“I would pay a lot of money to see a hairy half-elephant mammoth thing in a zoo or wildlife park, even knowing that it’s not authentic,” the geneticist Tom Gilbert exclaims. “But it would be a mistake to call it a mammoth.” His team at the University of Copenhagen just published a study that explores that idea: we will never have a mammoth identical to the ones who grazed millions of years ago during the ice age. None of the extinct species that his team is trying to revive will be the same. Tasmanian tigers, passenger pigeons and dodo birds will all be hybrids, a mix that resembles their extinct counterparts.
The fact doesn’t bother Harvard scientist George Church. “No surprise,” he says. The researcher has spent a decade working to revive the mammoth. To do so, he just raised over €14 million at his new company, Colossal. “We’re not working on bringing back an extinct species, but to bring back extinct genes and test them for their resistance to cold,” he explains to EL PAÍS. “The main principle isn’t to make perfect photocopies, but selective, diverse hybrids, with modern, ancient and synthetic DNA,” Church explains. He isn’t looking for a mammoth, but an Asian elephant with a handful of mammoth genes that allow it to resist polar temperatures, along with other characteristics that improve its capacity to adapt, including the resistance to modern viruses. Would that be a mammoth? Would it no longer be extinct?
Colossal’s webpage, which is seeking investors, speaks of “resurrecting the mammoth.” But many specialists prefer to call it a mammophant, as it will have features from both animals. Church wants to create a being that fills the mammoth’s ecological function to help combat the climate crisis. Should we make genetically modified species that are useful to us? “I think we design all kinds of hybrids,” responds the synthetic biology expert. “We’ve already done it intentionally and without realizing it, and those hybrids are a common way of creating new species and new functions through the course of evolution.”
Church’s technique is the most sophisticated of the three possible techniques that have been used for years in attempts to recover extinct animals. The simplest is through selective crossbreeding, a technique that has long been used to promote more desirable traits in domesticated animals and in this context seeks to recuperate the traits of an ancestral animal. Scientists have done so with cows, seeking to recuperate aurochs, and zebras, whose ancestor is the quagga.
The second technique is cloning. Since the 1996 cloning of “Dolly” the sheep, the same technique has been used with the DNA of disappeared animals. That technique allowed for the first and, so far, only successful attempt to resurrect an extinguished species. Technicians from Aragon managed to recover Celia, the last Pyrenean ibex, a mountain goat that went extinct in 2000 after decades of hunting. Celia’s clone was born with a lung defect that suffocated her less than ten minutes after her birth.
The third strategy for de-extinction is gene editing, the most promising because of technological capacities to rewrite DNA. In gene editing, DNA of the old animal is “copy and pasted” over an existing animal, the most similar animal possible. That’s what geneticist Tom Gilbert has attempted in his recent study, which took a rat as its subject.
The Christmas Island rat disappeared at the end of the 20th century after coming into contact with illnesses carried by European rats. For Gilbert and his team, it is an ideal candidate to analyze how far they can get with the technique they will use with the mammophants. When analyzing how much of its genome they could recuperate, they discovered that 5% of its genome differed from that of a similar modern rat.
“Imagine I give you a fragmented book in medieval English and I ask you to compare it with a modern English version of the same book. A large part will be recognizable, but some words will have changed so much that you wouldn’t be able to identify them. That’s our basic idea,” Gilbert explains.
That missing 5% isn’t in random points, but in concrete features. For example, the genes that define its sense of smell can’t be recovered. If the team were to resurrect it, the rat wouldn’t be able to smell like the original, changing its relationship with the environment and other animals. “Some of the most important genes that made the Christmas Island rat unique are irrecoverable. It’s almost impossible to hope to completely recreate an original species,” Gilbert summarizes.
