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

Posted by Jessica Cussins on September 29th, 2014

The editors at New Scientist have made a “U-turn” on “three-parent babies.” Their new conclusion: “It’s more messy than we thought."

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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 a report 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 important genes, 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.

Previously on Biopolitical Times:

Posted in Assisted Reproduction, Bioethics, Biopolitics, Parties & Pundits, Biotech & Pharma, Egg Retrieval, Inheritable Genetic Modification, Jessica Cussins's Blog Posts, Media Coverage, Public Opinion, Reproductive Justice, Health & Rights, Sequencing & Genomics, The United Kingdom


Comments are now closed for this item.

  1. Comment by Paula Boddington, Sep 30th, 2014 12:37pm

    Hi Jessica, yes, I had read your excellent earlier piece - I also commented last year along some similar lines about how the debate was being presented in the media, here:

    One thing that really concerns me, is what a tragedy it would be for families if they used an experimental new technique precisely in order to avoid known medical problems, only to create unknown medical problems!

  2. Comment by Jessica Cussins, Sep 30th, 2014 11:51am

    Thank you for this thoughtful and important comment, Paula Boddington! It has been so frustrating to see this experimental fertility technique falsely promoted as a way to save lives. (In fact, this point was "Misconception 1" in a blog I wrote a while back called Eight Misconceptions about “Three-Parent Babies”

  3. Comment by Paula Boddington, Sep 29th, 2014 1:49pm

    The emergence of these new realizations about the complexity of mitochondria and the safety implications of three person IVF is depressingly unsurprising. One part of what has been going on is that the rush to 'three person IVF' has been fueled not just by the formal arguments hurriedly advanced in its favour, but also by the rhetoric of how the technique has been presented - as about preventing disease, with the urgency of throwing whatever we can at serious disease seemingly justifying the haste. It was really clever, or really dumb, how piece after piece made this out to be about preventing disease. Now, everyone wants to do that, surely? Now that's something we should do right now, surely? But, none of this was ever going to cure a single person with mitochondrial disease. It was about treating the fertility of those who risked passing it on to their children. And it was not even about preventing carriers of mitochondrial disease passing it on, because the means to do that is not three person IVF itself, but the use of contraception. Sorry to be so harsh - of course I feel for those affected. But it's the rhetoric of 'quick, prevent this terrible disease' which was either by design or carelessness harnessed to act as cover for trying to rush this through the UK parliament. If it had been presented as a fertility technique that enabled women to have genetically related offspring, well, that seems much less urgent. After all, to use the technique, you have to have another woman's egg available. So you could just use that egg, to put it bluntly. In fact, if your aim is to prevent disease risk, it does look increasingly foolish not to, given the unknowns involved in three person IVF.
    What's more, it's easy to have half a hunch that maybe, just maybe, another underlying motivation was to make sure that the UK is seen as a good place to do biotech.



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