p.000004:
p.000004: – they can divide and multiply in their undifferentiated state for a long period.
p.000004:
p.000004: – under certain physiological or experimental conditions, they can also give rise to more specialised
p.000004: differentiated cells such as nerve cells, muscle cells or insulin producing cells etc.
p.000004:
p.000004: Stem cells are found in the early embryo, in the foetus and the umbilical cord blood, and in many tissues of the
p.000004: body after birth and in the adult. These stem cells are the source for tissues and organs of the foetus
p.000004: and for growth and repair in the new born and adult body. As development proceeds beyond the blastocyst stage (5-7 days
p.000004: after fertilisation), the proportion of stem cells decrease in the various tissues and their ability to differentiate
p.000004: into different cell types also decrease at least when they are situated in their natural environment.
p.000004:
p.000004: Classification of human stem cells
p.000004: In this report a distinction is made between three groups of stem cells, referring to their origin and method of
p.000004: derivation:
p.000004:
p.000004: 1. Human embryonic stem cells, which can be derived from a preimplantation embryo at the blastocyst stage.
p.000004:
p.000004: 2. Human embryonic germ cells, which can be isolated from the primordial germ cells of the foetus.
p.000004:
p.000004: 3. Human somatic stem cells, which can be isolated from adult or foetal tissues or organs or from umbilical cord blood.
p.000004:
p.000004: Potential application of human stem cell research
p.000004:
p.000004: Transplantation of haematopoïetic stem cells (from bone marrow, peripheral blood or umbilical cord blood of a
p.000004: healthy donor) has been used for more than a decade to treat e.g. haematological malignancies such as
p.000004: leukemia or congenital immuno-deficiencies.
p.000004:
p.000004:
p.000004: 3 Scientific terms are explained in the glossary.
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005: Autologous transplantation (transplantation of stem cells from the patient’s own bone marrow or peripheral blood) was
p.000005: introduced to rescue the bone marrow of patients who had received high dose of chemotherapy. It is now increasingly
p.000005: being used as primary treatment of other types of cancer such as breast cancer and neuroblastoma. Autologous stem cell
p.000005: transplantation is also used experimentally to treat difficult auto-immune conditions and as a vehicle for gene
p.000005: therapy. Today, over 350 centres in Europe are performing more than 18 000 bone marrow transplants a year4.
p.000005: Novel stem cell based therapies (often called regenerative medicine or cell based therapies) are also being
p.000005: investigated to develop new methods to repair or replace tissues or cells damaged by injuries or diseases and to
p.000005: treat serious chronic diseases, such as diabetes, Parkinson’s, chronic heart failure or stroke and spinal cord
p.000005: injuries. Stem cell research is expected to be equally important for basic science as well as for other specific
p.000005: medical applications.
p.000005:
p.000005: – For the development of novel stem cell based therapies. Three therapeutic concepts are currently being
p.000005: envisaged:
p.000005:
p.000005: – Transplantation of differentiated cells derived from stem cells: Stem cells may be grown and
p.000005: directed to differentiate into specific cell types in the laboratory and then be transplanted (e.g.
p.000005: insulin producing cells to treat diabetes, heart muscle cells to treat heart failure or dopamine
p.000005: producing neurones to treat Parkinson’s disease etc...) The source for the specific differentiated cell
p.000005: types could be embryonic or somatic stem cells, including the patient’s own stem cells.
p.000005:
p.000005: – Direct administration of stem cells: In some cases it may be possible and/or necessary to administer stem cells
p.000005: directly to the patient in such a way that they would colonise the correct site of the body and continuously
p.000005: differentiate into the desired cell type (e.g. systemic “Homing”).
p.000005:
p.000005: – Stimulation of endogenous stem cells: The possibility that self-repair could be induced or augmented by
p.000005: stimulating an individual’s own population of stem cells for example by administrating growth factors is also being
p.000005: explored.
p.000005:
p.000005: These novel stem cell based therapies are still at their very early stage of development.
p.000005: In particular regarding the transplantation of differentiated cells derived from stem cells, several
p.000005: scientific and technical hurdles needs to be resolved before clinical application of these therapies, including
p.000005:
p.000005: – Understanding of the mechanisms regulating stem cell growth, fate, differentiation and
p.000005: dedifferentiation.
p.000005:
p.000005: – Eliminating the risk of development of inappropriate differentiated cells and cancerous cells. The
p.000005: risk of tumorigenicity has in particular been highlighted concerning the use of human ES cells as these stem cells
p.000005: develop teratomas.
p.000005:
p.000005: – Ensuring the function and viability of the stem cells or their derivatives during the recipient’s life.
p.000005:
p.000005:
p.000005:
p.000005: 4 A. L. Lennard and G H Jackson, “Science, medicine and the future: Stem cell transplantation”, BMJ, 2000,
p.000005: 321: 433-437.
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006: – Overcoming the problem of immune rejection (which does not arise in the case where the patient’s own stem cells
p.000006: can be used).
p.000006:
p.000006: – For the generation of human cells lines to be used in drug development at pre- clinical stage and in
p.000006: toxicology. Normal human cell types generated from human stem cells can be genetically or
p.000006: pharmacologically manipulated and used for drug discovery. These cell lines may provide more clinically relevant
p.000006: biological systems than animal models for drug testing and are therefore expected to contribute to the development of
p.000006: safer and more effective drugs for human diseases and ultimately to reduce the use of animals. They also offer the
p.000006: possibility to develop better in vitro models to enhance the hazard identification of chemicals. It is
p.000006: possible that these applications will turn out to be the major medical impact of human ES cell research at least in
p.000006: a short-term perspective, as the problems of immune rejection, viability and tumorigenicity do not apply
p.000006: here.
p.000006:
p.000006: – For the understanding of human development. Human ES cells should offer insights into
p.000006: developmental events that cannot be studied directly in the intact human embryo but that have important
p.000006: consequences in clinical areas, including birth defects, infertility, and pregnancy loss.
p.000006:
p.000006: – For the understanding of the basic mechanisms of cell differentiation and proliferation. The
p.000006: understanding of the genes and molecules, such as growth factors and nutrients, that function during development of the
p.000006: embryo may be used to grow stem cells in the laboratory and direct their development into specialized cell types. Some
p.000006: of the most serious medical conditions, such as cancer, are due to abnormal cell division and
p.000006: differentiation. A better understanding of the genetic and molecular controls of these processes may yield information
p.000006: about how such diseases arise and suggest new strategies for therapies.
p.000006:
p.000006: The current advantages and limitations of human embryonic and somatic stem cells and the needs regarding the derivation
p.000006: of new human embryonic stem cell lines
p.000006:
p.000006: In light of the current state of knowledge, human embryonic and somatic stem cells each have advantages and
p.000006: limitations regarding their potential uses for basic research and novel stem cell based therapies.
p.000006:
p.000006: It is a matter of debate within the scientific community whether human embryonic stem cells have a greater potential
p.000006: than human somatic stem cells (isolated from foetal or adult tissue). Currently, human ES cells are of particular
p.000006: interest because they have the potential to differentiate into all cell types in the body (they are
p.000006: pluripotent). The recent reports5 indicating that somatic stem cells may have a greater potential for
p.000006: differentiation into different cell types than previously thought (for example bone marrow stem cells under
p.000006: certain experimental conditions may differentiate into neurones, skeletal and cardiac muscle cells), have
p.000006: opened up the question whether research on human embryonic stem cell is needed and ultimately whether the derivation of
p.000006: new human embryonic stem cell lines may be obsolete at this stage. In spite of the optimism generated by the
p.000006: recent research reports on the pluripotentiality of human somatic stem cells, many scientists, including those who
p.000006: conduct
p.000006:
p.000006:
p.000006:
p.000006:
p.000006: 5 e.g. Jiang, Yuehua et al., “Pluripotency of mesenchymal stem cells derived from adult marrow”, Nature,
p.000006: 2002, 418:41-49.
p.000006:
p.000006:
p.000006:
p.000007: 7
p.000007:
p.000007: somatic stem cell research, support the continuation of human embryonic stem cell research, and do not support the
p.000007: limitation of research to somatic stem cell research only6.
p.000007: The conclusions of many reports7 have highlighted that it is too early to know what important findings will come from
p.000007: embryonic or somatic stem cell research and which stem cells will best meet the needs of basic research and clinical
p.000007: applications.
p.000007:
p.000007: Several arguments have been put forward regarding the needs for derivation of new human embryonic stem cell lines.
p.000007:
p.000007: In particular that human embryonic stem cell research has only just begun and scientists do not yet know if they have
p.000007: developed the best procedures for isolating or maintaining human ES cells in culture. It has also been reported that
p.000007: many of the existing embryonic stem cell lines have been patented in the US. This could create a position of dependence
p.000007: from private industry in other parts of the world8.
p.000007:
p.000007: Governance of human stem cell research
p.000007:
p.000007: Human embryonic stem cell research raises complex ethical questions. The question whether it is ethically defensible to
p.000007: do research on embryonic stem cells can be described as a conflict between different values, between different
p.000007: actors’ rights and obligations, or between the short- and long-term interests of different groups. On the one
p.000007: hand, there is interest in new knowledge that can lead to treatment of hitherto incurable diseases. On the other hand,
p.000007: when this research involves the use of human embryos, it raises the question of ethical values at stake
p.000007: and of the limits and conditions for such research9. Opinions on the legitimacy of experiments using
p.000007: human embryos are divided according to the different ethical, philosophical, and religious traditions
p.000007: in which they are rooted. EU Member States have taken very different positions regarding the regulation of human
p.000007: embryonic stem cell research. It confirms that different views exist throughout the European Union
p.000007: concerning what is and what is not ethically defensible.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: 6 e.g. Dr. Catherine Verfaillie, University of Minnesota Medical School, stated during her presentation at
p.000007: the US President’s Council on Bioethics meeting on 25 April 2002, http://www.bioethics.gov/
p.000007: “Embryonic stem cells in humans are very much in their infancy, the same as we are for adult stem cell biology, too,
p.000007: and so I don’t think we are anywhere close to be able to come up with new therapies at this point in time. I would also
p.000007: like to reiterate that even though my laboratory and our group works on adult stem cells, we have actually
p.000007: actively pursued investigators in embryonic stem cell research, human embryonic stem cells, just so that within
p.000007: the same institution we would have laboratories that have one cell, and other laboratories that have the other cell, so
p.000007: we would be in a position to compare and contrast the potential of the different cell populations, and I think that it
p.000007: is very important”.
p.000007: 7 “Stem Cells: scientific progress and future research directions”, National Institute of Health
p.000007: (NIH), Bethesda, USA, June 2001; Swiss National Advisory Commission on Biomedical Ethics: opinion on human
p.000007: embryonic stem cell research, June 2002; The Health Council of the Netherlands’ report on “Stem cells for
p.000007: tissue repair. Research on therapy using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429
p.000007: ; House of Lords Select Committee UK, “Report on Stem cell research”, February 2002;
p.000007: http:/:www.parliament.the-stationery-office.co.uk/pa/ld200102/ldselect/ ldstem/83/8301.htm; Swedish National Council of
p.000007: Medical Ethics: statement of opinion on embryonic stem cell research, 17.01.2002, http://www.smer.gov.se/.
p.000007: 8 The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on
p.000007: therapy using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000007: 9 Annex E - Opinion No. 15 of the European Group on Ethics regarding the “Ethical aspects of human stem
p.000007: cell research and use”. http://europa.eu.int/comm/european_group_ethics/index_en.htm.
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: Ethical issues at stake:
p.000008:
p.000008: As highlighted in the opinion n° 15 of The European Group on Ethics in Sciences and New Technologies regarding «
p.000008: Ethical aspects of human stem cell research and use”, issued 14 November 2000,10 the following fundamental
p.000008: ethical principles are applicable to human embryonic stem cell research:
p.000008:
p.000008: – The principle of respect for human dignity.
p.000008:
p.000008: – The principle of individual autonomy (entailing the giving of informed consent, and respect for
p.000008: privacy and confidentiality of personal data).
p.000008:
p.000008: – The principle of justice and of beneficence (namely with regard to the improvement and
p.000008: protection of health).
p.000008:
p.000008: – The principle of freedom of research (which is to be balanced against other
p.000008: fundamental principles).
p.000008:
p.000008: – The principle of proportionality (including that research methods are necessary to the aims pursued and that
p.000008: no alternative more acceptable methods are available).
p.000008:
p.000008: In addition, the EGE considers it important to take into account, based on a precautionary approach, the potential
p.000008: long-term consequences of stem cell research and use for individuals and the society.”
p.000008:
p.000008: Concerning the creation of embryos for research purpose the EGE considered that “the creation of embryos
p.000008: for the sole purpose of research raises serious concerns since it represents a further step in the
p.000008: instrumentalisation of human life” and deemed “ the creation of embryos with gametes donated for the purpose of
p.000008: stem cell procurement ethically unacceptable, when spare embryos represent a ready alternative source”.
p.000008:
p.000008: Furthermore the EGE considered “that, at present, the creation of embryos by somatic cell nuclear transfer for research
p.000008: on stem cell therapy would be premature, since there is a wide field of research to be carried out with alternative
p.000008: sources of human stem cells (from spare embryos, foetal tissues and adult stem cells”.
p.000008:
p.000008: Concerning the ethical acceptability of human embryonic stem cell research in the context of the Community Framework
p.000008: Programme, the EGE concluded that «//… there is no argument for excluding funding of this kind of research from the
p.000008: Framework Programme of research of the European Union if it complies with ethical and legal requirements as
p.000008: defined in this programme”.
p.000008:
p.000008: Secondly the EGE stated, that:
p.000008:
p.000008: “Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells)
p.000008: requires a specific Community research budget. In particular, EU funding should be devoted to testing the validity of
p.000008: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000008: such research be widely disseminated and not hidden for reasons of commercial interest.”
p.000008:
p.000008:
p.000008: 10 Annex E - Opinion No. 15 of the European Group on Ethics regarding the “Ethical aspects of human stem
p.000008: cell research and use”. http://europa.eu.int/comm/european_group_ethics/index_en.htm.
p.000008:
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: The EGE identified the following principal requirements regarding human embryonic stem cell research and the
p.000009: procurement of embryonic stem cells from supernumerary embryos:
p.000009: – Free and informed consent from the donating couple or woman.
p.000009:
p.000009: – Approval of the research by an authority.
p.000009:
p.000009: – No financial gain for donors.
p.000009:
p.000009: – Anonymity of the donors and protection of the confidentiality of personal information of the donors.
p.000009:
p.000009: – Transparency regarding research results.
p.000009:
p.000009: Concerning clinical research the EGE stressed the importance of:
p.000009:
p.000009: – Free and informed consent of the patient.
p.000009:
p.000009: – Risk-benefit assessment.
p.000009:
p.000009: – Protection of the health of persons involved in clinical trials.
p.000009:
p.000009: Regulation of human embryonic stem cell research in EU Member States11
p.000009: EU Member States have taken different positions regarding the regulation of human embryonic stem
p.000009: cell research and new laws or regulations are being drafted or debated. Taking into account the situation,
p.000009: as of March 2003, the following distinctions can be made:
p.000009:
p.000009: – Allowing for the procurement of human embryonic stem cells from supernumerary
p.000009: embryos by law under certain conditions: Finland, Greece, the Netherlands, Sweden and the United Kingdom.
p.000009:
p.000009: – Prohibiting the procurement of human ES cells from supernumerary embryos but allowing by law for
...
p.000010: Commission for scientific medical research on embryos in vitro”.
p.000010:
p.000010: Denmark: A revision of the current legislation to allow for the procurement of human ES cells from
p.000010: supernumerary embryos is under discussion.
p.000010:
p.000010: France: A revision of the Bioethics Law of 1994 has been approved by the Senate in January 2003 and should be discussed
p.000010: by the Parliament in the first semester of 2003. It proposes to allow research on supernumerary human embryos
p.000010: including the procurement of human ES cells for 5 years under certain conditions. A central authorizing body will
p.000010: be created.
p.000010:
p.000010: Italy: a law on in vitro fertilisation is under discussion.
p.000010:
p.000010: Portugal: A committee has been established in Portugal for the preparation of a law on human embryo and
p.000010: human ES cell research.
p.000010:
p.000010: Spain: A revision of the current legislation is under discussion.
p.000010:
p.000010: In 1998 the National Committee for Human Artificial Reproduction was created. In its second opinion, delivered in 2002,
p.000010: it advised to conduct human embryonic stem cell research using as a source supernumerary embryos, estimated in Spain to
p.000010: be over 30 000.
p.000010:
p.000010: The Ethics Advisory Committee for Scientific and Technological Research was established in April 2002 and gave in
p.000010: February 2003 its first opinion on research on stem cells. It recommended to the government that research on
p.000010: both adult and embryonic stem cells should be implemented; that the legislation should be modified to allow
p.000010: the isolation of human embryonic stem cells from supernumerary embryos.
p.000010:
p.000010: Sweden: A revision of the current legislation is under discussion. The Parliamentary Committee on Genetic
p.000010: Integrity proposed, in their report published 29 January 2003, not to implement a general prohibition against
p.000010: producing fertilised eggs for research purposes. It
p.000010:
p.000010:
p.000010:
p.000010:
p.000011: 11
p.000011:
p.000011: should also be noted, however, that in the view of the Committee the creation of embryos by transfer of somatic cell
p.000011: nuclei (so called therapeutic cloning) should be treated in the same way and thus in principle be allowed.
p.000011:
p.000011: Regulations in countries acceding to the EU
p.000011:
p.000011: Cyprus, Czech Republic, Estonia, Hungary, Lithuania, Slovak Republic, Slovenia have ratified the Convention of
p.000011: the Council of Europe on biomedicine and human rights.
p.000011:
p.000011: Concerning the countries acceding to the EU, no specific regulations regarding human embryonic stem cell
p.000011: research have at present been implemented. Estonia, Hungary, Latvia, Slovenia have implemented legislation
p.000011: authorising research on human embryos under certain conditions. In Lithuania, Poland and the Slovak
p.000011: Republic human embryo research is prohibited. No specific regulation regarding embryo research exist in Cyprus,
p.000011: Malta and the Czech Republic. A bill is under preparation in Czech Republic.
p.000011:
p.000011: Governance of stem cell research in the context of FP6 As stated in the Treaty of the European Union, article 6:
...
p.000012:
p.000012: – research activities aiming at human cloning for reproductive purposes
p.000012:
p.000012: – research activity intended to modify the genetic heritage of human beings which could make such
p.000012: change heritable13
p.000012: – research activities intended to create human embryos solely for the purpose of research or for the purpose of
p.000012: stem cell procurement, including by means of somatic cell nuclear transfer (often referred to as therapeutic cloning).
p.000012:
p.000012: – … funding of research activities that are prohibited in all the Member States is in all circumstances
p.000012: excluded.”
p.000012:
p.000012: – “In compliance with the principle of subsidiarity and the diversity of approaches existing in
p.000012: Europe, participants in research projects must conform to current legislation, regulations and ethical rules in
p.000012: the countries where the research will be carried out.
p.000012:
p.000012: – In any case, national provisions apply and no research forbidden in any given Member State will
p.000012: be supported by Community funding in that Member State.
p.000012:
p.000012: – Where appropriate, participants in research projects must seek the approval of relevant national
p.000012: or local ethics committees prior to the start of the RTD activities. An ethical review will be implemented
p.000012: systematically by the Commission for proposals dealing with ethically sensitive issues, in particular
p.000012: proposals involving the use of human embryos and human embryonic stem cells”.
p.000012:
p.000012: – As stated in the Council minutes of 30 September 200214 “The Council and the Commission agree
p.000012: that detailed implementing provisions concerning research activities involving the use of human
p.000012: embryos and human embryonic stem cells…shall be established by 31 December 2003. The Commission will during
p.000012: that period…not propose to fund such research, with the exception of banked or isolated human embryonic stem cells in
p.000012: culture”.
p.000012:
p.000012: Socio-economic aspects
p.000012:
p.000012: While many of the demonstrations of the potential of stem cell research have arisen from academia, the
p.000012: development of this potential i.e. into therapeutic products requires industrial and commercial inputs. For
p.000012: example, industrial involvement will be needed for large scale and good manufacturing production of cell
p.000012: lines, to support multicentre clinical trials, marketing, distribution etc.
p.000012:
p.000012: In 2001 about 30 public and private biotechnology firms were doing stem cell research and about a dozen are currently
p.000012: investigating the potential of both somatic and embryonic stem cells. Few, if any, companies are investing solely in
p.000012: human embryonic stem cell research.
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 13 Research relating to cancer treatment of the gonads can be financed.
p.000012: 14 Annex F.
p.000012:
p.000012:
p.000012:
p.000013: 13
p.000013:
p.000013: Although considerable sums are available for investment in stem cell research, commercial returns on such
p.000013: investments are for the moment modest. This reflects the fact that most of this work is still at the basic
p.000013: research stage. Thus commercial interests are trying to position themselves for major profits in the
p.000013: future, but still face uncertain research prospects, therapeutic possibilities and the development of a
p.000013: regulatory environment, the latter largely influenced by ethical issues and public concerns.
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p.000014: 14
p.000014:
p.000014: INTRODUCTION
p.000014:
p.000014: This report, prepared by the Commission services, aims to provide an overview of:
p.000014:
p.000014: – Origin and characteristics of human stem cells and the potential application of stem cell
p.000014: research.
p.000014:
...
p.000014: dialogue.
p.000014:
p.000014: – Socio-economic aspects of human embryonic stem cell research and use. The report is complemented by a series
p.000014: of annexes, as follows:
p.000014: A. Biology of human development
p.000014:
p.000014: B. Possibilities to overcome immune rejection responses in stem cell therapy
p.000014:
p.000014: C. Examples of available human embryonic stem cell lines
p.000014:
p.000014: D. Details regarding provisions in non-EU countries relating to human embryonic stem cell research
p.000014:
p.000014: E. Opinion n° 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell research and use” issued
p.000014: 14 November 2002.
p.000014:
p.000014: F. Statement for the minutes of the Council meeting 30 September 2002 The report takes into account:
p.000014: – Information collected from the survey on opinions from National Ethics Committees or similar bodies,
p.000014: public debate and national legislation in relation to human embryonic stem cell research and use in EU Member
p.000014: States and non-EU countries. The survey was conducted by the European Commission, DG Research, Directorate E (last
p.000014: update March 2003);
p.000014:
p.000014: – Opinions and reports from the European Group on Ethics in Science and New Technologies to
p.000014: the European Commission http://europa.eu.int/comm/european
p.000014: _group_ethics/index_en.htm
p.000014:
p.000014: – Report and proceedings from the conference on “Stem cells: Therapies for the future?” organised by the
p.000014: European Commission, DG Research under the aegis of the European Group on Life Sciences; December
p.000014: 2001 http://europa.eu.int/comm/ research/quality-of-life/stemcells.html
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000015: 15
p.000015:
p.000015: – Candidate Countries legislation related to ethical issues in science and research Proceedings of
p.000015: the workshop of 8-10 December 2002 - Brussels - organised by the European Commission - DG Research – Directorate C
p.000015:
p.000015: – U. S. National Institutes of Health (NIH) documents regarding stem cells
p.000015: http://nih.gov/news/stemcell/
p.000015:
p.000015: – Review of recent literature;
p.000015:
p.000015: – Presentations and communications from the scientific community.
p.000015:
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p.000016: 16
p.000016:
p.000016: Chapter 1: Origin and characteristics of human stem cells and potential application for stem cell research
p.000016:
p.000016:
p.000016:
p.000016: 1.1. Origin and characteristics of human stem cells15
p.000016: Stem cells differ from other kind of cells in the body by their unique properties of: 1) being capable of dividing and
p.000016: renewing themselves for long periods, 2) being unspecialised and 3) being able to give rise to specialised cell types.
p.000016: They are found in the early embryo, in the foetus and the umbilical cord blood, and in some (possibly many)
p.000016: tissues of the body after birth and in the adult. These stem cells are the source for tissues and organs of the
p.000016: foetus and for growth and repair in the newborn and adult body. As development proceeds beyond the blastocyst stage
p.000016: (5-7 days after fertilisation), the proportion of stem cells decrease in the various tissues and their
p.000016: ability to differentiate into different cell types also decrease at least when they are situated in their natural
p.000016: environment. (See also chapter 1.2.).
p.000016:
p.000016:
p.000016:
p.000016: Figure 1
p.000016:
p.000016:
p.000016: Fertilisation day 0
p.000016:
p.000016:
p.000016:
p.000016: Day 4-5
p.000016:
p.000016: spermatozoid oocyte
p.000016:
p.000016: ORIIGIIN AND CLASSIIFIICATIIO N OF STEMXCELLS
p.000016:
p.000016:
p.000016: MoMruorlaula
p.000016:
p.000016: Embryonic stem cells
p.000016:
p.000016:
p.000016: Day 5-7
p.000016:
p.000016:
p.000016:
p.000016: From 8th week after fertilisation
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: + umbilical cord blood
p.000016:
p.000016: Human embryonic germ cells
p.000016: (from the primordial germ cells of the foetus )
p.000016:
p.000016:
p.000016: Somatic stem cells
p.000016:
p.000016:
p.000016:
p.000016: Adult
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: 15 The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy using
p.000016: somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429; US NIH, “Stem Cells: A primer” September
p.000016: 2002 http://www.nih.gov/news/stemcell/primer.htm.
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017: Classification of human stem cells:
p.000017:
p.000017: The classification of stem cells is still subject to discussion and the use of different definitions,
p.000017: both in the scientific literature and in public debates, often creates confusion. In this report a distinction is made
p.000017: between three groups of stem cells, referring to their origin and method of derivation16:
p.000017: 1. Human embryonic stem cells
p.000017: Human embryonic stem cells derived from preimplantation embryo at the blastocyst stage (see chapter 2 for
p.000017: further details)
p.000017:
p.000017: 2. Human embryonic germ cells
p.000017: Stem cells with embryonic characteristics have also been isolated from the primordial germ cells of the 5-10 weeks
p.000017: foetus. It is from these embryonic germ cells that the gametes (ova or sperm) normally develop. Research has shown
p.000017: that germ cell derived stem cells have the ability to differentiate into various cell types, although they are
p.000017: more limited in this respect than embryonic stem cells17. It should be noted that these research results
p.000017: have yet to be confirmed by other scientists and that the stability of these cells’ genetic material is still open
p.000017: to discussion.
p.000017:
p.000017: 3. Human somatic stem cells
p.000017: A somatic stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ, which can renew
p.000017: itself and can differentiate to yield the major specialised cell types of the tissue or organ. Although somatic
p.000017: stem cells are rare, many, if not most, tissues in the foetus and human body contain stem cells, which, in
p.000017: their normal location, have the potential to differentiate into a limited number of specific cell types in order to
p.000017: regenerate the tissue in which they normally reside. These stem cells, defined as somatic stem cells, are
p.000017: usually described as “multipotent”. Scientists have found evidence for somatic stem cells in many more
p.000017: tissues than they once thought possible. Examples of the tissues reported to contain stem cells include liver,
p.000017: pancreas, brain, bone marrow, muscle, olfactory epithelium, fat and skin18. Some stem cells remain very active during
p.000017: postnatal life (e.g. haematopoïetic stem cells, skin and gut stem cells), others seem relatively inactive (e.g. stem
p.000017: cells in the brain). It should be mentioned that recent published data have suggested that, for example cells in the
p.000017: liver and even the adult human brain may respond to injury by attempting repopulation19.
p.000017:
p.000017: Possible sources for human somatic stem cells:
p.000017:
p.000017: – Adult tissues and organs: Somatic stem cells can be obtained by means of invasive intervention, such as
p.000017: that used in connection with donation of bone marrow. Haematopoïetic stem cells are routinely collected through
p.000017: the peripheral blood. It has
p.000017:
p.000017:
p.000017: 16 The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on
p.000017: therapy using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429; US NIH “Stem Cells: A
p.000017: primer” September 2002 http://www.nih.gov./news/stemcell/primer.htm.
p.000017: 17 Shamblott, M.J. et al. “Human embryonic germ cell derivates express a broad range of developmentally
p.000017: distinct markers and proliferate extensively in vitro”, Proc Natl Acad Sci USA, 2001, 98: 113-8.
p.000017: 18 Jiang, Y. et al., “Pluripotency of mesenchymal stem cells derived from adult marrow”, Nature, 2002 , 418
p.000017: : 41-49.
p.000017: 19 Steindler, D.A. and Pincus D.W., “Stem cells and neuropoiesis in the adult brain”, Lancet,
p.000017: 2002, 359(9311):1047-1054.
p.000017:
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000018: also been reported that stem cells can be obtained following autopsy, from post mortem brain tissue for
p.000018: example.
p.000018:
p.000018: – Foetal organs or tissues: Foetal tissue or organs obtained after pregnancy termination can be used to derive
p.000018: stem cells, e.g. neural stem cells which can be isolated from foetal neural tissue and multiplied in culture.
p.000018:
p.000018: – Umbilical cord blood: Haematopoïetic stem cells can be retrieved from the umbilical cord blood at birth.
p.000018: Stem cells, which could give rise to other tissues, may also be present in cord blood.
p.000018:
p.000018: 1.2. Plasticity of human somatic stem cells
p.000018:
p.000018:
p.000018:
p.000018: Figure 2
p.000018:
p.000018: PLASTICITY OF STEMXCELLS
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: Dedifferentiation?
p.000018:
p.000018: Stem cell
p.000018:
p.000018:
p.000018: Transdifferentiation?
p.000018: Precursor Cell
p.000018:
p.000018: Differentiation
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: Adapted after
p.000018: D. Steindler,
p.000018: The University of Florida
p.000018:
p.000018:
p.000018: e.g. Blood
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: Or Brain Cells
p.000018: Differentiated Cell
p.000018:
p.000018:
p.000018: It has recently been reported that for example:
p.000018:
p.000018: – Brain stem cells may differentiate into blood cells20
p.000018: – Bone marrow stem cells in vitro may differentiate into neurons, skeletal and cardiac muscle cells and liver
p.000018: cells etc.21
p.000018: This later process might be explained by the persistence of very rare pluripotent stem cells through
p.000018: life, which under normal conditions are “dormant”. However, other hypotheses are envisaged. The potential of
p.000018: a stem cell may not be defined once and forever but may depend on the cellular environment. For example a
p.000018: somatic stem cell might be able to make more than one tissue by one of the following ways:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: 20 Bjornson, C et al., “Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells”,
p.000018: in vivo. Science, 1999, 283, 354-357.
p.000018: 21 Jiang Y, et al., “Pluripotency of mesenchymal stem cells derived from adult marrow”, Nature, 2002,
p.000018: 418:41-49; Orlic, D et al., “Bone marrow cell regenerate infarcted myocardium”, Nature, 2001, 410, 701-705; Petersen,
p.000018: B.E. et al., “Bone marrow as a potential source of hepatic oval cells. Science, 1999, 284, 1168-1170.
p.000018:
p.000018:
p.000018:
p.000019: 19
p.000019:
p.000019: In a changed environment, the original stem cell might dedifferentiate and then be reprogrammed
p.000019: to generate the alternative cell types
p.000019: or
p.000019: The original cell might change directly into another cell type without going through a dedifferentiated
p.000019: intermediate stage, a process sometimes called “transdifferentiation”.
p.000019: This is little short of a revolutionary concept in developmental cell biology where it has generally
p.000019: been considered that in mammalian cells, contrary to plants and lower micro- organisms, the process of
p.000019: differentiation was irreversible.
p.000019: Some scientists question the plasticity of stem cells22. Current research is aimed at
p.000019: determining the mechanisms that underlie somatic stem cell plasticity. If such mechanisms can be identified
p.000019: and controlled, existing stem cells from healthy tissue might be induced to repopulate and repair a diseased tissue23.
p.000019: 1.3. Potential application of human stem cell research
p.000019: Transplantation of haematopoïetic stem cells (from bone marrow, peripheral blood or umbilical cord blood
p.000019: of healthy donor) has been used for more than a decade to treat e.g. haematological malignancies such as
p.000019: leukemia or congenital immunodeficiencies. Autologous transplantation (transplantation of stem cells from
p.000019: the patient’s own bone marrow or peripheral blood) was introduced to rescue the bone marrow of
p.000019: patients who had received high dose of chemotherapy. It is now increasingly being used as primary treatment for
p.000019: other types of cancer such as breast cancer and neuroblastoma. Autologous transplantation is also used experimentally
p.000019: to treat difficult auto-immune conditions and as a vehicle for gene therapy. Today, over 350 centres in
p.000019: Europe are performing more than 18 000 bone marrow transplants a year24.
p.000019: Human stem cell research is expected to be of interest for several areas of science and medicine25:
p.000019:
p.000019: For the development of novel stem cell based therapies.
p.000019:
p.000019: – Novel stem cell based therapies (often called regenerative medicine or cell based therapies) are
p.000019: also being investigated to develop new methods to repair or replace tissues or cells damaged by injuries or
p.000019: diseases and to treat serious chronic diseases, such as diabetes, Parkinson’s, chronic heart failure or stroke and
p.000019: spinal cord injuries. (See chapter 1.4 for further details)
p.000019:
p.000019: – For the generation of normal human cell lines to be used in drug development at the preclinical stage and in
p.000019: toxicology Stem cells are a source for the generation of normal human cell types that can be genetically or
p.000019: pharmacologically manipulated
p.000019:
p.000019:
p.000019: 22 Wagers A.J. et al., “Little evidence for developmental plasticity of adult haematopoïetic
p.000019: stem cells”, Science, 2002, 297, 2256 2259; De Witt and Knight, “Biologists question adult stem cell
p.000019: versality”, Nature, 2002, 416, 354.
p.000019: 23 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm
p.000019: 24 A. L Lennard and G H Jackson. “Science, medicine and the future: Stem cell transplantation”, BMJ, 2000,
p.000019: 321:433-437.
p.000019: 25 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm Annex
p.000019: E - Opinion n° 15 of the European Group on Ethics http://europa.eu.int/comm/
p.000019: european_group_ethics/docs/avis15_EN.pdf
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: and used for drug discovery. They give scientists the ability to experimentally study - under carefully controlled
p.000020: conditions - the growth and development of many different human cell types that are important to
p.000020: diseases like cancer, diabetes, stroke, heart disease etc. These cell lines may provide more clinically
p.000020: relevant biological systems than animal models for drug testing and are therefore expected to contribute to the
p.000020: development of safer and more effective drugs for major human diseases. For example today, there exists no
p.000020: laboratory model for the human heart, and it is therefore very difficult (impossible) to know exactly what
p.000020: effect medicines have on the heart before performing human studies. The lack of availability of human cells, which
p.000020: express normal function, has so far been the main limiting factor for reducing animal testing in
p.000020: pharmaco-toxicology. It is possible that this application will turn out to be the major medical impact of human
p.000020: ES cell research at least in a short-term perspective. At present insufficient methods exist in some areas of in vitro
p.000020: toxicology predicting target organ toxicity. In other areas such as embryo-toxicity inter-species variation presents
p.000020: major obstacles and humanised systems may enhance the hazard identification of chemicals.
p.000020:
p.000020: – Use of stem cells in gene therapy: Stem cells could be used as vehicles i.e. bearers of genetic information
p.000020: for the therapeutic delivery of genes. A problem for research on gene therapy has been to find safe delivery
p.000020: systems and stem cells may provide a solution here. At present, experiments are being done with gene
p.000020: therapy to treat diseases of the blood system. Their aim is to introduce new healthy genes in the
p.000020: blood-forming stem cells, which can then develop into all types of blood cells and, moreover, are able to renew
p.000020: themselves and thereby provide a permanent cure.
p.000020:
p.000020: – For understanding of human development. Studies of human embryonic and foetal stem cells may yield a deeper
p.000020: understanding of evolutionary biology and the process leading from embryo to human being. Human ES cells
p.000020: should offer insights into developmental events that cannot be studied directly in the intact human embryo but that
p.000020: have important consequences in clinical areas, including birth defects, infertility, and pregnancy loss. Particularly
p.000020: in the early post implantation period, knowledge of normal human development is largely restricted to the
p.000020: description of a limited number of sectioned embryos and to analogies drawn from the
p.000020: experimental embryology of other species. Although the mouse is the main stay of experimental mammalian embryology,
p.000020: early structures including the placenta, extra-embryonic membranes, and the egg cylinder all differ
p.000020: substantially from the corresponding structure of the human embryo.
p.000020:
p.000020: – For understanding of the basic mechanisms of cell differentiation and proliferation. A
p.000020: primary goal of this work is to identify how undifferentiated stem cells become differentiated into particular types of
p.000020: cells. Scientists know that turning genes on and off are central to this process and molecules such as growth factors
p.000020: and nutrients, that function during embryonic development, also play a role. This knowledge can be used to
p.000020: grow stem cells from various sources in the laboratory and direct their differentiation into specialized cell
p.000020: types. Some of the most serious medical conditions, such as cancer, are due to abnormal cell
p.000020: division and differentiation. A better understanding of the genetic and molecular controls of these processes may
p.000020: yield information about how such diseases arise and suggest new strategies for therapies.
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021: 1.4. Novel stem cell based therapies
p.000021:
p.000021: Three therapeutic concepts are currently being envisaged26:
p.000021: – Transplantation of differentiated cells derived from stem cells: Stem cells may be grown and
p.000021: directed to differentiate into specific cell types in the laboratory and then be transplanted e.g. insulin producing
p.000021: cells to treat diabetes, skeletal muscle cells for muscle diseases, dopamine producing neurons for Parkinson’s
p.000021: disease etc. The source for the specific differentiated cell types could be embryonic or somatic stem cells including
p.000021: the patient’s own stem cells.
p.000021:
p.000021: – Direct administration of stem cells: In some cases it may be possible and/or necessary to administer stem
p.000021: cells directly to the patient in such a way that they would colonise the correct site of the body and continuously
p.000021: differentiate into the desired cell type (e.g. systemic “Homing”).
p.000021:
p.000021:
p.000021:
p.000021: Figure 3
p.000021: Three potential therapeutic approaches for stem cell based therapy for brain disorders
p.000021:
p.000021:
p.000021:
p.000021: Intra-brain injections of stem cell derived differentiated neural cells
p.000021:
p.000021:
p.000021:
p.000021: Stimulation of the patient’s
p.000021: own stem cells by factors such as “Neuropoietins”
p.000021:
p.000021:
p.000021: Direct administration of stem cells i.e. systemic “Homing”
p.000021:
p.000021:
p.000021: Adapted after D. Peace and D. Steindler
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: – Stimulation of endogenous stem cells: The possibility that self-repair could be induced or
p.000021: augmented by stimulating an individual’s own population of stem cells for example by administrating growth
p.000021: factors is also being explored.
p.000021:
p.000021: 1.5. Scientific and technical obstacles to overcome before realising the potential clinical uses of
p.000021: novel human stem cell based therapy
p.000021: The novel stem cell based therapies as described in chapter 1.4. are still at a an early stage of development. In
p.000021: particular regarding the transplantation of differentiated cells derived from stem cells several scientific
p.000021: and technical hurdles need to be resolved before clinical application of these therapies, including 27:
p.000021:
p.000021:
p.000021:
p.000021: 26 “La recherche sur les cellules souches embryonnaires”, Commission national d’éthique suisse pour la
p.000021: médicine humaine, Prise de position n° 3/2002; Steindler, D.A. and Pincus D.W., “Stem cells and
p.000021: neuropoiesis in the adult brain”, Lancet, 2002, 359(9311):1047-1054.
p.000021: 27 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm;
p.000021: House of Lords Select Committee – Report on Stem cell research, February 2002
p.000021:
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000022: – Differentiation, dedifferentiation and transdifferentiation: There is still a strong need to gain
p.000022: a better understanding of the underlying mechanisms regulating stem cell growth, migration, fate and
...
p.000022: (heterologous transplantation). Immune rejection is one of the major causes of transplant failure, and is one of the
p.000022: problems which will need to be overcome for stem cell-based therapy to be effective except in the case where the
p.000022: patient’s own stem cells can be used. Different approaches are currently being envisaged to overcome
p.000022: immune rejection e.g. immuno-suppressive drugs, generation of immunotolerance, use of “matching tissues or by
p.000022: somatic cell nuclear transfer (i.e. therapeutic cloning) as described in annex B.
p.000022:
p.000022: – Function and viability: The stem cells or their derivatives must function appropriately
p.000022: for the duration of the recipient’s life and survive in the recipient after transplantation. Methods to improve and
p.000022: properly assess the viability and functioning of the differentiated cells need to be worked out.
p.000022:
p.000022: – Culture conditions: Good manufacturing practice (GMP) needs to be defined including the
p.000022: establishment of germ-free culture conditions for the derivation and differentiation of specialised cell types.
p.000022:
p.000022: 1.6. Examples of novel stem cell based therapies, which are currently subject to extensive research.
p.000022: Neurological diseases and disorders (see also figure 3)
p.000022:
p.000022: Parkinson’s disease (PD) is caused by a progressive degeneration and loss of dopamine (DA)- producing neurons, which
p.000022: leads to rigidity, hypokinesia (abnormally decreased mobility) and tremor.
p.000022:
p.000022: Scientists are developing a number of strategies for producing dopamine neurons from human stem cells in the laboratory
p.000022: for transplantation into humans with Parkinson’s disease including
p.000022:
p.000022:
p.000022: http://www.parliament.the-stationery-office.co.uk/pa/ld200102/ldselect/ldstem/83/8301.htm ; The Health
p.000022: Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy using somatic and embryonic
p.000022: stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023: the use of neural dopamine producing cells derived from aborted foetuses. Clinical trials in patients with Parkinson’s
p.000023: disease have been performed on around 200 patients over the last 10 years especially in Sweden and in USA. They have
p.000023: shown that the transplantation of neural cells derived from the human foetus can have a therapeutic effect, with an
p.000023: important reduction of the symptoms of the disease in the treated patients28. However, the availability of neural
p.000023: foetal tissue is very limited. Efforts are now being made to expand fetal neural stem cells and control their
p.000023: differentiation into dopaminergic neurons.
p.000023:
p.000023: In a recent study, scientists directed mouse embryonic stem cells to differentiate into dopaminergic
p.000023: neurons by treatment with growth factors and by introducing the gene Nurr1. When transplanted into the brains of
p.000023: a rat model of Parkinson’s disease these stem cell- derived dopaminergic neurons re-innervated the brains
p.000023: of the rat, released dopamine and improved motor function.29
p.000023: The possibility to stimulate the patient’s own stem cells in the brain is also being explored. Self-repair could be
p.000023: induced or augmented with neuro-poïetins - small selective growth factors that trigger repair processes by
p.000023: an individual’s own indigenous population of stem cells30.
p.000023: Heart failure
p.000023:
p.000023: When heart muscle cells (cardiomyocytes) are destroyed, e.g. after a heart attack, functional contracting heart muscle
p.000023: is replaced with non-functional scar tissue. It is hoped that healthy heart muscle cells generated in culture in
p.000023: the laboratory and then transplanted into patients could be used to treat patients with e.g. chronic heart
p.000023: disease.
p.000023:
p.000023: Recent research in mice indicates that mouse cardiomyocytes derived from mouse embryonic stem cells, transplanted
p.000023: into a damaged heart, can generate new heart muscle cells and successfully repopulate the heart tissue.
p.000023: These results suggest that cardiomyocytes derived from human embryonic stem cells derived could be developed for
p.000023: cell transplantation therapy in humans suffering from heart failure31.
p.000023: It has also been reported from animal studies that bone marrow stem cells32 have the potential to be used to repair the
p.000023: infarcted heart. The transplantation of autologous bone marrow cells (transplantation of the patient’s own stem cells)
p.000023: into the infected heart has been reported in two small non randomized human studies33.
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: 28 Bjorklund, A. and Lindvall O., “Cell replacement therapies for central nervous system
p.000023: disorders”,
p.000023: Nature Neuroscience, 2000, 3, 537-544.
p.000023: 29 Björklund, L. M. et al. “Embryonic stem cells develop into functional dopaminergic neurons
p.000023: after transplantation in a Parkinson rat model”, Proc. Natl. Acad. Sci. USA , 2002, 99:2344-2349; Kim J-H. et al.,
p.000023: “Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease”,
p.000023: Nature, 2002, 418: 50-56.
p.000023: 30 Steindler, D.A. and Pincus D.W., “Stem cells and neuropoiesis in the adult brain”, Lancet,
p.000023: 2002, 359(9311):1047-1054.
p.000023: 31 Kehat et al., “Human embryonic stem cells can differentiate into myocytes with structural
p.000023: and functional properties”, J Clin Invest, 2001, 103:407-14.
p.000023: 32 Orlic, D. et al. “Bone marrow cells regenerate infarcted myocardium”, Nature, 2001, 410,
p.000023: 701-705. Orlic, D. et al. “Mobilized bone marrow cells repair the infacted heart, improving function and
p.000023: survival”, Proc Natl Acad Sci USA 2001, 98: 10344-9.
p.000023: 33 Assmus, B. et al. “Transplantation of progenitor cells and regeneration enhancement
p.000023: in acute myocardial infarction (TOPCARE-AMI)”, Circulation, 2002, 106: R53-R61; Strauer, B.E. et al.
p.000023:
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024: Diabetes
p.000024:
p.000024: In people who suffer from type I diabetes, the cells of the pancreas that normally produce insulin are
p.000024: destroyed by the patient’s own immune system. Although diabetics can be treated with daily injections of insulin, these
p.000024: injections enable only intermittent glucose control. As a result, patients with diabetes suffer chronic degeneration of
p.000024: many organs, including the eye, kidney, nerves and blood vessels. In some cases, patients with diabetes have been
p.000024: treated with islet beta cell transplantation. However, poor availability of suitable sources for islet beta cell
p.000024: transplantation from post mortem donors makes this approach difficult as a treatment for the growing numbers of
p.000024: individuals suffering from diabetes.
p.000024:
p.000024: Ways to overcome this problem include deriving islet cells from other sources such as:
p.000024:
p.000024: – Human adult pancreatic duct cells that have been grown successfully in vitro and induced to
p.000024: differentiate, but the ability of these cells to restore blood glucose in vivo is still unproven. This promising
p.000024: line of research is being pursued by several laboratories.
p.000024:
p.000024: – Fetal pancreatic stem cells and ß cell precursor. The identification of endocrine precursor cells
p.000024: in the developing pancreas and the regulation of their differentiation by a specific cellular pathway raises the
p.000024: possibility to grow and differentiate endocrine precursor cells in vitro taken from aborted foetus or by
p.000024: using adult pancreatic duct cells34.
p.000024: – Embryonic stem cells. Research in mice has demonstrated that mouse embryonic stem cells can differentiate
p.000024: into insulin- producing cells and other pancreatic endocrine hormones. The cells self-assemble to form
p.000024: three-dimensional clusters similar in topology to normal pancreatic islets. Transplantation of these cells
p.000024: was found to improve the conditions of experimental animals with diabetes35. New studies indicate that it is possible
p.000024: to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells.
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024: “Repair of infarcted myocardium by autologous intracoronary mononuclear bone narrow cell
p.000024: transplantation in humans”, Circulation, 2002, 106: 1913-1918.
p.000024: 34 Serup P. et al. “Islet and stem cell transplantation for treating diabetes”, BMJ, 2001, 322:29-32.
p.000024: 35 Lumelsky, N. et al. “Differentiation of embryonic stem cells to insulin - secreting structures similar to
p.000024: pancreas islets”, Science, 2001, 292: 1389-94.
p.000024:
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025: Chapter 2: Human embryonic stem cell research
p.000025:
p.000025:
p.000025:
p.000025: The first embryonic stem cells were isolated from mice in 1981 and a great deal of research has been undertaken on
p.000025: mouse embryonic stem cells. A new era of stem cell biology began in 1998, when the derivation of embryonic stem
p.000025: cells from human blastocysts was first demonstrated36. Since then, several research teams have been working on the
p.000025: characterisation of these cells and on improving the methods for culturing them.
p.000025:
p.000025: 2.1. Origin and characteristics of human embryonic stem cells
p.000025: Human embryonic stem cells can be derived from preimplantation embryo at the blastocyst stage. At this stage, which is
p.000025: reached after about 5 days’ embryonic development, the embryo appears as a hollow ball of 50-100 cells, called the
p.000025: blastocyst. The blastocyst includes three structures: the outer cell layer, which will develop into the placenta; the
p.000025: blastocoel, which is the fluid filled cavity inside the blastocyst; and the inner cell mass, from which the human ES
p.000025: cells can be isolated.
p.000025:
p.000025: The characteristics of human embryonic stem cells include:
p.000025:
p.000025: - Potential to differentiate into the various cell types in the body (more than 200 types are known)
p.000025: even after prolonged culture. The human ES cells are referred to as pluripotent.
p.000025:
p.000025: - Capacity to proliferate in their undifferentiated stage.
p.000025:
p.000025: 2.2. Possible sources for human embryonic stem cells
p.000025: Human embryonic stem cells can be isolated from preimplantation embryos (blastocysts) created by different in
p.000025: vitro techniques37 (i.e. embryos created outside the human body; these embryos cannot develop beyond the blastocyst
p.000025: stage without implantation into the uterus):
p.000025:
p.000025: 1. Supernumerary embryos:
p.000025: One possible source would be to use supernumerary embryos. These are embryos, which have been created by means of in
p.000025: vitro fertilisation (IVF) for the purpose of assisted reproduction but subsequently not used. In by far the
p.000025: majority of cases, assisted reproduction is used in connection with fertility problems, where supernumerary
p.000025: embryos may be created in order to increase the success of infertility treatment. In the countries where
p.000025: pre-implantation diagnosis is allowed, IVF is also used in connection with this practice and human ES cells can also be
p.000025: derived from embryos, which are discarded following pre-implantation diagnosis. These supernumerary embryos
p.000025: may be donated for research by the couples concerned with their fully informed consent.
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: 36 Thomson, J.A. et al. “Embryonic stem cell lines derived from human blastocysts”, Science, 1998, 282,
p.000025: 1145-1147.
p.000025: 37 Thomson, J.A. et al. “Embryonic stem cell lines derived from human blastocysts”, Science, 1998, 282,
p.000025: 1145-1147. Annex E - Opinions n°15 and 16 of the European Group on Ethics
p.000025: http://europa.eu.int/comm/european_group_ethics/docs/avis15_en.pdf
p.000025: http://europa.eu.int/comm/european_group_ethics/docs/avis16_en.pdf
p.000025:
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026: 2. Embryos created by IVF for research purposes and/or for the purpose of stem cell procurement38:
p.000026: Embryos created for the purpose of research may be produced with donated gametes, i. e. they are created by in vitro
p.000026: fertilisation of a human egg by human sperm.
p.000026:
p.000026: 3. Embryos created by somatic cell nuclear transfer for research purposes and/or for the purpose of stem cell
p.000026: procurement39:
p.000026: Embryos may be produced by somatic cell nuclear transfer i.e. they are created by introducing the nucleus of an adult
p.000026: somatic cell (e.g. a cell from the patient) into an enucleated human oocyte and then activating the egg’s further
p.000026: development without fertilisation (often referred to as therapeutic cloning). When the blastocyst stage is reached
p.000026: pluripotent stem cells can be isolated and cultured. These later stem cells have the advantage of being
p.000026: immunologically compatible with the patient. Laboratories currently attempt to replace the nuclei of human ES cell in
p.000026: culture by somatic nuclei from patients’ cells in order to overcome the problem of immune rejection.
p.000026:
p.000026: 4. Other possibilities:
p.000026: It is also possible to obtain human ES cells by parthenogenesis (by stimulation in vitro of an egg cell to initiate the
p.000026: duplication of the egg’s genetic information and then the division of the cell). Finally, it is speculated that ES
p.000026: cells may possibly be obtained by injecting stem cell or egg cytoplasm into differentiated cells transforming
p.000026: these cells into pluripotent stem cells (ovoplasmic transfer).
p.000026: It is possible that new ways of deriving human ES cells could be developed in the future.
p.000026:
p.000026: 2.3. Growing human embryonic stem cells in the laboratory40
p.000026: In order to derived embryonic stem cells, the outer membrane of the blastocyst is punctured, whereupon the inner cell
p.000026: mass with its stem cells is collected and transferred into a laboratory culture dish that contains a nutrient broth
p.000026: known as culture medium. The blastocyst is thereby destroyed and cannot develop further, but the isolated human
p.000026: ES cells can be cultivated in vitro and give rise to stem cell line. The stem cell lines can be cryopreserved and
p.000026: stored in a cell bank. To be successful, the cultivation requires, in addition to nutrient solution, so-called “feeder”
p.000026: cells or support cells. Until recently fibroblasts from mice have been used for this purpose, however
p.000026: scientists are now able to propagate human ES cell lines using human feeder layer or even culturing human ES
p.000026: cells without feeder layer. This eliminates the risk that viruses or infectious agents in the mouse cells might be
p.000026: transmitted to the human cells.
p.000026:
p.000026: If the stem cells are of good quality and if they show no sign of ageing, the same stem-cell line can yield
p.000026: unlimited amounts of stem cells. Besides their broad potential for
p.000026:
p.000026:
p.000026: 38 In accordance with the Council decision of 30 September adopting the specific
p.000026: programmes implementing FP 6 the creation of embryos for research purposes and for stem cell procurement,
p.000026: including by means of somatic cell nuclear transfer (i.e. therapeutic cloning) are excluded from funding under the 6th
p.000026: Framework Programme. OJ L 294 of 29.10.2002, p. 8.
p.000026: 39 In accordance with the Council decision of 30 September adopting the specific
p.000026: programmes implementing FP 6 the creation of embryos for research purposes and for stem cell procurement,
p.000026: including by means of somatic cell nuclear transfer (i.e. therapeutic cloning) are excluded from funding under the 6th
p.000026: Framework Programme. OJ L294 of 29.10.2002, p. 8.
p.000026: 40 US NIH, “Stem cells: a primer”, September 2002. http://www.nih.gov./news/stemcell/primer.htm
p.000026: Swedish National Council on Medical Ethics: statement of opinion on embryonic stem cell research, 17.01.2002,
p.000026: http://www.smer.gov.se.
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027: differentiation, embryonic stem cell lines have proved better able to survive in the laboratory than other types of
p.000027: stem cells. At the various points during the process of generating embryonic stem cell lines, scientists test
p.000027: the cells to see whether they exhibit the fundamental properties that make them, embryonic stem cells. As yet, there
p.000027: exists no standard battery of tests that measure the cells’ fundamental properties but several kinds of tests including
p.000027: tests based on the presence of specific surface and gene markers for undifferentiated cells.
p.000027:
p.000027: One can distinguish:
p.000027:
p.000027: – Human ES cells freshly derived from an embryo which have not yet been subjected to any modification and
p.000027: which have yet to be established as stem cell lines.
p.000027:
p.000027: – Unmodified (undifferentiated) human ES cell lines, which refer to cultured lines of cells, which have
p.000027: been propagated for an extended period originally from freshly human ES cells and which have not been modified
p.000027: in any other way.
p.000027:
p.000027: – Modified (differentiated) human ES derivates which refer to cultured lines of cells, derived from human
p.000027: ES cells or human ES cell lines, which have been modified either by genetic manipulation, or by treatment
p.000027: (e.g. growth factors) that causes the cells to differentiate in a particular way e.g. to differentiate into
p.000027: neural or muscle precursor cells (cells which are not fully differentiated, otherwise they will not
p.000027: multiply).
p.000027:
p.000027: 2.4. The current advantages and limitations of human embryonic stem cells and human somatic stem cells
p.000027: In light of current knowledge, human embryonic and somatic stem cells each have advantages and limitations regarding
p.000027: potential use for basic research and stem cell based therapy.
p.000027:
p.000027: 2.4.1. Human embryonic stem cells
p.000027:
p.000027: Advantages:
p.000027: – human ES cells have the potential to generate the various cell types in the body (they are pluripotent).
p.000027:
p.000027: – human ES cells are at present the only pluripotent stem cell that can be readily isolated and grown in
p.000027: culture in sufficient numbers to be useful.
p.000027:
p.000027: Limitations:
p.000027:
p.000027: – The most significant potential scientific limitation on the therapeutic use of human ES cells is the problem
p.000027: of immune rejection. Because human ES cells will not normally have been derived from the patient to be treated, they
p.000027: run the risk of rejection by the patient’s immune system. Annex B provides an overview of the possibilities
p.000027: to overcome immune rejection currently under investigation e.g. immuno-suppresive drugs, generation of
p.000027: immuno-tolerance, use of “matching tissues” or by somatic cell nuclear transfer (i.e. therapeutic cloning).
p.000027:
p.000027: – It has been argued that, because human ES cells have the potential to differentiate into all cell types, it
p.000027: might be difficult to ensure that, when used therapeutically, they do not differentiate into inappropriate cell
p.000027: types or generate tumors. It is clearly essential to guard against these risks in particular of tumorgenesis.
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028: – Current methods for growing human ES cell lines in culture are adequate for research purposes, but the
p.000028: co-culture of human ES cells with animal materials necessary for growth and differentiation would preclude their
p.000028: use in therapy. Scientists are now working on generating stem cell lines, which are grown on human
p.000028: feeder layer or without feeder layer and in completely defined culture media.
p.000028:
p.000028: 2.4.2. Human somatic stem cells
p.000028:
p.000028: Advantages:
p.000028:
p.000028: – The potential of somatic stem cells for therapeutic application is illustrated by the use of haematopoïetic
p.000028: stem cells to treat leukemias and other blood disorders38.
p.000028: – Recent studies suggesting that various somatic stem cells have much greater potential for differentiation
p.000028: than previously suspected have opened up the possibility that other routes to somatic stem cell therapy might be
p.000028: available.
p.000028:
p.000028: – The patient’s own stem cells could be expanded in culture and then reintroduced into the patient which
p.000028: would mean that the cells would not be rejected by the immune system. This represents a significant
p.000028: advantage, as immune rejection is a difficult problem.
p.000028:
p.000028: – In the future it might be possible to stimulate proliferation and fate control of the
p.000028: patient’s own indigenous somatic stem cell population in-situ by systemically- introduced “poïetins”.
p.000028:
p.000028: Limitations:
p.000028: – The isolation, growth and differentiation of adult stem cells have to date proved difficult.
p.000028: Stem cells generally represent a small proportion of cells in adult tissues. It should be recognised that although
p.000028: haematopoïetic stem cells represent a small proportion of cells in the peripheral blood (i.e.
p.000028: haematopoïetic stem cells, 1 out of 100,000 white blood cells), they are now the preferred source of
p.000028: autologous stem cells for transplantation in adults41.
p.000028: – Where a person suffers from a genetic disorder or some types of cancers, somatic stem cells isolated from
p.000028: that individual will retain the damaging genetic alterations underlying the disease and so be of little
p.000028: therapeutic value e.g. in the case of diabetes. However, they could be corrected by gene therapy.
p.000028:
p.000028: – It is not yet known whether somatic stem cells give rise to cells of different tissue types
p.000028: by transdifferentiation, or by dedifferentiation to a less differentiated stem cell, which then differentiates
p.000028: into the new cell types. The control and safety of dedifferentiation is a major challenge and one
p.000028: about which little is yet known.
p.000028:
p.000028: – Adult stem cells may contain more DNA abnormalities caused by sunlight, toxins and errors in making more DNA
p.000028: copies during the course of a lifetime.
p.000028:
p.000028:
p.000028:
p.000028:
p.000028: 41 Lennard, A. L. and Jackson G. H., “Science, medicine and the future: Stem cell transplantation”, BMJ,
p.000028: 2000, 321:433-437.
p.000028:
p.000028:
p.000028:
p.000029: 29
p.000029:
p.000029: It is a matter of debate within the scientific community whether human embryonic stem cells have a greater potential
p.000029: that human somatic stem cells (isolated from foetal or adult tissue). The recent reports regarding the plasticity of
p.000029: human somatic stem cells as described earlier in chapter 1.2, have led to the question of why embryonic stem cell
p.000029: research is needed if somatic stem cells are available. These issues have been exhaustively considered in
p.000029: many national reports from advisory bodies, ethics committees, learned societies etc. and in scientific
p.000029: publications. The conclusions of these reports published in the recent months have highlighted
p.000029: that it is too early to know what findings will come from embryonic or somatic stem cell research and which stem cells
p.000029: will best meet the needs of basic research and clinical application42.
p.000029: 2.5. Examining the need for new human embryonic stem cell lines.
p.000029: The question whether there are already enough embryonic stem cell lines that meet the criteria, which
p.000029: are considered ethically acceptable by Member States, is important in the debate. Although human embryonic
p.000029: stem cell lines have been registered, in particular at the US National Institutes of Health Human embryonic stem
p.000029: cell registry (see 2.6)43 several arguments have been put forward regarding the needs for derivation of new human
p.000029: embryonic stem cell lines44:
p.000029: – Human embryonic stem cell research is so new that scientists do not yet know if they have developed the best
p.000029: procedures for isolating or maintaining human ES cells. It is possible that all the current cell lines are
p.000029: compromised, as happened with the first mouse ES cell lines.
p.000029:
p.000029: – Many of the human embryonic stem cell lines currently available have not been sufficiently
p.000029: verified to see whether they exhibit the fundamental properties that make them embryonic stem cells e.g. the six
p.000029: human ES cell lines from the Karolinska Institute currently at the NIH registry are not available and have not
p.000029: yet been fully characterized45 (see annex C for further information).
p.000029: – Most currently available human ES cell lines have been cultivated in contact with mouse cells.
p.000029: The contact with animal cells and serum components involves an unknown risk of contamination with viruses and
p.000029: other infectious agents. Therefore, such cell lines or their derivatives can not be used for transplantation to humans.
p.000029:
p.000029:
p.000029: 42 “Stem Cells: scientific progress and future research directions”, National Institutes of
p.000029: Health (NIH), Bethesda, USA, June 2001 http://www.nih.gov/news/stemcell/scireport.htm; Swiss National Advisory
p.000029: Commission on Biomedical Ethics: opinion on human embryonic stem cell research, June 2002; The Health Council of the
p.000029: Netherlands’ report on “Stem cells for tissue repair. Research on therapy using somatic and embryonic stem cells”,
p.000029: June 2002. http://www.gr.nl/pdf.php?ID=429; House of Lords Select Committee UK “Report on Stem cell
p.000029: research”, February 2002; http://www.parliament.the- stationery-office.co.uk/pa/ld200102/ldselect/ldstem/83/8301.htm
p.000029: ; Swedish National Council of Medical Ethics: Statement of opinion on embryonic stem cell research,
p.000029: 17.01.2002.
p.000029: 43 http://escr.nih.gov/eligibilitycriteria.html. The US National Institute of Health (NIH) has identified 78
p.000029: human embryonic stem cell lines that meet the US eligibility criteria. The availability and the stage of development
p.000029: and characterisation of these human ES cell lines are unclear and the NIH has now indicated 9 human ES
p.000029: cell lines which are available for distribution to different laboratories. (James Battery, Head of NIH panel
p.000029: managing stem cell research). Science 2003 (299) 1509. The Wisconsin Alumni Research Foundation, which owns five
p.000029: stem cell lines, claims that it has enough to supply all scientists in the world.
p.000029: 44 e.g. The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy
p.000029: using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000029: 45 Communication from Carlstedt-Duke, Dean of Research, Karolinska Institute, Sweden.
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000030: – Currently available human ES cell lines represent only limited amount of genetic variation. It
p.000030: is important to notice that cell lines with a different genetic basis can have different characteristics.
p.000030:
p.000030: – Many of the existing embryonic stem cell lines have been patented in the US. It is important
p.000030: not to be in a dependent position with respect to private industry.
p.000030:
p.000030: Annex C provides examples of the currently available human ES cell lines.
p.000030: 2.6. Developments regarding establishment of human stem cell banks and registries. Human stem cell banks
p.000030: The need for public stem cell banks including human embryonic stem cell has been recognised at national
p.000030: level both in Sweden and UK.
p.000030:
p.000030: The British Medical Research Council (MRC) in autumn 2002, in collaboration with the Biotechnology and
p.000030: Biological Science Research Council (BBSRC) and with the full backing of the UK Government, took the initiative
p.000030: to establish the first large-scale publicly funded Stem Cell Bank worldwide. The National Institute for
p.000030: Biological Standards and Control (NIBSC) is hosting the UK Stem Cell Bank46, which officially started 1 January
p.000030: 2003.
p.000030: The general aim of the UK Stem Cell Bank will be to create an independent and competent facility to store, test and
p.000030: release seed stocks of existing and new stem cell lines derived from adult, foetal and embryonic human tissues.
...
p.000031: lines with the best matching phenotypes can later be selected for cell or tissue transplantation.
p.000031:
p.000031: Human embryonic stem cell registry
p.000031: The US National Institutes of Health (NIH) established in autumn 2001 an Human Embryonic Stem Cell Registry which
p.000031: at present lists 78 human ES cell lines that meet the eligibility criteria for Federally funded
p.000031: research49. The registry indicates 14 laboratories or companies across the world, which have developed human
p.000031: embryonic stem cell lines. The availability of these cell lines and their level of characterisation are unclear and the
p.000031: NIH Human Embryonic Cell Registry has recently been updated to reflect the human ES cell lines that meet
p.000031: the eligibility criteria for Federally funded research and which are currently available for shipping to other
p.000031: laboratories50. This list includes 9 human ES cell lines:
p.000031: 2 human ES cell lines from BresaGen, Inc. (a US based company)
p.000031: 5 human ES cell lines from ES Cell International (a company based in Singapore and Australia)
p.000031: 1 human ES cell line from University of California at San Francisco 1 human ES cell line from Wisconsin Alumni Research
p.000031: Foundation
p.000031: Both the European Group on Ethics in Science and New Technologies51 and the European Group on Life
p.000031: Sciences52 have highlighted the need for a European registry of stem cell lines. In particular, the EGE called in their
p.000031: opinion n°16 on “Ethical aspects of patenting inventions involving human stem cells” for the creation of an EU registry
p.000031: of unmodified human stem cell lines.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 48 Communication from Professor Hamberger, Goteborg University, Sweden.
p.000031: 49 http://escr.nih.gov/eligibilitycriteria.html. The following eligibility criteria must be
p.000031: met: (i) the derivation process has been initiated before 9 August 2001; (ii) the stem cells must have been derived
p.000031: from an embryo that was created for reproductive purposes but the embryo was not longer needed for those purposes;
p.000031: (iii) informed consent must have been obtained for the donation of the embryo; (iv) no financial inducements were
p.000031: provided for donation of the embryo.
p.000031: 50 http://escr.nih/
p.000031: 51 http://europa.eu.int/comm/european_group_ethics/docs/avis16_en.pdf
p.000031: 52 http://europa.eu.int/comm/research/life-sciences/egls/index_en.html
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032: “Such registry, which should include information on both embryonic stem cells and embryonic germ
p.000032: cell lines should be publicly accessible. Its aim would be to ensure transparency and thus facilitate
p.000032: access by the research community to the needed biological material for further research”51
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
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p.000032:
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p.000032:
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p.000032:
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p.000032:
p.000032:
p.000032:
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p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
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p.000032:
p.000032:
p.000032:
...
p.000033: no alternative more acceptable methods are available).
p.000033:
p.000033: In addition, the Group considers it important to take into account, based on a precautionary approach, the potential
p.000033: long-term consequences of stem cell research and use for individuals and the society.”
p.000033:
p.000033: Concerning the creation of embryos for research purpose the EGE considered that “the creation of embryos
p.000033: for the sole purpose of research raises serious concerns since it represents a further step in the
p.000033: instrumentalisation of human life” and deemed “ the creation
p.000033:
p.000033:
p.000033: 53 Annex E - Opinion No. 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell
p.000033: research and use”; http://europa.eu.int/comm/european_group_ethics/docs/avis15_en.pdf
p.000033: 54 Annex E: Opinion No. 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell
p.000033: research and use”; http://europa.eu.int/comm/european_group_ethics/docs/avis15_en.pdf
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034: of embryos with gametes donated for the purpose of stem cell procurement ethically unacceptable, when spare
p.000034: embryos55 represent a ready alternative source”.
p.000034: Furthermore the EGE considered “ that, at present, the creation of embryos by somatic cell nuclear transfer for
p.000034: research on stem cell therapy would be premature, since there is a wide field of research to be carried out with
p.000034: alternative sources of human stem cells (from spare embryos, foetal tissues and adult stem cells”.
p.000034:
p.000034: The ethical acceptability of human embryonic stem cell research in the context of Community Framework
p.000034: Programme for Research
p.000034: The EGE noted in the same opinion that “in some countries embryo research is forbidden. But when this research is
p.000034: allowed, with the purpose of improving treatment for infertility, it is hard to see any specific argument,
p.000034: which would prohibit extending the scope of such research in order to develop new treatments to cure severe
p.000034: diseases or injuries. As in the case of research on infertility, stem cell research aims to alleviate
p.000034: severe human suffering. In any case, the embryos that have been used for research are required
p.000034: to be destroyed. Consequently, there is no argument for excluding funding of this kind of research from the
p.000034: Framework Programme of research of the European Union if it complies with ethical and legal requirements
p.000034: as defined in this programme”.
p.000034:
p.000034: Secondly the EGE stated, that:
p.000034:
p.000034: “Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells)
p.000034: requires a specific Community research budget. In particular, EU funding should be devoted to testing the validity of
p.000034: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000034: such research be widely disseminated and not hidden for reasons of commercial interest.
p.000034: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000034: funding for stem cell research. This implies the establishment of appropriate procedures and provision of
p.000034: sufficient means to permit ethical assessment not only before the launching of a project but also in monitoring
p.000034: its implementation.”
p.000034:
p.000034: Principal requirements regarding human embryonic stem cell research.
p.000034: Concerning the use of human supernumerary embryos as a source of stem cells the EGE stressed in their
p.000034: opinion that “ the derivation of stem cells from embryonic blastocysts raises the issue of the moral status of the
p.000034: human embryo. In the context of European pluralism, it is up to each Member State to forbid or authorise embryo
p.000034: research. In the latter case, respect for human dignity requires regulation of embryo research and the
p.000034: provision of guarantees against risks of arbitrary experimentation and instrumentalisation of human embryos”.
p.000034:
p.000034: The EGE also stressed regarding stem cell research and rights of women that “Women who undergo infertility treatment
p.000034: are subject to high psychological and physical strain. The group stresses the necessity to ensure that the demand for
p.000034: spare embryos (supernumerary embryos) and oocyte donation does not increase the burden on women”.
