Concerns Related To The Development Of Reprogenetics

In his book on biotechnologies, Claude Debru (2003) provides an excellent historical account of genetic engineering: the beginnings (1972), the realization of the risks involved in research, the moratorium and the safety measures resulting from the

Asilomar process, the early successes - the synthesis of human insulin by a genetically-modified bacterium (and then a yeast) - (1978), the creation of transgenic plants (1980) and animals (1981), then human gene therapy trials (some inept or premature, indeed). According to an American report published in 2003 (see Parens and Knowles, 2003), what we should now be worrying about is the transfer of the technologies derived from genetic engineering to medically-assisted human procreation.

The idea that the human species will one day apply to itself the same technological tools as it has used to modify plants or animals is not new. Jean Rostand wrote in 1950 (92): "whether it is by the genes in the nucleus or by the genes in the cytoplasm, it looks as though Man may end up producing major structural improvements in the human body". Erik Parens and Lori Knowles, the authors of the American report, start from an observation. During the second half of the 20th century, medically-assisted procreation (MAP) and molecular genetic research developed separately. MAP, with the aim of treating sterile couples, invented its own methods (IVF, ICSI,3 etc.). Molecular genetics used bacteria, before launching itself into the investigation of more complex organisms, such as Arabidopsis thaliana, the mouse-ear cress, a small cruciferaceous plant, in order to map their genes (21000 genes, for Arabidopsis), and to identify the function of these genes. During the 1990s, the techniques developed by genomics entered the world of MAP. The word "reprogenetics" made its appearance in 1999.

Parens and Lowes have identified in recent publications some examples of the application of genetic technology to human procreation that cause them concern. One method that can be used to sort sperm on the basis of the weight of their DNA4 makes it possible to select the sex: 430 children whose sex has been selected by their parents have been born after their father's sperm had been sorted using this method (see Fugger et al., 1998). Little Molly Nash suffered from Fanconi anaemia, her parents decided that in order to help her they would have a 'baby-doctor'. A pre-implantation genetic diagnosis was carried out of their embryos obtained in vitro. The embryo for reimplantation was chosen so that it would provide Molly with a younger brother or sister who would be both histocompatible and free of the disease (see Verlinsky et al., 2001). Molly was to be given a blood transfusion from the umbilical cord (the baby was born in August 2000). A third example: about twenty women whose sterility was linked to an anomaly of their mitochon-drial DNA5 were able to conceive after their oocytes had undergone a transfer of cytoplasm from the oocytes of donor women who were not suffering from this disorder (see Cohen et al., 1998; Barritt et al., 2000, 2001; Templeton, 2002). The

3 IVF: in vitro fertilization; ICSI: intracytoplasmic sperm injection.

4 Deoxyribonucleic acid.

5 Mitochondria are organelles present in the cytoplasm of the cell. They contain different genes from those in the cell nucleus. The transmission of the mitochondrial genome is solely via the mother (in animals); the flagellum of the spermatozoon (which contains the mitochondria of the father) does not get into the oocyte during fertilization.

children born as a result of this procedure were 'apparently' normal (although two of the foetuses obtained did suffer from Turner's syndrome;6 it is not possible to say whether this was merely coincidence).

There are innumerable ways of tinkering with human reproduction in this way. Some authors do not hesitate to look forward to the genetic "enhancement" of our species (Gordon, 1999), by means of correcting reparable genetic defects at an early embryonic stage.7 Others fear deterioration, knowing that, for instance, ICSI allows a sterile father to have a male child who will also be sterile. Many worries have been expressed about ICSI (see American Society for Reproductive Medicine, 2000; Hansen et al., 2002). The concerns expressed by Parens and Lowes can be accounted for to some extent by the North-American context. In the United States the public debate has long been centred on the question of the right to abortion, the battle lines drawn between the pro-life and the pro-choice camps remain intact, and it has therefore been decided that nothing involving research on the human embryo or the creation of embryos for research purposes may be funded by public money. Consequently both MAP and embryo research have slipped into the private sector, with no state funding or control, and full freedom. The scientists who wanted to treat defective oocytes by transfusing cytoplasm were under no obligation to submit their protocol or to seek regulatory approval before proceeding unless the journals where they wanted to publish had specific ethical requirements. Parens and Lowes condemn this situation, and the alternative model they suggest is the British system, which is centralized, regulated and supervised, but at the same time, "one of the most liberal in the world". The British (and in their wake, the Swedes and the Canadians) have been able to define a policy on reprogenetics, and this policy has been a subject of public debate. At present modifications of the germ cell line are banned, as are gender selection for non-medical reasons and the creation of human-animal chimeras (all things that can be done legally in the USA within the private sector, where nothing is banned). Apart from these restrictions, British scientists are free to propose any experimental procedure they wish, including the creation of human embryo cells by nuclear transfer (for "therapeutic cloning"), but they have to persuade the regulatory authority that what they propose doing is of real scientific value. This flexible control provides protection against possible abuses.

