Introduction

The Royal Society of Edinburgh (RSE) is pleased to respond to the call for evidence from the House of Lords Select Committee on Stem Cell Research. The RSE is Scotland’s premier Learned Society, comprising Fellows elected on the basis of their distinction, from the full range of academic disciplines, and from industry, commerce and the professions. This response has been compiled by the General Secretary with the assistance of a number of Fellows and experts with substantial experience in this area.

The specific questions identified in the call for evidence are addressed below.

Do the additional purposes in the 2001 Regulations raise issues of principle different from the purposes specified in the 1990 Act?
The Society believes that there are no different real or substantive issues to be considered. Nevertheless, there are two more subtle issues which may be of importance. First, it could be argued that the purposes served by the additional grounds of permissible research on human embryos are of more importance than those which have been permitted since 1990. This is not in any way to lessen the value of research into infertility, but the possible therapeutic benefits of stem cell research which may provide therapy for more common, and more life-threatening, conditions may benefit many more people. Second, caution is required, in that these benefits are only potential. At a recent meeting of European experts in this field, the clear impression was given that the realisation of these benefits was still a long way in the future.

There is a range of different views world-wide on the acceptability of research on embryonic stem cells. What considerations underlie these differences? Do changes in the law here have implications for practice overseas and vice versa?
Attitudes in Europe differ greatly. Sweden already permits embryo research for stem cell derivation, and France and the Netherlands appear to be moving in a similar direction. Resistance in Germany, however, is on a par with their resistance to any manipulation of human embryos, and has an historical basis following the Nazi eugenics programme. In other European countries (such as Ireland), resistance appears to arise from religious conviction, which again would not readily permit the manipulation of embryos, and certainly would not endorse their deliberate creation for research purposes. Further consideration of the range of ethical and religious positions in Europe can be found in the European Group on Ethics in Science and New Technologies publication "Adoption of an Opinion on Ethical Aspects of Human Stem Cell Research and Use" (January 2001).

The UK legislation now provides the international community with a model framework in which embryonic stem cell research can proceed under statute and with due oversight. Other countries, such as Japan and France, are preparing to adopt similar measures, persuaded by the compelling scientific arguments for the use of human embryonic stem cells and the need to regulate research use of human embryos. In the USA it is illegal to use federal funds to isolate embryonic stem cells but not to work with cells isolated elsewhere, although many argue that this is illogical and the use of federal funds to isolate embryonic stem cells should be allowed. Changes in the law here could, therefore, set a precedent that could influence law changes elsewhere.

Changes in the law in the UK, however, are arguably unlikely to exert influence on those countries influenced by either the religious or historical ground mentioned above, although it is possible that a movement of scientific researchers towards the UK might result. In addition, if therapies that show sustained success at not unreasonable cost result from this work, it is likely for them to become available throughout the developed world, irrespective of where they are devised.

Have increased globalisation and other international commercial developments, in relation, for example, to e-commerce and patenting, changed the context of the debate in the UK? Would issues relating to research on embryos benefit from more attention at international level?
Increased globalisation has not, of itself, changed the context of the debate on this issue in the UK. However, should stem cell research prove effective, it is inevitable that issues of commercialisation and patenting will arise and it is likely that there will be a potential backlash against this research if profit from human embryos becomes a realistic possibility. Commercialisation of human bodies or their parts is already under active consideration in Scotland as part of the work of the Review group on Retention of Organs at Post Mortem which will be producing a final report later this year. Resistance to commodification of human parts is also evidenced in the terms of the Human Organ Transplants Act 1989, and in the debate over surrogacy. Generally speaking, although not-for-profit interventions are welcomed, the debate tends to shift when finance is involved.

In common with the scientific struggle between private and public research in relation to commercialisation of the Human Genome Project, this is an issue that merits considerable international concern and co-operation.

What are the potential medical benefits of stem cell research? What is the most likely time-scale for realising them? What are the potential risks?
The potential benefits of stem cell research are in providing treatments by in situ tissue repair for a wide range of common degenerative diseases, some of which are currently intractable, such as neurodegenerative diseases, and others like heart failure are treatable only by organ transplantation with all its problems of donor availability and tissue rejection. Enhanced tools for drug discovery may also become possible and stem cell research would also bring an understanding of the developmental determinative processes which will confer medical benefits in due course.

