Memorandum 35
Submission from the Medical Research Council
and the Wellcome Trust
INTRODUCTION
1. The Medical Research Council (MRC) and
the Wellcome Trust welcome the opportunity to provide input to
the Science and Technology Committee. It is our view that research
involving embryos, particularly the generation of embryonic stem
cells, holds great promise and has enormous potential to alleviate
human disease.
2. In 2004-05 the MRC was funding 140 projects
of direct relevance to stem cells, equating to an annual spend
of £14.2 million. The MRC, with the Biotechnology and Biological
Sciences Research Council (BBSRC), also funds the UK Stem Cell
Bank[13].
The research that MRC funds ranges from basic research into stem
cell growth and development, to studies that may be suitable for
clinical trials and ultimately, therapeutic use. We also have
an active programme of engagement with the general public on stem
cell research, including a touring exhibition[14]
and discussion documents.
3. Between 2002 and 2006 the Wellcome Trust
has awarded over £40 million for stem cell research, including
core funding for the newly created Wellcome Trust Centre for Stem
Cell Research at the University of Cambridge (also part funded
by the MRC). The Wellcome Trust also provides core support to
the Wellcome Trust/Cancer Research UK Gurdon Institute at Cambridge
and the Wellcome Trust Centre for Cell Matrix Research at Manchester,
both of which carry out significant stem cell research. The Trust
has also been involved in a multi-million pound joint funding
initiative with the Juvenile Diabetes Research Foundation in an
effort to promote the UK's contribution to stem cell research.
The Trust supports ethical and accountable research involving
embryonic and adult stem cells from humans and animals. The Trust
also funds research into the use of embryonic stem cells in research
through our Biomedical Ethics Funding Programme.
4. We have consulted the BBSRC and the Economic
and Social Research Council (ESRC), who have informed us that
they do not expect to fund the generation of animal/human chimeras
as the research is unlikely to fall within their remit. They will
therefore not be responding separately to this inquiry. However,
the BBSRC and ESRC recognise the importance of human stem cell
research for understanding the basic biology of human stem cell
development and differentiation, and support the view that research
on hybrid and chimera embryos is important, and should be permitted
within the current statutory requirements concerning human embryos.
5. There are obvious difficulties associated
with obtaining human eggs for use in the creation of embryos for
research purposes. Most donated human eggs are currently used
for infertility treatment. The availability of human eggs for
research is currently severely limited. [15]This
is the main reason at the moment that there is a need to create
human-animal embryos for research, but other reasons may arise
in the future. Moreover, the generation of human embryos from
which stem cells can be harvested using somatic cell nuclear transfer
is extremely inefficient, with a success rate currently less than
0.1%. Using animal eggs to uncover the reasons why this process
is so inefficient with human eggs should enable scientists to
make better use of human eggs in the future, and would accelerate
the progress of this work toward clinical applications.
6. The MRC and the Wellcome Trust recognise
that there are strongly held views both for and against the creation
and use of hybrid and chimera embryos for research. It seems that
most opposition to this research arises from those who are opposed
to any form of embryo research, on absolute moral grounds. Whilst
respecting this position, it is clear that the Government and
a substantial majority of the public accept stem cell research
aimed at producing new treatments and we strongly believe it is
in the interests of patients and the public for research involving
hybrid and chimera embryos to be permitted, under strict limits
and subject to regulatory control, including ethical and scientific
review by bodies with a mix of relevant scientific expertise and
lay involvement.
THE SCIENTIFIC
BACKGROUND
7. Fusing human and animal cells is not
a new research procedure. Previous research has created hybrid
cells, grown exclusively in tissue culture, between human cells
and other species, such as mice, which have been used for many
years as powerful tools in genetic research.
8. There is a vast array of scientific evidence
providing examples of the potential health benefits of carrying
out research using cells containing hybrid human and animal DNA.
For example, the mouse has long been used to model human genetic
diseases and much of this research has employed methods to modify
the genetic makeup of mice so as to provide more authentic and
relevant mouse models of human disease. Although most such models
involve simple "knock-out" of a single gene, others
are more complex and include the insertion of human genetic material
into the mouse genome—essentially the creation of genetic
hybrids. Two examples, both developed in this country, illustrate
the importance of such techniques to medical research. The first
is the creation, by Gillian Bates and colleagues of King's College
London, of two mouse strains whose genome includes the aberrant
human DNA sequence that underlies the neurodegenerative disorder
Huntington's Disease. These Huntington's mice have enormously
accelerated the progress of research on this devastating neurological
disorder[16].
A more recent example is the MRC- and Wellcome Trust-supported
research, published in the journal Science in 2006, and
widely reported in the media at the time, in which a mouse line
was created that carries an almost complete extra copy of human
chromosome 21. This development by researchers at the MRC National
Institute for Medical Research and at University College London[17]
is expected to have a huge impact on Down's Syndrome research;
researchers are able to study these mice to shed light on the
key gene (or genes) responsible for the many different symptoms
seen in Down's Syndrome.
9. Two key points should be borne in mind
when considering the issue of the creation of hybrid and chimera
embryos for research, in the manner proposed in, for example,
the two research projects recently submitted to the HFEA for consideration:
(a) The ultimate goal of the research is
not to create hybrid or chimera embryos that might be implanted
and develop further, but to create blastocysts containing only
human nuclear DNA, from which stem cell lines can then be derived.
