energy used to perform cellular functions. Curiously, the proteins
that carry out the most critical functions of the mitochondria
are encoded by a small genome contained within the mito-
chondrion itself. Mutations in this genome can result in a
serious loss of normal mitochondrial function and severe disease,
typically affecting the neurological and neuromuscular systems.
While these mitochondrial mutations can occur spontaneously
within individuals, they are often inherited with the oocyte.
A remarkable feature of sexual reproduction in almost all
organisms is that mitochondria are only inherited from one
parent. In mammals, this is the female. This means that if the
mother’s mitochondrial DNA has defects, this cannot be
compensated for by mitochondria from the sperm.
One potential therapy for inherited mitochondrial defects
is to remove the nucleus from a genetically affected oocyte (or
a fertilised one-cell embryo) and transfer it to a donor oocyte
that has normal mitochondria but from which the host nucleus
has been removed. The resulting embryo is commonly referred
to as a three-parent embryo. There is some controversy
surrounding the use of this technique.
Apart from any ethical qualms about having “three parents”,
scientific questions arise about the safety of this approach. It is
argued that the pervasive matrilineal inheritance of mito-
chondria throughout the evolution of complex organisms has
resulted in the genetic co-selection of the nuclear and mito-
chondrial genomes to ensure their close functional co ordination.
Modelling studies suggest that the use of donor mitochondria
may uncouple this tight coordination and potentially pre dispose
individuals to disease. It is difficult to
decide how serious such concerns
would be for the resulting individual
and what, if any, mitigating strategies
could be put in place to alleviate poten-
tially adverse outcomes.
Although this therapy has been
approved for use in the UK, caution
is needed in this area until a deeper
understanding of the biological and
safety issues is available. This contro-
versy reflects the understandable
conflict between the wishes of a couple
to conceive a child and our responsi-
bility to the unconceived child.
An alternative genetic editing
approach has been proposed and tested
in animals. This involves the use of
gene-editing technology to significantly
reduce the number of defective mito-
chondria in the embryo. It uses the
same form of technology described
above for nuclear gene editing, but it is instead directed at the
mitochondrial genome. Because affected oocytes typically
contain a mix of normal and genetically abnormal mitochon-
dria, the approach is to edit out many of the abnormal copies,
allowing the normal copies to gain numerical ascendancy. It is
unclear whether current legislation in Australia would prohibit
this approach.Embryonic Stem Cells
and Regenerative Medicine
When embryos grow to around 80 cells, they form a structure
resembling a soccer ball called the blastocyst. The cells in the
outer layer of this ball (~50 cells) will eventually form the
placenta. A small group of cells (~30) form a clump inside the
ball (the inner cell mass), and these eventually form the embryo
proper after the blastocyst invades the lining of the uterus.
The microsurgical isolation of the inner cells and their prop-
agation under special culture conditions creates a population
of cells that will proliferate indefinitely. These embryonic stem
cells are pluripotent – they have the potential to form every
different cell type within the organism.
As these pluripotent stem cells can be directed to differen-
tiate into any of the specialised cells of the body, they are a
potential source of “spare parts” for our bodies. Currently,
regenerative medicine trials for the treatment of type 1 diabetes,
spinal injury and macular degeneration are underway using the
transplantation of specialised cells derived from embryonic
stem cells.JAN/FEB 2016|| 15Mopic/Adobe