Select Committee on Science and Technology Written Evidence


Memorandum 52

Submission from Professor Sir Liam Donaldson, Chief Medical Officer of England

  1.  I have been asked to provide a memorandum to assist the above inquiry due to my original advice to the Government on stem cell research which led to the current legislation. I have seen the evidence submitted by the Department of Health and wish to add the following further commentary on the development of the recommendations relating to the mixing of human cells and animal eggs in 2000.

BACKGROUND TO THE CMO'S EXPERT ADVISORY GROUP REPORT

  2.  Following the announcement of the birth of "Dolly" the sheep and the isolation of human embryonic stem cells in 1997 the Government asked the Human Fertilisation and Embryology Authority (HFEA) and Human Genetics Advisory Commission (HGAC) to consider the issues. They issued a report called "Cloning Issues in Science and Medicine" in 1998 which endorsed the existing ban on human reproductive cloning. The Report called on the Government to make Regulations under the Human Fertilisation and Embryology Act 1990 to permit research on human embryos including those created by cell nuclear replacement ("therapeutic cloning") to develop new treatments for damaged or diseased tissues or organs.

  3.  The Government Response to the HFEA/HGAC report published in June 1999 asked me to give advice as Chief Medical Officer drawing on the help of an Expert Group to assess the anticipated benefits of research on stem cells and cell nuclear replacement and to advise whether further research uses of embryos should be permitted. The Terms of Reference and Membership of the Expert Group are at Annex A.

  4.  The Expert Group met five times and considered a range of evidence including over one hundred responses to a letter which I issued in August 1999 and which was widely circulated. The resulting Report is available at http://www.dh.gov.uk/assetRoot/04/06/50/85/04065085.pdf. I wrote the report myself but it was discussed and agreed by the expert group.

  5.  The report generated a great deal of public interest and some controversy in this country and internationally. The press conference when I launched the report attracted the largest attendance of the many press briefings I have given in my nine years as Chief Medical Officer. Eventually, public and parliamentary support for my proposals led to new legislation which enabled a new frontier of medical research (and possibly treatment) to be opened up with suitable safeguards to ensure that such progress was made responsibly.

THE MIXING OF HUMAN CELLS WITH ANIMAL EGGS

  6.  I will concentrate on the background to Recommendation 6 of the report, which related to the use of animal oocytes. My report recommended that the mixing of human adult (somatic) cells with the live eggs of any animal species should not be permitted (Recommendation 6).

  7.  This recommendation was made as a result of early discussions about the developments in the science. Indeed, at the first meeting we held (22 September 1999) the use of animal eggs was raised following press reports[51] of the creation of human-bovine hybrids by the company Advanced Cell Therapeutics in Massachusetts in November 1998.

  8.  It also arose in response to a discussion about the potential shortage of human eggs for stem cell research. The information available at that time was limited. We were aware of comments made by Professor Ian Wilmut in evidence to the 1997 House of Commons Science and Technology Committee inquiry into cloning (The Cloning of Animals from Adult Cells, (HC373-I)) considered that over 1000 eggs would be needed to clone a human. He had based this on the figure of 277 cell nuclear transfer need to clone Dolly the sheep. However, there were many attempts that were successful in creating an embryo which subsequently failed to implant in the surrogate ewe. In conclusion, the Expert Group felt that it would require fewer eggs—we quoted a figure of 12-13 (para 2.30)—to develop one blastocyst from which embryonic stem cells might be derived. The Expert Group's therefore did not consider in detail the need for alternative sources of eggs, such as fetally-derived eggs or animal eggs. It simply did not appear to us at the time that the supply of eggs would be a major constraint to research.

  9.  The Expert Group's primary role was to consider the possible benefits from embryonic stem cell research in general and cell nuclear replacement in particular. We took as our starting position to controls operating under the Human Fertilisation and Embryology Act which already contained a number of prohibitions on the mixing of human and animal gametes and the modification of the genetic structure of an embryo. We therefore considered that the ethical, safety and technical consideration together with public concern would rule out combinations human cell and animal eggs for the foreseeable future.

  10.  In light of the above, the possibility of mixing human cells and animal eggs was not felt to be necessary or desirable, as we concluded:

    "2.34  The alternative of using the eggs of another species, effectively acting as a `shell' to carry the human cell nucleus, has been suggested. Researchers in the United States of America claim to have used this technique to produce stem cell lines by using an egg from a cow in place of the human egg for cell nuclear replacement and then isolating and growing stem cells from the resulting embryo. This research has not been published. Such a technique would raise many technical and ethical issues. Most researchers active in this field do not regard this as a realistic or desirable way forward."

  and

    "2.62 The Expert Group concluded that the use of eggs from a non-human species to carry a human cell nucleus was not a realistic or desirable solution to the possible lack of human eggs for research or subsequent treatment."

Recommendation 6:

  The mixing of human adult (somatic) cells with the live eggs of any animal species should not be permitted.

  The Human Fertilisation and Embryology Act 1990 controls the circumstances in which human eggs or sperm can be mixed with the live eggs or sperm of any animal. These circumstances are primarily limited to testing the fertility or normality of human sperm. The 1990 Act does not control the mixing of animal eggs with other human cells. A new Act of Parliament would be required to implement this recommendation. In the meantime bodies funding research may wish to make a declaration that they would not fund or support research involving the creation of such hybrids.

  11.  I am pleased to say that the Government accepted all of the Expert Group recommendations. The Human Fertilisation and Embryology (Research Purposes) Regulations were debated and passed by the House of Commons on December 19, 2000 and the House of Lords on January 22, 2001.