Until recently, however, these arguments were essentially theoretical, derived by analogy with well-characterised mouse embryonic stem cells. It is significant therefore, that although only a handful of research groups have had access to human embryonic stem cells, there has already been important progress. Human embryonic stem cells can now be cultured in large numbers, clonally propagated, genetically manipulated, differentiated in alternative ways under the influence of specific growth factors, and induced to form mature cardiac and neuronal cell types. Thus there is now convincing evidence that human embryonic stem cells will provide a defined and expandable source of a wide range of normal cell types. Success with medical benefits, however, are only likely to come gradually. As an estimate, some limited success may be expected in experimental cases with more accessible conditions such as Parkinson's disease within a few years. 'Effective cures' in such cases and some success with less accessible conditions can be expected only much later, for example, in twenty years. It is expected, therefore, that developments will continue for the remainder of this century at least.

Risks fall into two categories. First, risk to the patient which, as for any treatment, would have to be assessed in preclinical experiments and in clinical trials, such as inability to control stem cell differentiation adequately leading to the formation of inappropriate tissues and possibly tumours. Second, risks for society that treatments may, at least initially, be too expensive for widespread use. However, this is often the case for 'novel' treatments (such as heart and liver transplants) which subsequently become widely available because technical refinements usually follow that bring down the cost.
There are differing views on the extent to which potential treatments could be developed from non-embryonic stem cells, such as adult and umbilical cord stem cells. What are the advantages and disadvantages of working with these alternative sources of stem cells?
There has been a revolution recently in our understanding of the plasticity of adult stem cells. While it used to be thought that their developmental capacity was restricted to cell types in the organs in which they reside, it is now clear that it can be much broader, and this opens up a range of new possibilities for using adult stem cells for regenerative medicine. The use of these cells would avoid the ethical issues raised by destruction of embryos and nuclear transfer.

However, this research is in its infancy and it is not yet clear that everything that might be achieved with embryonic stem cells would be possible with adult stem cells. For instance, adult stem cell numbers are limited and it is not yet clear to what extent their properties could be maintained in culture and, therefore, it is not clear whether or how they could be used clinically. By contrast, there is much greater understanding of embryonic stem cells, based on 20 years of investigation in the mouse. Most crucially, it is known how to propagate human embryonic stem cells in large numbers. It is, therefore, realistic to anticipate clinical applications of human embryonic stem cells in the near term.

For the moment at least, the necessary strategy is to appreciate that for the development of the best treatments, research on embryonic, foetal and adult stem cells are not alternatives but are highly complementary, and should be pursued in parallel.

What are the commercial interests involved in research in this area? Does increased commercial involvement create additional ethical difficulties?
The possibility of effective therapies will certainly be of great importance for commercial exploitation. For example, a single US corporation, Geron, is asserting a monopolistic position on human embryonic stem cells and also on "therapeutic cloning".

The business practices of the biotechnology industry, therefore, need to be carefully circumscribed so that second order ethical problems do not arise. For example, it is debatable whether the issuing of a patent on such a fundamental resource (and highly questionable "invention") as human embryonic stem cells is in the public interest given the potential healthcare implications. In addition, the drive to patent and reap rewards from specific developments has long meant their non-availability (on grounds of cost) in some regions of the world. There would also be potential resource issues even within the UK. Once a therapy becomes available, it may be that a legitimate claim to receive it could be mounted, particularly in light of the terms of the Human Rights Act 1998, and Strasbourg jurisprudence in this area.

Human reproductive cloning (the transfer of an embryo created by cell nuclear replacement into a woman's uterus) is unlawful in the UK, and the Government has announced its intention of reinforcing this ban by specific primary legislation. Is there likely to be any pressure to resist such a ban? What are the principal ethical (and scientific) arguments against human reproductive cloning?
There is likely to be limited opposition to an affirmation of, and extension to, the current ban on human reproductive cloning.

