Vikash Tatayah had never heard of Colossal Biosciences until the Texas-based company announced plans last year to bring back the dodo. Widely known for wanting to 鈥渄e-extinct鈥� the woolly mammoth, it said it was making strides in the genetic engineering of dodo-like birds, which would then be brought to Mauritius, one of the Indian Ocean鈥檚 Mascarene islands and the dodo鈥檚 sole habitat before extinction.
As conservation director at the Mauritian Wildlife Foundation, Tatayah had worked for decades to conserve the nation鈥檚 surviving endemic species, from the Mauritius fruit bat to the pink pigeon, a dodo relative. So he was surprised that his organisation wasn鈥檛 in the loop 鈥� and somewhat sceptical of the motives behind the multi-million-dollar project. 鈥淚 was the first to say, 鈥楬old on. There are a lot of other species of plants and animals on Mauritius that are threatened. That money could be better spent.'鈥�
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Whether genetic engineering should be used for conservation remains contentious, and many are especially wary of de-extinction. But a year later, Tatayah sees the potential return of the dodo as a way to simultaneously rescue endangered species 鈥� in particular the pink pigeon. 鈥淲e are very keen for the dodo to be brought back,鈥� he says.
Often overlooked is that the biotech breakthroughs Colossal and others are working on could have important collateral benefits. They could clear a path to using genetic tools to quickly help a whole range of animals resist the pressures they face from a changing environment. 鈥淭he pace of change is faster than evolution by natural selection can keep up with,鈥� says , the chief science officer at Colossal. Get the technology right and we could end up rescuing a whole range of species before they go the way of the dodo.
The dodo鈥檚 demise
The dodo鈥檚 disappearance from Mauritius ranks among the most notorious of human-caused extinctions. Less than a century after the first Dutch sailors arrived on the uninhabited island in 1598, the big-beaked, ungainly birds that the Europeans described as 鈥渢wise as bigge as swans鈥� . Only a few specimens remain preserved in museums. Even drawings of the birds are rare.
But the dodo was far from the only species on Mauritius decimated by the appearance of sailors and their non-human stowaways. 鈥淭here were so many species that went extinct before anyone had heard of them,鈥� says at the Earlham Institute in the UK, whose PhD focused on the plight of the pink pigeon on the island.
For centuries after the dodo鈥檚 demise, the pink pigeon 鈥� along with the rest of Mauritius鈥檚 native species 鈥� struggled to survive the new arrivals. Along with the sailors came cats and rats, and later macaques, all of which fed on bird eggs. Mongooses were introduced to deal with the rats 鈥� but they ate the eggs too. And a disease carried by the newly introduced species killed young birds. Invasive plants and sugar cane plantations fragmented the pink pigeon鈥檚 coastal forest habitat. 鈥淭here鈥檚 nowhere to escape,鈥� says Ryan.
How rare is a pink pigeon?
By 1990, there were just 10 pink pigeons identified living in the wild. 鈥淚t鈥檚 the last living pigeon of the Mascarenes,鈥� says Tatayah, who began captive breeding and habitat restoration efforts to boost the population around this time. Today, Tatayah says there are about 600 of the rose-tinted birds there, and the population appears to be stable. 鈥淲e鈥檝e turned back the tide,鈥� he says.
But a risk of extinction remains. Passing through a low-population bottleneck has resulted in a deficit of genetic diversity among the remaining birds 鈥� a situation common to many endangered species. In 2022, Ryan and her colleagues among more than 100 of them. They then modelled how interbreeding and the loss of diversity from random genetic drift would, over many generations, reduce the fitness of offspring and so affect the long-term survival of the species. They found that if no outside diversity was introduced, the pigeons were likely to go extinct by the end of the century. Considering the long-term picture is vital. 鈥淵ou cannot think in 10 or 20 years鈥� time,鈥� says Ryan. 鈥淵ou鈥檝e got to think in 200 years鈥� time.鈥�
One way to introduce diversity is to interbreed wild pink pigeons with their captive peers. As part of earlier conservation efforts in the 1970s and 80s spearheaded by the British naturalist Gerald Durrell and a far-sighted conservationist named Carl Jones, 17 of the birds had been brought into captivity at a zoo on the island of Jersey in the English Channel. Today, offspring of this population are held in several zoos in the UK and the US, and a handful have been reintroduced to Mauritius.
