Ethics, legal, social, counselling Regulation of therapeutic cloning in the UK

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1 RBMOnline - Vol 5. No Reproductive BioMedicine Online; on web 22 April 2002 Ethics, legal, social, counselling Regulation of therapeutic cloning in the UK Ruth Deech is Principal of St Anne s College, Oxford University and a lawyer by training. From she chaired the UK Human Fertilisation and Embryology Authority, a body established by law in 1990 to oversee and regulate the practices of IVF and embryo research and storage in the UK, to keep records and to give advice to the government and the public. She guided the Authority through many complex ethical and legal problems, while retaining the respect of patients, politicians and professionals within the field. The Authority stands as a model organization, making decisions that are accepted instantly. It is also admired overseas for the impartiality of its decisions. Dr Ruth Deech Ruth Deech St Anne s College, Oxford OX2 6HS, UK Correspondence: Ruth.deech@st-annes.ox.ac.uk Abstract The history and responsibilities of the British Human Fertilisation and Embryology Authority are described. Its establishment by law in 1990 and its duties of licensing clinics, issuing a Code of Practice, maintaining a Register of treatments, giving advice and licensing new treatments are traced. Although research on embryos was legalized in the UK in 1990, a change in the law was required in 2001 to permit therapeutic cloning and research on embryos for the purposes of seeking treatments for serious disease. The detailed process of licensing stem cell research is described, together with a description of new licences issued and the legal challenges to the new law and to the licences that have been issued by the Pro-Life Alliance. An account is given of the ban on reproductive cloning contained in the Human Reproductive Cloning Act 2001 and the findings of the House of Lords Select Committee on Stem Cell Research, It is concluded that the mechanisms exist in Britain to regulate stem cell research in an ethical fashion and to prohibit reproductive cloning by law. Keywords: cloning, embryo research, stem cells, therapeutic Cloning, embryo splitting, egg freezing, sex selection, storage of ovarian and testicular tissue, babies born to women of 62, and posthumous insemination: a few years ago, hardly any of us would even have heard of these things. Yet now they sound all too familiar, such has been the pace of development in assisted reproduction. Over 50,000 babies have been born by IVF in Britain since But the issues are not simply ones of science and medicine. People have quite rightly become very concerned about what the scientific possibilities are. They are more concerned today about ethical issues than they were 10 years ago, and particularly so in the wake of the publicity surrounding the completion of the Human Genome Project and its potential. While recognizing the benefits that scientific developments can bring to individuals, people are anxious about the effects on society as a whole, and fearful for the integrity of humanity and the welfare of babies. They have become alarmed at the growth of genetically modified crops, embryo use and the spread of mad cow and foot and mouth disease. Distrust of the motives of scientists and doctors has grown because of the intrusion of commercial gain in the growth of knowledge about ourselves. Uniquely in medicine, and almost uniquely in the world, social and legislative Paper based on contribution presented at the Second Expert Organon meeting in Rottach-Egern, Germany, March controls have been put in place in Britain by society over the way in which this field of medicine develops. The British Parliament recognized the mood of anxiety when in 1990 it passed the Human Fertilisation and Embryology Act, which established the Human Fertilisation and Embryology Authority (HFEA) to regulate certain assisted conception practices and embryo research. The Act broke new ground in the relationship between medicine and the law. In August 1991, the HFEA took up its task of regulating research using human embryos, the storage of gametes and embryos and the use in treatment of donated eggs and spermatozoa and of embryos produced outside the human body. As a regulatory body, much of the HFEA s work relates to the inspection and licensing of clinics carrying out IVF and donor insemination, and laboratories undertaking embryo research. The members of the Authority ensure that human embryos are used responsibly and that infertile patients are not exploited at a vulnerable time (80% of the treatments are carried out privately, not under the National Health Service). I was the Chairman of the Authority for over 7 years. This is a 7

