Coalition of embryo experts makes last ditch bid to persuade HFEA on hybrids

12.00.00am UTC (GMT +0000) Wed 10th Jan 2007

As a decision by the HFEA on whether to support human-animal hybrid embryo research up to 14 days is anticipated tomorrow, Tuesday 11th, leading scientists, ethicists, academics, clinicians and parliamentarians today made a final attempt to persuade the HFEA to support such research by submitting a dossier personally addressed to each HFEA member at its meeting this afternoon (10th).

The document, prepared by Liberal Democrat MP Dr Evan Harris, was from a coalition of scientists, including three Nobel prize-winners, stem cell researchers, medical ethicists, academics, clinicians and parliamentarians who also wrote a joint letter to the Times today.

The paper stressed the potential benefits of research where human nuclei are transferred to an animal egg whose own nucleus has been removed, and triggered to develop as an embryo. Such pseudo-hybrid embryos are 99% human in terms of their DNA. They would never be implanted and would be destroyed within 14 days in line with existing rules for normal human embryos.

"The current shortage of human eggs for research means that this sort of research is vital if we are to realise the potential of stem cells", said Dr Harris, a member of the BMA medical ethics committee.

The paper also argued that there was no ethical bar to allowing the research and offered a withering critique of the Government's announced policy to ban all such research.

Dr Harris, a member of the Science and Technology Select Committee, said, "The HFEA must have regard to the needs of patients, and the future of research in this country. So must the Government, whatever the HFEA decides."

1) The HFEA meeting to decide policy on research using human-animal hybrid embyos was held today, Wednesday 10th January 2007, and it is anticipated that the outcome will be announced tomorrow, Thursday 11th January 2007, at 11:00am

2) The full submission to member of the HFEA from the coalition appears below:

The case to support hybrid/chimera research

Submitted to the HFEA by the authors of the letter to the Times

Prepared by Dr Evan Harris MP

Introductory Points

If the legal view received by the HFEA is that cloning using human somatic cells or nuclei and enucleated animal ova produces an embryo (called below a pseudo-hybrid human embryo) that can be considered a human embryo for the purposes of the 1990 Act (as indicated by the conclusions of the ELC at their meeting in May 2006) then we would welcome this as it is clearly appropriate for such research to be regulated and licensed by the HFEA unless and until it is banned by Parliament (which we believe would be wrong and unlikely).

The authors of the letter to the Times believe that

• In vitro work up to the 14 day limit, for research purposes using embryos which mix human and animal material is both potentially scientifically useful and ethical within the ethical basis of the 1990 Act, and have significant practical advantages over the use of purely human material.

• That those who have looked at this question in detail and provided reasons for their views (such as the House of Lords Stem Cell Committee 2001, and the House of Commons Science Select Ctte 2005) have concluded that there are no ethical barriers to regulated research of this type. Those who have argued for a ban (Donaldson 2000 and Government White Paper 2006) have failed to cite any ethical arguments in favour of their position. Donaldson's only stated reason for a ban was a lack of scientific use, which now clearly falls.

What weight to give the Government White Paper Position?

• It is very dubious whether any more weight should be given to the Govt White Paper position than to the views of Parliamentary Select Committees, by the HFEA. It is not the role of the HFEA to try to decipher or interpret emerging Government thinking as opposed to the expression of the view of Parliament. Although Parliament has not expressed a view as a whole on the matter, the only two Parliamentary Select Committees (whose membership is broadly proportionate to Parliamentary numbers) have not called for a ban on this research.

• It is difficult and distorting for the HFEA to advise Government independently when it bases its advice on the view of Government in the first place.

• The HFEA's expressed view hitherto on this issue stems from its response to the Consultation and the conclusions/advice of the Ethics and Law Committee, both of which were supportive of this research being permitted and regulated. The advice to Parliament and Government should not change solely on the basis of one party expressing a different view.

• In an area where free votes (on non-Party lines) are the rule, Government policy has much less influence than in other areas (such as the establishment of RATE). Previous parliamentary votes on therapeutic cloning have overwhelmingly supported the research position, even if the "pay-roll (ministers) votes" are subtracted.

• The Government's own position is unclear, given the Prime Minister's statement about wanting to see this sort of research continue, and the minister's mistaken belief that the Government was merely proposing to continue an existing ban (World at One, Radio 4, 5th Jan).

• The framing of the Government's position is so vague and ill-defined as to imply the banning of existing research using animal models (such as the Down's Mouse) which have hybrid cells (containing human chromosomes) and were created via chimeric embryos (through fusing mouse embryos with mouse-human hybrid stem cells). It also would appear to seek to ban the research done by Sir John Gurdon (see Byrne JA, Simonsson S, Western PS, Gurdon JB. Nuclei of adult mammalian somatic cells are directly reprogrammed to oct-4 stem cell gene expression by amphibian oocytes. Curr Biol. 2003 Jul 15;13(14):1206-13.) who has been placing human somatic nuclei into frog oocytes to study cell biology. No evidence has been provided by the Government as to why this existing research is either unacceptable or now requires HFEA regulation.