Parens and Lowes fear that abuses may increase in the United States now that scientists have access to human embryonic stem cell lines derived from "spare"

6 Individuals suffering from Turner syndrome are phenotypically women, small in size, and have only one X chromosome (instead of two). The XO genotype is not always compatible with life, but it is a fairly frequent cause of miscarriage (5%).

7 In this context the threat has been voiced of a 'loss of genetic diversity', which is potentially dangerous for our species. Michel Morange rejects this argument: "The idea that genetic diversity is always a good in itself and that any manipulation intended to reduce this diversity, even to a limited extent, is bad, is highly contestable. Let us add that it will doubtless take several centuries, even with all world's biologists, to curb this genetic diversity as much as colonization or wars sometimes did within a few months in past centuries" (1998, 204).

human embryos left over from assisted procreation: which is ideal material for trying out genetic recombinations, and transform MAP into something like using a Meccano set, so that children manufactured to order could become consumer goods like any other. However, the problem extends far beyond the American context. It is a fact that MAP has opened a huge experimental field to genetic engineering. The boundary between human experimentation and clinical innovation has been blurred, it is accepted that in this field procedures may be tried out without previous animal testing, and there often is no reliable monitoring of outcomes. Couples who resort to these procedures tend to accept high and/or poorly evaluated risks. It is also a fact that something very important is at stake: since it involves the birth of human children, can people be allowed anything they want with no control? However, it isn't clear what we should be trying to achieve. Should we ban cloning as a method of reproduction, and not bother about the rest? This would mean permitting, in the context of MAP, for instance, that deaf children could be deliberately produced on demand, as has in fact happened. Should we compile a list of the genetic interventions that are authorized or banned in MAP (with the risk of seeing these lists rapidly becoming outdated)? Should we, as in France, be tolerant with regard to treatments for sterility, but ban outright all research concerning the technique of nuclear transfer, even though such research is going on elsewhere (in the United Kingdom, Israel, Singapore, for instance)? It is already complicated enough for a single country to adopt an overall policy for reprogenetics (Canada has had problems), it can only be even more difficult at the international level. In 2003 we saw how the efforts of conservative groups to have the UN ban all forms of human cloning failed, and that just a few months later a team of biologists in south-Korea announced that they had produced a human embryo by cloning. Even though that result was proved fabricated, other research groups are now on the same path.

A few philosophers have tried to formulate the principles for regulating technological progress. J├╝rgen Habermas (2001) finds it quite unacceptable that a human being could, to no matter how limited an extent, become a technological construct (because, for instance, a genetic defect had been corrected). Following Kant's distinction between the realm of nature and that of freedom, and fearful that increasing technicization of human nature could obscure the sense that we have of our dignity, he firmly resists the prospect of an invasion of the field of human procreation by genetic engineering: "If we get the habit of turning to biotechnology to rearrange human nature to fit in with our preferences, it is impossible that the understanding we have of ourselves from the point of view of an ethics of the human species could remain intact" (2002, 109). Claude Debru, tracing the history of the biotechnologies, observes that although we have had fantasies of Frankenstein, in reality we have produced insulin to treat people with diabetes. Having described the position of Habermas, he rejects its rigidity, on the grounds that our biotechnological tinkering is in evolutionary continuity with that which occurs in nature: "the tools and bases of biotechnological tinkering are the same as those that underlie evolutionary tinkering" (2003,420). He is inclined to prefer a flexible control of biotechnological progress, an approach which would keep confidence in the ability for optimization inherent in human nature, and which would avoid compromising the future: "we must be careful not to go into the future facing backwards" (ibid., 409).

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