The park’s vision of bringing back ancient grasslands is “an exciting hypothesis,” says University of Maine palaeoecologist Jacquelyn Gill, based on the effects that today’s elephants have on their habitats. However, she cautions that researchers still don’t know the full details of how woolly mammoths’ ecosystems functioned, which complicates efforts to remake them today.
“To use that as a justification for a project like this—that has large ecological, social, ethical, [and] bioethical considerations—very much feels like putting the cart before the horse,” she says.
Sparing no expense
Still, the Zimovs’ project spurred Church and the conservationists at Revive & Restore to more seriously pursue research on mammoth DNA and elephant cells.
Until now, the Church lab’s work on elephants and mammoths has been a part-time, volunteer effort among his regularly changing staff. As a result, none of this work has yet been published in the scientific literature, to the consternation of outside experts. Church says his lab is now on track to submit two studies for publication in the next several months.
Church’s lab had also been conducting its elephant research on a shoestring budget of roughly $10,000 (£7,200) a year, drawing on a $100,000 (£72,000) donation from investor Peter Thiel and support from Revive & Restore.
By contrast, Colossal has $15 million (£10.8 million) at its disposal, fundraised from a group of investors including Silicon Valley venture capital firms and prominent life coach Tony Robbins. Colossal’s funding will support the Church lab’s ongoing research on elephant cells, as well as the company’s own lab, which will be run by Eriona Hysolli, a former postdoctoral researcher in Church’s lab who is now the company’s head of biological sciences.
Beth Shapiro, a palaeogeneticist at the University of California, Santa Cruz, says that Colossal’s funding model may be transformative for geneticists who work on species conservation. “It’s a totally new source of money—a huge source, potentially—that’s being invested directly into things that we all care about,” she says.
To help guide its efforts, the company has recruited scientific advisers, including two with a background in elephants or mammoths: University of Potsdam geneticist Michael Hofreiter, who studies mammoths and other Pleistocene animals, and Oxford zoologist Fritz Vollrath, who studies the behaviour of spiders and modern elephants.
The company’s advisers also include two prominent bioethicists who study genome editing: R. Alta Charo of the University of Wisconsin at Madison, and S. Matthew Liao of New York University. (Stanford University chemical engineer Joseph DeSimone, a member of Colossal’s scientific advisory board, is also a member of the National Geographic Society’s board of trustees.)
Life scientists find a way
Colossal’s ultimate goal is to swap enough key genes into the Asian elephant genome to make a “proxy” species that’s adapted to the Arctic cold, as mammoths once were.
The last common ancestors of woolly mammoths and Asian elephants lived six million years ago, Herridge says, and the two species still share more than 99.9 percent of their DNA. But the elephant genome stretches about three billion base pairs long. That means there’s more than a million individual differences between the Asian elephant and woolly mammoth genomes that scientists must sift through.
So far, Lamm and Hysolli say that the Colossal team is targeting a minimum of 60 mammoth genes, including genes involved in the animal’s fat deposits, its blood’s ability to hold onto oxygen at low temperatures, and its trademark shaggy coat.
Inserting the relevant mammoth genes into Asian elephant DNA would require making many genetic edits at once, a problem that Church’s lab has chipped away at in other species. His team used the powerful gene-editing technique CRISPR-Cas9 to edit the pig genome at dozens of different places at once, with the goal of making pigs whose organs can be safely transplanted into humans.
At least one of these candidate mammoth genes has been tested in transgenic lab mice. But individual genes can have many potential effects across the whole genome, and a gene’s ultimate effect on an organism’s traits comes down to when, where, and how much that gene is expressed within the body. This sort of regulation partially depends on stretches of DNA that aren’t well understood in extinct mammoths.
Church says that Colossal’s researchers should be able to screen for many potential issues early in a hybrid embryo’s development. That said, he acknowledges that some engineered traits—such as the animal’s ears, which need to be small to prevent frostbite—couldn’t be checked until late stages of development.
But the single biggest source of uncertainty for Colossal is how it will develop its embryos. Asian elephants are endangered, so to avoid the use of surrogates, the company says that it will develop an artificial elephant womb.
Past experiments with lambs and mice have shown that artificial wombs can support premature fetuses for up to four weeks, or support five-day-old embryos for up to six days. But so far, Church says that no artificial womb has been used through any mammal’s full gestation period.
To meet its goals, Colossal would need to pull off this world first with modern elephants. Their gestation lasts nearly two years and yields calves that weigh more than 200 pounds at birth.
Colossal also needs a self-sustaining supply of Asian elephant cells. In particular, Church says, the company must develop a line of induced pluripotent stem cells, which have been biochemically nudged into a primordial state that lets them transform into many possible cell types, such as eggs. These kinds of stem cells have been created for other endangered mammals, including the northern white rhino—but not yet for elephants.
Stopping to think if they should
Any experiment that involves animals comes with ethical challenges. If Colossal does successfully create a healthy hybrid calf, that only further raises the stakes. Elephants are long-lived, highly intelligent creatures that maintain complex, multigenerational matriarchal societies.
Research into ancient mammoths suggests they shared many of these social traits. So how would the very first mammoth-elephant hybrid be properly cared for and socialized? And how would a future herd of these hybrids learn to survive in the Arctic—and effectively reboot mammoth culture from scratch?
“It’s not just about having them exist, but making sure that once they do exist that they can thrive and live a flourishing life,” says Liao, the New York University bioethicist on Colossal’s scientific advisory board. “Otherwise, you’re being cruel to these animals.”
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