Human Cloning and Stem Cell Research

The submission of the All-Party Parliamentary Pro-life Group

To the House of Lords Select Committee on Stem Cell Research 2001

Contents

1. Introduction
2. Legal issues
3. The Purposes of Research
4. "Therapeutic" and "Reproductive" Cloning
5. Embryonic and Adult Stem Cells
6. Mitochondrial Diseases
7. Conclusions
Appendix A. Medical Ethics and the Status of the Human Embryo
Appendix B. Recent Developments in Stem Cell Research
Appendix C. International opinion on Human Cloning
References
 

1. Introduction

1.1 On 7 March 2001 the House of Lords appointed a Select Committee [1] to consider and report on the issues connected with human cloning and stem cell research arising from the Human Fertilisation and Embryology (Research Purposes) Regulations 2001.[2]

1.2 We set out our views on the issue of human cloning in detail in our response [3] to the HFEA consultation document [4]. In that document we reiterated our view that a human embryo should be accorded the same respect as any other human being, and our consequent opposition to its treatment as an experimental subject. We addressed the specific issue of stem cell research in our response [5] to the Chief Medical Officer 's invitation [6] for views on questions relating to the use of human embryos in cloning research.

1.3 The Select Committee asks whether the regulations raise issues of principle different from the purposes specified in the 1990 [Human Fertilisation and Embryology] Act. We question whether the regulations are legally enforceable. We consider that the regulations allow 'pure' research on human embryos, without reference to clinical goals, for the first time.  We caution that the licensing of so-called 'therapetic' cloning will inevitably develop the techniques that will allow rogue scientists working outside the UK to effect the birth of a cloned baby.

1.4 Furthermore there have been recent rapid developments in stem cell research which remove all rational justification for the use of cloned embryos in treating diseases, and call into question whether he use of embryonic stem cells is required at all. We note reports that adult stem cells are already being used successfully to treat patients and regenerate heart tissue, before cell nuclear replacement in humans has even been attempted.

2. Legal Issues

2.1 The  Human Fertilisation and Embryology Act 1990 [7] (HFE Act) states that licenses shall  not be granted for research on human embryos unless
"it appears to the Authority to be necessary or desirable for the purpose of

a) promoting advances in the treatment of infertility,
b) increasing knowledge about the causes of genetic disease,
c) increasing knowledge about the causes of miscarriages,
d) developing more effective techniques of contraception, or
e) developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation,

 or for other such purpose as may be specified in regulations."

2.2 The Act further requires that such licences can only be granted if the HFEA is satisfied that any proposed use of embryos is "necessary for the purposes of the research".

2.3 In 1998 The Human Fertilisation and Embryology Authority  recommended [8]  that two further purposes be added to those listed above, namely:

and has indicated that it would grant licenses for the production of cloned human embryos by Cell Nuclear Replacement (CNR, the "Dolly technique") for such purposes. This involves the replacement of the nucleus of an egg cell by the nucleus of a somatic (body) cell, followed by stimulation of the egg with electricity to cause it to begin to divide. There is no fertilisation, and no sperm cell is involved in the process.

2.4 The Government has taken the view that CNR is covered by the 1990 Act, and that no change in the law is required to allow the HFEA to license research involving this technique:

"Yvette Cooper: Yes, our understanding of the current law is that the cell nuclear replacement technique is legal, but only under the strict regulations that apply, and only for purposes that are legitimate under the current law". [9]
2.5 This interpretation is disputed. In [3] we noted that:
"The HFE Act defines an embryo as 'a live human embryo where fertilisation is complete.' Since a cloned embryo has not undergone fertilisation, it might be argued that a cloned embryo is not an embryo for the purposes of the Act. If the courts were to adopt this interpretation, it would follow that the HFEA has no power to regulate the creation or keeping of cloned embryos."
2.6 On 26 January 2001 the Prolife Alliance was granted a judicial review of the new regulations based upon this argument. The hearing is due on 31 October 2001. If the Prolife Alliance wins its case, it follows that CNR, and embryos produced by CNR, are entirely outwith the HFE Act, and the regulatory powers of the HFEA. In this case the Government's repeated assertion that 'reproductive' cloning is illegal is also called into question. Primary legislation would be required to prevent the unregulated creation of cloned human embryos, for research or reproductive purposes.

