National Consultative Ethics Committee for Health and Life Sciences




Opinion n° 93

Commercialisation of human stem cells and other cell lines





Members of the Working Group:

Mmes :                     Anne CAMBON-THOMSEN (until 2005) Monique CANTO-SPERBER (rapporteur) Hélène GAUMONT-PRAT
Chantal LEBATARD Martine LOIZEAU Jacqueline MANDELBAUM Carole MOQUIN-PATTEY
Dominique STOPPA-LYONNET

MM. :                       Jean-Claude AMEISEN Sadek BELOUCIF Pierre Le COZ
Olivier de DINECHIN Alain FISCHER
Jean-Louis LORRAIN (until 2005) Jacques MONTAGUT (until 2005) Philippe ROUVILLOIS
Maxime SELIGMANN Alain-Gérard SLAMA

Were consulted:         Jacky BERNARD
Marina CAVAZZANA-CALVO Hervé CHNEIWEISS
Nicole LE DOUARIN Michel PUCEAT














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Professor Degos referred to the National Consultative Ethics Committee on problems arising from the commercialisation 
of therapeutic cells and, more generally, the products of cell  therapy or  of  cellular  and  tissular  
bioengineering.   To  respond  fully  to  the  referral  the Committee decided also to consider matters arising out of 
the possibility of commercialising human  stem  cells,  obtained,  processed  or  even  modified  by  recent  
biological  technology. This Opinion deals with the ethical difficulties which arise or could arise out of the possible 
commercialisation of human stem cells, both non-embryonic and embryonic, and of other cell lines1.   It also broaches a 
number of issues which are directly connected to such difficulties: the commercialisation of products of the human 
body, the relationship between ethics and the market and the various forms in which financial value becomes pertinent, 
from the time when a  stem  cell  is  harvested  until  it is  put  to therapeutic  use,  for  the  benefit  of  an  
identified  or indeterminate patient.
The   following   reflections   and   recommendations   bear   on   a   subject   for   which developments could be 
both rapid and unexpected so that it is difficult to lay down hard and fast rules once and for all.
Research   on   stem   cells,   both   embryonic   and   non-embryonic,   has   developed considerably in the last 
decade.  For many diseases, regenerative medicine based on the use of stem  cells  is  a  reasonable  therapeutic  
prospect.    Patients,  physicians  and  scientists  are considering any advances in this field with the closest 
attention.   Numerous research centres and pharmaceutical companies have already invested considerable financial 
resources in the sector.  Potential investors generally wish to be certain that inventions will benefit from legal 
protection in the form of a patent and that they will be able commercialise them.  This entry of  trade  in  the  field 
 of  research  and  medicine  bearing  on  an  entity,  the  cell,  which  is indisputably an element of the human 
body, raises ethical problems regarding the nature of the elements or products which would be the subject of possible 
commercial transactions: up to what stage is a stem cell an element of the human body in the strict sense of the 
meaning? Do  the  processes  it  must  undergo  to  preserve  or  put  it  to  use  change  its  status  so  that  it 
becomes a therapeutic product?
Elements  or  products  of  the  human  body   are  generally  considered  in  a  number  of countries as being 
protected from any form of commercialisation.  The possible patentability of genes has already raised considerable 
protest.  A fortiori, commercialisation of cells is even more  controversial.    However,  stem  cells,  both  
embryonic  and  non-embryonic,  generally undergo many transformations which condition the use to which they can be put 
in the future. It should be possible to compensate or even reward the work of transformation.   Inevitably, financial 
issues therefore arise as regards any manipulation of stem cells.  A first set of ethical problems  therefore  involves 
 the  nature  and  the  limits  of  acceptable  commercialisation  of human cells.  This examination forms the main 
body of this Opinion.
Another set of ethical problems is linked to consent.  The cell that will be marketed is the cell of a person.   
Transformation and subsequently the use of that cell therefore require that person's consent.  When the stem cell comes 
from an embryo, the question of the parents' consent is compounded by issues relating to the use for research and 
therapy of the product of a human embryo.
Finally  ethical  problems  are  connected  to  the  inevitable  conflict  of  interest  that  is raised  by biomedical 
 research:  the  best  interests  of  patients,  who  aspire  to  new  therapeutic advances  and  justifiably  want  
private  and  public  research  to  progress  quickly  and  be supported by substantial investments; the best interests 
of investors who are ready to facilitate

1  For  the  last  20  years  or  so,  stem  cells  (from  bone  marrow  and  blood)  have  been  used  as  autografts  
and allografts.  Such use has not given rise to any ethical debate since these cells are donated and do not enter into 
a commercial circuit.



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research  by  providing  money  on  the  condition  that  they  may  reap  the  benefits;  the protection of people who 
are the source of the biological material who must be able to consent to the use made of the elements of their body 
that they donated; the best interests of research for which the prohibition on the commercialisation of products of the 
human body has effects as  regards  scientific  development;  finally  the  best  interests  of  society  which  wishes 
 to preserve common standards and the principles on which they are based, underpinned by the respect owed to human 
beings.
These  ethical  issues  are  part  of  a  very specific  context.   A  French  national  context, regulated  by  law  
based  on  the  principle  of  the  non  commercialisation  of  elements  and products   of   the   human   body.     A 
  European   context   where   reticence   as   regards   the commercialisation of elements and products of the human 
body is far from being incorporated in proposed regulation.   Finally, an international context, where there is 
spirited competition between the various actors, both scientific and economic, in the field of stem cell research.
The products of cell therapy are one of the major prospects in contemporary scientific and  medical  development.   
This  situation  points  the  way  for  reflection  on  the  part  of  the National Consultative Ethics Committee on 
the general principles which should govern such regulations.  It is hoped that this work can provide guidelines to 
broach the increasingly grave problems which will doubtless emerge as regards the commercialisation of living material.
A  survey  of  the  present  situation  as  regards  the  modes  of  commercialisation  of products and  elements of 
the human body will precede an  analysis of  the various  facets of such  commercialisation.   The  future  prospects  
of  research  on  embryonic  or  non-embryonic stem cells will be presented with an examination of their possible uses 
and commercialisation. An ethical consideration of the issues raised will be followed by several recommendations.

1) The present situation
Today,  many  elements  and  products  are  extracted  from  the  living  human  body.   In some  cases,  the  donor  
receives  compensation.   It  may be  pertinent  to  indicate  the  types  of compensation awarded for these elements 
and products and the ethical and deontological rules which apply.  These indications could serve as a reference  for 
the further discussion of stem cells.
There are some products and elements which can be separated from the human body without any medical intervention nor 
with any resulting physical damage.  Such is the case of hair or milk which are marketed without the need for any 
special regulation.
This  is  not  the  case  however  for  products  of  the  human  body  which  cannot  be extracted without medical 
intervention.
The most frequent example is blood.   The law dated January 4,   1993 states that the donation of blood is voluntary, 
anonymous and free of charge2.  However, the Etablissement de  Transfusion  Sanguine  (ETS  -  Blood  Transfusion  
Centre)  sells  the  products  obtained without  profit  to  hospitals  as  perishable  products  (red  blood  cells,  
plasma,  platelets).   The Etablissement  Français  du  Fractionnement  (EFF  Blood  Fractionating  Centre)  sells  to  
the market stable blood products after pooling (albumin, factor VIII, fibrinogen, immunoglobulin, biological  products, 
 etc.).   These  blood  products,  once  they  have  been  processed,  become medicines and are marketed.  There is 
therefore a clear difference between blood cells which cannot  be  marketed  as   a  "profit-making"  transaction  and  
blood  products  obtained  by bioengineering so that they become products which can be marketed in the full meaning of 
the word.
The gift of bone marrow is voluntary and unpaid in the same way as the gift of cord blood.   Sperm  and  oocytes  are  
also  donated  free  of  charge,  but  sperm  straws  come  with  a

2 These principles apply for the donation of whole blood or apheresis donation (plasma, platelets, white blood cells).  
All such donations required prior consent.



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price3.  Embryos and fœtuses resulting from terminated pregnancies may also be donated for the purpose of scientific 
research, anonymously and free of charge, after consent has been secured.
For organs, such as kidneys, livers and lungs, they may be harvested from a live or cadaver donor.  With a live donor, 
the donation is voluntary and unpaid, but is obviously not anonymous since the donor is identified.  With a cadaver 
donor, organs (liver, heart, pancreas, intestine, cornea, kidney, lungs, bone, blood vessels) are harvested from 
brain-dead donors in compliance  with  the  1976  Caillavet  Law.    In  that  event,  the  donation  is  anonymous  
and unpaid.  Despite their scarcity, organs are therefore donated free of charge, be they harvested from live or dead 
donors.   They require complex processes which justifies reimbursement to the  institution  concerned  of  outlay  
(costs  connected  to  extraction,  transfer,  transport  and conservation of the graft, generally in the form of a 
lump sum payment).
We see emerging a fundamental principle.   The elements and products of the human body, detached through medical 
intervention, are freely and voluntarily donated.   This does not prevent some of them being sold for a price, once 
they are separated from the body, or even  acquiring the status of a medicine (blood products).  Issues as to whether 
an element of a human body can be equated to a product and whether elements and products can be treated differently  
therefore  have  a  direct  bearing  on  the  question  of  commercialisation  of  living material.

2) Definition issues: commercialisation
Since  "commercialisation" can  serve  to  designate  compensation  and  the  setting of  a transfer price as well as 
sale for profit, we must make clear what henceforth in this report we shall be designating under the term 
"commercialisation".

What is commercialisation?
Commercialisation is a process consisting in transforming a thing or a product into a marketable  object  and  
distributing it  within a  competitive  trading system.   This means  that commercialisation generally requires two 
conditions: 1) supply and demand, i.e. a market; 2) setting a price which produces a market balance4.
It does not seem to be essential for a profit to be made or a profit margin to exist for there  to  be  an  act  of  
trade5,  but  profit  is  still  the  general  rule,  all  the  more  so  when commercialisation is the follow-up of a 
complex manufacturing process, which is the case in the   field   of   biomedical   research   (testing   on   animals, 
  randomised   trials,   etc.).      The commercialisation of drugs materialises a sometimes risky long-term 
investment.

What would be the meaning of commercialisation of products of the human body?
The general principle according to which products and elements of the human body do not fall within the scope of 
commerce must be stated at the outset (according to article 16-1 of the  Code  Civil  "The  human  body,  its  elements 
 and  products  cannot  be  the  subject  of proprietary law").  This principle prohibits the transfer against payment 
of these elements and


3  Approximately  50  euros  per  sperm straw.  CECOS  (Centre  d'Étude  et  de  COnservation  du  Sperme  -  French 
sperm conservation centre) store the sperm straws and spare frozen embryos.
4  Barter  is just a  primitive  form of  commerce; it  does not  always  actually involve true  commercial  intent: cf
friendly swap systems between private citizens, biological sample exchanges between laboratories.
5 Certain transactions completed by non-profit making organisations (associations, foundations) can be liable for value 
 added  tax,  even  without  any  lucrative  intention,  for  the  simple  fact  that  they  are  in  competition  with 
operations of the same type performed by professionals in comparable conditions.   Furthermore, traders may in certain  
cases  be  selling  at  prices  which  are  close  to  cost  (bargain  sales),  even  though  loss-making  sales  are 
theoretically prohibited.



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products  by the  donor  so  as  to  prevent  donors  selling their  own  bodies  in  the  form  of organs, blood or 
gametes.
But  this  principle  of  non  commercialisation  is  not  incompatible  with  the  fact  that certain products (for 
instance, blood components) may, after being processed, be the object of commercialisation leading to profit-making.  
Nor is this same principle incompatible with the fact that a transfer price is attached to certain products6 and that 
their acquisition is paid for as reimbursement to cover the costs of preparation and processing.
It becomes apparent therefore that there is a need to distinguish between the various meanings of commercialisation 
depending on the one hand on whether the transaction aims or does  not  aim  at  making  a  profit,  or  on  the  other 
 hand  on  the  amount  of  processing  or conservation that is required to arrive at the biological product in 
question.
The presence of profit
When   there   is   no   intention   to   make   a   profit,   commercialisation   may   describe compensation, at cost 
price of the outlay on processing, preparation and transformation of the elements of living material.  Such 
compensation, which translates in this case into the setting of a price, seems legitimate if such outlay is 
considerable.  At the opposite end of the  scale,  profit  seeking  may  give  rise  to  commercialisation  if  price  
setting  is  simply dependent on the ratio between supply and demand, in other words, on the market 7.
The amount of work that has to be done on the biological product before use.
In certain cases, the elements of living material can be used practically as they come or after simple processing 
(freezing): for example, whole blood, organs harvested and then grafted, sperm, oocytes8.  Since transformation is 
minimal, there is reason to believe that money would not be much of a consideration, even though costs are high 
(transfer of the organ by air, medical teams on standby, etc.).  On the contrary, there are other cases where products 
are used after  multiple operations: for example stem cell lines for which there has to be harvesting, processing, 
culturing, multiplication and finally genetic modification. Product processing is extensive so that it is probable that 
money would play a major role.

