3-Parent IVF

In the last week, the UK government has launched a public consultation on regulating a proposed new reproductive technology, variously known as mitochondrial replacement/transfer/donation. At about the same time, it was announced that the US Food and Drug Administration was considering whether to allow clinical trials of mitochondrial replacement technology. And in response a number of commentators, like Marcy Danovsky of the New York Times, weighed in with opinions on the technology invoking the creation of “genetically modified humans” or “3-parent  babies”. See also this article from BioNews.

The fuss is about a still-experimental technology that, it is hoped, will enable women suffering from mitochondrial diseases to avoid passing them on to their children. Mitochondria, the tiny organelles responsible for energy metabolism in mammals, are popularly known as the “batteries” of the cell. They carry some very distinctive bits of DNA, which in part codes for their own assembly. Mutations in that DNA can give rise to malfunctioning mitochondria, and as a result a range of different symptoms, of varying – and unpredictable – severity. Mitochondria are found in the cytoplasm of cells, including the egg cell, and so everyone’s mitochondria are in fact inherited from his or her mother – including the DNA. It’s the only kind of DNA that comes solely from one parent.

This isn’t the place to go into deep technical detail about either mitochondrial disorders or the proposed technology, but the idea behind it in the case of women and families affected by mitochondrial disorders is to replace the malfunctioning mitochondria with ones provided by the cytoplasm of eggs from a donor. Although this has worked in animal models, it’s still unclear whether the same holds for humans, whose reproductive system and embryology may be rather different.

Last year the UK’s Human Fertilisation and Embryology Authority (HFEA) was asked to run a public consultation of attitudes to the changing of the wide-ranging British law governing reproductive medicine to permit further research into mitochondrial replacement, because the law as it stands forbids any kind of manipulation of the genetic makeup of an embryo. The consultation showed that the public, and numerous professional groups, were broadly in favour. (There were some notable, often predictable, exceptions, such as the Roman Catholic church for example.) Accepting this, the government’s next step in the process has been to launch the present consultation on the details of how this technology – always assuming it works at all – should be regulated.
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The problem is that mitochondrial replacement is indeed genetic manipulation – but of a very limited and specific kind, and not at all what most of us think of in terms of “playing God with genes”. Nothing about it is particularly targeted; “the genes” aren’t touched. It’s more like exchanging a box of genes that don’t work with one that does. And the number of genes involved is very small. The DNA of mitochondria codes for 37 genes, compared to the 20-30 000 or so found in the nuclear DNA of the human genome. So the percentage is vanishingly small, and these genes are all about constructing a weird little organelle, which some people hypothesise are evolved from engulfed bacteria; it’s nothing to do with the manipulation of characteristics that we tend to worry about ethically, such as height or skin colour or even intelligence. This also shows up the rhetoric of “3-person IVF” or “3-parent babies”. To my mind at least, you are straining definitions to consider the provider of 0.1% of the genome of a person to be in some sense a genetic parent, and that’s before we get anywhere near the difference between genetic and sociocultural ideas of what a “parent” is.

A disclosure here: I was part of the Oversight Group of the HFEA’s original public consultation on mitochondrial replacement last year. I joined that work with no strong preconceived ideas about the ethics of mitochondrial replacement; I had no particular axe to grind. However, the thing that has bothered me about the ethical debate here is almost total lack of attention being paid to the donors of the “healthy” mitochondria. These will have to come from the oocytes of women without mitochondrial disease. These potential donors have been invisible and voiceless in this debate. All ethical attention, it seems, has focused on the possibility that changing the law in the UK to allow mitochondrial replacement will open up the floodgates of genetic manipulation (possibly the case, but as noted above, the two kinds of genetic “change” are very different), and on the biological and social “unnaturalness” of having 3 people contribute, genetically, to a new individual.  When I have tried in public debate and elsewhere to raise questions about how we can safeguard the health and rights of the women who are the potential donors of mitochondria, I have been dismayed at the way in which crucial issues of recruitment, regulation, exploitation and the potential for global markets in eggs – all issues which have been raised around other areas of reproductive technologies – have been, and continue to be, neglected, while more speculative and science-fiction scenarios receive a lot of print and cyber attention.

Not everything about the bioethics of mitochondrial donation is about women. But it’s disheartening to see how some of the most crucial players in this emerging scenario – the women who donate the eggs which make mitochondrial replacement possible at all – are hidden from view.

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3-Parent IVF — 2 Comments

  1. One consideration I would add is that any directed interference in the human germ line – whether it be as hi-tech as ‘3 parent IVF’ or as low-tech as breeding for bloodlines – is eugenics and holds the potential for all the problems of bio-social elitism and reduction in genetic diversity that goes with it should it become more widespread and applicable to broader use.

    As far as I know all mitochondrial diseases discovered thus far are inherited, but that does not rule out the possibility of contagious ones or of contagious diseases that exploit particular configurations of mitochondria.

    Study of fossil DNA seems to suggest that many mitochondrial lines have gone extinct in the past 100,000 years. As mtDNA is passed down linearly and exclusively on the female line, much of that was probably due to pure chance. But selection pressure is also a possibility, so we need to be careful about eliminating mtDNA lines that may have evolutionary advantages we have not yet adduced.

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