The great mitochondria debate

On 19 November, Dr Geoff Watts, Council member and Chair of our Working Group on mitochondria, will discuss the Human Fertilisation and Embryology Authority’s (HFEA) consultation on mitochondrial transfer at a discussion event in London. In this article, adapted from a longer post which first appeared on the Wellcome Trust blog, he reflects on some of the Working Group’s conclusions.



“Bioethics body gives green light to three-parent babies.” That was the headline I least wanted 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.

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.

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.