2.7 It must be remembered that the HFE Act specifically prohibits cloning by the nuclear substitution of a cell which forms part of an embryo. ([7], section 3 (3)(d)). In 1990 it was assumed that cloning would involve the nuclear substitution of a fertilised egg. The intention of Parliament was clearly to ban human cloning whether for research or reproductive purposes. There was no discussion of cloning other than in this context, and certainly no suggestion that other methods of cloning such as the "Dolly" technique (then unknown) were to be permitted. The failure of the Act to cover such eventualities can only be described as a loophole.

2.8 It is not impossible that the courts would interpret this section in the sense in which it was clearly intended: as a ban on all human cloning. In this case cloning by CNR is currently illegal, and the HFEA has no power to license it.

2.9 The Government's contention that CNR is both legal and regulated by the HFEA requires the courts to take a 'narrow' interpretation of the ban on cloning in the 1990 Act, and at the same time a 'wide' interpretation of the definition of an embryo. Unless the courts concur on both counts the new regulations will be unenforceable. Indeed the fact that the Government has promised to introduce primary legislation to ban 'reproductive' cloning is evidence that it is unsure of its position.

2.10 In our view this situation is as objectionable in principle as it is unsafe in practice. It is to be hoped the position will be clarified by the outcome of the judicial review. However these issues can only properly be resolved by the introduction of new primary legislation to deal with all aspects of human cloning.

3. The Purposes of Research

3.1 The regulations laid before Parliament differ from those originally proposed by the HFEA and considered in the public consultations in 1998/99. They state:
"A licence may be issued for the purposes of--
(a) increasing knowledge about the development of embryos;
(b) increasing knowledge about serious disease; or
(c) enabling any such knowledge to be applied in developing treatments for serious disease".
3.2 The difference between this formulation and that of the consultation document, and the original 1990 Act is most significant. The effect of the 'or' is that "(a) increasing knowledge about the development of embryos" may stand alone without any reference to serious disease or the treatment thereof in (b) and (c). The reaction of Lord Habgood to this formulation was:
"Quite honestly, when I read them I was shocked.  ... That could legitimate almost anything. Anything one could think of could come under those headings". [10]
3.3 The basis of the 'safeguards' provided by the 1990 Act is that research on human embryos would be allowed only if directed towards certain clinical goals deemed sufficiently worthy. The new regulations for the first time allow pure research for "increasing knowledge about the development of embryos" without reference to any such goal. This makes a nonsense of many of the assurances given by Ministers in the the debates on the regulations in both Houses.
"Yvette Cooper: Of course embryo research should not be permitted for just any old thing. That is why the regulations specify serious disease. We are talking not about the common cold but about spinal injuries, burns, osteoporosis, stroke, cancer, heart disease--about serious disease and disability. ... The 1990 Act states that the HFEA must satisfy itself for each and every research proposal that the embryos are necessary for the research. If another way to do the research exists--through adult stem cells--the research cannot be licensed under the law. The checks are already built into the law, and so they should be.". [9]

"Lord Hunt of Kings Heath: In any event, the 1990 Act already provides the answer to the question of what happens if and when research into adult cells overtakes research using embryos: embryonic research would have to stop because the use of embryos would no longer be necessary for that research. [10]"

3.4 These assurances are entirely without foundation if the research has been licensed under (a) above. If and when embryonic stem cells are no longer being used in research relating to serious diseases, the use of embryos would still be permitted for pure research into embryology. It is also clear that any research licensed under (b) and (c) could and presumably would be licensed under (a) also.

