Select Committee on Stem Cell Research Report


The additional purposes in the Regulations

5.1 As described in Chapter 1, the 2001 Regulations extend the purposes for which research on early embryos may be undertaken from purposes connected with reproduction and treating infertility to certain purposes concerned with understanding the development of the embryo and increasing knowledge of, and developing treatments for, serious disease. The possibility of an extension was foreshadowed in the 1990 Act, which provides (in Schedule 2) for the original purposes to be extended by regulation.

5.2 In the debates on the Regulations one of the issues on which there was disagreement was whether the change effected by them was a matter of degree or such a substantial change that, as some argued, it should have been introduced by fresh primary legislation.

5.3 We asked all our witnesses if they saw the additional purposes as raising new issues of principle. Some—mostly (but not exclusively) those opposed to research of any kind on early embryos—contended that new issues of principle did arise, in so far as the original purposes were strictly limited to reproductive research, while the new purposes were much more widely drawn. In their view the purpose of understanding the development of the embryo entailed basic research rather than research directed at specified desirable objectives. The All-Party Parliamentary Pro-life Group, for example, argued that "the regulations allow 'pure' research on human embryos, without reference to clinical goals, for the first time" (p 213). In his memorandum Lord Habgood said: "they [the Regulations] are much too open-ended and are thus in danger of destroying the broad ethical consensus on which the original regulations are based" (p 390). It was also argued that under the Regulations the embryo would be used instrumentally, as a means to an end, whereas under the original purposes, the research, although it could not benefit the embryo that was the subject of it, was at least intended to benefit the class of embryos as a whole by improving reproductive techniques. On the other hand, the view was also put to us by the Society for the Protection of Unborn Children that there was no difference in principle because all destructive research on embryos is unethical (p 111).

5.4 The majority of our witnesses, however, did not see the additional purposes as raising new issues of principle. They regarded treating serious disease as at least as worthwhile as promoting advances in the treatment of infertility, and we find that a persuasive argument. In our view it is difficult to maintain that the embryo is being used instrumentally under the new purposes but not under the original purposes, one of which is developing more effective techniques of contraception, which can hardly be said to benefit the class of embryos. We accept that, as we explained in Chapter 2, at least initially, some of the research carried out under the Regulations is likely to be basic research, designed for example to understand the process of cell differentiation. Basic research is a necessary step to developing treatments and facilitating the potential use of adult stem cells and should be permitted under the Regulations in the same way as more directly applied research to which it is designed to lead, provided that it is subject to strict regulation.

Cell nuclear replacement

5.5 If the extension of the purposes had been the only point at issue in the Regulations, it is unlikely that they would have attracted the degree of attention that they did. What underlay anxiety about them was the perception that they would permit the creation of embryos by the technique of CNR—popularly described as cloning. That was seen as objectionable for two main reasons: first, because it would be one way of creating embryos specifically for research or therapeutic purposes; and, secondly, because it would be a step on the slippery slope to "reproductive cloning", that is the production of a baby by implanting the embryo generated by CNR in a woman's uterus and allowing full development. It was also seen as contrary to the spirit of the 1990 Act, section 3 (3)(d) of which prohibits "replacing a nucleus of a cell of an embryo with a nucleus taken from a cell of any person, embryo or subsequent development of an embryo", the only form of cloning known at the time.

5.6 CNR is the process of inserting the nucleus of an adult cell into a donated egg from which the original nucleus has been removed. Following CNR, if the recipient egg is induced to divide, an embryo can be produced. CNR was the first step in the process by which Dolly the sheep was created.

5.7 CNR is, potentially, a way of producing compatible tissues for patients which will not be rejected by their immune systems. It would involve creating a zygote by CNR using a nucleus from an adult cell of the individual to be treated, and growing it to the blastocyst stage. ES cells would be isolated from the blastocyst (which would be destroyed in the process) and differentiated in vitro to produce cells or tissue for implantation. The process is illustrated in diagram 1 The use for therapy of ES cells produced in this way has a potential advantage over the use of ES cells isolated from early embryos created by IVF, because the genetic material would be derived from the individual to be treated and so would not be rejected by the host immune system.

5.8 The procedure described in paragraph 5.7 is often referred to as "therapeutic cloning", to reflect the fact that it is envisaged only as a means of generating ES cells for direct application in treatment and therapies: the embryo itself is grown only to the blastocyst stage and is not implanted or allowed to develop further. This is in contrast with "reproductive cloning", in which the blastocyst would be implanted in a woman's uterus with a view to producing a baby. Thus, the distinction between "therapeutic" and "reproductive" cloning is based on the steps following CNR, and reflects the purpose for which it is undertaken. The initial process (to the blastocyst stage) is identical. Under the Human Reproductive Cloning Act 2001 the implantation in a woman of a CNR embryo is now a criminal offence. In this report we refer simply to the technique—cell nuclear replacement—by which a blastocyst is produced by CNR for non-reproductive purposes.