It would seem therefore that the more such manipulation generates "added value", the more expenditure is committed for 
its development in the experimental stage and the higher are the financial risks, the less biological products 
undergoing such manipulations can still be defined as  "elements of  the human body".   Also,  the more the  biological 
 products undergo transformation,  the  more  pressing  will  be  the  demand  to  not  just  recover  financially  the 
expenses incurred to develop them, but also to be able to draw a profit from the sale of these biological products so 
as to absorb the research expenditure and risks taken by investors.
In the following pages we intend to use the word "commercialisation" as meaning a profit-seeking  activity  and  not  
just  compensation  or  the  price  of  transfer.    In  so  far  as untransformed    products    of    the    human    
body    cannot    be    marketed,    the    issue    of commercialisation  will  mainly  arise  for  products  which  
are  already  to  a  great  degree  the object of transformation, which is obviously the case of stem cells and the 
products of cell therapy. Taking account of the value added by these processes and the purpose of covering


6 The transfer price is defined by the Code de la Santé: price of transfer of blood (art. 1221-9 Csp),  of sperm (art. 
L. 1244-5 Csp), of tissues and cells (art. L. 1243-1 Csp), and these rates do not at this point include the possibility 
of "profit".
7 As an illustration, a recent report in the French television broadcast "Envoyé Spécial" indicated that the price paid 
in the United States for the oocytes of a high quality donor (in biological, esthetical and intellectual terms) could 
be thousands of dollars.   There are advertisements in the Harvard University in-house publication for as much as 
$50,000.
8  Even  though  in  this  case,  medical  preparation  of  the  woman  donor  is  required  and  oocyte  freezing  is 
particularly difficult and still very imperfect.



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costs incurred and previous investment is sufficient reason to refer to commercialisation in such cases.
The link between commercialisation and patentability
For biotechnological innovation, commercialisation is generally connected to the legal protection  provided  by a  
patent  (it  is  possible  to commercialise  a  product  that  is  not  or  no longer  patented  but  is  protected  by 
 confidentiality;  conversely,  it  is  possible  to  patent  a product without being granted the benefit of an 
authorisation to market it).
The  intellectual  protection  afforded  by  a  patent  is  generally  designed  to  allow  for lucrative  exploitation 
 of  the  patent  in  the  form  of  sales  or  licensing  agreements.    In  this respect,  there  is  an  obvious  
link  between  the  debate  on  patentability  and  the  one  on  the commercialisation  of  cell  lines,  even  though 
 the  granting  of  a  patent  is  not  in  itself  an authorisation to use the invention as is stated regarding the 
patentability of biological material in preamble 14 of the Directive9.
An invention which is capable of industrial development may confer upon its author an exclusive right of exploitation 
for a given period of time (generally 20 years).  Granting a patent  bestows  institutional  recognition  on  the  
invention  while  it  gives  the  beneficiary  the possibility  of  recovering  the  expenses  incurred  to  develop  
the  invention  (amortisation).   It rewards the success of the inventor as it seeks to harmonise his own interests 
with those of the community.
The ethical justification of filing for a patent is threefold:
- A patent rewards the professional's worth and his innovating activity as evidenced by the development   of   a   new  
 instrument   for   investigation   or   of   a   novel   technical   process (manufacturing,   processing,   
conservation).      The   patent   represents   an   appreciation   of creativity.
- A patent is a method of protection of intellectual property by sheltering the expression of the  inventor's  talent  
from  invidious  appropriation  by  possible  competitors  who  happen  to possess rapid and effective means of 
commercial exploitation of his invention.
-  A  patent  provides  the  advantage  of  public  dissemination.    Holding  exclusive  rights  of exploitation of an 
invention is also an obligation as a counterpart on the part of the beneficiary of such rights to make his invention 
known and describe it in detail so that others may use it to  perfect  it  and  contribute  to  the  development  of  
other  inventions  based  on  it;  mandatory public dissemination makes patents the primary medium for the transmission 
of technological information.
In certain cases, however, the use of a patent can create the risk of monopolistic abuse. This unfortunate consequence 
of patents is due to the fact that exclusive rights of exploitation as  provided  by  the  patent  may,  when  its  
cost  is  prohibitive,  deter  attempts  on  the  part  of competing firms to improve the patented technique or to 
evidence other potential functions of the invention.  When the implementation of a technique is blocked by one or 
several patents, the financial investment which competitors would have to make to continue research on the patented  
invention,  if  they  decided  to  buy  licensing  rights  to  exploit  the  results  of  their research  could  be  a  
deterrent.     For  example,  if  a  patent  is  filed  for  a  targeted  gene, pharmaceutical companies will prefer to 
avoid research on that particular gene.  This is one of the  reasons  for  which  patents  are  sometimes  viewed  as  
hindering research  and  censured  as being contrary to public interest.  Ethical issues raised by the patentability of 
the genome ware raised in CCNE's Opinion n° 6410  and in a recent Opinion circulated by the German National Ethics 
Council11.

9 Preamble 14: "Whereas a patent for invention does not authorise the holder to implement that invention, but merely 
entitles him to prohibit third parties from exploiting it for industrial and commercial purposes".
10   Opinion 64 dated June 8, 2000   on "...a preliminary draft law incorporating transposition into the Code of 
intellectual property, of a European Parliament and Council Directive 98/44/CE, dated July 6, 1998, on the legal



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3) Stem cells: what is new about them? a) What is a stem cell?
A  stem  cell  is  an  undifferentiated  cell,  found  in  the  embryo,  the  fœtus  or  the  adult organism.  It is 
capable of self-replication (multiplication of identical cells) so as to provide a permanent reserve of cells of the 
same type and in certain conditions it can differentiate into more specialised cells.
There are several kinds of stem cells, classified according to the various cellular types they can give rise to:
-  Totipotent  stem  cells  are  capable  of  enabling  the  development  of  a  complete individual and of the annexes 
(placenta and membranes) essential for its intra-uterine survival.   This is the case of the fertilised egg (zygote) 
and of embryonic cells up to the 8-cell stage (blastomere).  Beyond that stage, cellular totipotence is lost.

- Pluripotent stem cells are capable of generating all the tissues in the body and are essentially  represented  by  
embryonic  stem  cells  (ES  cells)  present  in  the  inner  cell mass (ICM) of the embryo in the blastocyst stage 
(5th to 7th day after fertilisation). They are not able, however, to form the placenta and membranes which are 
necessary for viable gestation.

-  Multipotent  stem  cells  are  present  in  fœtal  and  adult  tissues  and  can  give  rise  to several types of 
cells, but they are already committed to a specific tissular programme. This  is  the  case  of  hematopoietic  stem  
cells  (HSC) in  adult  bone  marrow  and  fœtal cord blood which generate all the blood cells (red and white blood 
cells and platelets).

-  Unipotent  cells  can  only  form  a  single  type  of  differentiated  cell,  such  as  skin keratinocytes or liver 
hepatocytes.

b) Embryonic stem cells

They were described in 1981 for mice, by Evans and Kaufman, and the first human ES cell lines were derived in 1998 in 
the United States (J. Thomson).  Since then, some hundred lines  have  been  derived  and  cultured  in  the  United  
States,  Sweden,  Australia,  Israel, Singapore, India and the United Kingdom.  Some human lines have been in culture 
for several years.  They can also be frozen and stored in a cell bank.
Placing these cells in suspension in a culture medium and depriving them of the feeder cell layer, creates the 
conditions for them to cease to self-replicate and proliferate, instead of which they differentiate.




protection of biotechnological inventions". The retarding effect on research due to the granting of a patent to a 
physical or moral person is particularly marked in the field of preventive medicine when the development of a technique 
 for  the  manipulation  of  living  material  (a  biotechnology)  institutes  a  monopoly  on  a  method  for genome  
identification  (risk  of  appropriation  (through  patents)  of  the  tools  with  which  to  screen  for  diseases 
(which would only be accessible at prohibitive cost).
11   Opinion by the German National Ethics Council (2005) on the " The patenting of biotechnological inventions 
involving the use of biological material of human origin". Berlin, www.ethikrat.org. The "confiscation" through 
patenting of genes which are likely to play a role in the onset of serious diseases could well discourage initiatives 
by other researchers.  The Opinion draws attention to the danger of " ... monopolization of parts of the genome or of 
specific genes might also impede the development of medicinal products and cause problems with the treatment of 
patients." (4.1.1.3 Economic aspects, page 20 of the English version).



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Certain growth factors can direct ES cell differentiation in a repeatable manner.   In this way, certain cell types can 
be selected by specific molecular marking, isolated and made to produce pure cultures of, for instance, neural or 
cardiac cells.
The  source  of  human  ES  cells  is  invariably  the  Inner  Cell  Mass  (ICM)  of  the blastocyst which may have 
various origins. At the present time, the embryos surplus to IVF (in  vitro  fertilisation)  or  ICSI  
(intracytoplasmic  sperm  injection),  which  are  frozen  and  for which there is no longer any parental project, are 
the main origin.   In France, these embryos may henceforth, providing the parents give consent, be used in a research 
programme under the supervision of the Agence de Biomédecine (Biomedical Agency).

c)  Embryonic  stem  cells  derived  from  the  transfer  of  a  somatic  cell  nucleus ("therapeutic cloning"), at 
present prohibited by the Bioethics Law.

Transferring  the  nucleus  of  a  somatic  cell  into  a  denucleated  oocyte  allows  for  the reprogramming of the 
nucleus and the production of a totipotent cell which resumes the cell division  processes  which  are  characteristic  
of  the  embryo.    At  the  blastocyst  state,  it  is possible, using the  ICM,  to derive ES stem  cell  lines which 
are  genetically identical to the nucleus donor cell.
The feasibility of this technique seemed verified by the work of a Korean team headed by WS. Hwang (2005), but the 
results turned out to be fabricated.   However, the therapeutic efficacy of the approach has been reported in mice in 
two pathological models (see Annex, Rideout, 2002; Barberi, 2003).
The  main  advantage  of  the  ntES  (nuclear  transfer  ES)  cells  is  their  autologous character: these stem cells 
are particularly suitable for cellular therapy since there is no risk of rejection.  One of the disadvantages that is 
most often quoted is the ethical risk raised by the technical similarity between "therapeutic" cloning and 
"reproductive" cloning as well as the need for a large number of oocytes.

d) Fœtal stem cells

Fœtal tissues, derived from abortions (5 to 9 weeks) contain multipotent somatic stem cells (fœtal   neurons   have   
already  been   used   for   research   in   invalidating  neurodegenerative disorders such as Parkinson's or 
Huntington's diseases).
Cord  blood  also  contains  hematopoietic  stem  cells  (HSC)  in  sufficient  quantities  to restore a child's bone 
marrow.

e) Adult stem cells

The cells of three organs are endowed with the capacity for life-long constant renewal: blood, the epidermis and the 
intestine, which demonstrates the existence of active stem cells.  Those of the blood and the skin, easily accessible, 
are already used for therapy.
In recent years, there has been evidence to the effect that other organs or adult tissues (brain, blood  vessels,  
muscles,  skin,  digestive  epithelium,  dental  pulp,  retina,  liver,  pancreas,  etc.) contain stem cells.   They 
are capable of self renewal, of differentiation into the specialised cell  types  within  the  family  of  tissue  they 
 belong  to,  so  that  they  can  contribute  to  the replacement of cells that have died naturally or through injury. 
  They might also be able to differentiate into various cell lines (mesenchymal stem cells).

Be  they  derived  from  embryos,  fœtuses  or  adult  tissues,  stem  cells  are  likely  to  have  a significant  
therapeutic  future.    In  annex,  are  listed  stem  cell  characteristics,  specificities,



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origins,  advantages  and  drawbacks,  as  well  as  their  possible  uses.   The  modifications undergone by stem 
cells for therapeutic purposes are varied.   The nature and scope of these modifications can help to define criteria to 
guide ethical considerations and judge whether the cells are still products and elements of the human body.

4) Possible commercialisation: in search of a model for transactions
The possible uses to which stem cells could be put, for fundamental, therapeutic and pharmacological research, and the 
operational methods involved, now bring us to the need for an  examination  of  the  kind  of  business  model  that  
would  pertinently  apply.   Innovation  is required in this context.  By analogy, we have two extremely different 
models as regards the regulation of the distribution of biological components: the model given by the harvesting and 
graft  of  organs,  tissues  and  blood  on  the  one  hand,  and  the  model  which  regulates  the development of 
proteins for genetic engineering.  But neither of these models would seem to be suitable for wholesale application to 
stem cells and cell lines.
a) Models provided by organ grafts and blood-derived or genetic engineering products
-  The  business  model  regulating  the  harvesting  and  graft  of  organs  involves  three phases:
1 - harvesting: after unpaid donation with informed consent: the medical act of harvesting is independently 
remunerated;
2 - conserving, securing, processing or transforming: this is a sequence of operations that is liable to payment, as 
regards the actions, the products and the equipment required;
3 - distribution and use: this gives rise to the establishment of a cost after preparation of the organ or tissue 
received (graft, transfusion) and the payment of medical actions;

- The business model applied to stable blood-derived products; these products of the human body, obtained by voluntary 
donation, are nevertheless viewed in the same light as a medicine and are therefore part of the competitive market.

-  The  business  model  applied  for  genetic  engineering  is  the  one  used  for  mass production of a compound. 
Patents are at the core of the commercialisation system used for genetic engineering products.

