Scientists working to unlock the secrets of de-extinction recently announced what they say is a turning point for the movement: the creation of transgenic mice with long, luxurious golden locks of tufted fur inspired by the coats of woolly mammoths.
They’re called Colossal woolly mice. And yes, they are cute to boot.
Transgenic mice — those that have had their genomes altered through genetic engineering — are not new. But what’s novel is the ability to engineer eight edits across seven genes and to do so simultaneously in one animal. The researchers also note that across three experiments, each of which used different combinations of edits, the method worked with high efficiency, resulting in living animals that presented the traits they were bred for.
In other words, the scientists have shown not only that they can make woolly mice, but also that they can do so reliably and repeatedly — a necessity for the project’s next steps.
“That’s been overlooked [in the immediate aftermath of the announcement] as far as how actually big of a deal that is in genetic engineering,” says Beth Shapiro, chief science officer at Colossal Biosciences in Dallas. She and her colleagues described the team’s findings in a paper posted March 4 at bioRxiv.org.
In all, the team created 32 woolly mice, each of which varied slightly in appearance, but reflected the traits the scientists predicted. Shapiro says there were no misfires or surprises in the lot. “Other than that they were so absurdly adorable,” she says.
But what do a few extra-furry mice have to do with bringing mammoths back from extinction? That part is a little more complicated and has led to misunderstandings since the findings were announced. For instance, the New York Post described the woolly mouse as a new species — it isn’t — and one post on X with millions of views stated that the scientists “spliced woolly mammoth genes into mice,” which is also not true.
“We did not want to take elephant genes and shove them into a mouse,” Shapiro says, “because that wouldn’t make any sense.”
So what is a woolly mouse, exactly?
To create the woolly mouse, scientists analyzed the genetic instructions, or genomes, of 121 mammoth and elephant samples to identify genes that may have given woolly mammoths some of their characteristic traits. These include longer, thicker, golden hair, as well as genes associated with lipid metabolism and fatty acid absorption for a life spent in the bitter cold.
“We can do a lot with the mammoth genomes we have. We can line them up on a computer and compare them to elephant genomes and ask where all the mammoths are the same as each other but different from their elephant cousins,” says Shapiro, who is also an evolutionary biologist at the University of California, Santa Cruz.
Using these hints about what makes a mammoth a mammoth, the scientists searched for similar traits in mice, either naturally occurring or achievable through genetic engineering. Mice are much easier to work with than elephants, of course. The tiny rodents require little space, breed quickly and have already been extensively studied with regards to their genetics. For instance, scientists have known since 1994 that if you turn off the FGF5 gene, mice will grow much longer hair than usual. Similarly, a gene known as Mc1r makes mice blond, while Frzd6 makes that hair whorly and frizzled.
The final step was transforming edited embryos into living, breathing, gloriously furred mice.
“Of course, mice are not elephants, which people have helpfully pointed out to us, as if we didn’t know that,” says Shapiro, referring to some common critiques her team has received.
This is why, she says, the woolly mice are just one part of the de-extinction goal. Colossal Biosciences, founded in 2021, has also been experimenting directly with Asian elephant cells, because that species is most closely related to extinct woolly mammoths.
Another arm of research focuses on the artificial reproductive techniques necessary to implant a genetically modified elephant embryo into a living elephant and then bring that animal to term. Similarly, the scientists are also working on de-extinction projects for the dodo and a wolflike marsupial known as the thylacine.
“All of this work is happening simultaneously,” Shapiro says.
We can’t just clone woolly mammoths
Jacquelyn Gill, an ice age ecologist at the University of Maine in Orono, does not hide her excitement about the idea of seeing a woolly mammoth in person one day.
“I understand why someone would be compelled to see a mammoth,” Gill says. “I’ve never seen my study system in person, right? It only exists in my mind’s eye, because I study a past that is gone.”
Nor does she reject the idea of de-extinction outright. In fact, Gill says, “the science of de-extinction is exciting and has broad applications.”
