“De-extinction is as much a data problem as a biology problem,” said Colossal CEO and co-founder Ben Lamm in a statement. “[AI] learns how regulatory DNA shapes living birds, then identifies the genetic switches that may have contributed to the dodo’s distinctive anatomy.”
“The dodo never had a chance,” wrote New York Herald Tribune writer Will Cuppy, in his 1941 book How to Become Extinct. “He seems to have been invented for the sole purpose of becoming extinct and that was all he was good for. I’m not blaming the dodo, but he was just a mess. The Portuguese called the birds doudos, or fools, because they would associate with the Portuguese on friendly terms and allow themselves to be hit on the head with clubs.”
De-extincting a bird, which does its gestating outside of any womb, will be harder. For the dodo, the researchers will first harvest primordial germ cells (PGCs)—nascent cells that give rise to eggs and sperm—from the nicobar pigeon, the dodo’s closest living relative. The PGCs will then be rewritten to add dodo traits, in the same way the gray wolf was edited. Those cells will then be injected through the shell of a domestic chicken egg into a microscopic chick embryo. The PGC’s will migrate to the embryonic gonads of the chick-to-be, taking up residence there. When the edited female chick hatches and grows and mates with an edited male, she will lay eggs that will produce not a chicken like her, but a dodo.
—Lon Tweeten for TIMEBut editing the PGCs in the first place will be no small thing, simply because there are so many sites on the dodo genome that code for the species’s traits—especially its ice-cream-scoop-shaped beak. It’s not precisely the genes that the researchers are reading in their work, but the regulatory elements—or the parts of the genome that determine which genes get switched on and off. And for the beak alone, that’s a heavy lift. There are more than 650 regulatory elements associated with beak size and nearly 1,700 with beak thickness and breadth. Worse, the fragmentation of DNA in the ancient samples gives an imperfect record of which of those regulatory switches are to be flipped which way. A new AI platform the company calls GenoMorph can fill in those gaps.
“For an ancient genome, this one is extraordinary,” says Beth Shapiro, Colossal’s chief science officer. “There are a few small holes, but far fewer than we usually see with ancient DNA. We’re really not missing much of the dodo genome.”
In the same way that some of the work Colossal did to read and analyze the dire wolf genome helped in the later work developing GenoMorph to read the dodo genome, the dodo work can similarly pay itself forward to reading and editing the genomes of other species to be de-extincted.
“It’s been rewarding to see that an approach developed for the dire wolf is now producing value across another species program,” said Shapiro in a statement. “Every scientific breakthrough becomes part of a scalable technology platform that can accelerate the programs that follow.” For now, the dodo remains biological vaporware—but it’s vaporware that could, before too long, take shape in the 21st century.
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