The self-professed de-extinction company Colossal Biosciences revealed their latest creation this morning: a set of surprising hairy mice, bearing the nominal feature of the woolly mammoth on their little rodent bodies.
The living achievement is the Colossal woolly mouse, as the company has dubbed it. The animal is 100% mouse, but engineered to express several mammoth-like traits that set the stage for one of Colossal’s most (literally) massive goals: the resurrection of the woolly mammoth.
Ben Lamm, the CEO and co-founder of Colossal, told Gizmodo that the team has spawned nearly 100 of the woolly mice so far, and the team is getting approval to test whether the animals are cold-tolerant. Lamm said that the team is on track to generate a proxy woolly mammoth by the end of 2028, which the company plans to create out of a genetically engineered Asian elephant embryo and birth out of an artificial womb.
“I think our geoengineering tools and biotech, and our cognition biology tools are really, really interesting and will be very helpful for humanity, with disease and all that kind of stuff,” Lamm said, “but I think artificial wombs will be one of the most valuable things for both humanity and endangered species.”
The last mammoths went extinct about 4,000 years ago. The hairy proboscideans were close relatives of the mastodon and extant elephants. Colossal ultimately plans to engineer Asian elephants to express mammoth-like traits, so that their creation is—for all intents and purposes—a mammoth.
Colossal scientists generated the woolly mice by simultaneously editing seven genes in the animal’s genetic code. The critters’ coats (as you can tell) are thicker than in ordinary mice, made up of longer hairs with a more, erm, woolly texture than their typical fur.
Researchers on the project referenced 59 genomes of woolly, Columbian, and steppe mammoths that lived as recently as about 3,500 years ago to 1.2 million years ago to make the correct edits to the mice. The team also referenced over 60 elephant genomes to help identify genes in the proboscideans that affected hair growth and adaptation to the cold (if you’re just joining us, mammoths roamed a much cooler Earth than today, which culminated in the most recent Ice Age about 11,000 years ago).
Among the edits to the woolly mice was the switching off of the gene Fibroblast growth factor 5, which regulates hair growth cycles. Thus, the animals’ hair grew up to three times longer than in unedited rodents. The function of several other genes (FAM83G, FZD6, and TGM3) were also lost, making the animals’ hair woolier, their coats wavier, and their whiskers curlier.
“We didn’t go and shove mammoth genes into a mouse,” Shapiro said. “We have a bunch of different mammoth genomes that we’ve collected, and we can line them up against each other in a computer and compare them to genome sequences from elephants. Then we can ask where all of those mammoths in the genomes are the same as each other but different from the elephants.”
Where mammoth genes related to hair regulation overlapped with those in mice, the team edited the mice’s genomes to include the woollier variants. “All of these different variants have never occurred together in the same mouse,” Shapiro said. “Hopefully we were going to get something that was really, really wooly. An ultra woolly mouse.”
Though some of the team’s approach was this patchwork approach, “some of the genes were pure trait engineering,” Shapiro added. When the team found some genes associated with wooly phenotypes in mice, they added them. For the sake of this research, a shaggy, cold-resistant rodent was the goal.
Important for the pedants among us: The elephantine animal that Colossal ultimately brings to life will not be a mammoth, but a genetically edited Asian elephant. It is a proxy species, or an animal that suffices in lieu of the real thing.
Colossal is also working on creating proxy species of the thylacine (or Tasmanian tiger, Thylacinus cynocephalus) and the dodo bird (Raphus cucullatus), with the ultimate goal of releasing these animals in what was once their habitat, thereby filling environmental niches that have been vacant since their extinctions in the 1930s and late 17th century, respectively.
Lamm and Shapiro told Gizmodo that Colossal would have more updates before the year was out. Though they did not say what animals specifically would make major steps towards becoming proxy species, they noted that the company is very close on a breakthrough in handling bird embryos—which are a different beast altogether, as the animals lay eggs.
“What they’re [Colossal is] proposing to do is basically edit genes that control traits, and that’s fine for simple traits like hair,” said Alison Van Eenennaam, a geneticist and professor of biotechnology at the University of California, Davis, who is not affiliated with Colossal. “But for things like behavior, or other aspects of being an organism—where we don’t have a good understanding of the genetics behind it—those are the types of traits that I think are going to be difficult, because we don’t know actually what genes to edit.”
“Just because you have a hairy elephant doesn’t mean you have a mammoth,” Van Eenennaam added.
Lamm said the Colossal team is close to producing primordial germ cells in pigeons—a critical step towards the creation of a proxy dodo—which Lamm says could be achieved within six months, though it may take longer.
Somatic cell nuclear transfer and in-vitro fertilization of a dunnart—a small Australian marsupial—is a crucial challenge the team must overcome to get a living, breathing, proxy thylacine roaming the Earth. Lamm said a stripy dunnart may come along at some point—”probably the coolest looking dunnart ever,” he noted.
Shapiro added that generative AI could help the team improve their forthcoming artificial womb technology by helping the researchers understand how to make it safer and more efficient.
We’re still at least two years away from the team’s forecasted first “mammoth,” but the woolly mouse shows the very real genetic engineering going on at Colossal, and the mice that are paving the way for much larger shaggy mammals.
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