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: 55 Spare embryos: another word for supernumerary embryos.
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035: The EGE stressed also the importance of the following requirements regarding human embryonic stem cell
p.000035: research and the procurement of embryonic stem cells from supernumerary embryos:
p.000035:
p.000035: – Free and informed consent from the donating couple or woman.
p.000035: The EGE stated: “Free and informed consent is required not only from the donor but also from the
...
p.000036: derived from somatic cells. For example, the risks that transplanted stem cells cause abnormalities or
p.000036: induce creation of tumours or cancer have to be assessed. It is important that the potential benefits for the
p.000036: patients should be taken into account but not exaggerated. The grounds of a precautionary approach need to
p.000036: be taken into account”.
p.000036:
p.000036: – Protection of the health of persons involved in clinical trials
p.000036:
p.000036: “The possibility that irreversible and potentially harmful changes are introduced in clinical applications of stem
p.000036: cell research should be minimised. Techniques enhancing the possibilities of reversibility should be
p.000036: used whenever possible. If, for example, genetically modified cells were encapsulated when they are transplanted
p.000036: in order to stimulate neural cell growth, it should be possible for the procedure to be reversed if something goes
p.000036: wrong.”
p.000036:
p.000036: The opinion of the EGE regarding “Ethical aspects of human stem cell research and use” dates back to 14
p.000036: November 2000, but it is still considered to be relevant. Human stem cell research and in particular human embryonic
p.000036: stem cell research are still in an early stage of development and therefore the fundamental ethical principles
p.000036: at stake and the requirements for for human embryonic stem cell research are still relevant.
p.000036:
p.000036: Chapter 3.2 provides further information regarding the requirements applied in EU Member States allowing for the import
p.000036: and use of human embryonic stem cells and/or the procurement of human ES cells from supernumerary embryos.
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000037: 37
p.000037:
p.000037: 3.2. Regulations in EU Member States regarding human embryonic stem cell research56
p.000037: EU Member States have already taken very different positions regarding the regulation of human ES cell
p.000037: research and new legislation or regulations are being drafted or debated. Table 1 attempts to provide a comprehensive
p.000037: overview of the situation as of March 2003.
p.000037:
p.000037: The following distinctions can be made:
p.000037:
p.000037: 1. Allowing for the procurement of human embryonic stem cells from supernumerary embryos by law
p.000037: Finland
p.000037: The medical research Act of 1999 covers the preconditions and use of human embryos up to 14 days of embryonic
p.000037: development. The production of human embryonic stem cells from supernumerary embryos is allowed. The
p.000037: laboratories that do embryo research need a licence from the National Authority for Medicolegal Affairs. An
p.000037: ethics committee must approve research projects. The informed consent of both gamete donors is required.
p.000037:
p.000037: Greece
p.000037: The recent law 3089/2002 on medically assisted human reproduction allows for the procurement of
p.000037: human embryonic stem cells from supernumerary embryos. The Act requires the informed consent of both gamete donors and
p.000037: no financial inducement.
p.000037:
p.000037: The Netherlands
p.000037: The Embryo Act of September 2002 allows the use of supernumerary embryos for research including isolation of
p.000037: embryonic stem cells from such embryos. This research requires the favourable opinion of the Central
p.000037: committee for research involving human subjects. The informed consent of the donor is required. The
p.000037: research must have the aim to lead to new insights in medical science.
p.000037:
p.000037: Sweden
p.000037: The Act of 1991 on “Measures for Purposes of Research and Treatment involving Fertilised Human Ova” and the Health
p.000037: and Medical Care Act (18-982:763) apply. According to the Act(1991:115), in vitro embryo research is
p.000037: legally permitted until day 14 after conception, after which the embryo must be destroyed.. After some discussion
p.000037: there is consensus that this legislation permits human embryonic stem cell research. A revision of the law
p.000037: is under discussion (see chapter 3.3)
p.000037:
p.000037: United Kingdom
p.000037: The research purposes permitted by the Human Fertilisation and Embryology Act of 1990 were extended by
p.000037: the “Human Fertilisation and Embryology (Research Purposes ) Regulation” of 2001 to permit the use
...
p.000037: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000037: cell research and use (last update March 2003); “Survey on the National Regulations in the European Union
p.000037: regarding Research on Human Embryos” - B. Gratton - published by the Secretariat of the EGE - European Commission -
p.000037: July 2002.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: responsible for licensing research involving the creation and use of human embryos. The HFEA requires the
p.000038: informed consent of the donors and free donation. The first two licences for stem cell research under the 2001
p.000038: Regulations were issued by HFEA in February 2002.
p.000038:
p.000038: 2. Prohibition of the procurement of embryonic stem cells from human embryos but allowing by law
p.000038: the import and use of human embryonic stem cell lines under certain conditions.
p.000038: Germany
p.000038: The Embryo protection Act of 1990 forbids any research which is not for the benefit of the concerned embryo.
p.000038: A new Act ensuring protection of embryos in connection with the importation and utilisation of human embryonic stem
p.000038: cells – Stem Cell Act – (Stammzellgesetz – StZG) was adopted on 28 June 2002.
p.000038: Concerning importation and utilisation of embryonic stem cells the act specifies in section 4 , that:
p.000038: (1) The importation and utilisation of embryonic stem cells shall be prohibited.
p.000038: (2) Notwithstanding para 1, the importation and utilisation of embryonic stem cells for research purposes shall be
p.000038: permissible under the conditions stipulated in section 6 if
p.000038:
p.000038: 1. The competent agency has satisfied itself that
p.000038: a) The embryonic stem cells were derived before 1 January 2002 in the country of origin in accordance with relevant
p.000038: national legislation there and are kept in culture or are subsequently stored using
p.000038: cryopreservation methods (embryonic stem cell line)
p.000038: b) The embryos from which they were derived have been produced by medically-assisted in vitro fertilisation in order
p.000038: to induce pregnancy and were definitely no longer used for this purpose and that there is no evidence
p.000038: that this was due to reasons inherent in the embryos themselves.
p.000038: c) No compensation or other benefit in money’s worth has been granted or promised for the donation of
p.000038: embryos for the purpose of stem cell derivation and if
p.000038: 2. Other legal provisions, in particular those of the German Embryo Protection Act, do not conflict with the
p.000038: importation or utilisation of embryonic stem cells.
p.000038:
p.000038: (3) Approval shall be refused if the embryonic stem cells have obviously been derived in contradiction to major
p.000038: principles of the German legal system. Approval may not be refused by arguing that the stem cells have been derived
p.000038: from human embryos.
p.000038:
p.000038: Concerning using embryonic stem cells section 5 states:
p.000038: Research involving embryonic stem cells shall not be conducted unless it has been shown by giving scientific reasons
p.000038: that
p.000038:
p.000038: 1. Such research serves eminent research aims to generate scientific knowledge in basic research or to
p.000038: increase medical knowledge for the development of diagnostic, preventive or therapeutic methods to be
p.000038: applied to humans and that,
p.000038:
p.000038: 2. According to the state-of-the-art of science and technology,
p.000038: a) The questions to be studied in the research project concerned have been clarified as far as possible through in
p.000038: vitro models using animal cells or through animal experiments and
p.000038: b) The scientific knowledge to be obtained from the research project concerned cannot be expected to be
p.000038: gained by using cells other than embryonic stem cells.
p.000038: Concerning approval section 6 states:
p.000038: 1) Any importation and any utilisation of embryonic stem cells shall be subject to approval by the competent agency
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039: 2) Applications for approval must be submitted in writing. In the documents accompanying the application, the applicant
p.000039: shall provide the following information in particular:
p.000039: 1. Name and official address of the person responsible for the research project concerned,
p.000039: 2. A description of the research project including scientific reasons showing that the research project meets the
p.000039: requirements set forth in section 5 above,
p.000039: 3. A documentation concerning the embryonic stem cells to be imported or used showing that the
p.000039: requirements set forth in no. 1 of para 2 of section 4 above have been complied with or equivalent evidence that
p.000039: a) The embryonic stem cells to be imported or used are identical with those registered in a
p.000039: scientifically recognised, publicly accessible registry maintained by government agencies or agencies authorised by the
p.000039: government and that,
p.000039: b) By way of such registration, the requirements set forth in no. 1 of para 2 of section 4 above have been complied
p.000039: with.
p.000039: 3) The competent agency shall immediately acknowledge in writing receipt of the application and the attached documents.
p.000039: At the same time, the agency shall request the opinion of the Central Ethics Commission on Stem Cell Research. On
p.000039: receipt of the opinion, the agency shall notify the applicant of the content and the date of the opinion adopted by the
...
p.000039: request by the competent agency to this effect.
p.000039: 5) If the application, complete with documentation, and the opinion of the Central Ethics Commission on Stem Cell
p.000039: Research have been received, the agency shall decide in writing on the application within a period of two months. In
p.000039: doing so, the agency shall consider the opinion adopted by the Central Ethics Commission Stem Cell Research, the agency
p.000039: shall give its reasons in writing.
p.000039:
p.000039: 6) Approval can be limited in time or by imposing obligations to the extent necessary for complying with or continuing
p.000039: to meet the approval requirements pursuant to para 4 above. If, following approval, events occur which
p.000039: conflict with the granting of approval, approval can be withdrawn wholly or in part with effect in the
p.000039: future or be limited in time or be made dependent on the fulfilment of conditions to the extent
p.000039: necessary for complying with or continuing to meet the approval requirements set forth in para 4 above. Any objection
p.000039: to or action for rescission of withdrawal or revocation of approval shall not suspend the effect of the decision.
p.000039:
p.000039: The first authorisation to import human embryonic stem cell lines was given in December 2002.
p.000039:
p.000039: 3. Prohibition of the procurement of embryonic stem cells from human supernumerary embryos.
p.000039: Austria
p.000039: The Austrian Reproductive Medicine Act of 1992 states that cells capable of development may only be used
p.000039: for medical assisted reproduction. According to the interpretation of the Reproductive Medicine Act the
p.000039: procurement of stem cells from embryonic tissues is prohibited. The use of imported human ES
p.000039: cells is not explicitly prohibited and discussion regarding authorisation is still ongoing.
p.000039:
p.000039: Denmark
p.000039: The Act on Medically Assisted Procreation from 1997 only allows research intending to improve in vitro
p.000039: fertilisation technique or pre-implantation diagnosis techniques. Therefore, the isolation of human ES cells from
p.000039: supernumerary embryos is forbidden. The importation of
p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040: human ES cells is not explicitly forbidden. However, the Danish government will give its opinion on human
p.000040: embryonic stem cell research in spring 2003, and has recommended that no research with human ES cell lines should be
p.000040: commenced until the government has presented its decision to Parliament (See also chapter 3.3)
p.000040:
p.000040: France
p.000040: Under the Bioethics Law of 1994, research on human embryos in vitro is forbidden except for research which does not
p.000040: harm the embryo. The import and use of human ES cell lines derived from supernumerary embryos is not explicitly
p.000040: prohibited but the authorisation is still under discussion. A revision of the Bioethics law is under discussion
p.000040: (see chapter 3.3)
p.000040:
...
p.000040:
p.000040: Italy
p.000040: Italy has not enacted legislation.
p.000040: The Italian National Bioethics Committee has adopted an advice on “the therapeutic use of stem cells”. A majority
p.000040: of the members considered the research on human supernumerary embryos for the derivation of human ES cells as
p.000040: legitimate.
p.000040:
p.000040: Luxembourg
p.000040: There is no legislation covering human embryo research.
p.000040:
p.000040: Portugal
p.000040: Portugal has not enacted legislation but has ratified the Convention of the Council of Europe on Human Rights and
p.000040: Biomedicine signed in Oviedo on 4 April 1997, which prohibit the creation of human embryos for research
p.000040: purposes and has in addition the protocol on the prohibition of human cloning. The National Council of Ethics
p.000040: has adopted opinions covering these questions. It has taken the position that research with no benefit for
p.000040: the embryo concerned is not legitimated. The Ministry of Science has created in 2002 a Steering
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Committee for the preparation of a law on research on human embryos including human ES cells.
p.000041:
p.000041: 5. Allowing for the creation of human embryos for stem cell procurement by law
p.000041: UK is for the moment the only Member State with a specific law that permits the creation of human embryos by
p.000041: fertilisation of an egg with a sperm or by somatic cell nuclear transfer. The 1990 Act and the 2001
p.000041: Regulation (see above) allow for the isolation of stem cells for any of the 8 research purposes set out in the law.
p.000041:
p.000041: The Dutch Embryo Act of 2002 announces, as a general principle, the prohibition of the creation of human
p.000041: embryos solely for research purposes. However, this ban is not irreversible and could be lifted by Royal Decree within
p.000041: five years after the coming into force of the Act.
p.000041:
p.000041: 6. Prohibition of the creation of human embryos for research purposes and for the procurement of stem
p.000041: cells by law or by ratification of the Convention of the Council of Europe on Human rights and Biomedicine signed in
p.000041: Oviedo on 4 April 1997
p.000041: The creation of human embryos for research purposes and for the procurement of embryonic stem cells is for the
p.000041: moment prohibited in Austria, Denmark, Finland, France, Germany, Greece, Ireland, Netherlands, Portugal and
p.000041: Spain.
p.000041:
p.000041:
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p.000043: 43
p.000043:
p.000043: 3.3. New regulations under discussion in EU Member States57
p.000043: Belgium
p.000043: A bill on research on human embryos in vitro was approved by the Belgian Senate in 2002 and is now under discussion in
p.000043: the Parliament. The draft legislation proposes to authorise the procurement of embryonic stem cells from supernumerary
p.000043: embryos under certain conditions and the creation of a “Federal Commission for scientific medical research
p.000043: on embryos in vitro”.
p.000043: The bill also foresees to allow for the creation of human embryos for research purposes including by
p.000043: means of somatic cell nuclear transfer.
p.000043: Article 3 proposes to allow research on human embryos in vitro under the following conditions:
p.000043: – research for therapeutic purposes
p.000043: – based on recent scientific knowledge
p.000043: – carried by a registered laboratory
p.000043: – embryos up to 14 days of development
p.000043: – no alternative method of research as effective
p.000043: – the consent of the donors
p.000043: In addition the research is controlled at the local and federal levels.
p.000043:
p.000043: Denmark
p.000043: A revision of the current legislation to allow for the procurement of human ES cells from supernumerary
p.000043: embryos is under discussion.
p.000043:
p.000043: France
p.000043: A revision of the Bioethics Law of 1994 has been approved by the Senate in January 2003 and should be discussed by the
p.000043: Parliament in the first semester of 2003. It proposes to allow for research on supernumerary human embryos including
p.000043: the procurement of human ES cells for 5 years under certain conditions. A central authorising body will be created.
p.000043: The proposed revision of the Bioethics law (as amended by the Senate in January 2003) prohibits human
p.000043: embryo research but includes a derogation for five years allowing for research on supernumerary human
...
p.000043: The proposed bill will also allow the import of foetal or embryonic cells or tissues after prior authorisation by the
p.000043: central body.
p.000043:
p.000043:
p.000043:
p.000043: 57 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000043: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000043: cell research and use (last update March 2003).
p.000043:
p.000044: 44
p.000044:
p.000044: Italy
p.000044: A law on in vitro fertilisation is under discussion. The Ministry of Health recently produced a report about the banks
p.000044: conserving embryos and gametes.
p.000044:
p.000044: Portugal
p.000044: A committee has been established in Portugal for the preparation of a law on human embryo and human ES cell research.
p.000044:
p.000044: Spain
p.000044: A revision of the current legislation is under discussion.
p.000044: In 1998 the National Committee for Human Artificial Reproduction was created. In its second opinion, delivered in 2002,
p.000044: it advised to conduct human embryonic stem cell research using as a source supernumerary embryos, estimated in Spain to
p.000044: be over 30 000.
p.000044: The Ethics Advisory Committee for Scientific and Technological Research was established in April 2002 and gave in
p.000044: February 2003 its first opinion on research on stem cells. It recommended to the government that research on
p.000044: both adult and embryonic stem cells should be implemented; that the legislation should be modified to allow
p.000044: the isolation of human embryonic stem cells from supernumerary embryos under the following condition: The
p.000044: parents´ informed consent or, if this is not possible, the permission of the Centre of Assisted
p.000044: Reproduction in charge of keeping the embryos according to the regulation in force. The investigation
p.000044: must have the aim of alleviating human suffering and not just economic ends. It must be exclusively done by
p.000044: working groups with a proved experience in this field. The protocol of investigation must be previously
p.000044: evaluated by Ethics Committees and it must be under their exhaustive control. Therefore, the control and
p.000044: supervision of these investigations by a national committee is recommended.
p.000044:
p.000044: Sweden
p.000044: A revision of the current legislation is under discussion.
p.000044: The Parliamentary Committee on Genetic Integrity proposed, in their report published 29 January 2003, not
p.000044: to implement a general prohibition against producing fertilised eggs for research purposes. It is the opinion
p.000044: of the Committee that such production must take place in order for research to be carried out on infertility and the
p.000044: development of the fertilised egg etc. It is not possible to set a legal limit with sufficient clarity that would
p.000044: delineate what, on the contrary, would be forbidden. This delineation should rather be done on a case-by-case basis
...
p.000046: legislation, together with the older provisions contained in law No. 277/1994 on health care, especially the
p.000046: prohibition of the “non-therapeutic research” to be performed on human embryos and foetuses, were
p.000046: interpreted recently as effectively banning all human cloning (the so-called “reproductive” as well as
p.000046: “therapeutic”).
p.000046: There is a government proposal to amend the Slovak Republic’s Penal Code accordingly - i.e. making human cloning a
p.000046: penal offence in the Slovak Republic (relevant wording being taken basically from the Protocol, and the legislature
p.000046: implementing it in the Slovak Republic).
p.000046:
p.000046: Slovenia
p.000046: The law on medically assisted reproduction prohibits the creation of embryos for research purposes and
p.000046: cloning of embryos and the use of in vitro fertilization for any purpose other than the birth of a
p.000046: child. The Law on Medically assisted reproduction imposes strict conditions for the use of supernumerary
p.000046: embryos in research. Research can be performed on embryos that are not suitable for reproduction or storage, or on
p.000046: those at the end of the storage period which would be destroyed. Embryos should not be older than 14 days.
p.000046: The authorization of the National Medical Ethics committee should be obtained.
p.000046:
p.000046: Other countries:
p.000046: In Canada and USA there is no federal law regulating research on human embryos and/or the derivation of human embryonic
p.000046: stem cells. The House of Commons in Canada is discussing a draft law, which would regulate such research and allow for
p.000046: the procurement of human ES cells from supernumerary embryos.
p.000046: On 9 August, 2001, the President of the United States announced60 his decision to allow Federal funds to
p.000046: be used for research on existing human embryonic stem cell lines as long as prior to his announcement (1) the
p.000046: derivation process (which commences with the removal of the inner cell mass from the blastocyst) had already been
p.000046: initiated and (2) the embryo from which the stem cell lines was derived no longer had the possibility of
p.000046: development as a human being.
p.000046: In addition, the President established the following criteria that must be met:
p.000046: – The stem cells must have been derived from an embryo that was created for reproductive
p.000046: purposes;
p.000046: – The embryo was no longer needed for these purposes;
p.000046: – Informed consent must have been obtained for the donation of the embryo;
p.000046: – No financial inducements were provided for donation.
p.000046: The National Institutes of Health have implemented the above rules by setting a strategic vision for
p.000046: research using stem cells, including:
p.000046:
p.000046:
p.000046:
p.000046:
p.000046: 60 http://escr.nih.gov/eligibilitycriteria.html
p.000046:
p.000047: 47
p.000047:
p.000047: – Creation of the Human Embryonic Stem cells Registry, which list the human embryonic
p.000047: stem cells that meet the eligibility criteria,
p.000047:
p.000047: – Promoting the number of researchers with expertise in stem cell research. The NIH recognised
p.000047: this as one of the key factors to allow stem cell research to move forward and is currently soliciting grant
p.000047: applications to support training courses to teach researchers how best to grow existing banked stem cells into
p.000047: useful lines.
p.000047:
p.000047: – A number of initiatives to facilitate research on all types of stem cells. In particular, the NIH
p.000047: continues to support research on developing the therapeutic potential of adult stem cells.
p.000047: New federal legislation is under debate in the US Congress. The State of California has passed a law, in
p.000047: September 2002, allowing the procurement of human embryonic stem cells from supernumerary embryos. New legislation
p.000047: authorising the procurement of human ES cells from supernumerary embryos is under discussion in the
p.000047: States of New Jersey and Massachusetts.
p.000047: In Australia a new law is under discussion to allow for the derivation of human ES cells from supernumerary embryos.
p.000047:
p.000047: Laboratories in Singapore, Taiwan, South Korea, China… are actively conducting human ES cell research. Legislation
p.000047: regarding this research is under discussion in some of these countries.
p.000047: Annex D provides further information regarding provisions in non-EU countries relating to human embryonic
p.000047: stem cell research.
p.000047:
p.000047: 3.5. Governance of stem cell research in the context of FP6
p.000047: As stated in the Treaty of the European Union, article 6:
p.000047:
p.000047: “1. The Union is founded on the principles of liberty, democracy, respect for human rights and fundamental freedom, and
p.000047: the rule of law, principles which are common to the Member States.
p.000047:
p.000047: 2. The Union shall respect fundamental rights, as guaranteed by the European Convention for the protection of Human
p.000047: Rights and Fundamental Freedoms signed in Rome on 4 November 1950 and as they result from the constitutional traditions
p.000047: common to the Member States, as general principles of Community law.
p.000047:
p.000047: 3. The Union shall respect the national identities of its Member States.
p.000047:
...
p.000049: – The following fields of research shall not be financed under this programme:
p.000049:
p.000049: – research activities aiming at human cloning for reproductive purposes
p.000049:
p.000049: – research activity intended to modify the genetic heritage of human beings which could make such
p.000049: change heritable66
p.000049: – research activities intended to create human embryos solely for the purpose of research or for the purpose of
p.000049: stem cell procurement, including by means of somatic cell nuclear transfer (often referred to as therapeutic cloning).
p.000049:
p.000049: – In addition, funding of research activities that are prohibited in all the Member States is in all
p.000049: circumstances excluded.
p.000049:
p.000049: – In compliance with the principle of subsidiarity and the diversity of approaches existing in
p.000049: Europe, participants in research projects must conform to current legislation, regulations and ethical rules in
p.000049: the countries where the research will be carried out. In any case, national provisions apply and no research forbidden
p.000049: in any given Member State will be supported by Community funding in that Member State.
p.000049:
p.000049: – Where appropriate, participants in research projects must seek the approval of the relevant
p.000049: national or local ethics committees prior to the start of the RTD activities.
p.000049:
p.000049: – An ethical review will be implemented systematically by the Commission for proposals dealing with
p.000049: ethically sensitive issues, in particular proposals involving the use of human embryos and human embryonic
p.000049: stem cells.
p.000049:
p.000049: Research proposals, which raise sensitive ethical concerns, undergo an ethical review at EC level before funding.
p.000049: The proposals are reviewed by an independent, multidiciplinary and transnational panel, which is
p.000049: established by the DG Research in relation to each call for proposals. The review is conducted
p.000049: independently of the specific research programme and separated from the scientific evaluation. The ethical review
p.000049: aims to ensure that the proposers have identified all ethical issues, which the proposed research may raise,
p.000049: have taken the appropriate measures to fulfil all ethical and/or legal requirements at national and European level
p.000049: and finally have respected the ethical framework defined for the 6th Framework programme for Research.
p.000049:
p.000049: – Any research involving the use of human embryos and human embryonic stem cells, following the ethical
p.000049: review mentioned above, will be submitted to a Regulatory Committee.
p.000049:
p.000049: – In specific cases, an ethical review may take place during the implementation of the project.
p.000049:
p.000049:
p.000049:
p.000049: 65 OJ L294 of 29.10.2002, p. 8.
p.000049: 66 Research relating to cancer treatment of the gonads can be financed.
p.000049:
p.000050: 50
p.000050:
p.000050: – As stated in the Council minutes of 30 September 200267 “The Council and the Commission agree
p.000050: that detailed implementing provisions concerning research activities involving the use of human
p.000050: embryos and human embryonic stem cells…shall be established by 31 December 2003”.
p.000050:
p.000050: The Commission will during that period…not propose to fund such research, with the exception of banked or
p.000050: isolated human embryonic stem cells in culture.
p.000050:
p.000050: 3.6. Social scrutiny and dialogue
p.000050: There are significant differences in national attitudes towards specific techniques and areas of research. In
p.000050: particular, human embryonic stem cell research has recently provoked intense public and political debate. As
p.000050: the life sciences and biotechnology develop, they contribute considerably to securing welfare on the personal and
p.000050: societal levels as well as to creating new opportunities for our economies. At the same time, the general
p.000050: public is increasingly concerned about the social and ethical consequences of these advances in knowledge
p.000050: and techniques as well as about the conditions forming the choices made in these fields.
p.000050:
p.000050: The EGE stressed in its opinion regarding “Ethical aspects of human stem cell research and use” there is a need
p.000050: for continuing dialogue and education to promote the participation of citizens, including patients, in
p.000050: scientific governance, namely in social choices created by new scientific developments”.
p.000050:
p.000050: The need for public dialogue on scientific advances and new technologies has also been highlighted in both
p.000050: the Commission’s communication on “Life Sciences and Biotechnology”, published on 27 January 200268 and the
p.000050: Commission’s action plan on “Science and Society” published in December 200169.
p.000050: In this connection, the European Group on Life Sciences70, set up by the European Research Commissioner Philippe
p.000050: Busquin, organised on 18-19 December 2001,a forum entitled “Stem cells: therapies for the future?”. The aim was
p.000050: to offer a platform at European level for a debate between, on one side, scientists and experts
p.000050: concerned with the feasibility and consequences of stem cell research and, on the other side, a wide range of
p.000050: representatives of society. More than 600 people participated in the event.71. Much of the public discussion that took
p.000050: place, both at the forum itself and by e-mail exchanges concentrated on ethical issues, particularly those relating to
p.000050: the use of human embryos.
p.000050:
p.000050: As for any new potential treatment, the promises of stem cell research may create amongst patients suffering from
p.000050: incurable diseases and their families, high and sometimes unrealistic expectations from science and the imperative
p.000050: of treatment for whatever disease. Many negative research results are not published and may lead to an unbalanced
p.000050: presentation in the media and ultimately affect the dialogue in society. Since failure to deliver the promised cures
p.000050: will have very negative impact on the perception of science by the public, it is vital to communicate
p.000050: the state of the art and future possibilities in a most honest and realistic way. The more science is able to keep its
p.000050: promises, the more it will receive the public recognition necessary to reconcile the expansion of knowledge with social
p.000050: progress. There is a social role
p.000050:
p.000050:
p.000050:
p.000050: 67 Annex F.
p.000050: 68 http://europa.eu.int/comm/biotechnology
p.000050: 69 http://www.cordis.lu/science-society
p.000050: 70 http://europa.eu.int/comm/research/quality-of-life/genetics/en/13.html
p.000050: 71 http://europa.eu.int/comm/research/quality-of-life/stemcells.html
p.000050:
p.000051: 51
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p.000052:
p.000052: Chapter 4: Socio-economic aspects
p.000052:
p.000052:
p.000052:
p.000052: Biotechnology is an area with strong potential economic growth and welfare creation. Stem cell research plays a
p.000052: part in its development. Although considerable sums are available for investment in stem cell research,
p.000052: commercial returns on such investments are for the moment modest. This reflects the fact that most of this work is
p.000052: still at the basic research stage. Thus commercial interests are trying to position themselves for profitability in the
p.000052: future, but still face uncertain research prospects, therapeutic possibilities and the development of
p.000052: a regulatory environment, the latter largely influenced by ethical issues and public concerns.
p.000052:
p.000052: Regarding the exploitation of results of the stem cell research, many of the collaborations in this area with
p.000052: industry involve small, dedicated firms rather than large pharmaceutical companies. Small firms appear to play
p.000052: a key role in transferring technology from the science base into industry. A number of start-up companies have
p.000052: been created as spin-offs from academia in the sector.
p.000052:
p.000052: In 2001 about 30 public and private biotechnology firms were doing stem cells research and about a dozen are currently
p.000052: investigating the potential of both somatic and embryonic stem cells. Few, if any, companies are investing
p.000052: solely in human embryonic stem cell research. According to the Gilder Biotech report June 2001 the venture
p.000052: capital community is at present giving preference to human somatic stem cells, which are reported to be closer to
p.000052: therapeutic application than human embryonic stem cells72.
p.000052: The companies are concerned with the use of stem cells including human embryonic stem cells for:
p.000052:
p.000052: – Novel stem cell based therapies: direct stem cell transplantation, transplantation of stem cell
p.000052: derived differentiated cells, stimulation of the body’s own stem cells via
p.000052: e.g. growth factors or stem cells in gene therapy.
p.000052:
p.000052: – Drug discovery: use of stem cells for drug screening
p.000052:
p.000052: – Services and technologies: screening, isolation of stem cells, preparation and large scale culture
p.000052: of stem cells, storage of stem cells.
p.000052:
p.000052: One of the current framework conditions affecting stem cell research and commercialisation of stem cells therapies is
p.000052: the patenting of human ES cells and their derivatives. On the one hand patent rights are necessary to protect and
p.000052: secure industry’s huge investments to support innovative research and development. On the other hand academic research
p.000052: is stimulated by having free and open access to these cell lines, as they are essential starting materials for their
p.000052: research. Some scientists consider that human embryonic stem cell lines should not be patented at all. The
p.000052: debate on this issue is intense and includes the ethical dimension of this
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 72 Gilder Biotech report, The American Spectator, June 2001, “Adult cells do
p.000052: it better”; http://www.gilderbiotech.com/ArticlesByScott/Op%20Ed/AdultCells.htm
p.000052:
p.000053: 53
p.000053:
p.000053: research. The European Group on Ethics73 in Science and New Technologies (EGE) recommended in their
p.000053: opinion No.16 on patenting of human stem cells that:
p.000053:
p.000053: Isolated stem cells, which have not been modified do not, as product, fulfil the legal requirements,
p.000053: especially with regards to industrial applications, to be seen as patentable. In addition, such isolated cells are so
p.000053: close to the human body, to the foetus or to the embryo they have been isolated from, that their
p.000053: patenting may be considered as a form of commercialisation of the human body.
p.000053: When unmodified stem cell lines are established, they can hardly be considered as a patentable product.
p.000053: Such unmodified stem cell lines do not have indeed a specific use but a very large range of potential undescribed uses.
p.000053: Therefore, to patent such unmodified stem cell lines would also lead to too broad patents.
p.000053: Therefore only stem cell lines which have been modified by in vitro treatments or genetically modified so that they
p.000053: have acquired characteristics for specific industrial application, fulfil the legal requirements for patentability.
p.000053: As to the patentability of processes involving human stem cells, whatever their source, there is no specific ethical
p.000053: obstacle, in so far as they fulfil the requirements of patentability (novelty, inventive step and industrial
p.000053: application).
p.000053:
p.000053: Directive 98/44 on the legal protection of biotechnological inventions, adopted on 6 July 1998,
p.000053: establishes that an element isolated from the human body or otherwise produced by means of a technical
p.000053: process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if
p.000053: the structure of that element is identical to that of a natural element. Furthermore, the directive obliges
p.000053: Member States to consider unpatentable inventions where their commercial exploitation would be contrary to order
p.000053: public or morality. The processes for cloning human beings and uses of human embryos for industrial or
p.000053: commercial purposes are in particular excluded from patentability.
p.000053: The Commission published on 7 October 2002, the first annual report (provided for in article 16c of this Directive)
p.000053: on the implications of patent law for biotechnology and genetic engineering. The report raised the issue
p.000053: related to patentability of human stem cells and cells lines obtained from them.
p.000053: In view of the preparation of future reports provided for in Article 16c of the directive the
p.000053: Commission has set up a group of eminent experts from science, law, and economics, and representatives
p.000053: from the European Patent Office (EPO) and the World Intellectual Property Organisation (WIPO). The group’s
p.000053: mandate is to analyse important issues surrounding biotechnological inventions. It will not touch upon ethical
p.000053: issues, which are the mandate of the European Group on Ethics, but will focus more on legal and technical aspects and
p.000053: on the mutual impact of the legal framework and the research and innovation area. In this light, one of the issues
p.000053: identified and which will be further discussed by the expert committee will be the patentability of human stem cells
p.000053: and cell lines derived from them.
p.000053: The “16c expert group” will meet in May 2003 to discuss patenting of products and methods involving human embryonic
p.000053: stem cell and human ES derivatives. The report of the 16c expert group will be published at the same time as
p.000053: the 2003 annual monitoring report of the Commission is delivered, towards the end of the year.
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: 73 http://europa.eu.int/comm/european_group_ethics/docs/avis16_en.pdf
p.000053:
p.000054: 54
p.000054:
p.000054: While many of the demonstrations of the potential of stem cell research have arisen from academia, the
p.000054: development of this potential i.e. into therapeutic products requires industrial and commercial inputs. For
p.000054: example, industrial involvement will be needed for large scale and good manufacturing production of cell
p.000054: lines, to support multicentre clinical trials, marketing, distribution etc.
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p.000055: 55
p.000055:
p.000055: GLOSSARY
p.000055:
p.000055:
p.000055:
p.000055: Adult stem cell: a stem cell derived from the tissues or organs of an organism after birth (in contrast to embryonic or
p.000055: foetal stem cells)
p.000055:
p.000055: Blastocyst: a hollow ball of 50-100 cells reached after about 5 days embryonic development. The blastocyst consists of
p.000055: a sphere made up of an outer layer of cells (the trophectoderm), a fluid-filled cavity (the blastocoel), and a cluster
p.000055: of cells on the interior (the inner cell mass)
p.000055:
p.000055: Cell culture: growth of cells in vitro on an artificial environment
p.000055:
p.000055: Cell line: cells of common descent continuously cultured in the laboratory is referred to as a cell line
p.000055:
p.000055: Chromosomes: the carrier of genes, the hereditary information which resides in DNA
p.000055:
p.000055: Clone: a cell or organism derived from and genetically identical to another cell or organism
p.000055:
p.000055: Cloning: creating an organism that is genetically identical to another organism, or a cell that is genetically
p.000055: identical to another cell provided that the so-called mother and daughter cells are subsequently separated (see also
p.000055: reproductive and therapeutic cloning)
p.000055:
p.000055: Cloning by somatic cell nuclear transfer: involves replacing an egg’s nucleus with the nucleus of the adult
p.000055: cell to be cloned (or from an embryo or foetus) and then activating the egg’s further development without
p.000055: fertilisation. The egg genetically reprogrammes the transferred nucleus, enabling it to direct
p.000055: development of a whole new organism (Reproductive cloning by cell nuclear transfer).
p.000055:
p.000055: OR the development is stopped at the blastocyst stage and embryonic stem cells are derived from the inner cell mass.
p.000055: These stem cells would be differentiated into desired tissue using a cocktail of various growth and differentiation
p.000055: factors. The generated tissue/cells could then be transplanted into the original donor of the nucleus avoiding
p.000055: rejection (Therapeutic cloning by cell nuclear transfer).
p.000055:
p.000055: Culture medium: the broth that covers cells in a culture dish, which contains nutrients to feed the cells
p.000055: as well as other growth factors that may be added to direct desired changes in the cells
p.000055:
p.000055: Dedifferentiation: the process of inducing a specialised cell to revert towards less
p.000055: differentiated cell.
p.000055:
p.000055: Differentiation: the process whereby an unspecialized cell acquires the features of a specialised cell such
p.000055: as a heart, liver, or muscle cell.
p.000055:
p.000055: DNA: deoxyribonucleic acid, the genetic material; it is composed of long double stranded chains of
p.000055: nucleotides, the basis of genetics
p.000055:
p.000055: Embryo: in humans, the developing organism from the time of fertilization until the end of the eighth week of
p.000055: gestation, when it becomes known as a foetus.
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056: Early embryo: the term “early embryos” covers stages of the development up to the appearance of the
p.000056: primitive streak e. g. until 14 days after fertilisation.
p.000056:
p.000056: Embryonic germ cell: embryonic germ cells are isolated from the primordial germ cells of the gonadal ridge of the 5-10
p.000056: weeks foetus.
p.000056:
p.000056: Embryonic stem cell line: embryonic stem cells, which have been cultured under in vitro
p.000056: conditions that allow proliferation without differentiation for months to years Feeder layer: cells used in co-culture
p.000056: to maintain pluripotent stem cells Fertilization: the process whereby male and female gametes unite
p.000056: Foetus: a developing human from eight weeks after conception to birth
p.000056:
p.000056: Foetal stem cell: a stem cell derived from foetal tissue (in biological terms « embryo » covers all stages of
p.000056: development up to eight weeks of pregnancy, from then on the term « foetus » is used). A distinction is drawn between
p.000056: the foetal germ cells, from which the gametes develop, and the remaining foetal stem cells, which are the foetal
p.000056: somatic cells
p.000056:
p.000056: Gamete: the male sperm or female egg
p.000056:
p.000056: Gene: a functional unit of heredity that is a segment of DNA located in a specific site on a chromosome. A gene directs
p.000056: the formation of an enzyme or other protein.
p.000056:
p.000056: Germ cells: ova and sperm, and their precursors
p.000056:
p.000056: Haematopoïetic stem cell: a stem cell from which all red and white blood cells develop
p.000056:
p.000056: Human embryonic stem cell: pluripotent stem cell derived from the inner cell mass of the blastocyst
p.000056:
p.000056: Implantation: the embedding of a blastocyst in the wall of the uterus. In humans implantation
p.000056: takes place at day 8 after fertilization.
p.000056:
p.000056: In vitro and in vivo: outside and inside the body; in vitro (literally, in glass) generally means in the laboratory
p.000056:
p.000056: In vitro fertilization: the fertilization of an egg by a sperm outside the body
p.000056:
p.000056: Multipotent: Multipotent stem cells are those capable to give rise to several different types of specialised cells
p.000056: constituting a specific tissue or organ.
p.000056:
p.000056: Oocyte: the female egg
p.000056:
p.000056: Plasticity: the ability of stem cells from one tissue to generate the differentiated cell types of another tissue
p.000056:
p.000056: Pluripotent stem cell: a single pluripotent stem cell has the ability to give rise to types of cells
p.000056: that develop from the three germ layers (mesoderm, endoderm and ectoderm) from which all the cells of the
p.000056: body arise. Pluripotent stem cells have the potential to generate into every cell type in the body, but cannot develop
p.000056: into a embryo on their own.
p.000056:
p.000056:
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: Pre-implantation embryo: is an embryo in the stage prior to implantation in the wall of the uterus ; an embryo cannot
p.000057: develop beyond the blastocyst stage without implantation into the womb.
p.000057:
p.000057: Primitive streak: a collection of cells which appears at about 14 days after fertilisation from which the heart, blood
p.000057: and the central nervous system develops
p.000057:
p.000057: Proliferation: expansion of a population of cells by the continuous division of single cells into two
p.000057: identical daughter cells
p.000057:
p.000057: Redifferentiation: the process of inducing a dedifferentiated cell to differentiate into a (different)
p.000057: specialised cell type
p.000057:
p.000057: Somatic cell: cell of the body other than egg or sperm
p.000057:
p.000057: Somatic stem cell: an undifferentiated cell found among differentiated cells in a tissue or organ, which
p.000057: can renew itself and can differentiate to yield the major specialised cell types of the tissue or organ.
p.000057:
p.000057: Somatic cell nuclear transfer: the transfer of a cell nucleus to an egg (or another cell) from which the nucleus has
p.000057: been removed..
p.000057:
...
p.000060: canal; epithelium of the pineal gland, pituitary gland, and adrenal medulla; and cells of the neural
p.000060: crest (which gives rise to various facial structures, pigmented skin cells called melanocytes, and dorsal root
p.000060: ganglia, clusters of nerve cells along the spinal cord). The embryonic “middle” layer, or mesoderm, gives
p.000060: rise to skeletal, smooth, and cardiac muscle; structures of the urogenital systems (kidneys, ureters, gonads, and
p.000060: reproductive ducts); bone marrow and blood; fat; bone, and cartilage; other connective tissues; and the
p.000060: lining of the body cavity. The embryonic “inner” layer, or endoderm, gives rise to the epithelium of the
p.000060: entire digestive tract (excluding the mouth and anal canal); epithelium of the respiratory tract; structures associated
p.000060: with the digestive tract (liver and pancreas); thyroid, parathyroid, and thymus glands; epithelium of the reproductive
p.000060: ducts and glands; epithelium of the urethra and bladder.
p.000060:
p.000060: The term “early embryo” covers stages of development up to the appearance of the primitive streak e.g. until 14 days
p.000060: after fertilisation.
p.000060:
p.000060: 7. Eight week after fertilisation: Foetal stage
p.000060: After about seven weeks’ development, individual organs become recognisable and the embryonic stage is
p.000060: finished and the embryo can properly be described as a foetus. A distinction is drawn between the
p.000060: foetal germ cells from which the gametes (egg cells and sperm) develop and from which “pluripotent” embryonic
p.000060: germ stem cells (EG cells) can be derived during a brief period in the early foetal development and the remaining
p.000060: foetal tissue from which “multipotent” foetal somatic stem cells can be derived.
p.000060:
p.000060: 8. Nine months after fertilisation: birth
p.000060:
p.000060: At around nine months, given normal gestation, the baby is born.
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000061: 61
p.000061:
p.000061: ANNEX B: Possibilities to overcome immune rejection responses in stem cell therapy
p.000061:
p.000061:
p.000061:
p.000061:
p.000061: There are several ways of avoiding or repressing immune rejection of transplanted cells or tissues74:
p.000061: 1) Use of immune-suppressant drugs
p.000061: These drugs, which suppress the activity of the immune system, have been refined over many years, as part of organ
p.000061: transplantation research. However, they are not always effective; they must normally be taken over the lifetime
p.000061: of the patient; and they leave the patient open to infection.
p.000061:
p.000061: 2) Use of “matching” tissues
p.000061: The magnitude of rejection is dependent on the differences between the patients HLA system and that of the donor.
p.000061: For this reason, the differences should be as small as possible. Sometimes during transplantation it is
p.000061: possible to get a matched tissue type, usually from a near relative. This is often sought for bone marrow transplants.
p.000061: Finding a matching donor is unlikely to be a useful approach for most cell-based therapies. However, because stem cells
p.000061: can, in principle, be cultured indefinitely, it might be possible to establish stem cell banks of sufficient size to
p.000061: comprise stem cells with a reasonable (though never perfect) match to the majority of individuals in the
p.000061: population. If this proved possible, the appropriate matching stem cell from the bank could be selected
p.000061: and differentiated into the cell type required for therapy. Several thousand stem cell lines would be needed to
p.000061: obtain matches to the majority of the population comparable with those achieved with matched bone marrow transplants.
p.000061:
p.000061: 3) Generation of immunotolerance
p.000061: Rejection can also be reduced by the generation of immunotolerance. Previous administration of embryonic material,
p.000061: or haematopoietic cells from the stem cell donor, might cause the patient’s immune system to become
p.000061: habituated to some extent and smaller doses of immunosuppressive drugs would be required, or none
p.000061: at all. In addition, research is being carried out into the possibility of preventing an immune reaction by
p.000061: enclosing the cells to be transplanted in a capsule of inert material.
p.000061: The brain is normally a privileged site for transplantation as the brain does not have an immune system,
p.000061: which cause rejection. However, in many pathological situations the blood brain barrier is compromised and
p.000061: therefore the brain may not be as immunoprivileged as previously thought, because immune cells then can enter
p.000061: the brain from blood.
p.000061:
p.000061: 4) Using the individual’s own cells or tissues
p.000061: This would be the surest means of avoiding immune rejection. Adult stem cells isolated from an individual, and then
p.000061: used to treat him or her, offer one possible way of achieving this,
p.000061:
p.000061:
p.000061:
p.000061: 74 House of Lords Select Committee “Report on Stem cell research” http://www.parliament.the-stationery-
p.000061: office.co.uk/pa/ld200102/ldselect/ldstem/83/8301.htm; The Health Council of the Netherlands’ report on “Stem
p.000061: cells for tissue repair. Research on therapy using somatic and embryonic stem cells”, June 2002.
p.000061: http://www.gr.nl/pdf.php?ID=429.
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062: although not in all circumstances. Alternatively somatic cell nuclear transfer (to egg cells or human ES cells in
p.000062: culture) could be used to generate cells or tissues that match those of the patient.
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000063: 63
p.000063:
p.000063: ANNEX C: Examples of available human embryonic stem cell lines
p.000063:
p.000063:
p.000063:
p.000063:
p.000063: Sweden:
p.000063: Karolinska Institute:
p.000063: The US National Institutes of Health (NIH) register 75 contained initially six human ES cell lines from the Karolinska
p.000063: Institute in Stockholm. However, these cell lines are currently not available. The six cell lines have been
p.000063: frozen and the work on thawing, expanding and characterising have now started. Two of these human ES cell lines
p.000063: have been grown on mouse feeder layer. The remaining four preparations were frozen at an earlier stage. However, these
p.000063: four preparations were established using human feeder cells, not mouse cells, and they are therefore very
p.000063: valuable for the future. It is expected that the initial NIH lines thawed should be available for others researchers
p.000063: within the next 12 months.
p.000063: In addition to these original lines, there are at present three other stem cell lines in culture. One is fully
p.000063: characterised and has been expanded to such a degree that this is now being supplied to various groups
p.000063: for collaborative studies. The characterisation of the other two lines is expected to be completed shortly. A
p.000063: cell bank will be established, based on the various stem cell lines established at Karolinska Institute, and
p.000063: these will be available for other scientists76.
p.000063: Sahlgrenska Academy, Gothenburg University in collaboration with Cell Therapeutics Scandinavia, AB:
p.000063: 21 human ES cell lines have so far been established. Four of these have been fully characterized and two
p.000063: of these four fulfil all the criteria for self-renewal and pluripotency of human ES cells. The remaining 17 cell lines
p.000063: have been partially characterized77.
p.000063: Israel:
p.000063: Six human embryonic stem cell lines have been established and characterised at the Rambam Medical Center, Technion-
p.000063: Israel Institute of Technology. Four cell lines are available and have been registrated at the NIH registry.
p.000063: The institute has also cell lines initially produced at the Wisconsin. These cell lines are available for collaborative
p.000063: studies78.
p.000063: Australia:
p.000063: The Australian Senate passed the Research Involving Human Embryos Bill on 5 December, 2002 allowing the destruction
p.000063: of human embryos for research purposes including the procurement of embryonic stem cells from supernumerary
p.000063: embryos. The legislation, pending the decision of State and Territory Parliaments, is expected to take effect beginning
p.000063: of 2003.
p.000063:
p.000063:
p.000063:
p.000063: 75 http://escr.nih.gov/eligibilitycriteria.html
p.000063: 76 Communication from Professor Carlstedt - Duke, Dean of Research, Karolinska Institute, Sweden
p.000063: 77 Communication from Professor Hamberger, Goteborg University, Sweden.
p.000063: 78 Communication from Professor Itskovitz -Eldor, Rambam Medical Centre, Israel.
p.000063:
p.000063:
p.000063:
p.000064: 64
p.000064:
p.000064: Among others researchers at the Monash Institute are expecting to start deriving new human embryonic stem cell lines
p.000064: from supernumerary embryos however the stem cell lines will not be available until 200479.
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
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p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064:
p.000064: 79 Communication from Professor Pera, Monash Institute, Australia.
p.000064:
p.000064:
p.000064:
p.000065: 65
p.000065:
p.000065: ANNEX D: Details regarding provisions in non-EU countries relating to human embryonic stem cell research
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
...
p.000065: - free and informed consent,
p.000065: - no selling or buying of human embryos,
p.000065: - no in vitro culturing of human embryos beyond 2 weeks.
p.000065:
p.000065:
p.000065:
p.000065: 80 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000065: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000065: cell research and use (last update March 2003)
p.000065:
p.000065:
p.000065:
p.000066: 66
p.000066:
p.000066: - separation of the medical teams involved in the IVF treatment and in the stem cell research.
p.000066: The Advisory Committee also considers it ethically permissible to experiment with new technologies to
p.000066: produce ES cells such as nuclear transfer (so-called therapeutic cloning without reproductive purpose).
p.000066: The Advisory committee also recommends that the “National Helsinki committee for genetic research in humans” of the
p.000066: Israel Ministry of Health examine the research protocols. In November 2002, the National Helsinki
p.000066: Committee has accepted in principle to authorise applications in the two above categories.
p.000066:
p.000066: Norway
p.000066: "A bill amending the Act no 56 of 5 August 1994 relating to the application of biotechnology in medicine was
p.000066: assented by the King/sanctioned 13 December 2002. The amendments became effective 1 January 2003 and clarify
p.000066: that the prohibition against research on human embryos also includes research on stem cell lines created by isolating
p.000066: and culturing stem cells from human embryos. The bill also laid down a ban on therapeutic cloning."
p.000066:
p.000066: Switzerland
p.000066: The Federal law on medically assisted reproduction of 18 December 1998 regulates research on embryos. Research on
p.000066: existing embryos is forbidden as well as creation of embryos for research purposes. The donation of embryos
p.000066: is forbidden by the Constitution (article 119).
p.000066: At the end of May 2002, a draft of the Swiss "Federal Act on Research on Supernumerary Embryos and Embryonic Stem
p.000066: Cells" (EFG, Embryonenforschungsgesetz/ Embryonic Research Act) reached the pre-legislative
p.000066: consultation stage. The Federal Council (government) handed over a proposal for the act to parliament end of
p.000066: November 2002. It is the parliament’s aim to enact the law before end of 2003.
p.000066: This draft law proposes to allow research on "surplus" embryos from in vitro fertilisation for purposes of an
p.000066: important scientific interest in the context of reproductive medicine or developmental biology [and not “any
p.000066: possible purpose”] up to the 14th day after fertilisation, and the derivation of embryonic stem cells from
p.000066: supernumerary embryos for research purposes. The EFG draft defines an embryo as "the developing organism from the
p.000066: point of nuclear fusion until the completion of organ development". Interpreting the constitutional paragraph
p.000066: that bans “all kinds of cloning” it explicitly forbids therapeutic cloning.
p.000066:
p.000066:
p.000066: Examples of regulatory regimes in third countries
p.000066:
p.000066: Australia
...
p.000067: allows the funding of the procurement of human embryonic stem cell from supernumerary embryos.
p.000067:
p.000067: India81
p.000067: The National bioethics panel set up by the Indian Department of Biotechnology (Ministry of Science and Technology) has
p.000067: drafted new guidelines for human genomics research that cover the collection and use of human ES cells. The panel
p.000067: recommends that the embryos should not be older than 14 days, both donors should give informed consent and all
p.000067: projects should be approved by the National bioethics panel. The creation of embryos for research purposes
p.000067: should not be undertaken. In the case of commercial exploitation, a sharing of profits with the donors should be
p.000067: organized.
p.000067:
p.000067: Japan
p.000067: The Japanese Parliament enacted the “Human Cloning Regulation Act” on 30 November 2000. The act authorizes
p.000067: research on human embryos in vitro including the procurement of human embryonic stem cells. The detailed
p.000067: implementation of the act is left to the administrative guidelines.
p.000067:
p.000067: Singapore82
p.000067: Singapore's Bioethics Advisory Committee has recommended a complete ban on human reproductive cloning and
p.000067: recommends that human stem cell research and therapeutic cloning be permitted under strict regulation.
p.000067: The regulatory framework should
p.000067: - require the informed voluntary consent of donors,
p.000067: - prohibit the commerce and sale of donated materials, especially supernumerary embryos and
p.000067: - stipulate that no one shall be under a duty to participate in any manner of research on human stem cells to which he
p.000067: has a conscientious objection.
p.000067: The Government has announced that it will follow the recommendations of the Bioethics Advisory Committee
p.000067: published on 21 June 2002. It is the responsibility of the Health Minister to licence such research.
p.000067:
p.000067: South Korea
p.000067: The Government has annonced that that it will approve the use of less than 14 day-old embryos for stem
p.000067: cell research. A new regulation will be submitted to the Korean National Assembly.
p.000067:
p.000067: USA
p.000067: Only publicly funded research is regulated. On 9 August 2001, President Bush announced that federal funds might be
p.000067: awarded for research using human embryonic stem cell lines that meet certain criteria83. Such research is now eligible
p.000067: for federal funding as long as the derivation process (which begins with the destruction of the embryo) was
p.000067: initiated prior to 9 August 2001. These stem cells must have been derived from embryos created for
p.000067: reproductive
p.000067:
p.000067:
p.000067: 81 http://dbtindia.nic.in/consent.html
p.000067: 82 http://www.bioethics-singapore.org/bac/index.jsp
p.000067: 83 http://grants.nih.gov/grants/stem_cells.htm
p.000067:
p.000067:
p.000067:
p.000068: 68
p.000068:
p.000068: purposes and no longer needed for those purposes. In addition, informed consent must have been obtained for the
p.000068: donation of the embryo and the donation must not have involved financial inducements. The NIH Human Embryonic
...
p.000070: December 1998, in particular Article 11 which recommends to prohibit reproductive cloning of human beings, and Article
p.000070: 13 which refers to the responsibilities of researchers as well as of science policy makers;
p.000070:
p.000070: Having regard to national regulations on stem cell and on embryo research and to national ethics bodies opinions, at
p.000070: the European Union level, concerning these subjects;
p.000070:
p.000070: Having regard to the reports of the US National Bioethics Advisory Committee dated September 13, 1999 on
p.000070: the "Ethical Issues on Human Stem Cell Research", the hearings on the same subject by the US Congress, on April 2000
p.000070: and the guidelines published by the Clinton administration on August 26, 2000 to be forwarded to a NIH (National
p.000070: Institutes of Health) scientific review in 2001;
p.000070:
p.000070: Having regard to the Round Table organised by the Group on 26 June 2000 in Brussels with members of the European
p.000070: Parliament, jurists, philosophers, scientists, representatives of industries, of religions, of patients' associations,
p.000070: and of international organisations (Council of Europe, UNESCO, WHO);
p.000070:
p.000070: Having regard to the Hearings of scientific experts on 6 June 2000 and on 2 October 2000, and to the Hearings of
p.000070: representatives of religions on 8 September 2000;
p.000070:
p.000070: Having heard the rapporteurs Anne McLaren and Goran Hermerén;
p.000070:
p.000070:
p.000070:
p.000070: 1 - WHEREAS SCIENTIFIC BACKGROUND
p.000070: 1.1. How to define stem cells?
p.000070:
p.000070: Stem cells are cells that can divide to produce either cells like themselves (self-renewal), or cells
p.000070: of one or several specific differentiated types. Stem cells are not yet fully differentiated and therefore can
p.000070: reconstitute one or several types of tissues.
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000071: 71
p.000071:
p.000071: 1.2. What are the different kinds of stem cells?
p.000071:
p.000071: Different kinds of stem cells can be distinguished according to their potential to differentiate. They are progenitor,
p.000071: multipotent or pluripotent stem cells.
p.000071:
p.000071: • Progenitor stem cells are those whose terminally differentiated progeny consist of a single cell type
p.000071: only. For instance, epidermal stem cells or spermatogonial stem cells can differentiate respectively into
p.000071: only keratinocytes and spermatozoa.
p.000071:
p.000071: • Multipotent stem cells are those which can give rise to several terminally differentiated cell types constituting
p.000071: a specific tissue or organ. Examples are skin stem cells which give rise to epidermal cells, sebaceous glands and
p.000071: hair follicles or haematopoietic stem cells, which give rise to all the diverse blood cells (erythrocytes,
p.000071: lymphocytes, antibody-producing cells and so on), and neural stem cells, which give rise to all the cell types
p.000071: in the nervous system, including glia (sheath cells), and the many different types of neurons.
p.000071:
p.000071: • Pluripotent stem cells are able to give rise to all different cell types in vitro. Nevertheless, they cannot on
p.000071: their own form an embryo. Pluripotent stem cells, which are isolated from primordial germ cells in the
p.000071: foetus, are called: embryonic germ cells ("EG cells"). Those stem cells which are isolated from the inner cell mass of
p.000071: a blastocyst-stage embryo are called: embryonic stem cells ("ES cells”).
p.000071:
p.000071: It should be noted that scientists do not yet all agree on the terminology concerning these types of stem cells.
p.000071:
p.000071:
p.000071: 1.3. What are the characteristics of the different stem cells?
p.000071:
p.000071: Progenitor and multipotent stem cells may persist throughout life. In the foetus, these stem cells are
p.000071: essential to the formation of tissues and organs. In the adult, they replenish tissues whose cells have a limited
p.000071: life span, for instance skin stem cells, intestinal stem cells and haematopoietic stem cells. In the absence of stem
p.000071: cells, our various tissues would wear out and we would die. They are more abundant in the foetus than in the adult.
p.000071: For instance haematopoietic stem cells can be derived from adult bone marrow but they are particularly abundant in
p.000071: umbilical cord blood.
p.000071:
p.000071:
p.000071: Pluripotent stem cells do not occur naturally in the body, which distinguishes them from progenitor and
p.000071: multipotent stem cells.
p.000071:
p.000071:
p.000071:
p.000071: 1.4. Where can stem cells be found?
p.000071:
p.000071: The possible sources of stem cells include adult, foetus and embryos. Accordingly, there are:
p.000071:
p.000071: • Adult stem cells: progenitor and multipotent stem cells are present in adults. Mammals appear to contain some 20
p.000071: major types of somatic stem cells that can generate liver, pancreas, bone and cartilage but they are rather difficult
p.000071: to find and isolate. For instance, access to neural stem cells is limited since they are located in the brain.
p.000071: Haematopoietic stem cells are present in the blood, but their harvesting requires stimulatory treatment of
p.000071: the donor's bone marrow. By and large, adult stem cells are rare and do not have the same developmental potential as
p.000071: embryonic or foetal stem cells.
p.000071:
p.000071: • Stem cells of foetal origin:
p.000071:
p.000071: - Haematopoietic stem cells can be retrieved from the umbilical cord blood.
p.000071:
p.000071:
p.000071:
p.000072: 72
p.000072:
p.000072: - Foetal tissue obtained after pregnancy termination can be used to derive multipotent stem cells like neural stem
p.000072: cells which can be isolated from foetal neural tissue and multiplied in culture, though they have a limited life
p.000072: span. Foetal tissue can also give rise to pluripotent EG cells isolated from the primordial germ cells of
p.000072: the foetus.
p.000072:
p.000072: • Stem cells of embryonic origin: Pluripotent ES cells are those which are derived from an embryo at the blastocyst
p.000072: stage. Embryos could be produced either by in vitro fertilisation (IVF) or by transfer of an adult nucleus to an
p.000072: enucleated egg cell or oocyte (somatic cell nuclear transfer – SCNT).
p.000072:
p.000072:
p.000072: 1.5. Human embryonic development
p.000072:
p.000072: • At two to three days after fertilisation, an embryo consists of identical cells which are totipotent. That is to
p.000072: say that each could give rise to an embryo on its own producing for example identical twins or quadruplets. They are
p.000072: totally unspecialised and have the capacity to differentiate into any of the cells which will constitute the foetus as
p.000072: well as the placenta and membranes around the foetus.
p.000072:
p.000072: • At four to five days after fertilisation (morula stage), the embryo is still made up of
p.000072: unspecialised embryonic cells, but these cells can no longer give rise to an embryo on their own.
p.000072:
p.000072: • At five to seven days after fertilisation (blastocyst stage), a hollow appears in the centre of the morula, and
p.000072: the cells constituting the embryo start to be differentiated into inner and outer cells:
p.000072:
p.000072: - The outer cells will constitute the tissues around the foetus, including the placenta.
p.000072:
p.000072: - The inner cells (20 to 30 cells) will give rise to the foetus itself as well as to some of the surrounding tissues.
p.000072: If these inner cells are isolated and grown in the presence of certain chemical substances (growth
p.000072: factors), pluripotent ES cells can be derived. ES cells are pluripotent, not totipotent since they cannot develop
p.000072: into an embryo on their own. If they are transferred to a uterus, they would neither implant nor develop
p.000072: into an embryo.
p.000072:
p.000072:
p.000072: HISTORICAL BACKGROUND
p.000072:
p.000072: 1.6. Research on animals
p.000072:
p.000072: • Embryonic stem cells
p.000072:
p.000072: Scientists have been working with mouse embryonic stem cells in vitro for more than 20 years, noting very early their
p.000072: remarkable capacity to divide. Some mouse ES cell lines have been cultured for more than 10 years, while retaining
p.000072: their ability to differentiate.
p.000072:
p.000072: There is today some evidence from animal models that multipotent stem cells can be used for somatic
p.000072: therapy. Convincing evidence however has been provided up until now from ES cell-derived, and not adult derived
p.000072: multipotent somatic cells. For instance neural differentiated mouse ES cells when transplanted into a rat
p.000072: spinal cord several days after a traumatic injury can reconstitute neuronal tissue resulting in the
p.000072: (partial) recovery of hindlimb co-ordinated motility. Similarly, selected cardiomyocytes obtained from
p.000072: differentiating ES cells can be grafted into the heart of dystrophic mice to effect myocardial repair. Whether the
p.000072: same cellular derivatives when obtained from adult stem cells would be able to correct for the deficiencies induced in
p.000072: those animal models remains to be determined.
p.000072:
p.000072: Much research on mouse ES cells has also been focused on using these cells to create transgenic animals, in particular
p.000072: as disease models to study human genetic disorders.
p.000072:
p.000072:
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: • Adult stem cells
p.000073:
p.000073: Research is also carried out on mouse adult stem cells. While many scientists had assumed that these cells were
p.000073: programmed to produce specific tissues and were thus no longer able to produce other sorts of tissue, recent studies
p.000073: suggest that adult stem cells may be able to show more malleability than previously believed. For instance, it has been
p.000073: shown that mouse neural stem cells could give rise, in specific conditions of culture, to cells of other organs such as
p.000073: blood, muscle, intestine, liver and heart. Moreover marrow stromal cells can generate astrocytes, a non-neuronal type
p.000073: of cell of the central nervous system and haematopoietic stem cells can give rise to myocytes.
p.000073:
p.000073:
p.000073: 1.7. First grafts of human foetal cells
p.000073:
p.000073: Stem cells in tissues such as skin or blood are able to repair the tissues throughout life. By contrast, the nervous
p.000073: system has a very limited capacity for self-repair because the neural stem cells in the adult brain
p.000073: are few in number and have a poor capacity to generate new neurons for instance to repair injury.
p.000073:
p.000073: Based on the positive results of experimentation on rodents and primates, clinical trials in patients
p.000073: with Parkinson's disease have been performed on around 200 patients over the last 10 years especially in
p.000073: Sweden and the USA. They have shown that the transplantation of neural cells derived from the human foetus can have a
p.000073: therapeutic effect, with an important reduction of the symptoms of the disease in the treated patients. The clinical
p.000073: improvement among these patients has been observed for 6-24 months after transplantation and in some cases for 5-10
p.000073: years. It has recently been shown that 10 years after the transplantation surgery, the transplanted
p.000073: neural cells were still alive and producing dopamine, the compound which is deficient in the brain of patients with
p.000073: Parkinson's disease.
p.000073:
p.000073: However, this therapeutic approach still remains experimental. In addition, the availability of neural foetal tissue
p.000073: is very limited. Five to six aborted foetuses are needed to provide enough neural tissue to treat one
p.000073: Parkinson's patient. That is why new sources of neural cells have been explored in some countries such as the US and
p.000073: Sweden. The aim is to derive neural stem cells from foetuses: these stem cells could be induced to proliferate in
p.000073: culture, providing much greater amounts of neural tissue for transplantation.
p.000073:
p.000073:
p.000073: 1.8. Transplantation of human haematopoietic stem cells
p.000073:
p.000073: The transplantation of human haematopoietic stem cells is routinely used to restore the production of blood cells in
p.000073: patients affected by leukaemia or aplastic anaemia after chemotherapy. There are two sources of
p.000073: haematopoietic stem cells:
p.000073:
p.000073: • Adult stem cells: they can be retrieved under anaesthesia, from the bone marrow of donors, or from the patients
p.000073: themselves (before chemotherapy). Haematopoietic stem cells can also be retrieved directly from the blood, which
p.000073: requires a treatment to induce the passage of stem cells from the bone marrow into the blood circulation.
p.000073:
p.000073: • Stem cells of foetal origin: haematopoietic stem cells can be retrieved from the umbilical cord blood
p.000073: at birth, though care must be taken to ensure that the baby receives enough cord blood. There are at present cord blood
p.000073: banks designated to facilitate haematopoietic stem cell transplantation. The systematic retrieval and cryopreservation
p.000073: of cord blood, at birth, has even been considered in order to have autologous stem cells available in case of later
p.000073: need. Stem cells of foetal origin give rise to less rejection reaction than adult stem cells.
