Submission from Dr Jus St. John, Lecturer
in Mitochondrial and Reproductive Genetics, Medical School, University
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
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
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.