HOUSE OF LORDS SELECT COMMITTEE ON STEM CELL RESEARCH

  12.  In March 2001, the House of Lords agreed a motion appointing a committee "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". I was invited to give evidence to that Committee, which I did so with Department of Health officials on 8 May 2001. I subsequently followed this with further information on 30 July and 12 December[52].

  13.  The lines of inquiry followed by the Select Committee did not, to the best of my recollection, cover the matter of hybrids and Recommendation 6 of the Expert Group's report. It was becoming clearer that successful cell nuclear replacement in most species of mammals and particularly humans required a large number of healthy viable oocytes. Baroness Northover asked whether it would be ethically and legally acceptable to use immature oocytes from aborted fetuses or stillbirths. My response was that there was legislation from 1994 prohibiting the use of fetal tissue in fertility treatment and that there were also technical difficulties in the in vitro maturation of oocytes. My view at the time was that the solution to the supply of eggs might come from donors wished to assist the research, perhaps because they were from a family affected by the conditions being researched. This would be similar to the altruistic donation of blood.

  14.  The final report of the Select Committee made the following comments in relation to the my Expert Group's recommendation relating to human-animal hybrids:

    8.18 The Donaldson report identified a gap in the 1990 Act in that it did not control the mixing of animal eggs with other human cells. It recommended that the mixing of adult (somatic) cells with the live eggs of any animal species should not be permitted, although it did not discuss the thinking behind this recommendation. We are aware of reports of experiments in other countries involving the replacement of a nucleus of an animal egg with the nucleus of an adult human cell. These developments raise important issues. It would clearly be totally unacceptable to implant such an entity in a woman with a view to bringing it to term—and that would be prohibited by the Human Reproductive Cloning Act 2001. For any possible therapeutic applications there would also be significant concerns relating to safety, on which reassurance would be needed. However, if placing a human nucleus in an animal egg provided a way of creating human ES cells for research, some might argue that it was more acceptable to use such an entity for research, the creation of which involves no human gametes, than an embryo created by CNR.

  15.  The issues were discussed in further detail by the House of Commons Science and Technology Select Committee in 2005. Their report "Human Reproductive Technologies and the Law" recommended that the creation of hybrids should be made legal for research purposes. The Government undertook to consult on this and certain other recommendations. The outcome of the response and Government proposals are dealt with in considerable detail in the Department of Health memorandum.

  16.  The House of Commons Science and Technology Committee report and evidence heard during its inquiry appears to have related to clarification of the law relating to the creation of hybrids and the ethical acceptability of their creation. I did not give evidence to the Science and Technology Committee on these points.

CONCLUDING REMARKS

  17.  The principal conclusions and recommendations of my 2000 report identified the promise of regenerative medicine and the important role that research into human embryonic stem cells would play in achieving this goal. It recommended that the law was amended to permit such research to proceed by using surplus human embryos and, where necessary, embryos created by cell nuclear replacement. The group anticipated that cell nuclear replacement would be necessary research tool to understand how to "reprogramme" an adult cell, but that possible limitations on the supply of eggs would probably preclude the use of this as a treatment option.

  18.  On that point, I accept that our earlier assumption on the numbers of oocytes required to create a embryonic stem cell line by cell nuclear replacement was rather optimistic. To illustrate how thinking has evolved in this area, in 2004 the now discredited Professor Hwang reported using 242 oocytes to create a single embryonic stem cell line, and in 2005 to using 185 oocytes from a single donor to make 11 stem cell lines. However, the subsequent fraud enquiry[53] discovered that in fact Professor Hwang's laboratories had used 2,061 eggs without any conclusive evidence that a stem cell line had been produced by cell nuclear replacement.

  19.  However, the research team based in the University of Newcastle upon Tyne has published a report[54] of a single cloned blastocyst which failed to form an embryonic stem cell line. They report using as few as 36 oocytes which provided it is within the legal and regulatory frameworks agreed by Parliament were used immediately after collection. They have recently been granted a licence by the HFEA to collect further fresh oocytes from volunteers in an effort to improve the supply of oocytes.

  20.  The main reason for using animal eggs revolves around the perceived potential for it to aid research into cures for a number of presently incurable conditions. The use of cell nuclear replacement for developing disease-specific human cell lines for researching serious diseases and their potential drug treatments has my full support. This is an important field of research, as indicated by the UK Stem Cell Initiative report in 2005 by Sir John Pattison. The HFEA has issued licences to permit this work using human eggs.

  21.  However, I believe no conclusive evidence exists that undermines the original findings of my report in relation to the use of animal oocytes for such studies. There have been very few published reports in other countries of human cell nuclear replacement using animal oocytes. To my knowledge, the original 1998 research has not been published in a peer-reviewed journal. Some reports from the group under Professor Hwang are considered unreliable. The study in China by Dr Sheng's group using rabbit oocytes remains the only published study, which I understand has yet to be replicated elsewhere.

  22.  The lack of scientific literature available makes it difficult to form an evidence based opinion and I believe that the Government has sensibly decided to present the Bill to Parliament in draft form, this gives these difficult decisions a sufficient level of consideration and scrutiny before being considered appropriate. Moreover, it is important that scientific aspirations are underpinned by public understanding of the issues and public support. Allowing the arguments to be aired in the public domain can only be healthy to the eventual outcome.

  23.  I hope that this had shed further light on the thinking that underpinned the original recommendation from my Expert Group in 2000.


51   http://www.advancedcell.com/press-release/advanced-cell-technology-announces-use-of-nuclear-transfer-technology-for-successful-generation-of-human-embryonic-stem-cells Back

52   HL Paper 83 (ii) Evidence ISBN 0104420626 Back

53   http://www.iht.com/articles/2006/01/10/asia/web.0110clone.text.php Back

54   Reproductive BioMedicine Online 2005 http://www.rbmonline.com/Article/1872 Back


 
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