The fifth floor of George Church's laboratory at Harvard Medical School is off limits to visitors. "That's where the mammoths and Neanderthals live," the genetics professor says with a straight face. He's joking, obviously, because there aren't any Neanderthals. Mammoths? Not yet, but it may not be too long, he says.
Church and his team are aiming to do what many hitherto believed — and some still do — is impossible: bring a dead species back to life. Most woolly mammoths died out roughly 10,000 years ago amid a changing climate and possibly widespread hunting by humans. Isolated populations continued to roam on St Paul Island in the Bering Sea and Wrangel Island in the Arctic Ocean — but the species finally became extinct about 3700 years ago.
Just as Darwin's theories on evolution provoked controversy and were dismissed outright by some, so Church's claim that he is well on the way to bringing back the mammoth has divided scholars. He has already worked out genetic sequences for the elephant's shaggy ancestor using DNA extracted from remains preserved in frozen permafrost. But such scraps of DNA on their own are not enough to recreate a species. So instead he's editing DNA in the living cells of modern Asian elephants — the mammoth's closest living relative — with the aim of recreating some of the traits that allowed mammoths to survive very cold temperatures, including dense hair and thick layers of body fat.
Sporting a greying, Darwinian beard, Church looks something of a throwback himself. With a voice as rich as fruit cake and an unhurried delivery, he has the air of a 19th-century naturalist — except that instead of a Victorian dress coat he's wearing a campus T-shirt with a picture of a mammoth and the slogan "Extinction will soon be a thing of the past". The fifth floor of his genetics lab is out of bounds — accessible only by service lift — because it's a storage area for equipment, he eventually explains. But if he's right about reviving the dead, he'll need somewhere to put the fledgling mammoths.
Asian elephants and mammoths share a common ancestor that lived about six million years ago, which means the genetics of de-extinction are not as hard as some people think, he says. "[In the evolutionary sense] they're very close. We're taking information from frozen mammoths, decoding it into the computer and then resynthesising it and putting it into Asian elephant cells."
The result, he hopes, will be cells that it will soon be possible to turn into an embryo and implant into a living host. Growing a full-sized mammoth — or more precisely an elephant-mammoth hybrid — from those cells would be a scientific breakthrough. It still poses a huge — some say insurmountable — challenge, not least because of the difficulty of finding a surrogate that can carry the embryo to full term.
Church says his team is already looking at potential hosts. "We're considering all the options and the options include pygmy elephants, African elephants, Asian elephants, possibly even more distant animals."
If he succeeds, the end result would not be a creature instantly recognisable as a mammoth; more like a hairier elephant. "An Arctic elephant is a better term," he concedes. "We're just aiming for 50 or 100 [gene edits] initially, but we're probably going to be capable of doing 20,000 or more." Using Crispr gene-editing technology — a process that resembles using molecular scissors to find and bind exactly the right gene sequence — he has already succeeded in making thousands of changes to a cell nucleus. "Our record so far [outside the mammoth project] is 24,000 edits in a single cell."
Even creating a hairier elephant would be remarkable. The purpose is not just scientific curiosity: Church suggests the project could protect endangered elephants and boost their numbers by giving them genetic advantages to survive in the vast tracts of frozen wilderness once roamed by mammoths. "We'd like to see them occupying every continent of the world, except for the two [mammoths didn't inhabit] — Antarctica and Australia," he says. "We hope to set up stations away from human populations so the [Arctic] elephants have room to roam and prosper."
There's another, arguably more compelling reason, Church says: to reduce the risk of a catastrophic climate-change event. In the Arctic the permafrost that keeps carbon trapped underground like a huge freezer is gradually thawing. If it reaches a tipping point, the gases released could throw the planet's climate into a calamitous feedback loop and overwhelm any efforts to cut back man-made emissions. One factor exacerbating the thaw, says Church, is that herds of wild mammoths no longer roam the permafrost, trampling trees and other vegetation.
That trampling allowed carbon-capturing grasslands to dominate — and the grasslands allowed the permafrost to penetrate deep into the ground. But now trees, moss and scrubland have taken hold, preventing winter frost from penetrating the soil so easily. If herds of huge elephant-mammoths and other herbivores could be reintroduced, that process could be reversed, Church says. That's the theory, at least.
There's commercial interest in the quest too. What started as an experiment at the edges of genetics, confined to scientific literature, has caught the eye of tech entrepreneurs who like the possibilities of de-extinction. Church's collaborator is Ben Lamm, founder of Hypergiant Industries, a Texas-based artificial intelligence company. The two men have formed Colossal, a company that aims to patent the technology for genetically resurrecting the woolly mammoth. "Our goal is to have our first calves in the first four to six years, but like any hard engineering project that could move some," says Lamm, erring on the side of optimism. "But that's what we're targeting. Just remember, our goal isn't just to bring back functional mammoths but to rewild the Arctic. We want hundreds of our Arctic elephants in the nearest term possible."