However, she is skeptical that what Colossal Biosciences is pursuing will qualify as bringing a woolly mammoth back from the dead.
For starters, despite the discovery of many well-preserved mammoth remains in permafrost —some complete with fur, muscles and skin — thousands of years buried in ice have destroyed every cell. This degradation means researchers cannot clone a mammoth, as has already been achieved in sheep.
“That’s a whole pathway to cloning that is cut off from us,” Gill says.
While gene editing may allow altering an Asian elephant in ways that superficially resemble a woolly mammoth, any attempt to do so will probably miss innumerable genetic flourishes that made woolly mammoths a unique species.
“A mammoth is not an elephant in a fur coat,” says Tori Herridge, an evolutionary biologist at the University of Sheffield in England.
Skepticism about bringing back woolly mammoths abounds
While Herridge finds the candidate genes for mammoth fur types and cold adaptation “really exciting and interesting,” she cautions that we still don’t know “what makes a mammoth a mammoth.”
“We all know that genes are complicated,” Herridge says. “One gene can affect many things, and many genes can act in concert.” Furthermore, she says, researchers don’t yet know if the genes used to dictate hair length, texture or color in the woolly mice will produce the same effects in Asian elephants.
Some troubleshooting can be done in the lab, Shapiro says. For instance, the team is already growing elephant cells in cultures and then testing how those cells respond to things like changes in gene expression. This allows Colossal to learn more about which genes to target without having to grow or experiment on a whole elephant.
The team has also already created elephant pluripotent stem cells, which could potentially be used to create any kind of cell — a crucial step toward assisted reproduction and the ultimate goal of implanting a transgenic elephant embryo into a living host.
Complicating this step is the fact that Asian elephant gestation can last up to about 22 months, meaning the process to create just one transgenic elephant will take significantly longer than that of woolly mice, which are pregnant for just 18 to 21 days. Moreover, Asian elephants are classified as endangered by the International Union for Conservation of Nature, which will probably restrict how this process unfolds.
Even assuming that all of this will one day be possible, and in numbers sufficient to create a viable woolly mammoth–like herd, other questions remain. For instance, scientists have shown that modern-day elephants are complex animals with established social and cultural knowledge that gets passed down through generations.
“You can’t teach a transgenic elephant how to be a woolly mammoth,” Gill says.
And the habitat that mammoths once roamed has changed quite a bit since the Pleistocene epoch, which ended 11,700 years ago.
Back then, the tundra would have been covered in life, Gill says, much like today’s Serengeti. Scientists call this biome, once the most widespread on earth, the mammoth steppe. But modern day ecosystems in those northerly regions are less productive and diverse, Gill says. Interestingly, this may have occurred because mammoths were keystone species that changed their environment. The mammoths made the mammoth steppe, in other words. And when mammoths disappeared, the ecosystem disappeared with them.
But if mammoths made an ecosystem once, perhaps they could do it again. De-extincted mammoths could, in theory, reengineer an ecosystem in ways beneficial to them, Gill says. And that theoretical capability is key to one of Colossal Bioscience’s goals: Bring back herds of mammoths that will stamp down permafrost and help keep carbon stored in the ground, protecting against further climate change.
“The problem is we don’t actually know if that’s possible,” Gill says.
Woolly mammoth calves on the ground by 2028?
For her part, Shapiro acknowledges the legitimate criticisms of Colossal Biosciences’ goals but remains optimistic about the future. In fact, one of the company’s other projects might succeed first: Bringing back the dodo.
After all, while bird genetics present their own litany of challenges, there’s a lot to be said for an animal that requires an egg rather than a surrogate mother, she quips.
And while Colossal Biosciences’ founder, Ben Lamm, has stated that he wants to see woolly mammoth calves on the ground by 2028, Shapiro has always stressed that genetics is just one part of the equation.
“We will have elephant cells that are edited and ready to go in early ’27, which is what we would need to have something on the ground in 2028,” Shapiro says. “But then there’s a lot of hard biology that still hasn’t been solved that needs to be solved.”