Page URL:

Mitochondrial transfer and three-person IVF: What's in a name?

24 February 2014
Appeared in BioNews 743

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.

8 September 2014 - by Dr Ted Morrow 
The regulatory path to clinical trials of mitochondrial replacement therapy was recently debated in the House of Commons. While scientists are still unsure how genes and genomes cause disease and impact on our physical appearance and personality, there are clearly misconceptions about mitochondrial genetics repeated during the debate that are not supported by current scientific evidence...
21 July 2014 - by Professor Vardit Ravitsky, Dr John Appleby, Professor Stephen Wilkinson, Dr Anthony Wrigley and Dr Annelien Bredenoord 
Ethical dimensions of the emerging technology of mitochondrial replacement were the focus of a symposium that took place on 25 June at the 12th World Congress of Bioethics in Mexico City....
24 March 2014 - by Professor Janna Thompson 
MP Jacob Rees-Mogg recently implied that mitochondrial transfer is akin to eugenics, but it is a way of combating debilitating ailments rather than producing 'perfect' human beings...
17 March 2014 - by Dr Louisa Petchey 
The Conservative MP for North East Somerset, Jacob Rees-Mogg, has said that mitochondrial donation will produce 'genetically modified children' with 'three parents', and was 'effectively cloning'...
10 February 2014 - by Dr Calum MacKellar 
Those who are concerned about mitochondrial replacement techniques do not have any less compassion than those who believe that such procedures should be introduced: they just remain to be convinced that all the biological risks have been sufficiently addressed...
20 January 2014 - by Professor Sandy Raeburn 
Having worked with families affected by genetic disorders for more than 40 years, both in the UK (with its multi-faith society) and in the Sultanate of Oman (where the majority are Muslim but other religions are allowed), I have seen and looked after many people with hereditary illnesses, including those with disabling mitochondrial conditions....
6 January 2014 - by Dr Calum MacKellar 
Mitochondrial replacement techniques are not a form of therapy in which a person is being treated or cured for a disorder, but instead make sure that that certain persons are not brought into existence. This is a crucial difference since it then questions the equality in value and worth of every possible future person...
2 December 2013 - by Dr John Appleby, Professor Rosamund Scott and Professor Stephen Wilkinson 
A group of European parliamentarians from the Council of Europe recently issued a declaration objecting to the HFEA's policy advice on experimental mitochondrial replacement therapy claiming that MRT is eugenic and inconsistent with human dignity. These are substantial moral claims, ones that deserve closer scrutiny, and it is an interesting and important exercise to consider how successful such arguments are...
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.