PURPOSES OF SCNT OR "THERAPEUTIC CLONING"

  (i)  To avoid the problem of immune rejection when transplanting cells of therapeutic value that have been derived from hES cells. hES cells from conventional, IVF-derived embryos can not provide a sufficiently good match for many types of transplant, but an ES cell line derived using a somatic cell from the patient will be genetically identical and therefore seen as "self" by the patient's immune system.

  (ii)  Certain types of genetic disease are very hard to study in the patients themselves, especially if the effects of the mutation begin during embryonic development. The ability to derive hES cells corresponding to the patient, from which the appropriate tissue type could be obtained in cell culture, would allow not only the study of the disease in vitro, but also to screen potential therapies.

  (iii)  To explore basic mechanisms of nuclear reprogramming. This knowledge might help to derive methods of changing one type of adult cell to another.

REASONS FOR USING ANIMAL OOCYTES IN RESEARCH

  There are several reasons for carrying out SCNT experiments using animal oocytes, rather than human oocytes. These would lead to the formation of cybrids (each of which has a human nucleus and animal cytoplasm), which can develop to blastocyst stages from which ES cells can be derived. My own work together with that of others has shown this is feasible. There are interesting scientific questions that can be addressed using human somatic cells and animal oocytes, such as the species-specific nature of nuclear reprogramming and mitochondrial biology. However, the main reason is to overcome the shortage of human oocytes that are available for research.

  (i)  Practice with animal oocytes, which are readily available (eg, bovine ooctyes from slaughter houses), can be used to help train the team of scientists in the methods that could eventually be used with human oocytes. The methods require many separate steps to all work in concert, so training and experience are crucial to success.

  (ii)  It is unlikely that ES cell lines derived in this way would be used directly for therapy in human patients, but they could be used to test methods in animal models of the disease.

  (iii)  Using the system we can learn about the molecular mechanisms that are involved in efficiently reprogramming the somatic cell. This will allow us to improve the methods, so that fewer human oocytes would be required if SCNT was to be applied therapeutically.

  Cybrid embryos are unlikely to be viable as embryos much beyond the blastocyst stages due to inefficiencies in reprogramming all genes required for postimplantation development in all cells. However, ES cells derived from the blastocysts will have undergone another selection process where only relatively normal cells will survive in culture. These cells are therefore very likely to be useful for research.

  Simply banning this type of experiment will impede progress towards finding cures for many types of genetic and degenerative disease. It will also prevent the accumulation of knowledge about early human embryonic development and about reprogramming. Such knowledge is likely to be critical to allow us to find ways to directly reprogram adult somatic cells into therapeutically useful cell types, using defined factors, and thus avoiding the use of oocytes and early embryos.

INFLUENCE BEYOND UK

  UK is currently a world leader not only in embryological research and cloning, but also in policy making in this field. The government in UK has established an image to be able to balance scientific development and ethical issues with confidence and vision. Its regulatory policy in embryological research has provided a permissive but strictly regulated environment. Moreover, several UK organisations, such as the Wellcome Trust, the Nuffield Bioethics Council, the HFEA itself, have all put out reports and discussion papers that have been very useful in the debate worldwide. The UK policy has positively influenced the policy making in other countries, including China, Japan, USA et al. Banning these types of experiment in the UK would send a confusing and discouraging message to the rest of the world.

February 2007