The quest to resurrect the woolly mammoth on Earth has taken another, well, small step with the creation of the Colossal Woolly Mouse. The lab-engineered rodents have seven genes that have been tweaked by scientists, giving them "core traits" of the grand extinct beasts.
Readers may be familiar with US startup Colossal Biosciences, which has made headlines in recent years for various mammoth-related genetics feats. Back in 2021, it announced its plans for "de-extinction" of the species, which was wiped off the planet some 4,000 years ago. Almost a year ago, to the day, the team announced its progress in understanding the mammoth's genes, thanks to one of its closest extant relatives, the Asian elephant (Elephas maximus). The genetics researchers have also expressed keen interest in bringing back the thylacine and the dodo.
And yes, we should point out the elephant (or mammoth) in the room: Tiny fluffy mice are a far cry from the enormous tusked beasts that roamed the Earth, before succumbing to a warming planet and human interaction. But they're more than just rodents in winter coats.
"The Colossal Woolly Mouse marks a watershed moment in our de-extinction mission," said Ben Lamm, Co-Founder and CEO of Colossal Biosciences. "By engineering multiple coldtolerant traits from mammoth evolutionary pathways into a living model species, we've proven our ability to recreate complex genetic combinations that took nature millions of years to create. This success brings us a step closer to our goal of bringing back the woolly mammoth."
The team looked at 121 mammoth (Mammuthus primigenius) and elephant genomes in order to identify specific genes that impacted hair and other traits that would have equipped the extinct animals with the physiological toolkit to survive in cold weather. Using CRISPR/Cas9 ribonucleoprotein (RNP) to edit seven genes in single-cell zygotes from lab mice to influence their coat's length, color, texture, thickness and that distinctive mammoth-like "curl." Another tweak resulted in changes in fat tissue, making the mice "built" for cold climates.
"The multiplexed editing strategies and mouse models established here provide a foundation for evaluating complex combinations of genetic modifications leading to the mammoth phenotype," the researchers explained in their preprint paper. "Future work will evaluate additional mammoth-specific variants associated with other cold-adaptive traits."
While the woolly mouse is a step towards the team's lofty goal, it doesn't take a geneticist to see there's a big difference between small rodents with short life cycles and the huge, long-living mammals – to say the least. So if a mammoth is on your Christmas wish list, you might be disappointed come December 25.
"In my professional view, we won’t be seeing a woolly mammoth, a dodo, or a thylacine for decades, because it’s not a matter of changing seven genes, you would have to change thousands, and you have to do the reproductive biology too," noted Professor Merlin Crossley, a molecular biologist at the University of New South Wales (UNSW). "Overall, it would be like stacking up ladders to get to the moon. But I have to hand it to this group of gifted scientists, they do keep reminding us of the power of genetic modifications."
Other experts agree, but also point out that, while bringing back the mammoth is a long way off, precise genetic modification of phenotypes could be a game-changer when it comes to helping species better adapt to a warming planet. However, phenotype expression is incredibly complex, with genes influenced by interactions with each other, as well as the environment and other factors.
"The engineering of cold tolerant traits from woolly mammoths into a living model species is a fascinating scientific breakthrough, showing how far gene editing has advanced in recent years," said Associate Professor Damien Fordham, from the Environment Institute at the University of Adelaide. "In addition to the immense scientific challenge that still lies ahead for the Colossal team, the threats that caused the demise of the woolly mammoth have only worsened in recent years. Therefore, it is somewhat fanciful to believe that one day we will again have self-sustaining populations of mammoths roaming Siberia.
"Nevertheless, the technology could potentially rescue living species from extinction through engineering of their phenotypes," he added. "For example, it could be used to reestablish warm tolerant traits lost in dwindling populations of species who are at risk of extinction from human-driven climate change."
This is something most genetics scientists seem to agree on, however, Colossal researchers believe that at some point we'll have the technology and the knowledge to do large-scale gene editing of species that could indeed bring back animal kingdom icons like the mammoth.
"Beyond de-extinction, this research enhances our understanding of evolutionary biology, genetic adaptation, and conservation genetics," added Andrew Pask, a Genetics & Developmental Biology professor at the University of Melbourne, who has also partnered with Colossal Bioscience for thylacine research. "The ability to reintroduce lost traits could aid in biodiversity restoration and even climate resilience efforts. The Colossal Woolly Mouse is a milestone moving us closer to the ultimate goal of de-extinction."
Ultimately, the woolly mouse – besides being so darn cute – is the culmination of years of work that has enabled the scientists to identify genes and predict the outcomes of their edits. And it is a huge achievement to have reached this point in only a few short years.
"The Colossal Woolly Mouse showcases our ability to use the latest genome editing tools and approaches to drive predictable phenotypes," said Dr. Beth Shapiro, Chief Science Officer at Colossal. "It is an important step toward validating our approach to resurrecting traits that have been lost to extinction and that our goal is to restore."
Source: Colossal Biosciences via Scimex/Businesswire