How could these various models be used for stem cells and cell lines?
As is the case for grafts, in conformity with the non-patrimonial principle set out in Article 16-1 of the Code Civil, 
the donation of human stem cells must not give rise to donor remuneration12, no more than is the case for the donation 
of blood, for instance.  Donation is made  following consent.  The  medical  action  may be  remunerated.   However,  
the  stem  cell transformation  sequence  which  is  a  considerably  more  sophisticated  procedure  (not  to mention  
quality and  safety tests)  is  more  costly  by reason  of  the  expenditure  connected  to preparation and safety 
assurance.
Unlike  genetic  engineering  procedures,  a  cell,  once  modified,  cannot  be  reproduced artificially.   It seems 
possible that an increasing number of cell lines will be made available for experimental or therapeutic purposes.
Moreover,  for  stem  cells,  one  must  distinguish  from  the  outset  between  autologous uses (the beneficiary and 
the donor are one and the same person) and heterologous uses (the beneficiary is not the donor and there could be 
several, or even numerous, beneficiaries).
With autologous stem cells, treatment is customised, "at the patient's bedside".   The question then is to evaluate 
what is in essence a treatment and not a product that could be used

12  The  EGE's  Opinion  n°16  provides  for  donor  protection  in  point  2.6:  information  and  consent  seeking,  
non payment with the exception of fair compensation.



9

by others.  But the fact that treatment is only of use for a single person does not exclude per  se  any  notion  of  
commercialisation,  because  to  produce  such  treatment,  the  stem  cells were modified between the time when they 
were harvested and when they were used, all the more  so  if  a  specific  effect  is  sought.    (Incidentally,  if  
one  day  nuclear  transplantation becomes a practical reality, the same situation will apply since the cell produced 
will only be used by the patient who donated the cell nucleus).
Inversely,  heterologous  stem  cells  should  be  kept  in  "banks"  to  constitute  reference cell lines for 
research.  This "bankable" status normally leads to raising issues as regards their ownership or circulation, 
establishing a link with compounds in genetic engineering.
Such  an  analysis  leads  to  the  formulation  of  two  major  questions  regarding  the commercialisation of stem 
cells according to known business models: 1) Would the increase in value and financial protection system linked to 
patents, be applicable to cell lines?  2) How would stem cell banks be constituted?

b) The patentability of stem cells: should the development and transformation process be patented, or the product and 
its applications?
This Opinion is not proposing that all the results obtained by stem cell research should be taken as being non 
patentable.  Such a course — largely unrealistic — would be seriously harmful to research.
Furthermore,  to  prohibit  or  severely  restrict  the  scope  of  patent  protection  for inventions connected to 
stem cells would lead companies who have already invested in this field to withdraw their interest since it could not 
be profitable, which in the long term would have detrimental consequences for public health systems.
However, the issue of patents for living material has already been the subject of ample interest  and  discussion,  in  
particular  in  connection  with  the  human  genome.   It  takes  on  a slightly different aspect in connection with 
cell lines.  CCNE had reasserted at the time, as did the European Directive on the patentability of biotechnological 
inventions, that there was a difference between invention and discovery, since invention bears on the process of 
obtaining a result and discovery bears on the object itself, existing independently and "naturally"13. A similar 
distinction appears as regards cell lines since it is possible to file for either a product patent or a process patent.
1. A first option would be to consider the patentability of the product (the cells that are modified or produced) as 
legitimate, the product itself being viewed as inseparable from the process that makes it possible to produce it and 
make it accessible.   This option would have private  enterprise  or  public  institutions  be  given  the  task  —  as 
 is  the  case  today  for  most medicines — of  developing treatments for  which  they have  developed know-how that 
they wish to put to a profitable purpose.
Such an option does however have a practical drawback which is that development of treatment  is  left  to  the  
goodwill  of  industry  (which  is  of  course  the  case  today  for  most widespread  medications)  with  the  risk  
of  blocking  research  in  order  to  avoid  a  patented product even if there is every reason to believe that such 
research could lead to a number of highly beneficial discoveries for patients.  In fact, a fairly large number of 
genetic engineering companies are now emerging.

2.  A  second  option  would  be  to  prohibit  product  patents  (cell  lines)  and  to  only authorise patents for 
transformation processes
This  option  would guarantee  a  return  on  investment  in  the  culture  and  development techniques, but would 
allow the products that these techniques make possible to be entirely


13 Cf. Opinion n°27 dated 2.12.1991 on not using the human genome for commercial purposes.



10

free of access to the results of later research (be they focused on improving the patented processes or obtaining new 
cell lines).  In France and the rest of Europe, there is an exemption applying to  research  so  that it is possible, 
contrary to American  law, to  base  research  on a patented product.  However, as soon as exploitation of the result 
of that research arises, a new patent must be obtained, but its commercial exploitation remains in that case 
subordinated to the conclusion of a license with the holder of the first patent.
The two options mentioned above do not exclude the setting up of non-profit-making institutions capable of:  a) 
engaging in major  research  efforts on  the basis of other interests besides financial ones and, b) taking an active 
part in new technologies — as and when they are developed — if they would seem likely to be of benefit to patients.   
In that case, there would have to be an obligation on industrialists to grant a license for effective methods they may 
have developed (frequently in a foreign country).
This  latter  option  could  be  accompanied  by  the  prohibition  of  commercialising  non patented products.

c) Cell banks
Another  problem  arises  with  the  commercialisation  of  stem  cells  for  research  or therapeutic development, 
relating to the creation of cell reserves or "banks".  If one supposes that  numerous  cell  lines  can  be  developed, 
 it  remains  to  be  seen  how  to  ensure  their accessibility for various uses.
1. One possibility to make stem cells accessible would be to create cell banks.
One  could  for  example  consider  a  reserve  of  embryonic  stem  cells  covering  the various  HLA  specificities,  
which  could  be  used  on  a  "customised"  basis  since  it  would  be possible to choose cells which are 
"compatible" with those of the patient in need of treatment. This way of proceeding, which resembles in several ways 
the creation of an umbilical cord blood bank, could be regulated to organise remuneration of banking services while 
respecting the rule of not making a profit out of the elements of the human body.
2. A condition for the creation of cell banks is to constitute undifferentiated cell lines, using the collections kept 
in banks which could be used for therapeutic purposes for specific individuals, possibly in large numbers.  One 
possibility could  be the creation of allogenic cell banks, a possible source of very specifically characterised 
"medicine cells".   This is not the case of cells modified "on demand", for one-time use, and a differentiated 
technical process, the product of a true invention, would be required.
Examples:
. In vitro production of red blood cells of a certain blood group using stem cells,
.  Adoptive  immunotherapy  with  T  lymphocytes  expressing  frequently  encountered HLA molecules,
. In a central nervous system, using nerve cells derived from embryonic stem cells, a situation  in  which  
immunological  rejection  due  to  incompatibility  may  not  be  a  problem (which remains to be verified).
In cases of this type, would the inventor of the process be justified in claiming that the processed cell itself and 
not simply the method used could be commercialised?   This is the reason why the issue of choosing a business model 
arises with stem cells.   Could the same development model be used as when a compound is concerned?
As regards the patentability and the distribution of stem cells, various methods have already  been  adopted  and  
begun  to  be  implemented,  either  in  special  institutions  —  as  is shown by the example of WiCell given in the 
annex — or in international directives touching upon  commercial  transactions.    An  examination  of  these  
arrangements  will  provide  an opportunity    for    evaluating    on    a    more    specific    basis    the    
ethical    dimensions    of commercialisation.



11

5) The legal situation today
a.  Stipulations regarding the availability of embryonic stem cells.
In  France,  access  to  this  type  of  cell  is  regulated  by  Law  n°  2004-800  on  Bioethics (August  6,  2004,  
promulgation  of  implementing  decrees  in  February  2006),  regulating  the availability and distribution of 
embryos.   This latest law authorises research on embryos and human fœtal and embryonic stem cells, through a temporary 
five-year concession: "Research can only be conducted using embryos conceived in vitro in the process of medically 
assisted reproduction and which are no longer the subject of parental projects", providing the research "has been 
authorised by the Biomedicine Agency"14.
The  importation  of  embryonic  stem  cell  lines  for  research  purposes  is  also  authorised subject to the 
Biomedicine Agency's approval.

The situation differs from one country to another elsewhere. Some countries, for example Ireland, give unborn children 
the same rights to life as their mothers.   More generally, there are  no  specific  laws  governing  research  on  
stem  cells  but  regard  must  be  given  to  more general  law  governing  research  on  embryos  either  to  
authorise  it  subject  to  conditions (France, United Kingdom, Sweden) or to prohibit it (Germany, Austria). In 
certain countries, there is no legislation as regards embryo research (Belgium and the Netherlands), but there is 
ongoing research.
In most European countries, a legal framework is under consideration.
The Convention for the Protection of Human Rights and Biomedicine, signed in Oviedo in 1997, as yet not ratified in 
France, refers in article 18 to the fact that it is up to each Member State  to  forbid  or  authorise  embryo  
research  while stipulating conditions and  limitations of such research and prohibiting the creation of human embryos 
for research purposes.
In the United States, the NIH has set up a register of human embryonic stem cells which is kept  up  to  date  to  
record  the  existing  stem  cell  lines  complying  with  eligibility  criteria (embryonic stem cells obtained from 
supernumerary embryos for which there is no parental project, free and informed consent by the parental donors, absence 
of any financial gain for the donors).
These  cell  lines  are  available  for  research  only  and  reimbursement  for  the  expense  of preparation and 
distribution is requested.
On August 9, 2001, President Bush limited financing with federal funds to research using existing stem cell lines.  No 
research using stem cells from new embryos may be financed out of public resources.  Private research, however, is not 
concerned by this presidential decision.

b. Stipulations regarding commercialisation and patentability
Freedom granted for development research in this domain must be provided with the legal protection  given  to  
biotechnological  inventions  using  adult  or  embryonic  stem  cells.   The issue of the patentability of embryonic 
stem cells is therefore in the process of discussion all over Europe including France, even though patents on similar 
cells have already been granted in the United States.
The present situation and filings are summed up in Opinion n° 16 of the European Group on Ethics  in  Science  and  New 
 Technologies  (EGE)  dated  7  May  2002:  over  2000  claims  for patents have been filed worldwide for human and non 
human stem cells, of which a quarter concerned embryonic stem cells.  These claims concern:
- either processes: for isolation, enrichment, culturing, genetic modification, induction of    differentiation,    
induction    of    adult    stem    cells    for    retrodifferentiation    or


14 Articles 25 and 27



12

transdifferentiation and the transformation of somatic cells into stem cells,
-  or  products:  involving  stem  cells,  stem  cell  lines,  differentiated  stem  cells  and genetically modified 
stem cells.
Two different approaches seem to be adopted in existing legal documents.
In Europe, the European Directive 98/44 dated July 6, 1998 on the legal protection of biotechnological inventions 
proposes accepting the patentability of stem cells.  This directive has now been transposed in almost every member 
country of the European Union.  It was the subject  of  the  CCNE's  Opinion  n°  64  dated  June  8,  2000  as  
regards  the  limitations  on patentability  of  living  material.   The  Opinion  recalled  that  knowledge  of  a  
gene  sequence cannot be regarded as an invented product and is not, therefore, patentable.
An Opinion of the European Group on Ethics in Science and New Technologies (EGE) dated  May  7,  2002  gave  an  
ethical  interpretation  to  this  directive  as  regards  the  specific problem of stem cells.   Directive 98/44 and 
the  EGE Opinion broadly open the way to the possibility of patenting not just processes, but also products — the cells 
themselves — with some restrictions.
These two texts are considered below and in further detail in the annexes.
The European Directive 98/44 dated July 6, 1998, is exclusively aimed at harmonising patent law in Europe in the 
specific field of biotechnological inventions which it accepts.
Article 6 of the Directive, however, provides for a certain number of exclusions from patentability for reasons 
pertaining to "ordre public and morality".   It specifies in particular that  inventions  requiring  the  use  of  
embryos  for  industrial  or  commercial  purposes  are  not patentable,  but  in  para.  42  of  the  preamble  it  is 
 added  that  such  exclusion  does  not  affect inventions for therapeutic or diagnostic purposes.
Although  industrial  and  commercial  uses  of  human  embryos15  are  excluded  from patentability  by  virtue  of  
article  6  of  the  Directive,  this  prohibition  does  not  apply  to embryonic  stem  cells  which  can  not  
longer  be  considered  as  embryos.    Such  cells  can therefore be the subject of process or product patents16.
EGE Opinion 16 on the other hand states that article 6 of the Directive does not provide any definition of embryos 
concerned by the exclusion.  Therefore, certain embryos should be exempted:  non  viable  embryos17  (which  cannot  
lead  to  a  birth)  such  as  those  created  by parthogenesis.   However,  a  limitation  arising  out  of  Article  
6§2a  seems  to  be  established: "...are  not  patentable  "Processes  for  cloning  human  beings"  so  that,  notes  
Opinion  n°  16, should  be  excluded  from  patentability  processes  for  the  creation  of  human  embryos  by 
cloning with the purpose of obtaining stem cells.
However the issue of consent to ulterior exploitation by a patent is not to be found in texts on patent law and does 
not appear in the articles of the Directive:  only paragraph 26 of the preamble mentions such consent and recommends 
it.
EGE Opinion n° 16 therefore limits the scope of patentability of cells by making two distinctions  between  elements  
of  the  human  body  and  in  consequence  on  their  possible patentability, depending on whether or not the elements 
of the human body are detached and whether the cells are modified or isolated.
According to European recommendations, the patentability of adult and embryonic stem cells would be possible depending 
on the status conferred on cell lines: if they are products of


15 EGE's Opinion n°15 dated November 14, 2000 on "Ethical Aspects of Human Stem Cell Research and Use" recommended  
that  measures  be  taken  to  prevent  the  commercialisation  of  human  embryos  or  of  tissues  from dead fœtuses.
16 A decision to that effect, Paris Tribunal, January 21 2003, n° 0207626/6 confirmed on appeal by order dated May 9, 
2005, 3e ch B, n° 03PA00950.
17 Scientifically, their capacity to achieve birth is supposed to be very weak for a cloned embryo and close to zero 
for parthogenesis.