3.5 We believe this is a point at which the new regulations depart entirely from the principles laid down in the 1990 Act. These were well summarised by Lord Hunt:

"The principles underpinning the use of embryos in research, on which the 1990 Act is based, are that the embryo of human species has a special status, but not the same status as a living child or adult; that the human embryo is entitled to a measure of respect beyond that accorded to an embryo of other species; and that such respect is not absolute and may be weighed against the benefits arising from proposed research." [10]
In other words experimenting on embryos is at least to an extent undesirable, and could not be justified by mere curiosity, but may be justified by more concrete benefits.

3.6 We have never understood how one is supposed to weigh a certain amount of moral wrongness against a certain amount of utilitarian benefit. It is like trying say whether an object is heavier than it is tall. Traditional medical ethics requires that one must establish the moral probity of a course of research independently of its possible benefits. Certainly one may weigh the benefits of a course of treatment against the disbenefits for a particular subject. But one explicitly may not weigh the disbenefits to the subject against potential future benefits to others. [Appendix A]

3.7 One effect of the 1990 Act was to downgrade 'pure' in favour of 'clinical' research. This is not a principle the we would support at any level. Just as we do not believe morally illicit research can be justified by potential benefits, we would not wish to restrict any morally licit scientific research on the basis that it not obviously useful for any particular purpose.  Scientific progress in the long term requires pure just as much as clinical research. It is not appropriate for Governments to 'pick winners' in medical research any more than in commerce. Future benefits can not be reliably predicted by scientists, let alone by regulators. To attempt to regulate research according to an estimate of its future clinical benefits is fundamentally misguided.

3.8 Nevertheless that is the principle adopted in the 1990 Act, and it finds expression in the requirement that research should be aimed at certain outcomes deemed of sufficient importance to justify sacrificing embryonic humans. It is in that context that the requirement that a project must be "necessary for the purposes of the research" must be understood. Once the acquisition of pure knowledge is added to the list of purposes this principle loses all meaning. The question whether an experiment is "necessary" to acquire the results of that experiment is simply the question whether the experiment is well-designed.

3.9 When the supposed "safeguards" provided by the necessity of the research for stated clinical outcomes is removed, no safeguard at all remains. Any well-designed experiment that a scientist might want to conduct on a human embryo would be licensed under the new regulations. Despite the fact that we have always maintained that the principles of the 1990 Act were incoherent, and that the "safeguards" provided were illusory, we find it most significant that those principles are now being quietly abandoned.

4. "Therapeutic" and "Reproductive" Cloning

4.1 The Government has sought to make a clear distinction between "therapeutic" and "reproductive" cloning, and insists that the licensing of "therapeutic" cloning will not lead to "reproductive" cloning.
Yvette Cooper: ... It is illegal to develop embryos created through cell nuclear replacement beyond 14 days. It is a criminal offence to implant embryos created through cell nuclear replacement in the womb. Human reproductive cloning is illegal.  [10]
4.2 As we have already noted, if the Government is correct in contending that CNR is both legal, and regulated under the HFE Act, it follows that reproductive cloning is also currently legal on the same basis. There is nothing to prevent the HFEA granting such a license other than its own decision, as a matter of policy, not to do so. It is for this reason that the Government proposes primary legislation to prevent "reproductive" cloning.

4.3 The terms "therapeutic" and "reproductive" draw neither an ethical nor a scientific distinction. They refer simply to the reasons for which a cloned human embryo is created. (Indeed as we will see, "therapeutic" cloning is a misnomer, since it is most unlikely that CNR will ever form the basis of a clinical treatment).

4.4 In practical terms, these are not just related processes, they are one and the same process. The techniques that would be developed to allow CNR to result in a healthy, dividing human embryo, would be published in international journals and could then be used by "rogue" scientists anywhere in the world to produce a cloned baby. If it is the Government's policy to prevent reproductive cloning from occurring, then the licensing of CNR projects will work directly against that objective. Indeed under these regulations it is not unlikely that the main technical hurdles to reproductive cloning would be overcome by British researchers working under licenses granted by the HFEA.

