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Bioethic information and analysis newsletter

Following Letter

N°45 - September 2003

« Medicine babies » or the generalisation of pre-implant diagnostics

Pre-implant diagnostics (PID) or the biological diagnostics made using cells taken from an in-vitro embryo, are only authorised in France under exceptional circumstances. They are restricted to couples who have a « high probability of giving birth to a child suffering from a particularly serious genetic disease, which at the time of the diagnostic, is recognised as being incurable » (art. L2131-4 of the French Public Health code). In practice, this type of diagnostic enables the selection of embryos conceived in-vitro, in order to implant only healthy embryos. The diagnostics, even if controversial since they lead to the elimination of embryos suffering from the incurable disease, are claimed to be in the interest of the child.

Is it possible to conduct such diagnostics in the interest of a third party ? That is the question being asked with regard to the conception of « medicine babies ». In such cases, the intention is to bring a child into the world, whose immune system is compatible with that of a sick brother or sister, in order to be able to draw off the cells required to cure them. In a pronouncement made on 4th July 2002, the French National Consulting Committee on Ethics, was guarded, highlighting that « the essential problem is the reality of the parental project, and therefore the risk of instrumentalisation of the child ». The response in principle was therefore unfavourable to any extension of PID « if the embryo is conceived merely to act as a potential donor, and not primarily for itself ». On the other hand, « to allow a wanted child, additionally to represent a hope of cure for an elder brother or sister, is an acceptable objective, if it is secondary ». The border-line seems ill-defined and how can such a subjective criterion act as the basis for a legal rule if a change in the law is considered ?

Towards a broadening of the indications of pre-implant diagnostics ? This question could well be considered at the forthcoming review for the intended revision of the bioethics laws. Alain Claeys, the French national health delegate for the socialist party, has just announced that he will be submitting an amendment broadening the conditions for pre-implant diagnostics, in order to enable the conception of « medicine babies ». What could the consequences be ? In-vitro fertilisation must not become a therapeutic tool, and the risk is that certain parents will conceive a child with the sole purpose of finding a potential donor.

At what price ? We all remember that Adam, the first « medicine baby », born in the United States in October 2000, had been selected among 15 embryos, of which 14 were destroyed. The geneticist Axel Kahn underlines the disastrous effects at the family and psychological levels, that could be caused by such manipulations.

The embryo reprogrammed by artificial mechanical constraints

According to the work conducted by Emmanuel Farge, (UMR 168, CNRS/institut Curie) and recently published in the Current Biology periodical, certain development genes of the fruit fly are mechanically sensitive.
During its development, every embryo is subjected to mechanical deformations which define the physical shape to be adopted by the adult organism. These movements are today recognised as being controlled by the expression of certain so-called « development » genes.
The totally new question which is solved by this work is as follows : are the embryo's active changes in physical shape, in return susceptible to modulate the expression of the development genes, through the mechanical constraints generated by those movements ?
The work shows that 5 of the early development genes of the fruit fly are mechanically sensitive, i.e. that it is possible to deeply modify the expression model of the genes in response to a uni-axial mechanical deformation applied to the entire embryo. One of these genes, known as Twist, which provides the code for the formation of the upper gastric tube, is normally expressed exclusively in the ventral region of the embryo. However it is found to be expressed homogeneously all over the embryo in response to the mechanical deformation.
The formation of the upper gastric tube could well be expressed mechanically by a natural morphogenetic embryogenetic motion. The physical shape of the embryo is therefore likely to be, in itself, an inductive signal for the expression of the coding genes for the development of the physical morphologies which belong to the subsequent development stages, throughout the natural embryogenetic process.

The implications of this work
The mechanical induction of the expression of development genes in response to an artificial motion applied to the embryo, shows that even the genetic development programme is extremely plastic, when the embryo exchanges with the outside world. There is no absolute genetic determinism. The system is potentially plastic, even during the first hours of its development, subject to it not being isolated, and to it being able to exchange with the outside world.

Reprogramming the embryo ?
This work has demonstrated, for the first time, that it is possible to reprogram an embryo, to modify the expression of its genetic programme by a change to its physical shape. During the development stage studied, the fruit fly embryo has many common features with vertebrates such as the frog or the fish, and certain of the architectural genes present in the fly are also found in the animal world.

Other studies, on other species, must now be undertaken to verify whether this mechanism is universal or specific to certain vertebrates.

E. Farge, Current Biology (vol. 13, 1365-1377, 19 August 2003)

European funding for research on the human embryo ?

An agreement in stages
On 30th September 2002, the European Council of Research Ministers adopted a final decision relative to research on the embryo. This provided that « the precise arrangements for application concerning research activities involving the use of human embryos or human embryonic stem cells which could be funded under the sixth framework programme will be defined by the 31st December 2003 ».

Cell lines
The Commission declared that « in the interim, it would not undertake to fund such research activities, apart from the study of human embryonic stem cells stored in banks or isolated in cultures » (European Union Council Document 12374/02 ADD) ( cf. Gènéthique No. 34, October 2002).
The principle of funding research on human embryos was already acquired, one can therefore be justifiably astonished that certain member States, including France, will have to fund such research through their contribution to the Community budget, whereas their internal legislation prohibits the same research on their territory.

Supernumerary embryos
During the presentation, on 9th July of the major orientations of the 6th framework programme of research, the European Commission specified the « ethical » conditions to be complied with in order to qualify for funding for research projects involving stem cells obtained from supernumerary embryos.
The proposal under discussion is aimed at combining its execution with compliance with the ethical conditions specified under advice No. 15 of the European Ethics Group (EEG) headed « Ethical aspects of research on human stem cells and their use ».

The Commission's proposals
- The European Union does not fund research on human embryonic stem cells in its member States where this type of research is prohibited ;
- Human embryonic stem cells may only be isolated from supernumerary embryos whose parents donate them to science and which were conceived before 27th June 2002, date at which the 6th Framework Programme was adopted (this is in order to avoid that community funds could indirectly encourage the production of more embryos than are necessary for in-vitro fertilisation ;
- The potential partners of the research project, who apply for community funding, must obtain ethical approval from a local or national ethical authority in the member States where the research is to be undertaken ;
- Research may only be funded if it satisfies particularly important research objectives and if there is no other suitable method ;
- The protection of data and of privacy must be guaranteed and the traceability of the stem cells must be assured ;
- Research consortia must undertake to make the new lines of human embryonic stem cells available to other research workers.

Finally, the Commission intends to fund the establishment of a European register of stem cells and will contribute towards the constitution of public stem cell banks and their networking throughout Europe ; research workers should therefore have readier access to the various lines of stem cells available in Europe.

This proposal by the Commission will be debated by the European Parliament between 17th and 20th November 2003. The Council of Ministers should therefore take a final decision before the end of the year.

Proposed decision of the Council in modification of decision 2002/834/CE establishing a specific research, technological development and demonstration : « Integration and reinforcement of the European research space » (2002-2006)