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000074: 74
p.000074:
p.000074: 1.9. Discoveries on human stem cells
p.000074:
p.000074: In the late 70's, the progress of infertility treatment led to the birth of the first child by in vitro fertilisation.
p.000074: The formation of human embryos in vitro during the course of infertility treatment has made possible the
p.000074: study of human embryogenesis following fertilisation, and thus has increased our knowledge of the
p.000074: behaviour and characteristics of embryonic cells at a very early stage.
p.000074:
p.000074: Since 1998, derivation and culture of embryonic and foetal human pluripotent stem cells has been
p.000074: performed, a process which had never been achieved before with human cells. A team at the University of Wisconsin in
p.000074: Madison (USA) announced in November 1998 that it had successfully isolated and cultured for several months
p.000074: cells from 14 human blastocysts obtained from donated surplus embryos produced by in vitro fertilisation. This team
p.000074: established five embryonic ES cell lines with the ability to be grown continuously without losing their capacity to
p.000074: differentiate into the many kinds of cells that constitute the body. At the same time, a team at the Johns Hopkins
p.000074: University in Baltimore (USA) reported that foetal primordial germ cells had been isolated from the gonads of
p.000074: foetuses obtained after pregnancy termination and cultured to make EG cells. Cell lines derived from these
p.000074: cells were grown for many months while maintaining the same capacity to differentiate as the ES cell lines.
p.000074:
p.000074: In 1999, research on adult stem cells revealed that their plasticity was much higher than previously thought. Adult
p.000074: neural stem cells have been reported to give rise occasionally to other cell types including blood cells. A team at the
p.000074: University of Minnesota in Minneapolis, (USA) has shown that cells isolated from the bone marrow of adults or children
p.000074: were able to become neural or muscle cells. Nevertheless, bone marrow cells with such extraordinary malleability are
p.000074: extremely rare. In any case, these recent findings still require to be substantiated.
p.000074:
p.000074: The future challenge is to control the differentiation of human stem cells. It has been shown in animals that by
p.000074: culturing stem cells in the presence of certain chemical substances referred to as "growth factors", it
p.000074: is possible to induce differentiation of specific cell types. Experiments on human stem cells are less advanced but
p.000074: finding ways to direct differentiation is presently an active focus of research.
p.000074:
p.000074:
p.000074:
p.000074: 1.10. What is the main interest of stem cell research and what are the hopes?
p.000074:
p.000074: The main interests at present include:
p.000074:
p.000074: • Basic developmental biology. Culturing of human stem cells offers insights that cannot be studied directly in the
p.000074: human embryo or understood through the use of animal models. For instance, basic research on stem cells could help
p.000074: to understand the causes of birth defects, infertility and pregnancy loss. It could also be useful to
p.000074: give a better understanding of normal and abnormal human development.
p.000074:
p.000074: • Studies of human diseases on animal models. For example, mouse ES cells can be engineered to
p.000074: incorporate human mutated genes known to be associated with particular diseases and then used to make transgenic mouse
p.000074: strains. If such mice express the pathology of the human disease, this confirms the hypothesis that the
p.000074: gene is involved with the etiology of the disease. This strategy also yields an animal model of the
p.000074: human disease which has in most cases a much better predictability for the human situation than more conventional
p.000074: animal models. One of the most illustrative examples of that method is its use in order to address the potential causes
p.000074: of Alzheimer's disease.
p.000074:
p.000074: • Culturing specific differentiated cell lines to be used for pharmacology studies and toxicology
p.000074: testing. This is the most likely immediate biomedical application, making possible the rapid screening of
p.000074: large numbers of chemicals. By measuring how pure populations of specific differentiated cells respond to potential
p.000074: drugs, it will be possible to sort out medicinal products that may be either useful or on the contrary problematic in
p.000074: human medicine.
p.000074:
p.000074:
p.000074:
p.000074:
p.000074:
p.000074:
p.000075: 75
p.000075:
p.000075: • Use of stem cells in gene therapy. Stem cells could be used as vectors for the delivery of gene therapy. One
p.000075: current application in clinical trials is the use of haematopoietic stem cells genetically modified to make them
p.000075: resistant to the HIV (virus responsible for AIDS).
p.000075:
p.000075: • Production of specific cell lines for therapeutic transplantation. If feasible, this would be the
p.000075: most promising therapeutic application of ES cells. Research is being actively pursued, mostly in the mouse, with the
p.000075: aim of directing the differentiation of pluripotent stem cells to produce pure populations of particular cell types
p.000075: to be used for the repair of diseased or damaged tissues. For instance, the aim would be to produce
p.000075: cardiac muscle cells to be used to alleviate ischaemic heart disease, pancreatic islet cells for
p.000075: treatment of diabetes (juvenile onset diabetes mellitus), liver cells for hepatitis, neural cells for degenerative
p.000075: brain diseases such as Parkinson's disease, and perhaps even cells for treating some forms of cancer. The
p.000075: transplantation of stem cells could also help, for example, to repair spinal cord damage which occurs
p.000075: frequently, mainly following trauma (for instance car accidents) and is responsible for paraplegia. Results of that
p.000075: kind of cell therapy on animals are promising, but are still years away from clinical application. Even more remote
p.000075: (possibly decades away) is the prospect of being able to grow whole organs in vitro, but if tissues for
p.000075: the repair of organs become available, it would greatly relieve the existing unsatisfied demand for donated organs for
p.000075: transplantation. In providing a potentially unlimited source of specific clinically important cells such as bone,
p.000075: muscle, liver or blood cells, the use of human stem cells could open the way to a new "regenerative medicine".
p.000075:
p.000075:
p.000075:
p.000075: 1.11. Why is somatic cell nuclear transfer (SCNT) considered?
p.000075:
p.000075: Apart from its interest for basic research, SCNT is considered as a possible strategy, in "regenerative medicine", for
p.000075: the avoidance of immunological problems after transplantation. Neural tissues can sometimes be transplanted
p.000075: from one individual to another without suffering immunological rejection, but for all other tissues, stem
p.000075: cell therapy would need to be accompanied by long-term treatments with immunosuppressive drugs, leading to
p.000075: increased susceptibility to infections and even to cancer.
p.000075:
p.000075: • One approach to avoid this immune rejection problem would involve genetic engineering of stem cells to render
p.000075: them non-antigenic, or immunological manipulation of the patients to render them tolerant.
p.000075:
p.000075: • An alternative approach is based on somatic cell nuclear transfer. It consists of transferring nuclei from the
p.000075: patient's own body cells into donated human or even animal unfertilised eggs from which the nuclei have been removed.
p.000075: If these reconstructed eggs were stimulated for example with electricity to develop to the blastocyst
p.000075: stage, pluripotent stem cells could be derived from them to form cells genetically identical to the patient. No
p.000075: rejection of any transplanted cells would then occur.
p.000075:
p.000075: • Related technology could lead to the cloning of human individuals if the reconstructed embryos were
p.000075: transferred to a woman’s uterus. However, this is contrary to European Community law and prohibited in most European
p.000075: countries.
p.000075:
p.000075:
p.000075: 1.12. Possible origins of the embryos in countries which allow embryo research
p.000075:
p.000075: These embryos are:
p.000075:
p.000075: • either «spare embryos» (i.e. supernumerary embryos) created for infertility treatment to enhance the success rate
p.000075: of IVF, but no longer needed for this purpose. They are intended to be discarded but, instead, may be donated for
p.000075: research by the couples concerned,
p.000075:
p.000075: • or research embryos, created for the sole purpose of research.
p.000075:
p.000075:
p.000075:
p.000075:
p.000075:
p.000076: 76
p.000076:
p.000076: - These may either be produced with donated gametes, i.e. they are derived from the fertilisation in vitro of a human
p.000076: oocyte by a human sperm,
p.000076:
p.000076: - or they may be produced by embryo splitting or nuclear transfer. In the latter case they would be derived by
p.000076: introducing the nucleus of an adult somatic cell into an enucleated human oocyte (sometimes
p.000076: misleadingly termed “embryo cloning” or “therapeutic cloning”).
p.000076:
p.000076:
p.000076:
p.000076: LEGAL BACKGROUND
p.000076:
p.000076: 1.13. Legal situation in the Member States
p.000076:
...
p.000077: the Convention of the Council of Europe for the protection of human rights and dignity of the human being with regard
p.000077: to the application of biology and medicine and by any Member States regulations on this matter”.
p.000077:
p.000077: At this same level, the Charter on Fundamental rights of the European Union approved by the European Council in
p.000077: Biarritz (France) on October 14, 2000 prohibits different kinds of practices possibly related to embryo
p.000077: research, namely “eugenic practices, in particular those aiming at the selection of persons ” and “the
p.000077: reproductive cloning of human beings”.
p.000077:
p.000077:
p.000077:
p.000077: 1.15. US approach related to embryo research and stem cell research
p.000077:
p.000077: The situation in the US contrasts with that in Europe. A substantial difference is a sharp distinction
p.000077: between the public and the private sector. Since 1995 the US Congress has been adopting each year a
p.000077: provision in the Appropriation Bill to prohibit public funding for embryo research. Thus, the National Institutes of
p.000077: Health (NIH) cannot carry out embryo research, which, in the absence of legislation, remains free and beyond control in
p.000077: the private sector.
p.000077:
p.000077: New discoveries concerning the culturing of human stem cells in 1998 have led to the reopening of the debate. The
p.000077: National Bioethics Advisory Committee (NBAC) issued a report on September 1999; hearings took place in 1999 and 2000
p.000077: before the competent Committees of the US Congress and finally the Clinton administration proposed that,
p.000077: under certain conditions, the funding of research to derive and study human ES cells be permitted. New guidelines of
p.000077: the NIH were published in August 2000 according to which research on human ES cells can be publicly funded if two
p.000077: conditions are respected. First, the cells must be taken from frozen spare embryos from fertility clinics and
p.000077: already destined to be discarded; second, Federal funds could not be used to destroy the embryos to
p.000077: obtain the cells; privately funded researchers will have to pass them on to Federally supported
p.000077: scientists.
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000078: 78
p.000078:
p.000078: ETHICAL BACKGROUND
p.000078:
p.000078:
p.000078: 1.16. Main ethical issues with regard to stem cell research
p.000078:
p.000078: Human stem cell research is an example of bioethical value conflicts. On the one hand, the prospect
p.000078: of new therapies, even in the far future, is attractive in offering an alternative to organ and tissue
p.000078: donation. On the other hand, when this research involves the use of human embryos, it raises the question of its
p.000078: ethical acceptability and of the limits and conditions for such research. Embryo research has been extensively debated
p.000078: in the context of research carried out to improve IVF as a treatment for infertility. Embryonic stem cell research
p.000078: raises the following specific additional ethical questions:
p.000078:
p.000078: New types of research to be performed on human embryos. Up until now, research that involved destroying embryos,
p.000078: if allowed, was limited to research on reproduction, contraception or congenital diseases. With human stem
p.000078: cell research, a much wider scope of research is being considered.
p.000078:
p.000078: The use of ES cells and stem cell lines for therapeutic purposes. Human embryos used for research were destroyed after
p.000078: the research was completed and therefore were never used for fertility treatment. What remained was additional
p.000078: knowledge. Human embryonic stem cell research is aimed at creating cell lines with appropriate characteristics, in
p.000078: terms of purity and specificity. There is thus continuity from the embryonic cells to the therapeutic material obtained
p.000078: by culture.
p.000078:
p.000078: The creation of embryos for research purposes. This delicate issue is now raised again since there is a scientific
p.000078: justification of this practice, namely the possibility of producing stem cells identical to the patient's
p.000078: cells and thus avoiding problems of rejection in the context of the future “regenerative medicine”. At
p.000078: the same time, creating human embryos raises new ethical concerns. The ethical acceptability of stem cell
p.000078: research depends not only on the objectives but also on the source of the stem cells; each source raising partly
p.000078: different ethical questions. Those who condemn embryo research in general will not accept this difference, but for
p.000078: those who accept it, this issue is of major importance.
p.000078:
p.000078:
p.000078:
p.000078: 1.17. Ethical issues in transplantation of stem cells
p.000078:
p.000078: Clinical research and potential future applications in this field raise the same ethical issues as those dealt with in
p.000078: the EGE's Opinion on Human Tissue Banking (21/07/1998), concerning the respect of the donor, who should give informed
p.000078: consent to this use of the donated cells, the respect of the autonomy of the patients, their right to safety and to the
p.000078: protection of their private life and the right to a fair and equal access to new therapies.
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000079: 79
p.000079:
p.000079: 2 - OPINION
p.000079: The Group submits the following Opinion:
p.000079:
p.000079: SCOPE OF THE OPINION
p.000079:
p.000079: 2.1 Ethical issues of stem cell research and use for clinical purposes.
p.000079: This Opinion reviews ethical issues raised by human stem cell research and use, in the context of the European Union
p.000079: research policy and European Community public health competence to improve human health and to set high standards for
p.000079: the safety of substances of human origin.
p.000079: With regard to the specific ethical questions related to the patenting of inventions involving human stem cells, on
p.000079: which President Prodi requested an Opinion from the Group on 18 October 2000, this will be made public in Brussels at a
p.000079: later date. The following Opinion therefore excludes the patenting issue.
p.000079:
p.000079: GENERAL APPROACH
p.000079: 2.2. Fundamental ethical principles at stake
p.000079: The fundamental ethical principles applicable are those already recognised in former opinions of the EGE, and more
p.000079: specifically:
p.000079: - the principle of respect for human dignity
p.000079: - the principle of individual autonomy (entailing the giving of informed consent, and respect for privacy and
p.000079: confidentiality of personal data)
p.000079: - the principle of justice and of beneficence (namely with regard to the improvement and protection of health)
p.000079: - the principle of freedom of research (which is to be balanced against other fundamental principles)
p.000079: - the principle of proportionality (including that research methods are necessary to the aims pursued and that no
p.000079: alternative more acceptable methods are available).
p.000079: In addition, the Group considers it important to take into account, based on a precautionary approach,
p.000079: the potential long-term consequences of stem cell research and use for individuals and the society.
p.000079:
p.000079: 2.3. Pluralism and European ethics
p.000079: Pluralism is characteristic of the European Union, mirroring the richness of its tradition and adding a need for mutual
p.000079: respect and tolerance. Respect for different philosophical, moral or legal approaches and for diverse
p.000079: cultures is implicit in the ethical dimension of building a democratic European society.
p.000079: From a legal point of view, respect for pluralism is in line with Article 22 of the Charter on Fundamental Rights on
p.000079: “Cultural, religious and linguistic diversity” and with Article 6 of the Amsterdam Treaty which ensures
p.000079: the protection of fundamental rights at EU level, notably based on international instruments as well as
p.000079: common constitutional traditions, while also stressing the respect for the national identity of all Member States.
p.000079:
p.000079:
p.000079: BASIC RESEARCH ON HUMAN STEMXCELLS
p.000079:
p.000079: 2.4. Principal requirements according to the diverse sources of stem cells.
p.000079: • The retrieval of adult stem cells requires the same conditions as those required in the case of tissue
p.000079: donation, based on respect for the integrity of the human body and the free and informed consent of the donor.
p.000079: • The retrieval of stem cells from the umbilical cord blood after delivery requires that the donor (the woman or
p.000079: the couple concerned) is informed of possible uses of the cells for this specific purpose of research and
p.000079: that the consent of the donor is obtained.
p.000079: • The retrieval of foetal tissues to derive stem cells requires, besides informed consent, that no
p.000079: abortion is induced for the purpose of obtaining the tissues and that the termination timing and the way it is carried
p.000079: out are not influenced by this retrieval.
p.000079: • The derivation of stem cells from embryonic blastocysts raises the issue of the moral status of the human embryo.
p.000079: In the context of European pluralism, it is up to each Member State to forbid or authorise embryo
p.000079: research. In the latter case, respect for human dignity requires regulation of
p.000079:
p.000079:
p.000079:
p.000079:
p.000080: 80
p.000080:
p.000080: embryo research and the provision of guarantees against risks of arbitrary experimentation and
p.000080: instrumentalisation of human embryos.
p.000080:
p.000080: 2.5. Ethical acceptability of the field of the research concerned.
p.000080: The Group notes that in some countries embryo research is forbidden. But when this research is allowed, with the
p.000080: purpose of improving treatment for infertility, it is hard to see any specific argument which would prohibit extending
p.000080: the scope of such research in order to develop new treatments to cure severe diseases or injuries. As in the case of
p.000080: research on infertility, stem cell research aims to alleviate severe human suffering. In any case, the embryos that
p.000080: have been used for research are required to be destroyed. Consequently, there is no argument for excluding funding of
p.000080: this kind of research from the Framework Programme of research of the European Union if it complies with ethical and
p.000080: legal requirements as defined in this programme.
p.000080:
p.000080: 2.6. Public control of ES cell research.
p.000080:
p.000080: The Group deems it essential to underline the sensitivity attached to the use of embryonic stem cells, since this use
p.000080: may change our vision of the respect due to the human embryo.
p.000080:
p.000080: According to the Group, it is crucial to place ES cell research, in the countries where it is permitted, under strict
p.000080: public control by a centralised authority - following, for instance, the pattern of the UK licensing body (the Human
p.000080: Fertilisation and Embryology Authority) - and to provide that authorisations given to such research are highly
p.000080: selective and based on a case by case approach, while ensuring maximum transparency. This must apply whether the
p.000080: research in question is carried out by either the public or the private sector.
p.000080:
p.000080:
p.000080: 2.7. Alternative methods to the creation of embryos for the purpose of stem cell research.
p.000080: The Group considers that the creation of embryos for the sole purpose of research raises serious
p.000080: concerns since it represents a further step in the instrumentalisation of human life.
p.000080:
p.000080: • The Group deems the creation of embryos with gametes donated for the purpose of stem cell
p.000080: procurement ethically unacceptable, when spare embryos represent a ready alternative source.
p.000080:
p.000080: • The Group takes into account interest in performing somatic cell nuclear transfer (SCNT) with the
p.000080: objective of studying the conditions necessary for "reprogramming" adult human cells. It is also aware that, in view
p.000080: of future cell therapy, the creation of embryos by this technique may be the most effective way to
p.000080: derive pluripotent stem cells genetically identical to the patient and consequently to obtain perfectly
p.000080: histocompatible tissues, with the aim of avoiding rejection after transplantation. But, these remote therapeutic
p.000080: perspectives must be balanced against considerations related to the risks of trivialising the use of embryos
p.000080: and exerting pressure on women, as sources of oocytes, and increasing the possibility of their instrumentalisation.
p.000080: Given current high levels of inefficiency in SCNT, the provision of cell lines would require large numbers of oocytes.
p.000080: • In the opinion of the Group, in such a highly sensitive matter, the proportionality principle and
p.000080: a precautionary approach must be applied: it is not sufficient to consider the legitimacy of the pursued aim of
p.000080: alleviating human sufferings, it is also essential to consider the means employed. In particular, the hopes of
p.000080: regenerative medicine are still very speculative and debated among scientists. Calling for prudence, the
p.000080: Group considers that, at present, the creation of embryos by somatic cell nuclear transfer for research on
p.000080: stem cell therapy would be premature, since there is a wide field of research to be carried out with alternative
p.000080: sources of human stem cells (from spare embryos, foetal tissues and adult stem cells).
p.000080:
p.000080: 2.8. Stem cell research in the European Framework Programme of research
p.000080: Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells) requires a
p.000080: specific Community research budget. In particular, EU funding should be devoted to testing the validity
p.000080:
p.000080:
p.000080:
p.000080:
p.000080:
p.000081: 81
p.000081:
p.000081: of recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the
p.000081: results of such research be widely disseminated and not hidden for reasons of commercial interest.
p.000081: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000081: funding for stem cell research. This implies the establishment of appropriate procedures and provision of sufficient
p.000081: means to permit ethical assessment not only before the launching of a project but also in monitoring its
p.000081: implementation.
p.000081:
p.000081: 2.9. Stem cell research and rights of women
p.000081: Women who undergo infertility treatment are subject to high psychological and physical strain. The Group
p.000081: stresses the necessity to ensure that the demand for spare embryos and oocyte donation does not increase
p.000081: the burden on women.
p.000081:
p.000081: CLINICAL RESEARCH ON HUMAN STEMXCELLS
p.000081: The speed with which researchers, throughout the world, are moving to test stem cells in patients is remarkable, even
p.000081: if ES cell transplantation is unlikely to be attempted in the near future. Clinical trials with stem cells other than
p.000081: ES carried out on patients suffering from severe conditions such as Parkinson’s disease, heart disease or diabetes
p.000081: raise the following issues:
p.000081:
p.000081:
p.000081: 2.10. Free and informed consent
p.000081:
p.000081: Free and informed consent is required not only from the donor but also from the recipient as stated in the Group's
p.000081: opinion on Human Tissue Banking (21/07/1998). In each case, it is necessary to inform the donor (the woman or the
p.000081: couple) of the possible use of the embryonal cells for the specific purpose in question before
p.000081: requesting consent.
p.000081:
p.000081: 2.11. Risk-benefit assessment
p.000081: Risk-benefit assessment is crucial in stem cell research, as in any research, but is more difficult as
p.000081: the uncertainties are considerable given the gaps in our knowledge. Attempts to minimise the risks and increase the
p.000081: benefits should include optimising the strategies for safety. It is not enough to test the cultured
p.000081: stem cells or tissues derived from them for bacteria, viruses or toxicity. Safety and security aspects are of utmost
p.000081: importance in the transplantation of genetically modified cells and when stem cells are derived from somatic cells. For
p.000081: example, the risks that transplanted stem cells cause abnormalities or induce creation of tumours or cancer have to be
p.000081: assessed. It is important that the potential benefits for the patients should be taken into account but
p.000081: not exaggerated. The grounds of a precautionary approach need to be taken into account.
p.000081:
p.000081: 2.12. Protection of the health of persons involved in clinical trials
p.000081: The possibility that irreversible and potentially harmful changes are introduced in clinical applications of stem cell
p.000081: research should be minimised. Techniques enhancing the possibilities of reversibility should be used whenever possible.
p.000081: If, for example, genetically modified cells were encapsulated when they are transplanted in order to
p.000081: stimulate neural cell growth, it should be possible for the procedure to be reversed if something goes wrong.
p.000081:
p.000081: 2.13. Scientific evaluation of stem cell use for therapeutic purposes
p.000081:
p.000081: It is urgent to outline strategies and specific requirements for the best evaluation of ethically sound and safe use of
p.000081: stem cells as means of therapy (gene therapy, transplantation, etc.). Such an evaluation should be done in
p.000081: collaboration with the European Agency for the Evaluation of Medicinal Products.
p.000081:
p.000081: 2.14. Anonymity of the donation
p.000081:
p.000081: Steps must be taken to protect and preserve the identity of both the donor and the recipient in stem cell research and
p.000081: use. As stated in the EGE's Opinion on Human Tissue Banking (21/07/1998): "in the interests of anonymity, it
p.000081:
p.000081:
p.000081:
p.000082: 82
p.000082:
p.000082: is prohibited to disclose information that could identify the donor, and the recipient. In general, the donor should
p.000082: not know the identity of the recipient, nor should the recipient know the identity of the donor".
p.000082:
p.000082:
p.000082: 2.15. Stem cell banks and safety
p.000082:
p.000082: Procurement and storage of stem cells in stem cell banks leads to the collection and storage of a growing number of
p.000082: personal and familial data. Cell banks should be regulated at European level in order to facilitate the
p.000082: implementation of a precautionary approach. If unsatisfactory side effects occur, it should be possible to trace donor
p.000082: and recipient and to reach their medical files. Traceability must be one of the conditions required for the
p.000082: authorisation of cell banks at national or European level.
p.000082:
p.000082:
p.000082: 2.16. Stem cell banks and confidentiality
p.000082:
p.000082: In order to reconcile the traceability requirement and the need to protect the donor’s rights - medical confidentiality
p.000082: and privacy - cell banks must take the necessary steps to protect confidentiality of the data.
p.000082:
p.000082:
p.000082: 2.17. Prohibition of commerce in embryos and cadaveric foetal tissue
p.000082: The potential for coercive pressure should not be underestimated when there are financial incentives. Embryos as well
p.000082: as cadaveric foetal tissue must not be bought or sold, and not even offered for sale. Measures should be taken to
p.000082: prevent such commercialisation.
p.000082:
p.000082: 2.18. Export and import of stem cell products
p.000082:
p.000082: Stem cell imports or exports should be licensed by public authorities either at national or European
p.000082: level. Authorisation should be subject to ethical as well as safety rules.
p.000082:
p.000082:
p.000082: 2.19. Education and dialogue
p.000082:
...
p.000091: Commission states that, during that period and pending establishment of the detailed implementing provisions, it will
p.000091: not propose to fund such research, with the exception of the study of banked or isolated human embryonic stem
p.000091: cells in culture. The Commission will monitor the scientific advances and needs as well as the
p.000091: evolution of international and national legislation, regulations and ethical rules regarding this issue, taking into
p.000091: account also the opinions of the European Group of Advisers on the Ethical Implications of Biotechnology (1991–1997)
p.000091: and the opinions of the European Group on Ethics in Science and New Technologies (as from 1998), and report to the
p.000091: European Parliament and the Council by September 2003.
p.000091:
p.000091: The Council states that it intends to discuss this issue at a meeting in September 2003.
p.000091:
p.000091: In the review of any subsequent proposal submitted to Council when applying Article 5 of Decision
p.000091: 1999/468/EC, the Commission recalls its statement concerning Article 5 of Decision 1999/468/EC,
p.000091: according to which the Commission, in order to find a balanced solution, will act in such a way as to
p.000091: avoid going against any predominant position which might emerge within the Council against the appropriateness
p.000091: of an implementing measure (cf. OJ C 203, 17.7.1999, p. 1).
p.000091: The Council notes the intention of the Commission to submit to the Programme Committee, established under the specific
p.000091: research programme "Integrating and strengthening the ERA", procedural modalities concerning research involving
p.000091: the use of human embryos and human embryonic stem cells, in accordance with Article 6, paragraph 3, first indent.
p.000091: The Council further notes the intention of the Commission to present to Council and Parliament in spring
p.000091: 2003 a report on human embryonic stem cell research which will form the basis for discussion at an inter-institutional
p.000091: seminar on bioethics.
p.000091:
p.000091: Taking into account the seminar's outcome, the Commission will submit, based on Article 166(4) of the
p.000091: Treaty, a proposal establishing further guidelines on principles for deciding on the Community funding of research
p.000091: projects involving the use of human embryos and human embryonic stem cells.
p.000091:
p.000091: The Council and the Commission will do their utmost, counting on the support of the European Parliament,
p.000091: to complete the legislative procedure as early as possible and at the latest in December 2003.
p.000091:
p.000091: The Council and the Commission expect that the abovementioned seminar will contribute, as suggested by the European
p.000091: Parliament, to a Europe-wide and well-structured discussion process on the ethical issues of modern
p.000091: biotechnology, particularly on human embryonic stem cells, in order to enhance public understanding.
p.000091:
p.000091: The Council and the Commission note that the ethical acceptability of various research fields is related to the
p.000091: diversity among Member States, and is governed by national law in accordance with the principle of
p.000091: subsidiarity. Moreover, the Commission notes that research using human embryos and human embryonic stem cells is
p.000091: allowed in several Member States, but not in others.
p.000091:
p.000091:
p.000091:
p.000091:
p.000091:
p.000091:
p.000091:
p.000091:
p.000092: 92
p.000092:
p.000092: Re: COST
p.000092: The Council and the Commission share the view of the recent report of the COST Assessment Panel that COST represents a
p.000092: long track record in cross-border cooperation and coordination of nationally financed RTD activities which
p.000092: constitutes a feature of direct relevance to building the European Research Area, while also acknowledging
p.000092: the scope for significant changes to the way COST is organised. Moreover, the Council notes that the Commission
p.000092: will not provide the administrative and scientific secretariat to any COST actions initiated during the
p.000092: Sixth Framework Programme. It notes also that the Commission, recognising that a new COST secretariat may not be fully
p.000092: operational by the end of 2002, is however prepared to continue providing the secretariat to COST actions
p.000092: during a transition period of a few months.
p.000092: The Council and the Commission note that COST is in a process of being reformed and recognise that, following a
p.000092: successful outcome, and given also the recent expansion of COST and the growth in its number of Actions, a substantial
p.000092: grant from the Sixth Framework Programme could be justified.
p.000092: The Council welcomes the Commission's intention to become a partner of COST, with a view to further developing synergy
p.000092: between the Framework Programme and COST. The Council invites the Commission to take appropriate steps in this
p.000092: respect.
p.000092:
p.000092:
p.000092: 4. Specific programme "Structuring the European Research Area" Re: Human resources and mobility
...
p.000093: Article 6(2), when dealing with fusion related aspects. Accordingly, the Commission will take the appropriate steps
p.000093: with a view to amending the Council Decision of 16 December 1980 – as last amended by Council Decision 95/1/EC,
p.000093: Euratom, ECSC of 1 January 1995 – setting up the consultative committee for the fusion programme.
p.000093: Germany 5
p.000093: Austria 2
p.000093: Belgium 2
p.000093: Denmark 2
p.000093: Spain 3
p.000093: Finland 2
p.000093: France 5
p.000093: Greece 2
p.000093: Ireland 2
p.000093: Italy 5
p.000093: Luxembourg 1
p.000093: Netherlands 2
p.000093: Portugal 2
p.000093: United Kingdom 5
p.000093: Sweden 2
p.000093: Switzerland 2
p.000093: Total 44
p.000093: For the adoption of an opinion, the required majority is 23 votes in favour by at least eight delegations.
p.000093:
p.000093:
p.000093:
p.000094: 94
p.000094:
p.000094: 7. Unilateral and bilateral statements relating to the specific programmes
p.000094:
p.000094: (a) Statement by Germany and Austria on Article 3 of the specific programme "Integrating and strengthening the
p.000094: European research area"
p.000094: "Germany and Austria emphasise that they maintain their position that, even after the end of the moratorium in
p.000094: December 2003, research using human embryos and human embryonic stem cells, with the exception of stem cells
p.000094: already held in banks or isolated in culture, should not be funded under the 6th Framework Programme. Moreover,
p.000094: Germany and Austria assume that, under the second specific programme, "Structuring the European Research
p.000094: Area", the Commission will not fund any research activities ineligible for funding on account of the
p.000094: statement for the minutes concerning the first specific programme "Integrating and strengthening
p.000094: the European Research Area"."
p.000094:
p.000094:
p.000094: (b) Statement by Ireland (bioethics)
p.000094: "Ireland, in supporting the adoption of the specific programmes to implement the Sixth Framework Programme
p.000094: for reseach, recalls its statements pertaining to research that cannot be carried out in Ireland. Ireland also
p.000094: recalls the Council statement and its joint statement with Italy, Germany, Portugal and Austria, pertaining to
p.000094: the further elaboration of detailed guidelines on ethical aspects.
p.000094:
p.000094: Ireland welcomes
p.000094:
p.000094: – the progress achieved to date in the elaboration of detailed implementing provisions;
p.000094:
p.000094: – the recognition that its laws, regulations and guidelines apply in respect of any research carried
p.000094: out in Ireland;
p.000094:
p.000094: – the Commission statement regarding non-funding in respect of research activities on human embryos or
p.000094: human embryonic stem cells under the Sixth Framework Programme;
p.000094:
p.000094: – the Commission's intention to present a proposal in 2003, establishing further guidelines on
p.000094: principles for deciding on Community funding of research projects involving the use of human embryos or human
p.000094: embryonic stem cells. In the course of this process, Ireland which shares a number of the concerns
p.000094: expressed by Italy, Germany, Portugal and Austria, will continue to focus on the need to ensure utmost respect for
p.000094: human life and the protection of human dignity;
p.000094:
p.000094: - the establishment of a Regulatory Committee which will consider any project proposals for research
p.000094: funding in ethically sensitive areas."
p.000094:
p.000094:
p.000094: (c) Statement by Italy (bioethics and funding of ITER)
p.000094: "Italy notes the Council and Commission statements on the "bioethics question" in connection with the adoption of
p.000094: the Specific Programmes implementing the Sixth Framework Programme for research 2002-2006. These
p.000094: statements represent significant progress in the endeavour to reach a joint position. In this context Italy
p.000094: considers that only research using
p.000094:
p.000094:
p.000094:
p.000094:
p.000095: 95
p.000095:
p.000095: stem-cells derived from human embryos at a date preceding today or the date of the launch of the Sixth Framework
p.000095: Programme is admissible for Community funding.
p.000095:
p.000095: With regard to the Specific Programme on Integrating and strengthening the European Research Area, Italy
p.000095: must reaffirm its vote against this. In line with the views previously expressed in the Research
p.000095: Council on 10 December 2001 and 3 June 2002 on respect for human dignity and protection of human life, Italy
p.000095: believes that research on human embryos directly or indirectly involving the destruction of the embryo should not be
p.000095: funded under the Sixth Framework Programme.
p.000095:
p.000095: Regarding the EURATOM Specific Programme on Nuclear Energy, Italy takes a favourable view but points out that the
p.000095: funding provided for the ITER facility should not necessarily be interpreted as an endorsement of the scientific and
p.000095: technological choices made in the design of the facility. Italy believes that these choices should
p.000095: be given further scientific consideration before a final decision is taken on the feasibility of the ITER
p.000095: programme."
p.000095:
p.000095:
p.000095: (d) Statement by Portugal (bioethics)
p.000095:
p.000095: "Portugal congratulates the Presidency on the efforts it has made in the field of bioethics, without
p.000095: which it would not have been possible to launch the Sixth Framework Programme for research and technological
p.000095: development and the relevant specific programmes.
p.000095:
p.000095: Portugal can give its agreement to the compromise reached, because it believes that compromise
p.000095: recognises the importance it attaches to issues of bioethics and research as well as the sensitivity of any future
p.000095: financing of research work on human embryo cells and embryonic stem cells. Portugal points out that this is
p.000095: a position shared by a number of other Member States and that it associates itself with many of the concerns which
p.000095: Italy has raised within the Council.
p.000095:
p.000095: Portugal further stresses that research, especially through the Framework Programme, plays an important part in
p.000095: economic growth, employment and social cohesion, particularly in the context of a knowledge-based society and
p.000095: economy."
p.000095:
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Social / Access to Social Goods
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p.000031: of unmodified human stem cell lines.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 48 Communication from Professor Hamberger, Goteborg University, Sweden.
p.000031: 49 http://escr.nih.gov/eligibilitycriteria.html. The following eligibility criteria must be
p.000031: met: (i) the derivation process has been initiated before 9 August 2001; (ii) the stem cells must have been derived
p.000031: from an embryo that was created for reproductive purposes but the embryo was not longer needed for those purposes;
p.000031: (iii) informed consent must have been obtained for the donation of the embryo; (iv) no financial inducements were
p.000031: provided for donation of the embryo.
p.000031: 50 http://escr.nih/
p.000031: 51 http://europa.eu.int/comm/european_group_ethics/docs/avis16_en.pdf
p.000031: 52 http://europa.eu.int/comm/research/life-sciences/egls/index_en.html
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032: “Such registry, which should include information on both embryonic stem cells and embryonic germ
p.000032: cell lines should be publicly accessible. Its aim would be to ensure transparency and thus facilitate
p.000032: access by the research community to the needed biological material for further research”51
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p.000033: 33
p.000033:
p.000033: Chapter 3: Governance of human embryonic stem cell research
p.000033:
p.000033:
p.000033:
p.000033: Human embryonic stem cell research raises complex ethical questions. It confronts scientific progress with ethical
p.000033: concerns and it has triggered an intense public debate on its guiding ethical principles and limitations.
p.000033: The question whether it is ethically defensible to do research on embryonic stem cells can be described
p.000033: as a conflict between different values, between different actors’ rights and obligations, or between the short-
p.000033: and long-term interests of different groups. On the one hand, there is interest in new knowledge that can
p.000033: lead to treatment of hitherto incurable diseases. On the other hand, when this research involves the use of human
p.000033: embryos, it raises the question of ethical values at stake and of the limits and conditions for such research53.
p.000033: Opinions on the legitimacy of experiments using human embryos are divided according to the different ethical,
...
p.000052: capital community is at present giving preference to human somatic stem cells, which are reported to be closer to
p.000052: therapeutic application than human embryonic stem cells72.
p.000052: The companies are concerned with the use of stem cells including human embryonic stem cells for:
p.000052:
p.000052: – Novel stem cell based therapies: direct stem cell transplantation, transplantation of stem cell
p.000052: derived differentiated cells, stimulation of the body’s own stem cells via
p.000052: e.g. growth factors or stem cells in gene therapy.
p.000052:
p.000052: – Drug discovery: use of stem cells for drug screening
p.000052:
p.000052: – Services and technologies: screening, isolation of stem cells, preparation and large scale culture
p.000052: of stem cells, storage of stem cells.
p.000052:
p.000052: One of the current framework conditions affecting stem cell research and commercialisation of stem cells therapies is
p.000052: the patenting of human ES cells and their derivatives. On the one hand patent rights are necessary to protect and
p.000052: secure industry’s huge investments to support innovative research and development. On the other hand academic research
p.000052: is stimulated by having free and open access to these cell lines, as they are essential starting materials for their
p.000052: research. Some scientists consider that human embryonic stem cell lines should not be patented at all. The
p.000052: debate on this issue is intense and includes the ethical dimension of this
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 72 Gilder Biotech report, The American Spectator, June 2001, “Adult cells do
p.000052: it better”; http://www.gilderbiotech.com/ArticlesByScott/Op%20Ed/AdultCells.htm
p.000052:
p.000053: 53
p.000053:
p.000053: research. The European Group on Ethics73 in Science and New Technologies (EGE) recommended in their
p.000053: opinion No.16 on patenting of human stem cells that:
p.000053:
p.000053: Isolated stem cells, which have not been modified do not, as product, fulfil the legal requirements,
p.000053: especially with regards to industrial applications, to be seen as patentable. In addition, such isolated cells are so
p.000053: close to the human body, to the foetus or to the embryo they have been isolated from, that their
p.000053: patenting may be considered as a form of commercialisation of the human body.
p.000053: When unmodified stem cell lines are established, they can hardly be considered as a patentable product.
p.000053: Such unmodified stem cell lines do not have indeed a specific use but a very large range of potential undescribed uses.
p.000053: Therefore, to patent such unmodified stem cell lines would also lead to too broad patents.
...
p.000071: life span, for instance skin stem cells, intestinal stem cells and haematopoietic stem cells. In the absence of stem
p.000071: cells, our various tissues would wear out and we would die. They are more abundant in the foetus than in the adult.
p.000071: For instance haematopoietic stem cells can be derived from adult bone marrow but they are particularly abundant in
p.000071: umbilical cord blood.
p.000071:
p.000071:
p.000071: Pluripotent stem cells do not occur naturally in the body, which distinguishes them from progenitor and
p.000071: multipotent stem cells.
p.000071:
p.000071:
p.000071:
p.000071: 1.4. Where can stem cells be found?
p.000071:
p.000071: The possible sources of stem cells include adult, foetus and embryos. Accordingly, there are:
p.000071:
p.000071: • Adult stem cells: progenitor and multipotent stem cells are present in adults. Mammals appear to contain some 20
p.000071: major types of somatic stem cells that can generate liver, pancreas, bone and cartilage but they are rather difficult
p.000071: to find and isolate. For instance, access to neural stem cells is limited since they are located in the brain.
p.000071: Haematopoietic stem cells are present in the blood, but their harvesting requires stimulatory treatment of
p.000071: the donor's bone marrow. By and large, adult stem cells are rare and do not have the same developmental potential as
p.000071: embryonic or foetal stem cells.
p.000071:
p.000071: • Stem cells of foetal origin:
p.000071:
p.000071: - Haematopoietic stem cells can be retrieved from the umbilical cord blood.
p.000071:
p.000071:
p.000071:
p.000072: 72
p.000072:
p.000072: - Foetal tissue obtained after pregnancy termination can be used to derive multipotent stem cells like neural stem
p.000072: cells which can be isolated from foetal neural tissue and multiplied in culture, though they have a limited life
p.000072: span. Foetal tissue can also give rise to pluripotent EG cells isolated from the primordial germ cells of
p.000072: the foetus.
p.000072:
p.000072: • Stem cells of embryonic origin: Pluripotent ES cells are those which are derived from an embryo at the blastocyst
p.000072: stage. Embryos could be produced either by in vitro fertilisation (IVF) or by transfer of an adult nucleus to an
p.000072: enucleated egg cell or oocyte (somatic cell nuclear transfer – SCNT).
p.000072:
p.000072:
p.000072: 1.5. Human embryonic development
p.000072:
...
p.000078: by culture.
p.000078:
p.000078: The creation of embryos for research purposes. This delicate issue is now raised again since there is a scientific
p.000078: justification of this practice, namely the possibility of producing stem cells identical to the patient's
p.000078: cells and thus avoiding problems of rejection in the context of the future “regenerative medicine”. At
p.000078: the same time, creating human embryos raises new ethical concerns. The ethical acceptability of stem cell
p.000078: research depends not only on the objectives but also on the source of the stem cells; each source raising partly
p.000078: different ethical questions. Those who condemn embryo research in general will not accept this difference, but for
p.000078: those who accept it, this issue is of major importance.
p.000078:
p.000078:
p.000078:
p.000078: 1.17. Ethical issues in transplantation of stem cells
p.000078:
p.000078: Clinical research and potential future applications in this field raise the same ethical issues as those dealt with in
p.000078: the EGE's Opinion on Human Tissue Banking (21/07/1998), concerning the respect of the donor, who should give informed
p.000078: consent to this use of the donated cells, the respect of the autonomy of the patients, their right to safety and to the
p.000078: protection of their private life and the right to a fair and equal access to new therapies.
p.000078:
p.000078:
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p.000079: 79
p.000079:
p.000079: 2 - OPINION
p.000079: The Group submits the following Opinion:
p.000079:
p.000079: SCOPE OF THE OPINION
p.000079:
p.000079: 2.1 Ethical issues of stem cell research and use for clinical purposes.
p.000079: This Opinion reviews ethical issues raised by human stem cell research and use, in the context of the European Union
p.000079: research policy and European Community public health competence to improve human health and to set high standards for
p.000079: the safety of substances of human origin.
p.000079: With regard to the specific ethical questions related to the patenting of inventions involving human stem cells, on
p.000079: which President Prodi requested an Opinion from the Group on 18 October 2000, this will be made public in Brussels at a
p.000079: later date. The following Opinion therefore excludes the patenting issue.
p.000079:
p.000079: GENERAL APPROACH
p.000079: 2.2. Fundamental ethical principles at stake
p.000079: The fundamental ethical principles applicable are those already recognised in former opinions of the EGE, and more
p.000079: specifically:
p.000079: - the principle of respect for human dignity
...
Social / Child
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p.000045: Commission - DG Research - Unit C3 - Ethics and Science"; “Use of embryonic stem cells for therapeutic
p.000045: research”– Report of International Bioethics Committee – UNESCO – 6 April 2001.
p.000045: 59 http://conventions.coe.int/treaty/en/treaties/html/164.htm
p.000045:
p.000046: 46
p.000046:
p.000046: Poland
p.000046: Under the Physician profession’s Act of 1996, human embryos may not be use for non- therapeutic research.
p.000046:
p.000046: Slovak Republic
p.000046: The Slovak Republic’s signing and ratifying the Convention on Human Rights and Biomedicine and
p.000046: the Additional Protocol on the Prohibition of Cloning of the Human Beings, already implemented in the national
p.000046: legislation, together with the older provisions contained in law No. 277/1994 on health care, especially the
p.000046: prohibition of the “non-therapeutic research” to be performed on human embryos and foetuses, were
p.000046: interpreted recently as effectively banning all human cloning (the so-called “reproductive” as well as
p.000046: “therapeutic”).
p.000046: There is a government proposal to amend the Slovak Republic’s Penal Code accordingly - i.e. making human cloning a
p.000046: penal offence in the Slovak Republic (relevant wording being taken basically from the Protocol, and the legislature
p.000046: implementing it in the Slovak Republic).
p.000046:
p.000046: Slovenia
p.000046: The law on medically assisted reproduction prohibits the creation of embryos for research purposes and
p.000046: cloning of embryos and the use of in vitro fertilization for any purpose other than the birth of a
p.000046: child. The Law on Medically assisted reproduction imposes strict conditions for the use of supernumerary
p.000046: embryos in research. Research can be performed on embryos that are not suitable for reproduction or storage, or on
p.000046: those at the end of the storage period which would be destroyed. Embryos should not be older than 14 days.
p.000046: The authorization of the National Medical Ethics committee should be obtained.
p.000046:
p.000046: Other countries:
p.000046: In Canada and USA there is no federal law regulating research on human embryos and/or the derivation of human embryonic
p.000046: stem cells. The House of Commons in Canada is discussing a draft law, which would regulate such research and allow for
p.000046: the procurement of human ES cells from supernumerary embryos.
p.000046: On 9 August, 2001, the President of the United States announced60 his decision to allow Federal funds to
p.000046: be used for research on existing human embryonic stem cell lines as long as prior to his announcement (1) the
p.000046: derivation process (which commences with the removal of the inner cell mass from the blastocyst) had already been
p.000046: initiated and (2) the embryo from which the stem cell lines was derived no longer had the possibility of
p.000046: development as a human being.
p.000046: In addition, the President established the following criteria that must be met:
p.000046: – The stem cells must have been derived from an embryo that was created for reproductive
p.000046: purposes;
p.000046: – The embryo was no longer needed for these purposes;
...
p.000073: haematopoietic stem cells:
p.000073:
p.000073: • Adult stem cells: they can be retrieved under anaesthesia, from the bone marrow of donors, or from the patients
p.000073: themselves (before chemotherapy). Haematopoietic stem cells can also be retrieved directly from the blood, which
p.000073: requires a treatment to induce the passage of stem cells from the bone marrow into the blood circulation.
p.000073:
p.000073: • Stem cells of foetal origin: haematopoietic stem cells can be retrieved from the umbilical cord blood
p.000073: at birth, though care must be taken to ensure that the baby receives enough cord blood. There are at present cord blood
p.000073: banks designated to facilitate haematopoietic stem cell transplantation. The systematic retrieval and cryopreservation
p.000073: of cord blood, at birth, has even been considered in order to have autologous stem cells available in case of later
p.000073: need. Stem cells of foetal origin give rise to less rejection reaction than adult stem cells.
p.000073:
p.000073:
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p.000074: 74
p.000074:
p.000074: 1.9. Discoveries on human stem cells
p.000074:
p.000074: In the late 70's, the progress of infertility treatment led to the birth of the first child by in vitro fertilisation.
p.000074: The formation of human embryos in vitro during the course of infertility treatment has made possible the
p.000074: study of human embryogenesis following fertilisation, and thus has increased our knowledge of the
p.000074: behaviour and characteristics of embryonic cells at a very early stage.
p.000074:
p.000074: Since 1998, derivation and culture of embryonic and foetal human pluripotent stem cells has been
p.000074: performed, a process which had never been achieved before with human cells. A team at the University of Wisconsin in
p.000074: Madison (USA) announced in November 1998 that it had successfully isolated and cultured for several months
p.000074: cells from 14 human blastocysts obtained from donated surplus embryos produced by in vitro fertilisation. This team
p.000074: established five embryonic ES cell lines with the ability to be grown continuously without losing their capacity to
p.000074: differentiate into the many kinds of cells that constitute the body. At the same time, a team at the Johns Hopkins
p.000074: University in Baltimore (USA) reported that foetal primordial germ cells had been isolated from the gonads of
p.000074: foetuses obtained after pregnancy termination and cultured to make EG cells. Cell lines derived from these
p.000074: cells were grown for many months while maintaining the same capacity to differentiate as the ES cell lines.
p.000074:
p.000074: In 1999, research on adult stem cells revealed that their plasticity was much higher than previously thought. Adult
...
Searching for indicator children:
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p.000074: behaviour and characteristics of embryonic cells at a very early stage.
p.000074:
p.000074: Since 1998, derivation and culture of embryonic and foetal human pluripotent stem cells has been
p.000074: performed, a process which had never been achieved before with human cells. A team at the University of Wisconsin in
p.000074: Madison (USA) announced in November 1998 that it had successfully isolated and cultured for several months
p.000074: cells from 14 human blastocysts obtained from donated surplus embryos produced by in vitro fertilisation. This team
p.000074: established five embryonic ES cell lines with the ability to be grown continuously without losing their capacity to
p.000074: differentiate into the many kinds of cells that constitute the body. At the same time, a team at the Johns Hopkins
p.000074: University in Baltimore (USA) reported that foetal primordial germ cells had been isolated from the gonads of
p.000074: foetuses obtained after pregnancy termination and cultured to make EG cells. Cell lines derived from these
p.000074: cells were grown for many months while maintaining the same capacity to differentiate as the ES cell lines.
p.000074:
p.000074: In 1999, research on adult stem cells revealed that their plasticity was much higher than previously thought. Adult
p.000074: neural stem cells have been reported to give rise occasionally to other cell types including blood cells. A team at the
p.000074: University of Minnesota in Minneapolis, (USA) has shown that cells isolated from the bone marrow of adults or children
p.000074: were able to become neural or muscle cells. Nevertheless, bone marrow cells with such extraordinary malleability are
p.000074: extremely rare. In any case, these recent findings still require to be substantiated.
p.000074:
p.000074: The future challenge is to control the differentiation of human stem cells. It has been shown in animals that by
p.000074: culturing stem cells in the presence of certain chemical substances referred to as "growth factors", it
p.000074: is possible to induce differentiation of specific cell types. Experiments on human stem cells are less advanced but
p.000074: finding ways to direct differentiation is presently an active focus of research.
p.000074:
p.000074:
p.000074:
p.000074: 1.10. What is the main interest of stem cell research and what are the hopes?
p.000074:
p.000074: The main interests at present include:
p.000074:
p.000074: • Basic developmental biology. Culturing of human stem cells offers insights that cannot be studied directly in the
p.000074: human embryo or understood through the use of animal models. For instance, basic research on stem cells could help
p.000074: to understand the causes of birth defects, infertility and pregnancy loss. It could also be useful to
p.000074: give a better understanding of normal and abnormal human development.
p.000074:
p.000074: • Studies of human diseases on animal models. For example, mouse ES cells can be engineered to
p.000074: incorporate human mutated genes known to be associated with particular diseases and then used to make transgenic mouse
...
Social / Fetus/Neonate
Searching for indicator foetus:
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p.000003: cell research.
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003: 1 OJ L 294 of 29.10.2002, p. 10.
p.000003: 2 See annex F.
p.000003:
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000004: The purpose of the report is to provide a basis for an open and informed debate at the above- mentioned
p.000004: inter-institutional seminar3.
p.000004: Taking into account the seminar’s outcome, the Commission will submit a proposal establishing
p.000004: further guidelines on principles for deciding on the Community funding of research projects involving the use
p.000004: of human embryos and human embryonic stem cells.
p.000004:
p.000004:
p.000004: The content of the report
p.000004:
p.000004: Characteristics of human stem cells
p.000004:
p.000004: Stem cells have three characteristics that distinguish them from other types of cells:
p.000004:
p.000004: – they are non-differentiated (unspecialised) cells,
p.000004:
p.000004: – they can divide and multiply in their undifferentiated state for a long period.
p.000004:
p.000004: – under certain physiological or experimental conditions, they can also give rise to more specialised
p.000004: differentiated cells such as nerve cells, muscle cells or insulin producing cells etc.
p.000004:
p.000004: Stem cells are found in the early embryo, in the foetus and the umbilical cord blood, and in many tissues of the
p.000004: body after birth and in the adult. These stem cells are the source for tissues and organs of the foetus
p.000004: and for growth and repair in the new born and adult body. As development proceeds beyond the blastocyst stage (5-7 days
p.000004: after fertilisation), the proportion of stem cells decrease in the various tissues and their ability to differentiate
p.000004: into different cell types also decrease at least when they are situated in their natural environment.
p.000004:
p.000004: Classification of human stem cells
p.000004: In this report a distinction is made between three groups of stem cells, referring to their origin and method of
p.000004: derivation:
p.000004:
p.000004: 1. Human embryonic stem cells, which can be derived from a preimplantation embryo at the blastocyst stage.
p.000004:
p.000004: 2. Human embryonic germ cells, which can be isolated from the primordial germ cells of the foetus.
p.000004:
p.000004: 3. Human somatic stem cells, which can be isolated from adult or foetal tissues or organs or from umbilical cord blood.
p.000004:
p.000004: Potential application of human stem cell research
p.000004:
p.000004: Transplantation of haematopoïetic stem cells (from bone marrow, peripheral blood or umbilical cord blood of a
p.000004: healthy donor) has been used for more than a decade to treat e.g. haematological malignancies such as
p.000004: leukemia or congenital immuno-deficiencies.
p.000004:
p.000004:
p.000004: 3 Scientific terms are explained in the glossary.
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005: Autologous transplantation (transplantation of stem cells from the patient’s own bone marrow or peripheral blood) was
p.000005: introduced to rescue the bone marrow of patients who had received high dose of chemotherapy. It is now increasingly
p.000005: being used as primary treatment of other types of cancer such as breast cancer and neuroblastoma. Autologous stem cell
p.000005: transplantation is also used experimentally to treat difficult auto-immune conditions and as a vehicle for gene
p.000005: therapy. Today, over 350 centres in Europe are performing more than 18 000 bone marrow transplants a year4.
p.000005: Novel stem cell based therapies (often called regenerative medicine or cell based therapies) are also being
p.000005: investigated to develop new methods to repair or replace tissues or cells damaged by injuries or diseases and to
p.000005: treat serious chronic diseases, such as diabetes, Parkinson’s, chronic heart failure or stroke and spinal cord
p.000005: injuries. Stem cell research is expected to be equally important for basic science as well as for other specific
...
p.000015: the workshop of 8-10 December 2002 - Brussels - organised by the European Commission - DG Research – Directorate C
p.000015:
p.000015: – U. S. National Institutes of Health (NIH) documents regarding stem cells
p.000015: http://nih.gov/news/stemcell/
p.000015:
p.000015: – Review of recent literature;
p.000015:
p.000015: – Presentations and communications from the scientific community.
p.000015:
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p.000016: 16
p.000016:
p.000016: Chapter 1: Origin and characteristics of human stem cells and potential application for stem cell research
p.000016:
p.000016:
p.000016:
p.000016: 1.1. Origin and characteristics of human stem cells15
p.000016: Stem cells differ from other kind of cells in the body by their unique properties of: 1) being capable of dividing and
p.000016: renewing themselves for long periods, 2) being unspecialised and 3) being able to give rise to specialised cell types.
p.000016: They are found in the early embryo, in the foetus and the umbilical cord blood, and in some (possibly many)
p.000016: tissues of the body after birth and in the adult. These stem cells are the source for tissues and organs of the
p.000016: foetus and for growth and repair in the newborn and adult body. As development proceeds beyond the blastocyst stage
p.000016: (5-7 days after fertilisation), the proportion of stem cells decrease in the various tissues and their
p.000016: ability to differentiate into different cell types also decrease at least when they are situated in their natural
p.000016: environment. (See also chapter 1.2.).
p.000016:
p.000016:
p.000016:
p.000016: Figure 1
p.000016:
p.000016:
p.000016: Fertilisation day 0
p.000016:
p.000016:
p.000016:
p.000016: Day 4-5
p.000016:
p.000016: spermatozoid oocyte
p.000016:
p.000016: ORIIGIIN AND CLASSIIFIICATIIO N OF STEMXCELLS
p.000016:
p.000016:
p.000016: MoMruorlaula
p.000016:
p.000016: Embryonic stem cells
p.000016:
p.000016:
p.000016: Day 5-7
p.000016:
p.000016:
p.000016:
p.000016: From 8th week after fertilisation
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: + umbilical cord blood
p.000016:
p.000016: Human embryonic germ cells
p.000016: (from the primordial germ cells of the foetus )
p.000016:
p.000016:
p.000016: Somatic stem cells
p.000016:
p.000016:
p.000016:
p.000016: Adult
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: 15 The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy using
p.000016: somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429; US NIH, “Stem Cells: A primer” September
p.000016: 2002 http://www.nih.gov/news/stemcell/primer.htm.
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017: Classification of human stem cells:
p.000017:
p.000017: The classification of stem cells is still subject to discussion and the use of different definitions,
p.000017: both in the scientific literature and in public debates, often creates confusion. In this report a distinction is made
p.000017: between three groups of stem cells, referring to their origin and method of derivation16:
p.000017: 1. Human embryonic stem cells
p.000017: Human embryonic stem cells derived from preimplantation embryo at the blastocyst stage (see chapter 2 for
p.000017: further details)
p.000017:
p.000017: 2. Human embryonic germ cells
p.000017: Stem cells with embryonic characteristics have also been isolated from the primordial germ cells of the 5-10 weeks
p.000017: foetus. It is from these embryonic germ cells that the gametes (ova or sperm) normally develop. Research has shown
p.000017: that germ cell derived stem cells have the ability to differentiate into various cell types, although they are
p.000017: more limited in this respect than embryonic stem cells17. It should be noted that these research results
p.000017: have yet to be confirmed by other scientists and that the stability of these cells’ genetic material is still open
p.000017: to discussion.
p.000017:
p.000017: 3. Human somatic stem cells
p.000017: A somatic stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ, which can renew
p.000017: itself and can differentiate to yield the major specialised cell types of the tissue or organ. Although somatic
p.000017: stem cells are rare, many, if not most, tissues in the foetus and human body contain stem cells, which, in
p.000017: their normal location, have the potential to differentiate into a limited number of specific cell types in order to
p.000017: regenerate the tissue in which they normally reside. These stem cells, defined as somatic stem cells, are
p.000017: usually described as “multipotent”. Scientists have found evidence for somatic stem cells in many more
p.000017: tissues than they once thought possible. Examples of the tissues reported to contain stem cells include liver,
p.000017: pancreas, brain, bone marrow, muscle, olfactory epithelium, fat and skin18. Some stem cells remain very active during
p.000017: postnatal life (e.g. haematopoïetic stem cells, skin and gut stem cells), others seem relatively inactive (e.g. stem
p.000017: cells in the brain). It should be mentioned that recent published data have suggested that, for example cells in the
p.000017: liver and even the adult human brain may respond to injury by attempting repopulation19.
p.000017:
p.000017: Possible sources for human somatic stem cells:
p.000017:
p.000017: – Adult tissues and organs: Somatic stem cells can be obtained by means of invasive intervention, such as
p.000017: that used in connection with donation of bone marrow. Haematopoïetic stem cells are routinely collected through
p.000017: the peripheral blood. It has
p.000017:
p.000017:
...
p.000022: establishment of germ-free culture conditions for the derivation and differentiation of specialised cell types.
p.000022:
p.000022: 1.6. Examples of novel stem cell based therapies, which are currently subject to extensive research.
p.000022: Neurological diseases and disorders (see also figure 3)
p.000022:
p.000022: Parkinson’s disease (PD) is caused by a progressive degeneration and loss of dopamine (DA)- producing neurons, which
p.000022: leads to rigidity, hypokinesia (abnormally decreased mobility) and tremor.
p.000022:
p.000022: Scientists are developing a number of strategies for producing dopamine neurons from human stem cells in the laboratory
p.000022: for transplantation into humans with Parkinson’s disease including
p.000022:
p.000022:
p.000022: http://www.parliament.the-stationery-office.co.uk/pa/ld200102/ldselect/ldstem/83/8301.htm ; The Health
p.000022: Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy using somatic and embryonic
p.000022: stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023: the use of neural dopamine producing cells derived from aborted foetuses. Clinical trials in patients with Parkinson’s
p.000023: disease have been performed on around 200 patients over the last 10 years especially in Sweden and in USA. They have
p.000023: shown that the transplantation of neural cells derived from the human foetus can have a therapeutic effect, with an
p.000023: important reduction of the symptoms of the disease in the treated patients28. However, the availability of neural
p.000023: foetal tissue is very limited. Efforts are now being made to expand fetal neural stem cells and control their
p.000023: differentiation into dopaminergic neurons.
p.000023:
p.000023: In a recent study, scientists directed mouse embryonic stem cells to differentiate into dopaminergic
p.000023: neurons by treatment with growth factors and by introducing the gene Nurr1. When transplanted into the brains of
p.000023: a rat model of Parkinson’s disease these stem cell- derived dopaminergic neurons re-innervated the brains
p.000023: of the rat, released dopamine and improved motor function.29
p.000023: The possibility to stimulate the patient’s own stem cells in the brain is also being explored. Self-repair could be
p.000023: induced or augmented with neuro-poïetins - small selective growth factors that trigger repair processes by
p.000023: an individual’s own indigenous population of stem cells30.
p.000023: Heart failure
p.000023:
p.000023: When heart muscle cells (cardiomyocytes) are destroyed, e.g. after a heart attack, functional contracting heart muscle
p.000023: is replaced with non-functional scar tissue. It is hoped that healthy heart muscle cells generated in culture in
p.000023: the laboratory and then transplanted into patients could be used to treat patients with e.g. chronic heart
p.000023: disease.
p.000023:
p.000023: Recent research in mice indicates that mouse cardiomyocytes derived from mouse embryonic stem cells, transplanted
...
p.000023:
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024: Diabetes
p.000024:
p.000024: In people who suffer from type I diabetes, the cells of the pancreas that normally produce insulin are
p.000024: destroyed by the patient’s own immune system. Although diabetics can be treated with daily injections of insulin, these
p.000024: injections enable only intermittent glucose control. As a result, patients with diabetes suffer chronic degeneration of
p.000024: many organs, including the eye, kidney, nerves and blood vessels. In some cases, patients with diabetes have been
p.000024: treated with islet beta cell transplantation. However, poor availability of suitable sources for islet beta cell
p.000024: transplantation from post mortem donors makes this approach difficult as a treatment for the growing numbers of
p.000024: individuals suffering from diabetes.
p.000024:
p.000024: Ways to overcome this problem include deriving islet cells from other sources such as:
p.000024:
p.000024: – Human adult pancreatic duct cells that have been grown successfully in vitro and induced to
p.000024: differentiate, but the ability of these cells to restore blood glucose in vivo is still unproven. This promising
p.000024: line of research is being pursued by several laboratories.
p.000024:
p.000024: – Fetal pancreatic stem cells and ß cell precursor. The identification of endocrine precursor cells
p.000024: in the developing pancreas and the regulation of their differentiation by a specific cellular pathway raises the
p.000024: possibility to grow and differentiate endocrine precursor cells in vitro taken from aborted foetus or by
p.000024: using adult pancreatic duct cells34.
p.000024: – Embryonic stem cells. Research in mice has demonstrated that mouse embryonic stem cells can differentiate
p.000024: into insulin- producing cells and other pancreatic endocrine hormones. The cells self-assemble to form
p.000024: three-dimensional clusters similar in topology to normal pancreatic islets. Transplantation of these cells
p.000024: was found to improve the conditions of experimental animals with diabetes35. New studies indicate that it is possible
p.000024: to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells.
p.000024:
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p.000024:
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p.000024:
p.000024: “Repair of infarcted myocardium by autologous intracoronary mononuclear bone narrow cell
p.000024: transplantation in humans”, Circulation, 2002, 106: 1913-1918.
p.000024: 34 Serup P. et al. “Islet and stem cell transplantation for treating diabetes”, BMJ, 2001, 322:29-32.
p.000024: 35 Lumelsky, N. et al. “Differentiation of embryonic stem cells to insulin - secreting structures similar to
p.000024: pancreas islets”, Science, 2001, 292: 1389-94.
p.000024:
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025: Chapter 2: Human embryonic stem cell research
p.000025:
p.000025:
p.000025:
...
p.000052:
p.000052: One of the current framework conditions affecting stem cell research and commercialisation of stem cells therapies is
p.000052: the patenting of human ES cells and their derivatives. On the one hand patent rights are necessary to protect and
p.000052: secure industry’s huge investments to support innovative research and development. On the other hand academic research
p.000052: is stimulated by having free and open access to these cell lines, as they are essential starting materials for their
p.000052: research. Some scientists consider that human embryonic stem cell lines should not be patented at all. The
p.000052: debate on this issue is intense and includes the ethical dimension of this
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 72 Gilder Biotech report, The American Spectator, June 2001, “Adult cells do
p.000052: it better”; http://www.gilderbiotech.com/ArticlesByScott/Op%20Ed/AdultCells.htm
p.000052:
p.000053: 53
p.000053:
p.000053: research. The European Group on Ethics73 in Science and New Technologies (EGE) recommended in their
p.000053: opinion No.16 on patenting of human stem cells that:
p.000053:
p.000053: Isolated stem cells, which have not been modified do not, as product, fulfil the legal requirements,
p.000053: especially with regards to industrial applications, to be seen as patentable. In addition, such isolated cells are so
p.000053: close to the human body, to the foetus or to the embryo they have been isolated from, that their
p.000053: patenting may be considered as a form of commercialisation of the human body.
p.000053: When unmodified stem cell lines are established, they can hardly be considered as a patentable product.
p.000053: Such unmodified stem cell lines do not have indeed a specific use but a very large range of potential undescribed uses.
p.000053: Therefore, to patent such unmodified stem cell lines would also lead to too broad patents.
p.000053: Therefore only stem cell lines which have been modified by in vitro treatments or genetically modified so that they
p.000053: have acquired characteristics for specific industrial application, fulfil the legal requirements for patentability.
p.000053: As to the patentability of processes involving human stem cells, whatever their source, there is no specific ethical
p.000053: obstacle, in so far as they fulfil the requirements of patentability (novelty, inventive step and industrial
p.000053: application).
p.000053:
p.000053: Directive 98/44 on the legal protection of biotechnological inventions, adopted on 6 July 1998,
p.000053: establishes that an element isolated from the human body or otherwise produced by means of a technical
p.000053: process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if
p.000053: the structure of that element is identical to that of a natural element. Furthermore, the directive obliges
p.000053: Member States to consider unpatentable inventions where their commercial exploitation would be contrary to order
...
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p.000055: 55
p.000055:
p.000055: GLOSSARY
p.000055:
p.000055:
p.000055:
p.000055: Adult stem cell: a stem cell derived from the tissues or organs of an organism after birth (in contrast to embryonic or
p.000055: foetal stem cells)
p.000055:
p.000055: Blastocyst: a hollow ball of 50-100 cells reached after about 5 days embryonic development. The blastocyst consists of
p.000055: a sphere made up of an outer layer of cells (the trophectoderm), a fluid-filled cavity (the blastocoel), and a cluster
p.000055: of cells on the interior (the inner cell mass)
p.000055:
p.000055: Cell culture: growth of cells in vitro on an artificial environment
p.000055:
p.000055: Cell line: cells of common descent continuously cultured in the laboratory is referred to as a cell line
p.000055:
p.000055: Chromosomes: the carrier of genes, the hereditary information which resides in DNA
p.000055:
p.000055: Clone: a cell or organism derived from and genetically identical to another cell or organism
p.000055:
p.000055: Cloning: creating an organism that is genetically identical to another organism, or a cell that is genetically
p.000055: identical to another cell provided that the so-called mother and daughter cells are subsequently separated (see also
p.000055: reproductive and therapeutic cloning)
p.000055:
p.000055: Cloning by somatic cell nuclear transfer: involves replacing an egg’s nucleus with the nucleus of the adult
p.000055: cell to be cloned (or from an embryo or foetus) and then activating the egg’s further development without
p.000055: fertilisation. The egg genetically reprogrammes the transferred nucleus, enabling it to direct
p.000055: development of a whole new organism (Reproductive cloning by cell nuclear transfer).
p.000055:
p.000055: OR the development is stopped at the blastocyst stage and embryonic stem cells are derived from the inner cell mass.
p.000055: These stem cells would be differentiated into desired tissue using a cocktail of various growth and differentiation
p.000055: factors. The generated tissue/cells could then be transplanted into the original donor of the nucleus avoiding
p.000055: rejection (Therapeutic cloning by cell nuclear transfer).
p.000055:
p.000055: Culture medium: the broth that covers cells in a culture dish, which contains nutrients to feed the cells
p.000055: as well as other growth factors that may be added to direct desired changes in the cells
p.000055:
p.000055: Dedifferentiation: the process of inducing a specialised cell to revert towards less
p.000055: differentiated cell.
p.000055:
p.000055: Differentiation: the process whereby an unspecialized cell acquires the features of a specialised cell such
p.000055: as a heart, liver, or muscle cell.
p.000055:
p.000055: DNA: deoxyribonucleic acid, the genetic material; it is composed of long double stranded chains of
p.000055: nucleotides, the basis of genetics
p.000055:
p.000055: Embryo: in humans, the developing organism from the time of fertilization until the end of the eighth week of
p.000055: gestation, when it becomes known as a foetus.