2 8 part-time job, of 2 days a week. I am the Principal of an Oxford University College and a lawyer by training, having spent many years teaching Family Law. The HFEA has 21 members appointed by UK health ministers after advertisement. The members determine HFEA policies and scrutinize treatment and research licence applications. The 1990 Act requires that the Chairman, Deputy Chairman and at least half of the membership are not doctors or scientists involved in human embryo research or providing infertility treatment. The responsibilities of the HFEA are as follows: (i) To licence and regulate clinics carrying out IVF, the use of donated gametes, donor insemination, gamete and embryo storage, and human embryo research. (ii) To maintain a Code of Practice giving guidance on the proper conduct of licensed activities. (iii) To maintain a register of licensed treatments given, and of the children born as a result. (iv) To give advice and information to licensed clinics, to prospective patients and to the public. (v) To keep the field under review. (vi) To give advice, when asked, to the government. In Britain we believe we are ahead of the field, not only in the quality of research but in its public acceptability and respectability. This is, we believe, due to the legislation and the tight regulation. In this paper, I wish to examine how we have legislated for and regulated the two most innovative and potentially dramatic new developments in this field. Therapeutic cloning needed a change in secondary legislation in Britain in 2001 to ensure its legality. Preimplantation genetic diagnosis has been approved by the HFEA within the powers already granted to it within the Act of The 1990 Act permitted the use of embryos in research, and the creation of human embryos specifically for research provided certain conditions were met, but only for a number of purposes set out in the Act. These are mainly connected with problems related to conception. Parliament also recognized the potential, in the light of future developments, for embryos to be used in research into the causes of conditions other than those connected with conception. A regulation-making power was included in the 1990 Act [Schedule 2 para. 3 (3)] to extend the purposes to include research aimed at increased knowledge about the creation and development of embryos, increased knowledge about disease and enabling such knowledge to be applied. In February 1997, the birth of Dolly the sheep in Scotland was announced. Although a form of cloning was banned by the 1990 Act in relation to humans [S.3(3)(d): 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. ], prior to 1997 scientists did not consider that cloning by cell nuclear replacement using a nucleus taken from an adult cell was likely to be achievable in mammals for many years (although this had been shown as a possibility in frogs in the 1960s). Late in 1997, the Human Fertilisation and Embryology Authority together with the Human Genetics Advisory Commission undertook a public consultation on the issues raised by cloning. The resulting report, Cloning issues in reproduction, science and medicine, was published in December It reported that concern expressed about human reproductive cloning, including safety and other ethical issues, was widespread and supported a total ban on its use for any purpose. However, many saw benefit in new techniques that might be developed to treat serious medical conditions. The report considered these applications. It concluded that the legislation of 1990 had proved effective in dealing with new developments relating to human cloning and that in particular the Act was adequate to forbid human reproductive cloning in the UK. Nevertheless, it suggested that for the allaying of public fears the British Government might consider the possibility of introducing legislation that would explicitly ban human reproductive cloning regardless of the technique used. The Government has pledged to do so. The report also recommended that the Government should consider extending the law to permit two further purposes for which the HFEA might issue licences for research, so that potential benefits can clearly be explored. First, the development of methods of therapy for mitochondrial disease and second, the development of therapeutic treatments for diseased or damaged tissues or organs. The report considered also the need for international legislation to prohibit reproductive cloning. It recognized that what is prohibited in one country may become possible by migration of scientists or patients to another country where there is no legislation or a more liberal attitude. This possibility is reinforced by the European Treaty principles of freedom of movement to seek medical services and freedom of movement of goods and services. There is great difficulty in finding mutually acceptable and internationally agreed definitions for even quite simple concepts. An international lawyer will appreciate that it is well nigh impossible to frame an international treaty, widely agreed, that will prohibit any development in the limits of embryo research and cloning. The public attitude in Britain to cloning indicated that concerns were less about entitlement to a unique genetic identity, but more about collateral issues like confidentiality and consent. The consultation process also highlighted the need for greater public understanding of human genetics. The report saw, however, no new ethical issues in the use and creation of embryos for research, whether by standard IVF or by cell nuclear replacement (CNR), above and beyond those posed and accepted in Human embryo research was permitted in 1990 for the following purposes, to which therapeutic cloning has now been added: To promote advances in the treatment of infertility. To increase knowledge about the causes of congenital disease. To increase knowledge about causes of miscarriages. To develop more effective techniques to contraception. To develop methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation. All research that involves the creation, keeping or using of human embryos outside the body must be licensed by the HFEA. The HFEA cannot authorize the use of human embryos

