Mammoth-elephant hybrids could be created within the decade. Should they be?

A new startup co-founded by Harvard geneticist George Church wants to use cold-adapted elephants to remake the Arctic tundra—raising major scientific and ethical questions.

Published 14 Sept 2021, 06:26 BST
Mammoth
This Damien Hirst sculpture of a gilded mammoth skeleton, installed in Miami Beach, Florida, is called "Gone but not Forgotten." But if the new startup Colossal has its way, dozens of genes from the extinct woolly mammoth will find new life in hybridized, cold-adapted Asian elephants.
Photograph by Jeffrey Greenberg, Education Images, Universal Images Group via Getty

Harvard geneticist George Church has co-founded a new company with an audacious goal: engineer an elephant that resembles the extinct woolly mammoth. The company, named Colossal, aims to use woolly mammoth DNA to make a hybridised Asian elephant that could thrive in Arctic climates. 

Using these hybrids, Colossal’s long-term goal is to convert swaths of today’s mossy tundra into the grassy steppes they once were during the Pleistocene epoch, the period of multiple ice ages that ended 11,700 years ago. Some scientists hypothesise that at large scales, this reversal could reduce future climate change by slowing the thaw of Arctic permafrost. Along the way, Colossal hopes to create new—and lucrative—biotechnologies, including tools that would supplement traditional conservation approaches.

“We’re de-extincting genes, not species,” Church says. “The goal is really a cold-resistant elephant that is fully interbreedable with the endangered Asian elephant.”

The idea of using biotechnology to help endangered species, or even extinct ones, is not new. In 2009 researchers successfully cloned a subspecies of ibex that had died out in 2000, though the clone lived for only a few minutes. In April, the San Diego Zoo and California-based nonprofit Revive & Restore announced they had cloned an endangered black-footed ferret, with the goal of adding genetic diversity back into captive-breeding programs. 

And for years, Church’s plans to “resurrect” a mammoth using the extinct titan’s sequenced DNA made headlines around the world.

“Most of the science had been solved; they just needed that funding and focus,” says Colossal co-founder Ben Lamm, a serial entrepreneur who most recently founded the AI company Hypergiant. “It’s kind of exciting—after two years of working on this—to start to tell people what we’re doing.”

Don’t expect pseudo-mammoths to arrive anytime soon. Colossal’s plans rely on several technologies that are unproven in elephants. Even on the company’s most aggressive timeline, Church says that Colossal’s first hybrid calf is six years away. A self-sustaining herd could take decades to establish.

But even at this early stage, Colossal’s mission raises profound questions about what it means for a species to be extinct—and how biotechnology can and should be used to address today’s extinction crisis. With Colossal’s arrival, the conversation is no longer abstract, says Tori Herridge, a mammoth biologist at the Natural History Museum in London. “My initial reaction was one of like, Shit’s getting real,” she says.

Welcome to Pleistocene Park

Church’s dreams of engineering a hybrid mammoth first deepened after an interview he did with the New York Times in 2008 about efforts to sequence the woolly mammoth genome.

At first, the idea was more of a grand intellectual puzzle. But in the years that followed, Church started to collaborate with Stewart Brand and Ryan Phelan, the founders of the California-based Revive & Restore. Brand and Phelan aim to use biotechnology to help shore up threatened species and to bring back extinct ones. 

“De-extinction and the idea of what we call genetic rescue is really a story about hope and being able to repair some of the damage that humans have caused over the centuries,” says Phelan. “It’s not nostalgia—it’s really about increasing biodiversity.”

Brand and Phelan invited Church to the world’s first conferences on “de-extinction,” held in 2012 and 2013 at the Washington, D.C., headquarters of the National Geographic Society. (National Geographic Partners, which produced this article, is a joint venture between The Walt Disney Company and the nonprofit National Geographic Society.)

At these meetings, Church met Sergey Zimov, a Russian ecologist and director of the Northeast Science Station in Cherskiy, in the Republic of Sakha. Since the 1980s, Zimov has studied Siberian permafrost and has sounded the alarm on the vast amounts of methane and carbon dioxide that could seep into the atmosphere as it thaws. 

