Did Colossal Biosciences Really Bring Dire Wolves Back From Extinction?

The beginnings of a real-life “Jurassic Park” are playing out in a high-security, undisclosed location where three unusually large, fluffy, white wolf pups are growing up.

The gene-editing startup Colossal Biosciences, which recently raised $400 million for its de-extinction and conservation missions, announced the pups’ existence on Monday, saying they are the first living dire wolves since the species went extinct some 12,500 years ago.

Brothers Romulus and Remus were born in October, followed by female pup Khaleesi in January — all delivered by Caesarean section from their hound-dog surrogate moms to avoid complications from their large size.

“It’s the first time that we see an animal that carries multiple genes from an extinct species,” Love Dalén, a professor of evolutionary genomics who specializes in mammoth DNA and sits on Colossal’s Scientific Advisory Board, told BI in an email.

Colossal Biosciences says these are dire wolves. Some geneticists say they aren’t.

“I wouldn’t call this the world’s first de-extinction. I am not necessarily against the initiative, but these are not dire wolves,” Pontus Skoglund, a geneticist who leads an ancient DNA lab at the Francis Crick Institute, told BI in an email.

Even if they were real dire wolves, other scientists say, it may not be a good idea to bring them back.

How Colossal Biosciences made its wolves

Colossal acknowledges its animals aren’t perfect genetic matches to extinct dire wolves.

“It’s not possible to create something that is 100% genetically identical in every way to a species that used to be alive,” Beth Shapiro, Colossal’s chief science officer, told BI.

For one thing, scientists don’t have a complete genome for dire wolves. Shapiro said they filled in some gaps by extracting more DNA from the best available samples of ancient dire wolves — a 13,000-year-old tooth and a 72,000-year-old skull.

They say they did an ancestral analysis of that genome and determined, for the first time, that the dire wolf’s closest living relative is a gray wolf.

In the end, Colossal says it decided to target 20 edits in 14 genes to make pups with the large size, white fur color, extra-muscular legs, and other key traits they think dire wolves had.

Those dire wolf traits have been lost in the lineage of canids, Lamm said, so reviving the relevant genes “de-extincted” them.

The startup’s scientists created embryos from this new genome and implanted them in hound dog surrogates.

Why these ‘dire wolves’ are controversial

“Would a chimpanzee with 20 gene edits be called human?” Skoglund asked.

To defend his dire wolves, Lamm pointed to the film “Jurassic Park,” in which scientists use frog DNA to fill in gaps in ancient dinosaur DNA sequences.

“Are they dinosaurs? Or are they genetically modified organisms that have been engineered with ancient DNA and frog DNA and all this other stuff?” he asked.

Lamm says this is a philosophical question about how you define a species. Vincent Lynch, a scientist who uses genomics to study evolutionary history, disagrees.

“It’s not a dire wolf. It’s a cloned gray wolf that they transgenically modified to make it look like what we think dire wolves looked like,” Lynch, who is a professor at the University at Buffalo, told BI. “We don’t even really know what they looked like.”

Lynch added that the creatures in Jurassic Park would not be real dinosaurs either. Their frog genes might influence their behavior. Maybe they would hop around. Maybe they would be able to change sex like frogs, which is what happens in the movie.

“These are grey wolves with an impressive but ultimately small number of precise changes to their genomes,” Kevin Daly, a paleogeneticist at Trinity College Dublin, told BI in an email. “It might be best to think of these as being inspired by dire wolves.”

Bridging the divide between a grey wolf and a dire wolf would require more complex alterations, like deleting whole sections of the genome, Daly added.

Complicating matters is the fact that Colossal Biosciences has not published this work in a peer-reviewed journal. The company’s CEO, Ben Lamm, told BI it plans to submit a paper.

Daly said that, without a scientific manuscript from Colossal, “it is difficult for the scientific community to scrutinize its approach and claims.”

Colossal staff plans to monitor the three animals to see how their dire-wolf genes show up as the pups mature. They’re looking for bigger muscles and a slightly different head shape than unmodified adult grey wolves.

“It’s hard to tell that in puppies,” Lamm said.

Why de-extinction?

Lamm says the company is striving for “functional de-extinction,” which means reviving the traits of ancient animals like dire wolves, dodo birds, or woolly mammoths just enough for the new animals to play the same ecological role as their ancient counterparts.

Colossal’s classic example is a new woolly mammoth that can walk the plains of the Arctic, stamping away winter snow and beating down tree growth to form a cold grassland. This “mammoth steppe” would, in theory, absorb more carbon and prevent permafrost from thawing, slowing the climate crisis.

A Colossal mammoth doesn’t need to be exactly the same as an ancient woolly mammoth. It basically just needs to be a cold-adapted elephant.

Dalén said he sees the new animals as “Dire Wolf 1.0,” adding that, “The work presented here is just the beginning, and shows that Colossal could, in principle, keep doing edits of additional genes if they want.”

The movie “Jurassic Park” isn’t particularly flattering to this idea. The dinosaurs use their frog DNA to change sex and reproduce, threatening to overwhelm their human captors.

With Colossal, Lynch has a similar concern — not about human-eating mammoths, but about unintended consequences.

“Maybe it doesn’t behave like a woolly mammoth or a dire wolf,” Lynch said. After all, wolves and elephants are highly social animals that learn many basic behaviors from their parents.

These “dire wolves” are the first of their kind. All they have is their genetics.