Investors who've helped kick-start the US$15 million venture include the Winklevoss twins, made famous in The Social Network film for suing Mark Zuckerberg, whom they accused of stealing their idea for Facebook. They've since made billions from bitcoin and other ventures. "Cameron and Tyler [Winklevoss] are big supporters of the project," says Lamm. "They're also Harvard alumni, which is great."
Peter Thiel — one of the original Facebook investors and a PayPal cofounder — is also a backer. "Peter gave the original grant to George," Lamm confirms. "We haven't reached out to Peter yet in this seed round, but we'd love to collaborate with him.
"Our investors look at Colossal in a very similar way to the Apollo [space] programme. So, as we go down this journey, what are the interesting, innovative technologies that we can build and have massive applications to veterinary medicine, healthcare and beyond? Veterinarians and conservationists can use our technologies to help threatened species, not just extinct species."
Elon Musk, the Tesla and SpaceX billionaire , is said to have an interest in the subject. Max Hodak, Musk's former business partner in the biotech company Neuralink, tweeted: "We could probably build Jurassic Park if we wanted to. Wouldn't be genetically authentic dinosaurs but [shrug emoji] maybe 15 years of breeding [plus] engineering to get a super exotic novel species."
Colossal's advances could, for example, help save species under threat from diseases or climate change by giving them genes to resist infection or better tolerate heat and drought. As with the space race, the dash to be the first lab to resurrect a dead species has prompted rivalry between scientific superpowers. Japanese and Korean teams are also working on mammoth remains. China is intent on bringing back the Yangtze River dolphin. Other species ripe for revival include the passenger pigeon, the New Zealand moa bird, the Tasmanian tiger, the Cascade Mountain wolf and Steller's sea cow.
If you think it's impossible, consider the case of a black-footed ferret named Elizabeth Ann. She was the first member of an endangered species (once thought to be extinct) to be revived, and was created in 2020 from the remains of a female ferret that had died in the mid-1980s leaving no descendants. Scientists were able to clone Elizabeth Ann from cells that had been kept in a freezer.
The task of trying to recreate a long-dead species from scraps of DNA, with no good cells available, is much harder, but Church thinks it can be done. The mammoth is the favourite candidate partly because it would be such a novelty — a huge potential zoo attraction — and partly because mammoth DNA is relatively well preserved thanks to the cold climate in which the mammoths lived. DNA can stay intact for hundreds of thousands of years if frozen underground. The oldest sequenced DNA belongs to a woolly mammoth believed to have lived a million years ago.
Steven Spielberg's film Jurassic Park tells the story of a businessman who creates a theme park of cloned dinosaurs from prehistoric DNA, only to have his dreams ruined when the resurrected Tyrannosaurus rex and a pack of velociraptors start to snack on the human guests. Dinosaurs became extinct 65 million years ago — so although the idea is entertaining, it's unlikely enough dinosaur DNA could survive to make anything other than science fiction. Mammoths, though, roamed the Earth far more recently.
"I'm nearly certain that someone will claim to have achieved de-extinction within the next several years," says Beth Shapiro, a palaeogeneticist at the University of California Santa Cruz, in her book How to Clone a Mammoth. "The technology to do all this is available today. But what would the end product of this experiment be?" She continues, "Should de-extinction be declared a success if a hirsute elephant is born with a cold-temperature tolerance that exceeds that of every living elephant? I argue that [such an animal should be capable of] living where a mammoth would have lived and acting like a mammoth would have acted. What is the point, after all, of bringing a species back from the dead if not to re-establish a wild population?"
If anyone can do it, she says, the 6ft 5in Church can. "There are few people in the world who successfully straddle the gulf that separates genius from madness, and he is one of them — probably because his genius far outweighs his madness. The hurdles standing in the way of fully reconstructing the genomes of extinct species remain high. George Church, however, is very tall."
It's not unusual for Church, 67, to be out of step with prevailing thinking. A vegan since before it was fashionable, there's more than a touch of the rebel about him. Growing up in Clearwater, Florida, a 10-year-old Church was fascinated by biology and grafted the branches of one type of fruit tree on to another in his garden. By the time he reached his teens he had taught himself basic computer programming, even though the only way he could get his hands on a computer was to piece together components from an electrical supply shop.
At university in North Carolina he raced through the curriculum in just two years, finishing two bachelor's degrees in zoology and chemistry while simultaneously helping to determine the three-dimensional structure of "transfer RNA", a key genetic molecule. It was an important breakthrough, but he spent so much time in the lab he failed a course and was expelled from the doctoral programme.
Fortunately Harvard took him in and during the 1980s he helped develop DNA sequencing, a technique used today to investigate intractable diseases including cancer. His work has helped reduce research costs from billions of dollars to hundreds. He was among the first to use Crispr to splice mammalian cells, building on the pioneering work led by Jennifer Doudna of the University of California. He met his wife, Ting Wu, a geneticist, while a postgraduate at Harvard. They have one daughter, Marie, aged 30.
