Select Committee on Science and Technology Written Evidence


Memorandum 34

Submission from the United Kingdom National Stem Cell Network (UKNSCN)

  The UKNSCN was established in November 2006 in direct response to Recommendation 10 of the Government's UK Stem Cell Initiative report (the Pattison Report). It has been set up primarily to promote the coordination of research at the national level through promoting interdisciplinary collaboration across the various sub-disciplines of stem cell research. In addition, it will eventually become the national focal point for communication with overseas researchers, the media and the public, and will provide the "national voice" to policymakers and regulators in the field of stem cell research. The secretariat is based within the Research Councils in Swindon and operates under the guidance of a Steering Committee of eight members chaired by Lord Naren Patel of Dunkeld.

  The UKNSCN has submitted the following written evidence on behalf of the UK stem cell research community. However, given the short time available to collate evidence, the Select Committee is invited to note that the following evidence has essentially been prepared through the Steering Committee and a handful of selected academics from within the community. The opportunity to consult more widely was significantly limited.

EXECUTIVE SUMMARY

  This document focuses on the appropriateness of the legislative proposals for regulating the creation of hybrid and chimaera embryos (animal-human) set out in the Government's recent White Paper (December 2006), and on the impact of these proposals upon UK stem cell research. It presents a balanced view of the benefits, risks and requirements for the generation of hybrid and/or chimaera embryos (animal-human) for research purposes on behalf of selected experts in the UK academic research community. The regulatory body governing the use of the embryos in research is currently the Human Fertilisation and Embryology Authority (HFEA). The Select Committee is invited to note the UKNSCN's view that the current regulatory framework for embryo research via the HFEA would not cover animal-human hybrid embryos since these would be generated outside the IVF system and would have no fertility application at all. New legislation and possibly an entirely new regulatory body might be required, although the UK's current strict Home Office guidelines for animal experiments may cover this work. If that is indeed the case, then careful use of the current regulatory framework for both human and animal embryo experimentation may mean that there is no need for any further legislation. The UKNSCN considers that any form of "blanket" ban on the generation of animal-human chimaeras would be undesirable and that any new regulation should foster scientific progress whilst preventing misuse. At the same time, the UKNSCN recognises that the successful development and implementation of such regulation is dependent upon society's active consent in this new area of science.

1.   Terminology

  1.1  The UKNSCN considers that the use of the term "chimaera" for animal-human embryos generated using current somatic cell nuclear transfer (SCNT) technology is both misleading and unhelpful. It is misleading because it implies the mixing of chromosomal DNA from animals and humans (not the case with SCNT) and it is unhelpful because it refers to the beast of classical Greek mythology which manifests the head of a lion, the body of a goat and the tail of a serpent—quite literally a monster created by the grafting of tissues from different organisms, rather than anything generated by genetic recombination. Developmental biologists have used the term "chimaera" for any organism or embryo that contains the genomes from two different individuals, either from the same or different species, which never become mixed in the same cell. By this definition, animal-human embryos generated by SCNT are not chimaeras, save that they contain a small amount of animal mitochondrial DNA as well as human nuclear DNA. This issue is discussed further in paragraph 1.3 below.

  1.2  The Select Committee might therefore wish to consider adopting the terminology "animal-human hybrid embryos" to refer to the embryos which some researchers are seeking HFEA permission to generate using SCNT technology. Even this term is not wholly scientifically accurate and may, of course, not be palatable to the general public either. A more correct term would be "cybrid" (literally, cytoplasm hybrid), indicating that the embryo is essentially human and contains a vanishingly small amount of animal genetic material. A further new alternative term might be "composite". Scientifically accurate terminology is vital in deciding what might be prohibited and what might be permissible under regulation in any new legislation.

  1.3  The nature of mitochondrial DNA/nuclear DNA chimaerism has generally not been very well explained in the media. The number 99.5% has been suggested for the percentage of human genetic material, though the reality of the situation is that we do not know the precise division. If one divides the absolute amount of human DNA by the absolute amount of mitochondrial DNA then one reaches something approaching this figure. However, if one divides the unique genetic content of a mitochondrion into the total haploid human genome then the figure is closer to 99.9995%.

2.   Utility of Hybrid and/or Chimaera Embryos for Research

  2.1  The advantage of using animal-human hybrid embryos lies not in their hybrid nature per se but purely in the fact that the use of an animal oocyte overcomes the problem of the shortage of human oocytes and the associated ethical issues. This means that it will be feasible to investigate far more thoroughly how it might eventually be possible regularly to create SCNT embryos for therapeutic cloning. Success rates for generating embryos by SCNT are low in all vertebrates, due to key genes being switched off in somatic cell nuclei, and there is a need to better understand this process. In addition, animal oocytes are generally available fresh, unlike human oocytes which are predominantly frozen. Research experience thus far has shown that the success rates for SCNT are improved through the use of fresh oocytes as opposed to frozen oocytes. Furthermore, and perhaps most importantly, the use of the approach to speed the development of effective protocols for the generation of cloned embryos (and hence embryonic stem cells) from specific individuals with a genetically-based disease will enable detailed research into the nature of the disease and possible therapeutic strategies. It is too soon to say whether hybrid patient-specific ES cells would have a direct role in therapy, partly because of the ethical considerations, which would have to be fully and openly debated, but also because of the potential "conflict" between mitochondrial and nuclear gene products derived from different species. No-one is proposing the use of ES cells from hybrid embryos in stem cell therapy and prohibition of such activity is already implicit in the EU Tissue Directive; stem cell lines will be generated for research purposes only in order to demonstrate the principles of the approach.