13

the human body which are simply isolated and left unmodified, they are not patentable; if they are products derived 
from the human body, that is cell lines derived from isolated stem cells, obtained with a technical process, in vitro, 
they cannot be viewed as natural stem cell lines, and are therefore patentable.
Product patents for stem cells should therefore be obtainable, according to the Directive, on condition that the cells 
are considered to have been "processed and modified".  Similarly, process  patents  for  the  products  of  cell  
therapy  should  also  be  granted  once  the  technical conditions are filled.
Nevertheless, it can be expected that the cell lines themselves would cease to comply with patentability criteria 
because of insufficient novelty, invention, or industrial application (this because following chromosomal modification, 
they run the risk of becoming dangerous and  unusable),  but  that  is  a  technical  problem,  solved  by  patent  
offices  on  the  basis  of regulations.

In   France,  transposition  of  the   Directive   was   delayed   because   of   a   degree  of reluctance.   The  
matter  was  referred  to  the  European  Court  of  Justice  in  the  course  of  an action for failure to fulfil 
obligations, which led to the ECJ's ruling against France  on July 1, 2004, (Aff. C-448/03).
The  provisions  of  the  Law  on  Bioethics  voted  on  August  6,  2004  as  a  result  of  the transposition  of  
Directive  98/44  were  a  compromise  solution  and  attempted  to  temper  the scope of patents.   CPI Article L. 
611-18 transposes differently Article 5 of the Directive by stipulating that "only an  invention constituting the 
technical application of a function of an element  of  the  human  body  can  be  patent-protected".   Nevertheless,  
significant  divergence between the formulation of the above text (and that of CPI Article L. 613-2-1) and Article 5 of 
 the  Directive  dated  July  6,  1998,  is  problematic.  However,  the  Commission  is  still evaluating  the  
consequences  of  one  or  the  other  courses  and  its  position  may  change  over time.

II. Ethical examination of issues raised by the possible commercialisation of stem cells.

The possible commercialisation of stem cells and other cell lines raises many ethical problems.   Before considering 
the subject and outlining general guidelines for solving these problems,  it  is important to  identify the  criteria 
which  may have  ethical  dimensions  in this respect.
Some criteria are ontological and bear on the status of elements and products of the human body.   Others concern the 
degree of modification undergone by the stem cells.   Yet more are connected to the cells' origins, to the nature of 
consent given for their removal, to the purposes for which they are to be used and to the kind of regulation to be 
provided.

Ontological criteria: what of the nature of the elements for commercialisation?
Depending  on  the  manner  in  which  the  biological  entities  concerned  are  defined18, commercialisation takes on 
different dimensions.
If the biological material is unprocessed, as is the case for stem cells, embryonic or otherwise,  commercialisation  
which  can  lead   to  a  profit-making  endeavour  may  raise significant  issues   in  view  of   legal  provisions  
and  moral  reprobation  surrounding  any commercial use of the human body.  This ethical difficulty is due to the 
"living"  nature, not simply organic or chemical, of the cells concerned and what defines "life" is the capacity to


18  The  expressions  "biological  entities"  or  "biological  material"  designate  the  products  and  elements  of  
the human body.



14

reproduce  an  identical  being.    It  is  also  because  this  life  is  human  life  that  ethical questions arise, 
which would not be the case with animal biology.

Inversely,  taking  the  case  of  a  chemical  compound,  ethical  and  legal  problems regarding their possible 
commercial use can be dealt with according to the order regulating material things and possessions.

Between the two, there is a difficult grey area, somewhere between what is biological and what is chemical, for which 
most of the ethical problems arise.   This grey area includes the  intermediary entities,  biological  products,  but  
modified  to  such  a  degree  that  they have partially lost their biological status.   These are, for example, cell 
lines, products of cellular therapy,  or  of  cellular  and  tissular  bioengineering,  etc.   For  such  entities,  
the  question  of whether  they  can  be  considered  as  biological  realities  or  pharmaceutical  specialities  or 
manufactured medicines remains open.   In other words, do the manipulations to which these biological realities have 
been subjected change their very nature?
This is comparable to products derived from human blood (immunoglobulins, factor 8) which have been modified to such an 
extent that they are viewed as products detached from the body.   Can this be the case for stem cells, be they of 
embryonic, fœtal or adult origin? When do such cellular elements become sufficiently detached and different from the 
human body for them to be the object of trade?  It seems quite impossible to define either boundaries or criteria.
Another  criterion  which  is  closely  connected  to  ontology  is  related  to  the  type  of relationship   existing 
  between   the   entity   in   question   and   a   human   individual   viewed holistically.  It is obvious that an 
organ is not related to an individual in the same way as a cell or a molecule.  It would seem reasonable to consider 
that the closer is the integration with the individual  as  a  whole,  the  more  the  possibility  of  
commercialisation  would  raise  ethical problems.

It is therefore legitimate to consider that one of the main concerns in the ethical debate on  the  commercialisation  
of  stem  cells  will  relate  to  the  ontological  status  of  the  entities involved (whether cells are unprocessed 
or modified, what proportion of the human body is in question) and their degree of integration within the person.


Criteria   connected   to   the   degree   of   human   intervention,   processing   and modification: product of the 
human body or artificial product?
Depending on whether the biological entities under consideration are unprocessed or have undergone  a  greater  or  
lesser  degree  of  modification,  ethical  problems  connected  to  their commercialisation are more or less acute.   
We find here a criterion relating to the degree of modification to which the biological material is subjected (this 
criterion overlaps to a certain degree with the ontological criteria referred to above, to the extent that the degree 
of human intervention can modify the status of the entities concerned).
It  is  important  to  define  pertinent  thresholds  so  as  to  appreciate  the  various  levels  of intervention 
required to obtain the desired cells.   Minimal intervention, for example, would consist  in  processing  a  cell  for  
the  purpose  of  conservation.   Maximal  intervention  would involve  obtaining  a  cell  by  nuclear  transfer.    
Most  of  the  interventions  on  stem  cells  lie between these two extremes.
In such a transformation process, the first step is harvesting, which supposes some form of direct relationship to the 
source which may, or may not be modified as a result.  The process of harvesting does not modify the biological 
entity's status.



15

Further  intervention  is  exemplified  by processing,  comparable  to  what  is  practised today  with  organs,  blood 
 and  sperm,  for  the  purposes  of  conservation  and  security.    The ontological status of the biological product 
is not thereby changed, so that it is not what could properly be called a modification.  In other words, if 
commercialisation of the source product is an issue, this will also be true for commercialisation of the processed 
product.  The fact of covering  costs  arising  out  of,  for  example,  the  procurement  of  safe  conditions  for  
optimal conservation of the product will not, in itself, raise ethical problems.
Other types of intervention are connected to what can be called manipulation, — on the condition that the word is 
understood to be free  of any negative interpretation.   This is the kind of intervention that is undertaken when a 
laboratory seeks to obtain a modified cell line. A certain number of technical operations which come at a cost may be 
necessary to process these entities.  They include:

- Amplification of the number of cells
-  Transformation  as  such  or  induced  modifications  to  internal  characteristics  for experimental or therapeutic 
purposes
- Combination with other entities of the same level
- The concept of differentiating stem cells into functional cells of a given tissular type.

In each of these cases, there are safety and traceability requirements which must be met.
One final operation consists in transferring these biological products, once they have been transformed, into a tissue 
or organism.  This is theoretically the ultimate phase which may be for experimental or therapeutic ends.  As such, 
this last phase is not properly speaking a phase of  transformation  of  the  product,  but  it  has  an  effect  on  
the  ethical  appreciation  of  its commercialisation.

Criteria  connected  to  the  type  of  relationship  between  the  product's  source  and  the product's user: should 
autologous and heterologous cases be treated differently?

Should the prospect of commercialisation and the ethical problems arising as a result be viewed in a different light 
depending on whether beneficiaries are or are not themselves the source of the sample?

If  donor  and  beneficiary of  a  stem  cell  are  one  and  the  same  person  (a  situation  which mainly arises in 
the case of adult stem cells), a price is only set because of the cost of isolating and securing the  characteristics 
of a cell.   This is autologous therapy.   Even in this case, a price may be set in so far as the cells undergo in 
vitro modification.  Commercialisation based on the development of an ingenious process would seem legitimate.  As an 
example, should at some point in the future nuclear transfer become an effective practice, at some point between 
harvesting and before use, a highly "modified" cell will make its appearance, but it will be used only by the patient 
who was the donor of the cell nucleus.   Even in this case, however, commercialisation is still limited to the process.
Conversely, when the beneficiary and the donor are not the same person and therapy is heterologous, standardisation of 
the process may raise the issue of commercial exploitation. Attribution to a fully identified beneficiary which limits 
standardisation is tantamount to the previous case of an autologous donor.   A bank holding multiple beneficiary cell 
lines could raise   the   possibility   of   commercial   exploitation   of   the   product.     The   autologous   or 
heterologous status will not change the fact that it is still the same product for a single person or a number of 
persons.  Simply, the bank status will liken these stem cells to blood banks and





16

not to medicines.  There is a clear indication here of the temptation to drop the banking- for-conservation status in 
favour of the financial banking status.

Criteria connected to the origin of the stem cells: does embryonic, fœtal or adult origin create a difference as 
regards commercialisation?

Does the origin of the cells have an impact on the definition of the ethical problems which arise out of a possible 
commercialisation?

When the origin of the cells is an adult, a fœtus or cord blood, ethical problems are solely confined to the issue of 
whether it is possible to create commercial value using products of the human body.

If the origin is the embryo, to the above problem is added the decisive issue of whether it is morally acceptable to 
use embryonic biological material for research or for therapy.

Certain people are opposed to any use of embryonic cells leading to the destruction of the embryo.   For  those  who  
consider  that  it  is  not  morally  acceptable  to  perform  research  on embryos or to use them for therapeutic 
purposes, a fortiori the possibility of establishing cell lines sourced from embryonic stem cells is reprehensible. On 
this point, the French laws on bioethics  took  a  stand.   They  gave  legal  status  to  research  on  the  embryo.   
Nevertheless, knowing if the stem cells are, or are not, embryonic has an impact on the way in which the ethical issue 
of commercialisation of stem cells and other cell lines can be formulated.

The criterion of consent: can consent give legitimacy to the commercialisation of what should otherwise be excluded  
from commercialisation?

Insofar as the unprocessed biological material is donated by a person and it can then be used nonselectively, the 
question of that person's consent to using what is issued from his or her own body and to the commercial exploitation 
that could be made of a product of his or her own body becomes crucial.

However, securing consent at the time when the biological material was initially donated does  not  suffice  to  settle 
 all  ethical  problems.   In  the  case  of  reiterated  use  of  biological material, particularly if this use is for 
new and different purposes to those initially planned, the question arises of whether consent is still valid19.  Would 
it not be preferable to consider that consent fades away with successive derivations and that uses made of biological 
material at the end of the journey no longer benefit from a shred of consent?   Should some form of reiteration  be  
made  of  the  request  for  consent  at  each  new  use,  or  is  it  right  to  agree  that distance  de  facto  
creates  a  legal  distinction?   Would  not  any kind  of  commercial  use  raise grave ethical difficulties if it 
could no longer be justified by approval and consent?

Clearly, the issue of consent given by the source person differs in the case of adult stem cells and embryonic stem 
cells, since it will be parents who are consenting to any use made of embryonic cells.   But even in a case of this 
nature, is it ethically acceptable to consider that consent remains valid for undefined uses without such consent being 
regularly updated?



19  CCNE  Opinion  n°  77  dated  March  20,  on  Ethical  issues  raised  by  collections  of  biological  material  
and associated information data : “biobanks”, “biolibraries”.



17

The  criterion  of  end  use:  does  a  therapeutic  purpose,  rather  than  a  scientific  or pharmacological purpose, 
have an impact on the prospect  of commercialisation?

The   question   of   commercialisation   of   stem   cells   cannot   be   raised   without   some consideration of 
the purposes for which the introduction of commercial value is intended.

One  purpose  is  therapeutic.    When  the  introduction  of  monetary  worth  relates  to  the reimbursement of the 
processing costs required to enable therapeutic uses, be that for a single person  or  for  several,  the  financial  
element  appears  as  the  condition  without  which  a beneficial therapeutic use of this kind could not take place.  
When, however, the introduction of financial value aims not only to enable therapy but also to make a profit (even 
though the development of such therapies would not be accessible without the presence of a commercial dimension) the 
question of whether the introduction of monetary value raises or does not raise an ethical problem becomes crucial.  
That is why the nature of the link which exists between the introduction of a monetary dimension and the possibility of 
therapeutic use is decisive.