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056: Early embryo: the term “early embryos” covers stages of the development up to the appearance of the
p.000056: primitive streak e. g. until 14 days after fertilisation.
p.000056:
p.000056: Embryonic germ cell: embryonic germ cells are isolated from the primordial germ cells of the gonadal ridge of the 5-10
p.000056: weeks foetus.
p.000056:
p.000056: Embryonic stem cell line: embryonic stem cells, which have been cultured under in vitro
p.000056: conditions that allow proliferation without differentiation for months to years Feeder layer: cells used in co-culture
p.000056: to maintain pluripotent stem cells Fertilization: the process whereby male and female gametes unite
p.000056: Foetus: a developing human from eight weeks after conception to birth
p.000056:
p.000056: Foetal stem cell: a stem cell derived from foetal tissue (in biological terms « embryo » covers all stages of
p.000056: development up to eight weeks of pregnancy, from then on the term « foetus » is used). A distinction is drawn between
p.000056: the foetal germ cells, from which the gametes develop, and the remaining foetal stem cells, which are the foetal
p.000056: somatic cells
p.000056:
p.000056: Gamete: the male sperm or female egg
p.000056:
p.000056: Gene: a functional unit of heredity that is a segment of DNA located in a specific site on a chromosome. A gene directs
p.000056: the formation of an enzyme or other protein.
p.000056:
p.000056: Germ cells: ova and sperm, and their precursors
p.000056:
p.000056: Haematopoïetic stem cell: a stem cell from which all red and white blood cells develop
p.000056:
p.000056: Human embryonic stem cell: pluripotent stem cell derived from the inner cell mass of the blastocyst
p.000056:
p.000056: Implantation: the embedding of a blastocyst in the wall of the uterus. In humans implantation
p.000056: takes place at day 8 after fertilization.
p.000056:
p.000056: In vitro and in vivo: outside and inside the body; in vitro (literally, in glass) generally means in the laboratory
p.000056:
p.000056: In vitro fertilization: the fertilization of an egg by a sperm outside the body
p.000056:
p.000056: Multipotent: Multipotent stem cells are those capable to give rise to several different types of specialised cells
p.000056: constituting a specific tissue or organ.
p.000056:
p.000056: Oocyte: the female egg
p.000056:
p.000056: Plasticity: the ability of stem cells from one tissue to generate the differentiated cell types of another tissue
p.000056:
p.000056: Pluripotent stem cell: a single pluripotent stem cell has the ability to give rise to types of cells
...
p.000057:
p.000057: Proliferation: expansion of a population of cells by the continuous division of single cells into two
p.000057: identical daughter cells
p.000057:
p.000057: Redifferentiation: the process of inducing a dedifferentiated cell to differentiate into a (different)
p.000057: specialised cell type
p.000057:
p.000057: Somatic cell: cell of the body other than egg or sperm
p.000057:
p.000057: Somatic stem cell: an undifferentiated cell found among differentiated cells in a tissue or organ, which
p.000057: can renew itself and can differentiate to yield the major specialised cell types of the tissue or organ.
p.000057:
p.000057: Somatic cell nuclear transfer: the transfer of a cell nucleus to an egg (or another cell) from which the nucleus has
p.000057: been removed..
p.000057:
p.000057: Supernumerary embryo or spare embryo: an embryo created by means of in vitro
p.000057: fertilisation (IVF) for the purpose of assisted reproduction but subsequently not used for it.
p.000057:
p.000057: Totipotent: At two to three days after fertilisation, an embryo consists of identical cells, which are
p.000057: totipotent. That is to say that each could give rise to an embryo on its own producing for example
p.000057: identical twins or quadruplets. They are totally unspecialised and have the capacity to differentiate into any of the
p.000057: cells which will constitute the foetus as well as the placenta and membranes around the foetus.
p.000057:
p.000057: Transdifferentiation: the observation that stem cells from one tissue may be able to differentiate into
p.000057: cells of another tissue
p.000057:
p.000057: Undifferentiated: not having changed to become a specialized cell type
p.000057:
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p.000058:
p.000058:
p.000058: ANNEXES
p.000058:
p.000058:
p.000058:
p.000058:
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p.000058:
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p.000059: 59
p.000059:
p.000059: ANNEX A: Biology of human development
p.000059:
p.000059:
p.000059:
p.000059: The development of the embryo is a continual process of change, which can be described in terms of the following seven
p.000059: stages:
p.000059:
p.000059: 1. Day 0: Fertilisation
p.000059: The female egg (“oocyte”) is fertilised by the male sperm. The egg and sperm each carry half the genes of a normal
...
p.000060: tissues: central nervous system (brain and spinal cord) and peripheral nervous system; outer surface or skin
p.000060: of the organism; cornea and lens of the eye; epithelium that lines the mouth and nasal cavities and the anal
p.000060: canal; epithelium of the pineal gland, pituitary gland, and adrenal medulla; and cells of the neural
p.000060: crest (which gives rise to various facial structures, pigmented skin cells called melanocytes, and dorsal root
p.000060: ganglia, clusters of nerve cells along the spinal cord). The embryonic “middle” layer, or mesoderm, gives
p.000060: rise to skeletal, smooth, and cardiac muscle; structures of the urogenital systems (kidneys, ureters, gonads, and
p.000060: reproductive ducts); bone marrow and blood; fat; bone, and cartilage; other connective tissues; and the
p.000060: lining of the body cavity. The embryonic “inner” layer, or endoderm, gives rise to the epithelium of the
p.000060: entire digestive tract (excluding the mouth and anal canal); epithelium of the respiratory tract; structures associated
p.000060: with the digestive tract (liver and pancreas); thyroid, parathyroid, and thymus glands; epithelium of the reproductive
p.000060: ducts and glands; epithelium of the urethra and bladder.
p.000060:
p.000060: The term “early embryo” covers stages of development up to the appearance of the primitive streak e.g. until 14 days
p.000060: after fertilisation.
p.000060:
p.000060: 7. Eight week after fertilisation: Foetal stage
p.000060: After about seven weeks’ development, individual organs become recognisable and the embryonic stage is
p.000060: finished and the embryo can properly be described as a foetus. A distinction is drawn between the
p.000060: foetal germ cells from which the gametes (egg cells and sperm) develop and from which “pluripotent” embryonic
p.000060: germ stem cells (EG cells) can be derived during a brief period in the early foetal development and the remaining
p.000060: foetal tissue from which “multipotent” foetal somatic stem cells can be derived.
p.000060:
p.000060: 8. Nine months after fertilisation: birth
p.000060:
p.000060: At around nine months, given normal gestation, the baby is born.
p.000060:
p.000060:
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p.000060:
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p.000060:
p.000061: 61
p.000061:
p.000061: ANNEX B: Possibilities to overcome immune rejection responses in stem cell therapy
p.000061:
p.000061:
p.000061:
p.000061:
p.000061: There are several ways of avoiding or repressing immune rejection of transplanted cells or tissues74:
p.000061: 1) Use of immune-suppressant drugs
p.000061: These drugs, which suppress the activity of the immune system, have been refined over many years, as part of organ
p.000061: transplantation research. However, they are not always effective; they must normally be taken over the lifetime
p.000061: of the patient; and they leave the patient open to infection.
p.000061:
p.000061: 2) Use of “matching” tissues
p.000061: The magnitude of rejection is dependent on the differences between the patients HLA system and that of the donor.
p.000061: For this reason, the differences should be as small as possible. Sometimes during transplantation it is
...
p.000071: multipotent or pluripotent stem cells.
p.000071:
p.000071: • Progenitor stem cells are those whose terminally differentiated progeny consist of a single cell type
p.000071: only. For instance, epidermal stem cells or spermatogonial stem cells can differentiate respectively into
p.000071: only keratinocytes and spermatozoa.
p.000071:
p.000071: • Multipotent stem cells are those which can give rise to several terminally differentiated cell types constituting
p.000071: a specific tissue or organ. Examples are skin stem cells which give rise to epidermal cells, sebaceous glands and
p.000071: hair follicles or haematopoietic stem cells, which give rise to all the diverse blood cells (erythrocytes,
p.000071: lymphocytes, antibody-producing cells and so on), and neural stem cells, which give rise to all the cell types
p.000071: in the nervous system, including glia (sheath cells), and the many different types of neurons.
p.000071:
p.000071: • Pluripotent stem cells are able to give rise to all different cell types in vitro. Nevertheless, they cannot on
p.000071: their own form an embryo. Pluripotent stem cells, which are isolated from primordial germ cells in the
p.000071: foetus, are called: embryonic germ cells ("EG cells"). Those stem cells which are isolated from the inner cell mass of
p.000071: a blastocyst-stage embryo are called: embryonic stem cells ("ES cells”).
p.000071:
p.000071: It should be noted that scientists do not yet all agree on the terminology concerning these types of stem cells.
p.000071:
p.000071:
p.000071: 1.3. What are the characteristics of the different stem cells?
p.000071:
p.000071: Progenitor and multipotent stem cells may persist throughout life. In the foetus, these stem cells are
p.000071: essential to the formation of tissues and organs. In the adult, they replenish tissues whose cells have a limited
p.000071: life span, for instance skin stem cells, intestinal stem cells and haematopoietic stem cells. In the absence of stem
p.000071: cells, our various tissues would wear out and we would die. They are more abundant in the foetus than in the adult.
p.000071: For instance haematopoietic stem cells can be derived from adult bone marrow but they are particularly abundant in
p.000071: umbilical cord blood.
p.000071:
p.000071:
p.000071: Pluripotent stem cells do not occur naturally in the body, which distinguishes them from progenitor and
p.000071: multipotent stem cells.
p.000071:
p.000071:
p.000071:
p.000071: 1.4. Where can stem cells be found?
p.000071:
p.000071: The possible sources of stem cells include adult, foetus and embryos. Accordingly, there are:
p.000071:
p.000071: • Adult stem cells: progenitor and multipotent stem cells are present in adults. Mammals appear to contain some 20
p.000071: major types of somatic stem cells that can generate liver, pancreas, bone and cartilage but they are rather difficult
p.000071: to find and isolate. For instance, access to neural stem cells is limited since they are located in the brain.
p.000071: Haematopoietic stem cells are present in the blood, but their harvesting requires stimulatory treatment of
p.000071: the donor's bone marrow. By and large, adult stem cells are rare and do not have the same developmental potential as
p.000071: embryonic or foetal stem cells.
p.000071:
p.000071: • Stem cells of foetal origin:
p.000071:
p.000071: - Haematopoietic stem cells can be retrieved from the umbilical cord blood.
p.000071:
p.000071:
p.000071:
p.000072: 72
p.000072:
p.000072: - Foetal tissue obtained after pregnancy termination can be used to derive multipotent stem cells like neural stem
p.000072: cells which can be isolated from foetal neural tissue and multiplied in culture, though they have a limited life
p.000072: span. Foetal tissue can also give rise to pluripotent EG cells isolated from the primordial germ cells of
p.000072: the foetus.
p.000072:
p.000072: • Stem cells of embryonic origin: Pluripotent ES cells are those which are derived from an embryo at the blastocyst
p.000072: stage. Embryos could be produced either by in vitro fertilisation (IVF) or by transfer of an adult nucleus to an
p.000072: enucleated egg cell or oocyte (somatic cell nuclear transfer – SCNT).
p.000072:
p.000072:
p.000072: 1.5. Human embryonic development
p.000072:
p.000072: • At two to three days after fertilisation, an embryo consists of identical cells which are totipotent. That is to
p.000072: say that each could give rise to an embryo on its own producing for example identical twins or quadruplets. They are
p.000072: totally unspecialised and have the capacity to differentiate into any of the cells which will constitute the foetus as
p.000072: well as the placenta and membranes around the foetus.
p.000072:
p.000072: • At four to five days after fertilisation (morula stage), the embryo is still made up of
p.000072: unspecialised embryonic cells, but these cells can no longer give rise to an embryo on their own.
p.000072:
p.000072: • At five to seven days after fertilisation (blastocyst stage), a hollow appears in the centre of the morula, and
p.000072: the cells constituting the embryo start to be differentiated into inner and outer cells:
p.000072:
p.000072: - The outer cells will constitute the tissues around the foetus, including the placenta.
p.000072:
p.000072: - The inner cells (20 to 30 cells) will give rise to the foetus itself as well as to some of the surrounding tissues.
p.000072: If these inner cells are isolated and grown in the presence of certain chemical substances (growth
p.000072: factors), pluripotent ES cells can be derived. ES cells are pluripotent, not totipotent since they cannot develop
p.000072: into an embryo on their own. If they are transferred to a uterus, they would neither implant nor develop
p.000072: into an embryo.
p.000072:
p.000072:
p.000072: HISTORICAL BACKGROUND
p.000072:
p.000072: 1.6. Research on animals
p.000072:
p.000072: • Embryonic stem cells
p.000072:
p.000072: Scientists have been working with mouse embryonic stem cells in vitro for more than 20 years, noting very early their
p.000072: remarkable capacity to divide. Some mouse ES cell lines have been cultured for more than 10 years, while retaining
p.000072: their ability to differentiate.
p.000072:
p.000072: There is today some evidence from animal models that multipotent stem cells can be used for somatic
p.000072: therapy. Convincing evidence however has been provided up until now from ES cell-derived, and not adult derived
p.000072: multipotent somatic cells. For instance neural differentiated mouse ES cells when transplanted into a rat
p.000072: spinal cord several days after a traumatic injury can reconstitute neuronal tissue resulting in the
p.000072: (partial) recovery of hindlimb co-ordinated motility. Similarly, selected cardiomyocytes obtained from
...
p.000073: programmed to produce specific tissues and were thus no longer able to produce other sorts of tissue, recent studies
p.000073: suggest that adult stem cells may be able to show more malleability than previously believed. For instance, it has been
p.000073: shown that mouse neural stem cells could give rise, in specific conditions of culture, to cells of other organs such as
p.000073: blood, muscle, intestine, liver and heart. Moreover marrow stromal cells can generate astrocytes, a non-neuronal type
p.000073: of cell of the central nervous system and haematopoietic stem cells can give rise to myocytes.
p.000073:
p.000073:
p.000073: 1.7. First grafts of human foetal cells
p.000073:
p.000073: Stem cells in tissues such as skin or blood are able to repair the tissues throughout life. By contrast, the nervous
p.000073: system has a very limited capacity for self-repair because the neural stem cells in the adult brain
p.000073: are few in number and have a poor capacity to generate new neurons for instance to repair injury.
p.000073:
p.000073: Based on the positive results of experimentation on rodents and primates, clinical trials in patients
p.000073: with Parkinson's disease have been performed on around 200 patients over the last 10 years especially in
p.000073: Sweden and the USA. They have shown that the transplantation of neural cells derived from the human foetus can have a
p.000073: therapeutic effect, with an important reduction of the symptoms of the disease in the treated patients. The clinical
p.000073: improvement among these patients has been observed for 6-24 months after transplantation and in some cases for 5-10
p.000073: years. It has recently been shown that 10 years after the transplantation surgery, the transplanted
p.000073: neural cells were still alive and producing dopamine, the compound which is deficient in the brain of patients with
p.000073: Parkinson's disease.
p.000073:
p.000073: However, this therapeutic approach still remains experimental. In addition, the availability of neural foetal tissue
p.000073: is very limited. Five to six aborted foetuses are needed to provide enough neural tissue to treat one
p.000073: Parkinson's patient. That is why new sources of neural cells have been explored in some countries such as the US and
p.000073: Sweden. The aim is to derive neural stem cells from foetuses: these stem cells could be induced to proliferate in
p.000073: culture, providing much greater amounts of neural tissue for transplantation.
p.000073:
p.000073:
p.000073: 1.8. Transplantation of human haematopoietic stem cells
p.000073:
p.000073: The transplantation of human haematopoietic stem cells is routinely used to restore the production of blood cells in
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p.000022: for the duration of the recipient’s life and survive in the recipient after transplantation. Methods to improve and
p.000022: properly assess the viability and functioning of the differentiated cells need to be worked out.
p.000022:
p.000022: – Culture conditions: Good manufacturing practice (GMP) needs to be defined including the
p.000022: establishment of germ-free culture conditions for the derivation and differentiation of specialised cell types.
p.000022:
p.000022: 1.6. Examples of novel stem cell based therapies, which are currently subject to extensive research.
p.000022: Neurological diseases and disorders (see also figure 3)
p.000022:
p.000022: Parkinson’s disease (PD) is caused by a progressive degeneration and loss of dopamine (DA)- producing neurons, which
p.000022: leads to rigidity, hypokinesia (abnormally decreased mobility) and tremor.
p.000022:
p.000022: Scientists are developing a number of strategies for producing dopamine neurons from human stem cells in the laboratory
p.000022: for transplantation into humans with Parkinson’s disease including
p.000022:
p.000022:
p.000022: http://www.parliament.the-stationery-office.co.uk/pa/ld200102/ldselect/ldstem/83/8301.htm ; The Health
p.000022: Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy using somatic and embryonic
p.000022: stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023: the use of neural dopamine producing cells derived from aborted foetuses. Clinical trials in patients with Parkinson’s
p.000023: disease have been performed on around 200 patients over the last 10 years especially in Sweden and in USA. They have
p.000023: shown that the transplantation of neural cells derived from the human foetus can have a therapeutic effect, with an
p.000023: important reduction of the symptoms of the disease in the treated patients28. However, the availability of neural
p.000023: foetal tissue is very limited. Efforts are now being made to expand fetal neural stem cells and control their
p.000023: differentiation into dopaminergic neurons.
p.000023:
p.000023: In a recent study, scientists directed mouse embryonic stem cells to differentiate into dopaminergic
p.000023: neurons by treatment with growth factors and by introducing the gene Nurr1. When transplanted into the brains of
p.000023: a rat model of Parkinson’s disease these stem cell- derived dopaminergic neurons re-innervated the brains
p.000023: of the rat, released dopamine and improved motor function.29
p.000023: The possibility to stimulate the patient’s own stem cells in the brain is also being explored. Self-repair could be
p.000023: induced or augmented with neuro-poïetins - small selective growth factors that trigger repair processes by
p.000023: an individual’s own indigenous population of stem cells30.
p.000023: Heart failure
p.000023:
p.000023: When heart muscle cells (cardiomyocytes) are destroyed, e.g. after a heart attack, functional contracting heart muscle
...
p.000039: fertilisation technique or pre-implantation diagnosis techniques. Therefore, the isolation of human ES cells from
p.000039: supernumerary embryos is forbidden. The importation of
p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040: human ES cells is not explicitly forbidden. However, the Danish government will give its opinion on human
p.000040: embryonic stem cell research in spring 2003, and has recommended that no research with human ES cell lines should be
p.000040: commenced until the government has presented its decision to Parliament (See also chapter 3.3)
p.000040:
p.000040: France
p.000040: Under the Bioethics Law of 1994, research on human embryos in vitro is forbidden except for research which does not
p.000040: harm the embryo. The import and use of human ES cell lines derived from supernumerary embryos is not explicitly
p.000040: prohibited but the authorisation is still under discussion. A revision of the Bioethics law is under discussion
p.000040: (see chapter 3.3)
p.000040:
p.000040: Ireland
p.000040: There is no legislation dealing with research on embryos. However, the Irish constitution of 1937 (as amended in
p.000040: 1983) provides that “the State acknowledges the right to life of the unborn and, with due regard to the
p.000040: equal right to life of the mother, guarantees in its laws to respect, and, as far as practicable, by its laws to defend
p.000040: and vindicate that right”.
p.000040:
p.000040: Spain
p.000040: The laws of 1988 on Assisted Reproduction Techniques and on donation and use of embryos and foetuses or their cells
p.000040: authorises research on in vitro human embryos biologically non- viable under certain conditions. There is no clear
p.000040: interpretation of the concept of a non-viable embryo. Concerning viable human embryos, only research for the
p.000040: benefit of the concerned embryos is allowed. A revision of the law is under discussion (see chapter 3.3)
p.000040:
p.000040: 4. No specific legislation regarding human embryo research
p.000040: Belgium
p.000040: The Royal decree of 1999 fixes the requirement for in vitro fertilisation centres. There is no specific legislation
p.000040: on research but the current practice is that research must only be performed at in vitro fertilisation
p.000040: centres following approval from the local ethics committees. A new bill is under discussion (see chapter 3.3).
p.000040:
p.000040: Italy
p.000040: Italy has not enacted legislation.
p.000040: The Italian National Bioethics Committee has adopted an advice on “the therapeutic use of stem cells”. A majority
p.000040: of the members considered the research on human supernumerary embryos for the derivation of human ES cells as
p.000040: legitimate.
p.000040:
p.000040: Luxembourg
p.000040: There is no legislation covering human embryo research.
p.000040:
p.000040: Portugal
p.000040: Portugal has not enacted legislation but has ratified the Convention of the Council of Europe on Human Rights and
p.000040: Biomedicine signed in Oviedo on 4 April 1997, which prohibit the creation of human embryos for research
...
p.000045:
p.000045: Malta
p.000045: There is no specific regulation regarding human embryo research.
p.000045:
p.000045:
p.000045: 58 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000045: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000045: cell research and use (last update March 2003); “Candidate Countries legislation related to ethical issues in science
p.000045: and research” Proceedings of the workshop of 8-10 December 2002 - Brussels - organised by the European
p.000045: Commission - DG Research - Unit C3 - Ethics and Science"; “Use of embryonic stem cells for therapeutic
p.000045: research”– Report of International Bioethics Committee – UNESCO – 6 April 2001.
p.000045: 59 http://conventions.coe.int/treaty/en/treaties/html/164.htm
p.000045:
p.000046: 46
p.000046:
p.000046: Poland
p.000046: Under the Physician profession’s Act of 1996, human embryos may not be use for non- therapeutic research.
p.000046:
p.000046: Slovak Republic
p.000046: The Slovak Republic’s signing and ratifying the Convention on Human Rights and Biomedicine and
p.000046: the Additional Protocol on the Prohibition of Cloning of the Human Beings, already implemented in the national
p.000046: legislation, together with the older provisions contained in law No. 277/1994 on health care, especially the
p.000046: prohibition of the “non-therapeutic research” to be performed on human embryos and foetuses, were
p.000046: interpreted recently as effectively banning all human cloning (the so-called “reproductive” as well as
p.000046: “therapeutic”).
p.000046: There is a government proposal to amend the Slovak Republic’s Penal Code accordingly - i.e. making human cloning a
p.000046: penal offence in the Slovak Republic (relevant wording being taken basically from the Protocol, and the legislature
p.000046: implementing it in the Slovak Republic).
p.000046:
p.000046: Slovenia
p.000046: The law on medically assisted reproduction prohibits the creation of embryos for research purposes and
p.000046: cloning of embryos and the use of in vitro fertilization for any purpose other than the birth of a
p.000046: child. The Law on Medically assisted reproduction imposes strict conditions for the use of supernumerary
p.000046: embryos in research. Research can be performed on embryos that are not suitable for reproduction or storage, or on
p.000046: those at the end of the storage period which would be destroyed. Embryos should not be older than 14 days.
p.000046: The authorization of the National Medical Ethics committee should be obtained.
p.000046:
p.000046: Other countries:
p.000046: In Canada and USA there is no federal law regulating research on human embryos and/or the derivation of human embryonic
p.000046: stem cells. The House of Commons in Canada is discussing a draft law, which would regulate such research and allow for
p.000046: the procurement of human ES cells from supernumerary embryos.
p.000046: On 9 August, 2001, the President of the United States announced60 his decision to allow Federal funds to
...
p.000073: 1.7. First grafts of human foetal cells
p.000073:
p.000073: Stem cells in tissues such as skin or blood are able to repair the tissues throughout life. By contrast, the nervous
p.000073: system has a very limited capacity for self-repair because the neural stem cells in the adult brain
p.000073: are few in number and have a poor capacity to generate new neurons for instance to repair injury.
p.000073:
p.000073: Based on the positive results of experimentation on rodents and primates, clinical trials in patients
p.000073: with Parkinson's disease have been performed on around 200 patients over the last 10 years especially in
p.000073: Sweden and the USA. They have shown that the transplantation of neural cells derived from the human foetus can have a
p.000073: therapeutic effect, with an important reduction of the symptoms of the disease in the treated patients. The clinical
p.000073: improvement among these patients has been observed for 6-24 months after transplantation and in some cases for 5-10
p.000073: years. It has recently been shown that 10 years after the transplantation surgery, the transplanted
p.000073: neural cells were still alive and producing dopamine, the compound which is deficient in the brain of patients with
p.000073: Parkinson's disease.
p.000073:
p.000073: However, this therapeutic approach still remains experimental. In addition, the availability of neural foetal tissue
p.000073: is very limited. Five to six aborted foetuses are needed to provide enough neural tissue to treat one
p.000073: Parkinson's patient. That is why new sources of neural cells have been explored in some countries such as the US and
p.000073: Sweden. The aim is to derive neural stem cells from foetuses: these stem cells could be induced to proliferate in
p.000073: culture, providing much greater amounts of neural tissue for transplantation.
p.000073:
p.000073:
p.000073: 1.8. Transplantation of human haematopoietic stem cells
p.000073:
p.000073: The transplantation of human haematopoietic stem cells is routinely used to restore the production of blood cells in
p.000073: patients affected by leukaemia or aplastic anaemia after chemotherapy. There are two sources of
p.000073: haematopoietic stem cells:
p.000073:
p.000073: • Adult stem cells: they can be retrieved under anaesthesia, from the bone marrow of donors, or from the patients
p.000073: themselves (before chemotherapy). Haematopoietic stem cells can also be retrieved directly from the blood, which
p.000073: requires a treatment to induce the passage of stem cells from the bone marrow into the blood circulation.
p.000073:
p.000073: • Stem cells of foetal origin: haematopoietic stem cells can be retrieved from the umbilical cord blood
p.000073: at birth, though care must be taken to ensure that the baby receives enough cord blood. There are at present cord blood
p.000073: banks designated to facilitate haematopoietic stem cell transplantation. The systematic retrieval and cryopreservation
p.000073: of cord blood, at birth, has even been considered in order to have autologous stem cells available in case of later
...
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000074: 74
p.000074:
p.000074: 1.9. Discoveries on human stem cells
p.000074:
p.000074: In the late 70's, the progress of infertility treatment led to the birth of the first child by in vitro fertilisation.
p.000074: The formation of human embryos in vitro during the course of infertility treatment has made possible the
p.000074: study of human embryogenesis following fertilisation, and thus has increased our knowledge of the
p.000074: behaviour and characteristics of embryonic cells at a very early stage.
p.000074:
p.000074: Since 1998, derivation and culture of embryonic and foetal human pluripotent stem cells has been
p.000074: performed, a process which had never been achieved before with human cells. A team at the University of Wisconsin in
p.000074: Madison (USA) announced in November 1998 that it had successfully isolated and cultured for several months
p.000074: cells from 14 human blastocysts obtained from donated surplus embryos produced by in vitro fertilisation. This team
p.000074: established five embryonic ES cell lines with the ability to be grown continuously without losing their capacity to
p.000074: differentiate into the many kinds of cells that constitute the body. At the same time, a team at the Johns Hopkins
p.000074: University in Baltimore (USA) reported that foetal primordial germ cells had been isolated from the gonads of
p.000074: foetuses obtained after pregnancy termination and cultured to make EG cells. Cell lines derived from these
p.000074: cells were grown for many months while maintaining the same capacity to differentiate as the ES cell lines.
p.000074:
p.000074: In 1999, research on adult stem cells revealed that their plasticity was much higher than previously thought. Adult
p.000074: neural stem cells have been reported to give rise occasionally to other cell types including blood cells. A team at the
p.000074: University of Minnesota in Minneapolis, (USA) has shown that cells isolated from the bone marrow of adults or children
p.000074: were able to become neural or muscle cells. Nevertheless, bone marrow cells with such extraordinary malleability are
p.000074: extremely rare. In any case, these recent findings still require to be substantiated.
p.000074:
p.000074: The future challenge is to control the differentiation of human stem cells. It has been shown in animals that by
p.000074: culturing stem cells in the presence of certain chemical substances referred to as "growth factors", it
p.000074: is possible to induce differentiation of specific cell types. Experiments on human stem cells are less advanced but
p.000074: finding ways to direct differentiation is presently an active focus of research.
p.000074:
p.000074:
p.000074:
p.000074: 1.10. What is the main interest of stem cell research and what are the hopes?
p.000074:
p.000074: The main interests at present include:
p.000074:
...
Social / Incarcerated
Searching for indicator liberty:
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p.000010: Integrity proposed, in their report published 29 January 2003, not to implement a general prohibition against
p.000010: producing fertilised eggs for research purposes. It
p.000010:
p.000010:
p.000010:
p.000010:
p.000011: 11
p.000011:
p.000011: should also be noted, however, that in the view of the Committee the creation of embryos by transfer of somatic cell
p.000011: nuclei (so called therapeutic cloning) should be treated in the same way and thus in principle be allowed.
p.000011:
p.000011: Regulations in countries acceding to the EU
p.000011:
p.000011: Cyprus, Czech Republic, Estonia, Hungary, Lithuania, Slovak Republic, Slovenia have ratified the Convention of
p.000011: the Council of Europe on biomedicine and human rights.
p.000011:
p.000011: Concerning the countries acceding to the EU, no specific regulations regarding human embryonic stem cell
p.000011: research have at present been implemented. Estonia, Hungary, Latvia, Slovenia have implemented legislation
p.000011: authorising research on human embryos under certain conditions. In Lithuania, Poland and the Slovak
p.000011: Republic human embryo research is prohibited. No specific regulation regarding embryo research exist in Cyprus,
p.000011: Malta and the Czech Republic. A bill is under preparation in Czech Republic.
p.000011:
p.000011: Governance of stem cell research in the context of FP6 As stated in the Treaty of the European Union, article 6:
p.000011: “1. The Union is founded on the principles of liberty, democracy, respect for human rights and fundamental freedom, and
p.000011: the rule of law, principles which are common to the Member States.
p.000011:
p.000011: 2. The Union shall respect fundamental rights, as guaranteed by the European Convention for the protection of Human
p.000011: Rights and Fundamental Freedoms signed in Rome on 4 November 1950 and as they result from the constitutional traditions
p.000011: common to the Member States, as general principles of Community law.
p.000011:
p.000011: 3. The Union shall respect the national identities of its Member States.
p.000011:
p.000011: 4. The Union shall provide itself with the means necessary to attain its objectives and carry through its policies.”
p.000011:
p.000011: In accordance with the EU Treaty, each Member State retains its full prerogative to legislate on ethical matters. At
p.000011: the level of the Community, ethical principles have been defined with regard to the funding of research under the
p.000011: research Framework Programme.
p.000011:
p.000011: As far as FP6 is concerned, the following ethical principles have been established12:
p.000011: – “Fundamental ethical principles are to be respected. These include the principles reflected in the
p.000011: Charter of fundamental rights of the EU including the protection of human dignity and human life…”
p.000011:
p.000011: – “… in accordance with Community law”
p.000011:
p.000011: – “…in accordance with legislation, regulations and ethical guidelines in countries where the
p.000011: research will be carried out.”
p.000011:
p.000011:
p.000011:
...
p.000047: useful lines.
p.000047:
p.000047: – A number of initiatives to facilitate research on all types of stem cells. In particular, the NIH
p.000047: continues to support research on developing the therapeutic potential of adult stem cells.
p.000047: New federal legislation is under debate in the US Congress. The State of California has passed a law, in
p.000047: September 2002, allowing the procurement of human embryonic stem cells from supernumerary embryos. New legislation
p.000047: authorising the procurement of human ES cells from supernumerary embryos is under discussion in the
p.000047: States of New Jersey and Massachusetts.
p.000047: In Australia a new law is under discussion to allow for the derivation of human ES cells from supernumerary embryos.
p.000047:
p.000047: Laboratories in Singapore, Taiwan, South Korea, China… are actively conducting human ES cell research. Legislation
p.000047: regarding this research is under discussion in some of these countries.
p.000047: Annex D provides further information regarding provisions in non-EU countries relating to human embryonic
p.000047: stem cell research.
p.000047:
p.000047: 3.5. Governance of stem cell research in the context of FP6
p.000047: As stated in the Treaty of the European Union, article 6:
p.000047:
p.000047: “1. The Union is founded on the principles of liberty, democracy, respect for human rights and fundamental freedom, and
p.000047: the rule of law, principles which are common to the Member States.
p.000047:
p.000047: 2. The Union shall respect fundamental rights, as guaranteed by the European Convention for the protection of Human
p.000047: Rights and Fundamental Freedoms signed in Rome on 4 November 1950 and as they result from the constitutional traditions
p.000047: common to the Member States, as general principles of Community law.
p.000047:
p.000047: 3. The Union shall respect the national identities of its Member States.
p.000047:
p.000047: 4. The Union shall provide itself with the means necessary to attain its objectives and carry through its policies.”
p.000047:
p.000047: In accordance with the EU Treaty, each Member State retains its full prerogative to legislate on ethical matters. At
p.000047: the level of the Community, ethical principles have been defined with regard to the funding of research under the
p.000047: research Framework Programme.
p.000047:
p.000047: As far as FP6 is concerned, the following ethical principles have been established:
p.000047:
p.000047: The decision No. 1513/2002/EC of the European Parliament and of the Council of 27 June 2002 concerning the sixth
p.000047: framework programme of the European Community for research,
p.000047:
p.000047:
p.000047:
p.000048: 48
p.000048:
p.000048: technological development and demonstration activities, contributing to the creation of the European Research
p.000048: Area and to innovation (2002 to 2006) stipulates among others that61:
...
Searching for indicator restricted:
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p.000020: major obstacles and humanised systems may enhance the hazard identification of chemicals.
p.000020:
p.000020: – Use of stem cells in gene therapy: Stem cells could be used as vehicles i.e. bearers of genetic information
p.000020: for the therapeutic delivery of genes. A problem for research on gene therapy has been to find safe delivery
p.000020: systems and stem cells may provide a solution here. At present, experiments are being done with gene
p.000020: therapy to treat diseases of the blood system. Their aim is to introduce new healthy genes in the
p.000020: blood-forming stem cells, which can then develop into all types of blood cells and, moreover, are able to renew
p.000020: themselves and thereby provide a permanent cure.
p.000020:
p.000020: – For understanding of human development. Studies of human embryonic and foetal stem cells may yield a deeper
p.000020: understanding of evolutionary biology and the process leading from embryo to human being. Human ES cells
p.000020: should offer insights into developmental events that cannot be studied directly in the intact human embryo but that
p.000020: have important consequences in clinical areas, including birth defects, infertility, and pregnancy loss. Particularly
p.000020: in the early post implantation period, knowledge of normal human development is largely restricted to the
p.000020: description of a limited number of sectioned embryos and to analogies drawn from the
p.000020: experimental embryology of other species. Although the mouse is the main stay of experimental mammalian embryology,
p.000020: early structures including the placenta, extra-embryonic membranes, and the egg cylinder all differ
p.000020: substantially from the corresponding structure of the human embryo.
p.000020:
p.000020: – For understanding of the basic mechanisms of cell differentiation and proliferation. A
p.000020: primary goal of this work is to identify how undifferentiated stem cells become differentiated into particular types of
p.000020: cells. Scientists know that turning genes on and off are central to this process and molecules such as growth factors
p.000020: and nutrients, that function during embryonic development, also play a role. This knowledge can be used to
p.000020: grow stem cells from various sources in the laboratory and direct their differentiation into specialized cell
p.000020: types. Some of the most serious medical conditions, such as cancer, are due to abnormal cell
p.000020: division and differentiation. A better understanding of the genetic and molecular controls of these processes may
p.000020: yield information about how such diseases arise and suggest new strategies for therapies.
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021: 1.4. Novel stem cell based therapies
p.000021:
p.000021: Three therapeutic concepts are currently being envisaged26:
...
Social / Linguistic Proficiency
Searching for indicator linguistic:
(return to top)
p.000069: biotechnological inventions and in particular Article 6, concerning certain inventions excluded from
p.000069: patentability, and Article 7 giving mandate to the European Group on Ethics (EGE) to evaluate "all
p.000069: ethical aspects of biotechnology”;
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000070: 70
p.000070:
p.000070: Having regard to the Parliament and Council Decision of 22 December 1998 concerning the 5th Framework
p.000070: Programme of the European Community for research, technological development and demonstration activities
p.000070: (1998-2002) and in particular Article 7 requesting compliance with fundamental ethical principles;
p.000070:
p.000070: Having regard to the Council Decision of 25 January 1999 adopting the specific programme for research, technological
p.000070: development and demonstration activities on quality of life and management of living resources and in
p.000070: particular the ethical requirements mentioned in its Annex II;
p.000070:
p.000070: Having regard to the Charter of 28 September 2000 on Fundamental Rights of the European Union, approved
p.000070: by the European Council in Biarritz on October 14th 2000, in particular Article 1 on “Human dignity”, Article 3 on
p.000070: the “Right to the integrity of the person”, which refers to the principle of "free and informed consent" and prohibits
p.000070: "the reproductive cloning of human beings" and Article 22 on “Cultural, religious and linguistic diversity”;
p.000070:
p.000070: Having regard to the Council of Europe’s Convention on Human Rights and Biomedicine, signed on 4 April 1997 in Oviedo,
p.000070: in particular Article 18 on embryo research, and to the additional protocol to the Convention on the prohibition of
p.000070: cloning human beings signed on 12 January 1998 in Paris;
p.000070:
p.000070: Having regard to the Universal Declaration on the Human Genome and Human Rights adopted by the United Nations on 11
p.000070: December 1998, in particular Article 11 which recommends to prohibit reproductive cloning of human beings, and Article
p.000070: 13 which refers to the responsibilities of researchers as well as of science policy makers;
p.000070:
p.000070: Having regard to national regulations on stem cell and on embryo research and to national ethics bodies opinions, at
p.000070: the European Union level, concerning these subjects;
p.000070:
p.000070: Having regard to the reports of the US National Bioethics Advisory Committee dated September 13, 1999 on
p.000070: the "Ethical Issues on Human Stem Cell Research", the hearings on the same subject by the US Congress, on April 2000
p.000070: and the guidelines published by the Clinton administration on August 26, 2000 to be forwarded to a NIH (National
p.000070: Institutes of Health) scientific review in 2001;
p.000070:
p.000070: Having regard to the Round Table organised by the Group on 26 June 2000 in Brussels with members of the European
p.000070: Parliament, jurists, philosophers, scientists, representatives of industries, of religions, of patients' associations,
p.000070: and of international organisations (Council of Europe, UNESCO, WHO);
p.000070:
...
p.000079: - the principle of individual autonomy (entailing the giving of informed consent, and respect for privacy and
p.000079: confidentiality of personal data)
p.000079: - the principle of justice and of beneficence (namely with regard to the improvement and protection of health)
p.000079: - the principle of freedom of research (which is to be balanced against other fundamental principles)
p.000079: - the principle of proportionality (including that research methods are necessary to the aims pursued and that no
p.000079: alternative more acceptable methods are available).
p.000079: In addition, the Group considers it important to take into account, based on a precautionary approach,
p.000079: the potential long-term consequences of stem cell research and use for individuals and the society.
p.000079:
p.000079: 2.3. Pluralism and European ethics
p.000079: Pluralism is characteristic of the European Union, mirroring the richness of its tradition and adding a need for mutual
p.000079: respect and tolerance. Respect for different philosophical, moral or legal approaches and for diverse
p.000079: cultures is implicit in the ethical dimension of building a democratic European society.
p.000079: From a legal point of view, respect for pluralism is in line with Article 22 of the Charter on Fundamental Rights on
p.000079: “Cultural, religious and linguistic diversity” and with Article 6 of the Amsterdam Treaty which ensures
p.000079: the protection of fundamental rights at EU level, notably based on international instruments as well as
p.000079: common constitutional traditions, while also stressing the respect for the national identity of all Member States.
p.000079:
p.000079:
p.000079: BASIC RESEARCH ON HUMAN STEMXCELLS
p.000079:
p.000079: 2.4. Principal requirements according to the diverse sources of stem cells.
p.000079: • The retrieval of adult stem cells requires the same conditions as those required in the case of tissue
p.000079: donation, based on respect for the integrity of the human body and the free and informed consent of the donor.
p.000079: • The retrieval of stem cells from the umbilical cord blood after delivery requires that the donor (the woman or
p.000079: the couple concerned) is informed of possible uses of the cells for this specific purpose of research and
p.000079: that the consent of the donor is obtained.
p.000079: • The retrieval of foetal tissues to derive stem cells requires, besides informed consent, that no
p.000079: abortion is induced for the purpose of obtaining the tissues and that the termination timing and the way it is carried
p.000079: out are not influenced by this retrieval.
...
Social / Marital Status
Searching for indicator single:
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p.000056: the foetal germ cells, from which the gametes develop, and the remaining foetal stem cells, which are the foetal
p.000056: somatic cells
p.000056:
p.000056: Gamete: the male sperm or female egg
p.000056:
p.000056: Gene: a functional unit of heredity that is a segment of DNA located in a specific site on a chromosome. A gene directs
p.000056: the formation of an enzyme or other protein.
p.000056:
p.000056: Germ cells: ova and sperm, and their precursors
p.000056:
p.000056: Haematopoïetic stem cell: a stem cell from which all red and white blood cells develop
p.000056:
p.000056: Human embryonic stem cell: pluripotent stem cell derived from the inner cell mass of the blastocyst
p.000056:
p.000056: Implantation: the embedding of a blastocyst in the wall of the uterus. In humans implantation
p.000056: takes place at day 8 after fertilization.
p.000056:
p.000056: In vitro and in vivo: outside and inside the body; in vitro (literally, in glass) generally means in the laboratory
p.000056:
p.000056: In vitro fertilization: the fertilization of an egg by a sperm outside the body
p.000056:
p.000056: Multipotent: Multipotent stem cells are those capable to give rise to several different types of specialised cells
p.000056: constituting a specific tissue or organ.
p.000056:
p.000056: Oocyte: the female egg
p.000056:
p.000056: Plasticity: the ability of stem cells from one tissue to generate the differentiated cell types of another tissue
p.000056:
p.000056: Pluripotent stem cell: a single pluripotent stem cell has the ability to give rise to types of cells
p.000056: that develop from the three germ layers (mesoderm, endoderm and ectoderm) from which all the cells of the
p.000056: body arise. Pluripotent stem cells have the potential to generate into every cell type in the body, but cannot develop
p.000056: into a embryo on their own.
p.000056:
p.000056:
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: Pre-implantation embryo: is an embryo in the stage prior to implantation in the wall of the uterus ; an embryo cannot
p.000057: develop beyond the blastocyst stage without implantation into the womb.
p.000057:
p.000057: Primitive streak: a collection of cells which appears at about 14 days after fertilisation from which the heart, blood
p.000057: and the central nervous system develops
p.000057:
p.000057: Proliferation: expansion of a population of cells by the continuous division of single cells into two
p.000057: identical daughter cells
p.000057:
p.000057: Redifferentiation: the process of inducing a dedifferentiated cell to differentiate into a (different)
p.000057: specialised cell type
p.000057:
p.000057: Somatic cell: cell of the body other than egg or sperm
p.000057:
p.000057: Somatic stem cell: an undifferentiated cell found among differentiated cells in a tissue or organ, which
p.000057: can renew itself and can differentiate to yield the major specialised cell types of the tissue or organ.
p.000057:
p.000057: Somatic cell nuclear transfer: the transfer of a cell nucleus to an egg (or another cell) from which the nucleus has
p.000057: been removed..
p.000057:
p.000057: Supernumerary embryo or spare embryo: an embryo created by means of in vitro
p.000057: fertilisation (IVF) for the purpose of assisted reproduction but subsequently not used for it.
p.000057:
p.000057: Totipotent: At two to three days after fertilisation, an embryo consists of identical cells, which are
p.000057: totipotent. That is to say that each could give rise to an embryo on its own producing for example
p.000057: identical twins or quadruplets. They are totally unspecialised and have the capacity to differentiate into any of the
p.000057: cells which will constitute the foetus as well as the placenta and membranes around the foetus.
p.000057:
p.000057: Transdifferentiation: the observation that stem cells from one tissue may be able to differentiate into
p.000057: cells of another tissue
p.000057:
p.000057: Undifferentiated: not having changed to become a specialized cell type
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000058: 58
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: ANNEXES
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p.000059: 59
p.000059:
p.000059: ANNEX A: Biology of human development
p.000059:
p.000059:
p.000059:
p.000059: The development of the embryo is a continual process of change, which can be described in terms of the following seven
p.000059: stages:
p.000059:
p.000059: 1. Day 0: Fertilisation
p.000059: The female egg (“oocyte”) is fertilised by the male sperm. The egg and sperm each carry half the genes of a normal
p.000059: cell. The process of fertilisation consists of a number of steps, which ultimately result in a single cell, the
p.000059: “zygote”. The zygote contains all the genes necessary for the development of an individual, half derived from the
p.000059: mother and half from the father. A very small proportion of genes is contained in the mitochondria and is inherited
p.000059: exclusively from the mother.
p.000059:
p.000059: 2. Day 3-4:
p.000059: Up to the fourth cell stage at day 3-4 all the cells are essentially identical and all are thought to have the
p.000059: potential, if placed in the right environment, to develop into an individual – the cells are “ totipotent” (i.e. they
p.000059: have the capacity to develop into all type of cells needed for human development including the extra-embryonic
p.000059: tissues such as the placenta and the umbilical cord). Indeed, identical twins can result from the splitting of
p.000059: the cells at this early stage: they are genetically identical as a result of developing from the same
p.000059: fertilised egg (identical twins can arise later i.e. up to 14 days).
p.000059:
p.000059: 3. Days 4-5: Morula Stage
p.000059: At four to five days after fertilisation (morula stage), the embryo is still made up of unspecialised
p.000059: embryonic cells, but theses seems no longer to have the potential to give raise to an embryo on their own.
p.000059:
p.000059: 4. Days 5-7: Blastocyst stage
p.000059: At day 5 after fertilisation the cells constituting the embryo start to differentiate into inner and outer cells. The
p.000059: outer cells go on to develop into non-embryonic tissues such as the placenta or umbilical cord. The inner cell mass
...
p.000070: Parliament, jurists, philosophers, scientists, representatives of industries, of religions, of patients' associations,
p.000070: and of international organisations (Council of Europe, UNESCO, WHO);
p.000070:
p.000070: Having regard to the Hearings of scientific experts on 6 June 2000 and on 2 October 2000, and to the Hearings of
p.000070: representatives of religions on 8 September 2000;
p.000070:
p.000070: Having heard the rapporteurs Anne McLaren and Goran Hermerén;
p.000070:
p.000070:
p.000070:
p.000070: 1 - WHEREAS SCIENTIFIC BACKGROUND
p.000070: 1.1. How to define stem cells?
p.000070:
p.000070: Stem cells are cells that can divide to produce either cells like themselves (self-renewal), or cells
p.000070: of one or several specific differentiated types. Stem cells are not yet fully differentiated and therefore can
p.000070: reconstitute one or several types of tissues.
p.000070:
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p.000071: 71
p.000071:
p.000071: 1.2. What are the different kinds of stem cells?
p.000071:
p.000071: Different kinds of stem cells can be distinguished according to their potential to differentiate. They are progenitor,
p.000071: multipotent or pluripotent stem cells.
p.000071:
p.000071: • Progenitor stem cells are those whose terminally differentiated progeny consist of a single cell type
p.000071: only. For instance, epidermal stem cells or spermatogonial stem cells can differentiate respectively into
p.000071: only keratinocytes and spermatozoa.
p.000071:
p.000071: • Multipotent stem cells are those which can give rise to several terminally differentiated cell types constituting
p.000071: a specific tissue or organ. Examples are skin stem cells which give rise to epidermal cells, sebaceous glands and
p.000071: hair follicles or haematopoietic stem cells, which give rise to all the diverse blood cells (erythrocytes,
p.000071: lymphocytes, antibody-producing cells and so on), and neural stem cells, which give rise to all the cell types
p.000071: in the nervous system, including glia (sheath cells), and the many different types of neurons.
p.000071:
p.000071: • Pluripotent stem cells are able to give rise to all different cell types in vitro. Nevertheless, they cannot on
p.000071: their own form an embryo. Pluripotent stem cells, which are isolated from primordial germ cells in the
p.000071: foetus, are called: embryonic germ cells ("EG cells"). Those stem cells which are isolated from the inner cell mass of
p.000071: a blastocyst-stage embryo are called: embryonic stem cells ("ES cells”).
p.000071:
...
Social / Property Ownership
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p.000053: obstacle, in so far as they fulfil the requirements of patentability (novelty, inventive step and industrial
p.000053: application).
p.000053:
p.000053: Directive 98/44 on the legal protection of biotechnological inventions, adopted on 6 July 1998,
p.000053: establishes that an element isolated from the human body or otherwise produced by means of a technical
p.000053: process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if
p.000053: the structure of that element is identical to that of a natural element. Furthermore, the directive obliges
p.000053: Member States to consider unpatentable inventions where their commercial exploitation would be contrary to order
p.000053: public or morality. The processes for cloning human beings and uses of human embryos for industrial or
p.000053: commercial purposes are in particular excluded from patentability.
p.000053: The Commission published on 7 October 2002, the first annual report (provided for in article 16c of this Directive)
p.000053: on the implications of patent law for biotechnology and genetic engineering. The report raised the issue
p.000053: related to patentability of human stem cells and cells lines obtained from them.
p.000053: In view of the preparation of future reports provided for in Article 16c of the directive the
p.000053: Commission has set up a group of eminent experts from science, law, and economics, and representatives
p.000053: from the European Patent Office (EPO) and the World Intellectual Property Organisation (WIPO). The group’s
p.000053: mandate is to analyse important issues surrounding biotechnological inventions. It will not touch upon ethical
p.000053: issues, which are the mandate of the European Group on Ethics, but will focus more on legal and technical aspects and
p.000053: on the mutual impact of the legal framework and the research and innovation area. In this light, one of the issues
p.000053: identified and which will be further discussed by the expert committee will be the patentability of human stem cells
p.000053: and cell lines derived from them.
p.000053: The “16c expert group” will meet in May 2003 to discuss patenting of products and methods involving human embryonic
p.000053: stem cell and human ES derivatives. The report of the 16c expert group will be published at the same time as
p.000053: the 2003 annual monitoring report of the Commission is delivered, towards the end of the year.
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: 73 http://europa.eu.int/comm/european_group_ethics/docs/avis16_en.pdf
p.000053:
p.000054: 54
p.000054:
p.000054: While many of the demonstrations of the potential of stem cell research have arisen from academia, the
p.000054: development of this potential i.e. into therapeutic products requires industrial and commercial inputs. For
p.000054: example, industrial involvement will be needed for large scale and good manufacturing production of cell
p.000054: lines, to support multicentre clinical trials, marketing, distribution etc.
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Social / Religion
Searching for indicator religious:
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p.000007: embryonic or somatic stem cell research and which stem cells will best meet the needs of basic research and clinical
p.000007: applications.
p.000007:
p.000007: Several arguments have been put forward regarding the needs for derivation of new human embryonic stem cell lines.
p.000007:
p.000007: In particular that human embryonic stem cell research has only just begun and scientists do not yet know if they have
p.000007: developed the best procedures for isolating or maintaining human ES cells in culture. It has also been reported that
p.000007: many of the existing embryonic stem cell lines have been patented in the US. This could create a position of dependence
p.000007: from private industry in other parts of the world8.
p.000007:
p.000007: Governance of human stem cell research
p.000007:
p.000007: Human embryonic stem cell research raises complex ethical questions. The question whether it is ethically defensible to
p.000007: do research on embryonic stem cells can be described as a conflict between different values, between different
p.000007: actors’ rights and obligations, or between the short- and long-term interests of different groups. On the one
p.000007: hand, there is interest in new knowledge that can lead to treatment of hitherto incurable diseases. On the other hand,
p.000007: when this research involves the use of human embryos, it raises the question of ethical values at stake
p.000007: and of the limits and conditions for such research9. Opinions on the legitimacy of experiments using
p.000007: human embryos are divided according to the different ethical, philosophical, and religious traditions
p.000007: in which they are rooted. EU Member States have taken very different positions regarding the regulation of human
p.000007: embryonic stem cell research. It confirms that different views exist throughout the European Union
p.000007: concerning what is and what is not ethically defensible.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: 6 e.g. Dr. Catherine Verfaillie, University of Minnesota Medical School, stated during her presentation at
p.000007: the US President’s Council on Bioethics meeting on 25 April 2002, http://www.bioethics.gov/
p.000007: “Embryonic stem cells in humans are very much in their infancy, the same as we are for adult stem cell biology, too,
p.000007: and so I don’t think we are anywhere close to be able to come up with new therapies at this point in time. I would also
p.000007: like to reiterate that even though my laboratory and our group works on adult stem cells, we have actually
p.000007: actively pursued investigators in embryonic stem cell research, human embryonic stem cells, just so that within
p.000007: the same institution we would have laboratories that have one cell, and other laboratories that have the other cell, so
p.000007: we would be in a position to compare and contrast the potential of the different cell populations, and I think that it
p.000007: is very important”.
p.000007: 7 “Stem Cells: scientific progress and future research directions”, National Institute of Health
...
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p.000033: 33
p.000033:
p.000033: Chapter 3: Governance of human embryonic stem cell research
p.000033:
p.000033:
p.000033:
p.000033: Human embryonic stem cell research raises complex ethical questions. It confronts scientific progress with ethical
p.000033: concerns and it has triggered an intense public debate on its guiding ethical principles and limitations.
p.000033: The question whether it is ethically defensible to do research on embryonic stem cells can be described
p.000033: as a conflict between different values, between different actors’ rights and obligations, or between the short-
p.000033: and long-term interests of different groups. On the one hand, there is interest in new knowledge that can
p.000033: lead to treatment of hitherto incurable diseases. On the other hand, when this research involves the use of human
p.000033: embryos, it raises the question of ethical values at stake and of the limits and conditions for such research53.
p.000033: Opinions on the legitimacy of experiments using human embryos are divided according to the different ethical,
p.000033: philosophical, and religious traditions in which they are rooted. EU Member States have taken very different positions
p.000033: regarding the regulation of human embryonic stem cell research. This confirms that different views exist
p.000033: throughout the European Union concerning what is and what is not ethically defensible.
p.000033:
p.000033: 3.1. The ethical issues at stake
p.000033: The European Group on Ethics highlighted in its Opinion No.15 regarding “Ethical aspects of human stem cell research
p.000033: and use”, issued 14 November 200054, that “the fundamental ethical principles applicable to stem cell research are:
p.000033:
p.000033: – The principle of respect for human dignity
p.000033:
p.000033: – The principle of individual autonomy (entailing the giving of informed consent, and respect for
p.000033: privacy and confidentiality of personal data)
p.000033:
p.000033: – The principle of justice and of beneficence (namely with regard to the improvement and
p.000033: protection of health)
p.000033:
p.000033: – The principle of freedom of research (which is to be balanced against other
p.000033: fundamental principles)
p.000033:
p.000033: – The principle of proportionality (including that research methods are necessary to the aims pursued and that
p.000033: no alternative more acceptable methods are available).
p.000033:
...
p.000069: biotechnological inventions and in particular Article 6, concerning certain inventions excluded from
p.000069: patentability, and Article 7 giving mandate to the European Group on Ethics (EGE) to evaluate "all
p.000069: ethical aspects of biotechnology”;
p.000069:
p.000069:
p.000069:
p.000069:
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p.000070: 70
p.000070:
p.000070: Having regard to the Parliament and Council Decision of 22 December 1998 concerning the 5th Framework
p.000070: Programme of the European Community for research, technological development and demonstration activities
p.000070: (1998-2002) and in particular Article 7 requesting compliance with fundamental ethical principles;
p.000070:
p.000070: Having regard to the Council Decision of 25 January 1999 adopting the specific programme for research, technological
p.000070: development and demonstration activities on quality of life and management of living resources and in
p.000070: particular the ethical requirements mentioned in its Annex II;
p.000070:
p.000070: Having regard to the Charter of 28 September 2000 on Fundamental Rights of the European Union, approved
p.000070: by the European Council in Biarritz on October 14th 2000, in particular Article 1 on “Human dignity”, Article 3 on
p.000070: the “Right to the integrity of the person”, which refers to the principle of "free and informed consent" and prohibits
p.000070: "the reproductive cloning of human beings" and Article 22 on “Cultural, religious and linguistic diversity”;
p.000070:
p.000070: Having regard to the Council of Europe’s Convention on Human Rights and Biomedicine, signed on 4 April 1997 in Oviedo,
p.000070: in particular Article 18 on embryo research, and to the additional protocol to the Convention on the prohibition of
p.000070: cloning human beings signed on 12 January 1998 in Paris;
p.000070:
p.000070: Having regard to the Universal Declaration on the Human Genome and Human Rights adopted by the United Nations on 11
p.000070: December 1998, in particular Article 11 which recommends to prohibit reproductive cloning of human beings, and Article
p.000070: 13 which refers to the responsibilities of researchers as well as of science policy makers;
p.000070:
p.000070: Having regard to national regulations on stem cell and on embryo research and to national ethics bodies opinions, at
p.000070: the European Union level, concerning these subjects;
p.000070:
p.000070: Having regard to the reports of the US National Bioethics Advisory Committee dated September 13, 1999 on
p.000070: the "Ethical Issues on Human Stem Cell Research", the hearings on the same subject by the US Congress, on April 2000
p.000070: and the guidelines published by the Clinton administration on August 26, 2000 to be forwarded to a NIH (National
p.000070: Institutes of Health) scientific review in 2001;
p.000070:
p.000070: Having regard to the Round Table organised by the Group on 26 June 2000 in Brussels with members of the European
p.000070: Parliament, jurists, philosophers, scientists, representatives of industries, of religions, of patients' associations,
...
p.000079: specifically:
p.000079: - the principle of respect for human dignity
p.000079: - the principle of individual autonomy (entailing the giving of informed consent, and respect for privacy and
p.000079: confidentiality of personal data)
p.000079: - the principle of justice and of beneficence (namely with regard to the improvement and protection of health)
p.000079: - the principle of freedom of research (which is to be balanced against other fundamental principles)
p.000079: - the principle of proportionality (including that research methods are necessary to the aims pursued and that no
p.000079: alternative more acceptable methods are available).
p.000079: In addition, the Group considers it important to take into account, based on a precautionary approach,
p.000079: the potential long-term consequences of stem cell research and use for individuals and the society.
p.000079:
p.000079: 2.3. Pluralism and European ethics
p.000079: Pluralism is characteristic of the European Union, mirroring the richness of its tradition and adding a need for mutual
p.000079: respect and tolerance. Respect for different philosophical, moral or legal approaches and for diverse
p.000079: cultures is implicit in the ethical dimension of building a democratic European society.
p.000079: From a legal point of view, respect for pluralism is in line with Article 22 of the Charter on Fundamental Rights on
p.000079: “Cultural, religious and linguistic diversity” and with Article 6 of the Amsterdam Treaty which ensures
p.000079: the protection of fundamental rights at EU level, notably based on international instruments as well as
p.000079: common constitutional traditions, while also stressing the respect for the national identity of all Member States.
p.000079:
p.000079:
p.000079: BASIC RESEARCH ON HUMAN STEMXCELLS
p.000079:
p.000079: 2.4. Principal requirements according to the diverse sources of stem cells.
p.000079: • The retrieval of adult stem cells requires the same conditions as those required in the case of tissue
p.000079: donation, based on respect for the integrity of the human body and the free and informed consent of the donor.
p.000079: • The retrieval of stem cells from the umbilical cord blood after delivery requires that the donor (the woman or
p.000079: the couple concerned) is informed of possible uses of the cells for this specific purpose of research and
p.000079: that the consent of the donor is obtained.
p.000079: • The retrieval of foetal tissues to derive stem cells requires, besides informed consent, that no
p.000079: abortion is induced for the purpose of obtaining the tissues and that the termination timing and the way it is carried
p.000079: out are not influenced by this retrieval.
...
Social / Trade Union Membership
Searching for indicator union:
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p.000007:
p.000007: In particular that human embryonic stem cell research has only just begun and scientists do not yet know if they have
p.000007: developed the best procedures for isolating or maintaining human ES cells in culture. It has also been reported that
p.000007: many of the existing embryonic stem cell lines have been patented in the US. This could create a position of dependence
p.000007: from private industry in other parts of the world8.
p.000007:
p.000007: Governance of human stem cell research
p.000007:
p.000007: Human embryonic stem cell research raises complex ethical questions. The question whether it is ethically defensible to
p.000007: do research on embryonic stem cells can be described as a conflict between different values, between different
p.000007: actors’ rights and obligations, or between the short- and long-term interests of different groups. On the one
p.000007: hand, there is interest in new knowledge that can lead to treatment of hitherto incurable diseases. On the other hand,
p.000007: when this research involves the use of human embryos, it raises the question of ethical values at stake
p.000007: and of the limits and conditions for such research9. Opinions on the legitimacy of experiments using
p.000007: human embryos are divided according to the different ethical, philosophical, and religious traditions
p.000007: in which they are rooted. EU Member States have taken very different positions regarding the regulation of human
p.000007: embryonic stem cell research. It confirms that different views exist throughout the European Union
p.000007: concerning what is and what is not ethically defensible.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: 6 e.g. Dr. Catherine Verfaillie, University of Minnesota Medical School, stated during her presentation at
p.000007: the US President’s Council on Bioethics meeting on 25 April 2002, http://www.bioethics.gov/
p.000007: “Embryonic stem cells in humans are very much in their infancy, the same as we are for adult stem cell biology, too,
p.000007: and so I don’t think we are anywhere close to be able to come up with new therapies at this point in time. I would also
p.000007: like to reiterate that even though my laboratory and our group works on adult stem cells, we have actually
p.000007: actively pursued investigators in embryonic stem cell research, human embryonic stem cells, just so that within
p.000007: the same institution we would have laboratories that have one cell, and other laboratories that have the other cell, so
p.000007: we would be in a position to compare and contrast the potential of the different cell populations, and I think that it
p.000007: is very important”.
p.000007: 7 “Stem Cells: scientific progress and future research directions”, National Institute of Health
p.000007: (NIH), Bethesda, USA, June 2001; Swiss National Advisory Commission on Biomedical Ethics: opinion on human
p.000007: embryonic stem cell research, June 2002; The Health Council of the Netherlands’ report on “Stem cells for
...
p.000008: fundamental principles).
p.000008:
p.000008: – The principle of proportionality (including that research methods are necessary to the aims pursued and that
p.000008: no alternative more acceptable methods are available).
p.000008:
p.000008: In addition, the EGE considers it important to take into account, based on a precautionary approach, the potential
p.000008: long-term consequences of stem cell research and use for individuals and the society.”
p.000008:
p.000008: Concerning the creation of embryos for research purpose the EGE considered that “the creation of embryos
p.000008: for the sole purpose of research raises serious concerns since it represents a further step in the
p.000008: instrumentalisation of human life” and deemed “ the creation of embryos with gametes donated for the purpose of
p.000008: stem cell procurement ethically unacceptable, when spare embryos represent a ready alternative source”.
p.000008:
p.000008: Furthermore the EGE considered “that, at present, the creation of embryos by somatic cell nuclear transfer for research
p.000008: on stem cell therapy would be premature, since there is a wide field of research to be carried out with alternative
p.000008: sources of human stem cells (from spare embryos, foetal tissues and adult stem cells”.
p.000008:
p.000008: Concerning the ethical acceptability of human embryonic stem cell research in the context of the Community Framework
p.000008: Programme, the EGE concluded that «//… there is no argument for excluding funding of this kind of research from the
p.000008: Framework Programme of research of the European Union if it complies with ethical and legal requirements as
p.000008: defined in this programme”.
p.000008:
p.000008: Secondly the EGE stated, that:
p.000008:
p.000008: “Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells)
p.000008: requires a specific Community research budget. In particular, EU funding should be devoted to testing the validity of
p.000008: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000008: such research be widely disseminated and not hidden for reasons of commercial interest.”
p.000008:
p.000008:
p.000008: 10 Annex E - Opinion No. 15 of the European Group on Ethics regarding the “Ethical aspects of human stem
p.000008: cell research and use”. http://europa.eu.int/comm/european_group_ethics/index_en.htm.
p.000008:
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: The EGE identified the following principal requirements regarding human embryonic stem cell research and the
p.000009: procurement of embryonic stem cells from supernumerary embryos:
p.000009: – Free and informed consent from the donating couple or woman.
p.000009:
p.000009: – Approval of the research by an authority.
p.000009:
p.000009: – No financial gain for donors.
p.000009:
...
p.000009: as of March 2003, the following distinctions can be made:
p.000009:
p.000009: – Allowing for the procurement of human embryonic stem cells from supernumerary
p.000009: embryos by law under certain conditions: Finland, Greece, the Netherlands, Sweden and the United Kingdom.
p.000009:
p.000009: – Prohibiting the procurement of human ES cells from supernumerary embryos but allowing by law for
p.000009: the import and use of human embryonic stem cell lines under certain conditions: Germany. The import and use of human ES
p.000009: cell lines is not explicitly prohibited in e.g. Austria, Denmark and France and authorisation is still being
p.000009: discussed.
p.000009: – Prohibiting the procurement of human ES cells from supernumerary embryos: Austria, Denmark,
p.000009: France, Ireland and Spain. The legislation in Spain only allows the procurement of human ES cell from
p.000009: non-viable human embryos under certain conditions.
p.000009:
p.000009: – No specific legislation regarding human embryo research or human ES cell research: Belgium, Italy,
p.000009: Luxembourg and Portugal.
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: 11 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000009: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000009: cell research and use (last update March 2003). “Survey on the National Regulations in the European Union
p.000009: regarding Research on Human Embryos - B. Gratton - published by the Secretariat of the EGE - European Commission - July
p.000009: 2002”.
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: – Allowing by law for the creation of human embryos for research purposes: UK is for the moment the only
p.000010: Member State, which allows by law for the creation of human embryos either by fertilisation of an egg
p.000010: by a sperm, or by somatic cell nuclear transfer (SCNT, also called therapeutic cloning) for stem cell
p.000010: procurement. The bill under discussion in the Belgian Parliament would allow for the creation of human embryos for
p.000010: research purposes including by SCNT. The Dutch Embryo Act of 2002 includes a five-year moratorium for the
p.000010: creation of embryos for research purposes including by SCNT.
p.000010:
p.000010: – Prohibiting the creation of human embryos for research purposes and for the procurement of stem
p.000010: cells by law or by ratification of the Convention of the Council of Europe on Human rights and
p.000010: Biomedicine signed in Oviedo on 4 April 1997: Austria, Denmark, Finland, France, Germany, Greece,
p.000010: Ireland, Netherlands, Portugal and Spain.
p.000010:
p.000010: New regulations under discussion in EU Member States:
p.000010:
p.000010: Belgium: A bill on research on human embryos in vitro was approved by the Belgian Senate in 2002 and it is now
p.000010: under discussion in the Parliament. The draft legislation proposes to authorise the procurement of
p.000010: embryonic stem cells from supernumerary embryos under certain conditions, and to create a “Federal
p.000010: Commission for scientific medical research on embryos in vitro”.
...
p.000010:
p.000010: Sweden: A revision of the current legislation is under discussion. The Parliamentary Committee on Genetic
p.000010: Integrity proposed, in their report published 29 January 2003, not to implement a general prohibition against
p.000010: producing fertilised eggs for research purposes. It
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p.000011: 11
p.000011:
p.000011: should also be noted, however, that in the view of the Committee the creation of embryos by transfer of somatic cell
p.000011: nuclei (so called therapeutic cloning) should be treated in the same way and thus in principle be allowed.
p.000011:
p.000011: Regulations in countries acceding to the EU
p.000011:
p.000011: Cyprus, Czech Republic, Estonia, Hungary, Lithuania, Slovak Republic, Slovenia have ratified the Convention of
p.000011: the Council of Europe on biomedicine and human rights.
p.000011:
p.000011: Concerning the countries acceding to the EU, no specific regulations regarding human embryonic stem cell
p.000011: research have at present been implemented. Estonia, Hungary, Latvia, Slovenia have implemented legislation
p.000011: authorising research on human embryos under certain conditions. In Lithuania, Poland and the Slovak
p.000011: Republic human embryo research is prohibited. No specific regulation regarding embryo research exist in Cyprus,
p.000011: Malta and the Czech Republic. A bill is under preparation in Czech Republic.
p.000011:
p.000011: Governance of stem cell research in the context of FP6 As stated in the Treaty of the European Union, article 6:
p.000011: “1. The Union is founded on the principles of liberty, democracy, respect for human rights and fundamental freedom, and
p.000011: the rule of law, principles which are common to the Member States.
p.000011:
p.000011: 2. The Union shall respect fundamental rights, as guaranteed by the European Convention for the protection of Human
p.000011: Rights and Fundamental Freedoms signed in Rome on 4 November 1950 and as they result from the constitutional traditions
p.000011: common to the Member States, as general principles of Community law.
p.000011:
p.000011: 3. The Union shall respect the national identities of its Member States.
p.000011:
p.000011: 4. The Union shall provide itself with the means necessary to attain its objectives and carry through its policies.”
p.000011:
p.000011: In accordance with the EU Treaty, each Member State retains its full prerogative to legislate on ethical matters. At
p.000011: the level of the Community, ethical principles have been defined with regard to the funding of research under the
p.000011: research Framework Programme.
p.000011:
p.000011: As far as FP6 is concerned, the following ethical principles have been established12:
p.000011: – “Fundamental ethical principles are to be respected. These include the principles reflected in the
p.000011: Charter of fundamental rights of the EU including the protection of human dignity and human life…”
p.000011:
p.000011: – “… in accordance with Community law”
p.000011:
p.000011: – “…in accordance with legislation, regulations and ethical guidelines in countries where the
p.000011: research will be carried out.”
p.000011:
p.000011:
p.000011:
p.000011: 12 OJ L 232 of 29.8.2002, p.4; OJ L 294 of 29.10.2002, p. 8.
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012: – “The following fields of research shall not be financed under this programme:
p.000012:
p.000012: – research activities aiming at human cloning for reproductive purposes
p.000012:
p.000012: – research activity intended to modify the genetic heritage of human beings which could make such
p.000012: change heritable13
p.000012: – research activities intended to create human embryos solely for the purpose of research or for the purpose of
p.000012: stem cell procurement, including by means of somatic cell nuclear transfer (often referred to as therapeutic cloning).
p.000012:
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p.000033: 33
p.000033:
p.000033: Chapter 3: Governance of human embryonic stem cell research
p.000033:
p.000033:
p.000033:
p.000033: Human embryonic stem cell research raises complex ethical questions. It confronts scientific progress with ethical
p.000033: concerns and it has triggered an intense public debate on its guiding ethical principles and limitations.
p.000033: The question whether it is ethically defensible to do research on embryonic stem cells can be described
p.000033: as a conflict between different values, between different actors’ rights and obligations, or between the short-
p.000033: and long-term interests of different groups. On the one hand, there is interest in new knowledge that can
p.000033: lead to treatment of hitherto incurable diseases. On the other hand, when this research involves the use of human
p.000033: embryos, it raises the question of ethical values at stake and of the limits and conditions for such research53.
p.000033: Opinions on the legitimacy of experiments using human embryos are divided according to the different ethical,
p.000033: philosophical, and religious traditions in which they are rooted. EU Member States have taken very different positions
p.000033: regarding the regulation of human embryonic stem cell research. This confirms that different views exist
p.000033: throughout the European Union concerning what is and what is not ethically defensible.
p.000033:
p.000033: 3.1. The ethical issues at stake
p.000033: The European Group on Ethics highlighted in its Opinion No.15 regarding “Ethical aspects of human stem cell research
p.000033: and use”, issued 14 November 200054, that “the fundamental ethical principles applicable to stem cell research are:
p.000033:
p.000033: – The principle of respect for human dignity
p.000033:
p.000033: – The principle of individual autonomy (entailing the giving of informed consent, and respect for
p.000033: privacy and confidentiality of personal data)
p.000033:
p.000033: – The principle of justice and of beneficence (namely with regard to the improvement and
p.000033: protection of health)
p.000033:
p.000033: – The principle of freedom of research (which is to be balanced against other
p.000033: fundamental principles)
p.000033:
p.000033: – The principle of proportionality (including that research methods are necessary to the aims pursued and that
p.000033: no alternative more acceptable methods are available).
p.000033:
p.000033: In addition, the Group considers it important to take into account, based on a precautionary approach, the potential
p.000033: long-term consequences of stem cell research and use for individuals and the society.”
p.000033:
p.000033: Concerning the creation of embryos for research purpose the EGE considered that “the creation of embryos
...
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034: of embryos with gametes donated for the purpose of stem cell procurement ethically unacceptable, when spare
p.000034: embryos55 represent a ready alternative source”.
p.000034: Furthermore the EGE considered “ that, at present, the creation of embryos by somatic cell nuclear transfer for
p.000034: research on stem cell therapy would be premature, since there is a wide field of research to be carried out with
p.000034: alternative sources of human stem cells (from spare embryos, foetal tissues and adult stem cells”.
p.000034:
p.000034: The ethical acceptability of human embryonic stem cell research in the context of Community Framework
p.000034: Programme for Research
p.000034: The EGE noted in the same opinion that “in some countries embryo research is forbidden. But when this research is
p.000034: allowed, with the purpose of improving treatment for infertility, it is hard to see any specific argument,
p.000034: which would prohibit extending the scope of such research in order to develop new treatments to cure severe
p.000034: diseases or injuries. As in the case of research on infertility, stem cell research aims to alleviate
p.000034: severe human suffering. In any case, the embryos that have been used for research are required
p.000034: to be destroyed. Consequently, there is no argument for excluding funding of this kind of research from the
p.000034: Framework Programme of research of the European Union if it complies with ethical and legal requirements
p.000034: as defined in this programme”.
p.000034:
p.000034: Secondly the EGE stated, that:
p.000034:
p.000034: “Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells)
p.000034: requires a specific Community research budget. In particular, EU funding should be devoted to testing the validity of
p.000034: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000034: such research be widely disseminated and not hidden for reasons of commercial interest.
p.000034: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000034: funding for stem cell research. This implies the establishment of appropriate procedures and provision of
p.000034: sufficient means to permit ethical assessment not only before the launching of a project but also in monitoring
p.000034: its implementation.”
p.000034:
p.000034: Principal requirements regarding human embryonic stem cell research.
p.000034: Concerning the use of human supernumerary embryos as a source of stem cells the EGE stressed in their
p.000034: opinion that “ the derivation of stem cells from embryonic blastocysts raises the issue of the moral status of the
p.000034: human embryo. In the context of European pluralism, it is up to each Member State to forbid or authorise embryo
p.000034: research. In the latter case, respect for human dignity requires regulation of embryo research and the
p.000034: provision of guarantees against risks of arbitrary experimentation and instrumentalisation of human embryos”.
p.000034:
p.000034: The EGE also stressed regarding stem cell research and rights of women that “Women who undergo infertility treatment
p.000034: are subject to high psychological and physical strain. The group stresses the necessity to ensure that the demand for
p.000034: spare embryos (supernumerary embryos) and oocyte donation does not increase the burden on women”.
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: 55 Spare embryos: another word for supernumerary embryos.
