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“Three parent” headlines distract from the real issues of mitochondrial disorders

12 Jun, 2012
Three mitochondria surrounded by cytoplasm

Three mitochondria surrounded by cytoplasm

The Nuffield Council on Bioethics has published a report titled Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review. Geoff Watts, chairman of the working group that prepared it, reflects on some of its key conclusions.

“Bioethics body gives green light to three-parent babies.” That’s the headline I least want to see following the publication of our Nuffield Council on Bioethics report on the ethics of novel techniques for the prevention of mitochondrial DNA disorders.

Mitochondria, tiny organelles found in every cell, are in effect powerhouses supplying the body’s energy needs. Mitochondria have a small number of their own genes which, unlike the far greater number located within the cell nucleus, are inherited only through the female line. If a cell’s mitochondrial genes are mutated they may not function normally, and this can lead to a variety of debilitating, incurable and sometimes fatal diseases.

The object of the new technologies – there are two of them under active consideration, both involving IVF – is to rehouse the nuclear genetic material of an affected woman’s unfertilised egg or early embryo in a previously enucleated donor cell which contains normal healthy mitochondria. You can think of it as an exercise in cell reconstruction.

Nuffield Council working parties usually comprise a dozen or more people who have at least 18 months to produce a substantial document. We wanted our report on the ethics of these new cell reconstruction technologies to be ready by early summer, and so available to feed into a wider consultation on the treatment of mitochondrial disorders being prepared for the Government by the Human Fertilisation and Embryology Authority. The half dozen people in our working group aimed for a comprehensive but shorter document to be ready in six months. With only a few weeks slippage, and thanks to the diligence of project leader Laura Riley, we made it.

Our key conclusions are straightforward enough. We believe on balance that if cell reconstruction is proved to be safe and effective, then subject to the provision of appropriate information and support it would be ethical for affected families to use it. The health benefits would be likely to extend to descendants of any female child born using these therapies, although this would not be the primary intention of the treatment.

We are strongly of the opinion that cell reconstruction (or any comparable future treatment) should only be offered as part of a clinical trial in centres specialising in mitochondrial disorders. Because the effect of the treatments would be felt not only by the newborn child but by her descendants, we would like to see long term follow-up of families over generations. We recognise the difficulties of achieving this goal, but nonetheless recommend the creation of a centrally funded register of procedures performed in the UK, which would be maintained and accessible to researchers over several decades.

Thus far gene therapy has been confined to various of the body’s somatic cells. Because changes made to an egg or to a newly formed embryo will be passed to future generations our group has chosen to regard these cell reconstruction techniques as germline gene therapy. We are therefore giving ethical approval to an enterprise regarded by some people with suspicion if not downright hostility.

Two comments on this. First, as we presently understand it, the role of the small number of mitochondrial genes is confined to the smooth operation of the body’s energy production system. Furthermore the location of these genes, and their pattern of inheritance, mark them out as quite distinct from the far larger number of genes housed in the nucleus. Our group was confident that it is legitimate to distinguish between the two sets of genes when making ethical judgements.

Our view of the ethical acceptability of replacing mutated human genes with healthy human genes refers to mitochondrial genes and to no others. Indeed, if the Government were in due course to authorise the use of these techniques, they would be regulated by legislation (the Human Fertilisation and Embryology Act) that anticipated their advent, and refers specifically to the treatment of mitochondrial disease, not to disease in general. No floodgate is being opened.

And yet, and yet… We must be realistic. Several respondents to our group’s call for evidence talked of the “slippery slope” by which they meant that sanctioning germline therapy on mitochondrial genes would inevitably lead to calls for the work to be extended to nuclear genes. Personally I find slippery slope arguments unhelpful because pretty well every advance can be deemed a step to something potentially nasty. When crossing an actual slippery slope you rope yourself to something secure, or deploy an ice axe to maintain a purchase. Intellectually speaking you can do the same thing: remain constantly aware and critical of what you’re doing and why, and resist the blandishments of siren voices that would have you do just a little more, and a little more, and a little more…

We could have dodged the germline gene therapy issue by arguing – as some do – that the new mitochondrial techniques aren’t really germline gene therapy at all, but constitute some other category. We rejected that idea. We are also clear that any move to explore germline therapy on nuclear genes is a separate issue which should be preceded by further debate. The technical and ethical issues that would be raised by treatments of this kind are far more complex, more contentious and more fraught with uncertainty than the treatments we have been examining.

Finally, back to the three parent issue. It arises because children born following the use of cell reconstruction will inherit nuclear DNA from their mothers and fathers, plus mitochondrial DNA from a donor: the “third parent”.  In our view there is no justification for ascribing parenthood to this third individual, or indeed grounds for fears that offspring born through this technology might find their inheritance confusing or disturbing.

Among the witnesses from whom we took oral evidence were some who spoke to us about the highly variable basis of human kinship. Such relationships range from those entirely determined by genetic inheritance to others reflecting social factors alone. Many are based on a sometimes bewildering blend of the two. Placed within this context, the “three parent” tag which has been much emphasised in so many media reports seems unremarkable. But it does divert attention from more substantial issues.

I’m hopeful that the three parent headline has had its day. But am I confident? No.

Geoff Watts

Dr Geoff Watts FMedSci is a freelance science and medical writer and broadcaster and a member of the Nuffield Council on Bioethics. He chaired the working group on Mitochondrial DNA Disorders.

Read the report on the Nuffield Council website.

The Nuffield Council on Bioethics is funded by the Nuffield Foundation, Medical Research Council and the Wellcome Trust.

Image credit: Dr David Furness. Wellcome Images

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