5. Embryonic and Adult Stem Cells

5.1 There has been much debate about the relative merits of embryonic and adult stem cell research.  This debate has moved on considerably since the consultations on 1998/99, and indeed since the publication of the Donaldson report [11].

5.2 It is important to distinguish not only between the use of adult and embryonic stem cells, but between embryonic stem cells derived from IVF programs (whether 'spare' embryos or those created specifically for research), and cloned embryos derived from the proposed CNR technique. It appears that there is no longer any plausible reason to use cloned embryos in this research.

Stem Cells from Cloned Embryos

5.3 The original rationale for the use of  cloned embryos is that this would allow the creation of pluripotent stem cells genetically identical to each patient. In [5] we wrote

"Despite the fact that some have suggested using stem cells derived from cloned embryos directly as part of a programme of treatment, it is becoming increasingly clear that a mature regenerative technology would be unlikely to use such a methodology.  ... It is more likely that tissue regeneration could utilize stem cells taken from the patients own tissues, or even ordinary, fully differentiated tissue. By the application of appropriate genetic switches, it would in principle be possible to culture any kind of cell in vitro, or to convert it, in a number of steps, into a stem cell or into any other kind of cell. Direct regeneration of tissues in vivo might also be possible.  ...  Hence it does not seem likely that nuclear substitution (or the formation of a human embryo by any other means), would form any part of a mature treatment programme. "
5.4 It seems that this argument is now largely accepted. The Donaldson Committee said in its report:
"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 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." [11]
5.5 Similar statements have been made by ministers in the parliamentary debates. This argument has been strengthened by recent developments (see Appendix B) confirming that adult stem cells are indeed pluripotent, and are in fact already being used to treat patients. It must also be remembered that donated eggs are in extremely short supply, and waiting lists for donated eggs for IVF are long. A treatment which required the use of a donated egg for each patient was never a realistic prospect. However there is still some confusion over this point. The Donaldson report goes on to say
"The Expert Group concluded that the potential benefit of discovering the mechanism for reprogramming adult cells and thereby providing compatible tissue for treatment justifies this transitional research involving the creation of embryos by cell nuclear replacement." [11]
5.6 This does not make sense. If embryos are to be used, not as part of a program of treatment for a particular patient, but in research to discover the mechanisms of cell differentiation, and hence the mechanism to reprogram adult cells, there is no advantage whatever in using an embryo created by CNR. The use of 'spare' embryos from IVF programs, or indeed those created specifically for research, would be equally effective. The only advantage that has been proposed for using cloned embryos is that they would be a source of stems cells genetically identical to a particular patient.

5.7 The argument for using embryos in stem cell research has moved on. The argument is now (as we predicted) that embryo research is needed in order to understand how to reprogram adult cells. But it must be clearly understood that this is no longer an argument, to any degree, for using cloned embryos. We submit that the case for permitting human cloning by CNR has entirely evaporated.

Stem Cells from IVF Embryos

5.8 Despite the fact that the original rationale for using embryonic stem cells has largely been abandoned, the case for their use, alongside adult stem cells is still being made forcefully.

"Yvette Cooper: ... At the current point in our knowledge, adult stem cells are not the easy alternative that some have suggested. Adult derived stem cells are few in number and hard to find. We do not know whether there are stem cells for every part of the body. Those that we can find take longer to grow and develop, and their potential to turn into a wide variety of different cells appears more limited.  Embryonic stem cells are a different story. They can renew themselves and develop into many kinds of cells and tissues. They could hold the key to learning how to turn the clock back on adult cells, and turn them into other cells instead.  Many researchers and scientists agree with the hon. Gentleman's point that the eventual aim is to use adult cells. Perhaps that will mean adult stem cells, perhaps ordinary adult cells in which the clock can be turned back to make them stem cells again. However, we are not there yet. Many people believe that we will never get there until and unless embryonic stem cell research is carried out first. Those embryonic stem cells, with their power and potency, could teach scientists how cells grow and develop, and how to use adult cells as well. Until we make those breakthroughs--either from embryonic stem cells or from adult stem cells--the case for embryonic stem cell research is extremely strong." [10]
5.9 The greater "potency" of embryonic cells has clearly caught the imagination. But it must be understood that in a clinical context the ability of a stem cell to create many kinds of cell is a liability. The clinical aim will always be to treat a specific tissue with cells of a specific type: muscle with muscle stem cells, brain with neural stem cells etc. The possibility of muscle cells developing in a brain or vice versa is scarcely an advantage. This is one reason why the use of embryonic cells in treatment is much less desirable than the use of suitably reprogrammed adult cells.