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035: The EGE stressed also the importance of the following requirements regarding human embryonic stem cell
p.000035: research and the procurement of embryonic stem cells from supernumerary embryos:
p.000035:
p.000035: – Free and informed consent from the donating couple or woman.
p.000035: The EGE stated: “Free and informed consent is required not only from the donor but also from the
p.000035: recipient as stated in the Group's opinion on Human Tissue Banking (21/07/1998). In each case, it is necessary to
p.000035: inform the donor (the woman or the couple) of the possible use of the embryonal cells for the specific purpose
p.000035: in question before requesting consent.” The requirements may differ on the type of information that should
p.000035: be provided and on the definition of which persons should give their consent (the couple or the woman). The Charter
p.000035: of Fundamental Rights of the European Union recognised in article 3(2) that “In the fields of medicine and biology the
p.000035: following must be respected in particular – the free and informed consent of the person concerned, according to the
p.000035: procedures laid down by law…”.
p.000035:
p.000035: – Approval of the research by an authority.
p.000035: The EGE recommended that human ES cell research should be placed, “in the countries where it is
p.000035: permitted, under strict public control by a centralised authority - following, for instance, the pattern of
p.000035: the UK licensing body (the Human Fertilisation and Embryology Authority)” and provided that “ authorisations
p.000035: given to such research are highly selective and based on a case by case approach, while ensuring maximum transparency.
p.000035: This must apply whether the research in question is carried out by either the public or the private sector”.
p.000035:
p.000035: – No financial gain for donation
p.000035: The EGE recommended that “The potential for coercive pressure should not be underestimated when
p.000035: there are financial incentives. Embryos as well as cadaveric foetal tissue must not be bought or sold, and not
p.000035: even offered for sale. Measures should be taken to prevent such commercialisation”.
p.000035: The Charter of Fundamental Rights of the European Union recognised in article 3(2) that “In the fields of medicine
p.000035: and biology the following must be respected in particular… the prohibition on making the human body and its
p.000035: parts as such a source of financial gain”.
p.000035: Article 21 of the Council of Europe Convention on Human Rights and Biomedicine specifically prohibits
p.000035: financial gain from all or part of the human body.
p.000035:
p.000035: – Anonymity of the donors and protection of the confidentiality of personal information of the
p.000035: donors as it applies for donation of human biological material.
p.000035: The EGE recommended that “Steps must be taken to protect and preserve the identity of both the donor and the recipient
p.000035: in stem cell research and use”. As stated in the EGE's Opinion on Human Tissue Banking (21/07/1998): “in the
p.000035: interests of anonymity, it is prohibited to disclose information that could identify the donor, and the
p.000035: recipient. In general, the donor should not know the identity of the recipient, nor should the recipient know the
p.000035: identity of the donor”. In most cases the donors will not be anonymous in the sense that the embryo could be traced
p.000035: back to the donor of the egg and sperm. Although the identity of the donor should normally be
p.000035: protected though coding and other measures to ensure confidentiality, there would still be safety and quality
p.000035: requirements for clinical research demanding that the link to the donors not be completely removed. Anonymity will then
p.000035: not be possible.
p.000035:
p.000035:
p.000035:
p.000035:
...
p.000037: research must have the aim to lead to new insights in medical science.
p.000037:
p.000037: Sweden
p.000037: The Act of 1991 on “Measures for Purposes of Research and Treatment involving Fertilised Human Ova” and the Health
p.000037: and Medical Care Act (18-982:763) apply. According to the Act(1991:115), in vitro embryo research is
p.000037: legally permitted until day 14 after conception, after which the embryo must be destroyed.. After some discussion
p.000037: there is consensus that this legislation permits human embryonic stem cell research. A revision of the law
p.000037: is under discussion (see chapter 3.3)
p.000037:
p.000037: United Kingdom
p.000037: The research purposes permitted by the Human Fertilisation and Embryology Act of 1990 were extended by
p.000037: the “Human Fertilisation and Embryology (Research Purposes ) Regulation” of 2001 to permit the use
p.000037: of embryos in research to increase knowledge about serious diseases and their treatment. The Human
p.000037: Fertilisation and Embryology Authority is
p.000037:
p.000037:
p.000037: 56 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000037: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000037: cell research and use (last update March 2003); “Survey on the National Regulations in the European Union
p.000037: regarding Research on Human Embryos” - B. Gratton - published by the Secretariat of the EGE - European Commission -
p.000037: July 2002.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: responsible for licensing research involving the creation and use of human embryos. The HFEA requires the
p.000038: informed consent of the donors and free donation. The first two licences for stem cell research under the 2001
p.000038: Regulations were issued by HFEA in February 2002.
p.000038:
p.000038: 2. Prohibition of the procurement of embryonic stem cells from human embryos but allowing by law
p.000038: the import and use of human embryonic stem cell lines under certain conditions.
p.000038: Germany
p.000038: The Embryo protection Act of 1990 forbids any research which is not for the benefit of the concerned embryo.
p.000038: A new Act ensuring protection of embryos in connection with the importation and utilisation of human embryonic stem
p.000038: cells – Stem Cell Act – (Stammzellgesetz – StZG) was adopted on 28 June 2002.
p.000038: Concerning importation and utilisation of embryonic stem cells the act specifies in section 4 , that:
p.000038: (1) The importation and utilisation of embryonic stem cells shall be prohibited.
p.000038: (2) Notwithstanding para 1, the importation and utilisation of embryonic stem cells for research purposes shall be
...
p.000047: this as one of the key factors to allow stem cell research to move forward and is currently soliciting grant
p.000047: applications to support training courses to teach researchers how best to grow existing banked stem cells into
p.000047: useful lines.
p.000047:
p.000047: – A number of initiatives to facilitate research on all types of stem cells. In particular, the NIH
p.000047: continues to support research on developing the therapeutic potential of adult stem cells.
p.000047: New federal legislation is under debate in the US Congress. The State of California has passed a law, in
p.000047: September 2002, allowing the procurement of human embryonic stem cells from supernumerary embryos. New legislation
p.000047: authorising the procurement of human ES cells from supernumerary embryos is under discussion in the
p.000047: States of New Jersey and Massachusetts.
p.000047: In Australia a new law is under discussion to allow for the derivation of human ES cells from supernumerary embryos.
p.000047:
p.000047: Laboratories in Singapore, Taiwan, South Korea, China… are actively conducting human ES cell research. Legislation
p.000047: regarding this research is under discussion in some of these countries.
p.000047: Annex D provides further information regarding provisions in non-EU countries relating to human embryonic
p.000047: stem cell research.
p.000047:
p.000047: 3.5. Governance of stem cell research in the context of FP6
p.000047: As stated in the Treaty of the European Union, article 6:
p.000047:
p.000047: “1. The Union is founded on the principles of liberty, democracy, respect for human rights and fundamental freedom, and
p.000047: the rule of law, principles which are common to the Member States.
p.000047:
p.000047: 2. The Union shall respect fundamental rights, as guaranteed by the European Convention for the protection of Human
p.000047: Rights and Fundamental Freedoms signed in Rome on 4 November 1950 and as they result from the constitutional traditions
p.000047: common to the Member States, as general principles of Community law.
p.000047:
p.000047: 3. The Union shall respect the national identities of its Member States.
p.000047:
p.000047: 4. The Union shall provide itself with the means necessary to attain its objectives and carry through its policies.”
p.000047:
p.000047: In accordance with the EU Treaty, each Member State retains its full prerogative to legislate on ethical matters. At
p.000047: the level of the Community, ethical principles have been defined with regard to the funding of research under the
p.000047: research Framework Programme.
p.000047:
p.000047: As far as FP6 is concerned, the following ethical principles have been established:
p.000047:
p.000047: The decision No. 1513/2002/EC of the European Parliament and of the Council of 27 June 2002 concerning the sixth
p.000047: framework programme of the European Community for research,
p.000047:
p.000047:
p.000047:
p.000048: 48
p.000048:
p.000048: technological development and demonstration activities, contributing to the creation of the European Research
p.000048: Area and to innovation (2002 to 2006) stipulates among others that61:
p.000048: – “Fundamental ethical principles are to be respected. These include the principles reflected in the
p.000048: Charter of fundamental rights of the EU including the protection of human dignity and human life…”
p.000048:
p.000048: The Charter of Fundamental Rights of the European Union, proclaimed in Nice, France, on 7 December 2000, explicitly
p.000048: prohibits eugenic practices and reproductive cloning, but does not comment explicitly on embryo research (article 3)
p.000048:
p.000048: – … “in accordance with relevant international conventions and codes of conduct, e.g.
p.000048: … the Convention of the Council of Europe on Human Rights and Biomedicine signed in Oviedo on 4 April 1997,
p.000048: and the Additional Protocol on the Prohibition of Cloning Human Beings signed in Paris on 12 January 1998”
p.000048:
p.000048: The Council of Europe’s Convention for the Protection of Human Rights and Dignity of the Human Being with regard to
p.000048: the Application of Biology and Medicine of 199762 does not resolve the matter of the permissibility of
p.000048: embryo research and leaves every country responsibility for legislating on this matter, while stipulating two
p.000048: conditions: the prohibition of producing human embryos for research purposes and the adoption of rules
p.000048: designed to assure adequate protection for the embryo63. An Additional Protocol to the Convention on the Prohibition
p.000048: of Cloning Human Beings was approved in 1998 and took effect on 3 January 2001 in thirteen Member States
p.000048: of the Council of Europe64.
p.000048: – “… in accordance with Community law”
p.000048:
p.000048: Some EU Directives are relevant for human ES cell research. For instance, the Directive 2001/20/EC on
p.000048: the approximation of laws, regulations and administrative provisions of the Member States relating to the
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p.000069:
p.000069: ANNEX E: Opinion No.15 of the European Group on Ethics regarding ethical aspects of human stem cell research and use
p.000069:
p.000069:
p.000069:
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p.000069:
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p.000069:
p.000069: OPINION OF THE EUROPEAN GROUP ON ETHICS IN SCIENCE AND NEW TECHNOLOGIES
p.000069: No 15
p.000069: 14 November 2000
p.000069: ************************************************************************************************************************
p.000069: ***
p.000069:
p.000069: ETHICAL ASPECTS OF HUMAN STEM CELL RESEARCH AND USE
p.000069:
p.000069: Reference: Initiative of the Group
p.000069: Rapporteurs: Anne McLaren and Göran Hermerén
p.000069:
p.000069: ************************************************************************************************************************
p.000069: ***
p.000069:
p.000069: The European Group on Ethics in Science and New Technologies (EGE),
p.000069:
p.000069: Having regard to the Treaty on European Union as amended by the Treaty of Amsterdam, and in particular
p.000069: Article 6 (formerly Article F) of the common provisions, concerning the respect for fundamental rights, Article 152
p.000069: (formerly Article 129) of the EC Treaty on public health, (namely paragraph 4(a) referring to substances of
p.000069: human origin) and Articles 163-173 (formerly Articles 130F-130P) on research and technological development;
p.000069:
p.000069: Having regard to the European Parliament and Council Directive 65/65/CEE of 26 January 1965 and the modified Directive
p.000069: 75/319/CEE of 20 May 1975 concerning medicinal products;
p.000069:
p.000069: Having regard to the Council Directive 93/42/EEC of 14 June 1993 concerning medical devices and the European Parliament
p.000069: and Council Directive 98/79/EC of 27 October 1998 concerning in vitro diagnostic medical devices, in particular Article
p.000069: 1-4 which refers to ethics and requires the respect of the principles of the Convention of the Council of Europe
p.000069: on Human Rights and Biomedicine, with regard to the removal, collection and use of tissues, cells and
p.000069: substances of human origin;
p.000069:
p.000069: Having regard to the Council Directive 98/44/EC of 6 July 1998 on the legal protection of
p.000069: biotechnological inventions and in particular Article 6, concerning certain inventions excluded from
p.000069: patentability, and Article 7 giving mandate to the European Group on Ethics (EGE) to evaluate "all
p.000069: ethical aspects of biotechnology”;
p.000069:
p.000069:
p.000069:
p.000069:
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p.000070: 70
p.000070:
p.000070: Having regard to the Parliament and Council Decision of 22 December 1998 concerning the 5th Framework
p.000070: Programme of the European Community for research, technological development and demonstration activities
p.000070: (1998-2002) and in particular Article 7 requesting compliance with fundamental ethical principles;
p.000070:
p.000070: Having regard to the Council Decision of 25 January 1999 adopting the specific programme for research, technological
p.000070: development and demonstration activities on quality of life and management of living resources and in
p.000070: particular the ethical requirements mentioned in its Annex II;
p.000070:
p.000070: Having regard to the Charter of 28 September 2000 on Fundamental Rights of the European Union, approved
p.000070: by the European Council in Biarritz on October 14th 2000, in particular Article 1 on “Human dignity”, Article 3 on
p.000070: the “Right to the integrity of the person”, which refers to the principle of "free and informed consent" and prohibits
p.000070: "the reproductive cloning of human beings" and Article 22 on “Cultural, religious and linguistic diversity”;
p.000070:
p.000070: Having regard to the Council of Europe’s Convention on Human Rights and Biomedicine, signed on 4 April 1997 in Oviedo,
p.000070: in particular Article 18 on embryo research, and to the additional protocol to the Convention on the prohibition of
p.000070: cloning human beings signed on 12 January 1998 in Paris;
p.000070:
p.000070: Having regard to the Universal Declaration on the Human Genome and Human Rights adopted by the United Nations on 11
p.000070: December 1998, in particular Article 11 which recommends to prohibit reproductive cloning of human beings, and Article
p.000070: 13 which refers to the responsibilities of researchers as well as of science policy makers;
p.000070:
p.000070: Having regard to national regulations on stem cell and on embryo research and to national ethics bodies opinions, at
p.000070: the European Union level, concerning these subjects;
p.000070:
p.000070: Having regard to the reports of the US National Bioethics Advisory Committee dated September 13, 1999 on
p.000070: the "Ethical Issues on Human Stem Cell Research", the hearings on the same subject by the US Congress, on April 2000
p.000070: and the guidelines published by the Clinton administration on August 26, 2000 to be forwarded to a NIH (National
p.000070: Institutes of Health) scientific review in 2001;
p.000070:
p.000070: Having regard to the Round Table organised by the Group on 26 June 2000 in Brussels with members of the European
p.000070: Parliament, jurists, philosophers, scientists, representatives of industries, of religions, of patients' associations,
p.000070: and of international organisations (Council of Europe, UNESCO, WHO);
p.000070:
p.000070: Having regard to the Hearings of scientific experts on 6 June 2000 and on 2 October 2000, and to the Hearings of
p.000070: representatives of religions on 8 September 2000;
p.000070:
p.000070: Having heard the rapporteurs Anne McLaren and Goran Hermerén;
p.000070:
p.000070:
p.000070:
p.000070: 1 - WHEREAS SCIENTIFIC BACKGROUND
p.000070: 1.1. How to define stem cells?
p.000070:
p.000070: Stem cells are cells that can divide to produce either cells like themselves (self-renewal), or cells
p.000070: of one or several specific differentiated types. Stem cells are not yet fully differentiated and therefore can
p.000070: reconstitute one or several types of tissues.
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000071: 71
p.000071:
p.000071: 1.2. What are the different kinds of stem cells?
p.000071:
...
p.000076: response to the challenge of stem cell research.
p.000076:
p.000076: - In some countries, draft legislation is being prepared to allow research on stem cells derived from
p.000076: supernumerary embryos after in vitro fertilisation (The Netherlands).
p.000076:
p.000076: - In other countries, draft legislation provides for the possibility of creating embryos by nuclear transfer, for the
p.000076: sole purpose of stem cell research. This is the case in Belgium, and in the UK. (In the latter case, legislation
p.000076: allowed creation of embryos for the purpose of research, but only in relation to the treatment of infertility, to
p.000076: contraception or to the avoidance of genetic disease). In France legislation is under preparation.
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000077: 77
p.000077:
p.000077: 1.14. European legislation in the field
p.000077:
p.000077: At the Council of Europe’s level, the Convention on Human Rights and Biomedicine signed in Oviedo in 1997 in its
p.000077: Article 18 establishes that it is up to each country to decide whether to authorise or not embryo research. Each
p.000077: country is only obliged to respect two conditions: “to ensure adequate protection of the embryo”, that is to say to
p.000077: adopt a legislation fixing the conditions and limits of such research; and to prohibit “the creation of human embryos
p.000077: for research purposes”. The Convention is binding only for the States which have ratified it. In the
p.000077: European Union so far only three countries have completed the procedure and some are in the process of doing so.
p.000077:
p.000077: At EU level, although there is no legislative competence to regulate research, some Directives allude to the issue of
p.000077: embryo research and use. For instance, the Directive 98/44/EC on the legal protection of biotechnological
p.000077: inventions (patenting on life) stipulates that “processes for cloning human beings” and “uses of human embryos for
p.000077: industrial or commercial purposes”… “shall be considered unpatentable”. The Directive 98/79/EC on in vitro
p.000077: diagnostic medical devices (including the use of human tissues) provides that “ the removal, collection and use of
p.000077: tissues, cells and substances of human origin shall be governed, in relation to ethics, by the principles laid down in
p.000077: the Convention of the Council of Europe for the protection of human rights and dignity of the human being with regard
p.000077: to the application of biology and medicine and by any Member States regulations on this matter”.
p.000077:
p.000077: At this same level, the Charter on Fundamental rights of the European Union approved by the European Council in
p.000077: Biarritz (France) on October 14, 2000 prohibits different kinds of practices possibly related to embryo
p.000077: research, namely “eugenic practices, in particular those aiming at the selection of persons ” and “the
p.000077: reproductive cloning of human beings”.
p.000077:
p.000077:
p.000077:
p.000077: 1.15. US approach related to embryo research and stem cell research
p.000077:
p.000077: The situation in the US contrasts with that in Europe. A substantial difference is a sharp distinction
p.000077: between the public and the private sector. Since 1995 the US Congress has been adopting each year a
p.000077: provision in the Appropriation Bill to prohibit public funding for embryo research. Thus, the National Institutes of
p.000077: Health (NIH) cannot carry out embryo research, which, in the absence of legislation, remains free and beyond control in
p.000077: the private sector.
p.000077:
p.000077: New discoveries concerning the culturing of human stem cells in 1998 have led to the reopening of the debate. The
p.000077: National Bioethics Advisory Committee (NBAC) issued a report on September 1999; hearings took place in 1999 and 2000
p.000077: before the competent Committees of the US Congress and finally the Clinton administration proposed that,
p.000077: under certain conditions, the funding of research to derive and study human ES cells be permitted. New guidelines of
p.000077: the NIH were published in August 2000 according to which research on human ES cells can be publicly funded if two
...
p.000078: those who accept it, this issue is of major importance.
p.000078:
p.000078:
p.000078:
p.000078: 1.17. Ethical issues in transplantation of stem cells
p.000078:
p.000078: Clinical research and potential future applications in this field raise the same ethical issues as those dealt with in
p.000078: the EGE's Opinion on Human Tissue Banking (21/07/1998), concerning the respect of the donor, who should give informed
p.000078: consent to this use of the donated cells, the respect of the autonomy of the patients, their right to safety and to the
p.000078: protection of their private life and the right to a fair and equal access to new therapies.
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
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p.000078:
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p.000078:
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p.000078:
p.000078:
p.000078:
p.000078:
p.000079: 79
p.000079:
p.000079: 2 - OPINION
p.000079: The Group submits the following Opinion:
p.000079:
p.000079: SCOPE OF THE OPINION
p.000079:
p.000079: 2.1 Ethical issues of stem cell research and use for clinical purposes.
p.000079: This Opinion reviews ethical issues raised by human stem cell research and use, in the context of the European Union
p.000079: research policy and European Community public health competence to improve human health and to set high standards for
p.000079: the safety of substances of human origin.
p.000079: With regard to the specific ethical questions related to the patenting of inventions involving human stem cells, on
p.000079: which President Prodi requested an Opinion from the Group on 18 October 2000, this will be made public in Brussels at a
p.000079: later date. The following Opinion therefore excludes the patenting issue.
p.000079:
p.000079: GENERAL APPROACH
p.000079: 2.2. Fundamental ethical principles at stake
p.000079: The fundamental ethical principles applicable are those already recognised in former opinions of the EGE, and more
p.000079: specifically:
p.000079: - the principle of respect for human dignity
p.000079: - the principle of individual autonomy (entailing the giving of informed consent, and respect for privacy and
p.000079: confidentiality of personal data)
p.000079: - the principle of justice and of beneficence (namely with regard to the improvement and protection of health)
p.000079: - the principle of freedom of research (which is to be balanced against other fundamental principles)
p.000079: - the principle of proportionality (including that research methods are necessary to the aims pursued and that no
p.000079: alternative more acceptable methods are available).
p.000079: In addition, the Group considers it important to take into account, based on a precautionary approach,
p.000079: the potential long-term consequences of stem cell research and use for individuals and the society.
p.000079:
p.000079: 2.3. Pluralism and European ethics
p.000079: Pluralism is characteristic of the European Union, mirroring the richness of its tradition and adding a need for mutual
p.000079: respect and tolerance. Respect for different philosophical, moral or legal approaches and for diverse
p.000079: cultures is implicit in the ethical dimension of building a democratic European society.
p.000079: From a legal point of view, respect for pluralism is in line with Article 22 of the Charter on Fundamental Rights on
p.000079: “Cultural, religious and linguistic diversity” and with Article 6 of the Amsterdam Treaty which ensures
p.000079: the protection of fundamental rights at EU level, notably based on international instruments as well as
p.000079: common constitutional traditions, while also stressing the respect for the national identity of all Member States.
p.000079:
p.000079:
p.000079: BASIC RESEARCH ON HUMAN STEMXCELLS
p.000079:
p.000079: 2.4. Principal requirements according to the diverse sources of stem cells.
p.000079: • The retrieval of adult stem cells requires the same conditions as those required in the case of tissue
p.000079: donation, based on respect for the integrity of the human body and the free and informed consent of the donor.
p.000079: • The retrieval of stem cells from the umbilical cord blood after delivery requires that the donor (the woman or
...
p.000079: abortion is induced for the purpose of obtaining the tissues and that the termination timing and the way it is carried
p.000079: out are not influenced by this retrieval.
p.000079: • The derivation of stem cells from embryonic blastocysts raises the issue of the moral status of the human embryo.
p.000079: In the context of European pluralism, it is up to each Member State to forbid or authorise embryo
p.000079: research. In the latter case, respect for human dignity requires regulation of
p.000079:
p.000079:
p.000079:
p.000079:
p.000080: 80
p.000080:
p.000080: embryo research and the provision of guarantees against risks of arbitrary experimentation and
p.000080: instrumentalisation of human embryos.
p.000080:
p.000080: 2.5. Ethical acceptability of the field of the research concerned.
p.000080: The Group notes that in some countries embryo research is forbidden. But when this research is allowed, with the
p.000080: purpose of improving treatment for infertility, it is hard to see any specific argument which would prohibit extending
p.000080: the scope of such research in order to develop new treatments to cure severe diseases or injuries. As in the case of
p.000080: research on infertility, stem cell research aims to alleviate severe human suffering. In any case, the embryos that
p.000080: have been used for research are required to be destroyed. Consequently, there is no argument for excluding funding of
p.000080: this kind of research from the Framework Programme of research of the European Union if it complies with ethical and
p.000080: legal requirements as defined in this programme.
p.000080:
p.000080: 2.6. Public control of ES cell research.
p.000080:
p.000080: The Group deems it essential to underline the sensitivity attached to the use of embryonic stem cells, since this use
p.000080: may change our vision of the respect due to the human embryo.
p.000080:
p.000080: According to the Group, it is crucial to place ES cell research, in the countries where it is permitted, under strict
p.000080: public control by a centralised authority - following, for instance, the pattern of the UK licensing body (the Human
p.000080: Fertilisation and Embryology Authority) - and to provide that authorisations given to such research are highly
p.000080: selective and based on a case by case approach, while ensuring maximum transparency. This must apply whether the
p.000080: research in question is carried out by either the public or the private sector.
p.000080:
p.000080:
p.000080: 2.7. Alternative methods to the creation of embryos for the purpose of stem cell research.
p.000080: The Group considers that the creation of embryos for the sole purpose of research raises serious
p.000080: concerns since it represents a further step in the instrumentalisation of human life.
p.000080:
p.000080: • The Group deems the creation of embryos with gametes donated for the purpose of stem cell
p.000080: procurement ethically unacceptable, when spare embryos represent a ready alternative source.
p.000080:
p.000080: • The Group takes into account interest in performing somatic cell nuclear transfer (SCNT) with the
...
p.000080: • In the opinion of the Group, in such a highly sensitive matter, the proportionality principle and
p.000080: a precautionary approach must be applied: it is not sufficient to consider the legitimacy of the pursued aim of
p.000080: alleviating human sufferings, it is also essential to consider the means employed. In particular, the hopes of
p.000080: regenerative medicine are still very speculative and debated among scientists. Calling for prudence, the
p.000080: Group considers that, at present, the creation of embryos by somatic cell nuclear transfer for research on
p.000080: stem cell therapy would be premature, since there is a wide field of research to be carried out with alternative
p.000080: sources of human stem cells (from spare embryos, foetal tissues and adult stem cells).
p.000080:
p.000080: 2.8. Stem cell research in the European Framework Programme of research
p.000080: Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells) requires a
p.000080: specific Community research budget. In particular, EU funding should be devoted to testing the validity
p.000080:
p.000080:
p.000080:
p.000080:
p.000080:
p.000081: 81
p.000081:
p.000081: of recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the
p.000081: results of such research be widely disseminated and not hidden for reasons of commercial interest.
p.000081: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000081: funding for stem cell research. This implies the establishment of appropriate procedures and provision of sufficient
p.000081: means to permit ethical assessment not only before the launching of a project but also in monitoring its
p.000081: implementation.
p.000081:
p.000081: 2.9. Stem cell research and rights of women
p.000081: Women who undergo infertility treatment are subject to high psychological and physical strain. The Group
p.000081: stresses the necessity to ensure that the demand for spare embryos and oocyte donation does not increase
p.000081: the burden on women.
p.000081:
p.000081: CLINICAL RESEARCH ON HUMAN STEMXCELLS
p.000081: The speed with which researchers, throughout the world, are moving to test stem cells in patients is remarkable, even
p.000081: if ES cell transplantation is unlikely to be attempted in the near future. Clinical trials with stem cells other than
p.000081: ES carried out on patients suffering from severe conditions such as Parkinson’s disease, heart disease or diabetes
p.000081: raise the following issues:
p.000081:
p.000081:
p.000081: 2.10. Free and informed consent
p.000081:
p.000081: Free and informed consent is required not only from the donor but also from the recipient as stated in the Group's
...
p.000082: scientific governance, namely in the social choices created by new scientific developments.
p.000082:
p.000082:
p.000082: The European Group on Ethics in Science and New Technologies:
p.000082:
p.000082: The Members
p.000082:
p.000082: Paula Martinho da Silva Anne McLaren Marja Sorsa
p.000082:
p.000082: Ina Wagner Goran Hermerén Gilbert Hottois
p.000082:
p.000082: Dietmar Mieth Octavi Quintana Trias Stefano Rodota
p.000082:
p.000082: Egbert Schroten Peter Whittaker The Chairperson
p.000082: Noëlle Lenoir
p.000082:
p.000082:
p.000082:
p.000082:
p.000083: 83
p.000083:
p.000083: ANNEX F: Statement for the minutes of the Council meeting 30 September 2002
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p.000084: 84
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p.000084:
p.000084:
p.000084:
p.000084:
p.000084: COUNCIL OF
p.000084: THE EUROPEAN UNION
p.000084:
p.000084: Brussels, 21 October 2002 (24.10)
p.000084: (OR. fr)
p.000084:
p.000084:
p.000084: 12523/02
p.000084: ADD 1 REV 1
p.000084:
p.000084: LIMITE
p.000084:
p.000084: PV/CONS 48
p.000084: MI 186
p.000084: IND 65
p.000084: RECH 150
p.000084:
p.000084: ADDENDUM TO DRAFT MINUTES 1
p.000084: Subject: 2451st meeting of the COUNCIL OF THE EUROPEAN UNION (COMPETITIVENESS) (Internal Market,
p.000084: Industry and Research)
p.000084: held in Brussels on 30 September 2002
p.000084:
p.000084:
p.000084:
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p.000084:
p.000084:
p.000084:
p.000084:
p.000084: 1 The information from the Council minutes which is contained in this addendum is not confidential and may therefore
p.000084: be released to the public.
p.000084:
p.000084:
p.000084:
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p.000085: 85
p.000085:
p.000085:
p.000085:
p.000085:
p.000085: "A" ITEMS
p.000085: CONTENTS
p.000085:
p.000085:
p.000085: Page
p.000085:
p.000085: Item 5. Directive of the European Parliament and of the Council on insurance mediation.
p.000003: 3
p.000003: "B" ITEMS
p.000003: Item 3 (a) Council Decision adopting a specific programme for research, technological development and demonstration:
p.000003: "Integrating and strengthening the European Research Area" (2002-
p.000003: 2006).
p.000004: 4
p.000004: Item 3 (b) Council Decision adopting a specific programme for research, technological development and demonstration:
p.000004: "Structuring the European Research
p.000004: Area" (2002-2006) 4
p.000004: Item 3 (c) Council Decision adopting a specific programme of research, technological development and demonstration to
p.000004: be carried out by means of direct actions by the Joint Research Centre (2002-2006)…
p.000004: 4
...
Social / Victim of Abuse
Searching for indicator trauma:
(return to top)
p.000074: drugs, it will be possible to sort out medicinal products that may be either useful or on the contrary problematic in
p.000074: human medicine.
p.000074:
p.000074:
p.000074:
p.000074:
p.000074:
p.000074:
p.000075: 75
p.000075:
p.000075: • Use of stem cells in gene therapy. Stem cells could be used as vectors for the delivery of gene therapy. One
p.000075: current application in clinical trials is the use of haematopoietic stem cells genetically modified to make them
p.000075: resistant to the HIV (virus responsible for AIDS).
p.000075:
p.000075: • Production of specific cell lines for therapeutic transplantation. If feasible, this would be the
p.000075: most promising therapeutic application of ES cells. Research is being actively pursued, mostly in the mouse, with the
p.000075: aim of directing the differentiation of pluripotent stem cells to produce pure populations of particular cell types
p.000075: to be used for the repair of diseased or damaged tissues. For instance, the aim would be to produce
p.000075: cardiac muscle cells to be used to alleviate ischaemic heart disease, pancreatic islet cells for
p.000075: treatment of diabetes (juvenile onset diabetes mellitus), liver cells for hepatitis, neural cells for degenerative
p.000075: brain diseases such as Parkinson's disease, and perhaps even cells for treating some forms of cancer. The
p.000075: transplantation of stem cells could also help, for example, to repair spinal cord damage which occurs
p.000075: frequently, mainly following trauma (for instance car accidents) and is responsible for paraplegia. Results of that
p.000075: kind of cell therapy on animals are promising, but are still years away from clinical application. Even more remote
p.000075: (possibly decades away) is the prospect of being able to grow whole organs in vitro, but if tissues for
p.000075: the repair of organs become available, it would greatly relieve the existing unsatisfied demand for donated organs for
p.000075: transplantation. In providing a potentially unlimited source of specific clinically important cells such as bone,
p.000075: muscle, liver or blood cells, the use of human stem cells could open the way to a new "regenerative medicine".
p.000075:
p.000075:
p.000075:
p.000075: 1.11. Why is somatic cell nuclear transfer (SCNT) considered?
p.000075:
p.000075: Apart from its interest for basic research, SCNT is considered as a possible strategy, in "regenerative medicine", for
p.000075: the avoidance of immunological problems after transplantation. Neural tissues can sometimes be transplanted
p.000075: from one individual to another without suffering immunological rejection, but for all other tissues, stem
p.000075: cell therapy would need to be accompanied by long-term treatments with immunosuppressive drugs, leading to
p.000075: increased susceptibility to infections and even to cancer.
p.000075:
p.000075: • One approach to avoid this immune rejection problem would involve genetic engineering of stem cells to render
p.000075: them non-antigenic, or immunological manipulation of the patients to render them tolerant.
p.000075:
p.000075: • An alternative approach is based on somatic cell nuclear transfer. It consists of transferring nuclei from the
...
Social / Women
Searching for indicator women:
(return to top)
p.000034: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000034: such research be widely disseminated and not hidden for reasons of commercial interest.
p.000034: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000034: funding for stem cell research. This implies the establishment of appropriate procedures and provision of
p.000034: sufficient means to permit ethical assessment not only before the launching of a project but also in monitoring
p.000034: its implementation.”
p.000034:
p.000034: Principal requirements regarding human embryonic stem cell research.
p.000034: Concerning the use of human supernumerary embryos as a source of stem cells the EGE stressed in their
p.000034: opinion that “ the derivation of stem cells from embryonic blastocysts raises the issue of the moral status of the
p.000034: human embryo. In the context of European pluralism, it is up to each Member State to forbid or authorise embryo
p.000034: research. In the latter case, respect for human dignity requires regulation of embryo research and the
p.000034: provision of guarantees against risks of arbitrary experimentation and instrumentalisation of human embryos”.
p.000034:
p.000034: The EGE also stressed regarding stem cell research and rights of women that “Women who undergo infertility treatment
p.000034: are subject to high psychological and physical strain. The group stresses the necessity to ensure that the demand for
p.000034: spare embryos (supernumerary embryos) and oocyte donation does not increase the burden on women”.
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: 55 Spare embryos: another word for supernumerary embryos.
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035: The EGE stressed also the importance of the following requirements regarding human embryonic stem cell
p.000035: research and the procurement of embryonic stem cells from supernumerary embryos:
p.000035:
p.000035: – Free and informed consent from the donating couple or woman.
p.000035: The EGE stated: “Free and informed consent is required not only from the donor but also from the
p.000035: recipient as stated in the Group's opinion on Human Tissue Banking (21/07/1998). In each case, it is necessary to
p.000035: inform the donor (the woman or the couple) of the possible use of the embryonal cells for the specific purpose
p.000035: in question before requesting consent.” The requirements may differ on the type of information that should
p.000035: be provided and on the definition of which persons should give their consent (the couple or the woman). The Charter
p.000035: of Fundamental Rights of the European Union recognised in article 3(2) that “In the fields of medicine and biology the
p.000035: following must be respected in particular – the free and informed consent of the person concerned, according to the
p.000035: procedures laid down by law…”.
p.000035:
...
p.000080: Fertilisation and Embryology Authority) - and to provide that authorisations given to such research are highly
p.000080: selective and based on a case by case approach, while ensuring maximum transparency. This must apply whether the
p.000080: research in question is carried out by either the public or the private sector.
p.000080:
p.000080:
p.000080: 2.7. Alternative methods to the creation of embryos for the purpose of stem cell research.
p.000080: The Group considers that the creation of embryos for the sole purpose of research raises serious
p.000080: concerns since it represents a further step in the instrumentalisation of human life.
p.000080:
p.000080: • The Group deems the creation of embryos with gametes donated for the purpose of stem cell
p.000080: procurement ethically unacceptable, when spare embryos represent a ready alternative source.
p.000080:
p.000080: • The Group takes into account interest in performing somatic cell nuclear transfer (SCNT) with the
p.000080: objective of studying the conditions necessary for "reprogramming" adult human cells. It is also aware that, in view
p.000080: of future cell therapy, the creation of embryos by this technique may be the most effective way to
p.000080: derive pluripotent stem cells genetically identical to the patient and consequently to obtain perfectly
p.000080: histocompatible tissues, with the aim of avoiding rejection after transplantation. But, these remote therapeutic
p.000080: perspectives must be balanced against considerations related to the risks of trivialising the use of embryos
p.000080: and exerting pressure on women, as sources of oocytes, and increasing the possibility of their instrumentalisation.
p.000080: Given current high levels of inefficiency in SCNT, the provision of cell lines would require large numbers of oocytes.
p.000080: • In the opinion of the Group, in such a highly sensitive matter, the proportionality principle and
p.000080: a precautionary approach must be applied: it is not sufficient to consider the legitimacy of the pursued aim of
p.000080: alleviating human sufferings, it is also essential to consider the means employed. In particular, the hopes of
p.000080: regenerative medicine are still very speculative and debated among scientists. Calling for prudence, the
p.000080: Group considers that, at present, the creation of embryos by somatic cell nuclear transfer for research on
p.000080: stem cell therapy would be premature, since there is a wide field of research to be carried out with alternative
p.000080: sources of human stem cells (from spare embryos, foetal tissues and adult stem cells).
p.000080:
p.000080: 2.8. Stem cell research in the European Framework Programme of research
p.000080: Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells) requires a
p.000080: specific Community research budget. In particular, EU funding should be devoted to testing the validity
p.000080:
p.000080:
p.000080:
p.000080:
p.000080:
p.000081: 81
p.000081:
p.000081: of recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the
p.000081: results of such research be widely disseminated and not hidden for reasons of commercial interest.
p.000081: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000081: funding for stem cell research. This implies the establishment of appropriate procedures and provision of sufficient
p.000081: means to permit ethical assessment not only before the launching of a project but also in monitoring its
p.000081: implementation.
p.000081:
p.000081: 2.9. Stem cell research and rights of women
p.000081: Women who undergo infertility treatment are subject to high psychological and physical strain. The Group
p.000081: stresses the necessity to ensure that the demand for spare embryos and oocyte donation does not increase
p.000081: the burden on women.
p.000081:
p.000081: CLINICAL RESEARCH ON HUMAN STEMXCELLS
p.000081: The speed with which researchers, throughout the world, are moving to test stem cells in patients is remarkable, even
p.000081: if ES cell transplantation is unlikely to be attempted in the near future. Clinical trials with stem cells other than
p.000081: ES carried out on patients suffering from severe conditions such as Parkinson’s disease, heart disease or diabetes
p.000081: raise the following issues:
p.000081:
p.000081:
p.000081: 2.10. Free and informed consent
p.000081:
p.000081: Free and informed consent is required not only from the donor but also from the recipient as stated in the Group's
p.000081: opinion on Human Tissue Banking (21/07/1998). In each case, it is necessary to inform the donor (the woman or the
p.000081: couple) of the possible use of the embryonal cells for the specific purpose in question before
p.000081: requesting consent.
p.000081:
p.000081: 2.11. Risk-benefit assessment
p.000081: Risk-benefit assessment is crucial in stem cell research, as in any research, but is more difficult as
p.000081: the uncertainties are considerable given the gaps in our knowledge. Attempts to minimise the risks and increase the
p.000081: benefits should include optimising the strategies for safety. It is not enough to test the cultured
...
Social / education
Searching for indicator education:
(return to top)
p.000049:
p.000050: 50
p.000050:
p.000050: – As stated in the Council minutes of 30 September 200267 “The Council and the Commission agree
p.000050: that detailed implementing provisions concerning research activities involving the use of human
p.000050: embryos and human embryonic stem cells…shall be established by 31 December 2003”.
p.000050:
p.000050: The Commission will during that period…not propose to fund such research, with the exception of banked or
p.000050: isolated human embryonic stem cells in culture.
p.000050:
p.000050: 3.6. Social scrutiny and dialogue
p.000050: There are significant differences in national attitudes towards specific techniques and areas of research. In
p.000050: particular, human embryonic stem cell research has recently provoked intense public and political debate. As
p.000050: the life sciences and biotechnology develop, they contribute considerably to securing welfare on the personal and
p.000050: societal levels as well as to creating new opportunities for our economies. At the same time, the general
p.000050: public is increasingly concerned about the social and ethical consequences of these advances in knowledge
p.000050: and techniques as well as about the conditions forming the choices made in these fields.
p.000050:
p.000050: The EGE stressed in its opinion regarding “Ethical aspects of human stem cell research and use” there is a need
p.000050: for continuing dialogue and education to promote the participation of citizens, including patients, in
p.000050: scientific governance, namely in social choices created by new scientific developments”.
p.000050:
p.000050: The need for public dialogue on scientific advances and new technologies has also been highlighted in both
p.000050: the Commission’s communication on “Life Sciences and Biotechnology”, published on 27 January 200268 and the
p.000050: Commission’s action plan on “Science and Society” published in December 200169.
p.000050: In this connection, the European Group on Life Sciences70, set up by the European Research Commissioner Philippe
p.000050: Busquin, organised on 18-19 December 2001,a forum entitled “Stem cells: therapies for the future?”. The aim was
p.000050: to offer a platform at European level for a debate between, on one side, scientists and experts
p.000050: concerned with the feasibility and consequences of stem cell research and, on the other side, a wide range of
p.000050: representatives of society. More than 600 people participated in the event.71. Much of the public discussion that took
p.000050: place, both at the forum itself and by e-mail exchanges concentrated on ethical issues, particularly those relating to
p.000050: the use of human embryos.
p.000050:
p.000050: As for any new potential treatment, the promises of stem cell research may create amongst patients suffering from
p.000050: incurable diseases and their families, high and sometimes unrealistic expectations from science and the imperative
p.000050: of treatment for whatever disease. Many negative research results are not published and may lead to an unbalanced
p.000050: presentation in the media and ultimately affect the dialogue in society. Since failure to deliver the promised cures
...
p.000082:
p.000082: 2.15. Stem cell banks and safety
p.000082:
p.000082: Procurement and storage of stem cells in stem cell banks leads to the collection and storage of a growing number of
p.000082: personal and familial data. Cell banks should be regulated at European level in order to facilitate the
p.000082: implementation of a precautionary approach. If unsatisfactory side effects occur, it should be possible to trace donor
p.000082: and recipient and to reach their medical files. Traceability must be one of the conditions required for the
p.000082: authorisation of cell banks at national or European level.
p.000082:
p.000082:
p.000082: 2.16. Stem cell banks and confidentiality
p.000082:
p.000082: In order to reconcile the traceability requirement and the need to protect the donor’s rights - medical confidentiality
p.000082: and privacy - cell banks must take the necessary steps to protect confidentiality of the data.
p.000082:
p.000082:
p.000082: 2.17. Prohibition of commerce in embryos and cadaveric foetal tissue
p.000082: The potential for coercive pressure should not be underestimated when there are financial incentives. Embryos as well
p.000082: as cadaveric foetal tissue must not be bought or sold, and not even offered for sale. Measures should be taken to
p.000082: prevent such commercialisation.
p.000082:
p.000082: 2.18. Export and import of stem cell products
p.000082:
p.000082: Stem cell imports or exports should be licensed by public authorities either at national or European
p.000082: level. Authorisation should be subject to ethical as well as safety rules.
p.000082:
p.000082:
p.000082: 2.19. Education and dialogue
p.000082:
p.000082: There is a need for continuing dialogue and education to promote the participation of citizens, including patients, in
p.000082: scientific governance, namely in the social choices created by new scientific developments.
p.000082:
p.000082:
p.000082: The European Group on Ethics in Science and New Technologies:
p.000082:
p.000082: The Members
p.000082:
p.000082: Paula Martinho da Silva Anne McLaren Marja Sorsa
p.000082:
p.000082: Ina Wagner Goran Hermerén Gilbert Hottois
p.000082:
p.000082: Dietmar Mieth Octavi Quintana Trias Stefano Rodota
p.000082:
p.000082: Egbert Schroten Peter Whittaker The Chairperson
p.000082: Noëlle Lenoir
p.000082:
p.000082:
p.000082:
p.000082:
p.000083: 83
p.000083:
p.000083: ANNEX F: Statement for the minutes of the Council meeting 30 September 2002
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p.000084: COUNCIL OF
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Social / embryo
Searching for indicator embryo:
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p.000003: scientific, ethical, legal, social and economic issues related to human stem cell research and human embryonic stem
p.000003: cell research.
p.000003:
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p.000003:
p.000003: 1 OJ L 294 of 29.10.2002, p. 10.
p.000003: 2 See annex F.
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p.000003:
p.000004: 4
p.000004:
p.000004: The purpose of the report is to provide a basis for an open and informed debate at the above- mentioned
p.000004: inter-institutional seminar3.
p.000004: Taking into account the seminar’s outcome, the Commission will submit a proposal establishing
p.000004: further guidelines on principles for deciding on the Community funding of research projects involving the use
p.000004: of human embryos and human embryonic stem cells.
p.000004:
p.000004:
p.000004: The content of the report
p.000004:
p.000004: Characteristics of human stem cells
p.000004:
p.000004: Stem cells have three characteristics that distinguish them from other types of cells:
p.000004:
p.000004: – they are non-differentiated (unspecialised) cells,
p.000004:
p.000004: – they can divide and multiply in their undifferentiated state for a long period.
p.000004:
p.000004: – under certain physiological or experimental conditions, they can also give rise to more specialised
p.000004: differentiated cells such as nerve cells, muscle cells or insulin producing cells etc.
p.000004:
p.000004: Stem cells are found in the early embryo, in the foetus and the umbilical cord blood, and in many tissues of the
p.000004: body after birth and in the adult. These stem cells are the source for tissues and organs of the foetus
p.000004: and for growth and repair in the new born and adult body. As development proceeds beyond the blastocyst stage (5-7 days
p.000004: after fertilisation), the proportion of stem cells decrease in the various tissues and their ability to differentiate
p.000004: into different cell types also decrease at least when they are situated in their natural environment.
p.000004:
p.000004: Classification of human stem cells
p.000004: In this report a distinction is made between three groups of stem cells, referring to their origin and method of
p.000004: derivation:
p.000004:
p.000004: 1. Human embryonic stem cells, which can be derived from a preimplantation embryo at the blastocyst stage.
p.000004:
p.000004: 2. Human embryonic germ cells, which can be isolated from the primordial germ cells of the foetus.
p.000004:
p.000004: 3. Human somatic stem cells, which can be isolated from adult or foetal tissues or organs or from umbilical cord blood.
p.000004:
p.000004: Potential application of human stem cell research
p.000004:
p.000004: Transplantation of haematopoïetic stem cells (from bone marrow, peripheral blood or umbilical cord blood of a
p.000004: healthy donor) has been used for more than a decade to treat e.g. haematological malignancies such as
p.000004: leukemia or congenital immuno-deficiencies.
p.000004:
p.000004:
p.000004: 3 Scientific terms are explained in the glossary.
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005: Autologous transplantation (transplantation of stem cells from the patient’s own bone marrow or peripheral blood) was
p.000005: introduced to rescue the bone marrow of patients who had received high dose of chemotherapy. It is now increasingly
p.000005: being used as primary treatment of other types of cancer such as breast cancer and neuroblastoma. Autologous stem cell
p.000005: transplantation is also used experimentally to treat difficult auto-immune conditions and as a vehicle for gene
p.000005: therapy. Today, over 350 centres in Europe are performing more than 18 000 bone marrow transplants a year4.
p.000005: Novel stem cell based therapies (often called regenerative medicine or cell based therapies) are also being
p.000005: investigated to develop new methods to repair or replace tissues or cells damaged by injuries or diseases and to
...
p.000005: 321: 433-437.
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p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006: – Overcoming the problem of immune rejection (which does not arise in the case where the patient’s own stem cells
p.000006: can be used).
p.000006:
p.000006: – For the generation of human cells lines to be used in drug development at pre- clinical stage and in
p.000006: toxicology. Normal human cell types generated from human stem cells can be genetically or
p.000006: pharmacologically manipulated and used for drug discovery. These cell lines may provide more clinically relevant
p.000006: biological systems than animal models for drug testing and are therefore expected to contribute to the development of
p.000006: safer and more effective drugs for human diseases and ultimately to reduce the use of animals. They also offer the
p.000006: possibility to develop better in vitro models to enhance the hazard identification of chemicals. It is
p.000006: possible that these applications will turn out to be the major medical impact of human ES cell research at least in
p.000006: a short-term perspective, as the problems of immune rejection, viability and tumorigenicity do not apply
p.000006: here.
p.000006:
p.000006: – For the understanding of human development. Human ES cells should offer insights into
p.000006: developmental events that cannot be studied directly in the intact human embryo but that have important
p.000006: consequences in clinical areas, including birth defects, infertility, and pregnancy loss.
p.000006:
p.000006: – For the understanding of the basic mechanisms of cell differentiation and proliferation. The
p.000006: understanding of the genes and molecules, such as growth factors and nutrients, that function during development of the
p.000006: embryo may be used to grow stem cells in the laboratory and direct their development into specialized cell types. Some
p.000006: of the most serious medical conditions, such as cancer, are due to abnormal cell division and
p.000006: differentiation. A better understanding of the genetic and molecular controls of these processes may yield information
p.000006: about how such diseases arise and suggest new strategies for therapies.
p.000006:
p.000006: The current advantages and limitations of human embryonic and somatic stem cells and the needs regarding the derivation
p.000006: of new human embryonic stem cell lines
p.000006:
p.000006: In light of the current state of knowledge, human embryonic and somatic stem cells each have advantages and
p.000006: limitations regarding their potential uses for basic research and novel stem cell based therapies.
p.000006:
p.000006: It is a matter of debate within the scientific community whether human embryonic stem cells have a greater potential
p.000006: than human somatic stem cells (isolated from foetal or adult tissue). Currently, human ES cells are of particular
p.000006: interest because they have the potential to differentiate into all cell types in the body (they are
p.000006: pluripotent). The recent reports5 indicating that somatic stem cells may have a greater potential for
p.000006: differentiation into different cell types than previously thought (for example bone marrow stem cells under
...
p.000009:
p.000009: – Free and informed consent of the patient.
p.000009:
p.000009: – Risk-benefit assessment.
p.000009:
p.000009: – Protection of the health of persons involved in clinical trials.
p.000009:
p.000009: Regulation of human embryonic stem cell research in EU Member States11
p.000009: EU Member States have taken different positions regarding the regulation of human embryonic stem
p.000009: cell research and new laws or regulations are being drafted or debated. Taking into account the situation,
p.000009: as of March 2003, the following distinctions can be made:
p.000009:
p.000009: – Allowing for the procurement of human embryonic stem cells from supernumerary
p.000009: embryos by law under certain conditions: Finland, Greece, the Netherlands, Sweden and the United Kingdom.
p.000009:
p.000009: – Prohibiting the procurement of human ES cells from supernumerary embryos but allowing by law for
p.000009: the import and use of human embryonic stem cell lines under certain conditions: Germany. The import and use of human ES
p.000009: cell lines is not explicitly prohibited in e.g. Austria, Denmark and France and authorisation is still being
p.000009: discussed.
p.000009: – Prohibiting the procurement of human ES cells from supernumerary embryos: Austria, Denmark,
p.000009: France, Ireland and Spain. The legislation in Spain only allows the procurement of human ES cell from
p.000009: non-viable human embryos under certain conditions.
p.000009:
p.000009: – No specific legislation regarding human embryo research or human ES cell research: Belgium, Italy,
p.000009: Luxembourg and Portugal.
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: 11 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000009: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000009: cell research and use (last update March 2003). “Survey on the National Regulations in the European Union
p.000009: regarding Research on Human Embryos - B. Gratton - published by the Secretariat of the EGE - European Commission - July
p.000009: 2002”.
p.000009:
p.000009:
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p.000010: 10
p.000010:
p.000010: – Allowing by law for the creation of human embryos for research purposes: UK is for the moment the only
p.000010: Member State, which allows by law for the creation of human embryos either by fertilisation of an egg
p.000010: by a sperm, or by somatic cell nuclear transfer (SCNT, also called therapeutic cloning) for stem cell
p.000010: procurement. The bill under discussion in the Belgian Parliament would allow for the creation of human embryos for
p.000010: research purposes including by SCNT. The Dutch Embryo Act of 2002 includes a five-year moratorium for the
p.000010: creation of embryos for research purposes including by SCNT.
p.000010:
p.000010: – Prohibiting the creation of human embryos for research purposes and for the procurement of stem
p.000010: cells by law or by ratification of the Convention of the Council of Europe on Human rights and
p.000010: Biomedicine signed in Oviedo on 4 April 1997: Austria, Denmark, Finland, France, Germany, Greece,
p.000010: Ireland, Netherlands, Portugal and Spain.
p.000010:
p.000010: New regulations under discussion in EU Member States:
p.000010:
p.000010: Belgium: A bill on research on human embryos in vitro was approved by the Belgian Senate in 2002 and it is now
p.000010: under discussion in the Parliament. The draft legislation proposes to authorise the procurement of
p.000010: embryonic stem cells from supernumerary embryos under certain conditions, and to create a “Federal
p.000010: Commission for scientific medical research on embryos in vitro”.
p.000010:
p.000010: Denmark: A revision of the current legislation to allow for the procurement of human ES cells from
p.000010: supernumerary embryos is under discussion.
p.000010:
p.000010: France: A revision of the Bioethics Law of 1994 has been approved by the Senate in January 2003 and should be discussed
p.000010: by the Parliament in the first semester of 2003. It proposes to allow research on supernumerary human embryos
p.000010: including the procurement of human ES cells for 5 years under certain conditions. A central authorizing body will
p.000010: be created.
p.000010:
p.000010: Italy: a law on in vitro fertilisation is under discussion.
p.000010:
p.000010: Portugal: A committee has been established in Portugal for the preparation of a law on human embryo and
p.000010: human ES cell research.
p.000010:
p.000010: Spain: A revision of the current legislation is under discussion.
p.000010:
p.000010: In 1998 the National Committee for Human Artificial Reproduction was created. In its second opinion, delivered in 2002,
p.000010: it advised to conduct human embryonic stem cell research using as a source supernumerary embryos, estimated in Spain to
p.000010: be over 30 000.
p.000010:
p.000010: The Ethics Advisory Committee for Scientific and Technological Research was established in April 2002 and gave in
p.000010: February 2003 its first opinion on research on stem cells. It recommended to the government that research on
p.000010: both adult and embryonic stem cells should be implemented; that the legislation should be modified to allow
p.000010: the isolation of human embryonic stem cells from supernumerary embryos.
p.000010:
p.000010: Sweden: A revision of the current legislation is under discussion. The Parliamentary Committee on Genetic
p.000010: Integrity proposed, in their report published 29 January 2003, not to implement a general prohibition against
p.000010: producing fertilised eggs for research purposes. It
p.000010:
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p.000011: 11
p.000011:
p.000011: should also be noted, however, that in the view of the Committee the creation of embryos by transfer of somatic cell
p.000011: nuclei (so called therapeutic cloning) should be treated in the same way and thus in principle be allowed.
p.000011:
p.000011: Regulations in countries acceding to the EU
p.000011:
p.000011: Cyprus, Czech Republic, Estonia, Hungary, Lithuania, Slovak Republic, Slovenia have ratified the Convention of
p.000011: the Council of Europe on biomedicine and human rights.
p.000011:
p.000011: Concerning the countries acceding to the EU, no specific regulations regarding human embryonic stem cell
p.000011: research have at present been implemented. Estonia, Hungary, Latvia, Slovenia have implemented legislation
p.000011: authorising research on human embryos under certain conditions. In Lithuania, Poland and the Slovak
p.000011: Republic human embryo research is prohibited. No specific regulation regarding embryo research exist in Cyprus,
p.000011: Malta and the Czech Republic. A bill is under preparation in Czech Republic.
p.000011:
p.000011: Governance of stem cell research in the context of FP6 As stated in the Treaty of the European Union, article 6:
p.000011: “1. The Union is founded on the principles of liberty, democracy, respect for human rights and fundamental freedom, and
p.000011: the rule of law, principles which are common to the Member States.
p.000011:
p.000011: 2. The Union shall respect fundamental rights, as guaranteed by the European Convention for the protection of Human
p.000011: Rights and Fundamental Freedoms signed in Rome on 4 November 1950 and as they result from the constitutional traditions
p.000011: common to the Member States, as general principles of Community law.
p.000011:
p.000011: 3. The Union shall respect the national identities of its Member States.
p.000011:
p.000011: 4. The Union shall provide itself with the means necessary to attain its objectives and carry through its policies.”
p.000011:
p.000011: In accordance with the EU Treaty, each Member State retains its full prerogative to legislate on ethical matters. At
p.000011: the level of the Community, ethical principles have been defined with regard to the funding of research under the
p.000011: research Framework Programme.
p.000011:
p.000011: As far as FP6 is concerned, the following ethical principles have been established12:
...
p.000015: 15
p.000015:
p.000015: – Candidate Countries legislation related to ethical issues in science and research Proceedings of
p.000015: the workshop of 8-10 December 2002 - Brussels - organised by the European Commission - DG Research – Directorate C
p.000015:
p.000015: – U. S. National Institutes of Health (NIH) documents regarding stem cells
p.000015: http://nih.gov/news/stemcell/
p.000015:
p.000015: – Review of recent literature;
p.000015:
p.000015: – Presentations and communications from the scientific community.
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p.000016: 16
p.000016:
p.000016: Chapter 1: Origin and characteristics of human stem cells and potential application for stem cell research
p.000016:
p.000016:
p.000016:
p.000016: 1.1. Origin and characteristics of human stem cells15
p.000016: Stem cells differ from other kind of cells in the body by their unique properties of: 1) being capable of dividing and
p.000016: renewing themselves for long periods, 2) being unspecialised and 3) being able to give rise to specialised cell types.
p.000016: They are found in the early embryo, in the foetus and the umbilical cord blood, and in some (possibly many)
p.000016: tissues of the body after birth and in the adult. These stem cells are the source for tissues and organs of the
p.000016: foetus and for growth and repair in the newborn and adult body. As development proceeds beyond the blastocyst stage
p.000016: (5-7 days after fertilisation), the proportion of stem cells decrease in the various tissues and their
p.000016: ability to differentiate into different cell types also decrease at least when they are situated in their natural
p.000016: environment. (See also chapter 1.2.).
p.000016:
p.000016:
p.000016:
p.000016: Figure 1
p.000016:
p.000016:
p.000016: Fertilisation day 0
p.000016:
p.000016:
p.000016:
p.000016: Day 4-5
p.000016:
p.000016: spermatozoid oocyte
p.000016:
p.000016: ORIIGIIN AND CLASSIIFIICATIIO N OF STEMXCELLS
p.000016:
p.000016:
p.000016: MoMruorlaula
p.000016:
p.000016: Embryonic stem cells
p.000016:
p.000016:
p.000016: Day 5-7
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p.000016:
p.000016:
p.000016: From 8th week after fertilisation
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p.000016:
p.000016:
p.000016: + umbilical cord blood
p.000016:
p.000016: Human embryonic germ cells
p.000016: (from the primordial germ cells of the foetus )
p.000016:
p.000016:
p.000016: Somatic stem cells
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p.000016:
p.000016: Adult
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p.000016: 15 The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy using
p.000016: somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429; US NIH, “Stem Cells: A primer” September
p.000016: 2002 http://www.nih.gov/news/stemcell/primer.htm.
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p.000017: 17
p.000017:
p.000017: Classification of human stem cells:
p.000017:
p.000017: The classification of stem cells is still subject to discussion and the use of different definitions,
p.000017: both in the scientific literature and in public debates, often creates confusion. In this report a distinction is made
p.000017: between three groups of stem cells, referring to their origin and method of derivation16:
p.000017: 1. Human embryonic stem cells
p.000017: Human embryonic stem cells derived from preimplantation embryo at the blastocyst stage (see chapter 2 for
p.000017: further details)
p.000017:
p.000017: 2. Human embryonic germ cells
p.000017: Stem cells with embryonic characteristics have also been isolated from the primordial germ cells of the 5-10 weeks
p.000017: foetus. It is from these embryonic germ cells that the gametes (ova or sperm) normally develop. Research has shown
p.000017: that germ cell derived stem cells have the ability to differentiate into various cell types, although they are
p.000017: more limited in this respect than embryonic stem cells17. It should be noted that these research results
p.000017: have yet to be confirmed by other scientists and that the stability of these cells’ genetic material is still open
p.000017: to discussion.
p.000017:
p.000017: 3. Human somatic stem cells
p.000017: A somatic stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ, which can renew
p.000017: itself and can differentiate to yield the major specialised cell types of the tissue or organ. Although somatic
p.000017: stem cells are rare, many, if not most, tissues in the foetus and human body contain stem cells, which, in
p.000017: their normal location, have the potential to differentiate into a limited number of specific cell types in order to
p.000017: regenerate the tissue in which they normally reside. These stem cells, defined as somatic stem cells, are
p.000017: usually described as “multipotent”. Scientists have found evidence for somatic stem cells in many more
...
p.000019: 25 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm Annex
p.000019: E - Opinion n° 15 of the European Group on Ethics http://europa.eu.int/comm/
p.000019: european_group_ethics/docs/avis15_EN.pdf
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: and used for drug discovery. They give scientists the ability to experimentally study - under carefully controlled
p.000020: conditions - the growth and development of many different human cell types that are important to
p.000020: diseases like cancer, diabetes, stroke, heart disease etc. These cell lines may provide more clinically
p.000020: relevant biological systems than animal models for drug testing and are therefore expected to contribute to the
p.000020: development of safer and more effective drugs for major human diseases. For example today, there exists no
p.000020: laboratory model for the human heart, and it is therefore very difficult (impossible) to know exactly what
p.000020: effect medicines have on the heart before performing human studies. The lack of availability of human cells, which
p.000020: express normal function, has so far been the main limiting factor for reducing animal testing in
p.000020: pharmaco-toxicology. It is possible that this application will turn out to be the major medical impact of human
p.000020: ES cell research at least in a short-term perspective. At present insufficient methods exist in some areas of in vitro
p.000020: toxicology predicting target organ toxicity. In other areas such as embryo-toxicity inter-species variation presents
p.000020: major obstacles and humanised systems may enhance the hazard identification of chemicals.
p.000020:
p.000020: – Use of stem cells in gene therapy: Stem cells could be used as vehicles i.e. bearers of genetic information
p.000020: for the therapeutic delivery of genes. A problem for research on gene therapy has been to find safe delivery
p.000020: systems and stem cells may provide a solution here. At present, experiments are being done with gene
p.000020: therapy to treat diseases of the blood system. Their aim is to introduce new healthy genes in the
p.000020: blood-forming stem cells, which can then develop into all types of blood cells and, moreover, are able to renew
p.000020: themselves and thereby provide a permanent cure.
p.000020:
p.000020: – For understanding of human development. Studies of human embryonic and foetal stem cells may yield a deeper
p.000020: understanding of evolutionary biology and the process leading from embryo to human being. Human ES cells
p.000020: should offer insights into developmental events that cannot be studied directly in the intact human embryo but that
p.000020: have important consequences in clinical areas, including birth defects, infertility, and pregnancy loss. Particularly
p.000020: in the early post implantation period, knowledge of normal human development is largely restricted to the
p.000020: description of a limited number of sectioned embryos and to analogies drawn from the
p.000020: experimental embryology of other species. Although the mouse is the main stay of experimental mammalian embryology,
p.000020: early structures including the placenta, extra-embryonic membranes, and the egg cylinder all differ
p.000020: substantially from the corresponding structure of the human embryo.
p.000020:
p.000020: – For understanding of the basic mechanisms of cell differentiation and proliferation. A
p.000020: primary goal of this work is to identify how undifferentiated stem cells become differentiated into particular types of
p.000020: cells. Scientists know that turning genes on and off are central to this process and molecules such as growth factors
p.000020: and nutrients, that function during embryonic development, also play a role. This knowledge can be used to
p.000020: grow stem cells from various sources in the laboratory and direct their differentiation into specialized cell
p.000020: types. Some of the most serious medical conditions, such as cancer, are due to abnormal cell
p.000020: division and differentiation. A better understanding of the genetic and molecular controls of these processes may
p.000020: yield information about how such diseases arise and suggest new strategies for therapies.
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021: 1.4. Novel stem cell based therapies
p.000021:
p.000021: Three therapeutic concepts are currently being envisaged26:
p.000021: – Transplantation of differentiated cells derived from stem cells: Stem cells may be grown and
p.000021: directed to differentiate into specific cell types in the laboratory and then be transplanted e.g. insulin producing
p.000021: cells to treat diabetes, skeletal muscle cells for muscle diseases, dopamine producing neurons for Parkinson’s
p.000021: disease etc. The source for the specific differentiated cell types could be embryonic or somatic stem cells including
...
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024: “Repair of infarcted myocardium by autologous intracoronary mononuclear bone narrow cell
p.000024: transplantation in humans”, Circulation, 2002, 106: 1913-1918.
p.000024: 34 Serup P. et al. “Islet and stem cell transplantation for treating diabetes”, BMJ, 2001, 322:29-32.
p.000024: 35 Lumelsky, N. et al. “Differentiation of embryonic stem cells to insulin - secreting structures similar to
p.000024: pancreas islets”, Science, 2001, 292: 1389-94.
p.000024:
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025: Chapter 2: Human embryonic stem cell research
p.000025:
p.000025:
p.000025:
p.000025: The first embryonic stem cells were isolated from mice in 1981 and a great deal of research has been undertaken on
p.000025: mouse embryonic stem cells. A new era of stem cell biology began in 1998, when the derivation of embryonic stem
p.000025: cells from human blastocysts was first demonstrated36. Since then, several research teams have been working on the
p.000025: characterisation of these cells and on improving the methods for culturing them.
p.000025:
p.000025: 2.1. Origin and characteristics of human embryonic stem cells
p.000025: Human embryonic stem cells can be derived from preimplantation embryo at the blastocyst stage. At this stage, which is
p.000025: reached after about 5 days’ embryonic development, the embryo appears as a hollow ball of 50-100 cells, called the
p.000025: blastocyst. The blastocyst includes three structures: the outer cell layer, which will develop into the placenta; the
p.000025: blastocoel, which is the fluid filled cavity inside the blastocyst; and the inner cell mass, from which the human ES
p.000025: cells can be isolated.
p.000025:
p.000025: The characteristics of human embryonic stem cells include:
p.000025:
p.000025: - Potential to differentiate into the various cell types in the body (more than 200 types are known)
p.000025: even after prolonged culture. The human ES cells are referred to as pluripotent.
p.000025:
p.000025: - Capacity to proliferate in their undifferentiated stage.
p.000025:
p.000025: 2.2. Possible sources for human embryonic stem cells
p.000025: Human embryonic stem cells can be isolated from preimplantation embryos (blastocysts) created by different in
p.000025: vitro techniques37 (i.e. embryos created outside the human body; these embryos cannot develop beyond the blastocyst
p.000025: stage without implantation into the uterus):
p.000025:
p.000025: 1. Supernumerary embryos:
p.000025: One possible source would be to use supernumerary embryos. These are embryos, which have been created by means of in
p.000025: vitro fertilisation (IVF) for the purpose of assisted reproduction but subsequently not used. In by far the
p.000025: majority of cases, assisted reproduction is used in connection with fertility problems, where supernumerary
p.000025: embryos may be created in order to increase the success of infertility treatment. In the countries where
...
p.000026: including by means of somatic cell nuclear transfer (i.e. therapeutic cloning) are excluded from funding under the 6th
p.000026: Framework Programme. OJ L 294 of 29.10.2002, p. 8.
p.000026: 39 In accordance with the Council decision of 30 September adopting the specific
p.000026: programmes implementing FP 6 the creation of embryos for research purposes and for stem cell procurement,
p.000026: including by means of somatic cell nuclear transfer (i.e. therapeutic cloning) are excluded from funding under the 6th
p.000026: Framework Programme. OJ L294 of 29.10.2002, p. 8.
p.000026: 40 US NIH, “Stem cells: a primer”, September 2002. http://www.nih.gov./news/stemcell/primer.htm
p.000026: Swedish National Council on Medical Ethics: statement of opinion on embryonic stem cell research, 17.01.2002,
p.000026: http://www.smer.gov.se.
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027: differentiation, embryonic stem cell lines have proved better able to survive in the laboratory than other types of
p.000027: stem cells. At the various points during the process of generating embryonic stem cell lines, scientists test
p.000027: the cells to see whether they exhibit the fundamental properties that make them, embryonic stem cells. As yet, there
p.000027: exists no standard battery of tests that measure the cells’ fundamental properties but several kinds of tests including
p.000027: tests based on the presence of specific surface and gene markers for undifferentiated cells.
p.000027:
p.000027: One can distinguish:
p.000027:
p.000027: – Human ES cells freshly derived from an embryo which have not yet been subjected to any modification and
p.000027: which have yet to be established as stem cell lines.
p.000027:
p.000027: – Unmodified (undifferentiated) human ES cell lines, which refer to cultured lines of cells, which have
p.000027: been propagated for an extended period originally from freshly human ES cells and which have not been modified
p.000027: in any other way.
p.000027:
p.000027: – Modified (differentiated) human ES derivates which refer to cultured lines of cells, derived from human
p.000027: ES cells or human ES cell lines, which have been modified either by genetic manipulation, or by treatment
p.000027: (e.g. growth factors) that causes the cells to differentiate in a particular way e.g. to differentiate into
p.000027: neural or muscle precursor cells (cells which are not fully differentiated, otherwise they will not
p.000027: multiply).
p.000027:
p.000027: 2.4. The current advantages and limitations of human embryonic stem cells and human somatic stem cells
p.000027: In light of current knowledge, human embryonic and somatic stem cells each have advantages and limitations regarding
p.000027: potential use for basic research and stem cell based therapy.
p.000027:
p.000027: 2.4.1. Human embryonic stem cells
p.000027:
p.000027: Advantages:
p.000027: – human ES cells have the potential to generate the various cell types in the body (they are pluripotent).
p.000027:
p.000027: – human ES cells are at present the only pluripotent stem cell that can be readily isolated and grown in
p.000027: culture in sufficient numbers to be useful.
p.000027:
p.000027: Limitations:
p.000027:
...
p.000030: 2.6. Developments regarding establishment of human stem cell banks and registries. Human stem cell banks
p.000030: The need for public stem cell banks including human embryonic stem cell has been recognised at national
p.000030: level both in Sweden and UK.
p.000030:
p.000030: The British Medical Research Council (MRC) in autumn 2002, in collaboration with the Biotechnology and
p.000030: Biological Science Research Council (BBSRC) and with the full backing of the UK Government, took the initiative
p.000030: to establish the first large-scale publicly funded Stem Cell Bank worldwide. The National Institute for
p.000030: Biological Standards and Control (NIBSC) is hosting the UK Stem Cell Bank46, which officially started 1 January
p.000030: 2003.
p.000030: The general aim of the UK Stem Cell Bank will be to create an independent and competent facility to store, test and
p.000030: release seed stocks of existing and new stem cell lines derived from adult, foetal and embryonic human tissues.
p.000030: There will be two primary components in this work:
p.000030:
p.000030: 1) To provide stocks of well-characterised stem cell lines for use in research in the UK and abroad. These
p.000030: will be established under well regulated, but non-GMP, conditions and made available in order to promote fundamental
p.000030: research.
p.000030:
p.000030: 2) To provide stocks of stem cell lines prepared under GMP conditions, that could be used directly for
p.000030: production of human therapeutic materials.
p.000030:
p.000030: In February 2002, the Human Fertilisation and Embryology Authority (HFEA) in the UK granted the first
p.000030: two licences for embryo research under the 2001 Regulation to Imperial College in London and the
p.000030: University of Edinburgh. The protocols approved will create human embryonic stem cell lines from embryos
p.000030: originally created for IVF treatment but subsequently donated for research. At the time of writing this report no
p.000030: human ES cell lines had as yett been derived. When generated the cell lines will be placed in the UK
p.000030: stem cell bank. This is a requirement of HFEA research licence.
p.000030:
p.000030: The Karolinska Institute in Stockholm is also planning to establish a Stem Cell Bank, based on the various stem
p.000030: cell lines established at the Institute (about 9 human ES cell lines are expected to be available within
p.000030: the next 12 months). These lines will be available for other scientists worldwide47.
p.000030: Human ES cell research is also ongoing at the Sahlgrenska Academy, Gothenburg University, Sweden in collaboration with
p.000030: Cell Therapeutics Scandinavia, AB. The two centres are active
p.000030:
p.000030:
p.000030:
p.000030: 46 http://www.nibsc.ac.uk/divisions/cbi/stemcell.html
p.000030: 47 Communication from Professor Carlstedt-Duke, Dean of Research, Karolinska Institute, Sweden
p.000030:
p.000030:
p.000030:
p.000031: 31
p.000031:
p.000031: in generating human ES cell lines as well as in developing differentiated normal human cells.
p.000031: 21 human ES cell lines have so far been established. Four of these have been fully characterized and two
p.000031: of these four fulfil all the criteria for self-renewal and pluripotency of human ES cells. The remaining 17 cell lines
p.000031: have been partially characterized48.
