09 July 2022

The New Yorker: “CRISPR and the Splice to Survive”

If crispr confers the power to “rewrite the very molecules of life”, a synthetic gene drive increases that power exponentially. Suppose the researchers in San Diego had released their yellow fruit flies. Assuming that those flies had found mates, swarming around some campus dumpster, their offspring, too, would have been yellow. And assuming that those offspring survived and also successfully mated, their progeny would, in turn, have been yellow. The trait would have continued to spread, ineluctably, from the redwood forest to the Gulf Stream waters, until yellow ruled.

And there’s nothing special about color in fruit flies. Just about any gene in any plant or animal can—in principle, at least—be programmed to load the inheritance dice in its own favor. This includes genes that have themselves been modified, or borrowed from other species. It should be possible, for example, to engineer a drive that would spread a broken toxin gene among cane toads. It may also be possible one day to create a drive for corals that would push a gene for heat tolerance, to help them survive global warming.


But as is so often the case, solving one set of problems introduces new ones. In this case, big ones. Humongous ones. Gene-drive technology has been compared to Kurt Vonnegut’s ice-nine, a single shard of which is enough to freeze all the water in the world. A single X-shredder mouse on the loose could, it’s feared, have a similarly chilling effect—a sort of mice-nine.

To guard against a Vonnegutian catastrophe, various fail-safe schemes have been proposed, with names like killer rescue, multi-locus assortment, and daisy chain. All of them share a basic, hopeful premise: it should be possible to engineer a gene drive that’s effective but not too effective. Such a drive might be engineered so as to exhaust itself after a few generations, or it might be yoked to a gene variant that’s limited to a single population on a single island. It has also been suggested that if a gene drive did somehow manage to go rogue it might be possible to send out into the world another gene drive, featuring a “Cas9-triggered chain ablation”—or catcha—sequence, to chase it down. What could possibly go wrong?

Elizabeth Kolbert

I postponed reading the article above for quite some time, assuming it didn’t have much added information on genetic modifications and CRISPR – man, was I wrong! The story starts with a fairly common example of invasive species wreaking havoc in an ecosystem unprepared for its presence – in this case cane toads in Australia poisoning unsuspecting predators. And we continue onto the proposed solution from a team of scientists to gene-edit the toads to make them less toxic. The surprise twist for me was this potential technic called synthetic gene drive, which in theory could facilitate the spread of artificially inserted genes in wild populations.

A Cane Toad is exhibited at Taronga Zoo August 9, 2005 in Sydney, Australia
The cane toad, whose skin is toxic, has devastated the populations of some animals in Australia, where it is an invasive species. Credit: Ian Waldie/Getty

It’s absolutely astounding to me how scientists work on projects such as these with apparently no awareness of dangerous side-effects – I guess they’re only paid to deliver results, not to question their ultimate usage. At a time when many efforts are directed at preserving endangered species, or even resurrecting them, devising techniques for mass extermination seems wrong somehow. Even if these work, the damage done by invasive species to niche ecosystems may be too extensive by the time killer gene drives kick in. To me, this effort feels like intervention for intervention’s sake; just as people a century ago didn’t stop to evaluate the consequences of introducing foreign species, geneticists are now experimenting around with gene editing in the same manner, without knowing what their research may ultimately cause.

But there’s more! If gene drives can be used in mammals such as mice and rats to wipe out entire populations, invasive as these may be, the techniques may eventually be adapted to humans as well. There was a case already where a Chinese scientist covertly edited human embryos in vitro, which later resulted in the birth of two girls – who’s stopping some rogue scientist from introducing a human gene drive a decade or so from now?! Are we prepared to weaponize the human genome as we did with nuclear power in the 20th century?

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