5.9 The majority scientific view presented to the Committee was that for practical reasons CNR is unlikely to provide a general basis for therapies in the foreseeable future. We were told that individualised treatments using the patient's own cells[36] would be difficult and expensive and would require a continuing supply of human eggs, which is unlikely to be forthcoming on a large scale. Some medical charities and patients' support groups argued that female members of a patient's family would be prepared to donate eggs for altruistic motives, and this is no doubt true in some cases. Opponents of CNR argued that it would be difficult to avoid pressure being brought to bear on potential donors, although that is a problem that has up to now been dealt with successfully in the United Kingdom by strict regulation of gamete donation, including a prohibition on payment. As a response to these problems it has been suggested that CNR might be used to generate a bank of ES cells from which the best "match" with the patient could be selected to minimise the risk of immune rejection. Several thousand ES cell lines generated by this process would be required. Whether this is a realistic possibility remains to be seen.

5.10 However, even if CNR does not become a general basis for therapies in the foreseeable future, it still has significant potential as a research technique since it would provide a powerful approach to studying the process of dedifferentiation. In producing Dolly the sheep CNR has shown that dedifferentiation of adult cells is possible and gave a major impetus to research into that process. The biochemical signals which control the process of dedifferentiation and maintain the genetic material in a pluripotent state are contained in the oocyte (female egg). CNR research at present provides the only realistic means of identifying these factors and establishing how to reverse the signals that "mark" the DNA during differentiation and must be erased during dedifferentiation.

5.11 The Regulations make no direct reference to CNR. The 1990 Act did not specifically prohibit the creation of embryos by CNR—the technique had not been used successfully on mammals at that time, and was not until Dolly the sheep was created in 1996; and the Regulations did not specifically authorise it. When CNR became a practical possibility the Department of Health was of the opinion, on the basis of counsel's advice, that the definition of "embryo" in the Act would include CNR embryos so that research on them—whether under the Act or the Regulations—would be regulated by the HFEA in the same way as research on fertilised embryos. This view has now been upheld by the Court of Appeal (although, as noted in Chapter 1, there is the possibility of a final appeal to the House of Lords).

5.12 No application has been made to the HFEA for a licence to create embryos by CNR for research related to the original purposes in the Act. As long as the purposes were limited to reproductive purposes, there was little reason to seek to create embryos by CNR. However, it is generally accepted that extending the purposes to understanding the causes of (and by implication developing treatments for) serious disease is likely to stimulate applications to do research involving CNR embryos.

5.13 The 1990 Act already allows embryos to be created for research, although as noted in Chapter 3 only 118 have been created for research purposes since the Act came into force. A few of our witnesses drew a distinction between the creation of an embryo (for research) by IVF and by CNR on the ground that the latter represented a further step away from natural means of creating embryos. But the main ground of opposition to the creation of embryos by CNR was that it would increase the likelihood of such embryos being implanted in a woman. We discuss this "slippery slope" argument later in this Chapter. Although there is a clear distinction between an IVF embryo and an embryo produced by CNR (or other methods) in their method of production, the Committee does not see any ethical difference in their use for research purposes up to the 14 days limit.

5.14 The Committee concludes that, even if CNR is not itself used directly for many stem cell-based therapies, there is still a powerful case for its use, subject to strict regulation by the HFEA, as a research tool to enable cell-based therapies to be developed. However, as with embryos created by IVF for research, CNR embryos should not be created for research purposes unless there is a demonstrable and exceptional need which cannot be met by the use of surplus embryos.

Oocyte nucleus transfer

5.15 Oocyte nucleus transfer, a process akin to CNR, may have the potential for treating mitochondrial diseases. Mitochondria are small energy-producing structures present in every cell. They were described by one of our interlocutors as filling the role of batteries or a power pack. Most of a cell's DNA[37] is contained in the nucleus, but a very small amount (less than one per cent) is found in the mitochondria. Alterations in the mitochondrial DNA result in a number of relatively rare but very serious diseases. Mitochondria are present in the female egg, but are not transferred from the male sperm during fertilisation, so the mitochondria of the embryo are derived exclusively from the mother and mitochondrial diseases are transmitted only through the maternal line.