Though Church is clear that it’s enough for him to reproduce certain features of the mammoth, he trusts that improvements in gene sequencing will resolve those gaps in the near future. “It took from 2001 to 2021 to complete the last 5% of the human genome,” Church remembers, “and as we continue sequencing genomes like humans and rats, we’ll keep improving and eventually get complete and precise smell genes.”
Christmas rats and blue butterflies
That doesn’t seem like an issue to expert Beth Shapiro, who has worked on recovering the genome of the mythical dodo bird and now the passenger pigeon, which went extinct after being widely hunted in the 20th century. “No one is suggesting that the only possible path is to create something that’s identical to a specific organism that once lived. That’s not the point,” says the researcher at the University of California. The goal of those who work for de-extinction is “to recover particular features, particular roles, that can help re-establish connections between organisms that live in communities. To do that, a perfect genome isn’t necessary,” Shapiro, author of How to Clone A Mammoth, explains.
Barcelona evolutionary biologist Carlos Lalueza-Fox doesn’t consider the recovery of the wooly mammoth to be “doable” because of the challenge’s technical complexities. Genetic manipulation and embryo experiments have developed primarily with lab animals. That’s why Lalueza has joined Gilbert to try to resurrect the Christmas Island rat–or another candidate whose DNA they already have: they just sequenced the genome of the Xerces blue butterfly, which vanished in the mid-20th century because of urban development in San Francisco. “An insect and a rat are more doable, but because the mammoth is more spectacular, they chose an objective that would allow them to raise more money,” says Lalueza, author of the book Des-Extinciones and researcher at Pompeu-Fabra University’s Institute of Evolutionary Biology. Gilbert clarifies that he’s not against those de-extinctions, but he wants their funders to understand what they will get.
The project that seeks to resuscitate the thylacine, or Tasmanian tiger, a legendary Australian marsupial, just received €4.5 million of investment from a philanthropist who discovered it on YouTube. It is led by Andrew Pask, who in 2017 published the animal’s genome, which he called “the best of any extinct animal.” Pask believes that Gilbert’s conclusions are overstated and that they don’t apply for all species. Pask’s thylacine project will use the bush rat as a genetic model.
Pask recognizes that it’s worthwhile questioning what the result of his work will be. “That brings up an interesting debate. If you use filler DNA in the genome of an extinct animal to complete it, what would it mean for that species?”
Church initially believed that his team would reach their goal in a matter of decades, but with the millions raised, he sees the objective closer to the six years that his business partner is promising. (The gestation of an elephant alone takes about 20 months.) And Church recognizes that he still doesn’t know how much they will have to modify the Asian elephant. The species are separated by half a million genetic differences, but for Church, a few dozen changes in DNA could be enough. The objective isn’t to retrace all the differences, but to obtain the 50 features that his team has selected as necessary so that the new animal can move across the frozen tundra like a fish in water.
Return to their natural habitat
According to Shapiro, it all comes down to how the specimen interacts with the ecosystem. None of these projects want to produce specimens to showcase in museums or cages, but to fulfill their function in the wild. “Everyone who is working on serious de-extinction projects does it with the objective of creating a substitute for the extinct species, to reconstruct and revive extinct features, create new organisms that can replace the ones that have gone extinct and permit those new organisms to revitalize and, in some cases, recover ecosystems that still haven’t adapted to the loss of that extinct species,” she explains.
Pask agrees. “The justification to do this with thylacines is to return them to the ecosystem and make them return to their natural habitat.” That’s why he defends the resurrection of the thylacine: its habitat in Tasmania has remained nearly identical to before, offering the perfect environment to re-introduce it and benefit the entire ecosystem.
All de-extinction projects come up against significant ethical, legal and political issues. But these five synthetic biology specialists are convinced that they will develop tools that will also help save endangered species. Pask says that his advances will be “immediately” applied to conservation science, “particularly our work with stem cells, gene editing and surrogacy, to help with reproduction programs for other marsupials.” And Church insists, going even further, that “when we talk about losing species, we rarely mention that at the same time, we could be gaining species more quickly.”