5.10 The role of embryonic cells is now seen as providing the material for research into the basic mechanisms of cell differentiation, which may eventually allow adult cells to be reprogrammed, and tissue to be regenerated directly. It is quite plausible that embryonic stem cell research could contribute to the development of eventual treatments in this way. However the implication that embryonic stem cell research is necessary step in the process is simply not supported by the scientific evidence.

5.11 Early embryonic cells are many cell divisions, and many stages of differentiation away from adult tissue. Study of these cells may reveal the mechanism of the first few stages of cell differentiation. However clinical treatments will be mostly concerned with the last few stages of cell differentiation. It is simply not clear whether an understanding of the earliest stages of cell differentiation will have much bearing on an understanding of the later stages. It is not possible to anticipate the results of scientific research. (This is why it is so wrong-headed to decide the ethics of a research program on the basis of guesses at the results and the benefits that may derive from them).

5.12 On the other hand there are several other ways in which information on the processes of cell differentiation may be obtained:

5.13 The main animal model in embryological and developmental studies is the mouse. The higher animals share a basic body plan, and a complex of developmental genes (the Homeobox or Hox genes [12]) have been shown to be remarkably similar across a wide range of animals. The process of cell differentiation, particularly in its earliest stages, is expected to be equally similar. Of course there are differences between species and the differences between humans and animal models must ultimately be determined by comparisons with human tissue. There are two sources of human tissue which raise no ethical problems. Adult tissues may be studied in vivo, and increasingly in culture. Comparison of animal tissues with cultured human tissue will be one of the most powerful ways of determining the similarities and differences in the genetic switching mechanisms. Where direct evidence of human embryological development is required, naturally miscarried embryos may be studied post mortem. It must be remembered that prior to the development of IVF knowledge of human embryology was derived almost entirely from this source.

5.14 Of course all these methodologies have their problems. There are certainly circumstances in which the ability to experiment directly on live human embryos would provide a more straightforward means of resolving a question than drawing indirect inferences from other sources. Equally there are circumstances where the ability to sacrifice a baby or an adult would yield faster results than an ethically sanctioned research program. But it can not be said that any such process is necessary, or that science can not progress without it. The idea that there is only one route to scientific knowledge is naive. Medical science, in particular, has always operated under constraints protecting the welfare of human subjects. Where one avenue is closed for ethical reasons, another is found. Even when a major methodology is denied in human research (consider for example how often animal experiments require the sacrifice of the subject) it is possible to find alternatives. Yet there is no reason to believe that embryonic stem cell research is of greater importance than any of the other means of  research into the basic mechanisms of cell differentiation.

5.15 Some would have us believe that major advances are just around the corner, and would be prevented if research on stem cells derived from embryos is not allowed. Such claims are not credible and should not be believed. This is not the way science works. It is is never possible to predict future benefits with any certainly, and it is even less possible to say how they will be arrived at. To suggest that a particular ethically contentious avenue of research is absolutely necessary to save lives and effect cures amounts to moral blackmail, and in our view must be resisted.

5.16 It is not particularly surprising that such claims should be made. What is surprising is that so many parliamentarians should be unable to distinguish between scientific evidence, and mere assertion by scientists engaged in lobbying the Government.  In 1990 equally great and equally irresponsible claims were made for the results of embryo research in relation to infertility, genetic disease and miscarriages. Despite the notable lack of progress in any of these areas the proponents of embryo research have been able to sell the same horse twice.

