“The Colossal woolly mouse marks a watershed moment in our de-extinction mission,” company cofounder Ben Lamm said in a statement. “This success brings us a step closer to our goal of bringing back the woolly mammoth.”
Colossal’s researchers say their ultimate goal is not to re-create a woolly mammoth wholesale. Instead, the team is aiming for what they call “functional de-extinction”—creating a mammoth-like elephant that can survive in something like the extinct animal’s habitat and potentially fulfill the role it played in that ecosystem. Shapiro and her colleagues hope that an “Arctic-adapted elephant” might make that ecosystem more resilient to climate change by helping to spread the seeds of plants, for example.
But other experts take a more skeptical view. Even if they succeed in creating woolly mammoths, or something close to them, we can’t be certain that the resulting animals will benefit the ecosystem, says Kevin Daly, a paleogeneticist at Trinity College Dublin. “I think this is a very optimistic view of the potential ecological effects of mammoth reintroduction, even if everything goes to plan,” he says. “It would be hubristic to think we might have a complete grasp on what the introduction of a species such as the mammoth might do to an environment.”
Mice and mammoths
Woolly mammoth DNA has been retrieved from freeze-dried remains of animals that are tens of thousands of years old. Shapiro and her colleagues plan to eventually make changes to the genomes of modern-day elephants to make them more closely resemble those ancient mammoth genomes, in the hope that the resulting animals will look and behave like their ancient counterparts.
Before the team begins tinkering with elephants, Shapiro says, she wants to be confident that these kinds of edits work and are safe in mice. After all, Asian elephants, which are genetically related to woolly mammoths, are endangered. Elephants also have a gestation period of 22 months, which will make research slow and expensive. The gestation period of a mouse, on the other hand, is a mere 20 days, says Shapiro. “It makes [research] a lot faster.”
There are other benefits to starting in mice. Scientists have been closely studying the genetics of these rodents for decades. Shapiro and her colleagues were able to look up genes that have already been linked to wavy, long, and light-colored fur, as well as lipid metabolism. They made a shortlist of such genes that were also present in woolly mammoths but not in elephants.
The team identified 10 target genes in total. All were mouse genes but were thought to be linked to mammoth-like features. “We can’t just put a mammoth gene into a mouse,” says Shapiro. “There’s 200 million years of evolutionary divergence between them.”
Shapiro and her colleagues then carried out a set of experiments that used CRISPR and other gene-editing techniques to target these genes in groups of mice. In some cases, the team directly altered the genomes of mouse embryos before transferring them to surrogate mouse mothers. In other cases, they edited cells and injected the resulting edited cells into early-stage embryos before implanting them into other surrogates.
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