The use of animal egg cells (oocytes) has been proposed as a readily
available alternative to using human eggs, which are scarce. The
animal oocyte has its nucleus removed and the nucleus from a human
somatic cell (ie not a germ cell) is inserted. The animal
oocyte cytoplasm then acts as an "incubator" for the
human cell, allowing it to develop as a stem cell. The only residual
animal DNA is in the mitochondria, the "batteries" of
the cell. This equates to only a tiny proportion of the total
DNA in the cell (less than 1%); and has minimal impact upon the
cell's developmental programme, which is directed by the human
nuclear DNA. Indeed, there is the possibility that even the cytoplasm
of the animal egg, which contains the mitochondria, might be replaced
with that of the human somatic cell.
(b) Although the human cells would grow initially
in the form of an in vitro blastocyst, the intention is
to remove cells from the blastocyst and use these to develop disease-specific
embryonic stem cell lines. We are not aware of any intention,
reason or ability to develop such embryos beyond the blastocyst
stage, and certainly not beyond the 14-day limit currently imposed.
[We do not suggest that this requirement should be changed]. One
research proposal involves developing neuronal stem cells in order
to study brain cell function in relation to neurodegenerative
diseases. In these diseases, for obvious reasons, it is virtually
impossible to obtain samples of living brain cells from patients.
10. The MRC and the Wellcome Trust are continuing
to monitor the views of the academic and clinical community regarding
the scientific possibilities and challenges emanating from this
research. The Academy of Medical Sciences is convening a working
group, chaired by Professor Martin Bobrow FRS FMedSci, to discuss
issues surrounding embryos containing human and non-human material.
In addition to examining definitions of hybrid and chimera embryos,
this group will identify key research opportunities in the field,
together with an assessment of how these opportunities are balanced
by both safety and ethical concerns. Following an initial meeting
in March, the working group will publish its output later in the
Spring, to feed into the HFEA consultation and Parliamentary process
around the forthcoming Bill. It is likely that the MRC and the
Wellcome Trust will be observers on this working group.
PUBLIC ATTITUDES
11. While we have no evidence of general
public attitudes on the creation of hybrid embryos, in 2003 the
MRC, the Wellcome Trust and a coalition of organisations with
a common interest in stem cell research commissioned MORI Social
Research Institute to carry out a national survey of the public's
views about the use of human embryos in medical research. As far
as we are aware, this is the most recent representative public
opinion survey on this subject. The survey indicated that around
70% of the British public support the use of human embryos for
medical research to find treatments for serious diseases and for
fertility research[18].
GOVERNMENT PROPOSALS
FOR THE
REGULATION OF
HYBRID AND
CHIMERA EMBRYOS
12. We believe the creation of hybrid embryos
by combining human and animal embryos and/or stem cells is likely
to prove helpful in understanding the growth and development of
human embryonic stem cells and the treatment of serious diseases
and conditions.
13. Given this potential, we agree with
the view of the House of Commons Science and Technology Committee,
[19]that
it should be lawful to create hybrids or chimeras for research
purposes if they are destroyed in line with the current 14-day
rule for human embryo cultures subject to suitable legal and regulatory
controls, including the requirement that the embryos must not
be permitted to develop beyond 14 days.
14. If it is the Government's intention
to prohibit the creation of human-animal hybrid and chimera embryos
for research in all circumstances, we would not support this.
It would deny researchers the opportunity fully to pursue embryonic
stem cell research, and would also stifle research on transgenic
disease models that involve the transfer of human DNA to animal
lines. Such a prohibition would have a significant impact on the
progress of medical research. We also fear it would undermine
the UK's position as a world leader in stem cell research, a situation
that the Government, scientists, regulators, ethicists and funders
have worked hard to achieve. Much current stem cell research is
in relatively early development, but it is our view that we are
now at the stage where this research needs to be done—both
in terms of therapeutic potential, and scientific and economic
competitiveness.
15. If, on the other hand, it is the Government's
intention to introduce draft legislation prohibiting the creation
of human-animal hybrid and chimera embryos other than under licence
for the purposes of research, the MRC and the Wellcome Trust would
support that approach, in principle. In particular, we would support
a proposal to regulate and license the activity in the same way
that the use of human embryos is currently regulated and licensed,
and to modify or clarify the current law as necessary to achieve
this.
16. However, we are concerned that it might
prove impossible to create hybrid or chimera embryos, or use stem
cells derived from them, for research purposes, until new primary
and secondary legislation is put into place, and that the delay
this will cause to the progression of the research in this country
will be damaging for the reasons detailed above. We would therefore
wish to see urgent action to clarify or address the position,
so that the activity can continue to proceed.
17. In summary, the MRC and the Wellcome
Trust believe that, subject to appropriate controls, the creation
of human-animal embryos and cells for research purposes should
be permitted, and that if it were to be prohibited, temporarily
or permanently, this would significantly impede research involving
embryonic stem cells and the potential health benefits that could
flow from that.
January 2007
www.mrc.ac.uk/NewsViewsAndEvents/Events/Reports/StemCellScience-HopenotHype/
www.mrc.ac.uk/NewsViewsAndEvents/InvolvingThePublic/Consultations/Useofhumanembryosinmedicalresearch2003/index.htm
13 UK Stem Cell Bank website: www.ukstemcellbank.org.uk Back
14
Stem Cell Science: Hope not Hype? information at Back
15
The HFEA has recently consulted on egg sharing for research.
The MRC's response to the HFEA consultation is at: www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC003455.
The Wellcome Trust's response is at www.wellcome.ac.uk/assets/WTX035514.pdf Back
16
See www.sciencedaily.com/releases/1997/04/970402124046.htm Back
17
MRC press release: www.mrc.ac.uk/NewsViewsAndEvents/News/MRC001790. Back
18
More at Back
19
Human Reproductive Technologies and the Law: Fifth report
of the Science and Technology Committee, 2005; HC 7-I. Back
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