As is true in much of science, it is the intention behind and use of the technology which should be addressed, but all too often the technology itself is focussed on. There is nothing inherently wrong, arguably, in reproductive cloning, although there may be ‘bad’ reasons for undertaking it. Of course, there are sound practical reasons not to attempt it for the moment. In experimental animal studies the success rate from reproductive cloning has remained at about 1% despite considerable effort to increase it, and there is a high incidence of birth defects. This being the case, there is little prospect of developing a satisfactory technique for human cloning, since the experimental stage would not be acceptable. However, if the technology to provide it safely and efficaciously did exist, it would be important that a rational and reasoned debate took place.

There may be acceptable reasons for human cloning, which might, for example, include the creation of a child following the death of another- especially if the intending parents are now infertile, so long as it is clear that the clone will share only the physical characteristics of the deceased child. The use of cloning for some reasons might legitimately be banned but there may be merit in exploring whether or not cloning is always wrong, before implementing a blanket ban.

Does the extension of embryonic stem cell research, and, in particular, the technique of cell nuclear replacement therapy (therapeutic cloning) - designed to grow tissue for therapeutic purposes - increase the likelihood of human reproductive cloning in the future?
The extension of embryonic stem cell research and therapeutic cloning may have a peripheral impact on the likelihood of reproductive cloning in refining some of the necessary technology. However, this will only be minimal in terms of the complexities of the later stages of development and will not address the reasons for reproductive failure.

Has the regulatory framework established by the 1990 Act operated effectively? Is it likely to remain adequate for the foreseeable future? Have any gaps appeared in the regime as a result of developments since 1990?
The Human Fertilisation and Embryology Authority (HFEA), created by the 1990 Act, has proved itself to be an effective mechanism for regulation. When the law intervenes in these areas, it is preferable to have ‘permissive’ rather than ‘directive’ legislation, permitting the exercise of an element of discretion which renders the legislation flexible and able to reflect changing attitudes, whilst at the same time giving the authorities the power to monitor and police practices, and prevent practices which are regarded as unacceptable. One criticism, however, which would be true of any similar organisation, would be that in exercising discretion, the body assumes to itself the power and responsibility for setting, as well as reflecting, the boundaries of acceptable practice. In the light of the openness and accountability which such decisions may require, it might be argued that more could be done to ensure that any public unease about this is alleviated.

Do additional guidelines need to be developed to assist the Human Fertilisation and Embryology Authority in issuing licences in accordance with the new Regulations? If so, what should the guidelines contain?
The HFEA is well used to dealing with research proposals which are speculative, as would be the case with much early stem cell research. However, limited publicly debated regulation, in parliament and elsewhere, would be beneficial in respect of embryonic stem cell research, not least because it may help to ensure that any public unease about this technology is alleviated.

In addition, because of the concerns about the use of human embryos in research projects, care should be taken to ensure that the deliberate creation of embryos for research purposes should be kept to a minimum, in order to allay the fears of those who might see this as a ‘slippery slope’. In fact, once embryonic stem cells have been isolated from an embryo they appear to multiply without limit in the laboratory, although their properties can become compromised with extended multiplication. Consequently after an initial panel has been established, there should be only limited need for isolation of new stem cells from human embryos. In their guidelines for human embryonic stem cell research it may, therefore, be appropriate for the HFEA to require that all derived human embryonic stem cells should be deposited within a "Stem Cell Bank" from where they could be distributed to legitimate researchers. This would avoid the need for multiple laboratories to each derive their own stem cells and would enable HFEA to monitor the number of human embryonic stem cell lines being produced. The HFEA, in conjunction with the Medical Research Council, will then be in a position to ascertain the need for continued derivation of new lines in the future and to ensure that there is no unnecessary use of human embryos.

Additional information
In responding to this inquiry the RSE would like to draw attention to the following Royal Society of Edinburgh responses which are of relevance to this subject: Animal Tissue into Humans (April 1997); Consent and the Law (December 1997); Cloning Issues in Reproduction, Science and Medicine (April 1998); Review of the Common Law Provisions Relating to the Removal of Gametes and of the Consent Provisions in the Human Fertilisation and Embryology Act 1990 (April 1999); Chief Medical Officer’s Expert Group on Cloning (November 1999); Preimplantation Genetic Diagnosis (March 2000); Healthcare in 2020 (September 2000) and Inquiry into Human Genetic Databases (October 2000).

Professor Peter Wilson CBE
General Secretary

1 June 2001

Further information is available from the Research Officer, Dr Marc Rands