Submission from The Wellcome Trust/Cancer
Research UK Gurdon Institute of Cancer and Developmental Biology,
University of Cambridge
1. The Government's recent White Paper,
"Review of the HFE Act", proposes that legislation should
be revised in such a way as to prohibit the creation in vitro
of hybrids and chimeras, comprising both human and animal material,
while enabling regulations to set out circumstances in which the
creation of such hybrids and chimeras could be allowed under licence,
for research purposes only.
2. Legislation along these lines carries
two dangers: (a) it could bring confusion to the present legislative
situation, rather than providing clarification, and (b) it could
no doubt inadvertently prevent valuable research into the basis
of a range of intractable and little understood diseases (eg motor
neuron disease) that cause immense suffering, while delaying (perhaps
for years) therapeutic approaches to other common diseases (eg
diabetes, Parkinson's) that could be treated by embryonic stem
cell therapy. No doubt this research would eventually be carried
out in other countries, but at present UK scientists have a competitive
advantage, in part because of the sensible and scientifically-based
regulatory system that has functioned with few major problems
for the past 16 years.
3. The research that is under consideration
would be conducted either in vitro, or in laboratory animals.
No human embryo containing animal material should be placed in
a woman's uterus. After implantation, a foetus might in the course
of corrective surgery require an implant or stent of animal origin,
rather as adult heart defects may require transplants of pig heart
valves, but this combination of human and non-human material falls
outwith the present proposed legislation.
4. The phrase "hybrid and chimeras
embryos" in the Government proposals is probably intended
to refer to any early (ie preimplantation) embryo which includes
both human and non-human material. At present, such embryos would
comprise chimeras, in which cells of two different species are
included in one embryo; hybrids, in which chromosomes of two different
species are included in one cell; and pseudo-hybrids, in which
human chromosomes are placed in an animal egg of a different species
that has had its own chromosomes removed. Rather than lumping
all these together, it may be helpful to consider each in turn,
to see whether there are situations that might need to be prohibited
by law, rather than regulated under licence by an appropriate
5. The emphasis here would be on including
some embryonic stem cells in an early, preimplantation embryo,
or some later stage. It is hard to envisage any scientist applying
to put mouse embryonic stem cells into a human embryo; there would
be no point. One is therefore considering the situation where
human embryonic stem cells are placed into a mouse/rabbit/pig
embryo. Little significant development would occur in such an
embryo in vitro, so the animal embryo would need to be
transferred to the animal uterus. (Such an experiment might come
under Home Office regulations, rather than HFEA). This has been
tried with mouse embryos, with very unimpressive results. The
slower rate of development of the human embryo, and the different
developmental pattern, mean that the human cells are soon lost.
The experiment would probably work better with monkey embryos,
and might involve transfer of stem cells during uterine gestation,
rather than before implantation. It could yield valuable information
as to the developmental potential of the human ES cells, and their
tumorigenicity, but it would be ethically contentious and would
need strict regulation, such as ensuring that development was
terminated before birth, or that any progeny were not allowed
6. Chimeras involving adult animals are
widely used, and cause little ethical concern. For example human
embryonic stem cells are injected into immunologically compromised
mice, in order to assay the tumorigenicity of the stem cells,
and examine their developmental potential.
7. Aggregations of a human embryo with an
animal embryo, with subsequent transfer to the animal uterus.
Again the human cells would be unlikely to be maintained, unless
monkey embryos were involved. It is hard to see what arguments
for making such chimeras would be.
8. Conclusion: In vitro studies on human-animal
chimeras could impose no risk, but nor would they yield much information.
They would be better regulated by licensing than by legislation.
Studies on chimeras involving human embryonic stem cells in animal
embryos during gestation could be valuable, and may be required
before clinical trials with human embryonic stem cells are licensed.
They should not be prohibited, but may demand an alternative form
9. Full sexual hybrids between human and
animal gametes would not develop beyond early preimplantation
stages. It is hard to see what scientific information would be
gained by such an experiment. Fertilisation of hamster eggs by
human sperm is allowed as a test of sperm function, but the hybrid
is not allowed to develop past the 2-cell stage. Analysis of human
sperm chromosomes is said to be facilitated by injection into
mouse 2-cell stages. Such studies could be valuable, and should
be allowed under licence, not prohibited.
10. A single human chromosome has been integrated
into the mouse genome (the Down mouse), creating a partial hybrid.
It might be possible to insert larger numbers of human chromosomes
if the medical condition under study required this, but once genes
have been identified, it is more effective to make transgenic
mice. These experiments would not come within the HFEA remit.
11. Here a human somatic cell or nucleus
is injected into an enucleated animal egg (usually cow or rabbit),
which is then activated to develop into a blastocyst from which
embryonic stem cells can be derived. The human chromosomes control
development from the 2-cell stage onwards, the residual material
in the animal egg (mainly mitochondria, that provide energy) predominates
up to the blastocyst stage, but once a stem cell line has been
derived the animal component would be expected to gradually disappear,
since it is not supported by the nucleus. We have little data
on how rapidly and how completely this would occur, and whether
it would interfere with the research objectives, since such experiments
have not yet been licensed by the HFEA.
12. At the present time, this is the area
of greatest scientific need, since several UK groups now feel
competent to carry out these studies, and if they are successful
the long term consequences in terms of reducing human suffering
and disease are very great. The alternative, of using human rather
than animal enucleated eggs, is limited by the scarcity of human
13. Professor Huizhen Sheng from Shanghai,
who has experience of these procedures using both rabbit and cow
eggs, will be in the UK from 30 January to 7 February. I do not
know whether she would be available to give evidence to the Science
and Technology Committee inquiry.
14. Studies combining human and non-human
material in vitro pose no risk. Scientific and ethical
oversight by the licensing authority should provide adequate regulatory
power. Regulation would be much preferable to prohibition. Some
chimera and hybrid studies might require some alternative form