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A 'de-extinction' company wants to bring back the dodoOne of the biggest challenges in the reconstruction of the dodo is a problem for all avian genomics
International New York Times
Last Updated IST
The dodoes, which reproduced by laying a single egg on the ground, were also predated by other species, such as monkeys and rats, which humans brought with them. Credit: Pixabay Photo
The dodoes, which reproduced by laying a single egg on the ground, were also predated by other species, such as monkeys and rats, which humans brought with them. Credit: Pixabay Photo

Colossal Biosciences, the headline-grabbing, venture-capital-funded juggernaut of de-extinction science, announced plans on January 31 to bring back the dodo. Whether “bringing back” a semblance of the extinct flightless bird is feasible is a matter of debate.

Founded in 2021 by tech entrepreneur Ben Lamm and Harvard University geneticist George Church, the company first said it would re-create the mammoth. And a year later it announced such an effort for the thylacine, aka the Tasmanian tiger. Now, with the launch of a new Avian Genomics Group and a reported $150 million of additional investment, the long-gone dodo joins the lineup.

In the world of extinct animals, the dodo carries some heavy symbolic weight. Native to Mauritius in the Indian Ocean, it went extinct in the mid- to late 17th century, after humans arrived on the island. The ungainly bird, which stood around one meter tall and weighed about 15 to 20 kilograms, represents a particular kind of evolutionary misfortune: It should have been afraid of humans, but it wasn’t. The birds blithely walked up to sailors, so received history goes, and didn’t flinch as their peers were killed around them. The dodoes, which reproduced by laying a single egg on the ground, were also predated by other species, such as monkeys and rats, which humans brought with them. Now the creature represents extinction itself—you can’t get deader than a dodo.

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“This announcement is really just the start of this project,” says Beth Shapiro, lead paleogeneticist and a scientific advisory board member at Colossal Biosciences. Shapiro, also a professor of ecology and evolutionary biology at the University of California, Santa Cruz, has studied the dodo since the science of paleogenetics was in its infancy. In 2002 she published research in Science describing how her team had extracted a tiny piece of the bird’s mitochondrial DNA (mtDNA)—the DNA inside little organelles called mitochondria that gets passed down from mother to offspring. That snippet of mtDNA showed the dodo’s closest living relative was the Nicobar pigeon. Then, in 2022, Shapiro announced that her team at UC Santa Cruz had reconstructed the dodo’s entire genome.

Though the journey from mtDNA to genome took decades, the path from genome to a living, breathing animal is even more formidable, involving an enormous, interacting set of extraordinarily complex problems. Technically, a species could be resurrected by cloning DNA from a remnant cell. In reality, this has been impossible to achieve, mostly because viable DNA cannot be found. Most de-extinction programs aim to re-create a proxy of an extinct animal by genetic engineering, editing the genome of a closely related living species to replicate the target species’ genome. The edited genome would then be implanted into an egg cell of that related species to develop. The process must ensure that development proceeds correctly, that the animal is born successfully, that suitable surrogate parents nurture the creature, that it is administered a nutritious diet and that it is raised in an appropriate environment.

Colossal Biosciences is trying to solve all these problems at once. “Even though we’re nowhere near ready to start implanting embryos into surrogates,” Lamm says, the company currently has a team working on the cloning methodology necessary for that process. It also has multiple teams working in parallel on problems of computational biology, cellular engineering, stem cell reprogramming, embryology, protein engineering and animal husbandry, among other focuses.

One of the biggest challenges in the reconstruction of the dodo is a problem for all avian genomics. With mammals, the process is like that used in the creation of Dolly the sheep, the world’s first animal to be cloned successfully from adult cells. But, Shapiro says, “we can’t clone birds.” Cloning requires access to an egg cell that is ready for fertilization but not yet fertilized. “There is no access to a bird egg cell at the same developmental time as there is for a mammal,” she explains. Colossal Biosciences is exploring a process to extract avian primordial germ cells (PGCs) from bird eggs. If the process works, PGCs from pigeons would be manipulated to eventually develop into a dodolike bird. Ultimately, Shapiro says, “the final version of dodo will emerge from a pigeon that has been engineered to be the size of a dodo. So the size of eggs will be consistent.”

