Colossal Biosciences
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.
Colossal Biosciences
"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 Business Insider 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.
Colossal acknowledges its animals aren't perfect genetic matches to extinct dire wolves.
Colossal Biosciences
"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.
Colossal Biosciences
Those dire wolf traits have been lost in the lineage of canids, the company's CEO Ben Lamm told BI, 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.
"Would a chimpanzee with 20 gene edits be called human?" Skoglund asked.
Colossal Biosciences
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."
Colossal Biosciences
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. Lamm said 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.
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."
Colossal Biosciences
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.
On Monday, biotech company Colossal announced what it views as its first successful de-extinction: the dire wolf. These large predators were lost during the Late Pleistocene extinctions that eliminated many large land mammals from the Americas near the end of the most recent glaciation. Now, in a coordinated PR blitz, the company is claiming that clones of gray wolves with lightly edited genomes have essentially brought the dire wolf back. (Both Time and The New Yorker were given exclusive access to the animals ahead of the announcement.)
The dire wolf is a relative of the now-common gray wolf, with clear differences apparent between the two species' skeletons. Based on the sequence of two new dire wolf genomes, the researchers at Colossal conclude that dire wolves formed a distinct branch within the canids over 2.5 million years ago. For context, that's over twice as long as brown and polar bears are estimated to have been distinct species. Dire wolves are also large, typically the size of the largest gray wolf populations. Comparisons between the new genomes and those of other canids show that the dire wolf also had a light-colored coat.
That large of an evolutionary separation means there are likely a lot of genetic differences between the gray and dire wolves. Colossal's internal and unpublished analysis suggested that key differences could be made by editing 14 different areas of the genome, with 20 total edits required. The new animals are reported to have had 15 variants engineered in. It's unclear what accounts for the difference, and a Colossal spokesperson told Ars: "We are not revealing all of the edits that we made at this point."
© Colossal
About 252 million years ago, volcanic eruptions triggered the End-Permian Mass Extinction, also known as the Great Dying. About 96 percent of marine species were wiped out—but were things just as grim on land?
Scientists have debated whether this event caused nearly as much terrestrial destruction. Now, researchers from the Nanjing Institute of Geology and Paleontology (NIGPAS) of the Chinese Academy of Sciences suggest that terrestrial ecosystems did not suffer nearly as much as the oceans.
Led by paleontologist Feng Liu, the NIGPAS team found evidence for refugiums, oases where life thrived despite the devastation. Not only did these refugiums give life a chance to survive the mass extinction event, which lasted 200,000 years, but they are now thought to have been crucial to rebuilding ecosystems in much less time than was previously assumed.
© Corey Ford
On Tuesday, the team behind the plan to bring mammoth-like animals back to the tundra announced the creation of what it is calling wooly mice, which have long fur reminiscent of the woolly mammoth. The long fur was created through the simultaneous editing of as many as seven genes, all with a known connection to hair growth, color, and/or texture.
But don't think that this is a sort of mouse-mammoth hybrid. Most of the genetic changes were first identified in mice, not mammoths. So, the focus is on the fact that the team could do simultaneous editing of multiple genes—something that they'll need to be able to do to get a considerable number of mammoth-like changes into the elephant genome.
The team at Colossal Biosciences has started a number of de-extinction projects, including the dodo and thylacine, but its flagship project is the mammoth. In all of these cases, the plan is to take stem cells from a closely related species that has not gone extinct, and edit a series of changes based on the corresponding genomes of the deceased species. In the case of the mammoth, that means the elephant.
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