In 2012, the Human Fertilisation and Embryology Authority (HFEA) undertook a publicity campaign and public consultation on the subject of mitochondrial transfer, or, to use its more sexy name, 'three-person IVF'.
This emotive description may conjure up some unnerving perceptions of the consequences, and, as this concept challenges our very notion of parenthood and conception, may be met in the public arena with discomfort; a general 'yuk' factor. However, the potential of this technique to help treat a number of serious diseases that affect multiple organs in the body means it is worthwhile considering some of the fundamental aspects of this approach.
In order do this, it's worth starting with the role of mitochondria, a type of subcellular component, or organelle. The vast majority of cells contain mitochondria; notable exceptions include red blood cells and cells of the retina. They are often known as the cellular power stations, since their principle role is the generation of adenosine triphosphate, the energy currency of life.
In addition to this pivotal responsibility, mitochondria have a second important job as 'cell executioners', since they play a vital role in the initiation of programmed cell death (apoptosis).
Since nearly all cells have mitochondria, mitochondrial diseases are usually complex serious conditions that affect multiple organs in the body. Like many other characteristics, we inherit our mitochondria, but only from our mother – Dad's mitochondria, packaged in the midpiece of the sperm, are discarded as soon as the sperm has successfully fertilised the egg.
We can, of course screen for such diseases and inform potential parents of the likelihood of an embryo having damaged mitochondria, but now we have the opportunity to begin testing new techniques that may enable us to avoid mitochondrial diseases entirely.
There are currently two approaches that offer promise for prevention of mitochondrial disease; spindle transfer or pronuclear transfer. These names describe the process much more accurately than mitochondrial transfer, since the proposed techniques do not actually transfer the mitochondria! Instead, an egg is required from a donor who does not carry mitochondrial mutation, and the nuclear material is removed from that egg, in a process called enucleation. In parallel, the nuclear material from the woman whose eggs carry mutated mitochondria is removed by a very fine needle and replaced into the donor egg.
The key difference between the two approaches (spindle or pronuclear transfer) is the stage at which this transfer is performed. In pronuclear transfer, a woman who carries damaged mitochondria has her eggs fertilised in vitro. However, as soon as fertilisation is confirmed successful, as indicated by the formation of two structures call pronuclei, these are collected from the zygote, and injected into the enucleated donor egg.
By contrast, in spindle transfer, the donor egg, with the healthy mitochondria receives the nuclear component from the egg carrying the diseased mitochondria and this is then fertilised. In either case, if successful, a one-cell embryo, containing the nuclear DNA from the mother and father is created and this can be transplanted back into the uterus, hopefully to produce a healthy baby. However, because the egg that carried the nuclear material came from a healthy donor, the child will have inherited mitochondria free of disease.
The technology to enable this is a result of many years of research, but there is much that we still do not know. Whilst it may not be accurate to refer to this technique as 'three-parent IVF' it is true that offspring generated in this way possess DNA from three sources; over 99.9 percent from Mum and Dad but also with some DNA from the mitochondria inherited from the egg donor (since mitochondria have their own genome). It is this very concept that enables the prevention of mitochondrial disease.
In order for this approach to work, the mitochondria need to interact successfully with the nucleus from a different individual. All research to date shows that this is safe, but we need to increase our understanding of this process. It may also be important to consider matching mitochondrial subgroup between egg donor and egg recipient, in much the same way that blood donors must be matched according to blood type. One further important consideration is that if the child born after mitochondrial transfer is a girl, all of her eggs, and consequently any children that she has, will contain mitochondria descended from the original egg donor.
To begin to answer the outstanding questions surrounding this technological breakthrough, more research is needed. In the UK, we are truly fortunate in having a very open and permissive research environment, and whilst funding is very tight, the opportunity exists to perform groundbreaking research using early embryos from animal models and in the human. We have generous donors too – the unsung heroes of this type of research are the people who, after IVF, present scientists with the amazing gift of their surplus embryos which are not required for treatment and would otherwise be discarded.
This resource allows us to learn much about development of humans and investigate the effects of techniques such as mitochondria transfer. Uniquely, we in the UK have a guardian of such important research; the HFEA, who oversee research on human embryos, ensuring that researchers adhere to strict standards, enshrined in law. The public consultation on research on mitochondrial transfer, serves as an illustration of the way on which the HFEA conducts its business.
Finally, the UK is home to some of the world leaders in the understanding of human embryo development all of whom work to the highest standards of scientific conduct and adhere to the conditions of HFEA research licences. And it is for these reasons that we in the UK are uniquely empowered, and arguably have a duty, to perform the vital research to necessary to evaluate the importance and potential of mitochondrial transfer for the avoidance of mitochondrial disease.