Another  purpose  is  scientific.    It  is  difficult  to  argue  against  the  obvious  value  of developing  
knowledge  on  the  use  of  stem  cells.   It  is  conceivable  that  the  intervention  of financial   value   often  
 conditions   the   existence   of   scientific   achievements,   such   as   the development of research  and of 
knowledge.  If such is the case, the ethical issue raised by the introduction  of  a  monetary  dimension,  in  the  
form  of  investment,  in  the  use  of  biological material cannot but take into account the intrinsically useful 
nature of the achievement, that is the increase in the corpus of knowledge.

A third purpose is medical and pharmacological.   It appears when the introduction of a commercial  value  has  the  
effect  of  enabling  the  development  of  pharmaceuticals  and medicines which, instead of being aimed at specific 
patients, are of benefit to many people. In that case, the end purpose can be considered to be beneficial and 
commercialisation seen as a profit-seeking occupation becomes a necessary condition.

Other purposes can be considered as regards the use of stem cells, such as cosmetic ones which, unlike those previously 
mentioned, cannot be seen as obviously positive.  When even in  cases  where  the  purpose  considered  is  
indisputably positive  (therapy,  science,  medicine) the introduction of commercial value still raises ethical issues, 
this is a fortiori the case when the end purpose does not include positive characteristics.

Finally, it is important to state once again that any reproductive purpose must be excluded from  the  outset.    For  
legal  and  ethical  reasons  which  have  already  been  expressed  on numerous occasions, no manipulation of the 
embryo or of embryonic stem cells can aim at the birth of a human being.

Criteria  connected  to  interests  under  consideration:  interests  of  patients,  commercial interests, national 
interests

The  introduction  of  commercial  value  into  the  numerous  transformations  which  affect stem  cells  is  not  
limited  to  providing  profits  for  the  pharmaceutical  industry.   Many  other interests  are  involved.    
Depending  on  their  nature  and  their  proportional  importance  in relation  to  each  other,   the  ethical  
question  of  commercialisation  takes  on  a  different appearance.





18

The  first  interests  that  must  be  considered  are  those  of  patients.    If  therapy  is developed   through   
financial   investment   patients   benefit   directly   from   the   possible introduction of commercial value into 
the process.  When such interests are powerful, because patients  are  numerous  or  more  seriously  ill,  they  
bestow  upon  the  introduction  of  this commercial value — which is the condition of the development of a therapy — 
an even more positive  value.    In  such  a  case,  a  form  of  commercialisation  of  stem  cells  could  have 
beneficial consequences in the service of patients' interests.

Other interests concerned are commercial interests connected to profit-seeking, and these do not have any immediately 
obvious ethical value.   But to the extent that these commercial interests can condition investments without which no 
therapy would have been possible, their presence  may  lead  to  positive  consequences.    For  this  reason,  to  
decide  that  their  very presence must be the object of disapproval at the outset is a little hasty and 
counterproductive.

Other more general or abstract interests are linked to the development of research or to the ranking of national 
laboratories in the  global league-table for biotechnological research.   A decision to develop national or European 
research in this field can lead to the promotion of certain types of research, which requires financial investment.  
The assessment of interests of this nature cannot be detached from their financial aspect.

It  becomes  clear  therefore  that  taking  into  account  the  interests  involved  (interests  of patients, 
financial interests and interests of national research)   modifies the configuration in every case of the problem 
raised by the introduction of commercial values.  It cannot be said simply because economic interests enter into the 
equation that commercialisation is immoral. To  prohibit  any  kind  of  commercial  added  value  could  be  contrary  
to  the  interests  of  the public at large and those of patients.   The presence of such interests and the weight 
given to them have an impact on the ethical appreciation of stem cell commercialisation.

Criteria   connected   to   the   mode   of   commercialisation:   private   or   public   sector? competition or 
monopoly?
Accepting for the sake of argument that the intervention of commercial value is necessary for the creation of new 
therapies, does the fact that such intervention is based on private or public initiative create any moral difference?
On  could  consider  that  public  interests  necessarily  serve  the  public  at  large  whereas private  interests  
give  first  place  to  private  investors.   It  is  true  that  public  funds  are  State funds,  are  not  supposed  
to  serve  any  partisan  interests  and  are  intended  to  promote  the interests of the public.  Profits which 
accrue following the investment of public resources are of  benefit  to  the  community  as  a  whole.   On  the  
contrary,  private  funds  are  provided  by particular companies or individuals and the possible profits will go to 
specific companies and individuals.     Public  interests  are  not  directly  of  concern  in  these  profits,  except 
 very circuitously.   However, one must not be blinded by this dichotomy which would tend to put morality on the side 
of public investment and immorality on the side of private investment. To begin with, as regards development, public 
and private investors often work in partnership and tend to behave identically.  Furthermore, private investment can be 
made compatible with very strict specifications and be mindful of public interest.
When a public monopoly is the source of investment, the possibility still remains that the introduction  of  commercial 
 values,  while  obeying  profit-seeking  motives,  could  take  place according to mainly rigidly defined directives 
and without sufficient investment.  This kind of intervention tends to select a priori the interests it seeks to serve 
and in most cases might well be insufficiently reactive to market changes.   Or on the contrary, such investments might 
be



19

inclined to stick to promising research avenues even when they seem unlikely to lead to any immediate profit.
In a competitive environment, however, investment options will be defined according to the laws of the market, with no 
single project manager, so that research avenues which hold no promise of profit would be abandoned while substantial 
amounts could be invested in more promising research possibilities.  But some fundamental research, which is not very 
profitable in the short term, might be entirely neglected by a competitive research environment as might be also the 
case for rather unprofitable therapeutic research (rare diseases).
The reality of international competition is often mentioned to justify the abandonment of ethical demands.  However the 
increasing availability of products provided free of charge by public  or  private  non-profit  initiatives  is  
leading  the  way  in  permitting  the  coexistence  of several types of market.  States and companies who are making 
their products available to the public at large draw a moral benefit from that action which may also lead to economic 
benefit.

Criteria    connected    to    access    to    healthcare    and    to    distributive    justice:    can 
commercialisation respect  distributive justice?
A  set  of  fundamental  criteria  regarding  the  introduction  of  commercial  value  into  the exploitation of stem 
cells and other cell lines is connected to the access to healthcare that such commercialisation may lead to.
Depending  on  whether  the  introduction  of  financial  value  is  or  is  not  compatible  with extensive access to 
the therapies which are developed, its ethical appreciation will be more or less positive.  In the case of 
patentability, for instance, the prospect of being granted a patent will  be  the  condition  for the  investment  of  
substantial  amounts  of  money.   The  investment might  lead  to  the  development  of  medicines  which  will  be  
protected  by  a  patent  during several years before becoming accessible generally.  Depending on the length of the 
period of exclusive exploitation, depending on whether the disease affects rich countries where patients can afford to 
pay for therapy, or poor countries where patients are unable to pay, the ethical issue will appear in a different 
light.
More often than not, without investment there is no therapy and without therapy, there is no possibility of cure.   For 
this reason one cannot disqualify out of hand for ethical reasons any introduction of financial value.
From  another  angle,  if  a  certain  form  of  justice  is  not  respected  in  the  distribution  of healthcare, it 
becomes difficult to consider that the introduction of a financial value has any moral  effect  whatsoever.   The  way 
in  which  access  to  healthcare  and  an  equitable  form  of distribution  of  healthcare  are  ensured  play  a  
decisive  role  in  appreciating  whether  the introduction of financial value is morally acceptable.

In  conclusion,  this  Opinion  reiterates  that  it  is  necessary  to  distinguish  between  two meanings of 
commercialisation: the first of these covers possible compensation to the initial donor and the expenditure incurred 
for harvesting, processing, transforming and preserving to the highest safety and traceability standards; the second 
designates a profit-seeking activity entailing a cost and a benefit.   This second situation is what we shall be 
designating by the term  "commercialisation".    It  is  to  that  situation  that  the  ethical  guidance  which  
follows applies.
A reservation must be made at this point.   If the introduction of money depends only on the good will of investors and 
obeys no rule, there is reason to believe that commercialisation could  disregard  ethical  criteria.     Inversely,  
if  commercialisation  is  based  on  rules  and governance  plans  which  contribute  to  the  safeguard  of  public  
interests,  the  moral  issue relating to the introduction of financial value will appear in a very different light.  
That is the reason why the prospect of regulating the various forms of commercialisation can modify the



20

moral  appraisal  that  is  made  of  it,  to  the  extent  that  such  regulations  aim  to  respect specifications 
defining the demands of the community and are in phase with the public good, and to the extent particularly that they 
contribute to setting strict limits to regulate possible commercialisation.

III.      The main recommendations

1.
The source element, the stem cell, defined as an element or product of the human body
is,  as  a  general  principle,  neither  patentable  nor  open  to  commercialisation.    CCNE reaffirms in this 
Opinion the fundamental ethical principle according to which neither the human body nor any of its elements or products 
can be the "subject of patrimonial law", nor  give  rise  to  transactions  involving direct  or  indirect  
remuneration  of  the  donor,  nor revenues of a commercial nature accruing to any institution.  The dual foundation of 
this principle is: on the one hand that the body, its elements and products, are not "objects" (and cannot give rise to 
exploitation, for whatever purpose); on the other hand, any kind of  exploitation  would  be  all  the  more  
unacceptable  if  it  involved  for  a  human  being suffering, risk — possibly to life — and disregard for human 
dignity.   The principle that the human body, its elements and products are non patrimonial is absolute in the eyes of 
society  and  pertains  to  ordre  public.    Neither  the  person  concerned  nor  any  donor (individual or 
institution) can be regarded as the owners of a human body or of one of its elements  and  products.    In  so  far  as 
 stem  cells  derived  from  the  human  body  are elements of the human body, they cannot as such be the subject of 
commercialisation or give rise to remuneration.

2.
This  principle,  however,  does  not  prohibit  the  remuneration,  including  in  commercial form, of:
- on the one hand the actions, interventions and operations that accompany or follow the harvesting of cells, in 
particular the various transformations they may be subject to,

- on the other hand, the various uses that the transformed product could be put to after far-reaching modification.

3.
When ingenious human action has sufficiently modified a cell for it to become a product which has lost a cell's 
phenotypic and functional characteristics, the question of whether the product thus obtained can be commercialised 
should be submitted to an Agency such as the Biomedicine Agency.

4.
When transformation has radically modified the nature of the product, the general rule is that  the  modified  element  
can  be  commercialised  within  the  bounds  of  patentability of  the process and subject to the limits and 
conditions outlined above.   Were that element, having lost its status as element of the human body, to be reintroduced 
into a human body, it should be comparable to a "biomedicine".

5.
The  fact  that  cells  are  of  embryonic  origin  is  no  reason  for  exemption  from  the  above recommendations.  
However, there is a risk which must be kept in mind that the embryo could



21

be  treated  like  laboratory  material  or  a  medicine.   This  comment  does  not  imply  any disapproval of 
research on embryonic stem cells.  The possibility — at this point excluded by law — that stem cells could be obtained 
by nuclear transfer would raise an ethical issue as regards  their  commercialisation  in  the  same  terms  as  the  
commercialisation  of  embryonic stem  cells,  if  such  cells  were  to  be  considered  as  elements  of  the  human  
body  and  not  as simple laboratory artefacts.

6.
The  rules  governing the  granting of  process  patents  for  the  use  of  stem  cells  should  be fairly  
restrictive  so  as  to  avoid  hindering  new  research  developments  or  giving  exorbitant rights to inventors, 
disproportionate to the quality of the invention and detrimental to public health and access to healthcare.  Patents 
granted with too broad a scope could have that effect. The obligation by law to enter into licensing agreements would 
seem advisable.

7.
Informed consent by the donor remains essential.   Donors must be able to have their say regarding  the  use  made  of  
their  cells.    The  new  principles  of  ethical  trading  relying  on information given to the donor, to the 
participants in research and to the user could encourage market regulation and open the way to a method of exchange 
based on donation, which would make  it  clear  that  an  ethical  component  can  change the  nature  of  the  market  
and  lead  to  a modification of the behaviour of commercial competitors.

8.
Other conditions for the possible commercialisation of modified stem cells are connected to the accessibility of 
medicines derived from them. The cost of therapy must permit patients in need to have access. This concern, as well as 
other public health requirements, define the limitations put on the commercial use of cell-derived products.

9.
The  creation  of  cell  banks,  similar  to  existing  umbilical  cord  blood  banks,  should  be considered.  The 
patentability of processes which enable such cells to be obtained is sufficient to  guarantee  the  development  of  
pharmaceutical  research.    Inversely,  the  possibility  of patenting stem cells as products would violate the 
principle of the non commercialisation of products  of  the  human  body,  unless  they  have  become  derived  
products  which  no  longer retain the characteristics of a biological product.

