For months, researchers in a laboratory in Dallas, Texas, worked in secrecy, culturing grey-wolf blood cells and altering the DNA within. The scientists then plucked nuclei from these gene-edited cells and injected them into egg cells from a domestic dog to form clones.They transferred dozens of the cloned embryos into the wombs of surrogate dogs, eventually bringing into the world three animals of a type that had never been seen before. Two males named Romulus and Remus were born in October 2024, and a female, Khaleesi, was born in January.A few months later, Colossal Biosciences, the Texas-based company that produced the creatures, declared: “The first de-extinct animals are here.” Of 20 edits made to the animals’ genomes, the company says that 15 match sequences identified in dire wolves (Aenocyon dirus), a large-bodied wolf species that last roamed North America during the ice age that ended some 11,500 years ago.Ancient proteins rewrite the rhino family tree — are dinosaurs next?The company’s announcement of the pups in April, which described them as dire wolves, set off a media maelstrom. The ensuing debates over the nature of the animals — and the advisability of doing such work — have opened a chasm between Colossal’s team and other scientists.“I don’t think they de-extincted anything,” says Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California. She and many others say that the hype surrounding Colossal’s announcement has the potential to confuse the public about what de-extinction technologies can achieve.Colossal, meanwhile, has taken an increasingly combative tone in addressing criticisms, issuing rapid rebuttals to researchers and conservationists who have publicly questioned the company’s work. The firm has also been accused of taking part in a campaign to undermine the credibility of some critics. The company denies having played any part in this.Colossal stands by its claims and insists that it is listening to dissenters and seeking advice from them. “We have had this attitude of running towards critics, not away,” says Ben Lamm, a technology entrepreneur and co-founder of the company.Colossal ambitionsDe-extinction is an emerging field that represents the meeting point of several groundbreaking biotechnologies: ancient genomics, cloning and genome editing, ostensibly in the service of conservation. The field has roots in science fiction, with the term seeming first to have appeared in a 1979 novel by Piers Anthony called The Source of Magic. And Michael Crichton’s 1990 novel Jurassic Park — itself inspired by ancient-DNA investigations — popularized the possibility that long-dead organisms could be cloned from preserved DNA.There has never been perfect agreement on what counts as de-extinction — such as whether it means cloning exact replicas of extinct species, creating proxies that fulfil their roles in ecosystems, or something in between. Some count the birth of a cloned bucardo (Capra pyrenaica pyrenaica), a type of wild goat, as a first example. The animal’s genome was transferred into goat (Capra hircus) egg cells from frozen cell samples taken from one of the last living bucardo specimens in 2000. (The resulting creature died within minutes of birth1.) But this pathway to de-extinction isn’t an option for most species. DNA degrades over time, and without a sample of carefully preserved DNA, researchers would have to engineer the whole genome.The advent of CRISPR–Cas9 genome editing in 2012 provided another option. Researchers can identify genetic variants that contribute to key traits of extinct animals and edit these variants into cells of living relatives. They can then use that manipulated DNA to create a new animal through cloning.Plans to bring back animals such as the passenger pigeon (Ectopistes migratorius) and the woolly mammoth (Mammuthus primigenius) began to flourish. Even though there was interest among researchers and the public, funding was an issue. “We had been unable to get really any philanthropic interest in de-extinction,” says Ben Novak, who leads a passenger-pigeon de-extinction effort at the non-profit organization Revive & Restore in Sausalito, California.But in 2021, geneticist George Church at Harvard Medical School in Boston, Massachusetts, who was working with Revive & Restore, caught a break. He teamed up with Lamm to launch Colossal Biosciences with US$15 million in funding, much of which came from venture capitalists. De-extinction of the woolly mammoth would be the firm’s flagship project, using elephants as surrogates.Beth Shapiro joined US firm Colossal Biosciences in 2024 to focus on de-extinction work.Credit: Shelby Tauber/The Washington Post/GettyBeth Shapiro, an evolutionary geneticist who is chief scientific officer at Colossal, was initially sceptical that there was a strong conservation argument for creating elephants that had key mammoth traits. In 2015, she told Nature that her book on de-extinction, called How To Clone A Mammoth, might have been more accurately titled ‘How One Might Go About Cloning a Mammoth (Should It Become Technically Possible, And If It Were, In Fact, a Good Idea, Which It’s Probably Not)’.Shapiro turned down an offer to join the company at first, but started seriously entertaining the idea when Colossal expanded its de-extinction ambitions. It began projects to bring back the dodo (Raphus cucullatus), which was wiped out in the seventeenth century, and to restore thylacines (Thylacinus cynocephalus), the Australian marsupials that are sometimes referred to as Tasmanian tigers and that were hunted to extinction in the 1930s.She was especially interested in seeing de-extinction technologies applied to existing endangered species. Shapiro joined Colossal in 2024 as its chief scientist. “This is an opportunity to scale up the impact