False controversy over ‘three-person’ babies

I haven’t paid much attention to the “three-person babies” controversy, because it seems like a manufactured one. After all, we’re balancing people who might develop a severe illness, against vague and inchoate concerns. Very few (though some) biologists that I know of express any concern about this issue. Mostly it seems to be the public, whose fears are stoked by ethicists and religious moralists.

Nature now has an article, The hidden risks for ‘three-person’ babies, which smokes out the major concern. Much of the piece focuses on what looks to be some sort of “hybrid break-down” due to conflicts between mitchondria and differing genetic backgrounds in animal models (flies and mice, for example). The worry is that mitocondria specified by their unique sequences exhibit functional differences which may interact in a deleterious fashion with different nuclear genomes. In more plain language, there may be a problem when you mix racial heritages. This is not a thesis that I usually see proposed outside of racialist circles, but it’s pretty obviously what the author is dancing around. Rather than focus on animal models, why not acknowledge that there are plenty of “natural experiments” which test this thesis. Here’s the rejoinder on Twitter:

And here’s the relevant section in the article (which is rather abbreviated after all the focus on Drosophila!):

They also pointed out that most of the evidence for risk stems from studies that used strains of flies and mice that had been highly inbred — a process that would increase the genetic differences between the strains and therefore produce a greater ‘mismatch’ when the mitochondria are swapped. They argued that such studies have little relevance for human populations that interbreed all the time. The “lack of any reliable evidence of mitochondrial–nuclear interaction as a cause of disease in human outbred populations”, they wrote, “provides the necessary reassurance to proceed”.

Aside from very rare instances such as in Helgadottir et al. there isn’t any evidence of hybrid breakdown across human populations. Greg Cochran and Henry Harpending looked in the fertility literature about ten years ago, and they found no evidence of depressed fitness. Pontus Skoglund has looked for the sort of purifying selection you see in the Neanderthal-modern human admixture event (X chromosome and genic regions have less Neanderthal), and found none. The earliest branching human population are Khoisan, about ~200,000 years before the present, and there’s no good evidence that major incompabilities exist which are fundamentally racial except for the one I gave above (that is, differences are nearly fixed between populations, and crosses have reduced fitness due to lower fitness in heterozygote state). And of course there are the “natural experiments” of populations across the New World, and places like South Africa, where highly diverged mtDNA lineages are moving into different genetic backgrounds.

Presumably there have to be other issues that people worried about ‘three-person’ individuals are concerned with. What are they? I can accept the functional importance of variation in mitochondria, but I don’t see what this has to do with the three-person individual as opposed to people who are racially mixed. If the different genetic backgrounds are an issue, then it is more defensible to object to interracial relationships than three-person individuals, since in the latter case the only reason you’re introducing the novel mitochondria is to prevent illness.

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