Conclusion
The  recommendations  listed  in  this  Opinion  are  based  on  the  principle  of  the  non patrimonial nature of the 
human body and that the products of a human body cannot be the object  of  lucrative  commercialisation.    These  
recommendations  could  be  viewed  as  an obstacle to the development of certain kinds of research, in so far as such 
research  would be founded on the use of cells which, after manipulation, were to be multiplied and used, or even 
re-implanted, without losing their original nature.   CCNE is aware of this, but considers that strictly  regulated  
patentability  acquired  solely  for  the  process  is  the  optimal  condition  to enable the development of research 
and of new therapies in compliance  with the principles which have been defined.

This Opinion attempts to reconcile the present and future demands of therapeutic progress while it remains respectful 
of the founding ethical principles under examination.





22

This Opinion was approved by the members of the Committee as a whole with the exception  of  Marie-Thérèse  Hermange  
who  expressed  her  total  disagreement  with  the document.  Some members expressed reservations in complementary 
contributions.



June 22, 2006






















































23






COMPLEMENTARY   CONTRIBUTIONS   BY   CERTAIN   MEMBERS      TO   THE OPINION ON THE COMMERCIALISATION OF STEM CELLS


1

Observations on the conclusions of CCNE's Opinion on the commercialisation of cell lines.

Following  a  detailed  report,  the  recommendations  included  in  the  CCNE  Opinion  on  the Commercialisation of 
cell lines call for the following comments by certain members of the Committee:

1 - The Opinion recalls two fundamental ethical principles: the non patrimonial nature of the human body, of its 
elements and products on the one hand and on the other, the need to obtain informed consent from donors before any use 
is made of their cells.   The report itself lays  out  the  issues  which  are  raised  here  by the  application  of  
these  principles.   However, recommendation  n°  2  is  still  not  satisfactory  as  regards  the  non  patrimonial  
principle  and contradicts it.   It states that it "does not prohibit the remuneration, including in commercial form, 
of: on the one hand the actions, interventions and operations that accompany or follow the  harvesting  of  cells,  
(...)  and  on  the  other  hand,  the  various  uses  that  the  transformed product  could  be  put  to  after  
far-reaching  modification."    The  recommendation  therefore accepts  the  commercialisation  of  cell  lines.    
Furthermore,  it  leaves  unresolved  two  issues which would, at the very least, require clearer response.

-  Will  national  ethics  and  deontology  agencies  be  given  the  right,  and  according  to what criteria, to 
appreciate whether a cell has been sufficiently modified to be considered as no longer an element of the human body?
- Even if the sampling of initial stem cells is not remunerated, the operations which follow and which would be 
remunerated, are not free of charge; they would constitute the essential  part  of  the  profit  margins  thus  
indirectly encouraging  commercialisation  (as  is demonstrated by the analogy of human blood donation which does not 
in fact prevent the commercialisation of blood derivatives).   In this practical situation, would the distinction 
posited by the Opinion between initial cells and transformed cells be really functional?

One  might  well  fear  that  recommendation  n°  2  and  the  ones  that  follow  it  are  too imprecise to regulate 
supply and demand, or even the patenting of cell lines including human stem cell lines.

Inversely,  as  regards  adult  stem  cells,  there  is  legitimate  justification  to  allow  the remuneration  of  
actions,  interventions  and  operations  which  precede,  accompany or  follow their harvesting and the creation of 
cell banks as is already the case for umbilical cord blood cells.  The question remains open as to whether the 
transformations which they undergo could



24

deprive these cells of their original nature and possibly justify commercialisation of these derived products.

2  -  Secondly,  obtaining  certain  human  stem  cells  is  in  itself  the  source  of  serious  ethical issues.  The 
embryonic stem cell lines can only be obtained by harvesting them from human embryos which are then rejected.  These 
embryos are purely used as a means to procure stem cells   and   are   then   treated   "like   laboratory   material"  
 to   use   the   very   wording   in recommendation n° 5. This raises serious ethical objections in the name of human 
dignity and the report notes that some of its members feel very strongly in this respect. Furthermore, it is important 
to remember in this connection the point CCNE had underlined in its Opinion dated October 15, 1986: "Not only should 
the anthropological, cultural and ethical meaning of the beginning  of  life  be  taken  into  consideration,  but  
also  the  consequences  or  upheavals  that certain practices or research could imply for the overall representation 
of the human person". The way in which we treat future human beings obviously has weighty repercussions on our 
perception of the human person and therefore on our behaviour.  Recommendation n° 5 notes that such a risk exists, but 
does not devote much attention to it and it would seem that, without actually  saying  so,    this  is  crossing  a  
very  important  line  into  a  trivialisation  of  embryo research, at some distance from legislative precautions and 
disinterested motivations that were upheld  so  far.    Their  embryonic  origin  demands  that  harvesting  and  using 
 stem  cells  be excluded,  and  a  fortiori  any  remuneration  or  commercial  transaction  attached  to  such 
transactions.

3  -  For  the  same  reason,  recommendation  n°  9  considering  "the  creation  of  cell  banks", justifiably gives 
rise to grave disquiet, since it provides for no distinction between the various human  stem  cell  lines  which  would 
 be  "banked".     Such  a  recommendation  could  be interpreted  as  meaning  to  encourage  a  proliferation  of  
harvesting  of  cells  from  human embryos  in  vitro  and  giving  improper  legitimacy  to  opportunistic  research  
programmes  or even those with purely lucrative aims (cosmetic for example).

The  above  contribution,  drafted  by  Madame  HERMANGE,  Monsieur  de  DINECHIN  and Monsieur ROUVILLOIS, firmly 
emphasizes these ethical objections.




----------------------------------

2

The simple designation of what can legitimately be commercialised does not suffice to cover the ethical considerations 
connected to commercialisation.  The ethical outlook of each of the actors involved in stem cell research can have a 
far reaching influence on the way in which access is given to the useful applications of such research.

The meaning attached to "market" and "free competition" has evolved on the basis of ethical considerations that go 
beyond traditional ideological divides been public and private, with the opposition between a vision of public 
monopolies aiming for free access   but slowing down innovation by preventing the full play of competition on the one 
hand and of a free-market with open competition promoting innovation solely through profit-seeking, on the other.  The 
coexistence  of  various  kinds  of  competitive  systems  —  free  gifts,  non-profit  making  sales,



25

profit-making sales — is an incentive for the development of innovation, equity and for both producers and consumers to 
act more responsibly, thereby adding an ethical dimension to the market independently of concerns based entirely on 
economic profitability.

To  give  just  a  few  examples:  1)  the  decision  for  ethical  reasons  taken  by  the  scientists working on the 
Human Genome Project to publish all the gene sequences without taking out patents;   2)   the   development   by  
researchers   of   freely-accessible   high   level   biomedical scientific  publications  (the  PLoS/Public  Library  
of  Science  scientific  journals),  which  has completely  changed  the  face  of  a  market  which  up  till  then  
was  entirely  composed  of publications selling (at a very high price) the results of public research; 3) the 
development by researchers and users of the free software Linux in competition with (and now complementary to) 
Microsoft software sold for profit, etc.

So we find that innovation is not necessarily linked to economic and financial gain and that original individual and 
collective initiatives, powered by ethical considerations, in particular the  free  sharing  of  the  results  of  
research,  can  combine  innovation  and  accessibility  and thereby increase both the possibility of free choice on 
the part of users and distributive justice. But clearly such actions cannot be launched unless the market players 
understand that their ethical reflection can lead to changing the market.  It is perhaps at this level that 
deontological and ethical considerations differ most visibly.


For the above reasons, CCNE could have made the following recommendations:

1.  CCNE  considers  that  it  is  important  to  make  the  actors  of  research  aware  of  the need  for  reflection 
 on  the  major  role  they  may  be  playing  in  the  regulation  of  the ethical dimensions of the market when they 
select the method for making available the applications of their research.   CCNE encourages reflection that would give 
priority not just to technological innovation but also to innovation leading to the integration of the  ethical  
dimension,  thus  encouraging  researchers  to  accept  more  responsibility in the future and accessibility of the 
products of their work.  In other words, the fact that to  file  for  a  patent  and  to  engage  in  profit-making  
commercialisation  is  authorised should not be taken as automatic encouragement to take such a course.

2. Donors are  essential participants in these innovations, be they the donors of their own  cells  in  the  case  of  
adult  stem  cells,  or  the  parents  for  embryonic  stem  cells. CCNE considers that the concept of free and 
informed consent, which is at present one of  the  essential  components  of  biomedical  ethics,  should  not  solely  
depend  on  the provision   of   information   on   the   scientific   project   and   the   possible   biomedical 
applications, but also on the possibility or otherwise of these applications being put to commercial profit-making or 
non profit-making use.  Excluding donors from any form of commercial transaction because of the non patrimonial nature 
of the products of the human body should not lead to excluding donors from any choice in the commercial or non  
commercial  applications  which  could  be  made  as  a  result  of  their  donation. Donors of cells should be able to 
choose, on the basis of the information provided to them, the type of development and accessibility of innovations in 
which they would like  to  participate,  thereby  becoming  fully-fledged  actors  in  the  regulation  of  the ethical 
dimensions of the market.






26

3.  Empowering  each  of  the  actors  —  donors,  researchers,  administrators  of  research institutions  and  non  
profit-making foundations,  etc.  —  and  debate  on  these  subjects with   patients'   associations,   international  
 organisations,   representatives   of   the pharmaceutical industry and society as a whole, should encourage the 
development in this field, as in other domains touching on biomedical research, of an ethical vision for putting  on  
the  market  applications  which  are  beneficial  to  health  in  which  profit- making commercialisation would be 
just one option among others.  Choices should be justifiable   to   society   in   terms   which   are   not   only   
concerned   with   economic profitability.


Jean-Claude AMEISEN
















































27

ANNEX I


THE DIFFERENT KINDS OF STEM CELLS



1)   Embryonic stem cells
Background
The idea of using EC cells as a source of cellular therapy had been under study since the 1970s, but their tumoral 
origin and the frequent presence of chromosomal anomalies did not  recommend  them  for  this  task.    By  culturing,  
in  the  same  conditions,  mice  embryos, Evans and Kaufman (1981) obtained pluripotent cell lines from the inner cell 
mass (ICM) of the blastocyst: ES cells.
In  1998,  James  Thomson  and  co-workers  derived  the  first  human  ES  cell  at  the University of 
Wisconsin-Madison in the United States from the ICM of a blastocyst donated by a couple who had undergone in vitro 
fertilisation.   Since then, over a hundred cell lines have  been  derived  and  cultured  in  the  United  States,  
Sweden,  Australia,  Israel,  Singapore, India, Korea and the United Kingdom.

Production
The blastocyst is the ultimate stage in development of an embryo before implantation into the uterus (preimplantation 
embryo) and in humans corresponds to days 5, 6 and 7 after fertilisation.   The  blastocyst  is  made  up  of  50  to  
250  cells,  the  majority  of  which  line  the cavity that was formed in the centre of the blastocyst and filled with 
liquid (blastocœl).  These cells, called the trophectoderm, will develop into the placenta and membranes.  At one of 
the poles of the blastocyst, a group of 15 to 50 cells differentiate and are the origin of the fœtus (the  inner  cell  
mass).    They  go  on  to  produce  the  three  primitive  layers  of  the  embryo: ectoderm,  mesoderm,  endoderm,  
the  cells  and  tissues  that  derive  from  them  and  the  germ cells.
The  first  step  required  for  the  production  of  ES  cells  is  to  isolate  the  ICM,  by mechanical, chemical or 
immunological means.  In order to harvest the embryonic stem cells, the external membrane of the blastocyst is 
perforated, the inner cell cluster which contains the stem  cells  is  removed  and  transferred  to  a  Petri  dish  
containing  a  culture  medium.    The blastocyst is then destroyed and cannot continue to develop, but the embryonic 
stem cells can be cultured in vitro.   The ICM cells, dissociated or not, once they are put in culture on a layer of 
"feeder" cells, attach  themselves to that layer, proliferate and after a few weeks produce colonies   of   ES   cells, 
  which   continue   to   reproduce   while   maintaining   their   lack   of differentiation.  Some human cell lines 
have been kept in this way in culture for several years. They can also be frozen and stored in a cell bank.

To be successful, the culture needs, apart from the growth medium, so called "feeder" cells (fœtal fibroblasts).   
Scientists are now working on obtaining stem cell lines grown on human feeder culture material, or without feeder cells 
and in perfectly defined culture media.
Improving  culture  conditions  of  ES  cells  is  a  capital  issue  in  the  development  of cellular therapy 
strategies based on the use of stem cells.   It must be possible to amplify and control proliferation, maintaining the 
pluripotent nature of cells and also their chromosomal stability20.  The  sanitary  safety  of  the  culture  must  
also  be  ensured  through  adjustments  to

20 Several examples have been reported of anomalies after several weeks or months, Draper et al, 2004; Inzunza et al, 
2004



I

laboratory techniques and eliminating feeder cell layers or products derived from animal origins.
The  second  phase,  that  of  differentiation,  occurs  spontaneously  if  the  ES  cells  are suspended  in  a  
culture  medium  and  deprived  of  the  feeder  cell  layer.   Conditions  are  then sufficient for the ES cells to 
survive but not for their self-renewal and proliferation.  The cells then  form  spontaneously  into  cellular  
clusters  called  "embryoid  bodies"  which  acquire  a hollow structure resembling that of blastocysts from which 
differentiated cells characteristic of the three embryonic layers are detached.   Some cellular types form 
spontaneously: this is the case of hæmatopoietic cells and of cardiomyocytes which, after 14 days, when in contact with 
the endodermic type cells, appear and contract with the pulsatility which is characteristic of the human species21.  
Neural precursors, the neurospheres, can also be identified and they can be isolated and differentiated in vitro into 
neurons, astrocytes and oligodendocytes22.
Programming   this   differentiation   of   stem   cells   is   an   important   milestone   for therapeutic  uses.    
Certain  growth  factors  can  control  the  differentiation  of  ES  cells  in  a reproducible manner.  It is also 
possible to select certain cellular types for specific molecular marking, isolation and the development of pure 
cultures.

