Select Committee on Science and Technology Written Evidence

Memorandum 6

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 authority.


  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 to reproduce.

  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 of regulation.


  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 donated eggs.

  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 of licensing.

January 2007

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