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Myth replacement therapy: MPs debate the science of mitochondria

08 September 2014

By Dr Ted Morrow

Senior Research Fellow, University of Sussex

Appeared in BioNews 770

The regulatory path to clinical trials of mitochondrial replacement therapy (MRT) was recently debated in the House of Commons. MRT is under development in the UK as way of potentially eliminating mitochondrial disease. The techniques essentially swap diseased mitochondria in the unfertilised or fertilised eggs of affected women for putatively healthy ones obtained from a donor. The outcome is unknown and evidence from animals suggest mismatching may occur between the nuclear DNA from the mother and the mitochondrial DNA (mtDNA) derived from the donor (1). The debate was called by a group of backbenchers that are unhappy about the pace with which the Government is apparently moving towards changing the regulations. The split in views in the chamber was fairly even.

From my perspective as a research scientist, what I found most interesting was how the science behind mitochondrial disease and MRT was discussed. Genetics is an extremely complex subject; 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.

For example, David Willetts, the former minister for universities and science, who is widely respected within the scientific community, employed the much-used analogy that mitochondria are like batteries for the cell. He followed on to claim therefore that the DNA within 'does not affect identity'. It's true that mitochondria (the cellular subcomponent or organelle) are absolutely where energy is made available for all other cellular processes and so perhaps can be thought of as the cell's 'batteries'. But mtDNA is not a battery and the influence of genes in mtDNA on traits beyond battery-like function is well established (2).

Does mtDNA influence an individual's identity then? In its review, the Nuffield Council on Bioethics thought not, but the answer to this question depends on how you define identity (3). Genetic variation in the mitochondrial genome has been shown to influence a range of traits including cognition, fertility, ageing and lifespan (1); arguably these are indeed part of an individual's personal identity, they are certainly an important part of an individual's characteristics (consider, for example, contemporary ideas about masculinity).

Chi Onwurah supplemented this idea with actual numbers of genes involved: '13 out of 23,000' would be replaced (4). The numbers are approximately correct, but the mitochondrial genes are all essential – in contrast to many of the genes in the nuclear DNA. Consider for example the Y chromosome, which contains a couple of hundred genes, and yet half of the population do quite well without any of them (females). It is therefore a contradiction to claim that mtDNA is not important for an individual's characteristics (scientists call this the phenotype) while at the same time acknowledging that changes in the mitochondrial genetic code are important for an individual's risk of disease (again part of an individual's phenotype).

A second point of contention was whether MRT constituted a form of genetic modification (GM). This is a highly charged subject and there were several MP's that were adamant that it is not. The Department of Health's definition of GM is 'the germ-line modification of nuclear DNA (in the chromosomes)', thereby specifically excluding the mitochondrial genome. They do however state that MRT is a form of germ-line modification. This makes no sense logically or scientifically, since it is modification of the germ-line that is a key defining feature of genetic modification (also a point of confusion for the chief medical officer, Dame Sally Davies (5)). It has been argued that since the entire mitochondrial genome is replaced as a whole it does not constitute GM, but there will be differences between the sequences of the mtDNA removed and donated, and these will enter the germ-line.

How will accepting these points make a difference in the debate? First, if the general public and MPs understand that mtDNA does much more than just provide the genetic code for making more battery parts, then the idea of tinkering with the genetics of mitochondria may be a much less appealing prospect. Genetic modification is obviously a highly contentious proposal for the human germ-line. I can envisage scenarios where GM in humans could perhaps be justifiable (e.g. correcting point mutations) and ethical, but an informed debate on these issues, whether in Parliament or elsewhere, needs to start with the facts, and at the moment those facts do not seem to be filtering through.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

15 February 2016 - by Dr Peter Mills 
The US NAS has published a report on the ethical, social and policy considerations relating to mitochondrial replacement techniques. The recommendation that has inevitably attracted most attention, however, is that only male embryos should be transferred, an approach that was considered but rejected in the UK...
02 February 2015 - by Dr Iain Brassington 
It seems to have happened very quickly: it was only in 2012 that the public consultation process about allowing mitochondrial donation to be used on humans was underway; and now – if you'll allow the pun – the first child to have benefitted from them could be conceivable in the next few months...
24 November 2014 - by Professor Peter Braude and Professor Robin Lovell-Badge 
A response to the open letter to the UK Parliament by Dr Paul Knoepfler...
29 September 2014 - by Professor Frances Flinter 
Robust debate about the pros and cons of mitochondrial donation is essential, but the clinical reality of mitochondrial disorders is stark. Couples who have lost a child affected by a serious maternally-inherited mitochondrial disorder may have limited reproductive options...
22 September 2014 - by Dr Cathy Herbrand 
Following a backbench debate in the House of Commons on mitochondrial donation on 1 September, BBC Radio 4 explored some of the issues raised by these high profile techniques aimed at preventing the transmission of mitochondrial disorders...

08 September 2014 - by Sandy Starr 
A group of backbench MPs, led by Conservative MP Fiona Bruce, has sought to delay the laying before Parliament of regulations permitting the use of mitochondrial replacement techniques...
04 August 2014 - by Siobhan Chan 
The UK Government has been accused of deliberately misleading the public in order to win approval over its plans to implement mitochondrial replacement techniques in IVF...
28 July 2014 - by Rachel Brown 
The UK Government has announced that regulations around the use of mitochondrial replacement techniques will be presented to Parliament in the next few months...
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...
24 February 2014 - by Dr Roger Sturmey 
The description of mitochondrial transfer as 'three-person IVF' may conjure up some unnerving perceptions of the consequences, and may be met in the public arena with discomfort, but it's worth considering the fundamental aspects of this approach...

HAVE YOUR SAY
Analogy, essentialism & gender difference (unspecified21 - Updated on 08/09/2014)
Three points.
1. A good analogy is between organs and organelles. For the cell it's the functional output of the mitochondria that's important rather than its provenance or internal detail, as is the case with transplanted organs.If my heart is diseased I can't exercise my potential and so can't express my identity properly. The same is true if my mitochondria are wonky. Identity is a property of people not organs or cellular components. People should not be identified with their pathologies nor prevented from achieving by imposing that misconstrual.  If my parent is a surviving blind beggar I still don't want my eyes put out.
2. What's really at stake here with loose talk of identity at the organelle level is the final extinction of romantic, spiritualist and essentialist views as popular focus on biological reality gains sharper resolution as the science socially diffuses into the general population. That there is reactionary resistance to losing ignorant ontologies of souls or spirits is no surprise.
3 There is a very clear practical and ethical distinction between heritability after mitochondrial transfer for potential male organisms and potential female organisms. A males' new mitochondrion, whatever its state or origins, will not bother the next generation at all.

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