...
p.000031: embryonic stem cell lines. The availability of these cell lines and their level of characterisation are unclear and the
p.000031: NIH Human Embryonic Cell Registry has recently been updated to reflect the human ES cell lines that meet
p.000031: the eligibility criteria for Federally funded research and which are currently available for shipping to other
p.000031: laboratories50. This list includes 9 human ES cell lines:
p.000031: 2 human ES cell lines from BresaGen, Inc. (a US based company)
p.000031: 5 human ES cell lines from ES Cell International (a company based in Singapore and Australia)
p.000031: 1 human ES cell line from University of California at San Francisco 1 human ES cell line from Wisconsin Alumni Research
p.000031: Foundation
p.000031: Both the European Group on Ethics in Science and New Technologies51 and the European Group on Life
p.000031: Sciences52 have highlighted the need for a European registry of stem cell lines. In particular, the EGE called in their
p.000031: opinion n°16 on “Ethical aspects of patenting inventions involving human stem cells” for the creation of an EU registry
p.000031: of unmodified human stem cell lines.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 48 Communication from Professor Hamberger, Goteborg University, Sweden.
p.000031: 49 http://escr.nih.gov/eligibilitycriteria.html. The following eligibility criteria must be
p.000031: met: (i) the derivation process has been initiated before 9 August 2001; (ii) the stem cells must have been derived
p.000031: from an embryo that was created for reproductive purposes but the embryo was not longer needed for those purposes;
p.000031: (iii) informed consent must have been obtained for the donation of the embryo; (iv) no financial inducements were
p.000031: provided for donation of the embryo.
p.000031: 50 http://escr.nih/
p.000031: 51 http://europa.eu.int/comm/european_group_ethics/docs/avis16_en.pdf
p.000031: 52 http://europa.eu.int/comm/research/life-sciences/egls/index_en.html
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032: “Such registry, which should include information on both embryonic stem cells and embryonic germ
p.000032: cell lines should be publicly accessible. Its aim would be to ensure transparency and thus facilitate
p.000032: access by the research community to the needed biological material for further research”51
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
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p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033: Chapter 3: Governance of human embryonic stem cell research
p.000033:
p.000033:
p.000033:
p.000033: Human embryonic stem cell research raises complex ethical questions. It confronts scientific progress with ethical
p.000033: concerns and it has triggered an intense public debate on its guiding ethical principles and limitations.
p.000033: The question whether it is ethically defensible to do research on embryonic stem cells can be described
...
p.000033: for the sole purpose of research raises serious concerns since it represents a further step in the
p.000033: instrumentalisation of human life” and deemed “ the creation
p.000033:
p.000033:
p.000033: 53 Annex E - Opinion No. 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell
p.000033: research and use”; http://europa.eu.int/comm/european_group_ethics/docs/avis15_en.pdf
p.000033: 54 Annex E: Opinion No. 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell
p.000033: research and use”; http://europa.eu.int/comm/european_group_ethics/docs/avis15_en.pdf
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034: of embryos with gametes donated for the purpose of stem cell procurement ethically unacceptable, when spare
p.000034: embryos55 represent a ready alternative source”.
p.000034: Furthermore the EGE considered “ that, at present, the creation of embryos by somatic cell nuclear transfer for
p.000034: research on stem cell therapy would be premature, since there is a wide field of research to be carried out with
p.000034: alternative sources of human stem cells (from spare embryos, foetal tissues and adult stem cells”.
p.000034:
p.000034: The ethical acceptability of human embryonic stem cell research in the context of Community Framework
p.000034: Programme for Research
p.000034: The EGE noted in the same opinion that “in some countries embryo research is forbidden. But when this research is
p.000034: allowed, with the purpose of improving treatment for infertility, it is hard to see any specific argument,
p.000034: which would prohibit extending the scope of such research in order to develop new treatments to cure severe
p.000034: diseases or injuries. As in the case of research on infertility, stem cell research aims to alleviate
p.000034: severe human suffering. In any case, the embryos that have been used for research are required
p.000034: to be destroyed. Consequently, there is no argument for excluding funding of this kind of research from the
p.000034: Framework Programme of research of the European Union if it complies with ethical and legal requirements
p.000034: as defined in this programme”.
p.000034:
p.000034: Secondly the EGE stated, that:
p.000034:
p.000034: “Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells)
p.000034: requires a specific Community research budget. In particular, EU funding should be devoted to testing the validity of
p.000034: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000034: such research be widely disseminated and not hidden for reasons of commercial interest.
p.000034: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000034: funding for stem cell research. This implies the establishment of appropriate procedures and provision of
p.000034: sufficient means to permit ethical assessment not only before the launching of a project but also in monitoring
p.000034: its implementation.”
p.000034:
p.000034: Principal requirements regarding human embryonic stem cell research.
p.000034: Concerning the use of human supernumerary embryos as a source of stem cells the EGE stressed in their
p.000034: opinion that “ the derivation of stem cells from embryonic blastocysts raises the issue of the moral status of the
p.000034: human embryo. In the context of European pluralism, it is up to each Member State to forbid or authorise embryo
p.000034: research. In the latter case, respect for human dignity requires regulation of embryo research and the
p.000034: provision of guarantees against risks of arbitrary experimentation and instrumentalisation of human embryos”.
p.000034:
p.000034: The EGE also stressed regarding stem cell research and rights of women that “Women who undergo infertility treatment
p.000034: are subject to high psychological and physical strain. The group stresses the necessity to ensure that the demand for
p.000034: spare embryos (supernumerary embryos) and oocyte donation does not increase the burden on women”.
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: 55 Spare embryos: another word for supernumerary embryos.
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035: The EGE stressed also the importance of the following requirements regarding human embryonic stem cell
p.000035: research and the procurement of embryonic stem cells from supernumerary embryos:
p.000035:
p.000035: – Free and informed consent from the donating couple or woman.
p.000035: The EGE stated: “Free and informed consent is required not only from the donor but also from the
p.000035: recipient as stated in the Group's opinion on Human Tissue Banking (21/07/1998). In each case, it is necessary to
p.000035: inform the donor (the woman or the couple) of the possible use of the embryonal cells for the specific purpose
...
p.000035: The EGE recommended that “The potential for coercive pressure should not be underestimated when
p.000035: there are financial incentives. Embryos as well as cadaveric foetal tissue must not be bought or sold, and not
p.000035: even offered for sale. Measures should be taken to prevent such commercialisation”.
p.000035: The Charter of Fundamental Rights of the European Union recognised in article 3(2) that “In the fields of medicine
p.000035: and biology the following must be respected in particular… the prohibition on making the human body and its
p.000035: parts as such a source of financial gain”.
p.000035: Article 21 of the Council of Europe Convention on Human Rights and Biomedicine specifically prohibits
p.000035: financial gain from all or part of the human body.
p.000035:
p.000035: – Anonymity of the donors and protection of the confidentiality of personal information of the
p.000035: donors as it applies for donation of human biological material.
p.000035: The EGE recommended that “Steps must be taken to protect and preserve the identity of both the donor and the recipient
p.000035: in stem cell research and use”. As stated in the EGE's Opinion on Human Tissue Banking (21/07/1998): “in the
p.000035: interests of anonymity, it is prohibited to disclose information that could identify the donor, and the
p.000035: recipient. In general, the donor should not know the identity of the recipient, nor should the recipient know the
p.000035: identity of the donor”. In most cases the donors will not be anonymous in the sense that the embryo could be traced
p.000035: back to the donor of the egg and sperm. Although the identity of the donor should normally be
p.000035: protected though coding and other measures to ensure confidentiality, there would still be safety and quality
p.000035: requirements for clinical research demanding that the link to the donors not be completely removed. Anonymity will then
p.000035: not be possible.
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: – Transparency regarding research results.
p.000036:
p.000036: The EGE recommended in the context of funding stem cell research within the EU Framework Programmes for
p.000036: Research that “the EU should insist that the results of such research be widely disseminated and not hidden
p.000036: for reasons of commercial interest”
p.000036:
p.000036: Concerning clinical research on human stem cells the EGE stressed the importance of the following
p.000036: requirements:
p.000036:
p.000036: – Free and informed consent of the patient and the donor
p.000036:
p.000036: – Risk-benefit assessment
p.000036: “Risk-benefit assessment is crucial in stem cell research, as in any research, but is more difficult as
p.000036: the uncertainties are considerable given the gaps in our knowledge. Attempts to minimise the risks and increase
p.000036: the benefits should include optimising the strategies for safety. It is not enough to test the cultured
p.000036: stem cells or tissues derived from them for bacteria, viruses or toxicity. Safety and security aspects
...
p.000036: November 2000, but it is still considered to be relevant. Human stem cell research and in particular human embryonic
p.000036: stem cell research are still in an early stage of development and therefore the fundamental ethical principles
p.000036: at stake and the requirements for for human embryonic stem cell research are still relevant.
p.000036:
p.000036: Chapter 3.2 provides further information regarding the requirements applied in EU Member States allowing for the import
p.000036: and use of human embryonic stem cells and/or the procurement of human ES cells from supernumerary embryos.
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000037: 37
p.000037:
p.000037: 3.2. Regulations in EU Member States regarding human embryonic stem cell research56
p.000037: EU Member States have already taken very different positions regarding the regulation of human ES cell
p.000037: research and new legislation or regulations are being drafted or debated. Table 1 attempts to provide a comprehensive
p.000037: overview of the situation as of March 2003.
p.000037:
p.000037: The following distinctions can be made:
p.000037:
p.000037: 1. Allowing for the procurement of human embryonic stem cells from supernumerary embryos by law
p.000037: Finland
p.000037: The medical research Act of 1999 covers the preconditions and use of human embryos up to 14 days of embryonic
p.000037: development. The production of human embryonic stem cells from supernumerary embryos is allowed. The
p.000037: laboratories that do embryo research need a licence from the National Authority for Medicolegal Affairs. An
p.000037: ethics committee must approve research projects. The informed consent of both gamete donors is required.
p.000037:
p.000037: Greece
p.000037: The recent law 3089/2002 on medically assisted human reproduction allows for the procurement of
p.000037: human embryonic stem cells from supernumerary embryos. The Act requires the informed consent of both gamete donors and
p.000037: no financial inducement.
p.000037:
p.000037: The Netherlands
p.000037: The Embryo Act of September 2002 allows the use of supernumerary embryos for research including isolation of
p.000037: embryonic stem cells from such embryos. This research requires the favourable opinion of the Central
p.000037: committee for research involving human subjects. The informed consent of the donor is required. The
p.000037: research must have the aim to lead to new insights in medical science.
p.000037:
p.000037: Sweden
p.000037: The Act of 1991 on “Measures for Purposes of Research and Treatment involving Fertilised Human Ova” and the Health
p.000037: and Medical Care Act (18-982:763) apply. According to the Act(1991:115), in vitro embryo research is
p.000037: legally permitted until day 14 after conception, after which the embryo must be destroyed.. After some discussion
p.000037: there is consensus that this legislation permits human embryonic stem cell research. A revision of the law
p.000037: is under discussion (see chapter 3.3)
p.000037:
p.000037: United Kingdom
p.000037: The research purposes permitted by the Human Fertilisation and Embryology Act of 1990 were extended by
p.000037: the “Human Fertilisation and Embryology (Research Purposes ) Regulation” of 2001 to permit the use
p.000037: of embryos in research to increase knowledge about serious diseases and their treatment. The Human
p.000037: Fertilisation and Embryology Authority is
p.000037:
p.000037:
p.000037: 56 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000037: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000037: cell research and use (last update March 2003); “Survey on the National Regulations in the European Union
p.000037: regarding Research on Human Embryos” - B. Gratton - published by the Secretariat of the EGE - European Commission -
p.000037: July 2002.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: responsible for licensing research involving the creation and use of human embryos. The HFEA requires the
p.000038: informed consent of the donors and free donation. The first two licences for stem cell research under the 2001
p.000038: Regulations were issued by HFEA in February 2002.
p.000038:
p.000038: 2. Prohibition of the procurement of embryonic stem cells from human embryos but allowing by law
p.000038: the import and use of human embryonic stem cell lines under certain conditions.
p.000038: Germany
p.000038: The Embryo protection Act of 1990 forbids any research which is not for the benefit of the concerned embryo.
p.000038: A new Act ensuring protection of embryos in connection with the importation and utilisation of human embryonic stem
p.000038: cells – Stem Cell Act – (Stammzellgesetz – StZG) was adopted on 28 June 2002.
p.000038: Concerning importation and utilisation of embryonic stem cells the act specifies in section 4 , that:
p.000038: (1) The importation and utilisation of embryonic stem cells shall be prohibited.
p.000038: (2) Notwithstanding para 1, the importation and utilisation of embryonic stem cells for research purposes shall be
p.000038: permissible under the conditions stipulated in section 6 if
p.000038:
p.000038: 1. The competent agency has satisfied itself that
p.000038: a) The embryonic stem cells were derived before 1 January 2002 in the country of origin in accordance with relevant
p.000038: national legislation there and are kept in culture or are subsequently stored using
p.000038: cryopreservation methods (embryonic stem cell line)
p.000038: b) The embryos from which they were derived have been produced by medically-assisted in vitro fertilisation in order
p.000038: to induce pregnancy and were definitely no longer used for this purpose and that there is no evidence
p.000038: that this was due to reasons inherent in the embryos themselves.
p.000038: c) No compensation or other benefit in money’s worth has been granted or promised for the donation of
p.000038: embryos for the purpose of stem cell derivation and if
p.000038: 2. Other legal provisions, in particular those of the German Embryo Protection Act, do not conflict with the
p.000038: importation or utilisation of embryonic stem cells.
p.000038:
p.000038: (3) Approval shall be refused if the embryonic stem cells have obviously been derived in contradiction to major
p.000038: principles of the German legal system. Approval may not be refused by arguing that the stem cells have been derived
p.000038: from human embryos.
p.000038:
p.000038: Concerning using embryonic stem cells section 5 states:
p.000038: Research involving embryonic stem cells shall not be conducted unless it has been shown by giving scientific reasons
p.000038: that
p.000038:
p.000038: 1. Such research serves eminent research aims to generate scientific knowledge in basic research or to
p.000038: increase medical knowledge for the development of diagnostic, preventive or therapeutic methods to be
p.000038: applied to humans and that,
p.000038:
p.000038: 2. According to the state-of-the-art of science and technology,
p.000038: a) The questions to be studied in the research project concerned have been clarified as far as possible through in
p.000038: vitro models using animal cells or through animal experiments and
p.000038: b) The scientific knowledge to be obtained from the research project concerned cannot be expected to be
p.000038: gained by using cells other than embryonic stem cells.
p.000038: Concerning approval section 6 states:
...
p.000039:
p.000039: The first authorisation to import human embryonic stem cell lines was given in December 2002.
p.000039:
p.000039: 3. Prohibition of the procurement of embryonic stem cells from human supernumerary embryos.
p.000039: Austria
p.000039: The Austrian Reproductive Medicine Act of 1992 states that cells capable of development may only be used
p.000039: for medical assisted reproduction. According to the interpretation of the Reproductive Medicine Act the
p.000039: procurement of stem cells from embryonic tissues is prohibited. The use of imported human ES
p.000039: cells is not explicitly prohibited and discussion regarding authorisation is still ongoing.
p.000039:
p.000039: Denmark
p.000039: The Act on Medically Assisted Procreation from 1997 only allows research intending to improve in vitro
p.000039: fertilisation technique or pre-implantation diagnosis techniques. Therefore, the isolation of human ES cells from
p.000039: supernumerary embryos is forbidden. The importation of
p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040: human ES cells is not explicitly forbidden. However, the Danish government will give its opinion on human
p.000040: embryonic stem cell research in spring 2003, and has recommended that no research with human ES cell lines should be
p.000040: commenced until the government has presented its decision to Parliament (See also chapter 3.3)
p.000040:
p.000040: France
p.000040: Under the Bioethics Law of 1994, research on human embryos in vitro is forbidden except for research which does not
p.000040: harm the embryo. The import and use of human ES cell lines derived from supernumerary embryos is not explicitly
p.000040: prohibited but the authorisation is still under discussion. A revision of the Bioethics law is under discussion
p.000040: (see chapter 3.3)
p.000040:
p.000040: Ireland
p.000040: There is no legislation dealing with research on embryos. However, the Irish constitution of 1937 (as amended in
p.000040: 1983) provides that “the State acknowledges the right to life of the unborn and, with due regard to the
p.000040: equal right to life of the mother, guarantees in its laws to respect, and, as far as practicable, by its laws to defend
p.000040: and vindicate that right”.
p.000040:
p.000040: Spain
p.000040: The laws of 1988 on Assisted Reproduction Techniques and on donation and use of embryos and foetuses or their cells
p.000040: authorises research on in vitro human embryos biologically non- viable under certain conditions. There is no clear
p.000040: interpretation of the concept of a non-viable embryo. Concerning viable human embryos, only research for the
p.000040: benefit of the concerned embryos is allowed. A revision of the law is under discussion (see chapter 3.3)
p.000040:
p.000040: 4. No specific legislation regarding human embryo research
p.000040: Belgium
p.000040: The Royal decree of 1999 fixes the requirement for in vitro fertilisation centres. There is no specific legislation
p.000040: on research but the current practice is that research must only be performed at in vitro fertilisation
p.000040: centres following approval from the local ethics committees. A new bill is under discussion (see chapter 3.3).
p.000040:
p.000040: Italy
p.000040: Italy has not enacted legislation.
p.000040: The Italian National Bioethics Committee has adopted an advice on “the therapeutic use of stem cells”. A majority
p.000040: of the members considered the research on human supernumerary embryos for the derivation of human ES cells as
p.000040: legitimate.
p.000040:
p.000040: Luxembourg
p.000040: There is no legislation covering human embryo research.
p.000040:
p.000040: Portugal
p.000040: Portugal has not enacted legislation but has ratified the Convention of the Council of Europe on Human Rights and
p.000040: Biomedicine signed in Oviedo on 4 April 1997, which prohibit the creation of human embryos for research
p.000040: purposes and has in addition the protocol on the prohibition of human cloning. The National Council of Ethics
p.000040: has adopted opinions covering these questions. It has taken the position that research with no benefit for
p.000040: the embryo concerned is not legitimated. The Ministry of Science has created in 2002 a Steering
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Committee for the preparation of a law on research on human embryos including human ES cells.
p.000041:
p.000041: 5. Allowing for the creation of human embryos for stem cell procurement by law
p.000041: UK is for the moment the only Member State with a specific law that permits the creation of human embryos by
p.000041: fertilisation of an egg with a sperm or by somatic cell nuclear transfer. The 1990 Act and the 2001
p.000041: Regulation (see above) allow for the isolation of stem cells for any of the 8 research purposes set out in the law.
p.000041:
p.000041: The Dutch Embryo Act of 2002 announces, as a general principle, the prohibition of the creation of human
p.000041: embryos solely for research purposes. However, this ban is not irreversible and could be lifted by Royal Decree within
p.000041: five years after the coming into force of the Act.
p.000041:
p.000041: 6. Prohibition of the creation of human embryos for research purposes and for the procurement of stem
p.000041: cells by law or by ratification of the Convention of the Council of Europe on Human rights and Biomedicine signed in
p.000041: Oviedo on 4 April 1997
p.000041: The creation of human embryos for research purposes and for the procurement of embryonic stem cells is for the
p.000041: moment prohibited in Austria, Denmark, Finland, France, Germany, Greece, Ireland, Netherlands, Portugal and
p.000041: Spain.
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
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p.000041:
p.000041:
p.000041:
p.000042: 42
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
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p.000042:
p.000042:
p.000042:
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p.000042:
p.000042:
p.000042:
p.000043: 43
p.000043:
...
p.000043: the Parliament. The draft legislation proposes to authorise the procurement of embryonic stem cells from supernumerary
p.000043: embryos under certain conditions and the creation of a “Federal Commission for scientific medical research
p.000043: on embryos in vitro”.
p.000043: The bill also foresees to allow for the creation of human embryos for research purposes including by
p.000043: means of somatic cell nuclear transfer.
p.000043: Article 3 proposes to allow research on human embryos in vitro under the following conditions:
p.000043: – research for therapeutic purposes
p.000043: – based on recent scientific knowledge
p.000043: – carried by a registered laboratory
p.000043: – embryos up to 14 days of development
p.000043: – no alternative method of research as effective
p.000043: – the consent of the donors
p.000043: In addition the research is controlled at the local and federal levels.
p.000043:
p.000043: Denmark
p.000043: A revision of the current legislation to allow for the procurement of human ES cells from supernumerary
p.000043: embryos is under discussion.
p.000043:
p.000043: France
p.000043: A revision of the Bioethics Law of 1994 has been approved by the Senate in January 2003 and should be discussed by the
p.000043: Parliament in the first semester of 2003. It proposes to allow for research on supernumerary human embryos including
p.000043: the procurement of human ES cells for 5 years under certain conditions. A central authorising body will be created.
p.000043: The proposed revision of the Bioethics law (as amended by the Senate in January 2003) prohibits human
p.000043: embryo research but includes a derogation for five years allowing for research on supernumerary human
p.000043: embryos including the procurement of human ES cells under the following conditions:
p.000043: – the research should have the potential to lead to major therapeutic advances and only be undertaken if there
p.000043: is no alternative method of comparable effectiveness available;
p.000043: – the embryos must derive from an in vitro fertilisation, in the context of a medically assisted
p.000043: reproduction (supernumerary embryos);
p.000043: – written consent of the couple from which the embryos are issued;
p.000043: – authorisation by a central body to be created.
p.000043: The proposed bill will also allow the import of foetal or embryonic cells or tissues after prior authorisation by the
p.000043: central body.
p.000043:
p.000043:
p.000043:
p.000043: 57 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000043: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000043: cell research and use (last update March 2003).
p.000043:
p.000044: 44
p.000044:
p.000044: Italy
p.000044: A law on in vitro fertilisation is under discussion. The Ministry of Health recently produced a report about the banks
p.000044: conserving embryos and gametes.
p.000044:
p.000044: Portugal
p.000044: A committee has been established in Portugal for the preparation of a law on human embryo and human ES cell research.
p.000044:
p.000044: Spain
p.000044: A revision of the current legislation is under discussion.
p.000044: In 1998 the National Committee for Human Artificial Reproduction was created. In its second opinion, delivered in 2002,
p.000044: it advised to conduct human embryonic stem cell research using as a source supernumerary embryos, estimated in Spain to
p.000044: be over 30 000.
p.000044: The Ethics Advisory Committee for Scientific and Technological Research was established in April 2002 and gave in
p.000044: February 2003 its first opinion on research on stem cells. It recommended to the government that research on
p.000044: both adult and embryonic stem cells should be implemented; that the legislation should be modified to allow
p.000044: the isolation of human embryonic stem cells from supernumerary embryos under the following condition: The
p.000044: parents´ informed consent or, if this is not possible, the permission of the Centre of Assisted
p.000044: Reproduction in charge of keeping the embryos according to the regulation in force. The investigation
p.000044: must have the aim of alleviating human suffering and not just economic ends. It must be exclusively done by
p.000044: working groups with a proved experience in this field. The protocol of investigation must be previously
p.000044: evaluated by Ethics Committees and it must be under their exhaustive control. Therefore, the control and
...
p.000044: to implement a general prohibition against producing fertilised eggs for research purposes. It is the opinion
p.000044: of the Committee that such production must take place in order for research to be carried out on infertility and the
p.000044: development of the fertilised egg etc. It is not possible to set a legal limit with sufficient clarity that would
p.000044: delineate what, on the contrary, would be forbidden. This delineation should rather be done on a case-by-case basis
p.000044: within the framework of ethics review of research. It should also be noted, however, that in the view of the
p.000044: Committee the creation of embryos by transfer of somatic cell nuclei (so- called therapeutic cloning) should
p.000044: be treated in the same way and thus in principle be allowed.
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045: 3.4. Regulations in some non-EU countries regarding human embryonic stem cell research58
p.000045: Countries acceding to the EU:
p.000045: Cyprus, Czech Republic, Estonia, Hungary, Lithuania, Slovak Republic, Slovenia have ratified the Convention of
p.000045: the Council of Europe on biomedicine and human rights59.
p.000045: No specific regulations regarding human embryonic stem cell research have a present been implemented in the
p.000045: countries acceding to the EU.
p.000045:
p.000045: Cyprus:
p.000045: Cyprus has ratified the Convention of the Council of Europe on biomedicine and human rights. There is no
p.000045: specific regulation regarding human embryo research.
p.000045:
p.000045: Czech Republic:
p.000045: Czech Republic has ratified the Convention of the Council of Europe on biomedicine and human rights. There
p.000045: is no specific regulation regarding human embryo research, but a law is under preparation.
p.000045:
p.000045: Estonia
p.000045: Under the Embryo Protection and Artificial Fertilisation Act of 1997 the use of supernumerary
p.000045: human embryos for scientific research is permitted if informed consent has been obtained.
p.000045:
p.000045: Hungary
p.000045: Under the Act of 1997 on Health Care (Chapter IX), research on human embryos is permitted if these are supernumerary
p.000045: embryos and not older than 14 days. This research should be approved by the Committee for Human
p.000045: Reproduction.
p.000045:
p.000045: Latvia
p.000045: In January 2002, Latvia has adopted a Law on Reproductive and Sexual Health. Research on human embryos may be
p.000045: authorised if the conditions are met: absence of alternative method, positive assessment of the scientific merit and
p.000045: ethical acceptability by an authorised body and informed consent of the donors.
p.000045:
p.000045: Lithuania
p.000045: The Law on biomedical research adopted in 2000, allows only observational studies of human embryos.
p.000045:
p.000045: Malta
p.000045: There is no specific regulation regarding human embryo research.
p.000045:
p.000045:
p.000045: 58 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000045: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000045: cell research and use (last update March 2003); “Candidate Countries legislation related to ethical issues in science
p.000045: and research” Proceedings of the workshop of 8-10 December 2002 - Brussels - organised by the European
p.000045: Commission - DG Research - Unit C3 - Ethics and Science"; “Use of embryonic stem cells for therapeutic
p.000045: research”– Report of International Bioethics Committee – UNESCO – 6 April 2001.
p.000045: 59 http://conventions.coe.int/treaty/en/treaties/html/164.htm
p.000045:
p.000046: 46
p.000046:
p.000046: Poland
p.000046: Under the Physician profession’s Act of 1996, human embryos may not be use for non- therapeutic research.
p.000046:
p.000046: Slovak Republic
p.000046: The Slovak Republic’s signing and ratifying the Convention on Human Rights and Biomedicine and
p.000046: the Additional Protocol on the Prohibition of Cloning of the Human Beings, already implemented in the national
p.000046: legislation, together with the older provisions contained in law No. 277/1994 on health care, especially the
p.000046: prohibition of the “non-therapeutic research” to be performed on human embryos and foetuses, were
p.000046: interpreted recently as effectively banning all human cloning (the so-called “reproductive” as well as
p.000046: “therapeutic”).
...
p.000046: penal offence in the Slovak Republic (relevant wording being taken basically from the Protocol, and the legislature
p.000046: implementing it in the Slovak Republic).
p.000046:
p.000046: Slovenia
p.000046: The law on medically assisted reproduction prohibits the creation of embryos for research purposes and
p.000046: cloning of embryos and the use of in vitro fertilization for any purpose other than the birth of a
p.000046: child. The Law on Medically assisted reproduction imposes strict conditions for the use of supernumerary
p.000046: embryos in research. Research can be performed on embryos that are not suitable for reproduction or storage, or on
p.000046: those at the end of the storage period which would be destroyed. Embryos should not be older than 14 days.
p.000046: The authorization of the National Medical Ethics committee should be obtained.
p.000046:
p.000046: Other countries:
p.000046: In Canada and USA there is no federal law regulating research on human embryos and/or the derivation of human embryonic
p.000046: stem cells. The House of Commons in Canada is discussing a draft law, which would regulate such research and allow for
p.000046: the procurement of human ES cells from supernumerary embryos.
p.000046: On 9 August, 2001, the President of the United States announced60 his decision to allow Federal funds to
p.000046: be used for research on existing human embryonic stem cell lines as long as prior to his announcement (1) the
p.000046: derivation process (which commences with the removal of the inner cell mass from the blastocyst) had already been
p.000046: initiated and (2) the embryo from which the stem cell lines was derived no longer had the possibility of
p.000046: development as a human being.
p.000046: In addition, the President established the following criteria that must be met:
p.000046: – The stem cells must have been derived from an embryo that was created for reproductive
p.000046: purposes;
p.000046: – The embryo was no longer needed for these purposes;
p.000046: – Informed consent must have been obtained for the donation of the embryo;
p.000046: – No financial inducements were provided for donation.
p.000046: The National Institutes of Health have implemented the above rules by setting a strategic vision for
p.000046: research using stem cells, including:
p.000046:
p.000046:
p.000046:
p.000046:
p.000046: 60 http://escr.nih.gov/eligibilitycriteria.html
p.000046:
p.000047: 47
p.000047:
p.000047: – Creation of the Human Embryonic Stem cells Registry, which list the human embryonic
p.000047: stem cells that meet the eligibility criteria,
p.000047:
p.000047: – Promoting the number of researchers with expertise in stem cell research. The NIH recognised
p.000047: this as one of the key factors to allow stem cell research to move forward and is currently soliciting grant
p.000047: applications to support training courses to teach researchers how best to grow existing banked stem cells into
p.000047: useful lines.
p.000047:
p.000047: – A number of initiatives to facilitate research on all types of stem cells. In particular, the NIH
p.000047: continues to support research on developing the therapeutic potential of adult stem cells.
p.000047: New federal legislation is under debate in the US Congress. The State of California has passed a law, in
p.000047: September 2002, allowing the procurement of human embryonic stem cells from supernumerary embryos. New legislation
...
p.000047:
p.000047: 3. The Union shall respect the national identities of its Member States.
p.000047:
p.000047: 4. The Union shall provide itself with the means necessary to attain its objectives and carry through its policies.”
p.000047:
p.000047: In accordance with the EU Treaty, each Member State retains its full prerogative to legislate on ethical matters. At
p.000047: the level of the Community, ethical principles have been defined with regard to the funding of research under the
p.000047: research Framework Programme.
p.000047:
p.000047: As far as FP6 is concerned, the following ethical principles have been established:
p.000047:
p.000047: The decision No. 1513/2002/EC of the European Parliament and of the Council of 27 June 2002 concerning the sixth
p.000047: framework programme of the European Community for research,
p.000047:
p.000047:
p.000047:
p.000048: 48
p.000048:
p.000048: technological development and demonstration activities, contributing to the creation of the European Research
p.000048: Area and to innovation (2002 to 2006) stipulates among others that61:
p.000048: – “Fundamental ethical principles are to be respected. These include the principles reflected in the
p.000048: Charter of fundamental rights of the EU including the protection of human dignity and human life…”
p.000048:
p.000048: The Charter of Fundamental Rights of the European Union, proclaimed in Nice, France, on 7 December 2000, explicitly
p.000048: prohibits eugenic practices and reproductive cloning, but does not comment explicitly on embryo research (article 3)
p.000048:
p.000048: – … “in accordance with relevant international conventions and codes of conduct, e.g.
p.000048: … the Convention of the Council of Europe on Human Rights and Biomedicine signed in Oviedo on 4 April 1997,
p.000048: and the Additional Protocol on the Prohibition of Cloning Human Beings signed in Paris on 12 January 1998”
p.000048:
p.000048: The Council of Europe’s Convention for the Protection of Human Rights and Dignity of the Human Being with regard to
p.000048: the Application of Biology and Medicine of 199762 does not resolve the matter of the permissibility of
p.000048: embryo research and leaves every country responsibility for legislating on this matter, while stipulating two
p.000048: conditions: the prohibition of producing human embryos for research purposes and the adoption of rules
p.000048: designed to assure adequate protection for the embryo63. An Additional Protocol to the Convention on the Prohibition
p.000048: of Cloning Human Beings was approved in 1998 and took effect on 3 January 2001 in thirteen Member States
p.000048: of the Council of Europe64.
p.000048: – “… in accordance with Community law”
p.000048:
p.000048: Some EU Directives are relevant for human ES cell research. For instance, the Directive 2001/20/EC on
p.000048: the approximation of laws, regulations and administrative provisions of the Member States relating to the
p.000048: implementation of good clinical practice in the conduct of clinical trials on medical products for human
p.000048: use establishes among others that “written authorisation is required before commencing clinical trials
p.000048: involving medical products for gene therapy, somatic cell therapy including xenogenic cell therapy and all
p.000048: medicinal products containing genetically modified organisms” (ref. article 9.6). The Directive 98/44 on the legal
p.000048: protection of biotechnological inventions, adopted on 6 July 1998, stipulates that “processes for cloning
p.000048: human beings” and “uses of human embryos for industrial or commercial purposes…shall be considered
p.000048: unpatentable”.
p.000048:
p.000048: The draft Directive of the European Parliament and of the Council on setting standards of quality and
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p.000052: One of the current framework conditions affecting stem cell research and commercialisation of stem cells therapies is
p.000052: the patenting of human ES cells and their derivatives. On the one hand patent rights are necessary to protect and
p.000052: secure industry’s huge investments to support innovative research and development. On the other hand academic research
p.000052: is stimulated by having free and open access to these cell lines, as they are essential starting materials for their
p.000052: research. Some scientists consider that human embryonic stem cell lines should not be patented at all. The
p.000052: debate on this issue is intense and includes the ethical dimension of this
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 72 Gilder Biotech report, The American Spectator, June 2001, “Adult cells do
p.000052: it better”; http://www.gilderbiotech.com/ArticlesByScott/Op%20Ed/AdultCells.htm
p.000052:
p.000053: 53
p.000053:
p.000053: research. The European Group on Ethics73 in Science and New Technologies (EGE) recommended in their
p.000053: opinion No.16 on patenting of human stem cells that:
p.000053:
p.000053: Isolated stem cells, which have not been modified do not, as product, fulfil the legal requirements,
p.000053: especially with regards to industrial applications, to be seen as patentable. In addition, such isolated cells are so
p.000053: close to the human body, to the foetus or to the embryo they have been isolated from, that their
p.000053: patenting may be considered as a form of commercialisation of the human body.
p.000053: When unmodified stem cell lines are established, they can hardly be considered as a patentable product.
p.000053: Such unmodified stem cell lines do not have indeed a specific use but a very large range of potential undescribed uses.
p.000053: Therefore, to patent such unmodified stem cell lines would also lead to too broad patents.
p.000053: Therefore only stem cell lines which have been modified by in vitro treatments or genetically modified so that they
p.000053: have acquired characteristics for specific industrial application, fulfil the legal requirements for patentability.
p.000053: As to the patentability of processes involving human stem cells, whatever their source, there is no specific ethical
p.000053: obstacle, in so far as they fulfil the requirements of patentability (novelty, inventive step and industrial
p.000053: application).
p.000053:
p.000053: Directive 98/44 on the legal protection of biotechnological inventions, adopted on 6 July 1998,
p.000053: establishes that an element isolated from the human body or otherwise produced by means of a technical
p.000053: process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if
p.000053: the structure of that element is identical to that of a natural element. Furthermore, the directive obliges
p.000053: Member States to consider unpatentable inventions where their commercial exploitation would be contrary to order
p.000053: public or morality. The processes for cloning human beings and uses of human embryos for industrial or
...
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p.000055: 55
p.000055:
p.000055: GLOSSARY
p.000055:
p.000055:
p.000055:
p.000055: Adult stem cell: a stem cell derived from the tissues or organs of an organism after birth (in contrast to embryonic or
p.000055: foetal stem cells)
p.000055:
p.000055: Blastocyst: a hollow ball of 50-100 cells reached after about 5 days embryonic development. The blastocyst consists of
p.000055: a sphere made up of an outer layer of cells (the trophectoderm), a fluid-filled cavity (the blastocoel), and a cluster
p.000055: of cells on the interior (the inner cell mass)
p.000055:
p.000055: Cell culture: growth of cells in vitro on an artificial environment
p.000055:
p.000055: Cell line: cells of common descent continuously cultured in the laboratory is referred to as a cell line
p.000055:
p.000055: Chromosomes: the carrier of genes, the hereditary information which resides in DNA
p.000055:
p.000055: Clone: a cell or organism derived from and genetically identical to another cell or organism
p.000055:
p.000055: Cloning: creating an organism that is genetically identical to another organism, or a cell that is genetically
p.000055: identical to another cell provided that the so-called mother and daughter cells are subsequently separated (see also
p.000055: reproductive and therapeutic cloning)
p.000055:
p.000055: Cloning by somatic cell nuclear transfer: involves replacing an egg’s nucleus with the nucleus of the adult
p.000055: cell to be cloned (or from an embryo or foetus) and then activating the egg’s further development without
p.000055: fertilisation. The egg genetically reprogrammes the transferred nucleus, enabling it to direct
p.000055: development of a whole new organism (Reproductive cloning by cell nuclear transfer).
p.000055:
p.000055: OR the development is stopped at the blastocyst stage and embryonic stem cells are derived from the inner cell mass.
p.000055: These stem cells would be differentiated into desired tissue using a cocktail of various growth and differentiation
p.000055: factors. The generated tissue/cells could then be transplanted into the original donor of the nucleus avoiding
p.000055: rejection (Therapeutic cloning by cell nuclear transfer).
p.000055:
p.000055: Culture medium: the broth that covers cells in a culture dish, which contains nutrients to feed the cells
p.000055: as well as other growth factors that may be added to direct desired changes in the cells
p.000055:
p.000055: Dedifferentiation: the process of inducing a specialised cell to revert towards less
p.000055: differentiated cell.
p.000055:
p.000055: Differentiation: the process whereby an unspecialized cell acquires the features of a specialised cell such
p.000055: as a heart, liver, or muscle cell.
p.000055:
p.000055: DNA: deoxyribonucleic acid, the genetic material; it is composed of long double stranded chains of
p.000055: nucleotides, the basis of genetics
p.000055:
p.000055: Embryo: in humans, the developing organism from the time of fertilization until the end of the eighth week of
p.000055: gestation, when it becomes known as a foetus.
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056: Early embryo: the term “early embryos” covers stages of the development up to the appearance of the
p.000056: primitive streak e. g. until 14 days after fertilisation.
p.000056:
p.000056: Embryonic germ cell: embryonic germ cells are isolated from the primordial germ cells of the gonadal ridge of the 5-10
p.000056: weeks foetus.
p.000056:
p.000056: Embryonic stem cell line: embryonic stem cells, which have been cultured under in vitro
p.000056: conditions that allow proliferation without differentiation for months to years Feeder layer: cells used in co-culture
p.000056: to maintain pluripotent stem cells Fertilization: the process whereby male and female gametes unite
p.000056: Foetus: a developing human from eight weeks after conception to birth
p.000056:
p.000056: Foetal stem cell: a stem cell derived from foetal tissue (in biological terms « embryo » covers all stages of
p.000056: development up to eight weeks of pregnancy, from then on the term « foetus » is used). A distinction is drawn between
p.000056: the foetal germ cells, from which the gametes develop, and the remaining foetal stem cells, which are the foetal
p.000056: somatic cells
p.000056:
p.000056: Gamete: the male sperm or female egg
p.000056:
p.000056: Gene: a functional unit of heredity that is a segment of DNA located in a specific site on a chromosome. A gene directs
p.000056: the formation of an enzyme or other protein.
p.000056:
p.000056: Germ cells: ova and sperm, and their precursors
p.000056:
p.000056: Haematopoïetic stem cell: a stem cell from which all red and white blood cells develop
p.000056:
p.000056: Human embryonic stem cell: pluripotent stem cell derived from the inner cell mass of the blastocyst
p.000056:
p.000056: Implantation: the embedding of a blastocyst in the wall of the uterus. In humans implantation
p.000056: takes place at day 8 after fertilization.
p.000056:
p.000056: In vitro and in vivo: outside and inside the body; in vitro (literally, in glass) generally means in the laboratory
p.000056:
p.000056: In vitro fertilization: the fertilization of an egg by a sperm outside the body
p.000056:
p.000056: Multipotent: Multipotent stem cells are those capable to give rise to several different types of specialised cells
p.000056: constituting a specific tissue or organ.
p.000056:
p.000056: Oocyte: the female egg
p.000056:
p.000056: Plasticity: the ability of stem cells from one tissue to generate the differentiated cell types of another tissue
p.000056:
p.000056: Pluripotent stem cell: a single pluripotent stem cell has the ability to give rise to types of cells
p.000056: that develop from the three germ layers (mesoderm, endoderm and ectoderm) from which all the cells of the
p.000056: body arise. Pluripotent stem cells have the potential to generate into every cell type in the body, but cannot develop
p.000056: into a embryo on their own.
p.000056:
p.000056:
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: Pre-implantation embryo: is an embryo in the stage prior to implantation in the wall of the uterus ; an embryo cannot
p.000057: develop beyond the blastocyst stage without implantation into the womb.
p.000057:
p.000057: Primitive streak: a collection of cells which appears at about 14 days after fertilisation from which the heart, blood
p.000057: and the central nervous system develops
p.000057:
p.000057: Proliferation: expansion of a population of cells by the continuous division of single cells into two
p.000057: identical daughter cells
p.000057:
p.000057: Redifferentiation: the process of inducing a dedifferentiated cell to differentiate into a (different)
p.000057: specialised cell type
p.000057:
p.000057: Somatic cell: cell of the body other than egg or sperm
p.000057:
p.000057: Somatic stem cell: an undifferentiated cell found among differentiated cells in a tissue or organ, which
p.000057: can renew itself and can differentiate to yield the major specialised cell types of the tissue or organ.
p.000057:
p.000057: Somatic cell nuclear transfer: the transfer of a cell nucleus to an egg (or another cell) from which the nucleus has
p.000057: been removed..
p.000057:
p.000057: Supernumerary embryo or spare embryo: an embryo created by means of in vitro
p.000057: fertilisation (IVF) for the purpose of assisted reproduction but subsequently not used for it.
p.000057:
p.000057: Totipotent: At two to three days after fertilisation, an embryo consists of identical cells, which are
p.000057: totipotent. That is to say that each could give rise to an embryo on its own producing for example
p.000057: identical twins or quadruplets. They are totally unspecialised and have the capacity to differentiate into any of the
p.000057: cells which will constitute the foetus as well as the placenta and membranes around the foetus.
p.000057:
p.000057: Transdifferentiation: the observation that stem cells from one tissue may be able to differentiate into
p.000057: cells of another tissue
p.000057:
p.000057: Undifferentiated: not having changed to become a specialized cell type
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p.000058: 58
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p.000058:
p.000058: ANNEXES
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p.000059: 59
p.000059:
p.000059: ANNEX A: Biology of human development
p.000059:
p.000059:
p.000059:
p.000059: The development of the embryo is a continual process of change, which can be described in terms of the following seven
p.000059: stages:
p.000059:
p.000059: 1. Day 0: Fertilisation
p.000059: The female egg (“oocyte”) is fertilised by the male sperm. The egg and sperm each carry half the genes of a normal
p.000059: cell. The process of fertilisation consists of a number of steps, which ultimately result in a single cell, the
p.000059: “zygote”. The zygote contains all the genes necessary for the development of an individual, half derived from the
p.000059: mother and half from the father. A very small proportion of genes is contained in the mitochondria and is inherited
p.000059: exclusively from the mother.
p.000059:
p.000059: 2. Day 3-4:
p.000059: Up to the fourth cell stage at day 3-4 all the cells are essentially identical and all are thought to have the
p.000059: potential, if placed in the right environment, to develop into an individual – the cells are “ totipotent” (i.e. they
p.000059: have the capacity to develop into all type of cells needed for human development including the extra-embryonic
p.000059: tissues such as the placenta and the umbilical cord). Indeed, identical twins can result from the splitting of
p.000059: the cells at this early stage: they are genetically identical as a result of developing from the same
p.000059: fertilised egg (identical twins can arise later i.e. up to 14 days).
p.000059:
p.000059: 3. Days 4-5: Morula Stage
p.000059: At four to five days after fertilisation (morula stage), the embryo is still made up of unspecialised
p.000059: embryonic cells, but theses seems no longer to have the potential to give raise to an embryo on their own.
p.000059:
p.000059: 4. Days 5-7: Blastocyst stage
p.000059: At day 5 after fertilisation the cells constituting the embryo start to differentiate into inner and outer cells. The
p.000059: outer cells go on to develop into non-embryonic tissues such as the placenta or umbilical cord. The inner cell mass
p.000059: will give rise to the embryo itself. If these inner cells are isolated and grown in the presence of certain
p.000059: chemical substances (growth factors), pluripotent embryonic stem cells (ES cells) can be derived. The ES
p.000059: cells, which have the potential to generate into the various cell type in the body (more than 200 types are known),
p.000059: are referred to as “ pluripotent”.
p.000059:
p.000059: A pre-implantation embryo is an embryo in the stage prior to implantation in the wall of the uterus; an embryo cannot
p.000059: develop beyond the blastocyst stage without implantation into the uterus.
p.000059:
p.000059: 5. Day 8: Implantation stage
p.000059:
p.000059: About day 8 after fertilisation implantation of the blastocyst in the womb takes place. If implantation
p.000059: does not take place, the blastocyst does not develop, as it will lack specific
p.000059:
p.000059:
p.000059:
p.000060: 60
p.000060:
p.000060: biochemical signals and nutrients from the mother, which are required for further development. A
p.000060: substantial proportion of the human embryos – many estimate it as high as 75 per cent – are naturally lost before
p.000060: implantation. At this stage the cells are still relatively undifferentiated and there is no trace of human
p.000060: structure such as a nervous system.
p.000060:
p.000060: 6. Days 14-21: Gastrula stage
p.000060:
p.000060: At about 14 days after fertilisation, following implantation, the early embryo consists of about 2000 cells. It is
p.000060: only at this stage that the cells begin to become differentiated into more specialised cell types. The
p.000060: “primitive streak”, which gives rise to heart and blood, and from which the central nervous system develops, begins to
p.000060: appear at day 15. By the end of the third week of embryonic development the evolving organism consists of three
p.000060: different cell layers, the ectoderm, mesoderm and endoderm. Each cell layer is “programmed” to give rise
p.000060: to defined tissues and organs. The embryonic “outer” layer, or ectoderm, gives rise to the following
p.000060: tissues: central nervous system (brain and spinal cord) and peripheral nervous system; outer surface or skin
p.000060: of the organism; cornea and lens of the eye; epithelium that lines the mouth and nasal cavities and the anal
p.000060: canal; epithelium of the pineal gland, pituitary gland, and adrenal medulla; and cells of the neural
p.000060: crest (which gives rise to various facial structures, pigmented skin cells called melanocytes, and dorsal root
p.000060: ganglia, clusters of nerve cells along the spinal cord). The embryonic “middle” layer, or mesoderm, gives
p.000060: rise to skeletal, smooth, and cardiac muscle; structures of the urogenital systems (kidneys, ureters, gonads, and
p.000060: reproductive ducts); bone marrow and blood; fat; bone, and cartilage; other connective tissues; and the
p.000060: lining of the body cavity. The embryonic “inner” layer, or endoderm, gives rise to the epithelium of the
p.000060: entire digestive tract (excluding the mouth and anal canal); epithelium of the respiratory tract; structures associated
p.000060: with the digestive tract (liver and pancreas); thyroid, parathyroid, and thymus glands; epithelium of the reproductive
p.000060: ducts and glands; epithelium of the urethra and bladder.
p.000060:
p.000060: The term “early embryo” covers stages of development up to the appearance of the primitive streak e.g. until 14 days
p.000060: after fertilisation.
p.000060:
p.000060: 7. Eight week after fertilisation: Foetal stage
p.000060: After about seven weeks’ development, individual organs become recognisable and the embryonic stage is
p.000060: finished and the embryo can properly be described as a foetus. A distinction is drawn between the
p.000060: foetal germ cells from which the gametes (egg cells and sperm) develop and from which “pluripotent” embryonic
p.000060: germ stem cells (EG cells) can be derived during a brief period in the early foetal development and the remaining
p.000060: foetal tissue from which “multipotent” foetal somatic stem cells can be derived.
p.000060:
p.000060: 8. Nine months after fertilisation: birth
p.000060:
p.000060: At around nine months, given normal gestation, the baby is born.
p.000060:
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p.000061: 61
p.000061:
p.000061: ANNEX B: Possibilities to overcome immune rejection responses in stem cell therapy
p.000061:
p.000061:
p.000061:
p.000061:
p.000061: There are several ways of avoiding or repressing immune rejection of transplanted cells or tissues74:
p.000061: 1) Use of immune-suppressant drugs
p.000061: These drugs, which suppress the activity of the immune system, have been refined over many years, as part of organ
p.000061: transplantation research. However, they are not always effective; they must normally be taken over the lifetime
p.000061: of the patient; and they leave the patient open to infection.
p.000061:
p.000061: 2) Use of “matching” tissues
p.000061: The magnitude of rejection is dependent on the differences between the patients HLA system and that of the donor.
p.000061: For this reason, the differences should be as small as possible. Sometimes during transplantation it is
...
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p.000064:
p.000064: 79 Communication from Professor Pera, Monash Institute, Australia.
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p.000065: 65
p.000065:
p.000065: ANNEX D: Details regarding provisions in non-EU countries relating to human embryonic stem cell research
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: Examples of regulatory regimes in some countries associated to the 6th Framework Programme for Research80
p.000065: Iceland
p.000065: The act of 1996 on Artificial Fertilisation regulates research on human embryos. The creation of embryos for
p.000065: research is prohibited, as is cloning. Research on human supernumerary embryos is allowed:
p.000065: - if it is part of an in vitro fertilisation treatment,
p.000065: - if the intention is to diagnose hereditary diseases in the embryos themselves,
p.000065: - if the purpose is to advance the treatment of infertility, or
p.000065: - if the purpose is to improve understanding of the causes of congenital diseases and miscarriages.
p.000065:
p.000065: Israel
p.000065: The currently existing Public Health (Extra-Corporeal Fertilization) Regulations, 1997 address neither
p.000065: the question of the fate of frozen embryos at the end of the freezing period nor the issue of supernumerary embryos
p.000065: (i.e. embryos initially formed in the course and for the sake of infertility treatment and not replaced or donated for
p.000065: implantation for some bona fide reason). Likewise, the currently proposed law for the regulation of the donation of
p.000065: eggs for purposes of in vitro fertilization does not address the possibilities of embryo stem cell
p.000065: research. In 1999, the Israel Parliament enacted the Prohibition of genetic intervention Act 1999-5759
p.000065: (human cloning and genetic modification of reproductive cells). The law prohibits specifically human reproductive
p.000065: cloning but does not relate to cloning for non-reproductive purposes, such as ES cell derivation
p.000065: The Bioethics Advisory Committee of the Israel National Academy of Sciences and Humanities,
p.000065: adopted a recommendation on 8 August 2001 stating that it should be permissible to donate human supernumerary
p.000065: embryos no longer destined to implantation for research under certain conditions, such as:
p.000065: - free and informed consent,
p.000065: - no selling or buying of human embryos,
p.000065: - no in vitro culturing of human embryos beyond 2 weeks.
p.000065:
p.000065:
p.000065:
p.000065: 80 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000065: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000065: cell research and use (last update March 2003)
p.000065:
p.000065:
p.000065:
p.000066: 66
p.000066:
p.000066: - separation of the medical teams involved in the IVF treatment and in the stem cell research.
p.000066: The Advisory Committee also considers it ethically permissible to experiment with new technologies to
p.000066: produce ES cells such as nuclear transfer (so-called therapeutic cloning without reproductive purpose).
p.000066: The Advisory committee also recommends that the “National Helsinki committee for genetic research in humans” of the
...
p.000066:
p.000066: Norway
p.000066: "A bill amending the Act no 56 of 5 August 1994 relating to the application of biotechnology in medicine was
p.000066: assented by the King/sanctioned 13 December 2002. The amendments became effective 1 January 2003 and clarify
p.000066: that the prohibition against research on human embryos also includes research on stem cell lines created by isolating
p.000066: and culturing stem cells from human embryos. The bill also laid down a ban on therapeutic cloning."
p.000066:
p.000066: Switzerland
p.000066: The Federal law on medically assisted reproduction of 18 December 1998 regulates research on embryos. Research on
p.000066: existing embryos is forbidden as well as creation of embryos for research purposes. The donation of embryos
p.000066: is forbidden by the Constitution (article 119).
p.000066: At the end of May 2002, a draft of the Swiss "Federal Act on Research on Supernumerary Embryos and Embryonic Stem
p.000066: Cells" (EFG, Embryonenforschungsgesetz/ Embryonic Research Act) reached the pre-legislative
p.000066: consultation stage. The Federal Council (government) handed over a proposal for the act to parliament end of
p.000066: November 2002. It is the parliament’s aim to enact the law before end of 2003.
p.000066: This draft law proposes to allow research on "surplus" embryos from in vitro fertilisation for purposes of an
p.000066: important scientific interest in the context of reproductive medicine or developmental biology [and not “any
p.000066: possible purpose”] up to the 14th day after fertilisation, and the derivation of embryonic stem cells from
p.000066: supernumerary embryos for research purposes. The EFG draft defines an embryo as "the developing organism from the
p.000066: point of nuclear fusion until the completion of organ development". Interpreting the constitutional paragraph
p.000066: that bans “all kinds of cloning” it explicitly forbids therapeutic cloning.
p.000066:
p.000066:
p.000066: Examples of regulatory regimes in third countries
p.000066:
p.000066: Australia
p.000066: A new bill was voted by the Senate in 2002, which will authorize derivation of human ES cells from
p.000066: supernumerary human embryos. The law may be voted by the House of Representatives in early 2003.
p.000066:
p.000066: Canada
p.000066: No legislation is currently in place. A new draft law on assisted human reproduction is now in discussion in the
p.000066: House of Commons and addresses the questions of research on human embryos. It proposes to prohibit the
p.000066: creation of embryos for research purposes but would allow research on supernumerary embryos including the
p.000066: procurement of human embryonic stem cell from supernumerary embryos. It also requires the informed consent of the
p.000066: donor of the gametes.
p.000066:
p.000066:
p.000066:
p.000067: 67
p.000067:
p.000067: The Canadian Institute for Health has established guidelines concerning human stem cell research. It
p.000067: allows the funding of the procurement of human embryonic stem cell from supernumerary embryos.
p.000067:
p.000067: India81
p.000067: The National bioethics panel set up by the Indian Department of Biotechnology (Ministry of Science and Technology) has
p.000067: drafted new guidelines for human genomics research that cover the collection and use of human ES cells. The panel
...
p.000067: research on human embryos in vitro including the procurement of human embryonic stem cells. The detailed
p.000067: implementation of the act is left to the administrative guidelines.
p.000067:
p.000067: Singapore82
p.000067: Singapore's Bioethics Advisory Committee has recommended a complete ban on human reproductive cloning and
p.000067: recommends that human stem cell research and therapeutic cloning be permitted under strict regulation.
p.000067: The regulatory framework should
p.000067: - require the informed voluntary consent of donors,
p.000067: - prohibit the commerce and sale of donated materials, especially supernumerary embryos and
p.000067: - stipulate that no one shall be under a duty to participate in any manner of research on human stem cells to which he
p.000067: has a conscientious objection.
p.000067: The Government has announced that it will follow the recommendations of the Bioethics Advisory Committee
p.000067: published on 21 June 2002. It is the responsibility of the Health Minister to licence such research.
p.000067:
p.000067: South Korea
p.000067: The Government has annonced that that it will approve the use of less than 14 day-old embryos for stem
p.000067: cell research. A new regulation will be submitted to the Korean National Assembly.
p.000067:
p.000067: USA
p.000067: Only publicly funded research is regulated. On 9 August 2001, President Bush announced that federal funds might be
p.000067: awarded for research using human embryonic stem cell lines that meet certain criteria83. Such research is now eligible
p.000067: for federal funding as long as the derivation process (which begins with the destruction of the embryo) was
p.000067: initiated prior to 9 August 2001. These stem cells must have been derived from embryos created for
p.000067: reproductive
p.000067:
p.000067:
p.000067: 81 http://dbtindia.nic.in/consent.html
p.000067: 82 http://www.bioethics-singapore.org/bac/index.jsp
p.000067: 83 http://grants.nih.gov/grants/stem_cells.htm
p.000067:
p.000067:
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p.000068:
p.000068: purposes and no longer needed for those purposes. In addition, informed consent must have been obtained for the
p.000068: donation of the embryo and the donation must not have involved financial inducements. The NIH Human Embryonic
p.000068: Stem Cell Registry has been created and is updated to reflect stem cell lines that meet the eligibility
p.000068: criteria (see also chapter 2.6). There is no federal law regulating research on human embryos and the derivation of
p.000068: human ES cells when such research is funded by the private sector.
p.000068: However, California has passed a law, in September 2002, allowing the procurement of human embryonic stem
p.000068: cells from supernumerary embryos. New legislation authorising the procurement of human ES cells from
p.000068: supernumerary embryos is under discussion in the States of New Jersey and Massachusetts.
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p.000069:
p.000069: ANNEX E: Opinion No.15 of the European Group on Ethics regarding ethical aspects of human stem cell research and use
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
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p.000069:
p.000069:
p.000069:
...
p.000069: ethical aspects of biotechnology”;
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000070: 70
p.000070:
p.000070: Having regard to the Parliament and Council Decision of 22 December 1998 concerning the 5th Framework
p.000070: Programme of the European Community for research, technological development and demonstration activities
p.000070: (1998-2002) and in particular Article 7 requesting compliance with fundamental ethical principles;
p.000070:
p.000070: Having regard to the Council Decision of 25 January 1999 adopting the specific programme for research, technological
p.000070: development and demonstration activities on quality of life and management of living resources and in
p.000070: particular the ethical requirements mentioned in its Annex II;
p.000070:
p.000070: Having regard to the Charter of 28 September 2000 on Fundamental Rights of the European Union, approved
p.000070: by the European Council in Biarritz on October 14th 2000, in particular Article 1 on “Human dignity”, Article 3 on
p.000070: the “Right to the integrity of the person”, which refers to the principle of "free and informed consent" and prohibits
p.000070: "the reproductive cloning of human beings" and Article 22 on “Cultural, religious and linguistic diversity”;
p.000070:
p.000070: Having regard to the Council of Europe’s Convention on Human Rights and Biomedicine, signed on 4 April 1997 in Oviedo,
p.000070: in particular Article 18 on embryo research, and to the additional protocol to the Convention on the prohibition of
p.000070: cloning human beings signed on 12 January 1998 in Paris;
p.000070:
p.000070: Having regard to the Universal Declaration on the Human Genome and Human Rights adopted by the United Nations on 11
p.000070: December 1998, in particular Article 11 which recommends to prohibit reproductive cloning of human beings, and Article
p.000070: 13 which refers to the responsibilities of researchers as well as of science policy makers;
p.000070:
p.000070: Having regard to national regulations on stem cell and on embryo research and to national ethics bodies opinions, at
p.000070: the European Union level, concerning these subjects;
p.000070:
p.000070: Having regard to the reports of the US National Bioethics Advisory Committee dated September 13, 1999 on
p.000070: the "Ethical Issues on Human Stem Cell Research", the hearings on the same subject by the US Congress, on April 2000
p.000070: and the guidelines published by the Clinton administration on August 26, 2000 to be forwarded to a NIH (National
p.000070: Institutes of Health) scientific review in 2001;
p.000070:
p.000070: Having regard to the Round Table organised by the Group on 26 June 2000 in Brussels with members of the European
p.000070: Parliament, jurists, philosophers, scientists, representatives of industries, of religions, of patients' associations,
p.000070: and of international organisations (Council of Europe, UNESCO, WHO);
p.000070:
p.000070: Having regard to the Hearings of scientific experts on 6 June 2000 and on 2 October 2000, and to the Hearings of
p.000070: representatives of religions on 8 September 2000;
p.000070:
p.000070: Having heard the rapporteurs Anne McLaren and Goran Hermerén;
p.000070:
p.000070:
p.000070:
p.000070: 1 - WHEREAS SCIENTIFIC BACKGROUND
p.000070: 1.1. How to define stem cells?
p.000070:
p.000070: Stem cells are cells that can divide to produce either cells like themselves (self-renewal), or cells
p.000070: of one or several specific differentiated types. Stem cells are not yet fully differentiated and therefore can
p.000070: reconstitute one or several types of tissues.
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
...
p.000071:
p.000071: Different kinds of stem cells can be distinguished according to their potential to differentiate. They are progenitor,
p.000071: multipotent or pluripotent stem cells.
p.000071:
p.000071: • Progenitor stem cells are those whose terminally differentiated progeny consist of a single cell type
p.000071: only. For instance, epidermal stem cells or spermatogonial stem cells can differentiate respectively into
p.000071: only keratinocytes and spermatozoa.
p.000071:
p.000071: • Multipotent stem cells are those which can give rise to several terminally differentiated cell types constituting
p.000071: a specific tissue or organ. Examples are skin stem cells which give rise to epidermal cells, sebaceous glands and
p.000071: hair follicles or haematopoietic stem cells, which give rise to all the diverse blood cells (erythrocytes,
p.000071: lymphocytes, antibody-producing cells and so on), and neural stem cells, which give rise to all the cell types
p.000071: in the nervous system, including glia (sheath cells), and the many different types of neurons.
p.000071:
p.000071: • Pluripotent stem cells are able to give rise to all different cell types in vitro. Nevertheless, they cannot on
p.000071: their own form an embryo. Pluripotent stem cells, which are isolated from primordial germ cells in the
p.000071: foetus, are called: embryonic germ cells ("EG cells"). Those stem cells which are isolated from the inner cell mass of
p.000071: a blastocyst-stage embryo are called: embryonic stem cells ("ES cells”).
p.000071:
p.000071: It should be noted that scientists do not yet all agree on the terminology concerning these types of stem cells.
p.000071:
p.000071:
p.000071: 1.3. What are the characteristics of the different stem cells?
p.000071:
p.000071: Progenitor and multipotent stem cells may persist throughout life. In the foetus, these stem cells are
p.000071: essential to the formation of tissues and organs. In the adult, they replenish tissues whose cells have a limited
p.000071: life span, for instance skin stem cells, intestinal stem cells and haematopoietic stem cells. In the absence of stem
p.000071: cells, our various tissues would wear out and we would die. They are more abundant in the foetus than in the adult.
p.000071: For instance haematopoietic stem cells can be derived from adult bone marrow but they are particularly abundant in
p.000071: umbilical cord blood.
p.000071:
p.000071:
p.000071: Pluripotent stem cells do not occur naturally in the body, which distinguishes them from progenitor and
p.000071: multipotent stem cells.
p.000071:
p.000071:
p.000071:
p.000071: 1.4. Where can stem cells be found?
p.000071:
...
p.000071: major types of somatic stem cells that can generate liver, pancreas, bone and cartilage but they are rather difficult
p.000071: to find and isolate. For instance, access to neural stem cells is limited since they are located in the brain.
p.000071: Haematopoietic stem cells are present in the blood, but their harvesting requires stimulatory treatment of
p.000071: the donor's bone marrow. By and large, adult stem cells are rare and do not have the same developmental potential as
p.000071: embryonic or foetal stem cells.
p.000071:
p.000071: • Stem cells of foetal origin:
p.000071:
p.000071: - Haematopoietic stem cells can be retrieved from the umbilical cord blood.
p.000071:
p.000071:
p.000071:
p.000072: 72
p.000072:
p.000072: - Foetal tissue obtained after pregnancy termination can be used to derive multipotent stem cells like neural stem
p.000072: cells which can be isolated from foetal neural tissue and multiplied in culture, though they have a limited life
p.000072: span. Foetal tissue can also give rise to pluripotent EG cells isolated from the primordial germ cells of
p.000072: the foetus.
p.000072:
p.000072: • Stem cells of embryonic origin: Pluripotent ES cells are those which are derived from an embryo at the blastocyst
p.000072: stage. Embryos could be produced either by in vitro fertilisation (IVF) or by transfer of an adult nucleus to an
p.000072: enucleated egg cell or oocyte (somatic cell nuclear transfer – SCNT).
p.000072:
p.000072:
p.000072: 1.5. Human embryonic development
p.000072:
p.000072: • At two to three days after fertilisation, an embryo consists of identical cells which are totipotent. That is to
p.000072: say that each could give rise to an embryo on its own producing for example identical twins or quadruplets. They are
p.000072: totally unspecialised and have the capacity to differentiate into any of the cells which will constitute the foetus as
p.000072: well as the placenta and membranes around the foetus.
p.000072:
p.000072: • At four to five days after fertilisation (morula stage), the embryo is still made up of
p.000072: unspecialised embryonic cells, but these cells can no longer give rise to an embryo on their own.
p.000072:
p.000072: • At five to seven days after fertilisation (blastocyst stage), a hollow appears in the centre of the morula, and
p.000072: the cells constituting the embryo start to be differentiated into inner and outer cells:
p.000072:
p.000072: - The outer cells will constitute the tissues around the foetus, including the placenta.
p.000072:
p.000072: - The inner cells (20 to 30 cells) will give rise to the foetus itself as well as to some of the surrounding tissues.
p.000072: If these inner cells are isolated and grown in the presence of certain chemical substances (growth
p.000072: factors), pluripotent ES cells can be derived. ES cells are pluripotent, not totipotent since they cannot develop
p.000072: into an embryo on their own. If they are transferred to a uterus, they would neither implant nor develop
p.000072: into an embryo.
p.000072:
p.000072:
p.000072: HISTORICAL BACKGROUND
p.000072:
p.000072: 1.6. Research on animals
p.000072:
p.000072: • Embryonic stem cells
p.000072:
p.000072: Scientists have been working with mouse embryonic stem cells in vitro for more than 20 years, noting very early their
p.000072: remarkable capacity to divide. Some mouse ES cell lines have been cultured for more than 10 years, while retaining
p.000072: their ability to differentiate.
p.000072:
p.000072: There is today some evidence from animal models that multipotent stem cells can be used for somatic
p.000072: therapy. Convincing evidence however has been provided up until now from ES cell-derived, and not adult derived
p.000072: multipotent somatic cells. For instance neural differentiated mouse ES cells when transplanted into a rat
p.000072: spinal cord several days after a traumatic injury can reconstitute neuronal tissue resulting in the
p.000072: (partial) recovery of hindlimb co-ordinated motility. Similarly, selected cardiomyocytes obtained from
p.000072: differentiating ES cells can be grafted into the heart of dystrophic mice to effect myocardial repair. Whether the
p.000072: same cellular derivatives when obtained from adult stem cells would be able to correct for the deficiencies induced in
p.000072: those animal models remains to be determined.
p.000072:
p.000072: Much research on mouse ES cells has also been focused on using these cells to create transgenic animals, in particular
p.000072: as disease models to study human genetic disorders.
p.000072:
p.000072:
p.000072:
p.000072:
p.000073: 73
p.000073:
...
p.000074:
p.000074: In 1999, research on adult stem cells revealed that their plasticity was much higher than previously thought. Adult
p.000074: neural stem cells have been reported to give rise occasionally to other cell types including blood cells. A team at the
p.000074: University of Minnesota in Minneapolis, (USA) has shown that cells isolated from the bone marrow of adults or children
p.000074: were able to become neural or muscle cells. Nevertheless, bone marrow cells with such extraordinary malleability are
p.000074: extremely rare. In any case, these recent findings still require to be substantiated.
p.000074:
p.000074: The future challenge is to control the differentiation of human stem cells. It has been shown in animals that by
p.000074: culturing stem cells in the presence of certain chemical substances referred to as "growth factors", it
p.000074: is possible to induce differentiation of specific cell types. Experiments on human stem cells are less advanced but
p.000074: finding ways to direct differentiation is presently an active focus of research.
p.000074:
p.000074:
p.000074:
p.000074: 1.10. What is the main interest of stem cell research and what are the hopes?
p.000074:
p.000074: The main interests at present include:
p.000074:
p.000074: • Basic developmental biology. Culturing of human stem cells offers insights that cannot be studied directly in the
p.000074: human embryo or understood through the use of animal models. For instance, basic research on stem cells could help
p.000074: to understand the causes of birth defects, infertility and pregnancy loss. It could also be useful to
p.000074: give a better understanding of normal and abnormal human development.
p.000074:
p.000074: • Studies of human diseases on animal models. For example, mouse ES cells can be engineered to
p.000074: incorporate human mutated genes known to be associated with particular diseases and then used to make transgenic mouse
p.000074: strains. If such mice express the pathology of the human disease, this confirms the hypothesis that the
p.000074: gene is involved with the etiology of the disease. This strategy also yields an animal model of the
p.000074: human disease which has in most cases a much better predictability for the human situation than more conventional
p.000074: animal models. One of the most illustrative examples of that method is its use in order to address the potential causes
p.000074: of Alzheimer's disease.
p.000074:
p.000074: • Culturing specific differentiated cell lines to be used for pharmacology studies and toxicology
p.000074: testing. This is the most likely immediate biomedical application, making possible the rapid screening of
p.000074: large numbers of chemicals. By measuring how pure populations of specific differentiated cells respond to potential
p.000074: drugs, it will be possible to sort out medicinal products that may be either useful or on the contrary problematic in
p.000074: human medicine.
p.000074:
p.000074:
p.000074:
p.000074:
p.000074:
p.000074:
p.000075: 75
p.000075:
...
p.000075: the avoidance of immunological problems after transplantation. Neural tissues can sometimes be transplanted
p.000075: from one individual to another without suffering immunological rejection, but for all other tissues, stem
p.000075: cell therapy would need to be accompanied by long-term treatments with immunosuppressive drugs, leading to
p.000075: increased susceptibility to infections and even to cancer.
p.000075:
p.000075: • One approach to avoid this immune rejection problem would involve genetic engineering of stem cells to render
p.000075: them non-antigenic, or immunological manipulation of the patients to render them tolerant.
p.000075:
p.000075: • An alternative approach is based on somatic cell nuclear transfer. It consists of transferring nuclei from the
p.000075: patient's own body cells into donated human or even animal unfertilised eggs from which the nuclei have been removed.
p.000075: If these reconstructed eggs were stimulated for example with electricity to develop to the blastocyst
p.000075: stage, pluripotent stem cells could be derived from them to form cells genetically identical to the patient. No
p.000075: rejection of any transplanted cells would then occur.
p.000075:
p.000075: • Related technology could lead to the cloning of human individuals if the reconstructed embryos were
p.000075: transferred to a woman’s uterus. However, this is contrary to European Community law and prohibited in most European
p.000075: countries.
p.000075:
p.000075:
p.000075: 1.12. Possible origins of the embryos in countries which allow embryo research
p.000075:
p.000075: These embryos are:
p.000075:
p.000075: • either «spare embryos» (i.e. supernumerary embryos) created for infertility treatment to enhance the success rate
p.000075: of IVF, but no longer needed for this purpose. They are intended to be discarded but, instead, may be donated for
p.000075: research by the couples concerned,
p.000075:
p.000075: • or research embryos, created for the sole purpose of research.
p.000075:
p.000075:
p.000075:
p.000075:
p.000075:
p.000076: 76
p.000076:
p.000076: - These may either be produced with donated gametes, i.e. they are derived from the fertilisation in vitro of a human
p.000076: oocyte by a human sperm,
p.000076:
p.000076: - or they may be produced by embryo splitting or nuclear transfer. In the latter case they would be derived by
p.000076: introducing the nucleus of an adult somatic cell into an enucleated human oocyte (sometimes
p.000076: misleadingly termed “embryo cloning” or “therapeutic cloning”).
p.000076:
p.000076:
p.000076:
p.000076: LEGAL BACKGROUND
p.000076:
p.000076: 1.13. Legal situation in the Member States
p.000076:
p.000076: At national level, stem cell research is not regulated as such.
p.000076:
p.000076: With regard to embryonic stem cell research, it is thus necessary to refer to the general legislation on embryo
p.000076: research. In this respect, the situation in the Member States is diverse:
p.000076:
p.000076: - Ireland is the only country of the EU whose Constitution affirms the right to life of the “unborn” and that this
p.000076: right is equal to that of the mother.
p.000076:
p.000076: - In some Member States no legislation on embryo research exists. This is the case of Belgium and of the Netherlands,
p.000076: where embryo research is nevertheless carried out. In Portugal however, in the absence of legislation, no
p.000076: embryo research seems to be performed. This also seems to be the case in Italy although artificial reproductive
p.000076: techniques are widely practised.
p.000076:
p.000076: - Where embryo research is legislated, legislation either prohibits any kind of embryo research (Austria, Germany), or
p.000076: authorises this research under specified conditions (Finland, Spain, Sweden, and UK). In France, where embryo
p.000076: research is still prohibited, the law authorises “the study of embryos without prejudicing their integrity”
p.000076: as well as preimplantation diagnosis.
p.000076:
p.000076: - In some countries the Constitutional Courts have dealt with the use of human embryos (judgement of the French
p.000076: Constitutional Court of July 27, 1994 on Bioethics, and judgement of the Spanish Constitutional Court of
p.000076: July 10, 1999 on the legislation concerning assisted human reproduction techniques).
p.000076:
p.000076: The legal situation of many countries in Europe is under development. New legislation is being drafted mainly in
p.000076: response to the challenge of stem cell research.
p.000076:
p.000076: - In some countries, draft legislation is being prepared to allow research on stem cells derived from
p.000076: supernumerary embryos after in vitro fertilisation (The Netherlands).
p.000076:
p.000076: - In other countries, draft legislation provides for the possibility of creating embryos by nuclear transfer, for the
p.000076: sole purpose of stem cell research. This is the case in Belgium, and in the UK. (In the latter case, legislation
p.000076: allowed creation of embryos for the purpose of research, but only in relation to the treatment of infertility, to
p.000076: contraception or to the avoidance of genetic disease). In France legislation is under preparation.