  2.2  The availability (under current regulation) of fully human embryos for research purposes in the UK means that the generation of animal-human hybrid embryos is not strictly necessary and has no real utility per se. If more human oocyte donors were encouraged to come forward and consent to their use for research purposes, then the requirement for animal-human hybrid embryos would evaporate and the HFEA would retain full regulatory control of the embryo research field.

  2.3  The Select Committee is invited to note that the scientific evidence for being able to successfully produce animal-human hybrid embryos is in relatively short supply. There is one key research paper from Professor Huizhen Sheng's team in Shanghai, China published in 2003 which reports the derivation of stem cell lines from enucleated rabbit eggs reprogrammed by the transfer of human nuclei from skin cells. To the best of UKNSCN's knowledge, this research has not yet been adequately reproduced and further proof-of-concept research is necessary.

  2.4  The utility of studies with animal-human chimaeras, as distinct from animal-human hybrid embryos, lies in their facilitation of our basic understanding of human ES cells and our need to definitively assess the function of differentiated cells arising from them. This knowledge is pivotal in our ability to safely translate human stem cell research into clinical applications in regenerative medicine. Such experimental chimaeras would be required to exist for approximately three days in vitro and would therefore not reach the stage where they become protected by the Animal Scientific Research Regulations.

3.   Ethical Benefits in the Generation and Use of Hybrid and/or Chimaera Embryos

  3.1  The UKNSCN considers that the positive ethical benefit in generating animal-human hybrid embryos derives from not having to use consented oocytes from human donors. Not only are these in short supply, but they can only be obtained by hormone treatment to induce superovulation. As with any medical intervention, this carries a degree of risk, in this case the risk of ovarian hyperstimulation syndrome.

4.   Necessity and Alternatives

  4.1  The UKNSCN believes that hybrid animal-human embryos are probably necessary in the short-term if clones (and subsequently ES cells for research) are to be made on a regular basis in sufficiently large numbers for experimental purposes.

  4.2  There are two possible alternatives, only one of which is a proven to work thus far. The first is through the use of donated human oocytes. The second alternative would be the ability to reprogram any tissue (adult) cell so that it becomes or behaves like a pluripotent embryonic stem cell. Recent ground-breaking research from Japan has reported that this might be possible simply by expressing four specific transcription factors in a fibroblast. This is essentially "proof-of-principle", but it will be quite some time before this is likely to be useful (not least because it entails introducing strong expression vectors into the cells). The work needs to be replicated and performed routinely first, in line with accepted due scientific process. Nonetheless, if the potential becomes a reality, then there will no longer be any need to use donated embryos, or produce them through somatic cell nuclear transfer, in order to generate human embryonic stem cells for research purposes. Until this research produces a reliable technology however, it may be argued that the creation of human-animal hybrid embryos for generating stem cells should be permissible (under current regulation) in the short-term.

5.   Ethical Objections to the Generation of Hybrid and/or Chimaera Embryos for Stem Cell Research

  5.1  The UKNSCN believes that the ethical objection to the generation of hybrid and/or chimaera embryos for stem cell research centres quite simply on the view that human and animal genetic material should not be mixed, whether one is talking about chromosomal DNA or mitochondrial DNA. For many, the mixing of genetic material from human and animal species is a taboo, though genetic "mixing" is already a widespread practice in both academic research and commerce. For example, many human protein drugs (eg erythropoetin) can only be manufactured by inserting a relevant human gene (or genes) into an animal cell in order to obtain the correct glycosylation of the final patient therapy. The fact that the animal genetic material (mitochondrial DNA) carried over during the SCNT process is almost certainly in no way part of what defines that animal as being distinct from a human will probably not carry much weight with the general public. Clearly, however, some forms of mixing of human and animal tissues have become generally acceptable in that animal organs and tissue derivatives (such as heart valves) are used in transplantation.

6.   Scientific and Public Opinion

  6.1  The UKNSCN believes that the scientific community in the UK is largely in favour of the generation of hybrid animal-human embryos for stem cell research, though there are several detractors from this view. However, the detractors do not generally object on ethical grounds but rather on the basis that the generation of hybrid animal-human embryos is probably unnecessary in the UK when researchers already enjoy a permissive (but tightly regulated) research environment which allows the use of 100% human embryos. They generally wish to see more human donors consenting to the use of oocytes for research purposes.

  6.2  There is a genuine concern amongst some scientists that the UK public has thus far trusted science with the derivation of human ES cell lines and even therapeutic cloning, but with very little so far to show by way of patient therapies. The latter will take time but, against this background, the UKNSCN is aware of the view that it is not yet time to move to the next level (namely animal-human hybrids) which would appear to have much less public support at present.

  6.3  The UKNSCN believes that public opinion has not been assessed sufficiently, despite the on-line public consultation conducted by the Department of Health in 2005. Certainly, the small number of responses received during this consultation, that were the basis for the comments in the White Paper, can in no way be viewed as a representative cross-section of the UK population. It is the view of several stem cell researchers in the UK that once the nature of the research and its aims are explained properly, and that the public recognises the media's tendency to stir up what might be colloquially referred to as the "yuk" factor, then a large proportion of the general public will be supportive. Indeed, an ethical scales argument may work well in helping to crystallise opinion—does the public prefer to see lots more women donating oocytes for research (in a procedure that is not without risk) or to see fresh oocytes utilised from cows that have already been slaughtered for the meat industry?

January 2007





 
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