Origin
Although  the  provenance  of  ES  cells  is  invariably  the  blastocyst  ICM,  there  are multiple starting points 
and origins for the blastocyst, among which the main sources are:
-   the   most   obvious   are   supernumerary   embryos   resulting   from   IVF   (in   vitro fertilisation)  or  
ICSI  (intracytoplasmic  sperm  injection),  frozen  embryos  for  which  a parental  project  no  longer  applies.    
It  will  now  be  possible  in  France  to  use  these embryos with the consent of the parental couple and as part of 
a research programme controlled by the Agence de Biomédecine. Every year, 40 to 45,000 embryos are frozen, most of 
which are thawed for later use as part of the original parental project.   As of December 31, 2001, there were 96,584 
cryopreserved embryos stored in liquid nitrogen containers in ART (Assisted Reproduction Technology) centres.  Some 
60,000 of those embryos were still involved in a parental project and 15,000 were no longer claimed by couples  who  
were  not  responding  to  reminders  or  could  not  be  contacted.   That  left 23,000  embryos  for  which  the  
future  potentially  held  the  possibility  of  cessation  of conservation,  donation  to  another  sterile  couple  
(embryo  hosting)  or  donation  for research.  The ART centres find that this latter option seems only to be chosen 
for 20% only of the embryos  for  whom there is no further parental project.   Such evaluations may of course vary as 
time goes by and exciting research programmes are developed, but  this  represents  at  this  time,  4,600  embryos  of 
 which  75%  survive  thawing,  i.e. potentially  3,500  embryos  for  "French"  research.    As  of  now,  the  
various  groups attempting to derive stable ES cell lines using supernumerary human embryos, claim a success  rate  of  
approximately  20%,  which  will  probably  be  improved  with  time. Therefore,  existing  frozen  supernumerary  
embryos  could  be  the  origin  of  several hundred cell lines.
-  embryos  derived  from  ART  with  mediocre  morphological  and  kinetic  qualities  are considered to be incapable 
of implantation; they are more often than "normal" embryos (>80%) the carriers of chromosomal anomalies.   They are 
therefore eliminated.   They represent some 100,000 human embryos conceived in vitro in France every year.  And yet, in 
a small number of cases and despite a discouraging appearance, some of these embryos  are  still  capable  of  
development.   Recently,  two  teams  of  researchers  have published the results of tests to grow these "poor quality" 
embryos: 15% of them were

21 Mummery et al, 2005.
22  Reubinoff et al 2001.



II

still able to develop into blastocysts.  It is true that these blastocysts were not of the best quality either, but in 
10% of cases they were the origin of stable cell lines (pluripotence maintained for over 12 months, with a normal 
karyotype23.  It is difficult to say whether these embryos could have, after transfer in utero, given birth to normal 
children since at this  time  it  is  impossible  to  distinguish  with  any certainty those  that  would  not  have 
developed.  This would add up to 1500 ES cell lines that could be grown every year.
One  of  the  major  problems  in  cell  therapy  is  the  immune  tolerance  of  the  cells. Although animal 
experiments seem to show that embryonic cell immunogenicity is low, in  order  to  avoid  having  to  use  
immunosuppressive  treatment,  it  would  be  helpful  to benefit from the availability of cell banks of various HLA 
types, which requires a large number  of  cell  lines  and  a  large  number  of  embryos.    For  that  reason  it  
would  be worthwhile  to  diversify  the  source  of  available  human  embryos.    Another  problem, highlighted by 
recent research, is also inherent to all sources of embryonic stem cells. If cell lines are derived from blastocysts 
which were not implanted because they were not viable, would the cells in question have good therapeutic value and be 
biologically safe to use?
- In the United States human embryos have been created using oocytes and sperm from young and fertile donors to isolate 
ES cells24 (in France, this process is prohibited).
- Other avenues have been explored which could not be exploited for cellular therapy but    illustrate    the    
diversity    of    ongoing    research:    blastocysts    derived    from parthenogenetic   zygotes   following   
spontaneous25   or   inducted   oocyte26   activation; blastocysts derived from the chimeric aggregation of blastomeres 
from morphologically abnormal  embryos;  and  particularly embryos  carrying  a  genetic  anomaly  detected  by 
preimplantation diagnosis as the origin of cell lines available for research27.

Advantages and drawbacks
Among the advantages of ES cells, three are particularly noteworthy: 1) pluripotence making  it  theoretically possible 
 to  derive  the  majority of  the  various  differentiated  cellular types; 2) the possibility of getting these cells 
to proliferate in culture and thereby amplify the number of cells available for therapy and; 3) the capacity to 
maintain these cells and freeze them in the form of stable undifferentiated cell lines.
Among  their  drawbacks,  their  embryonic  origin,  their  antigenicity,  their  capacity  to form tumours in vivo if 
their prior differentiation is not assured, are so many limiting factors.

2)  Embryonic  stem  cells  derived  from  nuclear  transfer  (also  called  therapeutic cloning)
Before  any  discussion  of  this  theme,  it  must  be  emphasised  that  nuclear  transfer  is prohibited in France 
and in a majority of countries in the Western world at this time.  We are discussing the subject here because nuclear 
transfer can be one way of obtaining embryonic stem cells; under no circumstances would cell lines derived from nuclear 
transfer be put in the same category as "natural" stem cells.   As a consequence, the mention of the subject   in this 
Opinion is in no way to be understood as either approval or disapproval by CCNE of nuclear transfer.

Background

23 Chen et al, 2005; Mitalipova M, 2003.
24 Lanzendorf, 2001.
25 Suss-Toby, 2004.
26 Lin, 2003
27 Pickering, 2003.



III

Recently,  immune  deficient  mice  (Rideout,  2002)  or  with  Parkinson's  (Barberi, 2003) were successfully treated 
by the transplant of autologous embryonic stem cells derived from blastocysts obtained by somatic cell nuclear transfer 
(SCNT).   This combination of the technology  that  produced  Dolly  and  the  one  which  is  at  the  origin  of  ES  
cells  solves  the problem  of  the  immunogenecity  of  embryonic  stem  cells,  using  a  procedure  which  is 
commonly  called  "therapeutic  cloning".  At  this  time,  despite  some  premature  attention- catching 
announcements, the nuclear transfer method for humans  is not mature.

Advantages and drawbacks
Among the advantages, the autologous nature of the ntES cells must be emphasised. Such stem cells would be particularly 
well suited to cell therapy because of the absence of the risk of rejection.
Among the drawbacks, the most frequently raised problem is the ethical risk involved in the technical proximity of  
"therapeutic" or  "scientific" cloning and reproductive cloning. Harvesting  the  number  of  oocytes  required  to  
arrive  at  large  scale  cellular  therapy  seems hardly compatible with respect for women's health and free will.

3) Embryonic Carcinoma stem cells (EC cells)
These cells have very similar properties to those of ES cells and differentiated neural cells derived from EC cells 
have been used, despite their tumoral nature in a Phase 1 trial on 11 stroke victims, without any apparent side effects 
but without any great benefit28.

4) Fœtal stem cells
These cells are derived from fœtal tissues from aborted fœtuses (5 to 9 weeks).  They are abundant and of different 
types:
Somatic  fœtal  cells:  fœtal  tissues  contain  multipotent  stem  cells;  stem  cells  derived  from neural tissue 
have already been used in the treatment of neurodegenerative diseases such as Parkinson's  and  Huntington's  diseases  
and  the  allograft  of  fœtal  neurons  has  proved  to  be effective with lasting benefit since the grafted cells are 
still functional years later as has been verified (with Positron Emission Tomography/PET scans) in patients treated in 
Sweden.  The technique  however  requires  a  considerable  amount  of  fœtal  tissue  and  logistic  constraints limit 
development.
EG germ cells: In 1988, Shamblott et al showed that it was possible to grow pluripotent cells, very similar  to  ES  
cells,  from  primordial  germ  cells  present  in  the  genital  crest  of  aborted fœtuses.  Such cells however are 
difficult to isolate and culture and only the Shamblott group has managed to do so.
Hæmatopoietic stem cells (HSC) derived from cord blood: in the first few hours after birth, the HSC in fœtal 
circulation migrate to the bone marrow where they form the progenitors of all the blood cells.  Also found in the 100 
ml of blood contained in the cord and the placenta, which are eliminated after delivery, are HSCs in sufficient 
quantities to repopulate a child's bone marrow.   Such HSCs are obviously perfectly compatible with the donor but also 
with siblings  or  other  relatives  (see  Opinion  N°  74  dated  December  12,  2003:  "Umbilical  Cord Blood Banks 
for Autologous use or for Research".)

5. Adult stem cells
Background:
Blood cells and those of the epidermis and intestine are in constant renewal throughout life, which is evidence of the 
existence of active stem cells.   The stem cells of blood, bone


28 Kondziolka, 2000.



IV

marrow and the skin are easily accessible and already in therapeutic use.  In recent years, there  has  been  evidence  
that  other  organ  or  adult  tissues  (brain,  blood  vessels,  muscles, digestive epithelium, dental pulp, retina, 
liver and pancreas) contain stem cells.
Adult stem cells from a donor organ
Such  cells  are  capable   of  self   renewal  and   capable  of  differentiating  into  the specialised cell types of 
the tissue they come from.   They could therefore contribute to the replacement of cells that have died a natural death 
or after a lesion.   However, they do not seem to be very active if at all and do not seem to mobilise very much 
spontaneously if at all to repair extensive lesions or dysfunctions.
Potentially pluripotent adult stem cells
It was a long held belief that adult stem cells could only form the cellular types of the organs  they  were  located  
in.   Recently  however,  it  has  been  demonstrated  that  they  could differentiate into cells derived from the same 
embryonic layer: bone marrow cells becoming muscle cells from the same mesodermic cell line.
Transdifferentiation  also  seems  possible:  bone  marrow  cells  transforming  into  hepatocytes. But it was also 
demonstrated that this event was secondary to a cellular fusion process.  The picture is not yet entirely clear as 
regards the reality of such events nor whether they occur spontaneously or after in vitro induction.   Several 
observations on the beneficiaries of bone marrow donation, when the donor was of the opposite sex, plead in favour of 
the reality of the phenomenon.   Several  years  after  the  graft,  autopsy  reveals  myoblasts  and  epithelial  
cells completely integrated in the beneficiary's muscular tissue but which originated in the donor. Human 
mesenchymalatous stem cells derived from bone marrow do seem to be gifted with multipotentiality29.    There  have  
been  reports  that  there  are,  in  particular  in  human  bone marrow, stem cells capable of giving birth to cells 
from all three embryonic layers, but this is still very controversial.   Although they may be few in number, if their 
existence were to be confirmed, these cells would be accessible and therefore could become good candidates for cellular 
therapy.

Advantages and drawbacks:
A patient's stem cells could be used for self-repair while avoiding any immunological risks and ethical controversy.  
Such cells would ideal for regenerative medicine.
The  drawbacks  reside  essentially  in  the  feasibility  of  this  approach.    Compared  to embryonic stem cells, 
adult stem cells are very scarce, their proliferation potential diminishes with donor age, they are more difficult to 
maintain undifferentiated in culture and confirmed, but restricted, plasticity limits their capacity to differentiate 
into specific cell types.

