3 in any research project unless it appears to be necessary or desirable for the purposes outlined in the 1990 Act. Any research applications submitted to the HFEA must have Research Ethics Committee approval. The project must explain its objectives, protocols and why the research is necessary. The peer review process is very important. Before considering a research application the HFEA obtains at least two peer review reports on the project s merits. The HFEA has a panel of peer reviewers who are recognized national and international experts in the field of reproductive biology and infertility. Peer reviewers are required to declare any conflict of interest in relation to an application that is being considered. Additional peer reviewers are recruited when there is a need for specialist expertise not currently available on the panel. Licence Committees consisting of five HFEA members are arranged to consider applications and the peer review reports, and they also consider the information given to donors. The HFEA considers the detailed research application by the laboratory, which includes the CVs of all staff participating, information given to patients, relevant clinical and laboratory protocols, consent forms regarding use of embryos and any relevant publications. Before any licence is granted, the laboratory is inspected by the HFEA, an inspection that lasts 1 day. The HFEA holds data on the number of embryos created for IVF at each clinic, and also the number of embryos used in research, so that this ratio can be monitored carefully. Peer reviewers are routinely asked to comment on the numbers of embryos that the clinic proposes to use in the project. In the 1990s 118 embryos were created solely for research purposes, but 55,000 were donated for research as surplus to IVF requirements. About 30 embryo research projects are licensed at any one time. In 2000 the whole country and its legislators were engaged in a deep debate on whether it was moral or practicable to extend the purposes for which embryo research may be permitted. Although, as described, embryo research has been carried out since 1990, many members of the public were unaware of this, although their susceptibilities have been heightened by the publicity given to the Human Genome Project and advances in reproductive medicine. The prospect of creating embryos for research by cell nuclear replacement caused especial alarm and the deeply held belief on the part of a section of the public that the soul enters the body at the moment of fertilization was again aired. In the end, after a passionate debate in the House of Commons and the House of Lords, a large majority in each House approved new regulations which came into force on 31 January 2001 specifying additional legal purposes for embryo research: increasing knowledge about the development of embryos, increasing knowledge about serious disease, or enabling any such knowledge to be applied in developing treatments for serious disease. In response to the new regulations, the HFEA has enhanced its existing licensing system. Applicants to do this research will be required to justify why embryonic stem cells are to be used, rather than adult stem cells or animal stem cells. They will be required to provide detailed information on the fate of the stem cells throughout the project, keeping them within the licence project. Six-monthly progress reports will have to be submitted to the HFEA. Additional guidance has been provided to peer reviewers and new ones with expertise in the field have been sought. Three clinics are currently licensed to generate stem cells under the terms of the current research licences, and two more have applied to join them. The Centre for Genome Research in Edinburgh currently holds a research licence for stem cells, but the CNR technique is not involved. The objective is to investigate the optimal culture medium for human embryos and a way of ascertaining what a good embryo looks like. The Sheffield Fertility Centre and Jessop Hospital holds a licence to establish stem cell lines, again without using CNR. The objective is to study the genes and proteins expressed during implantation. The International Centre for Life, Newcastle, holds the third licence to study the cellular stress response and its effect on cellular differentiation. In February 2002, the HFEA granted the first two research licences involving the derivation of embryonic stem cells. The first was to the Centre for Genome Research to obtain embryonic stem cell lines to study preimplantation embryos, their development and congenital disease; to study teratocarcinoma; to provide a source of differentiated cells; to develop tissue regenerative therapies and to provide a model for placental development and reference for malignant trophoblast choriocarcinoma. The second licence is to Guy s Hospital, London, to isolate cells from human blastocyst stage embryos and to study the isolation and differentiation of neural and pancreatic cells from any stem cell lines. Although the monitoring will be a detailed and sensitive task, it is fundamentally no different from that which has been carried out by the HFEA over the last 10 years. We considered it all worthwhile because of the enormous potential of stem cells as a source of new tissue for therapeutic uses in the repair of damaged tissue and organs for a wide range of currently incurable disorders. Work in animals and early work