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000077: 77
p.000077:
p.000077: 1.14. European legislation in the field
p.000077:
p.000077: At the Council of Europe’s level, the Convention on Human Rights and Biomedicine signed in Oviedo in 1997 in its
p.000077: Article 18 establishes that it is up to each country to decide whether to authorise or not embryo research. Each
p.000077: country is only obliged to respect two conditions: “to ensure adequate protection of the embryo”, that is to say to
p.000077: adopt a legislation fixing the conditions and limits of such research; and to prohibit “the creation of human embryos
p.000077: for research purposes”. The Convention is binding only for the States which have ratified it. In the
p.000077: European Union so far only three countries have completed the procedure and some are in the process of doing so.
p.000077:
p.000077: At EU level, although there is no legislative competence to regulate research, some Directives allude to the issue of
p.000077: embryo research and use. For instance, the Directive 98/44/EC on the legal protection of biotechnological
p.000077: inventions (patenting on life) stipulates that “processes for cloning human beings” and “uses of human embryos for
p.000077: industrial or commercial purposes”… “shall be considered unpatentable”. The Directive 98/79/EC on in vitro
p.000077: diagnostic medical devices (including the use of human tissues) provides that “ the removal, collection and use of
p.000077: tissues, cells and substances of human origin shall be governed, in relation to ethics, by the principles laid down in
p.000077: the Convention of the Council of Europe for the protection of human rights and dignity of the human being with regard
p.000077: to the application of biology and medicine and by any Member States regulations on this matter”.
p.000077:
p.000077: At this same level, the Charter on Fundamental rights of the European Union approved by the European Council in
p.000077: Biarritz (France) on October 14, 2000 prohibits different kinds of practices possibly related to embryo
p.000077: research, namely “eugenic practices, in particular those aiming at the selection of persons ” and “the
p.000077: reproductive cloning of human beings”.
p.000077:
p.000077:
p.000077:
p.000077: 1.15. US approach related to embryo research and stem cell research
p.000077:
p.000077: The situation in the US contrasts with that in Europe. A substantial difference is a sharp distinction
p.000077: between the public and the private sector. Since 1995 the US Congress has been adopting each year a
p.000077: provision in the Appropriation Bill to prohibit public funding for embryo research. Thus, the National Institutes of
p.000077: Health (NIH) cannot carry out embryo research, which, in the absence of legislation, remains free and beyond control in
p.000077: the private sector.
p.000077:
p.000077: New discoveries concerning the culturing of human stem cells in 1998 have led to the reopening of the debate. The
p.000077: National Bioethics Advisory Committee (NBAC) issued a report on September 1999; hearings took place in 1999 and 2000
p.000077: before the competent Committees of the US Congress and finally the Clinton administration proposed that,
p.000077: under certain conditions, the funding of research to derive and study human ES cells be permitted. New guidelines of
p.000077: the NIH were published in August 2000 according to which research on human ES cells can be publicly funded if two
p.000077: conditions are respected. First, the cells must be taken from frozen spare embryos from fertility clinics and
p.000077: already destined to be discarded; second, Federal funds could not be used to destroy the embryos to
p.000077: obtain the cells; privately funded researchers will have to pass them on to Federally supported
p.000077: scientists.
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000078: 78
p.000078:
p.000078: ETHICAL BACKGROUND
p.000078:
p.000078:
p.000078: 1.16. Main ethical issues with regard to stem cell research
p.000078:
p.000078: Human stem cell research is an example of bioethical value conflicts. On the one hand, the prospect
p.000078: of new therapies, even in the far future, is attractive in offering an alternative to organ and tissue
p.000078: donation. On the other hand, when this research involves the use of human embryos, it raises the question of its
p.000078: ethical acceptability and of the limits and conditions for such research. Embryo research has been extensively debated
p.000078: in the context of research carried out to improve IVF as a treatment for infertility. Embryonic stem cell research
p.000078: raises the following specific additional ethical questions:
p.000078:
p.000078: New types of research to be performed on human embryos. Up until now, research that involved destroying embryos,
p.000078: if allowed, was limited to research on reproduction, contraception or congenital diseases. With human stem
p.000078: cell research, a much wider scope of research is being considered.
p.000078:
p.000078: The use of ES cells and stem cell lines for therapeutic purposes. Human embryos used for research were destroyed after
p.000078: the research was completed and therefore were never used for fertility treatment. What remained was additional
p.000078: knowledge. Human embryonic stem cell research is aimed at creating cell lines with appropriate characteristics, in
p.000078: terms of purity and specificity. There is thus continuity from the embryonic cells to the therapeutic material obtained
p.000078: by culture.
p.000078:
p.000078: The creation of embryos for research purposes. This delicate issue is now raised again since there is a scientific
p.000078: justification of this practice, namely the possibility of producing stem cells identical to the patient's
p.000078: cells and thus avoiding problems of rejection in the context of the future “regenerative medicine”. At
p.000078: the same time, creating human embryos raises new ethical concerns. The ethical acceptability of stem cell
p.000078: research depends not only on the objectives but also on the source of the stem cells; each source raising partly
p.000078: different ethical questions. Those who condemn embryo research in general will not accept this difference, but for
p.000078: those who accept it, this issue is of major importance.
p.000078:
p.000078:
p.000078:
p.000078: 1.17. Ethical issues in transplantation of stem cells
p.000078:
p.000078: Clinical research and potential future applications in this field raise the same ethical issues as those dealt with in
p.000078: the EGE's Opinion on Human Tissue Banking (21/07/1998), concerning the respect of the donor, who should give informed
p.000078: consent to this use of the donated cells, the respect of the autonomy of the patients, their right to safety and to the
p.000078: protection of their private life and the right to a fair and equal access to new therapies.
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
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p.000079:
p.000079: 2 - OPINION
p.000079: The Group submits the following Opinion:
p.000079:
p.000079: SCOPE OF THE OPINION
p.000079:
p.000079: 2.1 Ethical issues of stem cell research and use for clinical purposes.
...
p.000079: common constitutional traditions, while also stressing the respect for the national identity of all Member States.
p.000079:
p.000079:
p.000079: BASIC RESEARCH ON HUMAN STEMXCELLS
p.000079:
p.000079: 2.4. Principal requirements according to the diverse sources of stem cells.
p.000079: • The retrieval of adult stem cells requires the same conditions as those required in the case of tissue
p.000079: donation, based on respect for the integrity of the human body and the free and informed consent of the donor.
p.000079: • The retrieval of stem cells from the umbilical cord blood after delivery requires that the donor (the woman or
p.000079: the couple concerned) is informed of possible uses of the cells for this specific purpose of research and
p.000079: that the consent of the donor is obtained.
p.000079: • The retrieval of foetal tissues to derive stem cells requires, besides informed consent, that no
p.000079: abortion is induced for the purpose of obtaining the tissues and that the termination timing and the way it is carried
p.000079: out are not influenced by this retrieval.
p.000079: • The derivation of stem cells from embryonic blastocysts raises the issue of the moral status of the human embryo.
p.000079: In the context of European pluralism, it is up to each Member State to forbid or authorise embryo
p.000079: research. In the latter case, respect for human dignity requires regulation of
p.000079:
p.000079:
p.000079:
p.000079:
p.000080: 80
p.000080:
p.000080: embryo research and the provision of guarantees against risks of arbitrary experimentation and
p.000080: instrumentalisation of human embryos.
p.000080:
p.000080: 2.5. Ethical acceptability of the field of the research concerned.
p.000080: The Group notes that in some countries embryo research is forbidden. But when this research is allowed, with the
p.000080: purpose of improving treatment for infertility, it is hard to see any specific argument which would prohibit extending
p.000080: the scope of such research in order to develop new treatments to cure severe diseases or injuries. As in the case of
p.000080: research on infertility, stem cell research aims to alleviate severe human suffering. In any case, the embryos that
p.000080: have been used for research are required to be destroyed. Consequently, there is no argument for excluding funding of
p.000080: this kind of research from the Framework Programme of research of the European Union if it complies with ethical and
p.000080: legal requirements as defined in this programme.
p.000080:
p.000080: 2.6. Public control of ES cell research.
p.000080:
p.000080: The Group deems it essential to underline the sensitivity attached to the use of embryonic stem cells, since this use
p.000080: may change our vision of the respect due to the human embryo.
p.000080:
p.000080: According to the Group, it is crucial to place ES cell research, in the countries where it is permitted, under strict
p.000080: public control by a centralised authority - following, for instance, the pattern of the UK licensing body (the Human
p.000080: Fertilisation and Embryology Authority) - and to provide that authorisations given to such research are highly
p.000080: selective and based on a case by case approach, while ensuring maximum transparency. This must apply whether the
p.000080: research in question is carried out by either the public or the private sector.
p.000080:
p.000080:
p.000080: 2.7. Alternative methods to the creation of embryos for the purpose of stem cell research.
p.000080: The Group considers that the creation of embryos for the sole purpose of research raises serious
p.000080: concerns since it represents a further step in the instrumentalisation of human life.
p.000080:
p.000080: • The Group deems the creation of embryos with gametes donated for the purpose of stem cell
p.000080: procurement ethically unacceptable, when spare embryos represent a ready alternative source.
p.000080:
p.000080: • The Group takes into account interest in performing somatic cell nuclear transfer (SCNT) with the
p.000080: objective of studying the conditions necessary for "reprogramming" adult human cells. It is also aware that, in view
p.000080: of future cell therapy, the creation of embryos by this technique may be the most effective way to
p.000080: derive pluripotent stem cells genetically identical to the patient and consequently to obtain perfectly
p.000080: histocompatible tissues, with the aim of avoiding rejection after transplantation. But, these remote therapeutic
...
p.000094: expressed by Italy, Germany, Portugal and Austria, will continue to focus on the need to ensure utmost respect for
p.000094: human life and the protection of human dignity;
p.000094:
p.000094: - the establishment of a Regulatory Committee which will consider any project proposals for research
p.000094: funding in ethically sensitive areas."
p.000094:
p.000094:
p.000094: (c) Statement by Italy (bioethics and funding of ITER)
p.000094: "Italy notes the Council and Commission statements on the "bioethics question" in connection with the adoption of
p.000094: the Specific Programmes implementing the Sixth Framework Programme for research 2002-2006. These
p.000094: statements represent significant progress in the endeavour to reach a joint position. In this context Italy
p.000094: considers that only research using
p.000094:
p.000094:
p.000094:
p.000094:
p.000095: 95
p.000095:
p.000095: stem-cells derived from human embryos at a date preceding today or the date of the launch of the Sixth Framework
p.000095: Programme is admissible for Community funding.
p.000095:
p.000095: With regard to the Specific Programme on Integrating and strengthening the European Research Area, Italy
p.000095: must reaffirm its vote against this. In line with the views previously expressed in the Research
p.000095: Council on 10 December 2001 and 3 June 2002 on respect for human dignity and protection of human life, Italy
p.000095: believes that research on human embryos directly or indirectly involving the destruction of the embryo should not be
p.000095: funded under the Sixth Framework Programme.
p.000095:
p.000095: Regarding the EURATOM Specific Programme on Nuclear Energy, Italy takes a favourable view but points out that the
p.000095: funding provided for the ITER facility should not necessarily be interpreted as an endorsement of the scientific and
p.000095: technological choices made in the design of the facility. Italy believes that these choices should
p.000095: be given further scientific consideration before a final decision is taken on the feasibility of the ITER
p.000095: programme."
p.000095:
p.000095:
p.000095: (d) Statement by Portugal (bioethics)
p.000095:
p.000095: "Portugal congratulates the Presidency on the efforts it has made in the field of bioethics, without
p.000095: which it would not have been possible to launch the Sixth Framework Programme for research and technological
p.000095: development and the relevant specific programmes.
p.000095:
p.000095: Portugal can give its agreement to the compromise reached, because it believes that compromise
p.000095: recognises the importance it attaches to issues of bioethics and research as well as the sensitivity of any future
p.000095: financing of research work on human embryo cells and embryonic stem cells. Portugal points out that this is
p.000095: a position shared by a number of other Member States and that it associates itself with many of the concerns which
p.000095: Italy has raised within the Council.
p.000095:
p.000095: Portugal further stresses that research, especially through the Framework Programme, plays an important part in
p.000095: economic growth, employment and social cohesion, particularly in the context of a knowledge-based society and
p.000095: economy."
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Social / parents
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p.000043: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000043: cell research and use (last update March 2003).
p.000043:
p.000044: 44
p.000044:
p.000044: Italy
p.000044: A law on in vitro fertilisation is under discussion. The Ministry of Health recently produced a report about the banks
p.000044: conserving embryos and gametes.
p.000044:
p.000044: Portugal
p.000044: A committee has been established in Portugal for the preparation of a law on human embryo and human ES cell research.
p.000044:
p.000044: Spain
p.000044: A revision of the current legislation is under discussion.
p.000044: In 1998 the National Committee for Human Artificial Reproduction was created. In its second opinion, delivered in 2002,
p.000044: it advised to conduct human embryonic stem cell research using as a source supernumerary embryos, estimated in Spain to
p.000044: be over 30 000.
p.000044: The Ethics Advisory Committee for Scientific and Technological Research was established in April 2002 and gave in
p.000044: February 2003 its first opinion on research on stem cells. It recommended to the government that research on
p.000044: both adult and embryonic stem cells should be implemented; that the legislation should be modified to allow
p.000044: the isolation of human embryonic stem cells from supernumerary embryos under the following condition: The
p.000044: parents´ informed consent or, if this is not possible, the permission of the Centre of Assisted
p.000044: Reproduction in charge of keeping the embryos according to the regulation in force. The investigation
p.000044: must have the aim of alleviating human suffering and not just economic ends. It must be exclusively done by
p.000044: working groups with a proved experience in this field. The protocol of investigation must be previously
p.000044: evaluated by Ethics Committees and it must be under their exhaustive control. Therefore, the control and
p.000044: supervision of these investigations by a national committee is recommended.
p.000044:
p.000044: Sweden
p.000044: A revision of the current legislation is under discussion.
p.000044: The Parliamentary Committee on Genetic Integrity proposed, in their report published 29 January 2003, not
p.000044: to implement a general prohibition against producing fertilised eggs for research purposes. It is the opinion
p.000044: of the Committee that such production must take place in order for research to be carried out on infertility and the
p.000044: development of the fertilised egg etc. It is not possible to set a legal limit with sufficient clarity that would
p.000044: delineate what, on the contrary, would be forbidden. This delineation should rather be done on a case-by-case basis
p.000044: within the framework of ethics review of research. It should also be noted, however, that in the view of the
p.000044: Committee the creation of embryos by transfer of somatic cell nuclei (so- called therapeutic cloning) should
...
Social / philosophical differences/differences of opinion
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p.000023: 2.4. The current advantages and limitations of human embryonic stem cells and human somatic stem cells
p.000028: 28
p.000028: 2.5. Examining the need for new human embryonic stem cell lines. 30
p.000028: 2.6. Developments regarding establishment of human stem cell banks and registries. 31
p.000028: 3. Chapter 3: Governance of human embryonic stem cell research 34
p.000028: 3.1. The ethical issues at stake
p.000034: 34
p.000034: 3.2. Regulations in EU Member States regarding human embryonic stem cell research. 38
p.000034: 3.3. New regulations under discussion in EU Member States 44
p.000034: 3.4. Regulations in some non-EU countries regarding human embryonic stem cell research
p.000046: 46
p.000046: 3.5. Governance of stem cell research in the context of FP6 48
p.000046: 3.6. Social scrutiny and dialogue
p.000051: 51
p.000051: 4. Chapter 4: Socio-economic aspects
p.000053: 53
p.000053: GLOSSARY
p.000056: 56
p.000056: ANNEX A: Biology of human development 60
p.000056: ANNEX B: Possibilities to overcome immune rejection responses in stem cell therapy 62
p.000056:
p.000056:
p.000056:
p.000002: 2
p.000002:
p.000002: ANNEX C: Examples of available human embryonic stem cell lines 64
p.000002: ANNEX D: Details regarding provisions in non-EU countries relating to human embryonic stem cell research
p.000066: 66
p.000066: ANNEX E: Opinion No.15 of the European Group on Ethics regarding ethical aspects of human stem cell research and use E
p.000066: - Opinion EGE 70
p.000066: ANNEX F: Statement for the minutes of the Council meeting 30 September 2002 84
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p.000003: 3
p.000003:
p.000003: EXECUTIVE SUMMARY
p.000003:
p.000003: Background:
p.000003: Stem cell research is one of the promising areas of biotechnology, which offers the prospect of developing new
p.000003: methods to repair or replace tissues or cells damaged by injuries or diseases and to treat serious
p.000003: chronic diseases, such as diabetes, Parkinson’s, chronic heart failure as well as stroke and spinal cord
p.000003: injuries. Stem cell research is expected to be equally important for basic science to understand cell differentiation
p.000003: and growth as well as for other specific medical applications such as for the understanding of disease development and
p.000003: for the development of safer and more effective drugs. Scientists are intensively studying the fundamental
p.000003: properties of stem cells.
p.000003:
p.000003: One of the possible sources for stem cells is human pre-implantation embryos. However, when this research
p.000003: involves the use of human embryos it raises the question of ethical values at stake and of the limits and conditions
p.000003: for such research.
...
p.000007: in which they are rooted. EU Member States have taken very different positions regarding the regulation of human
p.000007: embryonic stem cell research. It confirms that different views exist throughout the European Union
p.000007: concerning what is and what is not ethically defensible.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: 6 e.g. Dr. Catherine Verfaillie, University of Minnesota Medical School, stated during her presentation at
p.000007: the US President’s Council on Bioethics meeting on 25 April 2002, http://www.bioethics.gov/
p.000007: “Embryonic stem cells in humans are very much in their infancy, the same as we are for adult stem cell biology, too,
p.000007: and so I don’t think we are anywhere close to be able to come up with new therapies at this point in time. I would also
p.000007: like to reiterate that even though my laboratory and our group works on adult stem cells, we have actually
p.000007: actively pursued investigators in embryonic stem cell research, human embryonic stem cells, just so that within
p.000007: the same institution we would have laboratories that have one cell, and other laboratories that have the other cell, so
p.000007: we would be in a position to compare and contrast the potential of the different cell populations, and I think that it
p.000007: is very important”.
p.000007: 7 “Stem Cells: scientific progress and future research directions”, National Institute of Health
p.000007: (NIH), Bethesda, USA, June 2001; Swiss National Advisory Commission on Biomedical Ethics: opinion on human
p.000007: embryonic stem cell research, June 2002; The Health Council of the Netherlands’ report on “Stem cells for
p.000007: tissue repair. Research on therapy using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429
p.000007: ; House of Lords Select Committee UK, “Report on Stem cell research”, February 2002;
p.000007: http:/:www.parliament.the-stationery-office.co.uk/pa/ld200102/ldselect/ ldstem/83/8301.htm; Swedish National Council of
p.000007: Medical Ethics: statement of opinion on embryonic stem cell research, 17.01.2002, http://www.smer.gov.se/.
p.000007: 8 The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on
p.000007: therapy using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000007: 9 Annex E - Opinion No. 15 of the European Group on Ethics regarding the “Ethical aspects of human stem
p.000007: cell research and use”. http://europa.eu.int/comm/european_group_ethics/index_en.htm.
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: Ethical issues at stake:
p.000008:
p.000008: As highlighted in the opinion n° 15 of The European Group on Ethics in Sciences and New Technologies regarding «
p.000008: Ethical aspects of human stem cell research and use”, issued 14 November 2000,10 the following fundamental
p.000008: ethical principles are applicable to human embryonic stem cell research:
p.000008:
p.000008: – The principle of respect for human dignity.
p.000008:
p.000008: – The principle of individual autonomy (entailing the giving of informed consent, and respect for
p.000008: privacy and confidentiality of personal data).
p.000008:
p.000008: – The principle of justice and of beneficence (namely with regard to the improvement and
p.000008: protection of health).
p.000008:
p.000008: – The principle of freedom of research (which is to be balanced against other
p.000008: fundamental principles).
p.000008:
p.000008: – The principle of proportionality (including that research methods are necessary to the aims pursued and that
p.000008: no alternative more acceptable methods are available).
p.000008:
p.000008: In addition, the EGE considers it important to take into account, based on a precautionary approach, the potential
p.000008: long-term consequences of stem cell research and use for individuals and the society.”
p.000008:
p.000008: Concerning the creation of embryos for research purpose the EGE considered that “the creation of embryos
p.000008: for the sole purpose of research raises serious concerns since it represents a further step in the
p.000008: instrumentalisation of human life” and deemed “ the creation of embryos with gametes donated for the purpose of
p.000008: stem cell procurement ethically unacceptable, when spare embryos represent a ready alternative source”.
p.000008:
p.000008: Furthermore the EGE considered “that, at present, the creation of embryos by somatic cell nuclear transfer for research
p.000008: on stem cell therapy would be premature, since there is a wide field of research to be carried out with alternative
p.000008: sources of human stem cells (from spare embryos, foetal tissues and adult stem cells”.
p.000008:
p.000008: Concerning the ethical acceptability of human embryonic stem cell research in the context of the Community Framework
p.000008: Programme, the EGE concluded that «//… there is no argument for excluding funding of this kind of research from the
p.000008: Framework Programme of research of the European Union if it complies with ethical and legal requirements as
p.000008: defined in this programme”.
p.000008:
p.000008: Secondly the EGE stated, that:
p.000008:
p.000008: “Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells)
p.000008: requires a specific Community research budget. In particular, EU funding should be devoted to testing the validity of
p.000008: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000008: such research be widely disseminated and not hidden for reasons of commercial interest.”
p.000008:
p.000008:
p.000008: 10 Annex E - Opinion No. 15 of the European Group on Ethics regarding the “Ethical aspects of human stem
p.000008: cell research and use”. http://europa.eu.int/comm/european_group_ethics/index_en.htm.
p.000008:
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: The EGE identified the following principal requirements regarding human embryonic stem cell research and the
p.000009: procurement of embryonic stem cells from supernumerary embryos:
p.000009: – Free and informed consent from the donating couple or woman.
p.000009:
p.000009: – Approval of the research by an authority.
p.000009:
p.000009: – No financial gain for donors.
p.000009:
p.000009: – Anonymity of the donors and protection of the confidentiality of personal information of the donors.
p.000009:
p.000009: – Transparency regarding research results.
p.000009:
p.000009: Concerning clinical research the EGE stressed the importance of:
p.000009:
p.000009: – Free and informed consent of the patient.
p.000009:
p.000009: – Risk-benefit assessment.
p.000009:
p.000009: – Protection of the health of persons involved in clinical trials.
p.000009:
p.000009: Regulation of human embryonic stem cell research in EU Member States11
p.000009: EU Member States have taken different positions regarding the regulation of human embryonic stem
...
p.000010: Biomedicine signed in Oviedo on 4 April 1997: Austria, Denmark, Finland, France, Germany, Greece,
p.000010: Ireland, Netherlands, Portugal and Spain.
p.000010:
p.000010: New regulations under discussion in EU Member States:
p.000010:
p.000010: Belgium: A bill on research on human embryos in vitro was approved by the Belgian Senate in 2002 and it is now
p.000010: under discussion in the Parliament. The draft legislation proposes to authorise the procurement of
p.000010: embryonic stem cells from supernumerary embryos under certain conditions, and to create a “Federal
p.000010: Commission for scientific medical research on embryos in vitro”.
p.000010:
p.000010: Denmark: A revision of the current legislation to allow for the procurement of human ES cells from
p.000010: supernumerary embryos is under discussion.
p.000010:
p.000010: France: A revision of the Bioethics Law of 1994 has been approved by the Senate in January 2003 and should be discussed
p.000010: by the Parliament in the first semester of 2003. It proposes to allow research on supernumerary human embryos
p.000010: including the procurement of human ES cells for 5 years under certain conditions. A central authorizing body will
p.000010: be created.
p.000010:
p.000010: Italy: a law on in vitro fertilisation is under discussion.
p.000010:
p.000010: Portugal: A committee has been established in Portugal for the preparation of a law on human embryo and
p.000010: human ES cell research.
p.000010:
p.000010: Spain: A revision of the current legislation is under discussion.
p.000010:
p.000010: In 1998 the National Committee for Human Artificial Reproduction was created. In its second opinion, delivered in 2002,
p.000010: it advised to conduct human embryonic stem cell research using as a source supernumerary embryos, estimated in Spain to
p.000010: be over 30 000.
p.000010:
p.000010: The Ethics Advisory Committee for Scientific and Technological Research was established in April 2002 and gave in
p.000010: February 2003 its first opinion on research on stem cells. It recommended to the government that research on
p.000010: both adult and embryonic stem cells should be implemented; that the legislation should be modified to allow
p.000010: the isolation of human embryonic stem cells from supernumerary embryos.
p.000010:
p.000010: Sweden: A revision of the current legislation is under discussion. The Parliamentary Committee on Genetic
p.000010: Integrity proposed, in their report published 29 January 2003, not to implement a general prohibition against
p.000010: producing fertilised eggs for research purposes. It
p.000010:
p.000010:
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p.000011:
p.000011: should also be noted, however, that in the view of the Committee the creation of embryos by transfer of somatic cell
p.000011: nuclei (so called therapeutic cloning) should be treated in the same way and thus in principle be allowed.
p.000011:
p.000011: Regulations in countries acceding to the EU
p.000011:
p.000011: Cyprus, Czech Republic, Estonia, Hungary, Lithuania, Slovak Republic, Slovenia have ratified the Convention of
p.000011: the Council of Europe on biomedicine and human rights.
p.000011:
p.000011: Concerning the countries acceding to the EU, no specific regulations regarding human embryonic stem cell
p.000011: research have at present been implemented. Estonia, Hungary, Latvia, Slovenia have implemented legislation
p.000011: authorising research on human embryos under certain conditions. In Lithuania, Poland and the Slovak
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p.000014: 14
p.000014:
p.000014: INTRODUCTION
p.000014:
p.000014: This report, prepared by the Commission services, aims to provide an overview of:
p.000014:
p.000014: – Origin and characteristics of human stem cells and the potential application of stem cell
p.000014: research.
p.000014:
p.000014: – Human embryonic stem cell research (somatic stem cell research will be addressed so far as it is relevant to
p.000014: the discussion on human embryonic stem cell research).
p.000014:
p.000014: – Governance of human embryonic stem cell research including the ethical issues at stake,
p.000014: regulations in the EU Member States, governance of stem cell research in the context of FP6 and social scrutiny and
p.000014: dialogue.
p.000014:
p.000014: – Socio-economic aspects of human embryonic stem cell research and use. The report is complemented by a series
p.000014: of annexes, as follows:
p.000014: A. Biology of human development
p.000014:
p.000014: B. Possibilities to overcome immune rejection responses in stem cell therapy
p.000014:
p.000014: C. Examples of available human embryonic stem cell lines
p.000014:
p.000014: D. Details regarding provisions in non-EU countries relating to human embryonic stem cell research
p.000014:
p.000014: E. Opinion n° 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell research and use” issued
p.000014: 14 November 2002.
p.000014:
p.000014: F. Statement for the minutes of the Council meeting 30 September 2002 The report takes into account:
p.000014: – Information collected from the survey on opinions from National Ethics Committees or similar bodies,
p.000014: public debate and national legislation in relation to human embryonic stem cell research and use in EU Member
p.000014: States and non-EU countries. The survey was conducted by the European Commission, DG Research, Directorate E (last
p.000014: update March 2003);
p.000014:
p.000014: – Opinions and reports from the European Group on Ethics in Science and New Technologies to
p.000014: the European Commission http://europa.eu.int/comm/european
p.000014: _group_ethics/index_en.htm
p.000014:
p.000014: – Report and proceedings from the conference on “Stem cells: Therapies for the future?” organised by the
p.000014: European Commission, DG Research under the aegis of the European Group on Life Sciences; December
p.000014: 2001 http://europa.eu.int/comm/ research/quality-of-life/stemcells.html
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000015: 15
p.000015:
p.000015: – Candidate Countries legislation related to ethical issues in science and research Proceedings of
p.000015: the workshop of 8-10 December 2002 - Brussels - organised by the European Commission - DG Research – Directorate C
p.000015:
...
p.000019:
p.000019: For the development of novel stem cell based therapies.
p.000019:
p.000019: – Novel stem cell based therapies (often called regenerative medicine or cell based therapies) are
p.000019: also being investigated to develop new methods to repair or replace tissues or cells damaged by injuries or
p.000019: diseases and to treat serious chronic diseases, such as diabetes, Parkinson’s, chronic heart failure or stroke and
p.000019: spinal cord injuries. (See chapter 1.4 for further details)
p.000019:
p.000019: – For the generation of normal human cell lines to be used in drug development at the preclinical stage and in
p.000019: toxicology Stem cells are a source for the generation of normal human cell types that can be genetically or
p.000019: pharmacologically manipulated
p.000019:
p.000019:
p.000019: 22 Wagers A.J. et al., “Little evidence for developmental plasticity of adult haematopoïetic
p.000019: stem cells”, Science, 2002, 297, 2256 2259; De Witt and Knight, “Biologists question adult stem cell
p.000019: versality”, Nature, 2002, 416, 354.
p.000019: 23 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm
p.000019: 24 A. L Lennard and G H Jackson. “Science, medicine and the future: Stem cell transplantation”, BMJ, 2000,
p.000019: 321:433-437.
p.000019: 25 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm Annex
p.000019: E - Opinion n° 15 of the European Group on Ethics http://europa.eu.int/comm/
p.000019: european_group_ethics/docs/avis15_EN.pdf
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: and used for drug discovery. They give scientists the ability to experimentally study - under carefully controlled
p.000020: conditions - the growth and development of many different human cell types that are important to
p.000020: diseases like cancer, diabetes, stroke, heart disease etc. These cell lines may provide more clinically
p.000020: relevant biological systems than animal models for drug testing and are therefore expected to contribute to the
p.000020: development of safer and more effective drugs for major human diseases. For example today, there exists no
p.000020: laboratory model for the human heart, and it is therefore very difficult (impossible) to know exactly what
p.000020: effect medicines have on the heart before performing human studies. The lack of availability of human cells, which
p.000020: express normal function, has so far been the main limiting factor for reducing animal testing in
p.000020: pharmaco-toxicology. It is possible that this application will turn out to be the major medical impact of human
p.000020: ES cell research at least in a short-term perspective. At present insufficient methods exist in some areas of in vitro
p.000020: toxicology predicting target organ toxicity. In other areas such as embryo-toxicity inter-species variation presents
p.000020: major obstacles and humanised systems may enhance the hazard identification of chemicals.
p.000020:
...
p.000026: scientists are now able to propagate human ES cell lines using human feeder layer or even culturing human ES
p.000026: cells without feeder layer. This eliminates the risk that viruses or infectious agents in the mouse cells might be
p.000026: transmitted to the human cells.
p.000026:
p.000026: If the stem cells are of good quality and if they show no sign of ageing, the same stem-cell line can yield
p.000026: unlimited amounts of stem cells. Besides their broad potential for
p.000026:
p.000026:
p.000026: 38 In accordance with the Council decision of 30 September adopting the specific
p.000026: programmes implementing FP 6 the creation of embryos for research purposes and for stem cell procurement,
p.000026: including by means of somatic cell nuclear transfer (i.e. therapeutic cloning) are excluded from funding under the 6th
p.000026: Framework Programme. OJ L 294 of 29.10.2002, p. 8.
p.000026: 39 In accordance with the Council decision of 30 September adopting the specific
p.000026: programmes implementing FP 6 the creation of embryos for research purposes and for stem cell procurement,
p.000026: including by means of somatic cell nuclear transfer (i.e. therapeutic cloning) are excluded from funding under the 6th
p.000026: Framework Programme. OJ L294 of 29.10.2002, p. 8.
p.000026: 40 US NIH, “Stem cells: a primer”, September 2002. http://www.nih.gov./news/stemcell/primer.htm
p.000026: Swedish National Council on Medical Ethics: statement of opinion on embryonic stem cell research, 17.01.2002,
p.000026: http://www.smer.gov.se.
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027: differentiation, embryonic stem cell lines have proved better able to survive in the laboratory than other types of
p.000027: stem cells. At the various points during the process of generating embryonic stem cell lines, scientists test
p.000027: the cells to see whether they exhibit the fundamental properties that make them, embryonic stem cells. As yet, there
p.000027: exists no standard battery of tests that measure the cells’ fundamental properties but several kinds of tests including
p.000027: tests based on the presence of specific surface and gene markers for undifferentiated cells.
p.000027:
p.000027: One can distinguish:
p.000027:
p.000027: – Human ES cells freshly derived from an embryo which have not yet been subjected to any modification and
p.000027: which have yet to be established as stem cell lines.
p.000027:
p.000027: – Unmodified (undifferentiated) human ES cell lines, which refer to cultured lines of cells, which have
p.000027: been propagated for an extended period originally from freshly human ES cells and which have not been modified
p.000027: in any other way.
p.000027:
p.000027: – Modified (differentiated) human ES derivates which refer to cultured lines of cells, derived from human
p.000027: ES cells or human ES cell lines, which have been modified either by genetic manipulation, or by treatment
p.000027: (e.g. growth factors) that causes the cells to differentiate in a particular way e.g. to differentiate into
p.000027: neural or muscle precursor cells (cells which are not fully differentiated, otherwise they will not
p.000027: multiply).
...
p.000029: cell registry (see 2.6)43 several arguments have been put forward regarding the needs for derivation of new human
p.000029: embryonic stem cell lines44:
p.000029: – Human embryonic stem cell research is so new that scientists do not yet know if they have developed the best
p.000029: procedures for isolating or maintaining human ES cells. It is possible that all the current cell lines are
p.000029: compromised, as happened with the first mouse ES cell lines.
p.000029:
p.000029: – Many of the human embryonic stem cell lines currently available have not been sufficiently
p.000029: verified to see whether they exhibit the fundamental properties that make them embryonic stem cells e.g. the six
p.000029: human ES cell lines from the Karolinska Institute currently at the NIH registry are not available and have not
p.000029: yet been fully characterized45 (see annex C for further information).
p.000029: – Most currently available human ES cell lines have been cultivated in contact with mouse cells.
p.000029: The contact with animal cells and serum components involves an unknown risk of contamination with viruses and
p.000029: other infectious agents. Therefore, such cell lines or their derivatives can not be used for transplantation to humans.
p.000029:
p.000029:
p.000029: 42 “Stem Cells: scientific progress and future research directions”, National Institutes of
p.000029: Health (NIH), Bethesda, USA, June 2001 http://www.nih.gov/news/stemcell/scireport.htm; Swiss National Advisory
p.000029: Commission on Biomedical Ethics: opinion on human embryonic stem cell research, June 2002; The Health Council of the
p.000029: Netherlands’ report on “Stem cells for tissue repair. Research on therapy using somatic and embryonic stem cells”,
p.000029: June 2002. http://www.gr.nl/pdf.php?ID=429; House of Lords Select Committee UK “Report on Stem cell
p.000029: research”, February 2002; http://www.parliament.the- stationery-office.co.uk/pa/ld200102/ldselect/ldstem/83/8301.htm
p.000029: ; Swedish National Council of Medical Ethics: Statement of opinion on embryonic stem cell research,
p.000029: 17.01.2002.
p.000029: 43 http://escr.nih.gov/eligibilitycriteria.html. The US National Institute of Health (NIH) has identified 78
p.000029: human embryonic stem cell lines that meet the US eligibility criteria. The availability and the stage of development
p.000029: and characterisation of these human ES cell lines are unclear and the NIH has now indicated 9 human ES
p.000029: cell lines which are available for distribution to different laboratories. (James Battery, Head of NIH panel
p.000029: managing stem cell research). Science 2003 (299) 1509. The Wisconsin Alumni Research Foundation, which owns five
p.000029: stem cell lines, claims that it has enough to supply all scientists in the world.
p.000029: 44 e.g. The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy
p.000029: using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000029: 45 Communication from Carlstedt-Duke, Dean of Research, Karolinska Institute, Sweden.
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000030: – Currently available human ES cell lines represent only limited amount of genetic variation. It
p.000030: is important to notice that cell lines with a different genetic basis can have different characteristics.
p.000030:
p.000030: – Many of the existing embryonic stem cell lines have been patented in the US. It is important
p.000030: not to be in a dependent position with respect to private industry.
p.000030:
p.000030: Annex C provides examples of the currently available human ES cell lines.
...
p.000031: individual teams. It will also offer the opportunity to collect stem cell lines with different immuno- phenotypes. Cell
p.000031: lines with the best matching phenotypes can later be selected for cell or tissue transplantation.
p.000031:
p.000031: Human embryonic stem cell registry
p.000031: The US National Institutes of Health (NIH) established in autumn 2001 an Human Embryonic Stem Cell Registry which
p.000031: at present lists 78 human ES cell lines that meet the eligibility criteria for Federally funded
p.000031: research49. The registry indicates 14 laboratories or companies across the world, which have developed human
p.000031: embryonic stem cell lines. The availability of these cell lines and their level of characterisation are unclear and the
p.000031: NIH Human Embryonic Cell Registry has recently been updated to reflect the human ES cell lines that meet
p.000031: the eligibility criteria for Federally funded research and which are currently available for shipping to other
p.000031: laboratories50. This list includes 9 human ES cell lines:
p.000031: 2 human ES cell lines from BresaGen, Inc. (a US based company)
p.000031: 5 human ES cell lines from ES Cell International (a company based in Singapore and Australia)
p.000031: 1 human ES cell line from University of California at San Francisco 1 human ES cell line from Wisconsin Alumni Research
p.000031: Foundation
p.000031: Both the European Group on Ethics in Science and New Technologies51 and the European Group on Life
p.000031: Sciences52 have highlighted the need for a European registry of stem cell lines. In particular, the EGE called in their
p.000031: opinion n°16 on “Ethical aspects of patenting inventions involving human stem cells” for the creation of an EU registry
p.000031: of unmodified human stem cell lines.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 48 Communication from Professor Hamberger, Goteborg University, Sweden.
p.000031: 49 http://escr.nih.gov/eligibilitycriteria.html. The following eligibility criteria must be
p.000031: met: (i) the derivation process has been initiated before 9 August 2001; (ii) the stem cells must have been derived
p.000031: from an embryo that was created for reproductive purposes but the embryo was not longer needed for those purposes;
p.000031: (iii) informed consent must have been obtained for the donation of the embryo; (iv) no financial inducements were
p.000031: provided for donation of the embryo.
p.000031: 50 http://escr.nih/
p.000031: 51 http://europa.eu.int/comm/european_group_ethics/docs/avis16_en.pdf
p.000031: 52 http://europa.eu.int/comm/research/life-sciences/egls/index_en.html
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032: “Such registry, which should include information on both embryonic stem cells and embryonic germ
p.000032: cell lines should be publicly accessible. Its aim would be to ensure transparency and thus facilitate
...
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033: Chapter 3: Governance of human embryonic stem cell research
p.000033:
p.000033:
p.000033:
p.000033: Human embryonic stem cell research raises complex ethical questions. It confronts scientific progress with ethical
p.000033: concerns and it has triggered an intense public debate on its guiding ethical principles and limitations.
p.000033: The question whether it is ethically defensible to do research on embryonic stem cells can be described
p.000033: as a conflict between different values, between different actors’ rights and obligations, or between the short-
p.000033: and long-term interests of different groups. On the one hand, there is interest in new knowledge that can
p.000033: lead to treatment of hitherto incurable diseases. On the other hand, when this research involves the use of human
p.000033: embryos, it raises the question of ethical values at stake and of the limits and conditions for such research53.
p.000033: Opinions on the legitimacy of experiments using human embryos are divided according to the different ethical,
p.000033: philosophical, and religious traditions in which they are rooted. EU Member States have taken very different positions
p.000033: regarding the regulation of human embryonic stem cell research. This confirms that different views exist
p.000033: throughout the European Union concerning what is and what is not ethically defensible.
p.000033:
p.000033: 3.1. The ethical issues at stake
p.000033: The European Group on Ethics highlighted in its Opinion No.15 regarding “Ethical aspects of human stem cell research
p.000033: and use”, issued 14 November 200054, that “the fundamental ethical principles applicable to stem cell research are:
p.000033:
p.000033: – The principle of respect for human dignity
p.000033:
p.000033: – The principle of individual autonomy (entailing the giving of informed consent, and respect for
p.000033: privacy and confidentiality of personal data)
p.000033:
p.000033: – The principle of justice and of beneficence (namely with regard to the improvement and
p.000033: protection of health)
p.000033:
p.000033: – The principle of freedom of research (which is to be balanced against other
p.000033: fundamental principles)
p.000033:
p.000033: – The principle of proportionality (including that research methods are necessary to the aims pursued and that
p.000033: no alternative more acceptable methods are available).
p.000033:
p.000033: In addition, the Group considers it important to take into account, based on a precautionary approach, the potential
p.000033: long-term consequences of stem cell research and use for individuals and the society.”
p.000033:
p.000033: Concerning the creation of embryos for research purpose the EGE considered that “the creation of embryos
p.000033: for the sole purpose of research raises serious concerns since it represents a further step in the
p.000033: instrumentalisation of human life” and deemed “ the creation
p.000033:
p.000033:
p.000033: 53 Annex E - Opinion No. 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell
p.000033: research and use”; http://europa.eu.int/comm/european_group_ethics/docs/avis15_en.pdf
p.000033: 54 Annex E: Opinion No. 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell
p.000033: research and use”; http://europa.eu.int/comm/european_group_ethics/docs/avis15_en.pdf
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034: of embryos with gametes donated for the purpose of stem cell procurement ethically unacceptable, when spare
p.000034: embryos55 represent a ready alternative source”.
p.000034: Furthermore the EGE considered “ that, at present, the creation of embryos by somatic cell nuclear transfer for
p.000034: research on stem cell therapy would be premature, since there is a wide field of research to be carried out with
p.000034: alternative sources of human stem cells (from spare embryos, foetal tissues and adult stem cells”.
p.000034:
p.000034: The ethical acceptability of human embryonic stem cell research in the context of Community Framework
p.000034: Programme for Research
p.000034: The EGE noted in the same opinion that “in some countries embryo research is forbidden. But when this research is
p.000034: allowed, with the purpose of improving treatment for infertility, it is hard to see any specific argument,
p.000034: which would prohibit extending the scope of such research in order to develop new treatments to cure severe
p.000034: diseases or injuries. As in the case of research on infertility, stem cell research aims to alleviate
p.000034: severe human suffering. In any case, the embryos that have been used for research are required
p.000034: to be destroyed. Consequently, there is no argument for excluding funding of this kind of research from the
p.000034: Framework Programme of research of the European Union if it complies with ethical and legal requirements
p.000034: as defined in this programme”.
p.000034:
p.000034: Secondly the EGE stated, that:
p.000034:
p.000034: “Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells)
p.000034: requires a specific Community research budget. In particular, EU funding should be devoted to testing the validity of
p.000034: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000034: such research be widely disseminated and not hidden for reasons of commercial interest.
p.000034: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000034: funding for stem cell research. This implies the establishment of appropriate procedures and provision of
p.000034: sufficient means to permit ethical assessment not only before the launching of a project but also in monitoring
p.000034: its implementation.”
p.000034:
p.000034: Principal requirements regarding human embryonic stem cell research.
p.000034: Concerning the use of human supernumerary embryos as a source of stem cells the EGE stressed in their
p.000034: opinion that “ the derivation of stem cells from embryonic blastocysts raises the issue of the moral status of the
p.000034: human embryo. In the context of European pluralism, it is up to each Member State to forbid or authorise embryo
p.000034: research. In the latter case, respect for human dignity requires regulation of embryo research and the
p.000034: provision of guarantees against risks of arbitrary experimentation and instrumentalisation of human embryos”.
p.000034:
p.000034: The EGE also stressed regarding stem cell research and rights of women that “Women who undergo infertility treatment
p.000034: are subject to high psychological and physical strain. The group stresses the necessity to ensure that the demand for
p.000034: spare embryos (supernumerary embryos) and oocyte donation does not increase the burden on women”.
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: 55 Spare embryos: another word for supernumerary embryos.
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035: The EGE stressed also the importance of the following requirements regarding human embryonic stem cell
p.000035: research and the procurement of embryonic stem cells from supernumerary embryos:
p.000035:
p.000035: – Free and informed consent from the donating couple or woman.
p.000035: The EGE stated: “Free and informed consent is required not only from the donor but also from the
p.000035: recipient as stated in the Group's opinion on Human Tissue Banking (21/07/1998). In each case, it is necessary to
p.000035: inform the donor (the woman or the couple) of the possible use of the embryonal cells for the specific purpose
p.000035: in question before requesting consent.” The requirements may differ on the type of information that should
p.000035: be provided and on the definition of which persons should give their consent (the couple or the woman). The Charter
p.000035: of Fundamental Rights of the European Union recognised in article 3(2) that “In the fields of medicine and biology the
p.000035: following must be respected in particular – the free and informed consent of the person concerned, according to the
p.000035: procedures laid down by law…”.
p.000035:
p.000035: – Approval of the research by an authority.
p.000035: The EGE recommended that human ES cell research should be placed, “in the countries where it is
p.000035: permitted, under strict public control by a centralised authority - following, for instance, the pattern of
p.000035: the UK licensing body (the Human Fertilisation and Embryology Authority)” and provided that “ authorisations
p.000035: given to such research are highly selective and based on a case by case approach, while ensuring maximum transparency.
p.000035: This must apply whether the research in question is carried out by either the public or the private sector”.
p.000035:
p.000035: – No financial gain for donation
p.000035: The EGE recommended that “The potential for coercive pressure should not be underestimated when
p.000035: there are financial incentives. Embryos as well as cadaveric foetal tissue must not be bought or sold, and not
p.000035: even offered for sale. Measures should be taken to prevent such commercialisation”.
p.000035: The Charter of Fundamental Rights of the European Union recognised in article 3(2) that “In the fields of medicine
p.000035: and biology the following must be respected in particular… the prohibition on making the human body and its
p.000035: parts as such a source of financial gain”.
p.000035: Article 21 of the Council of Europe Convention on Human Rights and Biomedicine specifically prohibits
p.000035: financial gain from all or part of the human body.
p.000035:
p.000035: – Anonymity of the donors and protection of the confidentiality of personal information of the
p.000035: donors as it applies for donation of human biological material.
p.000035: The EGE recommended that “Steps must be taken to protect and preserve the identity of both the donor and the recipient
p.000035: in stem cell research and use”. As stated in the EGE's Opinion on Human Tissue Banking (21/07/1998): “in the
p.000035: interests of anonymity, it is prohibited to disclose information that could identify the donor, and the
p.000035: recipient. In general, the donor should not know the identity of the recipient, nor should the recipient know the
p.000035: identity of the donor”. In most cases the donors will not be anonymous in the sense that the embryo could be traced
p.000035: back to the donor of the egg and sperm. Although the identity of the donor should normally be
p.000035: protected though coding and other measures to ensure confidentiality, there would still be safety and quality
p.000035: requirements for clinical research demanding that the link to the donors not be completely removed. Anonymity will then
p.000035: not be possible.
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: – Transparency regarding research results.
p.000036:
p.000036: The EGE recommended in the context of funding stem cell research within the EU Framework Programmes for
p.000036: Research that “the EU should insist that the results of such research be widely disseminated and not hidden
p.000036: for reasons of commercial interest”
p.000036:
p.000036: Concerning clinical research on human stem cells the EGE stressed the importance of the following
p.000036: requirements:
p.000036:
p.000036: – Free and informed consent of the patient and the donor
p.000036:
p.000036: – Risk-benefit assessment
p.000036: “Risk-benefit assessment is crucial in stem cell research, as in any research, but is more difficult as
p.000036: the uncertainties are considerable given the gaps in our knowledge. Attempts to minimise the risks and increase
p.000036: the benefits should include optimising the strategies for safety. It is not enough to test the cultured
p.000036: stem cells or tissues derived from them for bacteria, viruses or toxicity. Safety and security aspects
p.000036: are of utmost importance in the transplantation of genetically modified cells and when stem cells are
p.000036: derived from somatic cells. For example, the risks that transplanted stem cells cause abnormalities or
p.000036: induce creation of tumours or cancer have to be assessed. It is important that the potential benefits for the
p.000036: patients should be taken into account but not exaggerated. The grounds of a precautionary approach need to
p.000036: be taken into account”.
p.000036:
p.000036: – Protection of the health of persons involved in clinical trials
p.000036:
p.000036: “The possibility that irreversible and potentially harmful changes are introduced in clinical applications of stem
p.000036: cell research should be minimised. Techniques enhancing the possibilities of reversibility should be
p.000036: used whenever possible. If, for example, genetically modified cells were encapsulated when they are transplanted
p.000036: in order to stimulate neural cell growth, it should be possible for the procedure to be reversed if something goes
p.000036: wrong.”
p.000036:
p.000036: The opinion of the EGE regarding “Ethical aspects of human stem cell research and use” dates back to 14
p.000036: November 2000, but it is still considered to be relevant. Human stem cell research and in particular human embryonic
p.000036: stem cell research are still in an early stage of development and therefore the fundamental ethical principles
p.000036: at stake and the requirements for for human embryonic stem cell research are still relevant.
p.000036:
p.000036: Chapter 3.2 provides further information regarding the requirements applied in EU Member States allowing for the import
p.000036: and use of human embryonic stem cells and/or the procurement of human ES cells from supernumerary embryos.
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000037: 37
p.000037:
p.000037: 3.2. Regulations in EU Member States regarding human embryonic stem cell research56
p.000037: EU Member States have already taken very different positions regarding the regulation of human ES cell
p.000037: research and new legislation or regulations are being drafted or debated. Table 1 attempts to provide a comprehensive
p.000037: overview of the situation as of March 2003.
p.000037:
p.000037: The following distinctions can be made:
p.000037:
p.000037: 1. Allowing for the procurement of human embryonic stem cells from supernumerary embryos by law
p.000037: Finland
p.000037: The medical research Act of 1999 covers the preconditions and use of human embryos up to 14 days of embryonic
p.000037: development. The production of human embryonic stem cells from supernumerary embryos is allowed. The
p.000037: laboratories that do embryo research need a licence from the National Authority for Medicolegal Affairs. An
p.000037: ethics committee must approve research projects. The informed consent of both gamete donors is required.
p.000037:
p.000037: Greece
p.000037: The recent law 3089/2002 on medically assisted human reproduction allows for the procurement of
p.000037: human embryonic stem cells from supernumerary embryos. The Act requires the informed consent of both gamete donors and
p.000037: no financial inducement.
p.000037:
p.000037: The Netherlands
p.000037: The Embryo Act of September 2002 allows the use of supernumerary embryos for research including isolation of
p.000037: embryonic stem cells from such embryos. This research requires the favourable opinion of the Central
p.000037: committee for research involving human subjects. The informed consent of the donor is required. The
p.000037: research must have the aim to lead to new insights in medical science.
p.000037:
p.000037: Sweden
p.000037: The Act of 1991 on “Measures for Purposes of Research and Treatment involving Fertilised Human Ova” and the Health
p.000037: and Medical Care Act (18-982:763) apply. According to the Act(1991:115), in vitro embryo research is
p.000037: legally permitted until day 14 after conception, after which the embryo must be destroyed.. After some discussion
p.000037: there is consensus that this legislation permits human embryonic stem cell research. A revision of the law
p.000037: is under discussion (see chapter 3.3)
p.000037:
p.000037: United Kingdom
p.000037: The research purposes permitted by the Human Fertilisation and Embryology Act of 1990 were extended by
p.000037: the “Human Fertilisation and Embryology (Research Purposes ) Regulation” of 2001 to permit the use
p.000037: of embryos in research to increase knowledge about serious diseases and their treatment. The Human
p.000037: Fertilisation and Embryology Authority is
p.000037:
p.000037:
p.000037: 56 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000037: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
...
p.000038: b) The scientific knowledge to be obtained from the research project concerned cannot be expected to be
p.000038: gained by using cells other than embryonic stem cells.
p.000038: Concerning approval section 6 states:
p.000038: 1) Any importation and any utilisation of embryonic stem cells shall be subject to approval by the competent agency
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039: 2) Applications for approval must be submitted in writing. In the documents accompanying the application, the applicant
p.000039: shall provide the following information in particular:
p.000039: 1. Name and official address of the person responsible for the research project concerned,
p.000039: 2. A description of the research project including scientific reasons showing that the research project meets the
p.000039: requirements set forth in section 5 above,
p.000039: 3. A documentation concerning the embryonic stem cells to be imported or used showing that the
p.000039: requirements set forth in no. 1 of para 2 of section 4 above have been complied with or equivalent evidence that
p.000039: a) The embryonic stem cells to be imported or used are identical with those registered in a
p.000039: scientifically recognised, publicly accessible registry maintained by government agencies or agencies authorised by the
p.000039: government and that,
p.000039: b) By way of such registration, the requirements set forth in no. 1 of para 2 of section 4 above have been complied
p.000039: with.
p.000039: 3) The competent agency shall immediately acknowledge in writing receipt of the application and the attached documents.
p.000039: At the same time, the agency shall request the opinion of the Central Ethics Commission on Stem Cell Research. On
p.000039: receipt of the opinion, the agency shall notify the applicant of the content and the date of the opinion adopted by the
p.000039: Central Ethics Commission on Stem Cell Research.
p.000039:
p.000039: 4) Approval shall be given if:
p.000039: 1. The requirements set forth in para 2 of section 4 above have been complied with,
p.000039: 2. The requirements set forth in section 5 above have been complied with and, accordingly, the research
p.000039: project is ethically acceptable, and if
p.000039: 3. An opinion by the Central Ethics Commission on Stem Cell Research has been submitted following a
p.000039: request by the competent agency to this effect.
p.000039: 5) If the application, complete with documentation, and the opinion of the Central Ethics Commission on Stem Cell
p.000039: Research have been received, the agency shall decide in writing on the application within a period of two months. In
p.000039: doing so, the agency shall consider the opinion adopted by the Central Ethics Commission Stem Cell Research, the agency
p.000039: shall give its reasons in writing.
p.000039:
p.000039: 6) Approval can be limited in time or by imposing obligations to the extent necessary for complying with or continuing
p.000039: to meet the approval requirements pursuant to para 4 above. If, following approval, events occur which
p.000039: conflict with the granting of approval, approval can be withdrawn wholly or in part with effect in the
p.000039: future or be limited in time or be made dependent on the fulfilment of conditions to the extent
p.000039: necessary for complying with or continuing to meet the approval requirements set forth in para 4 above. Any objection
p.000039: to or action for rescission of withdrawal or revocation of approval shall not suspend the effect of the decision.
p.000039:
p.000039: The first authorisation to import human embryonic stem cell lines was given in December 2002.
p.000039:
p.000039: 3. Prohibition of the procurement of embryonic stem cells from human supernumerary embryos.
p.000039: Austria
p.000039: The Austrian Reproductive Medicine Act of 1992 states that cells capable of development may only be used
p.000039: for medical assisted reproduction. According to the interpretation of the Reproductive Medicine Act the
p.000039: procurement of stem cells from embryonic tissues is prohibited. The use of imported human ES
p.000039: cells is not explicitly prohibited and discussion regarding authorisation is still ongoing.
p.000039:
p.000039: Denmark
p.000039: The Act on Medically Assisted Procreation from 1997 only allows research intending to improve in vitro
p.000039: fertilisation technique or pre-implantation diagnosis techniques. Therefore, the isolation of human ES cells from
p.000039: supernumerary embryos is forbidden. The importation of
p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040: human ES cells is not explicitly forbidden. However, the Danish government will give its opinion on human
p.000040: embryonic stem cell research in spring 2003, and has recommended that no research with human ES cell lines should be
p.000040: commenced until the government has presented its decision to Parliament (See also chapter 3.3)
p.000040:
p.000040: France
p.000040: Under the Bioethics Law of 1994, research on human embryos in vitro is forbidden except for research which does not
p.000040: harm the embryo. The import and use of human ES cell lines derived from supernumerary embryos is not explicitly
p.000040: prohibited but the authorisation is still under discussion. A revision of the Bioethics law is under discussion
p.000040: (see chapter 3.3)
p.000040:
p.000040: Ireland
p.000040: There is no legislation dealing with research on embryos. However, the Irish constitution of 1937 (as amended in
p.000040: 1983) provides that “the State acknowledges the right to life of the unborn and, with due regard to the
p.000040: equal right to life of the mother, guarantees in its laws to respect, and, as far as practicable, by its laws to defend
p.000040: and vindicate that right”.
p.000040:
p.000040: Spain
p.000040: The laws of 1988 on Assisted Reproduction Techniques and on donation and use of embryos and foetuses or their cells
p.000040: authorises research on in vitro human embryos biologically non- viable under certain conditions. There is no clear
p.000040: interpretation of the concept of a non-viable embryo. Concerning viable human embryos, only research for the
p.000040: benefit of the concerned embryos is allowed. A revision of the law is under discussion (see chapter 3.3)
p.000040:
...
p.000043: embryos including the procurement of human ES cells under the following conditions:
p.000043: – the research should have the potential to lead to major therapeutic advances and only be undertaken if there
p.000043: is no alternative method of comparable effectiveness available;
p.000043: – the embryos must derive from an in vitro fertilisation, in the context of a medically assisted
p.000043: reproduction (supernumerary embryos);
p.000043: – written consent of the couple from which the embryos are issued;
p.000043: – authorisation by a central body to be created.
p.000043: The proposed bill will also allow the import of foetal or embryonic cells or tissues after prior authorisation by the
p.000043: central body.
p.000043:
p.000043:
p.000043:
p.000043: 57 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000043: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000043: cell research and use (last update March 2003).
p.000043:
p.000044: 44
p.000044:
p.000044: Italy
p.000044: A law on in vitro fertilisation is under discussion. The Ministry of Health recently produced a report about the banks
p.000044: conserving embryos and gametes.
p.000044:
p.000044: Portugal
p.000044: A committee has been established in Portugal for the preparation of a law on human embryo and human ES cell research.
p.000044:
p.000044: Spain
p.000044: A revision of the current legislation is under discussion.
p.000044: In 1998 the National Committee for Human Artificial Reproduction was created. In its second opinion, delivered in 2002,
p.000044: it advised to conduct human embryonic stem cell research using as a source supernumerary embryos, estimated in Spain to
p.000044: be over 30 000.
p.000044: The Ethics Advisory Committee for Scientific and Technological Research was established in April 2002 and gave in
p.000044: February 2003 its first opinion on research on stem cells. It recommended to the government that research on
p.000044: both adult and embryonic stem cells should be implemented; that the legislation should be modified to allow
p.000044: the isolation of human embryonic stem cells from supernumerary embryos under the following condition: The
p.000044: parents´ informed consent or, if this is not possible, the permission of the Centre of Assisted
p.000044: Reproduction in charge of keeping the embryos according to the regulation in force. The investigation
p.000044: must have the aim of alleviating human suffering and not just economic ends. It must be exclusively done by
p.000044: working groups with a proved experience in this field. The protocol of investigation must be previously
p.000044: evaluated by Ethics Committees and it must be under their exhaustive control. Therefore, the control and
p.000044: supervision of these investigations by a national committee is recommended.
p.000044:
p.000044: Sweden
p.000044: A revision of the current legislation is under discussion.
p.000044: The Parliamentary Committee on Genetic Integrity proposed, in their report published 29 January 2003, not
p.000044: to implement a general prohibition against producing fertilised eggs for research purposes. It is the opinion
p.000044: of the Committee that such production must take place in order for research to be carried out on infertility and the
p.000044: development of the fertilised egg etc. It is not possible to set a legal limit with sufficient clarity that would
p.000044: delineate what, on the contrary, would be forbidden. This delineation should rather be done on a case-by-case basis
p.000044: within the framework of ethics review of research. It should also be noted, however, that in the view of the
p.000044: Committee the creation of embryos by transfer of somatic cell nuclei (so- called therapeutic cloning) should
p.000044: be treated in the same way and thus in principle be allowed.
p.000044:
p.000044:
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p.000045: 45
p.000045:
p.000045: 3.4. Regulations in some non-EU countries regarding human embryonic stem cell research58
p.000045: Countries acceding to the EU:
p.000045: Cyprus, Czech Republic, Estonia, Hungary, Lithuania, Slovak Republic, Slovenia have ratified the Convention of
p.000045: the Council of Europe on biomedicine and human rights59.
p.000045: No specific regulations regarding human embryonic stem cell research have a present been implemented in the
p.000045: countries acceding to the EU.
p.000045:
p.000045: Cyprus:
p.000045: Cyprus has ratified the Convention of the Council of Europe on biomedicine and human rights. There is no
p.000045: specific regulation regarding human embryo research.
p.000045:
p.000045: Czech Republic:
p.000045: Czech Republic has ratified the Convention of the Council of Europe on biomedicine and human rights. There
...
p.000049:
p.000049:
p.000049:
p.000049: 65 OJ L294 of 29.10.2002, p. 8.
p.000049: 66 Research relating to cancer treatment of the gonads can be financed.
p.000049:
p.000050: 50
p.000050:
p.000050: – As stated in the Council minutes of 30 September 200267 “The Council and the Commission agree
p.000050: that detailed implementing provisions concerning research activities involving the use of human
p.000050: embryos and human embryonic stem cells…shall be established by 31 December 2003”.
p.000050:
p.000050: The Commission will during that period…not propose to fund such research, with the exception of banked or
p.000050: isolated human embryonic stem cells in culture.
p.000050:
p.000050: 3.6. Social scrutiny and dialogue
p.000050: There are significant differences in national attitudes towards specific techniques and areas of research. In
p.000050: particular, human embryonic stem cell research has recently provoked intense public and political debate. As
p.000050: the life sciences and biotechnology develop, they contribute considerably to securing welfare on the personal and
p.000050: societal levels as well as to creating new opportunities for our economies. At the same time, the general
p.000050: public is increasingly concerned about the social and ethical consequences of these advances in knowledge
p.000050: and techniques as well as about the conditions forming the choices made in these fields.
p.000050:
p.000050: The EGE stressed in its opinion regarding “Ethical aspects of human stem cell research and use” there is a need
p.000050: for continuing dialogue and education to promote the participation of citizens, including patients, in
p.000050: scientific governance, namely in social choices created by new scientific developments”.
p.000050:
p.000050: The need for public dialogue on scientific advances and new technologies has also been highlighted in both
p.000050: the Commission’s communication on “Life Sciences and Biotechnology”, published on 27 January 200268 and the
p.000050: Commission’s action plan on “Science and Society” published in December 200169.
p.000050: In this connection, the European Group on Life Sciences70, set up by the European Research Commissioner Philippe
p.000050: Busquin, organised on 18-19 December 2001,a forum entitled “Stem cells: therapies for the future?”. The aim was
p.000050: to offer a platform at European level for a debate between, on one side, scientists and experts
p.000050: concerned with the feasibility and consequences of stem cell research and, on the other side, a wide range of
p.000050: representatives of society. More than 600 people participated in the event.71. Much of the public discussion that took
p.000050: place, both at the forum itself and by e-mail exchanges concentrated on ethical issues, particularly those relating to
p.000050: the use of human embryos.
p.000050:
p.000050: As for any new potential treatment, the promises of stem cell research may create amongst patients suffering from
p.000050: incurable diseases and their families, high and sometimes unrealistic expectations from science and the imperative
...
p.000052:
p.000052: – Services and technologies: screening, isolation of stem cells, preparation and large scale culture
p.000052: of stem cells, storage of stem cells.
p.000052:
p.000052: One of the current framework conditions affecting stem cell research and commercialisation of stem cells therapies is
p.000052: the patenting of human ES cells and their derivatives. On the one hand patent rights are necessary to protect and
p.000052: secure industry’s huge investments to support innovative research and development. On the other hand academic research
p.000052: is stimulated by having free and open access to these cell lines, as they are essential starting materials for their
p.000052: research. Some scientists consider that human embryonic stem cell lines should not be patented at all. The
p.000052: debate on this issue is intense and includes the ethical dimension of this
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 72 Gilder Biotech report, The American Spectator, June 2001, “Adult cells do
p.000052: it better”; http://www.gilderbiotech.com/ArticlesByScott/Op%20Ed/AdultCells.htm
p.000052:
p.000053: 53
p.000053:
p.000053: research. The European Group on Ethics73 in Science and New Technologies (EGE) recommended in their
p.000053: opinion No.16 on patenting of human stem cells that:
p.000053:
p.000053: Isolated stem cells, which have not been modified do not, as product, fulfil the legal requirements,
p.000053: especially with regards to industrial applications, to be seen as patentable. In addition, such isolated cells are so
p.000053: close to the human body, to the foetus or to the embryo they have been isolated from, that their
p.000053: patenting may be considered as a form of commercialisation of the human body.
p.000053: When unmodified stem cell lines are established, they can hardly be considered as a patentable product.
p.000053: Such unmodified stem cell lines do not have indeed a specific use but a very large range of potential undescribed uses.
p.000053: Therefore, to patent such unmodified stem cell lines would also lead to too broad patents.
p.000053: Therefore only stem cell lines which have been modified by in vitro treatments or genetically modified so that they
p.000053: have acquired characteristics for specific industrial application, fulfil the legal requirements for patentability.
p.000053: As to the patentability of processes involving human stem cells, whatever their source, there is no specific ethical
p.000053: obstacle, in so far as they fulfil the requirements of patentability (novelty, inventive step and industrial
p.000053: application).
p.000053:
p.000053: Directive 98/44 on the legal protection of biotechnological inventions, adopted on 6 July 1998,
p.000053: establishes that an element isolated from the human body or otherwise produced by means of a technical
...
p.000067: 83 http://grants.nih.gov/grants/stem_cells.htm
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p.000067:
p.000068: 68
p.000068:
p.000068: purposes and no longer needed for those purposes. In addition, informed consent must have been obtained for the
p.000068: donation of the embryo and the donation must not have involved financial inducements. The NIH Human Embryonic
p.000068: Stem Cell Registry has been created and is updated to reflect stem cell lines that meet the eligibility
p.000068: criteria (see also chapter 2.6). There is no federal law regulating research on human embryos and the derivation of
p.000068: human ES cells when such research is funded by the private sector.
p.000068: However, California has passed a law, in September 2002, allowing the procurement of human embryonic stem
p.000068: cells from supernumerary embryos. New legislation authorising the procurement of human ES cells from
p.000068: supernumerary embryos is under discussion in the States of New Jersey and Massachusetts.