29 Jiang, 2002.



V

ANNEX II


POTENTIAL USES OF STEM CELLS

"Adult" stem cells and fœtal cells
Adult  stem  cells  are  used  for  cellular  therapy,  that  is  using  cells  whose  properties  or characteristics 
have been  modified after they were harvested from a living individual.   The prototype of organ stem cells of the 
adult kind are the hæmatopoietic stem cells (derived from bone marrow, mobilised in the blood, or from cord blood).  
They have been in use for about forty years.   Stem cells from the skin, cartilage and bones are now beginning to be 
used for therapeutic purposes.
The possibility of extending the therapeutic use of stem cells from various organs could give rise to the development 
of regenerative therapy.  It would be possible to repair cell losses observed  in  the  nervous  system  with  
Parkinson's  disease,  or  in  the  pancreas  in  the  various forms of diabetes, in the myocardium after an infarct, 
or in tissue development disorders such as myopathies.
The donor's organ stem cells could conceivably be used autologously (donor and patient one and the same) or 
allogenically (donor and patient not the same person).   To enable the transfer of cells from one person to another, 
cell banks could be set up which would solve the problem of tissular HLA group compatibility (as is already the case 
for cord blood cell banks, see Opinon n° 74 dated December 12, 2002 on "Umbilical Cord Blood Banks for Autologous use 
or for Research".).
Adult  stem  cells  can  be  modified  for  therapeutic  purposes  by  gene  transfer.   This  has already been 
successful with medullar cells in various forms of immune deficit and could be considered in the case for example of 
cystic fibrosis or certain genetic liver diseases.   More recently, multipotent adult stem cells, i.e. capable of 
giving rise to various types of tissue, and stem  cells  capable  of  plasticity  and  therefore  of  differentiating  
into  a  different  tissue  than those  that  stem  cell  differentiates  into  in  vivo,  have  been  the  subject  of 
 study.   Such  cells could also be used in therapy, either autologously or allogenically.
However, the use of adult stem cells raise a number of scientific problems which have not been solved as yet.
Some organ stem cells, other than hæmatopoietic stem cells, for instance skin, cartilage and bone stem cells which 
would seem to be present in each of these organs, are only present in very small quantities.  They are therefore very 
difficult to obtain.  Also, amplification and differentiation of these cells (and decoupling conditions) are not 
perfectly controlled at this time.
For multipotent stem cells, much remains to be done as regards their characterisation, the study of their potential and 
repeatability of the data.  The conditions in which such cells could be  amplified  to  enable  therapeutic  uses  
remain  to  be  defined  as  well  as  the  conditions  in which it might be possible to obtain, repeatedly, 
differentiation into a given tissue.  The very notion of tissular plasticity is disputed and requires further cognitive 
research  activity before any therapeutic development is attempted.
Comparable therapeutic prospects are conceivable for stem cells derived from fœtal tissue.
The potential existence of pluripotent stem cells in fœtal organs is presently being explored.
Embryonic stem cells
The  multipotent  capacity  of  embryonic  stem  cells  seems  encouraging  for  their  use  in regenerative therapy.  
However, two other potential uses should be considered:
-  obtaining  embryonic  stem  cell  lines  capable  of  differentiation  into  other  tissues,  for  the purpose of 
pharmacological and pharmacogenetic study;



VI

- obtaining pathological embryonic stem cell lines from pathological embryos originating in preimplantation diagnosis 
(see Opinion n° 72 dated July 4, 2002: "Reflections Concerning an Extension of Preimplantation Genetic Diagnosis".).   
Cell lines such as these could be the object of physiopathological studies and possibly of therapeutic testing for the 
genetic disease concerned.
In  scientific  terms,  embryonic  stem  cells  are  an  essential  element  for  studying developmental biology.
The questions raised by the study of these cells are numerous: detailed knowledge of the  molecular  processes  
involved  in  the  preservation  of  self-renewal  capacity,  detailed analysis of the molecular programmes for 
cellular differentiation, capacity to control in vitro cellular  differentiation  conditions  (in  particular  as  
regards  the  use  of  cytokines  or  stromal cells) and completely safe optimal culture conditions.
Apart  from  the  difficulties  connected  to  insufficient  knowledge  of  embryonic  stem cells, the potential limits 
of use of such cells for therapeutic purposes must also be mentioned:
- limitations in the precise control of the differentiation programme in order to obtain the required cell type (for 
example: a certain type of neurons located in a certain type of basal ganglia)
- risk of cancer development if cells were not completely differentiated in vitro
- and above all the inherent risk of incompatibility within the major histocompatibility complex  between  donor  and  
potential  beneficiary.    The  risk  of  rejection  must  be further  studied  to  ensure  that  it  can  be  avoided. 
   Here  again,  the  development  of embryonic  stem  cell  banks  expressing  various  combinations  of  HLA  tissue  
groups could be considered following the model adopted for cord blood cells.

Nuclear transfer
Nuclear transfer is prohibited in France at this time.  The following is therefore purely hypothetical.
Obtaining embryonic stem cells by nuclear transfer could offer glimpses of potential uses for regenerative therapy.   
However, it is infinitely probable that this technique will first be  used  to  obtain  cell  lines  derived  from  
pathological  material  so  as  to  enable  extremely valuable physiopathological work to be done (for instance, 
obtaining precursor neuron cells from nuclei derived from a somatic cell in a patient suffering from a serious 
developmental disorder of the central nervous system).  Such cells could also be used for therapeutic tests in vitro, 
and in the longer term perhaps also for gene transfer.
Scientific  problems  are  legion  among  which,  first  and  foremost,  controlling  the nuclear reprogramming 
process.
The  methodology  of  nuclear  transfer  encompasses  of  course  all  the  difficulties inherent in the development of 
the use of embryonic stem cells with perhaps the exception, as regards  therapeutic applications, of incompatibility 
and  therefore  the risk  of immunological rejection, since the genetic material of such cells would have the patient 
himself as its source.
Cell lines not derived from stem cells
Finally,  it  must  also  be  said  that  cellular  therapies  involving  the  injection  of  T lymphocytes  obtained  
from  the  donors'  blood  and  selected  in  vitro  on  the  basis  of  their specificity (antiviral, antitumoral) are 
in the process of development.  It may be surmised that in the future  other  cell lines (non stem  cells)  could also 
be used for  cellular therapy (other lymphocyte populations or dendritic cells).








VII

ANNEX III

The patentability of stem cells: the WiCell example

As an illustration of this issue, this is an example of patent transfer to a not-for-profit foundation for the  
development of research on embryonic stem cells.   This example shows how a foundation and a company set up conditions 
ensuring both protection and absence of payment for the use of such stem cells.
Following work on obtaining human embryonic stem cells, a patent was granted to the principal author, James Thomson 
from the University of Wisconsin.  The patent covered both the method used to isolate embryonic stem cells (process 
patent) and the five stem cell lines (product patent30).  In compliance with the University of Wisconsin's own 
regulations, James Thomson  transferred  the  patent  to  his  University's  supporting  organisation,  the  Wisconsin 
Alumni  Research  Foundation  (WARF)  —  a  non  profit  foundation  which  negotiates  and establishes licensing 
agreements.  In particular WARF, which owns the patent, includes in all its contracts a clause which stipulates 
unimpeded and free-of-charge distribution of patented material to be used for research.
Furthermore,  WARF  has  created  another  non-profit  organisation,  the  WiCell  Research Institute   (headed   by  
James   Thomson)   to   manage   the   conservation,   multiplication   and distribution of these stem cells which 
requires constant and intensive attention.
Stem  cells  are    distributed  free  of  charge    to  scientists  requesting  them  under  the following conditions:
1.         WiCell retain ownership of the cells made available to researchers.
2.         These cells must not be used for diagnostic or therapeutic purposes; their use is solely confined to 
education and non commercial research.
3.         Use of the cells must comply with applicable rules, regulations and guidelines. In particular, it is not 
permitted to:
- mix the material with an intact human or non-human embryo;
- implant these cells in a uterus;
- to attempt to make whole embryos derived from the cells.
4.         Should  a  scientific  discovery  based  on  this  material  be  usable  for  commercial purposes,  a  
separate  written  agreement  will  be  arrived  at  between  WiCell  and  the scientist concerned to define and 
regulate the commercial outcome of the discovery.
5.         WiCell  may  demand  payment  for  the  preparation  and  distribution  of  stem  cells  to recipients.
In France and the rest of Europe, legislation differs in that there is exemption at the outset in favour of research, 
which means that research may be conducted on elements or products covered by a patent on the condition that such 
research is not associated with any commercial exploitation.   It  is  therefore  unnecessary to  refer  specifically 
to  exemptions  for  research  in technology transfer contracts.










30 EGE Auditions, November 20, 2001



VIII

ANNEX IV

OPINION  OF  THE  EUROPEAN  GROUP  ON  ETHICS  OF  7  MAY,  2002  ON  THE PATENTABILITY OF STEM CELLS

According  to  the  EGE  Opinion31    dated  May  7,  2002,  there  have  been  over  2000 patent applications 
involving human and non human stem cells, of which one quarter refer to embryonic stem cells.
These patent applications bear on:
-  either  processes:  processes  for  isolating  stem  cells  from  embryos   or  tissues; processes  for  enrichment  
of  stem  cells  in  mixtures  of  cells;  processes  for  culturing stem cells; processes for genetically modifying 
stem cells; processes for inducing the differentiation  of  stem  cells;  processes  for  inducing  adult  stem  cells  
to  undergo 'retrodifferentiation' or  'transdifferentiation';  processes  for  transforming somatic  cells into stem 
cells,
-  or  products:  involving  stem  cells,  stem  cell  lines,  differentiated  stem  cells  and genetically modified 
stem cells.
As regards the patentability of stem cells, the European Directive 98/44/EC of 6 July, 1998 and its transposition to 
the French laws on Bioethics in 2004 are very explicit32.
EGE's  Opinion  n°  16  concludes  that  it  would  not  be  advisable  to  prohibit  any patenting of stem cells or 
stem cell lines as it would, according to that Opinion, be contrary to public interest in general and patients' 
interests in particular.
The Opinion also recommends that a distinction be made according to the nature of the material: isolated stem cells or 
stem cell lines that have not been modified do not as a product fulfil the legal requirements to be seen as patentable. 
  Inversely, stem cell lines which have been  modified  by  in  vitro  treatments  or  genetically  modified  so  that  
they  have  acquired characteristics  for  specific  applications  would  seem  to  fulfil  the  legal  requirements  
for patentability.  In fine, the Opinion insisted on the need for Patent Offices to avoid granting too broad patents 
for stem cell lines that could impair further research and development.
As a result,  stem cells of adult origin could be patented following the status conferred on cell lines:
- if they are products of the human body which have simply been detached and have undergone no transformation, they do 
not fulfil the legal requirements to be seen as patentable,
-  if  they are  products  derived  from  the  human  body,  that  is  cell  lines  derived  from isolated stem cells, 
obtained by a technical process in vitro, that could not be viewed as natural stem cell lines, they could be patented.


31 Opinion n°16 of the European Group on Ethics in Science and New Technologies (EGE) dated May 7, 2002: Ethical 
Aspects of Patenting Inventions Involving Human Stem Cells.
32  " Art. L.611-17: (code de la propriété intellectuelle - code of intellectual property): are not patentable
inventions whose commercial exploitation would be contrary to the dignity of human beings, public order and 
morality..."
"Art.  L.611-18:  the  human  body,  at  various  stages  of  its  constitution  and  development,  as  well  as  the  
simple discovery  of  one  of  its  elements,  including  a  total  or  partial  gene  sequence,  cannot  be  taken  as 
 patentable inventions.   Only an invention involving the technical application of a function or element of the human 
body can be patent-protected.  Such protection only covers the element of the human body in so far as this is necessary 
to the realisation and exploitation of that particular application.  In particular, are not patentable: a) processes 
for the cloning of human beings, b) processes for the modification of the genetic identity of human beings, c) the use 
of human embryos for industrial or commercial purposes, d) total or partial gene sequences as such".




IX

Product patenting for stem cells would therefore be acceptable, according to the directive, on the condition that such 
cells are viewed as being "processed and transformed". Similarly,  process  patents  for  obtaining  cellular  therapy  
products  could  be   granted  if  the technical conditions are fulfilled.
However, it is to be expected that the cell lines themselves cease to fulfil patentability criteria  for  insufficient  
novelty,  invention  or  industrial  application  (following  chromosomal rearrangement, they could become dangerous 
and ineffective), but that is a technical problem to be solved by Patent Offices on the basis of applicable rules.
The European Group on Ethics' Opinion n° 1633 also underlines that those who oppose embryo  research   will be in 
principle opposed to any kind of patentability.   But those who accept embryo  research  may be  reluctant  to accept 
the notion of patenting embryonic stem cells.    Others,  considering  the  expected  medical  benefits,  would  
consider  patentability  as acceptable.
Article  6  of  directive  98/44  provides  for  a  certain  number  of  exclusions  from patentability for reasons of 
'ordre public' and morality and in particular specifies that the use of embryos for industrial or commercial purposes 
is not patentable.   But paragraph 42 of the Preamble adds that the exclusion does not concern inventions relating to 
human embryos for therapeutic or diagnostic purposes.
Although  the  industrial  or  commercial  use  of  human  embryos34  is  excluded  from patentability  by  virtue  of  
article  6  of  the  directive,  this  prohibition  does  not  apply  to embryonic stem cell lines which can no longer 
be considered embryos.   Such cell lines can therefore be process- or product-patented35.
The  Opinion  also  specifies  that  this  article  does  not  give  any definition  of  embryos concerned  by  the  
exclusion  so  that  certain  embryos  could  be  exempt:  these  would  be  non viable  (that  cannot  lead  to  any  
birth)  embryos  such  as  those  created  by  parthogenesis. However,  a  limitation  arising  out  of  article  6  
paragraph  2  a  would  seem  to  apply:  are  not patentable  "the  proceeds  of  cloning  of  human  beings",  clause 
 according  to  which,  notes Opinion  n°  16,  should  be  excluded  from  patentability  the  proceeds  of  creation  
of  human embryos by cloning in order to obtain stem cells.
Inversely, the question of consent for later exploitation by a patent is not to be found in  legal patent regulations 
and does not appear in the articles of the directive.  Only paragraph 26 of the Preamble mentions such consent and 
recommends its use.















33 Previously quoted, note 48
34  EGE's  Opinion  n°15  of  November  14,  2000,  "Ethical  Aspects  of  Human  Stem  Cell  Research  and  Use" 
recommended  that  steps  be  taken  to  prevent  the  commercialisation  of  human  embryos  of  tissues  from  dead 
fœtuses.

35 To that effect, TA Paris, January 21 2003 confirmed on appeal by decision of May 9, 2005.




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