“De-extinction and the idea of what we call genetic rescue is... about being able to repair some of the damage that humans have caused over the centuries.”

Ryan Phelan

Zimov also has an idea for how to keep that carbon in the ground. Since 1996, Zimov and his son, Nikita, have worked on Pleistocene Park, a fenced-off parcel of tundra near Cherskiy. The Zimovs have introduced elk, bison, reindeer, Bactrian camels, and other large herbivores there to test the creatures’ effects on the landscape.

Tens of thousands of years ago during the Pleistocene, much of Europe, Asia, and North America was covered in highly productive grassy steppes that were densely populated by diverse herbivores. By 10,000 years ago, many of these herbivores—including mammoths—had gone extinct across much of the world, probably in part because of human activity such as hunting. As these animals died out, the grasslands they maintained through grazing gave way to shrubs, trees, and mosses, yielding the tundra and taiga we see today.

Mammoths, the Zimovs suspect, were essential to maintaining the ancient Arctic’s highly productive grasslands. The massive creatures knocked down trees, stirred up earth, and fertilised the soil with their dung, helping the grasslands thrive. Their heavy footfalls also punched through layers of snow and ice, letting the Arctic chill more deeply penetrate the permafrost. 

“Consider the ecosystem kind of as a body,” says Nikita Zimov. “The mammoth is the right fist.”

Though Pleistocene Park doesn’t have that fist yet, the enclosure’s current herbivores may already be shaping its soils. In a study published last year, the Zimovs found that during winter, the compacted soils within Pleistocene Park can get nearly 6 degrees Celsius colder than the soils outside the park.

The lush green of Pleistocene Park weaves its way around northern Russia's blue lakes in this aerial view of the refuge.
Photograph by Katie Orlinsky, Nat Geo Image Collection

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.”

Colossal and the Zimovs have a friendly, unofficial agreement that Pleistocene Park could host some of the company’s future mammoths. For now, that experiment is confined to 7.7 square miles (20 square kilometres) of land, with eventual plans to fill out an area spanning 55.6 square miles (144 square kilometres).

But today’s migratory elephants can cover very long distances, and so did woolly mammoths. One recent study of a 17,000-year-old woolly mammoth tusk found that the young male walked tens of thousands of miles over its 28-year lifespan, crisscrossing much of modern-day Alaska. If Colossal’s full vision were ever to be realised, it would require rewilding millions of square miles of Arctic tundra to affect the global climate. 

The scale of these proposed changes would create thorny problems around land use, the effects on existing Arctic wildlife, and global governance. And what effects would there be on the approximately 180,000 Inuit in Russia, Canada, the United States, and Greenland—the peoples most directly at risk in a stressed, rapidly changing Arctic?

“Quite frankly, I get quite dubious when settler scientists want to remake the world in a particular image,” says Daniel Heath Justice, an Indigenous studies scholar and animal cultural historian at Vancouver’s University of British Columbia. He notes that biotechnology can be a useful tool for conservation, but he adds that work along these lines, such as Colossal’s research, “cannot only be led by non-Indigenous interests.”

In a statement, Colossal said that “there will be no impact on the Indigenous tribes that currently live in the area” and that its “highest priority is its commitment to conservation and the preservation of all species, including humans.”

If Colossal can deliver on that priority, the company’s supporters argue, living species will reap the benefit, even if an elephant-mammoth hybrid never arrives. With Colossal’s funding, the Church lab is working on a way to synthesise elephant endotheliotropic herpesvirus. This virus infects and kills many young Asian elephants, but it can’t be grown reliably in the lab. Culturing it would be a crucial first step toward making treatments and vaccines.

“The only realistic, reasonable line of argument for these kinds of technologies,” says Shapiro, the UC Santa Cruz geneticist, “is to help species that are alive thrive in a rapidly changing human environment.”

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