鈥淭here is a lot of diversity still present in the zoos. That is the first port of call,鈥� says at the University of East Anglia in the UK, an expert on pink pigeon genetics. But, he says, this still may not be enough to avoid extinction in the long run. The birds were captured from an already declining population, and many may be related to birds on the island today.
There is, however, another source of pink pigeon diversity: DNA preserved in museum specimens. But resurrecting that lost genetic variety would require much the same techniques as resurrecting an extinct species. 鈥淢aybe we need to reach into the toolbox of de-extinction,鈥� says Shapiro.
Since launching in 2021, has raised hundreds of millions of dollars of investment and captured headlines for its plans to bring back the woolly mammoth, the thylacine (also called the Tasmanian tiger) and now the dodo.
But, strictly speaking, it isn鈥檛 planning to bring back animals identical to those that went extinct, which company leaders acknowledge is essentially impossible. Even high-quality reconstructions of extinct genomes using preserved DNA will contain important gaps. This means that any organisms developed using the this DNA would have significant differences from the extinct species.
Instead, the company aims to engineer proxies of extinct species that can serve similar ecological functions. Instead of creating woolly mammoths, Colossal aims to use the mammoth genome as a guide to edit the genomes of contemporary elephants in order to create furry elephants that can survive in frigid conditions. In the case of the dodo, it plans to edit the genome of a related pigeon species called the Nicobar pigeon to create a big-beaked, flightless bird. 鈥淭he dodo is just a fat pigeon,鈥� says Shapiro.
Why is de-extinction controversial?
The spotlight created by these and other de-extinction projects has also spurred debate about the ethics of trying to bring back extinct species. For instance, a De-extinction Task Force at the International Union for Conservation of Nature (IUCN) identified a , including threats to the welfare of cloned animals, unknown ecological impacts of introducing proxy species and the prospect of 鈥渞e-extinction鈥�, in which a resurrected species gets wiped out again.
Another common criticism from conservationists is that a focus on futuristic de-extinction efforts undermines work to prevent the disappearance of the estimated 1 million still-living species that are on the brink. 鈥淚 think things like the dodo and the woolly mammoth are a distraction,鈥� says a zoologist at the University of Otago in New Zealand, who chaired the IUCN task force. 鈥淭he best application of de-extinction technologies is to avoid extinction in the first place,鈥� he says.
, Colossal鈥檚 CEO, counters that the company has been working on conservation projects beyond de-extinction from the beginning. 鈥淲e just weren鈥檛 talking about it,鈥� he tells me over coffee at a hotel in Manhattan, where he has come for a screening of a documentary about the American bison, another genetically restricted species he says the company鈥檚 technology could aid. 鈥淢ost people just want to talk about de-extinction.鈥�
Colossal鈥檚 publicity material now makes this wider mission clear. Each extinct species it has targeted is paired with a living 鈥渟ister species鈥�, which Lamm says the company will use its considerable financial and technological resources to help. Alongside the woolly mammoth, for instance, it is studying gene editing methods to reduce the Asian elephant鈥檚 susceptibility to a deadly herpesvirus. The company鈥檚 researchers recently reported they had figured out how to make regular elephant cells into stem cells that could be used for this and other purposes in a breeding programme. Alongside efforts to bring back the thylacine in Tasmania, they are supporting conservation of the Tasmanian devil. And a related project will edit northern quoll cells in an effort to make the tiny Australian marsupial resistant to the toxins of the invasive cane toad.
The pink pigeon is another example. After Tatayah heard about the dodo project, he got in touch with Colossal to discuss the organisation鈥檚 conservation work on Mauritius. He says the company was receptive. And, in November last year, Colossal and the Mauritian Wildlife Foundation to restore habitat on Mauritius in preparation for the arrival of dodo-like birds. Moreover, the gene editing tools being developed for the dodo will be used to restore lost genetic diversity to the pink pigeon. 鈥淐onventional conservation works. It just doesn鈥檛 work at the speed and scale we need it to,鈥� says Lamm.
In many ways, the technical challenges involved in restoring lost diversity to the pink pigeon are the same as those involved in bringing back the dodo, says Shapiro. Both require sequencing DNA from degraded samples, determining where those fragments fit in the genome, then editing DNA in living cells to match key sequences.
