Colossal Biosciences, a company focused on de-extinction, has revealed its latest creation: genetically modified mice with a distinctly woolly mammoth-like coat. These “woolly mice,” as the company calls them, are entirely mouse but possess several mammoth-like traits, signifying a step towards Colossal’s ambitious goal: resurrecting the woolly mammoth.
Ben Lamm, CEO and co-founder of Colossal, stated that nearly 100 woolly mice have been created, and the team is seeking approval to test their cold tolerance. He indicated that Colossal is on track to produce a proxy woolly mammoth by the end of 2028. This proxy, genetically engineered from an Asian elephant embryo, will be gestated in an artificial womb. Lamm emphasized the potential of artificial wombs, not only for de-extinction efforts but also for human and endangered species conservation.
Woolly mammoths, close relatives of mastodons and modern elephants, went extinct approximately 4,000 years ago. Colossal aims to engineer Asian elephants to express mammoth-like traits, effectively creating a functional equivalent of the extinct species.
Two of the mice in an enclosure, a toy woolly mammoth at right.Two genetically modified “woolly” mice exhibiting mammoth-like hair traits. Photo: Colossal Biosciences
Colossal scientists achieved this by simultaneously editing seven genes in the mice’s DNA. The resulting coat is significantly thicker than in ordinary mice, comprised of longer, woollier hairs. The research team referenced 59 genomes of woolly, Columbian, and steppe mammoths, dating from 3,500 years ago to 1.2 million years ago, to guide the genetic modifications. They also consulted over 60 elephant genomes to pinpoint genes influencing hair growth and cold adaptation, crucial given the mammoths’ Ice Age environment.
One key modification involved deactivating the Fibroblast growth factor 5 gene, which regulates hair growth cycles, leading to hair up to three times longer than in unmodified mice. The function of several other genes (FAM83G, FZD6, and TGM3) was also altered, resulting in a woolier, wavier coat and curlier whiskers.
Beth Shapiro, Colossal’s chief science officer and a paleogeneticist, explained that the process wasn’t simply inserting mammoth genes into mice. Instead, they compared mammoth genomes to elephant genomes, identifying common mammoth genes that differed from elephants. Where these mammoth genes overlapped with hair regulation genes in mice, they edited the mice DNA to incorporate the woolly mammoth variants. This approach, combined with adding genes known to produce woolly phenotypes in mice, resulted in the “ultra woolly mouse.”
It’s important to note that Colossal’s eventual creation will not be a true mammoth, but a genetically modified Asian elephant – a proxy species standing in for the extinct animal.
Ethical concerns regarding animal welfare and the justification for these projects have been raised. Heather Browning, a philosopher specializing in animal welfare, questions the potential benefits of re-engineering mammoth-like elephants for Arctic environments and the overall justification for such projects.
Colossal is also working on proxy species for the thylacine (Tasmanian tiger) and the dodo bird, with the eventual goal of reintroducing them to their former habitats. Lamm and Shapiro hinted at upcoming updates regarding these projects, particularly in handling bird embryos, a distinct challenge due to their egg-laying nature.
Alison Van Eenennaam, a geneticist and professor of biotechnology at UC Davis, cautions that while gene editing for simple traits like hair is feasible, complex traits like behavior pose significant challenges due to our limited understanding of the underlying genetics. She emphasizes that a hairy elephant does not necessarily equate to a mammoth.
Browning further points out that while using proxy species circumvents some welfare issues, questions remain about ensuring their well-being, providing appropriate learned behaviors, and establishing suitable social structures. She highlights the reduced overall benefit of the project given the uncertainties and the need for a deeper exploration of the underlying justifications.
Lamm indicated potential progress with primordial germ cells in pigeons, a crucial step towards a proxy dodo, within the next six months. He also mentioned the challenges in somatic cell nuclear transfer and in-vitro fertilization of dunnarts, a key hurdle for creating a proxy thylacine.
Shapiro added that generative AI could enhance their artificial womb technology by improving its safety and efficiency.
While the first “mammoth” is still at least two years away, the woolly mouse demonstrates the tangible progress in genetic engineering at Colossal, with these small rodents paving the way for potentially larger, shaggier mammals.