Adult Stem Cells

5.17 The suggestion that cells derived from embryos, even at the present time, have greater clinical potential than adult stem cells is unsupported by the evidence. Where CNR is concerned, it is impossible to say if the technique has any potential at all, since it has not been demonstrated that the successful creation of a cloned human embryo can be achieved.

5.18 On the other hand there have been major recent advances in the use of adult stem cells, culminating in the apparently successful treatment of six heart patients with bone marrow stems cells by Professor Strauer of the Dusseldorf University Cardiac Clinic. Professor Strauer said

"Our results should show that it is possible to do this work without the ethically controversial embryonic stem cells [13]".
For a review of recent advances in the study of adult stem cells see Appendix B.

6. Mitochondrial Diseases

6.1 We have previously noted [5] that the proposed technique of Oocyte Nuclear Transfer (ONT) constitutes germ-line gene therapy, which is widely condemned by the international community [14]. The Donaldson Committee acknowledges this, but concludes:

While treatments developed from such research could be seen technically as constituting a modification of the human genome which would be passed on to the next generation, this modification was likely to be of a modest nature. Considerable research would
be necessary to investigate the feasibility and efficacy of the technique and the significance of any germ line effect before its use in treatment could be considered. Such basic research is allowed under international conventions.
6.2 In its response the Government agrees that such research should be licensed, and does not even note the concerns over germ-line intervention [15].

6.3 We find it wholy inadequate to say that a breach of international principles of medical ethics may be overlooked because it is "only a small one". It is clear that if this approach is adopted then we will have germ-line gene modification by the back door. What can be the justification for using human embryos in research aimed at an outcome that is itself prohibited by international convention?

7. Conclusions

7.1 The forthcoming judicial review of the regulations is likely to conclude that cell nuclear replacement (CNR) is not covered by the Human Fertilisation and Embryology Act.

7.2 The new regulations allow 'pure' research on embryos, with no clinical goal, for the first time.

7.3 Adult stem cell research currently shows more clinical promise than embryonic stem cell research.

7.4 Stem cells derived from cloned human embryos have no plausible use in research into human diseases.

7.5 Cell nuclear replacement research will advance reproductive cloning.

7.6 The 'treatment' of mitochondrial diseases by oocyte nuclear replacement is contrary to international conventions.

7.7 These regulations are ill-considered and unnecessary. They should be repealed and primary legislation should be introduced to ban all forms of human cloning for whatever purpose.
 

Appendix A. Medical Ethics and the Status of the Human Embryo

The established international principles of medical ethics are set out in the  Declarations of Geneva and Helsinki. The most relevant sections are :

The Geneva Convention Code of Medical Ethics (WMA in 1949)

"I will maintain the utmost respect for human life from the time of conception; even under threat. I will not use my medical knowledge contrary to the laws of humanity."
The Declaration of Helsinki (WMA, as revised 1975)
"In research on man, the interest of science and society should never take precedence over considerations related to the well-being of the subject."

"The doctor can combine medical research with professional care, the objective being the acquisition of new medical knowledge, only to the extent that medical research is justified by its potential diagnostic and  therapeutic value for the patient."

These may be applied, with some modifications for the special situation of the embryo or fetus, but with no changes of fundamental principle.This is the approach we take with regard to the treatment of human embryos and fetuses, and we would recommend it to the Select Committee.

Appendix B. Recent Developments in Stem Cell Research

This appendix gives a brief survey of recent developments in stem cell research, involving non-embryonic sources of stem cells and of potential relevance to the treatment of disease in humans. A regularly updated report on advances in stem cell research may be found at [16], from which many of these reports are taken.
J.G. Toma et. al., "Isolation of multipotent adult stem cells from the dermis of mammalian skin," Nature Cell Biology 3, 778-784; Sept. 2001
  • Scientists at Australia's Walter and Eliza Hall Institute of Medical Research have  demonstrated the transformation of adult mouse neural stem cells into muscle cells. Perry Bartlett, a member of the Australian team, says the research shows unequivocally that adult stem cells can become other types of cells: "It's important in the sense that there's been a debate about whether stem cells from adult tissues, whether that be brain or blood or elsewhere, do have the potential to give rise to various tissues. I guess this is one of the very first unequivocal demonstrations that these cells are able to give rise to a larger number of cell types than was previously thought."