However, long before approaching the egg-laying stage, the researchers face a hurdle unique to avian species. For other animals, edits can be made to adult body cells. These can then be cloned and grown into a full organism by replacing the nucleus of a fertilised embryo with the nucleus of one of the edited cells. But this form of cloning isn鈥檛 possible for birds because the microscopic nucleus is hidden within the vast yolk of the egg. 鈥淚t is a universal problem for advancing biotech in birds,鈥� says at Revive and Restore, an organisation developing genetic engineering tools for conservation and de-extinction.
A workaround is to make edits to the precursors of reproductive cells called primordial germ cells (PGCs). These can be collected from an embryo and then grown in a lab, where multiple edits are made to their DNA. After PGCs differentiate into full sperm or egg cells within a surrogate parent, they can be used to create an embryo that will grow into a bird with all the edited DNA. But so far, growing PGCs has proven challenging for most bird species. 鈥淏irds are among the most endangered species in the world, and we don鈥檛 have any way of using genetic tools to edit their genome,鈥� says Shapiro.
Colossal鈥檚 approach to dodo de-extinction requires growing PGCs of the Nicobar pigeon in the lab. And it seems to be making progress. In November, the company announced it had successfully cultured Nicobar pigeon PGCs and found they could survive within a chicken, which could be used a surrogate parent for future clones. It is using a similar approach to culture the PGCs of pink pigeons. And in principle, these methods could be developed to genetically rescue any other bird, says Shapiro.
Increasing genetic diversity
Similar approaches have already been used for conservation efforts of some other animals with less challenging embryos than birds (see 鈥淏iotech to the rescue?鈥�, below). In 2020, Novak and his colleagues successfully cloned the endangered black-footed ferret, one of North America鈥檚 most threatened mammals, from a cell that had been frozen in the 1980s taken from a ferret named Willa. Two other Willa clones were born just last year. Those clones could add Willa鈥檚 genetic diversity to the population of black-footed ferrets, but, as with the pink pigeon, museum specimens might contain even more genetic variety. Given the pace of change and the scale of the threat to biodiversity, there isn鈥檛 time to wait, says Novak. 鈥淲e have to stop being afraid of using nature as an experiment.鈥�
This approach could be helpful for other species with similarly restricted genetic diversity, says van Oosterhout. However, he doesn鈥檛 think this elaborate and intensive genetic rescue on its own can hold the line against the threats faced by thousands of other species. 鈥淚t鈥檚 a bit like Sisyphus pushing a boulder up a hill,鈥� he says. 鈥淎t the same time there are hundreds of boulders running down.鈥�
Meanwhile, Tatayah, while continuing to push boulders on Mauritius, is planning in earnest for the arrival of dodo-like birds. He points to the endangered tambalacoque tree 鈥� sometimes called 鈥渢he dodo tree鈥� 鈥� which has struggled to reproduce in the centuries since the dodo vanished. The planned dodo-like birds may help to disperse the seeds of this long-lived plant by chewing and digesting its fruit, as dodos themselves may have done. However, so little is known about the dodo that it isn鈥檛 clear whether it actually ate this fruit. It isn鈥檛 even known where on the much-abused island of Mauritius the dodo preferred to spend its days, says Tatayah. 鈥淭here鈥檚 going to be a lot of discovery.鈥�
Biotech to the rescue?
Researchers are already using biotechnology to support the "genetic rescue" of several species threatened with extinction, due in part to their low genetic diversity. Here are some of the latest examples:
Przewalski's horse
Two stallions of this endangered central Asian horse were recently the cells of a specimen frozen in the 1980s. The researchers say this is the first example of two healthy clones born from an endangered species.
American chestnut
Billions of American chestnut trees were wiped out in the 20th century by an invasive fungal disease. Researcher have now developed a gene-edited version of the tree that is resistant to this pathogen. However, it has struggled to gain government approval to be planted beyond the lab.
Northern white rhino
Just two northern white rhinos are still living 鈥� and both are female. Researchers have developed a method to reprogram rhino skin cells so they can develop into sperm and egg cells. If those cells produced viable offspring, they may create enough genetic diversity to ensure the rhino's long-term survival
Black-footed ferret
Researchers are working on ways to edit the black- footed ferret's genome so it is resistant to sylvatic plague. Susceptibility to the disease prevents captive ferrets from being released back to the wild.
James Dinneen is an environment聽reporter at聽New聽杏吧原创
