In addition to placing dire wolves more firmly in the Canidae family tree (they’re slightly closer to jackals than to gray wolves, but more than 99.9% identical to both at a genetic level) and determining when dire wolves split from the pack (about 4 million years ago), the team also located around 80 genes where dire wolves seemed to be most different. If you wanted to turn a gray wolf into a dire wolf, this would be the obvious list to start from.
Crying wolf
Colossal then began the process of using base editing, an updated form of the CRISPR gene-modification technique, to introduce some of those exact DNA variations into blood cells of a gray wolf kept in its labs. Each additional edit, the company hoped, would make the eventual animal a little more dire-wolf-like, even it involved changing just a single letter of a gene.
Shapiro says all the edits involve “genetic enhancers,” bits of DNA that help control how strongly certain genes are expressed. These can influence how big animals grow, as well as affecting the shape of their ears, faces, and skulls. This tactic was not as dramatic as intervening right in the middle of a gene, which would change what protein is made. But it was less risky—more like turning knobs on an unfamiliar radio than cutting wires and replacing circuits.
That left the scientists to engineer into the animals what would become the showstopper trait—the dramatic white fur. Shapiro says the genome code indicated that dire wolves might have had light coats. But the specific pigment genes involved are linked to a risk of albinism, deafness, and blindness, and they didn’t want sick wolves.
That’s when Colossal opted for a shortcut. Instead of reproducing precise DNA variants seen in dire wolves, they disabled two genes entirely. In dogs and other species, the absence of those genes is known to produce light fur.
The decision to make the wolves white did result in dramatic photos of the animals. “It’s the most striking thing about them,” says Mairin Balisi, a paleontologist who studies dire wolf fossils. But she doubts it reflects what the animals actually looked like: “A white coat might make sense if you are in a snowy landscape, but one of the places where dire wolves were most abundant was around Los Angeles and the tar pits, and it was not a snowy landscape even in the Ice Age. If you look at mammals in this region today, they are not white. I am just confused by the declaration that dire wolves are back.”
Bergström also says he doesn’t think the edits add up to a dire wolf. “I doubt that 20 changes are enough to turn a gray wolf to a dire wolf. You’d probably need hundreds or thousands of changes—no one really knows,” he says. “This is one of those unsolved questions in biology. People argue [about] the extent to which many small differences make a species distinct, versus a small number of big-effect differences. Nobody knows, but I lean to the ‘many small differences’ view.”
Some genes have big, visible effects—changing a single gene can make a dog hairless, for instance. But it might be many more small changes that account for the difference in size and appearance between, say, a Great Dane and a Chihuahua. And that is just looks. Bergström says science has much less idea which changes would account for behavior—even if we could tell from a genome how an extinct animal acted, which we can’t.
