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Bioethic information and analysis newsletter

Following Letter

N°40 - April 2003

Nature defeats cloning of primates

Primates are resisting
Dr Gérald Schatten's team at the Magge-Womens Research centre at the University of Pittsburgh has put forward an explanation for the failure of the successive attempts at cloning of monkeys. According to the team, certain cells have a kind of biological device which protects against cloning, a device which is not found in other mammals. It is a natural mechanism which prevents the cloning of primates and therefore of human beings.

A chromosomic obstacle
Before reaching this conclusion, the team attempted to clone a macaque : they obtained 724 ova which formed 33 embryos and in the end zero pregnancies. This failure is claimed to be due to a fundamental molecular obstacle : "when cells divide, there are certain very fundamental things which must happen, and they do not happen" comments one of the researchers in "Science " magazine dated 11th April.

In fact for cells to divide correctly, the chromosomes must duplicate themselves before dividing. However, at this very early stage, the cells of cloned primates do not divide normally, and this leads to an untidy mixture of chromosomes. The embryos do not have the right number of chromosomes, and this explains the failure to implant. These chromosomic properties are therefore thought to be the reason for the failure of this cloning.

All cloning thrown into doubt ?
The research scientists at the University of Pittsburgh made use of four different techniques of nuclear transfer, and each time the result was the same : there are fundamental molecular obstacles which prevent the normal cellular development. "Using the current approaches to nuclear transfer, it could be difficult to obtain stem cells for non-human primates, and reproductive cloning could be impossible" concluded the researchers.
This discovery could also jeopardise therapeutic cloning.
Ref : Molecular Correlates of Primate Nuclear Transfer Failures – Science - Vol 300 – 11th April 2003  

Therapeutic cloning : the European Parliament says « no ! »

All cloning is prohibited
On 9th April, the European Members of Parliament approved the draft directive on "Human cells and tissues" aimed at prohibiting all forms of cloning including for therapeutic reasons. The presenter of this text was the German MP Pieter Liese. The Parliament thus intends to "reject any technique consisting of using the human being as a material, including at the embryonic stage".

Research on the embryo
The text adopted concentrates clearly on questions of public health.
In the field of embryonic research, for example, the European MPs chose to protect a few key elements.
Thus, amendment 30, which was adopted, provides that member-states prohibit at least :
- research activities aimed at human cloning for reproductive reasons;
- research activities aimed at creating human embryos for research purposes only or for providing stem cells, including for the transfer of somatic cell nuclei (ndlr : so-called therapeutic cloning)."

Finally, an amendment intended to prohibit research resulting in the destruction of human embryos was not adopted :
"the member-states prohibit at least :
- research work aimed at cloning human beings for reproductive purposes ;
- research work aimed at creating human embryos for research purposes only or for obtaining stem cells, and that includes the transfer of somatic cell nuclei ;
- research work involving the destruction of human embryos."

232 MPs voted in favour of the amendment, 232 MPs voted against it and 11 abstained : the amendment was therefore not adopted, as in the event of equal voting, the amendment is rejected.

Cloning : No transplants
Amendment 51 which was adopted, provides that "cloned human embryos and hybrid animal/human embryos produced by cloning, aggregation or any other method, as well as tissues and cells taken from them cannot be used as a source of material for the purposes of transplants."
Finally, under amendment 31, the European MPs called on member-states to govern at the national level, the use of germinal cells and embryonic stem cells in the event that their national laws do not prohibit such practices.

No pressure on women
An amendment (No. 86) specifying that it is "prohibited to take tissues from foetuses resulting from voluntary termination of pregnancy" was rejected; however, the MPs adopted an amendment (No. 93) which specifies : "No abortion may be performed in view of obtaining foetal tissues. It is essential to ensure by appropriate measures that no pregnant woman is subjected to any kind of pressure whether to submit to an abortion or in view of obtaining tissues. The opportunity of an abortion and the way in which it is conducted must not be influenced by any desire to obtain foetal tissues.

Acceptance at 1st reading
The text was put up for vote at a plenary session and was adopted by 234 votes to 217. Having been adopted at its first reading, it must now be presented before the ministers of the Fifteen, who may amend it. It must then be submitted for second reading at a plenary session, which must approve it by an absolute majority of 314 votes. The date of the voting has not yet been fixed.

Biomedical research on man : Revision of the Huriet law

The European directive
In 1988 the Huriet-Sérusclat law¹ established a legal framework for biomedical research. One of its characteristics was that it distinguished between two types of research : research for the direct benefit of individuals (DBI), and research without DBI. The latter was undertaken under strict conditions restricted to persons who were able to consent "freely and in full awareness".
In 2001, the European directive² relative to clinical testing of medicines, provided new orientations. The provisions transposing this European directive into French law, have necessarily to be applied by no later than 1st April 2004.
The European directive removes the distinction between research with DBI and that without DBI for a notion of "balance between benefits and risks". Under article 3, a clinical test can only be undertaken "if the predictable risks and drawbacks have been established with respect to the individual benefit for the subject participating in the test".
This obligation, together with the need to improve the provisions of the December 1988 Huriet law, led to the elaboration of a draft revision of that law. For the last 2 years, the law has therefore been the subject of a new text.

Review of the law
On 9th May 2000 Claude Huriet, as the spokesman for the social affairs committee for the 20th December 1988 law, raised nine questions concerning the functioning of the consultation committees for the protection of persons taking part in biomedical research (CCPPRB). Ten years after the implementation of the law, it is high time to review the functioning of the CCPPRB, in order to be in a position to put forward any improvements.

A year later, C. Huriet has reported on the activity of the structures established following the adoption of the 20th December 1988 law thanks to the answers to a questionnaire forwarded to all the committees, together with a programme of hearings³. After that survey, C. Huriet proposed to come back to certain matters, of which the main ones are as follows : clarification of the definition of tests "with" or "without" DBI. Greater involvement of persons taking part in the research, recognition of the committee council, encouragement of relations between the committees and other players in biomedical research (AFSSAPS...).

Additionally, a forum was circulated from various knowledgeable societies, aimed at obtaining an amendment to the 20th December 1988 law⁴. Even if the evaluation of medicines is being performed properly through that law, certain fields of application, such as non-medicine related research on healthy volunteers, research without DBI on patients, research on patients not fit to give consent, medico-economic studies, genetic studies, etc. leave some room for improvement.

Draft revision of the law⁵
A draft revision of the law has therefore been submitted to the biomedical research partners (CCPPRB, users, etc.) in order to obtain their views in the context of the draft law on the "public health policies" which is due to be examined shortly. The draft, elaborated by the Health Ministry, provides, among other things, the possibility of conducting research on patients who are not in a state to give consent, with the agreement of a trusted person. The current declaration procedure would be superseded by a system of authorisation given by a "competent authority" in the event of favourable advice from the ethical committee.
Dr F. Lemaire, who was tasked by the last government, with preparing the reform of the 1988 law, is satisfied with the text, as it is currently proposed. C. Huriet, on the other hand, denounces it as "sabotage" of the law : "the provisions considered do not provide adequate protection". He is opposed to the fact that tests may be undertaken on people who are not in a fit state to be able to give their consent. In his view, the notion of benefits / risks "has no sense" : "it is impossible to say in advance whether a particular item of research involves more benefits than risks".

1- 1988 Huriet law.
2- European directive 2001/20/CE
3- Information report on behalf of the Social Affairs Committee on the functioning of the CCPPRB.
4- Revision of the law dated 20th December 1988 : common forum for proposals from knowledgeable societies organisations and associations of patients
5- Draft revision to the Huriet law, 27th March 2003