The first major frontier of “de-extinction” has just been crossed. Earlier today, the company Colossal Biosciences reported that its scientists have successfully brought back a version of the dire wolf—purportedly the first such resurrection of a previously extinct species.
Colossal announced its seismic accomplishment Monday morning, accompanied by a lengthy cover article in Time magazine. Using a combination of gene-editing and surrogate dogs, the company has reportedly bred three sibling dire wolves since last fall, all of which appear to be healthy so far. The feat follows Colossal’s genetic engineering of “woolly mice” and should bode well for their larger resurrection project: bringing back the woolly mammoth.
Dire wolves (Aenocyon dirus) were canines that emerged during the Late Pleistocene, between 129,000 and 11,700 years ago, before becoming extinct around 9,500 years ago. They lived throughout the Americas and likely evolved to hunt down the especially massive megafauna seen during the Ice Age.
One difference from modern canines was their size; on average, they were as big as the largest gray wolves seen today, and with larger and more robust teeth. The general public might be more familiar with them lately thanks to their appearance on the HBO show Game of Thrones, where they were the trusted companions of the Starks.
Colossal’s dire wolves are named Romulus, Remus, and Khaleesi (the latter a reference to the show). All were born separately to surrogate large hound mixes, with Romulus and Remus born close together in October, and Khaleesi the youngest in the winter. The wolves are reportedly doing well in a 2,000-acre ecological preserve (its location has been kept hidden to protect the animals) and are being carefully and constantly watched by a staff of veterinarians.
“I could not be more proud of the team. This massive milestone is the first of many coming examples demonstrating that our end-to-end de-extinction technology stack works,” said Colossal CEO Ben Lamm in a statement. “Our team took DNA from a 13,000 year old tooth and a 72,000 year old skull and made healthy dire wolf puppies. It was once said, ‘any sufficiently advanced technology is indistinguishable from magic.’ Today, our team gets to unveil some of the magic they are working on and its broader impact on conservation.”
To be crystal clear, Colossal’s scientists didn’t create these so-called dire wolves by directly copying DNA over from ancient samples. Instead, after reconstructing and analyzing the wolves’ genomes, they made precise edits to the DNA of existing cells taken from a gray wolf. They made 20 edits in total, 15 of which were intended to make genes resemble the variants found in their dire wolf samples.
It’s these variants, the company says, that make dire wolves truly distinct from wolves alive today. Some of these variants, they say, are thought to influence the wolves’ size and facial shape. The nucleus of these reconstructed cells was then transplanted into donor egg cells that had their nucleus scooped out, which gave rise to viable embryos that were implanted into surrogate mothers (large hound mixes).
For context, the gray wolf—the closest living relative of the dire wolf—has a genome of about 2.45 billion base pairs (the fundamental building blocks of DNA). Given that dire wolf DNA differs by roughly 0.5% from that of gray wolves, the researchers have barely scratched the surface. This 0.5% disparity amounts to roughly 12 million base pairs that set the dire wolf genome apart from its gray wolf counterpart. Accordingly—and not to minimize the achievement—Colossal remains very far from capturing the genetic differences between the two species.
That said, Colossal says that its analysis of the dire wolf genome is the most comprehensive to date, and seemingly even resolves long-standing questions about the animals’ evolutionary history. Based on its work, they argue that gray wolves are indeed the dire wolves’ closest living relative, rather than jackals, as some recent research has suggested. But this feat of resurrection, while certainly impressive, does have its caveats.
The researchers avoided making certain changes that would more closely match dire wolf DNA if they believed those changes could potentially harm the health of the pups. Sometimes, they opted to make different but safer genetic changes that still resulted in the phenotype (a trait influenced by a genetic variant, like height) they expected from their analysis. One example of this highlighted by the researchers is the wolves’ white coloring.
In other words, the genetic makeup of these wolves isn’t a one-to-one copy of a dire wolf’s—it’s the company’s interpretation of how to safely create an animal they say is close enough. They’ve dubbed this approach “functional de-extinction.”
“Functional de-extinction uses the safest and most effective approach to bring back the lost phenotypes that make an extinct species unique,” said Beth Shapiro, Colossal’s Chief Science Officer, in an emailed statement. “We turn to ancient DNA to learn as much as we can about each species and, whenever possible, to link specific extinct DNA sequence variants to each key trait. In some cases, we learn that variants already present in the surrogate species can be used to engineer that key trait. In those cases, engineering existing variants into the donor genome is an optimal path, as that path provides strong confidence in the outcome with minimal risk to the animal.”
Some people might disagree that Colossal’s wolves are truly dire wolves, and the team’s claims about the dire wolf’s ancestry will be certainly studied further by other scientists. Scientific questions aside, there are also moral concerns about whether it’s appropriate to try bringing back extinct species in the first place.
But the company’s accomplishment shouldn’t be minimized either. This is a major barrier that has been broken, and the company isn’t done. Colossal also announced today that its cloning technology was recently used to birth four red wolves, which are the most critically endangered wolves around today (between 17 and 19 wolves exist in the wild, while 270 more are captive). And it still plans to birth the world’s first resurrected woolly mammoth by 2028.
The world has definitely changed now, and whatever you want to call them, these wolves likely only mark the beginning of a new era in genetic engineering.
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