  • R.L. Rietze et al., "Purification of a pluripotent neural stem cell from the adult mouse brain," Nature 412 736-739, Aug. 16, 2001.

    Appendix C. International opinion on Human Cloning

    References

    1. House of lords Select Committee on Stem Cell Research, 2001. http://www.publications.parliament.uk/pa/ld199697/ldselect/ldscenqs.htm#stem
    2. Human Fertilisation and Embryology (Research Purposes) Regulations 2001 http://www.hmso.gov.uk/si/si2001/20010188.htm
    3. Response to the HGAC/HFEA consultation paper Cloning Issues in Reproduction, Science and Medicine, The All-Party Parliamentary Pro-life Group, April 1998. http://www.dgwsoft.co.uk/homepages/cloning/cloning1.htm
    4. Cloning Issues in Reproduction, Science and Medicine Consultation Document, HGAC/HFEA, January 1998. http://www.dti.gov.uk/hgac/papers/paperc1.htm
    5. Stem Cell Research and the Human Embryo, The All-Party Parliamentary Pro-life Group, December 1999. http://www.dgwsoft.co.uk/homepages/cloning/stemcells1.html
    6. CMO's Letter on the Expert Advisory Group on Therapeutic Cloning in Humans, 2 September 1999. http://www.doh.gov.uk/cegc/cmolet.htm
    7. The Human Fertilisation and Embryology Act, SCH. 2   3.-(2).
    8. Cloning Issues in Reproduction, Science and Medicine, HGAC/HFEA, December 1998. http://www.dti.gov.uk/hgac/papers/paperd1.htm
    9. House of Commons Hansard, 19 December 2000. http://www.publications.parliament.uk/pa/cm200001/cmhansrd/vo001219/debtext/01219-07.htm
    10. House of Lords Hansard, 22 January 2001. http://www.publications.parliament.uk/pa/ld200001/ldhansrd/vo010122/text/10122-04.htm#10122-04_head2
    11. Stem Cell Research: Medical Progress with Responsibility (The Report of the Donaldson Committee), August 2000. http://www.doh.gov.uk/cegc/stemcellreport.htm
    12.  See for example The Homeobox Page, Thomas R. Bürglin, University of Basel, Switzerland http://www.biosci.ki.se/groups/tbu/homeo.html,Homeobox Genes in Flies and Mammals, Robert J Huskey, http://www.people.virginia.edu/~rjh9u/homeo.html
    13. The Daily Telegraph, p1, 25 August 2001.
    14. Convention on Human Rights and Biomedicine, 1997. Article 13. http://conventions.coe.int/treaty/en/Treaties/Html/164.htm
    15. Government Response to "Stem Cell Research: Medical Progress with Responsibility" August 2000.  http://www.doh.gov.uk/cegc/govresp.htm
    16. Do No Harm: The Coalition of Americans for Research Ethics http://www.stemcellresearch.org
    17. European Parliament resolution on human cloning, adopted 17 September 2000. http://www3.europarl.eu.int/omk/omnsapir.so/pv2?PRG=CALDOC&FILE=000907&LANGUE=EN&TPV=DEF&SDOCTA=8&TXTLST=1&Type_Doc=FIRST&POS=1
    18. Charter of Fundamental Rights of the European Union http://www.europarl.eu.int/charter/pdf/text_en.pdf
    19. Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, on the Prohibition of Cloning Human Beings (ETS No.168) http://www.legal.coe.int/bioethics/gb/pdf/proto.pdf
    20. Human cloning: scientific, ethical and regulatory aspects of human cloning and stem cell research. A report of the Standing Committee on Legal and Constitutional Affairs of the House of Representatives of the Commonwealth of Australia.
    http://www.aph.gov.au/house/committee/laca/humancloning/contents.htm