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.
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
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.
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
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 eggswe 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."
"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."
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.
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.
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 termand 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.
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
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
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
HL Paper 83 (ii) Evidence ISBN 0104420626 Back
Reproductive BioMedicine Online 2005 http://www.rbmonline.com/Article/1872 Back