Although the first stage of genome editing is harder with birds, the next stage should be easier. With mammals, scientists don’t yet know how the modified embryo of an extinct species will interact with the intrauterine environment of the host species. That stage will be simpler in birds, Shapiro explains, “because everything happens in an egg.”

Once a re-created animal is born, more questions arise. Most animals have a mix of instinctive behavior, which arises from their genetic programming, and social behavior, which is learned from their parents and, in the case of social animals, their pack or group. But there is no way to re-create the unique natural history that shaped the social behavior of the dodo or other extinct animals—or even, in many cases, to know what it was. Mikkel Sinding, a postdoctoral researcher in paleogenomics at the University of Copenhagen, says, “There is nobody around to teach the dodo how to be a dodo.” In this sense, the word de-extinction is a misnomer. It’s not possible to bring back the dodo, even if it becomes possible to build a bird with a dodo genome.

Beyond behavior, the dodo proxy must survive in a world that is significantly different from that of more than 300 years ago, when the dodo went extinct. Yet not much is known about how dodoes functioned in their ecosystem. The birds lived only in forests on Mauritius. They had no large predators. They were slow to reproduce, laying one egg per year. And it’s believed from ancient sailors’ reports that there were once thousands of them. Another challenge for de-extinction is ensuring the well-being of the genetically engineered dodoes.

“A goal here is to create an animal that can be physically and psychologically well in the environment in which it lives,” Shapiro says. “If we are going to bring back something that's functionally equivalent to a dodo, then we will have to find, identify or create habitats in which they’re able to survive.” Shapiro points to environmental restoration on Mauritius and surrounding islands. There is hope that work focused on dodo habitat restoration could have knock-on benefits for other endemic plants and animals and even that the reintroduced bird may directly contribute to restoring its own ecosystem. Giant tortoises introduced to an island near Mauritius to replace an extinct species have helped revive native ebony trees by eating their fruit and distributing their seeds around the landscape.

Sinding, who has extracted ancient DNA from Pleistocene wolves, woolly rhinoceroses and aurochs, was surprised and excited to hear that Colossal Biosciences planned to re-create the dodo. He thinks the company is more likely to find success sooner with the bird than the mammoth or thylacine. He adds that this will depend on one’s definition of success, however. “You can genome edit the hell out of something and say you have remade a species,” Sinding says. “But is it really the species?”

“The dodo is a good choice because the fetus development happens in a short time span inside an egg and not in a surrogate mother, unlike a mammoth, which would have to be gestated by an elephant for nearly two years,” Sinding says. “It would be slightly easier to work with a chick than with a thylacine cub.” The ethical question with the dodo, he adds, is “whether the money is well spent or if we should spend that money trying to preserve some other living pigeons that are almost extinct.”

Tom Gilbert, director of the Danish National Research Foundation Center for Evolutionary Hologenomics, recently joined the Colossal Biosciences’ scientific advisory board. In 2022, before he was on the board, Gilbert told Technology Networks that he loved “the idea and technology behind rewilding with extinct species.” But he wondered about the influence of human morality on the choice of species. As the article put it, “Why stop at the good things?” Gilbert added, “What about the bad things? The pathogens now eradicated?”

The de-extinction of the dodo is “not a solution to the extinction crisis,” Shapiro says. “Extinction is forever.” But by pursuing the problem of dodo de-extinction, she explains, Colossal Biosciences is also developing critically needed tools for avian genomics, including for the genetic rescue of currently threatened species, such as editing genetic diversity back into a shrunken, threatened bird population. In this way, a 21st-century dodo may assist all avian conservation.

The dodo is only one of many lost birds: 161 avian species have been classified as extinct since 1500, according to a 2022 report from BirdLife International. But Colossal Biosciences is relying on the creature’s significance to inspire scientists and the general public to engage with all the problems of extinction. “We could have picked lots of different birds,” says Shapiro, raising her right arm to reveal a dodo tattoo. “I happen to really love the dodo.”

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(Published 02 February 2023, 22:33 IST)