Will a herd of elephant-mammoths roam the Arctic in Marie's lifetime? Church believes they will. Another way of looking at the project, he says, is that he is not "de-extincting a species but de-extincting mammoth genes". Already he has isolated a mammoth gene for cold-resistant haemoglobin — blood protein that works well in low temperatures — and is closing in on a way to shrink the elephant's ears so they don't freeze in the Arctic wind. "We don't know exactly how many genes it is [that we need to edit to create a hairy Arctic elephant], but the good news is that mammoths are really closely related to Asian elephants. Asian elephants already have predispositions to like the cold. They'll build giant snowballs, or they'll break through the ice in the lakes and swim in the winter."
Already other laboratories have created genetically modified mice to use in medical research. Genetically modifying an elephant is much trickier, not least because an embryo implanted into a surrogate elephant mother would take 22 months to come to term compared with a 20-day gestation period for a mouse. Asian elephants are also endangered — conservationists working to protect the species may well object to the idea of using elephant mothers for mammoth experiments.
Does Church think it's possible to find an alternative mammal he can use as a host? "It's feasible," he says. "In addition we have in vitro development and artificial wombs. We're pursuing all the avenues in parallel until we get a clear green light."
If it can be done, phase two of Colossal's plan would be to introduce Arctic elephants into the wild. Church is collaborating with Sergey Zimov and his son Nikita, who are attempting to restore a vast area of Siberian wilderness to a state similar to that of the Pleistocene epoch that ended 12,000 years ago, having begun 2.6 million years earlier. Pleistocene Park — another project that sounds like a Spielberg spin-off — is a giant experiment to see whether the unfreezing of the permafrost can be halted by restoring grasslands that during the Pleistocene stretched across Siberia, Alaska and much of Canada's Yukon.
"We've been collaborating with Sergey and Nikita for years," Church says. "It's a very impressive experiment. Probably one of the few of its kind, maybe the only one. They've put a lot of sweat into clearing the land the way that a mammoth would and then populating it with other herbivores to see what would happen. Then they're measuring methane and carbon dioxide, and the plant growth and soil temperature, all sorts of things. It's 160 sq km. It's an amazing, gigantic experiment."
The Zimovs' research base is an abandoned Soviet satellite station, complete with giant dish that once beamed propaganda to this remote corner of northeastern Siberia. In harsher times Stalin sent political prisoners into exile here. Church arrived in the summer of 2018, travelling across 15 time zones to reach Cherskiy, a dying goldmining town that sits on the Kolyma River. "It was 53 hours from point to point," he recalls.
This is the epicentre of what climate scientists call the Siberian carbon bomb. Micro-organisms are locked underground in what amounts to a giant deep freeze. As temperatures rise they are slowly awakening, releasing carbon and methane and threatening to cause runaway global warming. Since the start of industrialisation, humans have managed to release about 350 billion tonnes of anthropomorphic CO2. Locked up in the Siberian deep freeze are about 1500 billion tonnes of carbon.
Could elephant-mammoth hybrids survive there today? They might at least face less of a threat from humans, who seem to have hunted them thousands of years ago. A recent documentary presented by Sir David Attenborough revealed how Neville and Sally Hollingsworth, a husband and wife team of amateur fossil hunters, unearthed a mammoth graveyard near Swindon in Wiltshire. They zeroed in on a gravel quarry using Google Earth and when they visited it they spotted the tip of a huge fossilised leg bone sticking out of the mud. Nearby they found a hand axe used by Neanderthal hunters. Further excavation of the site revealed bones from a group of mammoths, believed to be two adults and two juveniles. Some displayed marks thought to be caused by butchery, lending weight to the claim they fell victim to hunters.
Even if all the practical problems are overcome and Arctic elephants are created to roam once again in Siberia, another elephant is still left in the room. What legal limits, if any, should be placed on attempts to resurrect extinct animals? Should scientists be permitted to research and experiment freely? Any tinkering with the fabric of nature carries risk. Even if the hybrid elephant-mammoth is a necessary invention, what if the next engineered species becomes invasive? What if it takes an unexpected turn and damages the ecosystem into which it is introduced? Most countries have laws banning the release of non-native species and this would most likely apply to elephants modified with mammoth traits.
Professor Helen Sang, a genetics expert at the Roslin Institute, the research centre at the University of Edinburgh famous for cloning Dolly the sheep, said Church faced a huge challenge in overcoming technical hurdles and regulatory controls: "You could probably get an elephant that had long reddish hair, which is what I believe mammoths had, but would it really be a mammoth?
"The editing, making the genetic changes, is amazing and George Church has pioneered a lot in that area. But it's an enormous challenge and I just wonder whether it's really, really worth it."
There will also be objections on moral grounds, similar to the criticism of genetically engineered crops. Just as protesters decried "Frankenstein foods", so too will there be those who warn that Church's attempts to bring animals back from extinction will end badly for humans, as Jurassic Park did.
The trump card is the Siberian carbon bomb. The plan to release herds of magnificent beasts back on the tundra sounds like the longest of long shots. But what if it turned out that one thing that could help save life on Earth was something that must first be brought back from the dead?
Written by: Nick Rufford
© The Times of London
