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Reflections from the Church of England on mitochondrial DNA

13 February 2015


From the Revd Dr David de Pomerai

Sir, - For once the House of Commons has got it right, and the Church of England has got it sadly wrong. My duties are currently split between ordained parish ministry and an academic position at the University of Nottingham, teaching biology students about bioethics, as well as genetics and animal development. Knowing this field in some detail, I believe that medical science can offer a real prospect of relief from the otherwise untreatable suffering for that small number of children whose mothers carry mitochondrial genetic diseases.

Without the approval of the Human Fertilisation and Embryology Authority, and a change to the law (the HFE Act 2008), this technique cannot enter clinical trials in humans. Numerous animal trials have already proved successful, even when using macaques in Oregon a few years ago. All the evidence so far suggests that the technique is safe - insofar as any kind of human transplantation technique is safe. We won't really know till we try on human patients. Paradoxically, it is impossible to do a standard phase-one trial of this treatment in healthy humans. No mother would volunteer for such an untried procedure - of replacing her own egg mitochondria with those from a donor egg - unless her own egg mitochondria were defective and very likely to result in a child condemned to a life of illness and early death.

Could there be long-term adverse consequences? Much has been said about so-called mitochondrial incompatibility, although the evidence for this is inconclusive at best. It is true that many of the energy-producing functions of the mitochondria are dependent on nuclear genes, working in co- operation with the very small set of genes encoded in the mitochondrial (mt) DNA; it is only genetic malfunctions involving these mtDNA genes which will be addressed by mitochondrial replacement. But any set of mtDNA genes seems to work satisfactorily in collaboration with pretty well any set of paternal genes, since we all get our mitochondria from mum but not from dad (maternal inheritance).

Remember that all of dad's nuclear genes were used to working with a different set of mitochondrial genes (maternal grandma's); so those genes have to get used to working with mum's mitochondrial genes in each and every one of us. By and large, that doesn't seem to cause serious problems - although, of course, as a scientist, I am bound to add the caveat that we can never be 100 per cent sure. But it is probably well into the high-90-plus-per-cent-probability range.

Could mitochondrial replacement lead to genetic engineering of humans, either for therapeutic purposes (a permanent cure for a range of genetic diseases affecting nuclear genes) or for "improvement" (off-the-shelf sets of genes designed to maximise IQ, sporting, or musical ability)? The short answer is "No," and for a reason that is self-evident to any practising animal geneticist. Mitochondria are little semi-autonomous genetic entities: the functions that are not encoded by the mitochondrial genes themselves are simply imported from the rest of the cell.

If the fault lies within the mtDNA, then replacing the faulty set of mitochondria with non-faulty ones should work in the vast majority of cases. And, even if problems did arise, they are very unlikely to be as severe as those caused by leaving the faulty mitochondria in place -which is the alternative on offer.

But putting new genes into the nucleus of a cell is much riskier, with remarkably low success rates (usually below ten per cent), even though this technique has been around since Richard Palmiter's giant mice in the early 1980s.

I have engineered genetically nematode worms - most recently as a model for Parkinson's disease - and there's still a moment of joyous discovery when you find one line out of dozens which actually expresses the inserted gene properly. There are no guarantees of success in these "transgenic" techniques, and it therefore follows that no one will want to try such methods out on humans. A 90-per-cent failure rate means that the doctors and scientists involved will be sued for failing to deliver the goods in nine cases out of ten.

Whatever our views on litigation in medical cases, in this instance it serves to protect us against a technique that would be genuinely risky and unpredictable in outcome. Those who understand even a little of the science can see not merely clear blue water, but a veritable ocean separating mitochondrial replacement from germ-line gene therapy or designer babies.

If Jesus calls us to join him in healing the sick, we in this Church should not be seen to side with hand-wringing and delay, trying to block what looks like a promising treatment for genetic diseases that have caused one woman to lose seven babies in early childhood. The key point about mitochondria is that they are self-contained functional genetic packages, and therein lies the best possible guarantee that they will work appropriately.

David de Pomerai
Associate Minister, and Science Adviser in the diocese of Derby; Associate Professor in the School of Life Sciences at Nottingham University
74 Woodville Road, Hartshorne
Swadlincote DE11 7ET


From the Revd Dr Michael Perry

Sir, - When the Revd Dr Brendan McCarthy releases a statement using the collective "we" for the Church of England, it would be helpful to know what the collective process is for "us" to arrive at this conclusion. Certainly, in regard to mitochondrial replacement therapy (MRT), as a parish priest and former biochemist with research experience in developmental biochemistry, I would echo Bishop Lee Rayfield reported regret about the Church's communication of its position.

I would also urge us to be informed when raising questions of safety. Your otherwise excellent report (News, 7 February) cites a New Scientist editorial concerning suggestions that mitochondria may have a "greater influence" in cells. New Scientist articles are often speculative. In this case, that piece needs to be read alongside the devastating counter-critique by Dr Robin Lovell-Badge FRS the following month.

I welcome the vote in favour of MRT, and believe that the dedicated and inspired scientific research that makes this now a possibility, together with the years of careful ethical reflection, should be welcomed by the Church at large.

Michael Perry
The Vicarage
Middle Woodford
Salisbury SP4 6NR

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