that I have the potential to make,” she says. “Maybe it’s a mid-life crisis.”The company, now valued at around US$10 billion, has attracted celebrity investors, including the media personality Paris Hilton and film director Peter Jackson, alongside a handful of leading scientists as staff and advisers.Dire disagreementsThe dire-wolf project was different from many of Colossal’s other efforts because it proceeded quietly. Few people knew about the work until this year, and that irked some researchers. “They didn’t invite any kind of conversation about whether or not that is a good use of funds or a good project to do,” says Novak.Shapiro says the secrecy around the dire-wolf project was designed to generate surprise, and to counter public perceptions that the company overpromises and under-delivers. She also says that the company talked extensively to scientists, conservationists and others about the project and how it should proceed.The firm has not released the full list of edits that it made — 20 changes to 14 genome locations. Fifteen of the changes were identified in two dire-wolf genomes obtained from the remains of animals that lived 13,000 and 72,000 years ago. The genome differs from that of the grey wolf (Canis lupus) by about 12 million DNA letters.The dodo (Raphus cucullatus) went extinct in the seventeenth century. Colossal Biosciences aims to edit the genome of a related pigeon species to mimic the dodo’s traits.Credit: Klaus Nigge/Nature Picture LibraryColossal says that other edits, including changes that led to the creatures’ white coats and contributed to their large size, were intended to replicate dire-wolf traits using gene variants found in grey wolves. Many scientists say that the coat colour in particular was probably inspired more by the animals’ appearance in the fantasy television series Game of Thrones than by reality.“There is no chance in hell a dire wolf is going to look like that,” says Tom Gilbert, an evolutionary geneticist at the University of Copenhagen and a scientific adviser to Colossal. He says he agrees with other scientists who have argued that, on the basis of what is known about the dire wolf’s range, it “basically would have looked like a slightly larger coyote”. Colossal notes that the coat colour is based on the discovery of variants in two dire-wolf genomes that it says would have resulted in light-coloured fur.According to an update from Colossal in late June, Romulus and Remus weigh around 40 kilograms, around 20% heavier than a standard grey wolf of the same age, and Khaleesi is about 16 kilograms. They live on an 800-hectare ecological preserve surrounded by a 3-metre wall. Colossal plans to make more of the animals, and to study their health and development in depth. It says it will not release them into the wild.The mysterious extinction of the dire wolfShapiro argued in her 2015 book that forming a wild population is a requirement for successful de-extinction. She nevertheless considers the dire wolves to be an example of de-extinction, and says that creating them will have conservation benefits for wolves and other species.Many scientists disagree. A group of experts on canids that advises the International Union for Conservation of Nature (IUCN) issued a statement in mid-April rejecting Colossal’s claim that gene-edited wolves could be considered dire wolves, or even proxies for the extinct species. The statement cites a 2016 IUCN definition for de-extinction that emphasizes that the animal must fill an ecological niche. The work, the group said, “may demonstrate technical capabilities, but it does not contribute to conservation”. Colossal has disputed this on the social-media platform X (formerly Twitter) saying that the dire-wolf project “develops vital conservation technologies and provides an ideal platform for the next stage of this research”.Novak says: “The dire wolf fits the Jurassic Park model of de-extinction beautifully.” The animals have the traits of extinct species and are, to his knowledge, not intended for release into the wild, he says. “It is clearly for spectacle.”Gilbert, who was a co-author of a preprint describing the ancient dire-wolf genomes2, says he is concerned that Colossal is not being sufficiently clear to the public about what it has done. “It’s a dog with 20 edits,” he says. “If you’re putting out descriptions that are going to be so easily falsified, the risk is you do damage to science’s reputation.”The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was a carnivorous marsupial that once roamed Australia, Tasmania and New Guinea. The last known specimen died in the 1930s. Credit: Chronicle/AlamyLamm rejects the idea that Colossal’s messaging undermines public credibility in science, pointing to what he says was an overwhelmingly positive reaction.Loring, who is part of an effort to use stem-cell technology in conservation, says that she sees merit in Colossal’s work. It has, she says, changed her views on how to repopulate northern white rhinoceroses (Ceratotherium simum cottoni). But she worries that Colossal’s messaging overshadows those contributions. “It may create an opportunity for us to educate the public,” she says. “More often, it creates an opportunity for us to be ignored.”To Love Dalén, a palaeogeneticist at the University of Stockholm and a scientific adviser to Colossal, the controversy is “a storm in a teacup” that detracts from Colossal’s achievement. “It makes me a little bit sad there is this huge debate and angry voices about the common name,” he says.DogfightShapiro says she was surprised and saddened by the strength of reactions to Colossal’s announcement. “It was harder than I thought it would be, and the questions were getting meaner and meaner,” she says.
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