to extract stem cells from human embryos support this position. At present, stem cells from embryos appear to have the greatest potential to be developed into the widest range of tissues. In the long term, but not in the short term, the scientific view is that it will be possible to reprogramme adult cells to make them behave like stem cells with the full potential of embryonic stem cells but without the morally more contestable need to create an embryo. Ethical opinion on the use of embryos in research as a source of stem cells is divided, but the view seems to have prevailed in Britain that it is more ethical to use scientific knowledge to relieve existing human disease than it is to block this research, especially when in the alternative embryos not required for infertility treatment may be allowed to perish, or scientists may go abroad to unregulated countries to carry out research forbidden in Britain. A remaining international problem regards lack of control over the stem cells themselves. Once isolated, they are not subject to the HFE Act, which does not cover them, and they could be imported from overseas without the need for regulatory control or, indeed, exported. The British Medical Research Council is leading a project to develop integrated systems for the banking of embryonic, fetal and adult stem cell lines, and developing mechanisms for the regulation of the derivation and use of such lines. A central stem cell bank will facilitate access to and the supply of stem cell lines for research, and ensure the quality of lines used, thus enhancing 9

4 10 the progress of research and ensuring thorough monitoring. A suitable site for the Stem Cell Bank is to be selected in Although the new law allowing extended categories of purposes of embryo research was passed by Parliament, in order to quieten political dissent the Government set up a Select Committee of the House of Lords to review the situation. The Committee was directed in particular to examine whether: (i) the use of embryonic stem cells was unnecessary because developments in adult stem cell research would suffice; (ii) it was unethical to use early human embryos, and (iii) the new law would put the UK on the slippery slope to human reproductive cloning. The Select Committee Report of February 2002 concluded that there is a clear scientific case for continued research in embryonic stem cells. It also concluded that research on embryos should continue and was not unethical, but that embryos should not be created specifically for research purposes unless there was a demonstrable and exceptional need that could not be met by the use of surplus embryos generated in IVF treatment. The use of cell nuclear replacement was approved with the same limitation. The Committee opined that it trusted the HFEA with its legal backing to stop any attempt at human reproductive cloning. It recommended monitoring of the outcome of embryo research projects and pointed out the need for guidelines illustrating the meaning of serious disease, as required in the new Regulations. Nevertheless, the Pro-Life Alliance opened an attack on stem cell research and on the use of embryos generally. In 2001 it had initiated a legal case attacking the breadth of the definition of embryo in the Act of It argued that there could be no embryo without fertilization and that since the procedure of CNR stimulated an embryo into growth by artificial means and not by the penetration of the egg by spermatozoa, this was no embryo. This argument succeeded at first instance in the High Court. This success meant that the HFEA would have had no control over cell nuclear replacement research and that there would have been no means of stopping human reproductive cloning. This seemed an odd result for the Pro-Life Alliance to seek, but presumably it brought the case in order to demonstrate that controls were weak and should be greatly strengthened by the Government. The Government responded to the judgment at first instance by a most speedily enacted new law, the Human Reproductive Cloning Act 2001, which says: A person who places in a woman a human embryo which has been created other than by fertilization is guilty of an offence. This could be punished by up to 10 years imprisonment. This statute should be sufficient to stop human reproductive cloning unless the day comes when embryos can be brought from fertilization to the birth of a baby by use only of an artificial environment and not the uterus. (This is not impossible to imagine: already the embryo can survive outside the womb for its first few days, and premature babies are kept alive if delivered after only around 23 weeks gestation, so an artificial womb environment would be required for only about 22 weeks of development.) The Government appealed against the first judgment and won a reversal in the Court of Appeal, where a constructive approach was adopted to the intentions of the 1990 Act in banning cloning. The Pro-Life Alliance announced their intention of appealing to the House of Lords. In a second attack, the Pro-Life Alliance challenged legally the vires of the two licences granted in February 2002 by the HFEA to researchers applying to do stem cell research under the new wider categories of research permitted by the 2001 Regulations. The basis of the case is that the diseases which might ultimately benefit from the stem cell research envisaged by the researchers are not serious, the qualification imposed by the Regulations. Examples