5.16 If a woman is a carrier of mitochondrial disease, oocyte nucleus transfer might offer the possibility of preventing its transmission to her children. Using this technique, the nucleus would be extracted from the woman's egg and transferred to a donated egg from which the nucleus had been removed. The egg could then be fertilised by IVF and implanted in the mother. The procedure is illustrated in Diagram 2. The resulting embryo would receive the vast majority of its genes from the mother and father in the normal way—it would not be a clone—but the small number of mitochondrial genes would come from a third person, the woman who donated the egg. This is sometimes characterised as the resulting baby having two genetic mothers.[38]

5.17 The Donaldson report noted that very little research has been carried out on this procedure, and that it would need extensive testing in animal models, and with human eggs, before it could be used therapeutically in humans. [39]

5.18 It has been suggested that oocyte nucleus transfer would constitute a breach of the prohibition on germ-line gene therapy.[40] Because of the transmission of mitochondrial DNA, the procedure would involve a (relatively small) modification of the human genome.[41] However, this issue does not arise at the research stage, which is the extent of our remit, and should not therefore be a barrier to research.

5.19 A further objection that has been raised is that the procedure would breach the 14 days limit for human embryo research. We do not see that research into oocyte nucleus transfer would breach the 14 days limit any more than it does with CNR. The Human Genetics Advisory Commission and the HFEA concluded in their 1998 Report that CNR would not breach the 14 days limit.[42] They said, "whether the nucleus to be replaced in an enucleated oocyte is taken from an adult or from another embryo, the clock is put back to the beginning, embryonic development starts over again and the primitive streak stage specified in the Act would still not be reached within the 14 day time limit".

5.20 The Regulations with which we are concerned relate only to research. There is no doubt that mitochondrial diseases are serious diseases and oocyte nucleus transfer may have great potential for treating them. There is a strong scientific and medical case for further research into it and we conclude that if CNR is permitted in certain limited circumstances, oocyte nucleus transfer should also be allowed for research purposes.

"Reproductive cloning"

5.21 The question of human reproductive cloning is not central to our terms of reference, since it was never envisaged that it would be permitted under the Regulations. However, we have examined the issues surrounding it because of the argument that the use of CNR for research purposes represents a slippery slope to reproductive cloning.

We set out our analysis in more detail in Appendix 6. In summary the Committee's conclusions are that:

    (a)  given the high risk of abnormalities, the scientific objections to human reproductive cloning are currently overwhelming;

    (b)  there are further strong ethical objections in addition to those based on the risk of abnormalities, although not all the arguments deployed against reproductive cloning are equally valid. The most powerful are the unacceptability of experimenting on a human being and the familial and child welfare considerations arising from the ambiguity of the cloned child's relationships; and

    (c)  the Commitee unreservedly endorses the legislative prohibition on reproductive cloning now contained in the Human Reproductive Cloning Act 2001.

5.22 Is there then a risk that allowing the use of CNR for research purposes would make reproductive cloning more likely? In so far as the starting point is the same, there is no doubt that developing the CNR technique would in technical terms facilitate reproductive cloning. But the fact that a technique developed for a worthwhile purpose may be used for different, unacceptable, purposes is not a conclusive argument for prohibiting it. Both the potential benefits and disadvantages and the level of risk and possible safeguards need to be taken into account.

5.23 Some pronouncements give the impression that it would be a simple matter to produce a cloned baby. This is far from the case. Apart from the practical problems referred to in Appendix 6, it would require a well-equipped fertility clinic and the services of a number of different specialists. Any clinic participating in this work would lose its licence from the HFEA, and the personnel involved would now be at risk of committing a criminal offence punishable with ten years' imprisonment.

5.24 The HFEA has an excellent record in ensuring that IVF clinics comply with the law, and we are satisfied that its regulatory powers, now reinforced by a specific statutory prohibition, provide sufficient protection against the development of CNR leading to reproductive cloning in the United Kingdom.

5.25 The regulatory system in the United Kingdom cannot, of course, prevent attempts to undertake reproductive cloning in other countries. We discuss in Chapter 7 the case for seeking to negotiate an international ban on reproductive cloning.

i.e. using CNR to produce cells or tissue genetically identical to the patient's. These considerations would not apply to the same extent if CNR were used to create stem cell lines. Back

37   Deoxyribonucleic acid-the cell's and the body's genetic material. Back

38   An alternative approach to preventing the transmission of mitochondrial disease would be simply to use a donated egg for fertilisation by the father's sperm, but the resulting embryo would not, of course, then contain any of the mother's genetic material. Back

39   Paragraph 4.25. Back

40   A modification of the human genome in which a person's genetic material (DNA) is altered in the germ cells such that the alteration can be passed to the next generation. Back

41   The complete genetic material of an individual. Back

42   Cloning Issues in Reproduction, Science and Medicine, December 1998. Back

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