The need to consider the interests of patients

1. The research is potentially beneficial to patients

a) There is a growing body of evidence that stem cell lines can be obtained following Nuclear Transfer between species. Blastocysts and cells have been obtained following transfer of human nuclei into rabbit eggs and mouse into bovine eggs. Blastocysts have been produced after transfer of non-human primate nuclei into rabbit eggs. It would be used (in the case of one of the groups at least) to practise the techniques of Somatic Cell Nuclear Transfer and hopefully increase its efficiency and effectiveness at generating good quality embryos and human embryonic stem (hES) cell lines.

b) It would be used (in the case of at least one of the groups) to generate hES cell lines with established genetic mutations known to cause human disease to provide a model for study of the disease in cell culture and in a particular cell type. The diseases concerned (e.g. Parkinson's and Alzheimer's) are devastating and have inadequate or no treatments.

c) Embryo stem cell lines that have the same potential as those from fertilised embryos are obtained at high efficiency from mouse embryos produced by Somatic Cell Nuclear Transfer. Significantly more of such embryos yield stem cell lines than would have become offspring.

d) There may be benefit in using eggs from a species in which Nuclear Transfer has been successful as there are no non-human primate offspring produced after Somatic Cell Nuclear Transfer. This contrast in success rates may reflect as yet unidentified differences between species in oocyte function and early development.

2. The research methodology proposed is the best practical way to do this work

a) There is a real shortage of human embryos (and especially human eggs) which are currently only available as surplus from IVF or PGD and are therefore very rare, often poor quality, (and in the case of eggs from older women which may be less useful), and do not contain all the genetic abnormalities which need to be studied (i.e. only those for early onset monogenetic disease).

b) While human eggs are potentially available from altruistic or egg-sharing donors, it is extremely unlikely there would ever be enough made available from such sources.

c) As the HFEA is aware, altruistic egg donation for research is not free from ethical controversy due to i) the invasive nature of the procedure ii) the small risk associated with hyper-ovulation and iii) that such eggs as are available, arguably should be directed towards infertility treatment subject to the wishes of the donor.. Some of these issues equally apply to egg-sharing for research. Even those of us who strongly support egg donation for research recognise the issues raised by an efficiency rate which may be as low as 1%. Lots of eggs and donors are used with potentially no embryos produced.

d)Alternative sources of human eggs - e.g. derived from stem cell lines themselves - or "artificially" from adult cells are not available as technologies and indeed the latter is also proposed by the Government for banning.

e)In contrast mammalian eggs are in plentiful supply from farming and food industries

The need to consider the interests of UK science

1. The UK has an excellent has a high reputation for research in this area. Funding has been made available by the MRC, Wellcome Trust and the Stem Cell Foundation to promote research in this area, including through CNR techniques.

2. In addition to the authors of the letter to the Times, the Academy of Medical Sciences, MRC and Wellcome Trust have expressed their opposition to a ban on hybrid/embryo research.

3. The climate for venture capital funding of research and development in this area is not as easy as it could be, due the position of the US market as a result of the policy of US administration and any furthr sign that the UK was weakening its support for embryo research, before Parliament expresses a view, would be very damaging.

4. It would be unfortunate to say the least if research teams left this country to do work on hybrids and embryos prior to any Parliamentray move banning it, and also taking out of the country other research that is supported by the HFEA. Such might well be a consequence of the HFEA adopting policy opposed to this work.

Is the research ethical? Would a ban be more ethical or rational?

a) There appears to be no good ethical basis for providing greater respect to hybrid or chimeric embryos by banning their creation and use in research up to 14 days, than there currently is for totally human embryos where such creation, use and destruction is allowed.

b) If there is a legitimate objection to mixing material from different species in embryos then the pseudo-hybrid human embryo (as proposed in the applications for research licences) one is the least "problematic" because it is not a true hybrid. There is nuclear DNA from only one species, and even the mitochondrial component from the mammal would be lost if human cells were transferred and not just nuclei).

c) Full hybrids have been created (albeit transiently) for years under the authority of the HFEA when human sperm viability is tested by assessing the ability to penetrate the shell of hamster ova. No ethical objection was used to outlaw this work.

d) Ethical objections to creating hybrid embryos should also apply to creating born human-animal hybrids, yet such hybrids have been produced for many years as mouse models for human genetic or chromosomal diseases (eg Down Mouse).

e) We note that no ethical objections were cited by the Ethics and Law Committee when it considered this matter in May 2006.

What is the role of Public Opinion?

1. We would contend that it is not the role of the HFEA to make policy in respect of embryo research based on perceived or actual public opinion (as opposed to the views of patients when considering fertility treatment). That is more properly a matter for Parliament to consider and seek to represent, and no doubt it will do so when considering the new legislation.

2. In any event no proper research has been done on the views of the public on this issue, so even if was a factor it is impossible to know what to make of it.

3. In respect of the destruction of human embryos for research, public opinion supports the existing position in opinion polls (varying from narrow majorities to more than three to one, depending on the question and the context).

4. It is not acceptable practice to base even perceptions of public opinion on the headlines in tabloid newspapers as this would be to subcontract the role of regulation to those people.

5. The Science and Technology Select Committee in its recent report on Evidence-based Policy making severely criticised the practice of using responses to consultations as a measure of public opinion, describing it as so biased as to worse than useless.

6. The fact therefore that of the 350 individual responses to the consultation that dealt with this question the majority were opposed to hybrids is of little value or relevance especially given that

a) a BBC "poll" subject to the same type of biases, last week on the same question elicited over 12,000 responses of which over 60% were in favour of the research.

b) The majority of those opposed to hybrid research are opposed to all embryo research

c) The major representative or membership organisations that responded were in favour (eg BMA, Academy of Medical Sciences, British Fertility Society, RCOG) but their responses would be given equal weight to an individual in a simple tally.