have been given of diseases likely to be the subject of stem cell research including: repairs for spinal cord injuries, replacing lost heart muscles in cases of congestive heart failure, bone cells in osteoporosis and liver cells in cases of hepatitis, nerve cells in Parkinson s disease and following stroke, and replacing insulin producing cells in diabetes. Stem cell research does not mean that embryos will be allowed to develop into fetuses from which organs may be harvested. Nor does it mean that reproductive cloning allowing the development of a cloned individual will take place. Safeguards are the requirement that each individual research project will require a licence from the HFEA, that the proposed use of embryos is necessary for the purposes of the research, and that the consent of the couple whose gametes have been used to create the embryo have been given for the use of the embryo in this way. Breaches of the HFE Act are punishable under criminal law. It is hoped that it may be said with confidence that the research monitoring framework established by the 1990 legislation has been remarkably successful. The underlying principle that gametes and embryos may only be used in accordance with the specific informed consent of the individuals concerned has been a real strength. The clear framework, together with a degree of flexibility in implementation, have meant that the HFEA has been able to oversee progress on the medical and scientific front in a responsible and controlled manner. Problems that have arisen have been from individual failings and the paperwork rather than the structure and it is hoped that lessons have been learned. As Yvette Cooper, Parliamentary Under-Secretary of State for Public Health, said in Parliament on 19 December 2000, having referred to the debates in Parliament in 1990 on the moral issues of using embryos in research: If embryo research on infertility is acceptable, surely research for Parkinson s disease should be too? If embryo research for contraception is acceptable, surely research for muscular dystrophy should be too? Developments in stem cell research will be monitored in the future and it is hoped that some authority in Britain will be given the task of overseeing the guarding of stem cells once created. Even before the birth of Dolly the sheep in 1997 and the extraction and maintenance of stem cells from human embryos in 1998, there was considerably diversity around the world in the approach to embryo research generally. There is no international consensus on embryo research, nor any European consensus. Some countries within Europe ban embryo research altogether, others have no regulation at all. Germany, as the result of aspects of its history, bans any research that does not benefit the embryo itself. The USA has adopted the

5 approach of banning Federal funds for all cloning and research involving the extraction of stem cells from embryos, but does not prevent this being undertaken in the private sector. A recent report by the European Group on Ethics in Science and New Technologies to the European Commission, Adoption of an opinion on ethical aspects of stem cell research and use recognized the pluralism of approaches to these ethical questions. Britain is aware that its legalization of the research has led to considerable debate around the world. These issues are now the focus of attention and in some cases proposals for legal changes in the USA, France, Canada, Italy and Germany among others. They will no doubt continue to dominate debate into the foreseeable future as the potential (and ultimately real) benefits of this research for human health are recognized. The regulatory system in the UK is often held up as an example to other countries considering their own system of regulation of this area. To summarize, in the UK research using embryos is strictly governed by the HFE Act Among other things the Act requires: (i) that any research which involves the creation, keeping or using of human embryos must be licensed by the HFEA; (ii) that a separate licence is required for each research project; (iii) that the HFEA must be satisfied that the proposed use of embryos is necessary for the purposes of the research; (iv) that the people whose gametes are used have consented to their use in any research project; (v) that embryos cannot be kept or used after the appearance of the primitive streak or after 14 days, whichever is the earlier; (vi) that any embryo used in research cannot be implanted in a woman. In addition the HFEA requires that a properly constituted Ethics Committee should approve each research project before an application is made to the HFEA for a licence and reports must be made on the progress of the research. Over the past 10 years of its operation, the 1990 Act has shown that it is sufficiently flexible to meet the demands of the considerable advances in new technology. This is due in part to the way these issues are regulated, with the Act providing the framework within which the HFEA has some discretion to develop policies in line with developments. This has been demonstrated on many occasions, from licensing of intracytoplasmic sperm injection (ICSI) treatments in the early 1990s to more recent discussions with the Human Genetics Commission about Preimplantation Genetic Diagnosis. The Authority has been in place for just over 10 years and has overseen a remarkable increase in the number and complexity of treatments available. 11