The Collapse of a Dangerous Analogy: Or, why mitochondria are much more than batteries

Cross-posted with Biopolitical Times on September 29th, 2014.

If you’ve read anything at all promoting 3-person IVF, you’ve no doubt seen the analogy that the cellular organelles called mitochondria “just” produce energy, and that the biologically extreme technique often misleadingly called “mitochondrial replacement,” which would combine genetic material from three people into an embryo, is comparable to merely “changing a battery.”

The connotation is immediate: Just as changing a battery in a computer doesn’t affect the hard disk, so too, the logic goes, would this technique – more accurately termed nuclear genome transfer – merely provide the resulting person with a healthy new source of energy (from the second woman’s mitochondria.)

The mitochondria-as-batteries analogy has always been spurious, and for numerous reasons. But it has now, thankfully, collapsed.

A new article in New Scientist lays out the evidence. It reviews case after case that supports a “new paradigm” whereby mitochondria are understood not merely as energy sources, but as important actors in and of themselves, greatly influencing numerous complex traits that do in fact make people who they are.

In short, this is because mitochondrial DNA “generates thousands of distinct small non-coding RNAs,” which “are able to influence how the nuclear genetic code is expressed through processes such as methylation, which alters gene activity, thus modifying which proteins are produced.”

And what does this mean?

The author explains that “the picture of the enslaved organelle seems to be precisely the wrong way around – in many ways, these bacterial “slaves” are in fact “masters of our fates.” In fact, he continues, this “suggests that the mitochondrion isn’t an evolutionary bystander, but a bona fide second genome.” (Emphasis mine.)

And as the article spells out, this suggests serious trouble for the safety and efficacy of nuclear genome transfer or 3-person IVF.

Most debate around the issue has worked on the assumption that mitochondria are simply cellular powerhouses. However, given their new-found influence over our bodies the implications of this technology may be far more radical than we have assumed.

No doubt about it, this article is a game changer. Along with its publication, New Scientist put out an editorial in which it admitted that the creation of “three-parent babies” is “more messy than we thought.” This was a necessary corrective, given that the editors confidently told their readers last year that “the mitochondrial genome is tiny, so the changes involved are minimal,” and that therefore there was no need to “fear babies made with genes from three parents.”

The editors’ new statement is a good one, and its importance in this ongoing debate could be critical. But they might have acknowledged that they are not the first in the scientific community to raise these concerns. Instead, they include the assertion that critics of nuclear genome transfer “may be right – albeit for the wrong reasons.” (They give no explanation of what those “wrong reasons” are.)

Did New Scientists’ editors not notice when evolutionary biologists published areport in Science last year arguing that mitochondrial DNA influences a range of important traits? Or when one of the authors later wrote in his blog that this “evidence indicates that the battery analogy is really an inaccurate simplification of how the mitochondrial genome exerts its influence”?

Where were they when a New York Medical College cell biologist pointed out in an article at the Huffington Post that if a nucleus is moved into a different egg, that egg and the mitochondria it contains are absolutely essential to the development of a resulting child because this information will direct the expression of genes at the earliest stages of development?

The New Scientist may have missed its moment to offer a hat tip to those who have been right on this point for years, but at least there is now no excuse for the UK House of Commons to make the same mistake. When its Science and Technology Committee meets on October 22 for a final inquiry into the science of what it calls “mitochondrial donation,” it will have to contend with the expanding evidence that mitochondria are not just batteries for the importantgenes, but that the genes they contain exert powerful influences of their own on traits ranging from memory, to aging, adaptation and obesity.

That also means acknowledging just how drastic toying with the mitochondrial genome would be. The “new paradigm” changes the safety profile of the proposed techniques, as well as the ethical and practical calculus of evaluating them: even if they may be able to reduce the risk of inheriting mitochondrial disorders, they will also alter the phenotype of the resulting child in unknowable ways.

The accumulating evidence about mitochondrial function makes it clear that issues of critical scientific importance were either overlooked or minimized in recent reports on safety and efficacy from the Human Fertilisation and Embryology Authority (HFEA) and the Department of Health. Will anyone now have enough faith in the merits of their conclusions to actually change UK law based upon their recommendations?

With the UK Parliamentary vote planned for this fall, we will soon find out. In the meantime, let’s put this dangerous analogy to rest.

Creating embryos or children with 3-person IVF is not like changing a battery at all. It’s more like suddenly realizing that the pages of your cookbook were stuck together and you just accidentally combined two different recipes in one bowl. It could end up all working out, but you probably wouldn’t want to bet your child’s life on it.

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