Nuclear transfer (cloning) is a technique that involves the transfer of a donor cell into an oocyte that has had its nucleus removed (enucleation). For the purposes of deriving human embryonic stem cells through nuclear transfer, the donor cell is most likely to be a somatic cell, such as a skin cell. Using a somatic cell from a patient with a genetic defect would allow embryonic stem cell lines to be developed that would possess such a genetic fault. Such cell lines would provide valuable resources for scientists to understand the mechanisms that result in the phenotypic onset of such a disease. This is especially so as animal models are not always available for such studies. It would also be of considerable benefit to the pharmaceutical industry for drug screening.

  The generation of human embryonic stem cells through nuclear transfer is hindered by the lack of human oocytes available to support such an outcome. Animal oocytes are readily available from slaughterhouses, which would otherwise not be used. Indeed, it has been demonstrated that human embryonic stem cells can be generated through the use of a human somatic cell and rabbit oocytes (Chen et al Cell Res 2003; 13: 251-63).

  Each eukaryotic cell has a population of mitochondria, which are the energy powerhouses of the cell through an intra-mitochondrial apparatus known as the electron transport chain. The mitochondrion possesses a small circular genome, mitochondrial DNA (mtDNA), which we inherit solely from our mothers, through her oocytes at fertilisation. mtDNA encodes some of the genes associated with the electron transfer chain. Nuclear transfer can result in mixed populations of mtDNA being present in embryos and offspring (reviewed in St. John et al Reproduction 2004; 127: 631-641). Consequently, the mixing of human and animal DNA would require us to determine whether the cells generated would be functional and able to sustain sufficient energy. Furthermore, as the remainder of the genes of the electron transfer chain are encoded by the nucleus, we would also need to determine whether the mixing of nuclear genes from one species with mtDNA genes from another would reduce functionality. We also do not know whether it would be possible to isolate those cells that possessed human mtDNA only. However, until such work is undertaken, it is impossible to determine the feasibility of using human-animal hybrid embryos and embryonic stem cells.

  In terms of understanding human mitochondrial genetics, hybrid embryos and embryonic stem cells would offer us the opportunity to elucidate some of the causes of mitochondrial DNA disease. They would also allow us to study nuclear-mitochondrial interaction. Not to allow this work to go ahead would considerably disadvantage experimental work in these fields.

January 2007