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p.000069: 69
p.000069:
p.000069: ANNEX E: Opinion No.15 of the European Group on Ethics regarding ethical aspects of human stem cell research and use
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: OPINION OF THE EUROPEAN GROUP ON ETHICS IN SCIENCE AND NEW TECHNOLOGIES
p.000069: No 15
p.000069: 14 November 2000
p.000069: ************************************************************************************************************************
p.000069: ***
p.000069:
p.000069: ETHICAL ASPECTS OF HUMAN STEM CELL RESEARCH AND USE
p.000069:
p.000069: Reference: Initiative of the Group
p.000069: Rapporteurs: Anne McLaren and Göran Hermerén
p.000069:
p.000069: ************************************************************************************************************************
p.000069: ***
p.000069:
p.000069: The European Group on Ethics in Science and New Technologies (EGE),
p.000069:
p.000069: Having regard to the Treaty on European Union as amended by the Treaty of Amsterdam, and in particular
p.000069: Article 6 (formerly Article F) of the common provisions, concerning the respect for fundamental rights, Article 152
p.000069: (formerly Article 129) of the EC Treaty on public health, (namely paragraph 4(a) referring to substances of
p.000069: human origin) and Articles 163-173 (formerly Articles 130F-130P) on research and technological development;
p.000069:
p.000069: Having regard to the European Parliament and Council Directive 65/65/CEE of 26 January 1965 and the modified Directive
p.000069: 75/319/CEE of 20 May 1975 concerning medicinal products;
p.000069:
p.000069: Having regard to the Council Directive 93/42/EEC of 14 June 1993 concerning medical devices and the European Parliament
p.000069: and Council Directive 98/79/EC of 27 October 1998 concerning in vitro diagnostic medical devices, in particular Article
...
p.000078: cell research, a much wider scope of research is being considered.
p.000078:
p.000078: The use of ES cells and stem cell lines for therapeutic purposes. Human embryos used for research were destroyed after
p.000078: the research was completed and therefore were never used for fertility treatment. What remained was additional
p.000078: knowledge. Human embryonic stem cell research is aimed at creating cell lines with appropriate characteristics, in
p.000078: terms of purity and specificity. There is thus continuity from the embryonic cells to the therapeutic material obtained
p.000078: by culture.
p.000078:
p.000078: The creation of embryos for research purposes. This delicate issue is now raised again since there is a scientific
p.000078: justification of this practice, namely the possibility of producing stem cells identical to the patient's
p.000078: cells and thus avoiding problems of rejection in the context of the future “regenerative medicine”. At
p.000078: the same time, creating human embryos raises new ethical concerns. The ethical acceptability of stem cell
p.000078: research depends not only on the objectives but also on the source of the stem cells; each source raising partly
p.000078: different ethical questions. Those who condemn embryo research in general will not accept this difference, but for
p.000078: those who accept it, this issue is of major importance.
p.000078:
p.000078:
p.000078:
p.000078: 1.17. Ethical issues in transplantation of stem cells
p.000078:
p.000078: Clinical research and potential future applications in this field raise the same ethical issues as those dealt with in
p.000078: the EGE's Opinion on Human Tissue Banking (21/07/1998), concerning the respect of the donor, who should give informed
p.000078: consent to this use of the donated cells, the respect of the autonomy of the patients, their right to safety and to the
p.000078: protection of their private life and the right to a fair and equal access to new therapies.
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p.000079: 79
p.000079:
p.000079: 2 - OPINION
p.000079: The Group submits the following Opinion:
p.000079:
p.000079: SCOPE OF THE OPINION
p.000079:
p.000079: 2.1 Ethical issues of stem cell research and use for clinical purposes.
p.000079: This Opinion reviews ethical issues raised by human stem cell research and use, in the context of the European Union
p.000079: research policy and European Community public health competence to improve human health and to set high standards for
p.000079: the safety of substances of human origin.
p.000079: With regard to the specific ethical questions related to the patenting of inventions involving human stem cells, on
p.000079: which President Prodi requested an Opinion from the Group on 18 October 2000, this will be made public in Brussels at a
p.000079: later date. The following Opinion therefore excludes the patenting issue.
p.000079:
p.000079: GENERAL APPROACH
p.000079: 2.2. Fundamental ethical principles at stake
p.000079: The fundamental ethical principles applicable are those already recognised in former opinions of the EGE, and more
p.000079: specifically:
p.000079: - the principle of respect for human dignity
p.000079: - the principle of individual autonomy (entailing the giving of informed consent, and respect for privacy and
p.000079: confidentiality of personal data)
p.000079: - the principle of justice and of beneficence (namely with regard to the improvement and protection of health)
p.000079: - the principle of freedom of research (which is to be balanced against other fundamental principles)
p.000079: - the principle of proportionality (including that research methods are necessary to the aims pursued and that no
p.000079: alternative more acceptable methods are available).
p.000079: In addition, the Group considers it important to take into account, based on a precautionary approach,
p.000079: the potential long-term consequences of stem cell research and use for individuals and the society.
p.000079:
p.000079: 2.3. Pluralism and European ethics
p.000079: Pluralism is characteristic of the European Union, mirroring the richness of its tradition and adding a need for mutual
p.000079: respect and tolerance. Respect for different philosophical, moral or legal approaches and for diverse
p.000079: cultures is implicit in the ethical dimension of building a democratic European society.
...
p.000080: research in question is carried out by either the public or the private sector.
p.000080:
p.000080:
p.000080: 2.7. Alternative methods to the creation of embryos for the purpose of stem cell research.
p.000080: The Group considers that the creation of embryos for the sole purpose of research raises serious
p.000080: concerns since it represents a further step in the instrumentalisation of human life.
p.000080:
p.000080: • The Group deems the creation of embryos with gametes donated for the purpose of stem cell
p.000080: procurement ethically unacceptable, when spare embryos represent a ready alternative source.
p.000080:
p.000080: • The Group takes into account interest in performing somatic cell nuclear transfer (SCNT) with the
p.000080: objective of studying the conditions necessary for "reprogramming" adult human cells. It is also aware that, in view
p.000080: of future cell therapy, the creation of embryos by this technique may be the most effective way to
p.000080: derive pluripotent stem cells genetically identical to the patient and consequently to obtain perfectly
p.000080: histocompatible tissues, with the aim of avoiding rejection after transplantation. But, these remote therapeutic
p.000080: perspectives must be balanced against considerations related to the risks of trivialising the use of embryos
p.000080: and exerting pressure on women, as sources of oocytes, and increasing the possibility of their instrumentalisation.
p.000080: Given current high levels of inefficiency in SCNT, the provision of cell lines would require large numbers of oocytes.
p.000080: • In the opinion of the Group, in such a highly sensitive matter, the proportionality principle and
p.000080: a precautionary approach must be applied: it is not sufficient to consider the legitimacy of the pursued aim of
p.000080: alleviating human sufferings, it is also essential to consider the means employed. In particular, the hopes of
p.000080: regenerative medicine are still very speculative and debated among scientists. Calling for prudence, the
p.000080: Group considers that, at present, the creation of embryos by somatic cell nuclear transfer for research on
p.000080: stem cell therapy would be premature, since there is a wide field of research to be carried out with alternative
p.000080: sources of human stem cells (from spare embryos, foetal tissues and adult stem cells).
p.000080:
p.000080: 2.8. Stem cell research in the European Framework Programme of research
p.000080: Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells) requires a
p.000080: specific Community research budget. In particular, EU funding should be devoted to testing the validity
p.000080:
p.000080:
p.000080:
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p.000080:
p.000081: 81
p.000081:
p.000081: of recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the
p.000081: results of such research be widely disseminated and not hidden for reasons of commercial interest.
p.000081: At European Union level, within the Framework Programme of research, there is a specific responsibility to provide
p.000081: funding for stem cell research. This implies the establishment of appropriate procedures and provision of sufficient
p.000081: means to permit ethical assessment not only before the launching of a project but also in monitoring its
p.000081: implementation.
p.000081:
p.000081: 2.9. Stem cell research and rights of women
p.000081: Women who undergo infertility treatment are subject to high psychological and physical strain. The Group
p.000081: stresses the necessity to ensure that the demand for spare embryos and oocyte donation does not increase
p.000081: the burden on women.
p.000081:
p.000081: CLINICAL RESEARCH ON HUMAN STEMXCELLS
p.000081: The speed with which researchers, throughout the world, are moving to test stem cells in patients is remarkable, even
p.000081: if ES cell transplantation is unlikely to be attempted in the near future. Clinical trials with stem cells other than
p.000081: ES carried out on patients suffering from severe conditions such as Parkinson’s disease, heart disease or diabetes
p.000081: raise the following issues:
p.000081:
p.000081:
p.000081: 2.10. Free and informed consent
p.000081:
p.000081: Free and informed consent is required not only from the donor but also from the recipient as stated in the Group's
p.000081: opinion on Human Tissue Banking (21/07/1998). In each case, it is necessary to inform the donor (the woman or the
p.000081: couple) of the possible use of the embryonal cells for the specific purpose in question before
p.000081: requesting consent.
p.000081:
p.000081: 2.11. Risk-benefit assessment
p.000081: Risk-benefit assessment is crucial in stem cell research, as in any research, but is more difficult as
p.000081: the uncertainties are considerable given the gaps in our knowledge. Attempts to minimise the risks and increase the
p.000081: benefits should include optimising the strategies for safety. It is not enough to test the cultured
p.000081: stem cells or tissues derived from them for bacteria, viruses or toxicity. Safety and security aspects are of utmost
p.000081: importance in the transplantation of genetically modified cells and when stem cells are derived from somatic cells. For
p.000081: example, the risks that transplanted stem cells cause abnormalities or induce creation of tumours or cancer have to be
p.000081: assessed. It is important that the potential benefits for the patients should be taken into account but
p.000081: not exaggerated. The grounds of a precautionary approach need to be taken into account.
p.000081:
p.000081: 2.12. Protection of the health of persons involved in clinical trials
p.000081: The possibility that irreversible and potentially harmful changes are introduced in clinical applications of stem cell
p.000081: research should be minimised. Techniques enhancing the possibilities of reversibility should be used whenever possible.
p.000081: If, for example, genetically modified cells were encapsulated when they are transplanted in order to
p.000081: stimulate neural cell growth, it should be possible for the procedure to be reversed if something goes wrong.
p.000081:
p.000081: 2.13. Scientific evaluation of stem cell use for therapeutic purposes
p.000081:
p.000081: It is urgent to outline strategies and specific requirements for the best evaluation of ethically sound and safe use of
p.000081: stem cells as means of therapy (gene therapy, transplantation, etc.). Such an evaluation should be done in
p.000081: collaboration with the European Agency for the Evaluation of Medicinal Products.
p.000081:
p.000081: 2.14. Anonymity of the donation
p.000081:
p.000081: Steps must be taken to protect and preserve the identity of both the donor and the recipient in stem cell research and
p.000081: use. As stated in the EGE's Opinion on Human Tissue Banking (21/07/1998): "in the interests of anonymity, it
p.000081:
p.000081:
p.000081:
p.000082: 82
p.000082:
p.000082: is prohibited to disclose information that could identify the donor, and the recipient. In general, the donor should
p.000082: not know the identity of the recipient, nor should the recipient know the identity of the donor".
p.000082:
p.000082:
p.000082: 2.15. Stem cell banks and safety
p.000082:
p.000082: Procurement and storage of stem cells in stem cell banks leads to the collection and storage of a growing number of
p.000082: personal and familial data. Cell banks should be regulated at European level in order to facilitate the
p.000082: implementation of a precautionary approach. If unsatisfactory side effects occur, it should be possible to trace donor
p.000082: and recipient and to reach their medical files. Traceability must be one of the conditions required for the
p.000082: authorisation of cell banks at national or European level.
p.000082:
p.000082:
p.000082: 2.16. Stem cell banks and confidentiality
p.000082:
p.000082: In order to reconcile the traceability requirement and the need to protect the donor’s rights - medical confidentiality
p.000082: and privacy - cell banks must take the necessary steps to protect confidentiality of the data.
p.000082:
p.000082:
p.000082: 2.17. Prohibition of commerce in embryos and cadaveric foetal tissue
p.000082: The potential for coercive pressure should not be underestimated when there are financial incentives. Embryos as well
p.000082: as cadaveric foetal tissue must not be bought or sold, and not even offered for sale. Measures should be taken to
p.000082: prevent such commercialisation.
p.000082:
...
p.000089: subsequent adjustment to their use, the content of the calls for proposals as well as the draft implementing measures
p.000089: concerning the approval of funding of RTD actions within the relevant field.
p.000089: As for themes encompassing more than one domain, the agenda should be defined in such a way as to ensure, whenever
p.000089: appropriate, both the overall coherence as well as the more specific articulation of themes and expertise.
p.000089: This should apply in particular where calls for proposals and project funding are on the agenda.
p.000089:
p.000089: The reimbursement of one representative and one expert/adviser, from each Member State, participating in
p.000089: programme committee meetings will be effected from the budget of each respective specific programme in full
p.000089: respect of its budgetary envelope. The reimbursement of the second person (expert/adviser) will not constitute a
p.000089: precedent for committees operating in other fields of Community policy.
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000090: 90
p.000090:
p.000090: (b) The Commission states that:
p.000090:
p.000090: In order to ensure efficiency and transparency of implementation, it will systematically make available to the
p.000090: Programme Committee comprehensive information covering all the proposals received for RTD actions as well as those
p.000090: eventually funded, regardless of their size.
p.000090:
p.000090: The Commission will provide the information in a user-friendly form, including whenever possible in
p.000090: electronic form, in time for the Committee to take due account of it, at least two weeks in advance for matters
p.000090: for the committee's opinion and one week for matters for information.
p.000090:
p.000090: In addition to information periodically made public through the Annual Report under Article 173 of the Treaty, as well
p.000090: as through the monitoring and the 5-year assessment reports, data for each priority or area will be made available
p.000090: during the last quarter of each year that will encompass, in a consolidated presentation, the information regularly
p.000090: supplied to committees on programme implementation and budget execution.
p.000090:
p.000090: This information will cover all stages, from calls for proposals, through the evaluation of proposed RTD
p.000090: actions, their selection, as well as the signature of contracts and their subsequent implementation.
p.000090:
p.000090: It will in particular include an overview of each call and for each proposal:
p.000090:
p.000090: – summary information;
p.000090:
p.000090: – the evaluation panels' ranking and summary reports; and
p.000090:
p.000090: – the Commission's intentions as to proposals to be rejected or to be retained for negotiation;
p.000090:
p.000090: – total budget and requested Community contribution.
p.000090:
p.000090: The Commission will provide information regularly, and at least annually, on:
p.000090: – the contracts signed (including partners, areas, content, resources and Member States'
p.000090: participation) and on their major developments, together with
p.000090:
p.000090: – overviews of programme progress and implementation achievements, as well as
p.000090:
p.000090: – the lists of persons having acted as evaluators over the previous period once all decisions have been made on
p.000090: the relevant call.
p.000090:
p.000090:
p.000090: 3. Specific programme "Integrating and strengthening the European Research Area"
p.000090:
...
p.000092: JRC.
p.000092:
p.000092: The Commission wishes to confirm that the JRC multiannual work programme will be available on the JRC
p.000092: website: http://www.jrc.org.
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
p.000093: 93
p.000093:
p.000093: 6. Specific programme “Nuclear Energy” (Euratom) Re: Voting rights at the consultative committee
p.000093: The Council and the Commission acknowledge the unanimous agreement of the consultative committee for the fusion
p.000093: programme (CCFP) on the following weighted voting system, which should be applied within the Committee referred to in
p.000093: Article 6(2), when dealing with fusion related aspects. Accordingly, the Commission will take the appropriate steps
p.000093: with a view to amending the Council Decision of 16 December 1980 – as last amended by Council Decision 95/1/EC,
p.000093: Euratom, ECSC of 1 January 1995 – setting up the consultative committee for the fusion programme.
p.000093: Germany 5
p.000093: Austria 2
p.000093: Belgium 2
p.000093: Denmark 2
p.000093: Spain 3
p.000093: Finland 2
p.000093: France 5
p.000093: Greece 2
p.000093: Ireland 2
p.000093: Italy 5
p.000093: Luxembourg 1
p.000093: Netherlands 2
p.000093: Portugal 2
p.000093: United Kingdom 5
p.000093: Sweden 2
p.000093: Switzerland 2
p.000093: Total 44
p.000093: For the adoption of an opinion, the required majority is 23 votes in favour by at least eight delegations.
p.000093:
p.000093:
p.000093:
p.000094: 94
p.000094:
p.000094: 7. Unilateral and bilateral statements relating to the specific programmes
p.000094:
p.000094: (a) Statement by Germany and Austria on Article 3 of the specific programme "Integrating and strengthening the
p.000094: European research area"
p.000094: "Germany and Austria emphasise that they maintain their position that, even after the end of the moratorium in
p.000094: December 2003, research using human embryos and human embryonic stem cells, with the exception of stem cells
p.000094: already held in banks or isolated in culture, should not be funded under the 6th Framework Programme. Moreover,
p.000094: Germany and Austria assume that, under the second specific programme, "Structuring the European Research
p.000094: Area", the Commission will not fund any research activities ineligible for funding on account of the
p.000094: statement for the minutes concerning the first specific programme "Integrating and strengthening
p.000094: the European Research Area"."
p.000094:
p.000094:
p.000094: (b) Statement by Ireland (bioethics)
p.000094: "Ireland, in supporting the adoption of the specific programmes to implement the Sixth Framework Programme
p.000094: for reseach, recalls its statements pertaining to research that cannot be carried out in Ireland. Ireland also
p.000094: recalls the Council statement and its joint statement with Italy, Germany, Portugal and Austria, pertaining to
p.000094: the further elaboration of detailed guidelines on ethical aspects.
p.000094:
p.000094: Ireland welcomes
p.000094:
...
Economic / Economic/Poverty
Searching for indicator poor:
(return to top)
p.000023: after transplantation in a Parkinson rat model”, Proc. Natl. Acad. Sci. USA , 2002, 99:2344-2349; Kim J-H. et al.,
p.000023: “Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease”,
p.000023: Nature, 2002, 418: 50-56.
p.000023: 30 Steindler, D.A. and Pincus D.W., “Stem cells and neuropoiesis in the adult brain”, Lancet,
p.000023: 2002, 359(9311):1047-1054.
p.000023: 31 Kehat et al., “Human embryonic stem cells can differentiate into myocytes with structural
p.000023: and functional properties”, J Clin Invest, 2001, 103:407-14.
p.000023: 32 Orlic, D. et al. “Bone marrow cells regenerate infarcted myocardium”, Nature, 2001, 410,
p.000023: 701-705. Orlic, D. et al. “Mobilized bone marrow cells repair the infacted heart, improving function and
p.000023: survival”, Proc Natl Acad Sci USA 2001, 98: 10344-9.
p.000023: 33 Assmus, B. et al. “Transplantation of progenitor cells and regeneration enhancement
p.000023: in acute myocardial infarction (TOPCARE-AMI)”, Circulation, 2002, 106: R53-R61; Strauer, B.E. et al.
p.000023:
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024: Diabetes
p.000024:
p.000024: In people who suffer from type I diabetes, the cells of the pancreas that normally produce insulin are
p.000024: destroyed by the patient’s own immune system. Although diabetics can be treated with daily injections of insulin, these
p.000024: injections enable only intermittent glucose control. As a result, patients with diabetes suffer chronic degeneration of
p.000024: many organs, including the eye, kidney, nerves and blood vessels. In some cases, patients with diabetes have been
p.000024: treated with islet beta cell transplantation. However, poor availability of suitable sources for islet beta cell
p.000024: transplantation from post mortem donors makes this approach difficult as a treatment for the growing numbers of
p.000024: individuals suffering from diabetes.
p.000024:
p.000024: Ways to overcome this problem include deriving islet cells from other sources such as:
p.000024:
p.000024: – Human adult pancreatic duct cells that have been grown successfully in vitro and induced to
p.000024: differentiate, but the ability of these cells to restore blood glucose in vivo is still unproven. This promising
p.000024: line of research is being pursued by several laboratories.
p.000024:
p.000024: – Fetal pancreatic stem cells and ß cell precursor. The identification of endocrine precursor cells
p.000024: in the developing pancreas and the regulation of their differentiation by a specific cellular pathway raises the
p.000024: possibility to grow and differentiate endocrine precursor cells in vitro taken from aborted foetus or by
p.000024: using adult pancreatic duct cells34.
p.000024: – Embryonic stem cells. Research in mice has demonstrated that mouse embryonic stem cells can differentiate
p.000024: into insulin- producing cells and other pancreatic endocrine hormones. The cells self-assemble to form
p.000024: three-dimensional clusters similar in topology to normal pancreatic islets. Transplantation of these cells
p.000024: was found to improve the conditions of experimental animals with diabetes35. New studies indicate that it is possible
...
p.000072:
p.000072: Much research on mouse ES cells has also been focused on using these cells to create transgenic animals, in particular
p.000072: as disease models to study human genetic disorders.
p.000072:
p.000072:
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: • Adult stem cells
p.000073:
p.000073: Research is also carried out on mouse adult stem cells. While many scientists had assumed that these cells were
p.000073: programmed to produce specific tissues and were thus no longer able to produce other sorts of tissue, recent studies
p.000073: suggest that adult stem cells may be able to show more malleability than previously believed. For instance, it has been
p.000073: shown that mouse neural stem cells could give rise, in specific conditions of culture, to cells of other organs such as
p.000073: blood, muscle, intestine, liver and heart. Moreover marrow stromal cells can generate astrocytes, a non-neuronal type
p.000073: of cell of the central nervous system and haematopoietic stem cells can give rise to myocytes.
p.000073:
p.000073:
p.000073: 1.7. First grafts of human foetal cells
p.000073:
p.000073: Stem cells in tissues such as skin or blood are able to repair the tissues throughout life. By contrast, the nervous
p.000073: system has a very limited capacity for self-repair because the neural stem cells in the adult brain
p.000073: are few in number and have a poor capacity to generate new neurons for instance to repair injury.
p.000073:
p.000073: Based on the positive results of experimentation on rodents and primates, clinical trials in patients
p.000073: with Parkinson's disease have been performed on around 200 patients over the last 10 years especially in
p.000073: Sweden and the USA. They have shown that the transplantation of neural cells derived from the human foetus can have a
p.000073: therapeutic effect, with an important reduction of the symptoms of the disease in the treated patients. The clinical
p.000073: improvement among these patients has been observed for 6-24 months after transplantation and in some cases for 5-10
p.000073: years. It has recently been shown that 10 years after the transplantation surgery, the transplanted
p.000073: neural cells were still alive and producing dopamine, the compound which is deficient in the brain of patients with
p.000073: Parkinson's disease.
p.000073:
p.000073: However, this therapeutic approach still remains experimental. In addition, the availability of neural foetal tissue
p.000073: is very limited. Five to six aborted foetuses are needed to provide enough neural tissue to treat one
p.000073: Parkinson's patient. That is why new sources of neural cells have been explored in some countries such as the US and
p.000073: Sweden. The aim is to derive neural stem cells from foetuses: these stem cells could be induced to proliferate in
p.000073: culture, providing much greater amounts of neural tissue for transplantation.
...
General/Other / Dependent
Searching for indicator dependent:
(return to top)
p.000029: 17.01.2002.
p.000029: 43 http://escr.nih.gov/eligibilitycriteria.html. The US National Institute of Health (NIH) has identified 78
p.000029: human embryonic stem cell lines that meet the US eligibility criteria. The availability and the stage of development
p.000029: and characterisation of these human ES cell lines are unclear and the NIH has now indicated 9 human ES
p.000029: cell lines which are available for distribution to different laboratories. (James Battery, Head of NIH panel
p.000029: managing stem cell research). Science 2003 (299) 1509. The Wisconsin Alumni Research Foundation, which owns five
p.000029: stem cell lines, claims that it has enough to supply all scientists in the world.
p.000029: 44 e.g. The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on therapy
p.000029: using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000029: 45 Communication from Carlstedt-Duke, Dean of Research, Karolinska Institute, Sweden.
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000030: – Currently available human ES cell lines represent only limited amount of genetic variation. It
p.000030: is important to notice that cell lines with a different genetic basis can have different characteristics.
p.000030:
p.000030: – Many of the existing embryonic stem cell lines have been patented in the US. It is important
p.000030: not to be in a dependent position with respect to private industry.
p.000030:
p.000030: Annex C provides examples of the currently available human ES cell lines.
p.000030: 2.6. Developments regarding establishment of human stem cell banks and registries. Human stem cell banks
p.000030: The need for public stem cell banks including human embryonic stem cell has been recognised at national
p.000030: level both in Sweden and UK.
p.000030:
p.000030: The British Medical Research Council (MRC) in autumn 2002, in collaboration with the Biotechnology and
p.000030: Biological Science Research Council (BBSRC) and with the full backing of the UK Government, took the initiative
p.000030: to establish the first large-scale publicly funded Stem Cell Bank worldwide. The National Institute for
p.000030: Biological Standards and Control (NIBSC) is hosting the UK Stem Cell Bank46, which officially started 1 January
p.000030: 2003.
p.000030: The general aim of the UK Stem Cell Bank will be to create an independent and competent facility to store, test and
p.000030: release seed stocks of existing and new stem cell lines derived from adult, foetal and embryonic human tissues.
p.000030: There will be two primary components in this work:
p.000030:
p.000030: 1) To provide stocks of well-characterised stem cell lines for use in research in the UK and abroad. These
p.000030: will be established under well regulated, but non-GMP, conditions and made available in order to promote fundamental
p.000030: research.
p.000030:
p.000030: 2) To provide stocks of stem cell lines prepared under GMP conditions, that could be used directly for
p.000030: production of human therapeutic materials.
p.000030:
p.000030: In February 2002, the Human Fertilisation and Embryology Authority (HFEA) in the UK granted the first
...
p.000039: Central Ethics Commission on Stem Cell Research.
p.000039:
p.000039: 4) Approval shall be given if:
p.000039: 1. The requirements set forth in para 2 of section 4 above have been complied with,
p.000039: 2. The requirements set forth in section 5 above have been complied with and, accordingly, the research
p.000039: project is ethically acceptable, and if
p.000039: 3. An opinion by the Central Ethics Commission on Stem Cell Research has been submitted following a
p.000039: request by the competent agency to this effect.
p.000039: 5) If the application, complete with documentation, and the opinion of the Central Ethics Commission on Stem Cell
p.000039: Research have been received, the agency shall decide in writing on the application within a period of two months. In
p.000039: doing so, the agency shall consider the opinion adopted by the Central Ethics Commission Stem Cell Research, the agency
p.000039: shall give its reasons in writing.
p.000039:
p.000039: 6) Approval can be limited in time or by imposing obligations to the extent necessary for complying with or continuing
p.000039: to meet the approval requirements pursuant to para 4 above. If, following approval, events occur which
p.000039: conflict with the granting of approval, approval can be withdrawn wholly or in part with effect in the
p.000039: future or be limited in time or be made dependent on the fulfilment of conditions to the extent
p.000039: necessary for complying with or continuing to meet the approval requirements set forth in para 4 above. Any objection
p.000039: to or action for rescission of withdrawal or revocation of approval shall not suspend the effect of the decision.
p.000039:
p.000039: The first authorisation to import human embryonic stem cell lines was given in December 2002.
p.000039:
p.000039: 3. Prohibition of the procurement of embryonic stem cells from human supernumerary embryos.
p.000039: Austria
p.000039: The Austrian Reproductive Medicine Act of 1992 states that cells capable of development may only be used
p.000039: for medical assisted reproduction. According to the interpretation of the Reproductive Medicine Act the
p.000039: procurement of stem cells from embryonic tissues is prohibited. The use of imported human ES
p.000039: cells is not explicitly prohibited and discussion regarding authorisation is still ongoing.
p.000039:
p.000039: Denmark
p.000039: The Act on Medically Assisted Procreation from 1997 only allows research intending to improve in vitro
p.000039: fertilisation technique or pre-implantation diagnosis techniques. Therefore, the isolation of human ES cells from
p.000039: supernumerary embryos is forbidden. The importation of
p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040: human ES cells is not explicitly forbidden. However, the Danish government will give its opinion on human
p.000040: embryonic stem cell research in spring 2003, and has recommended that no research with human ES cell lines should be
p.000040: commenced until the government has presented its decision to Parliament (See also chapter 3.3)
...
p.000060: finished and the embryo can properly be described as a foetus. A distinction is drawn between the
p.000060: foetal germ cells from which the gametes (egg cells and sperm) develop and from which “pluripotent” embryonic
p.000060: germ stem cells (EG cells) can be derived during a brief period in the early foetal development and the remaining
p.000060: foetal tissue from which “multipotent” foetal somatic stem cells can be derived.
p.000060:
p.000060: 8. Nine months after fertilisation: birth
p.000060:
p.000060: At around nine months, given normal gestation, the baby is born.
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000060:
p.000061: 61
p.000061:
p.000061: ANNEX B: Possibilities to overcome immune rejection responses in stem cell therapy
p.000061:
p.000061:
p.000061:
p.000061:
p.000061: There are several ways of avoiding or repressing immune rejection of transplanted cells or tissues74:
p.000061: 1) Use of immune-suppressant drugs
p.000061: These drugs, which suppress the activity of the immune system, have been refined over many years, as part of organ
p.000061: transplantation research. However, they are not always effective; they must normally be taken over the lifetime
p.000061: of the patient; and they leave the patient open to infection.
p.000061:
p.000061: 2) Use of “matching” tissues
p.000061: The magnitude of rejection is dependent on the differences between the patients HLA system and that of the donor.
p.000061: For this reason, the differences should be as small as possible. Sometimes during transplantation it is
p.000061: possible to get a matched tissue type, usually from a near relative. This is often sought for bone marrow transplants.
p.000061: Finding a matching donor is unlikely to be a useful approach for most cell-based therapies. However, because stem cells
p.000061: can, in principle, be cultured indefinitely, it might be possible to establish stem cell banks of sufficient size to
p.000061: comprise stem cells with a reasonable (though never perfect) match to the majority of individuals in the
p.000061: population. If this proved possible, the appropriate matching stem cell from the bank could be selected
p.000061: and differentiated into the cell type required for therapy. Several thousand stem cell lines would be needed to
p.000061: obtain matches to the majority of the population comparable with those achieved with matched bone marrow transplants.
p.000061:
p.000061: 3) Generation of immunotolerance
p.000061: Rejection can also be reduced by the generation of immunotolerance. Previous administration of embryonic material,
p.000061: or haematopoietic cells from the stem cell donor, might cause the patient’s immune system to become
p.000061: habituated to some extent and smaller doses of immunosuppressive drugs would be required, or none
p.000061: at all. In addition, research is being carried out into the possibility of preventing an immune reaction by
p.000061: enclosing the cells to be transplanted in a capsule of inert material.
...
General/Other / Impaired Autonomy
Searching for indicator autonomy:
(return to top)
p.000007: ; House of Lords Select Committee UK, “Report on Stem cell research”, February 2002;
p.000007: http:/:www.parliament.the-stationery-office.co.uk/pa/ld200102/ldselect/ ldstem/83/8301.htm; Swedish National Council of
p.000007: Medical Ethics: statement of opinion on embryonic stem cell research, 17.01.2002, http://www.smer.gov.se/.
p.000007: 8 The Health Council of the Netherlands’ report on “Stem cells for tissue repair. Research on
p.000007: therapy using somatic and embryonic stem cells”, June 2002. http://www.gr.nl/pdf.php?ID=429.
p.000007: 9 Annex E - Opinion No. 15 of the European Group on Ethics regarding the “Ethical aspects of human stem
p.000007: cell research and use”. http://europa.eu.int/comm/european_group_ethics/index_en.htm.
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: Ethical issues at stake:
p.000008:
p.000008: As highlighted in the opinion n° 15 of The European Group on Ethics in Sciences and New Technologies regarding «
p.000008: Ethical aspects of human stem cell research and use”, issued 14 November 2000,10 the following fundamental
p.000008: ethical principles are applicable to human embryonic stem cell research:
p.000008:
p.000008: – The principle of respect for human dignity.
p.000008:
p.000008: – The principle of individual autonomy (entailing the giving of informed consent, and respect for
p.000008: privacy and confidentiality of personal data).
p.000008:
p.000008: – The principle of justice and of beneficence (namely with regard to the improvement and
p.000008: protection of health).
p.000008:
p.000008: – The principle of freedom of research (which is to be balanced against other
p.000008: fundamental principles).
p.000008:
p.000008: – The principle of proportionality (including that research methods are necessary to the aims pursued and that
p.000008: no alternative more acceptable methods are available).
p.000008:
p.000008: In addition, the EGE considers it important to take into account, based on a precautionary approach, the potential
p.000008: long-term consequences of stem cell research and use for individuals and the society.”
p.000008:
p.000008: Concerning the creation of embryos for research purpose the EGE considered that “the creation of embryos
p.000008: for the sole purpose of research raises serious concerns since it represents a further step in the
p.000008: instrumentalisation of human life” and deemed “ the creation of embryos with gametes donated for the purpose of
p.000008: stem cell procurement ethically unacceptable, when spare embryos represent a ready alternative source”.
p.000008:
p.000008: Furthermore the EGE considered “that, at present, the creation of embryos by somatic cell nuclear transfer for research
p.000008: on stem cell therapy would be premature, since there is a wide field of research to be carried out with alternative
...
p.000033: The question whether it is ethically defensible to do research on embryonic stem cells can be described
p.000033: as a conflict between different values, between different actors’ rights and obligations, or between the short-
p.000033: and long-term interests of different groups. On the one hand, there is interest in new knowledge that can
p.000033: lead to treatment of hitherto incurable diseases. On the other hand, when this research involves the use of human
p.000033: embryos, it raises the question of ethical values at stake and of the limits and conditions for such research53.
p.000033: Opinions on the legitimacy of experiments using human embryos are divided according to the different ethical,
p.000033: philosophical, and religious traditions in which they are rooted. EU Member States have taken very different positions
p.000033: regarding the regulation of human embryonic stem cell research. This confirms that different views exist
p.000033: throughout the European Union concerning what is and what is not ethically defensible.
p.000033:
p.000033: 3.1. The ethical issues at stake
p.000033: The European Group on Ethics highlighted in its Opinion No.15 regarding “Ethical aspects of human stem cell research
p.000033: and use”, issued 14 November 200054, that “the fundamental ethical principles applicable to stem cell research are:
p.000033:
p.000033: – The principle of respect for human dignity
p.000033:
p.000033: – The principle of individual autonomy (entailing the giving of informed consent, and respect for
p.000033: privacy and confidentiality of personal data)
p.000033:
p.000033: – The principle of justice and of beneficence (namely with regard to the improvement and
p.000033: protection of health)
p.000033:
p.000033: – The principle of freedom of research (which is to be balanced against other
p.000033: fundamental principles)
p.000033:
p.000033: – The principle of proportionality (including that research methods are necessary to the aims pursued and that
p.000033: no alternative more acceptable methods are available).
p.000033:
p.000033: In addition, the Group considers it important to take into account, based on a precautionary approach, the potential
p.000033: long-term consequences of stem cell research and use for individuals and the society.”
p.000033:
p.000033: Concerning the creation of embryos for research purpose the EGE considered that “the creation of embryos
p.000033: for the sole purpose of research raises serious concerns since it represents a further step in the
p.000033: instrumentalisation of human life” and deemed “ the creation
p.000033:
p.000033:
p.000033: 53 Annex E - Opinion No. 15 of the European Group on Ethics regarding “Ethical aspects of human stem cell
p.000033: research and use”; http://europa.eu.int/comm/european_group_ethics/docs/avis15_en.pdf
...
p.000078: knowledge. Human embryonic stem cell research is aimed at creating cell lines with appropriate characteristics, in
p.000078: terms of purity and specificity. There is thus continuity from the embryonic cells to the therapeutic material obtained
p.000078: by culture.
p.000078:
p.000078: The creation of embryos for research purposes. This delicate issue is now raised again since there is a scientific
p.000078: justification of this practice, namely the possibility of producing stem cells identical to the patient's
p.000078: cells and thus avoiding problems of rejection in the context of the future “regenerative medicine”. At
p.000078: the same time, creating human embryos raises new ethical concerns. The ethical acceptability of stem cell
p.000078: research depends not only on the objectives but also on the source of the stem cells; each source raising partly
p.000078: different ethical questions. Those who condemn embryo research in general will not accept this difference, but for
p.000078: those who accept it, this issue is of major importance.
p.000078:
p.000078:
p.000078:
p.000078: 1.17. Ethical issues in transplantation of stem cells
p.000078:
p.000078: Clinical research and potential future applications in this field raise the same ethical issues as those dealt with in
p.000078: the EGE's Opinion on Human Tissue Banking (21/07/1998), concerning the respect of the donor, who should give informed
p.000078: consent to this use of the donated cells, the respect of the autonomy of the patients, their right to safety and to the
p.000078: protection of their private life and the right to a fair and equal access to new therapies.
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000079: 79
p.000079:
p.000079: 2 - OPINION
p.000079: The Group submits the following Opinion:
p.000079:
p.000079: SCOPE OF THE OPINION
p.000079:
p.000079: 2.1 Ethical issues of stem cell research and use for clinical purposes.
p.000079: This Opinion reviews ethical issues raised by human stem cell research and use, in the context of the European Union
p.000079: research policy and European Community public health competence to improve human health and to set high standards for
p.000079: the safety of substances of human origin.
p.000079: With regard to the specific ethical questions related to the patenting of inventions involving human stem cells, on
p.000079: which President Prodi requested an Opinion from the Group on 18 October 2000, this will be made public in Brussels at a
p.000079: later date. The following Opinion therefore excludes the patenting issue.
p.000079:
p.000079: GENERAL APPROACH
p.000079: 2.2. Fundamental ethical principles at stake
p.000079: The fundamental ethical principles applicable are those already recognised in former opinions of the EGE, and more
p.000079: specifically:
p.000079: - the principle of respect for human dignity
p.000079: - the principle of individual autonomy (entailing the giving of informed consent, and respect for privacy and
p.000079: confidentiality of personal data)
p.000079: - the principle of justice and of beneficence (namely with regard to the improvement and protection of health)
p.000079: - the principle of freedom of research (which is to be balanced against other fundamental principles)
p.000079: - the principle of proportionality (including that research methods are necessary to the aims pursued and that no
p.000079: alternative more acceptable methods are available).
p.000079: In addition, the Group considers it important to take into account, based on a precautionary approach,
p.000079: the potential long-term consequences of stem cell research and use for individuals and the society.
p.000079:
p.000079: 2.3. Pluralism and European ethics
p.000079: Pluralism is characteristic of the European Union, mirroring the richness of its tradition and adding a need for mutual
p.000079: respect and tolerance. Respect for different philosophical, moral or legal approaches and for diverse
p.000079: cultures is implicit in the ethical dimension of building a democratic European society.
p.000079: From a legal point of view, respect for pluralism is in line with Article 22 of the Charter on Fundamental Rights on
p.000079: “Cultural, religious and linguistic diversity” and with Article 6 of the Amsterdam Treaty which ensures
...
General/Other / Manipulable
Searching for indicator manipulated:
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p.000005: scientific and technical hurdles needs to be resolved before clinical application of these therapies, including
p.000005:
p.000005: – Understanding of the mechanisms regulating stem cell growth, fate, differentiation and
p.000005: dedifferentiation.
p.000005:
p.000005: – Eliminating the risk of development of inappropriate differentiated cells and cancerous cells. The
p.000005: risk of tumorigenicity has in particular been highlighted concerning the use of human ES cells as these stem cells
p.000005: develop teratomas.
p.000005:
p.000005: – Ensuring the function and viability of the stem cells or their derivatives during the recipient’s life.
p.000005:
p.000005:
p.000005:
p.000005: 4 A. L. Lennard and G H Jackson, “Science, medicine and the future: Stem cell transplantation”, BMJ, 2000,
p.000005: 321: 433-437.
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006: – Overcoming the problem of immune rejection (which does not arise in the case where the patient’s own stem cells
p.000006: can be used).
p.000006:
p.000006: – For the generation of human cells lines to be used in drug development at pre- clinical stage and in
p.000006: toxicology. Normal human cell types generated from human stem cells can be genetically or
p.000006: pharmacologically manipulated and used for drug discovery. These cell lines may provide more clinically relevant
p.000006: biological systems than animal models for drug testing and are therefore expected to contribute to the development of
p.000006: safer and more effective drugs for human diseases and ultimately to reduce the use of animals. They also offer the
p.000006: possibility to develop better in vitro models to enhance the hazard identification of chemicals. It is
p.000006: possible that these applications will turn out to be the major medical impact of human ES cell research at least in
p.000006: a short-term perspective, as the problems of immune rejection, viability and tumorigenicity do not apply
p.000006: here.
p.000006:
p.000006: – For the understanding of human development. Human ES cells should offer insights into
p.000006: developmental events that cannot be studied directly in the intact human embryo but that have important
p.000006: consequences in clinical areas, including birth defects, infertility, and pregnancy loss.
p.000006:
p.000006: – For the understanding of the basic mechanisms of cell differentiation and proliferation. The
p.000006: understanding of the genes and molecules, such as growth factors and nutrients, that function during development of the
p.000006: embryo may be used to grow stem cells in the laboratory and direct their development into specialized cell types. Some
p.000006: of the most serious medical conditions, such as cancer, are due to abnormal cell division and
...
p.000019: leukemia or congenital immunodeficiencies. Autologous transplantation (transplantation of stem cells from
p.000019: the patient’s own bone marrow or peripheral blood) was introduced to rescue the bone marrow of
p.000019: patients who had received high dose of chemotherapy. It is now increasingly being used as primary treatment for
p.000019: other types of cancer such as breast cancer and neuroblastoma. Autologous transplantation is also used experimentally
p.000019: to treat difficult auto-immune conditions and as a vehicle for gene therapy. Today, over 350 centres in
p.000019: Europe are performing more than 18 000 bone marrow transplants a year24.
p.000019: Human stem cell research is expected to be of interest for several areas of science and medicine25:
p.000019:
p.000019: For the development of novel stem cell based therapies.
p.000019:
p.000019: – Novel stem cell based therapies (often called regenerative medicine or cell based therapies) are
p.000019: also being investigated to develop new methods to repair or replace tissues or cells damaged by injuries or
p.000019: diseases and to treat serious chronic diseases, such as diabetes, Parkinson’s, chronic heart failure or stroke and
p.000019: spinal cord injuries. (See chapter 1.4 for further details)
p.000019:
p.000019: – For the generation of normal human cell lines to be used in drug development at the preclinical stage and in
p.000019: toxicology Stem cells are a source for the generation of normal human cell types that can be genetically or
p.000019: pharmacologically manipulated
p.000019:
p.000019:
p.000019: 22 Wagers A.J. et al., “Little evidence for developmental plasticity of adult haematopoïetic
p.000019: stem cells”, Science, 2002, 297, 2256 2259; De Witt and Knight, “Biologists question adult stem cell
p.000019: versality”, Nature, 2002, 416, 354.
p.000019: 23 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm
p.000019: 24 A. L Lennard and G H Jackson. “Science, medicine and the future: Stem cell transplantation”, BMJ, 2000,
p.000019: 321:433-437.
p.000019: 25 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm Annex
p.000019: E - Opinion n° 15 of the European Group on Ethics http://europa.eu.int/comm/
p.000019: european_group_ethics/docs/avis15_EN.pdf
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: and used for drug discovery. They give scientists the ability to experimentally study - under carefully controlled
p.000020: conditions - the growth and development of many different human cell types that are important to
p.000020: diseases like cancer, diabetes, stroke, heart disease etc. These cell lines may provide more clinically
p.000020: relevant biological systems than animal models for drug testing and are therefore expected to contribute to the
p.000020: development of safer and more effective drugs for major human diseases. For example today, there exists no
...
General/Other / Natural Hazards
Searching for indicator hazard:
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p.000005: risk of tumorigenicity has in particular been highlighted concerning the use of human ES cells as these stem cells
p.000005: develop teratomas.
p.000005:
p.000005: – Ensuring the function and viability of the stem cells or their derivatives during the recipient’s life.
p.000005:
p.000005:
p.000005:
p.000005: 4 A. L. Lennard and G H Jackson, “Science, medicine and the future: Stem cell transplantation”, BMJ, 2000,
p.000005: 321: 433-437.
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006: – Overcoming the problem of immune rejection (which does not arise in the case where the patient’s own stem cells
p.000006: can be used).
p.000006:
p.000006: – For the generation of human cells lines to be used in drug development at pre- clinical stage and in
p.000006: toxicology. Normal human cell types generated from human stem cells can be genetically or
p.000006: pharmacologically manipulated and used for drug discovery. These cell lines may provide more clinically relevant
p.000006: biological systems than animal models for drug testing and are therefore expected to contribute to the development of
p.000006: safer and more effective drugs for human diseases and ultimately to reduce the use of animals. They also offer the
p.000006: possibility to develop better in vitro models to enhance the hazard identification of chemicals. It is
p.000006: possible that these applications will turn out to be the major medical impact of human ES cell research at least in
p.000006: a short-term perspective, as the problems of immune rejection, viability and tumorigenicity do not apply
p.000006: here.
p.000006:
p.000006: – For the understanding of human development. Human ES cells should offer insights into
p.000006: developmental events that cannot be studied directly in the intact human embryo but that have important
p.000006: consequences in clinical areas, including birth defects, infertility, and pregnancy loss.
p.000006:
p.000006: – For the understanding of the basic mechanisms of cell differentiation and proliferation. The
p.000006: understanding of the genes and molecules, such as growth factors and nutrients, that function during development of the
p.000006: embryo may be used to grow stem cells in the laboratory and direct their development into specialized cell types. Some
p.000006: of the most serious medical conditions, such as cancer, are due to abnormal cell division and
p.000006: differentiation. A better understanding of the genetic and molecular controls of these processes may yield information
p.000006: about how such diseases arise and suggest new strategies for therapies.
p.000006:
p.000006: The current advantages and limitations of human embryonic and somatic stem cells and the needs regarding the derivation
p.000006: of new human embryonic stem cell lines
p.000006:
...
p.000019: european_group_ethics/docs/avis15_EN.pdf
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: and used for drug discovery. They give scientists the ability to experimentally study - under carefully controlled
p.000020: conditions - the growth and development of many different human cell types that are important to
p.000020: diseases like cancer, diabetes, stroke, heart disease etc. These cell lines may provide more clinically
p.000020: relevant biological systems than animal models for drug testing and are therefore expected to contribute to the
p.000020: development of safer and more effective drugs for major human diseases. For example today, there exists no
p.000020: laboratory model for the human heart, and it is therefore very difficult (impossible) to know exactly what
p.000020: effect medicines have on the heart before performing human studies. The lack of availability of human cells, which
p.000020: express normal function, has so far been the main limiting factor for reducing animal testing in
p.000020: pharmaco-toxicology. It is possible that this application will turn out to be the major medical impact of human
p.000020: ES cell research at least in a short-term perspective. At present insufficient methods exist in some areas of in vitro
p.000020: toxicology predicting target organ toxicity. In other areas such as embryo-toxicity inter-species variation presents
p.000020: major obstacles and humanised systems may enhance the hazard identification of chemicals.
p.000020:
p.000020: – Use of stem cells in gene therapy: Stem cells could be used as vehicles i.e. bearers of genetic information
p.000020: for the therapeutic delivery of genes. A problem for research on gene therapy has been to find safe delivery
p.000020: systems and stem cells may provide a solution here. At present, experiments are being done with gene
p.000020: therapy to treat diseases of the blood system. Their aim is to introduce new healthy genes in the
p.000020: blood-forming stem cells, which can then develop into all types of blood cells and, moreover, are able to renew
p.000020: themselves and thereby provide a permanent cure.
p.000020:
p.000020: – For understanding of human development. Studies of human embryonic and foetal stem cells may yield a deeper
p.000020: understanding of evolutionary biology and the process leading from embryo to human being. Human ES cells
p.000020: should offer insights into developmental events that cannot be studied directly in the intact human embryo but that
p.000020: have important consequences in clinical areas, including birth defects, infertility, and pregnancy loss. Particularly
p.000020: in the early post implantation period, knowledge of normal human development is largely restricted to the
p.000020: description of a limited number of sectioned embryos and to analogies drawn from the
...
General/Other / Relationship to Authority
Searching for indicator authority:
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p.000008: Programme, the EGE concluded that «//… there is no argument for excluding funding of this kind of research from the
p.000008: Framework Programme of research of the European Union if it complies with ethical and legal requirements as
p.000008: defined in this programme”.
p.000008:
p.000008: Secondly the EGE stated, that:
p.000008:
p.000008: “Stem cell research based on alternative sources (spare embryos, foetal tissues and adult stem cells)
p.000008: requires a specific Community research budget. In particular, EU funding should be devoted to testing the validity of
p.000008: recent discoveries about the potential of differentiation of adult stem cells. The EU should insist that the results of
p.000008: such research be widely disseminated and not hidden for reasons of commercial interest.”
p.000008:
p.000008:
p.000008: 10 Annex E - Opinion No. 15 of the European Group on Ethics regarding the “Ethical aspects of human stem
p.000008: cell research and use”. http://europa.eu.int/comm/european_group_ethics/index_en.htm.
p.000008:
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: The EGE identified the following principal requirements regarding human embryonic stem cell research and the
p.000009: procurement of embryonic stem cells from supernumerary embryos:
p.000009: – Free and informed consent from the donating couple or woman.
p.000009:
p.000009: – Approval of the research by an authority.
p.000009:
p.000009: – No financial gain for donors.
p.000009:
p.000009: – Anonymity of the donors and protection of the confidentiality of personal information of the donors.
p.000009:
p.000009: – Transparency regarding research results.
p.000009:
p.000009: Concerning clinical research the EGE stressed the importance of:
p.000009:
p.000009: – Free and informed consent of the patient.
p.000009:
p.000009: – Risk-benefit assessment.
p.000009:
p.000009: – Protection of the health of persons involved in clinical trials.
p.000009:
p.000009: Regulation of human embryonic stem cell research in EU Member States11
p.000009: EU Member States have taken different positions regarding the regulation of human embryonic stem
p.000009: cell research and new laws or regulations are being drafted or debated. Taking into account the situation,
p.000009: as of March 2003, the following distinctions can be made:
p.000009:
p.000009: – Allowing for the procurement of human embryonic stem cells from supernumerary
p.000009: embryos by law under certain conditions: Finland, Greece, the Netherlands, Sweden and the United Kingdom.
p.000009:
p.000009: – Prohibiting the procurement of human ES cells from supernumerary embryos but allowing by law for
p.000009: the import and use of human embryonic stem cell lines under certain conditions: Germany. The import and use of human ES
p.000009: cell lines is not explicitly prohibited in e.g. Austria, Denmark and France and authorisation is still being
p.000009: discussed.
...
p.000030:
p.000030: Annex C provides examples of the currently available human ES cell lines.
p.000030: 2.6. Developments regarding establishment of human stem cell banks and registries. Human stem cell banks
p.000030: The need for public stem cell banks including human embryonic stem cell has been recognised at national
p.000030: level both in Sweden and UK.
p.000030:
p.000030: The British Medical Research Council (MRC) in autumn 2002, in collaboration with the Biotechnology and
p.000030: Biological Science Research Council (BBSRC) and with the full backing of the UK Government, took the initiative
p.000030: to establish the first large-scale publicly funded Stem Cell Bank worldwide. The National Institute for
p.000030: Biological Standards and Control (NIBSC) is hosting the UK Stem Cell Bank46, which officially started 1 January
p.000030: 2003.
p.000030: The general aim of the UK Stem Cell Bank will be to create an independent and competent facility to store, test and
p.000030: release seed stocks of existing and new stem cell lines derived from adult, foetal and embryonic human tissues.
p.000030: There will be two primary components in this work:
p.000030:
p.000030: 1) To provide stocks of well-characterised stem cell lines for use in research in the UK and abroad. These
p.000030: will be established under well regulated, but non-GMP, conditions and made available in order to promote fundamental
p.000030: research.
p.000030:
p.000030: 2) To provide stocks of stem cell lines prepared under GMP conditions, that could be used directly for
p.000030: production of human therapeutic materials.
p.000030:
p.000030: In February 2002, the Human Fertilisation and Embryology Authority (HFEA) in the UK granted the first
p.000030: two licences for embryo research under the 2001 Regulation to Imperial College in London and the
p.000030: University of Edinburgh. The protocols approved will create human embryonic stem cell lines from embryos
p.000030: originally created for IVF treatment but subsequently donated for research. At the time of writing this report no
p.000030: human ES cell lines had as yett been derived. When generated the cell lines will be placed in the UK
p.000030: stem cell bank. This is a requirement of HFEA research licence.
p.000030:
p.000030: The Karolinska Institute in Stockholm is also planning to establish a Stem Cell Bank, based on the various stem
p.000030: cell lines established at the Institute (about 9 human ES cell lines are expected to be available within
p.000030: the next 12 months). These lines will be available for other scientists worldwide47.
p.000030: Human ES cell research is also ongoing at the Sahlgrenska Academy, Gothenburg University, Sweden in collaboration with
p.000030: Cell Therapeutics Scandinavia, AB. The two centres are active
p.000030:
p.000030:
p.000030:
p.000030: 46 http://www.nibsc.ac.uk/divisions/cbi/stemcell.html
p.000030: 47 Communication from Professor Carlstedt-Duke, Dean of Research, Karolinska Institute, Sweden
p.000030:
p.000030:
p.000030:
p.000031: 31
p.000031:
p.000031: in generating human ES cell lines as well as in developing differentiated normal human cells.
p.000031: 21 human ES cell lines have so far been established. Four of these have been fully characterized and two
p.000031: of these four fulfil all the criteria for self-renewal and pluripotency of human ES cells. The remaining 17 cell lines
...
p.000034:
p.000034:
p.000034:
p.000034: 55 Spare embryos: another word for supernumerary embryos.
p.000034:
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035: The EGE stressed also the importance of the following requirements regarding human embryonic stem cell
p.000035: research and the procurement of embryonic stem cells from supernumerary embryos:
p.000035:
p.000035: – Free and informed consent from the donating couple or woman.
p.000035: The EGE stated: “Free and informed consent is required not only from the donor but also from the
p.000035: recipient as stated in the Group's opinion on Human Tissue Banking (21/07/1998). In each case, it is necessary to
p.000035: inform the donor (the woman or the couple) of the possible use of the embryonal cells for the specific purpose
p.000035: in question before requesting consent.” The requirements may differ on the type of information that should
p.000035: be provided and on the definition of which persons should give their consent (the couple or the woman). The Charter
p.000035: of Fundamental Rights of the European Union recognised in article 3(2) that “In the fields of medicine and biology the
p.000035: following must be respected in particular – the free and informed consent of the person concerned, according to the
p.000035: procedures laid down by law…”.
p.000035:
p.000035: – Approval of the research by an authority.
p.000035: The EGE recommended that human ES cell research should be placed, “in the countries where it is
p.000035: permitted, under strict public control by a centralised authority - following, for instance, the pattern of
p.000035: the UK licensing body (the Human Fertilisation and Embryology Authority)” and provided that “ authorisations
p.000035: given to such research are highly selective and based on a case by case approach, while ensuring maximum transparency.
p.000035: This must apply whether the research in question is carried out by either the public or the private sector”.
p.000035:
p.000035: – No financial gain for donation
p.000035: The EGE recommended that “The potential for coercive pressure should not be underestimated when
p.000035: there are financial incentives. Embryos as well as cadaveric foetal tissue must not be bought or sold, and not
p.000035: even offered for sale. Measures should be taken to prevent such commercialisation”.
p.000035: The Charter of Fundamental Rights of the European Union recognised in article 3(2) that “In the fields of medicine
p.000035: and biology the following must be respected in particular… the prohibition on making the human body and its
p.000035: parts as such a source of financial gain”.
p.000035: Article 21 of the Council of Europe Convention on Human Rights and Biomedicine specifically prohibits
p.000035: financial gain from all or part of the human body.
p.000035:
p.000035: – Anonymity of the donors and protection of the confidentiality of personal information of the
p.000035: donors as it applies for donation of human biological material.
p.000035: The EGE recommended that “Steps must be taken to protect and preserve the identity of both the donor and the recipient
p.000035: in stem cell research and use”. As stated in the EGE's Opinion on Human Tissue Banking (21/07/1998): “in the
...
p.000036: stem cell research are still in an early stage of development and therefore the fundamental ethical principles
p.000036: at stake and the requirements for for human embryonic stem cell research are still relevant.
p.000036:
p.000036: Chapter 3.2 provides further information regarding the requirements applied in EU Member States allowing for the import
p.000036: and use of human embryonic stem cells and/or the procurement of human ES cells from supernumerary embryos.
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000037: 37
p.000037:
p.000037: 3.2. Regulations in EU Member States regarding human embryonic stem cell research56
p.000037: EU Member States have already taken very different positions regarding the regulation of human ES cell
p.000037: research and new legislation or regulations are being drafted or debated. Table 1 attempts to provide a comprehensive
p.000037: overview of the situation as of March 2003.
p.000037:
p.000037: The following distinctions can be made:
p.000037:
p.000037: 1. Allowing for the procurement of human embryonic stem cells from supernumerary embryos by law
p.000037: Finland
p.000037: The medical research Act of 1999 covers the preconditions and use of human embryos up to 14 days of embryonic
p.000037: development. The production of human embryonic stem cells from supernumerary embryos is allowed. The
p.000037: laboratories that do embryo research need a licence from the National Authority for Medicolegal Affairs. An
p.000037: ethics committee must approve research projects. The informed consent of both gamete donors is required.
p.000037:
p.000037: Greece
p.000037: The recent law 3089/2002 on medically assisted human reproduction allows for the procurement of
p.000037: human embryonic stem cells from supernumerary embryos. The Act requires the informed consent of both gamete donors and
p.000037: no financial inducement.
p.000037:
p.000037: The Netherlands
p.000037: The Embryo Act of September 2002 allows the use of supernumerary embryos for research including isolation of
p.000037: embryonic stem cells from such embryos. This research requires the favourable opinion of the Central
p.000037: committee for research involving human subjects. The informed consent of the donor is required. The
p.000037: research must have the aim to lead to new insights in medical science.
p.000037:
p.000037: Sweden
p.000037: The Act of 1991 on “Measures for Purposes of Research and Treatment involving Fertilised Human Ova” and the Health
p.000037: and Medical Care Act (18-982:763) apply. According to the Act(1991:115), in vitro embryo research is
p.000037: legally permitted until day 14 after conception, after which the embryo must be destroyed.. After some discussion
p.000037: there is consensus that this legislation permits human embryonic stem cell research. A revision of the law
p.000037: is under discussion (see chapter 3.3)
p.000037:
p.000037: United Kingdom
p.000037: The research purposes permitted by the Human Fertilisation and Embryology Act of 1990 were extended by
p.000037: the “Human Fertilisation and Embryology (Research Purposes ) Regulation” of 2001 to permit the use
p.000037: of embryos in research to increase knowledge about serious diseases and their treatment. The Human
p.000037: Fertilisation and Embryology Authority is
p.000037:
p.000037:
p.000037: 56 European Commission, DG Research, Directorate E: Survey on opinions from National Ethics
p.000037: Committees or similar bodies, public debate and national legislation in relation to human embryonic stem
p.000037: cell research and use (last update March 2003); “Survey on the National Regulations in the European Union
p.000037: regarding Research on Human Embryos” - B. Gratton - published by the Secretariat of the EGE - European Commission -
p.000037: July 2002.
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: responsible for licensing research involving the creation and use of human embryos. The HFEA requires the
p.000038: informed consent of the donors and free donation. The first two licences for stem cell research under the 2001
p.000038: Regulations were issued by HFEA in February 2002.
p.000038:
p.000038: 2. Prohibition of the procurement of embryonic stem cells from human embryos but allowing by law
p.000038: the import and use of human embryonic stem cell lines under certain conditions.
p.000038: Germany
p.000038: The Embryo protection Act of 1990 forbids any research which is not for the benefit of the concerned embryo.
p.000038: A new Act ensuring protection of embryos in connection with the importation and utilisation of human embryonic stem
p.000038: cells – Stem Cell Act – (Stammzellgesetz – StZG) was adopted on 28 June 2002.
...
p.000079:
p.000079:
p.000079:
p.000080: 80
p.000080:
p.000080: embryo research and the provision of guarantees against risks of arbitrary experimentation and
p.000080: instrumentalisation of human embryos.
p.000080:
p.000080: 2.5. Ethical acceptability of the field of the research concerned.
p.000080: The Group notes that in some countries embryo research is forbidden. But when this research is allowed, with the
p.000080: purpose of improving treatment for infertility, it is hard to see any specific argument which would prohibit extending
p.000080: the scope of such research in order to develop new treatments to cure severe diseases or injuries. As in the case of
p.000080: research on infertility, stem cell research aims to alleviate severe human suffering. In any case, the embryos that
p.000080: have been used for research are required to be destroyed. Consequently, there is no argument for excluding funding of
p.000080: this kind of research from the Framework Programme of research of the European Union if it complies with ethical and
p.000080: legal requirements as defined in this programme.
p.000080:
p.000080: 2.6. Public control of ES cell research.
p.000080:
p.000080: The Group deems it essential to underline the sensitivity attached to the use of embryonic stem cells, since this use
p.000080: may change our vision of the respect due to the human embryo.
p.000080:
p.000080: According to the Group, it is crucial to place ES cell research, in the countries where it is permitted, under strict
p.000080: public control by a centralised authority - following, for instance, the pattern of the UK licensing body (the Human
p.000080: Fertilisation and Embryology Authority) - and to provide that authorisations given to such research are highly
p.000080: selective and based on a case by case approach, while ensuring maximum transparency. This must apply whether the
p.000080: research in question is carried out by either the public or the private sector.
p.000080:
p.000080:
p.000080: 2.7. Alternative methods to the creation of embryos for the purpose of stem cell research.
p.000080: The Group considers that the creation of embryos for the sole purpose of research raises serious
p.000080: concerns since it represents a further step in the instrumentalisation of human life.
p.000080:
p.000080: • The Group deems the creation of embryos with gametes donated for the purpose of stem cell
p.000080: procurement ethically unacceptable, when spare embryos represent a ready alternative source.
p.000080:
p.000080: • The Group takes into account interest in performing somatic cell nuclear transfer (SCNT) with the
p.000080: objective of studying the conditions necessary for "reprogramming" adult human cells. It is also aware that, in view
p.000080: of future cell therapy, the creation of embryos by this technique may be the most effective way to
p.000080: derive pluripotent stem cells genetically identical to the patient and consequently to obtain perfectly
p.000080: histocompatible tissues, with the aim of avoiding rejection after transplantation. But, these remote therapeutic
p.000080: perspectives must be balanced against considerations related to the risks of trivialising the use of embryos
p.000080: and exerting pressure on women, as sources of oocytes, and increasing the possibility of their instrumentalisation.
p.000080: Given current high levels of inefficiency in SCNT, the provision of cell lines would require large numbers of oocytes.
...
Orphaned Trigger Words
p.000021: factors is also being explored.
p.000021:
p.000021: 1.5. Scientific and technical obstacles to overcome before realising the potential clinical uses of
p.000021: novel human stem cell based therapy
p.000021: The novel stem cell based therapies as described in chapter 1.4. are still at a an early stage of development. In
p.000021: particular regarding the transplantation of differentiated cells derived from stem cells several scientific
p.000021: and technical hurdles need to be resolved before clinical application of these therapies, including 27:
p.000021:
p.000021:
p.000021:
p.000021: 26 “La recherche sur les cellules souches embryonnaires”, Commission national d’éthique suisse pour la
p.000021: médicine humaine, Prise de position n° 3/2002; Steindler, D.A. and Pincus D.W., “Stem cells and
p.000021: neuropoiesis in the adult brain”, Lancet, 2002, 359(9311):1047-1054.
p.000021: 27 US NIH, “Stem Cells: A primer”, September 2002 http://www.nih.gov./news/stemcell/primer.htm;
p.000021: House of Lords Select Committee – Report on Stem cell research, February 2002
p.000021:
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000022: – Differentiation, dedifferentiation and transdifferentiation: There is still a strong need to gain
p.000022: a better understanding of the underlying mechanisms regulating stem cell growth, migration, fate and
p.000022: differentiation in order to ensure controlled and stable differentiation. If somatic stem cells are
p.000022: dedifferentiated to enhance their normal potential, scientists must be able to control this process.
p.000022:
p.000022: – Inappropriate tissue development: One possible risk of clinical use of stem cell transplantation
p.000022: is that the cells will not simply grow into replacement or supportive tissue, but inappropriate differentiated tissue
p.000022: will develop.
p.000022:
p.000022: – Tumorigenicity: The risk of tumour development does present an important risk, in particular if human ES
p.000022: cells are transplanted directly to the patient, as human ES cells do form teratoma.
p.000022:
p.000022: – Isolation and purification: The isolation of many adult stem cells is still difficult.
p.000022: Purification methods need to be developed in order to avoid the transplant of inappropriate cells.
p.000022:
p.000022: – Immune rejection: The human body possesses an immune system, which recognises cells that are not its own and
p.000022: rejects them for example following transplantation of organs, tissues or cells derived from other individuals
p.000022: (heterologous transplantation). Immune rejection is one of the major causes of transplant failure, and is one of the
p.000022: problems which will need to be overcome for stem cell-based therapy to be effective except in the case where the
p.000022: patient’s own stem cells can be used. Different approaches are currently being envisaged to overcome
p.000022: immune rejection e.g. immuno-suppressive drugs, generation of immunotolerance, use of “matching tissues or by
p.000022: somatic cell nuclear transfer (i.e. therapeutic cloning) as described in annex B.
p.000022:
p.000022: – Function and viability: The stem cells or their derivatives must function appropriately
p.000022: for the duration of the recipient’s life and survive in the recipient after transplantation. Methods to improve and
p.000022: properly assess the viability and functioning of the differentiated cells need to be worked out.
p.000022:
p.000022: – Culture conditions: Good manufacturing practice (GMP) needs to be defined including the
p.000022: establishment of germ-free culture conditions for the derivation and differentiation of specialised cell types.
p.000022:
...
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| HIV | HIV/AIDS |
| access | Access to Social Goods |
| authority | Relationship to Authority |
| autonomy | Impaired Autonomy |
| child | Child |
| children | Child |
| dependence | Drug Dependence |
| dependent | Dependent |
| drug | Drug Usage |
| education | education |
| embryo | embryo |
| family | Motherhood/Family |
| foetus | Fetus/Neonate |
| foetuses | Fetus/Neonate |
| hazard | Natural Hazards |
| indigenous | Indigenous |
| liberty | Incarcerated |
| linguistic | Linguistic Proficiency |
| manipulated | Manipulable |
| opinion | philosophical differences/differences of opinion |
| parents | parents |
| political | political affiliation |
| poor | Economic/Poverty |
| property | Property Ownership |
| religious | Religion |
| restricted | Incarcerated |
| single | Marital Status |
| stem cells | stem cells |
| terminally | Terminally Ill |
| trauma | Victim of Abuse |
| union | Trade Union Membership |
| women | Women |
Indicator Peers (Indicators in Same Vulnerability)
| Indicator | Peers |
|---|
| child | ['children'] |
| children | ['child'] |
| foetus | ['foetuses'] |
| foetuses | ['foetus'] |
| liberty | ['restricted'] |
| restricted | ['liberty'] |
Trigger Words
capacity
consent
cultural
developing
ethics
harm
justice
protect
protection
risk
sensitive
welfare
Applicable Type / Vulnerability / Indicator Overlay for this Input