Colossal Biosciences Unveils Woolly Mice: A Step Towards Mammoth Resurrection
Colossal Biosciences, the ambitious de-extinction company, has announced a significant milestone in its quest to resurrect the woolly mammoth: the creation of woolly mice. These genetically engineered rodents, dubbed "Colossal woolly mice," exhibit key characteristics of their extinct, giant relatives, marking tangible progress in the company’s ambitious project. While the furry critters are undoubtedly 100% mouse, they represent a crucial stepping stone towards Colossal’s ultimate goal: bringing back a mammoth proxy species.
Ben Lamm, CEO and co-founder of Colossal, revealed that the team has successfully produced nearly 100 of these woolly mice. The company is now seeking approval to conduct tests to determine the animals’ tolerance to cold temperatures, a critical adaptation for mammoths that roamed the icy landscapes of the past. Lamm remains optimistic that Colossal is on track to generate a proxy woolly mammoth by the end of 2028, utilizing a genetically engineered Asian elephant embryo gestated in an artificial womb.
Colossal envisions a future where its biotechnology advancements, including geoengineering and cognition biology tools, contribute significantly to human well-being, particularly in the fight against disease. Lamm believes artificial wombs will prove invaluable for both human applications and the preservation of endangered species.
The quest to resurrect the mammoth centers on engineering Asian elephants to express mammoth-like traits. By carefully selecting and introducing specific genetic modifications, Colossal aims to create an animal that, for all practical purposes, resembles a mammoth.
To create the woolly mice, Colossal scientists simultaneously edited seven genes within the animal’s genetic code. The most noticeable result is the mice’s thicker coats, characterized by longer hairs with a woolly texture distinct from typical mouse fur.
Researchers relied on an extensive database of 59 woolly, Columbian, and steppe mammoth genomes, spanning a period from 3,500 to 1.2 million years ago. By comparing these mammoth genomes with over 60 elephant genomes, the team identified key genes that influenced hair growth and adaptation to cold environments in proboscideans. This comparative analysis allowed them to pinpoint the precise genetic edits needed to imbue the mice with mammoth-like characteristics.
One crucial edit involved "turning off" the Fibroblast growth factor 5 (FGF5) gene, which regulates hair growth cycles. This modification resulted in hair that grew up to three times longer than in ordinary mice. Additionally, the loss of function in several other genes – FAM83G, FZD6, and TGM3 – contributed to the animals’ woollier hair, wavier coats, and curlier whiskers.
Beth Shapiro, a paleogeneticist on the Colossal team, emphasized that the project did not involve simply inserting mammoth genes into mice. Instead, the researchers meticulously compared the genomes of mammoths and elephants to identify specific regions where the mammoth genome differed from the elephant genome. This allowed them to target those specific areas for modification in the mice.
"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," Shapiro explained. "Then we can ask where all of those mammoths in the genomes are the same as each other but different from the elephants."
By incorporating these mammoth-like variants into the mice’s DNA, the team aimed to create an "ultra woolly mouse" – a rodent with a coat far more akin to that of a mammoth than a typical mouse.
While some aspects of the process involved carefully selected patchwork, Shapiro also noted that "some of the genes were pure trait engineering." When the team identified genes associated with woolly phenotypes in mice, they actively incorporated them into the genome. The ultimate objective was to create a shaggy, cold-resistant rodent, regardless of the origin of the genetic modifications.
It’s important to note that the elephantine animal Colossal ultimately creates will not be a true mammoth, but a genetically edited Asian elephant – a proxy species representing the extinct giant.
Colossal is simultaneously working on creating proxy species of the thylacine (Tasmanian tiger) and the dodo bird. The company’s long-term vision is to reintroduce these proxy species into their former habitats, thereby restoring ecological niches that have remained vacant since their respective extinctions.
Lamm and Shapiro hinted at further updates from Colossal before the end of the year, suggesting potential breakthroughs in the creation of other proxy species. They specifically mentioned significant progress in handling bird embryos, which presents unique challenges due to the animals’ egg-laying nature.
Alison Van Eenennaam, a geneticist and professor of biotechnology at the University of California, Davis, while not affiliated with Colossal, offered a nuanced perspective on the project. She acknowledged the feasibility of editing genes that control simple traits like hair but expressed skepticism about the possibility of recreating complex traits like behavior, which are governed by a complex interplay of genes that are not yet fully understood.
"Just because you have a hairy elephant doesn’t mean you have a mammoth," Van Eenennaam cautioned.
Lamm countered by stating that the Colossal team is close to producing primordial germ cells in pigeons – a vital step toward the creation of a proxy dodo. He believes this milestone could be achieved within six months, although the process may take longer.
The creation of a proxy thylacine faces a different set of challenges. Somatic cell nuclear transfer and in-vitro fertilization of a dunnart – a small Australian marsupial – are crucial steps that must be overcome to bring a living, breathing proxy thylacine into existence. Lamm even suggested that a stripy dunnart could emerge from this process, potentially becoming "the coolest looking dunnart ever."
Shapiro added that generative AI could play a crucial role in refining Colossal’s artificial womb technology, helping researchers understand how to make it safer and more efficient.
While the first "mammoth" is still at least two years away, the creation of the woolly mice demonstrates the tangible genetic engineering taking place at Colossal and highlights the crucial role these rodents are playing in paving the way for much larger, shaggy mammals. This project underscores the potential of biotechnology to not only resurrect extinct species but also advance our understanding of genetics and contribute to the conservation of endangered animals.
