Meet scientists who bring extinct species from the dead

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Meet scientists who bring extinct species from the dead


The pigeons are apparently normal. Thirteen birds, two weeks to three months old, occupy a cooperative in an animal research center west of Melbourne, Australia. They are descendants of the common rocky pigeon, recognizable inhabitants of city squares and park benches, with a small but crucial distinction. These are the first pigeons in history with reproductive systems that contain the Cas9 gene, an essential component of the Crispr gene editing tool. The beetles of this herd will be born with the Cas9 gene in each of their cells, which will allow scientists to edit their descendants with the DNA of the extinct migratory pigeon. Those birds, if everything goes according to plan, will be the first live animals edited with features of a species that no longer exists. The herd was created by Ben Novak, an American scientist who has spent the last six years obsessively working on a process known as de-extinction. Its objective: to recover a bird that disappeared from the face of the Earth in 1914.


In the last six years, the new technology of gene editing has given us previously Unimaginable control over genetics.. The Crispr-Cas9 system consists of two main parts: an RNA guide, which scientists program to identify specific locations in a genome, and the Cas9 protein, which acts as a molecular scissor. The cuts cause repairs, allowing scientists to edit the DNA in the process. Think of Crispr as a cut and paste tool that can add or remove genetic information. Crispr can also edit the DNA of sperm, ova and embryos, implementing changes that will be transmitted to future generations. Advocates say it offers unprecedented power to Direct the evolution of the species..


In January 2013, scientists published articles demonstrating that, for the first time, they had successfully edited human and animal cells using Crispr. The news aroused the fears of the so-called design babies edited for traits such as intelligence and athletics, something that scientists are still far away due to the complexity of those traits. But the embryo edition for research is already underway. In the last 18 months, researchers in the United States and China have successfully published diseases that cause diseases. mutations in viable human embryos Not intended for implants or birth.


The technology is widely used in animals. Crispr has produced chickens resistant to disease and dairy cattle without horns. Scientists around the world routinely edit genes in mice for research, adding mutations to human diseases such as autism and Alzheimer's in a search for possible cures. Edited crispr pigs They contain kidneys that scientists hope to test as transplants in humans.


Crispr has been discussed as an extinction tool since its early days. In March 2013, the conservation group Revive & Restore co-organized the first TedXDeExtinction conference in Washington, D.C. Revive & Restore was co-founded by Stewart Brand, the creator of the entire Earth Catalog counterculture and vocal advocate of the revitalization of the migratory pigeon.


At the conference, George Church, a pioneer and geneticist of Crispr at Harvard Medical School, presented a scientific road map to revive a species. The church did not focus on the migratory pigeon, but on its own pet project, the woolly mammoth. Scientists, Church explained, had partially sequenced the mammoth genome using DNA extracted from ancient bones and other remains. Armed with that information, they could use Crispr to edit the DNA of the Asian elephant, the closest living relative of the mammoth. By genetic cutting and pasting, the physical and behavioral characteristics of the mammoth, its homonym coat and its ability to withstand temperatures below zero, could be added to live elephant cells.


The idea that woolly mammoths could roam the Earth once again made headlines around the world. But in his talk, titled "Hybridization with Extinct Species," Church said that the expected result of his extinction experiment was not a genetic facsimile of the mammoth. With enough mammoth DNA, Church explained, an Asian elephant edited by Crispr would become something completely different: a modern hybrid that looked and behaved like a mammoth but shared DNA with a living species.


For many in that day's audience, an idea that came directly out of science fiction suddenly seemed plausible. "Crispr put the extinction on the plate," says Novak, who spoke at the TedXDeExtinction conference and directs the migratory pigeon project for Revive & Restore.


The migratory pigeon has a similar cult: a global network of "pigeons" that includes scientists, conservationists, ornithologists, pigeon breeders, poultry geneticists and avid birdwatchers anxious to see how species revive. Even among these obsessives, Novak's passion stands out. Of the 1,500 stuffed pigeons in museums and private collections, he has personally seen 497.


He understands that his obsession is difficult for most people to understand. He has difficulty explaining it himself. Novak grew up in a city of 200 people in North Dakota. Long before he could read, he was fascinated by the idea of ​​extinction, digging unsuccessfully for fossils in his backyard. "I was a strange child," he says.





There is no plan to return the pterodactyl. Extinction does not mean



There is no plan to return the pterodactyl. Extinction does not mean "Jurassic Park".


Illustration:
Sagmeister and Walsh




In eighth grade, Novak was working on a science fair project about the dodo bird when he discovered that the species was essentially "an extinct giant pigeon". Nothing prepared him for the rush he felt when, at age 14, he found photos. of a passenger pigeon while leafing through a book by the National Audubon Society. "I thought it was a beautiful bird," says Novak.


The male pigeons were particularly colorful, with red breasts, feet and legs and iridescent pink patches that shone on the sides of their throats. The birds traveled in flocks that could add three billion, and were known for their grace and speed, and flew at 60 miles per hour. Novak read stories that described flocks of pigeons so large that they darkened the skies for days as they passed overhead. These massive flocks played an important ecological role, breaking branches to allow sunlight to rejuvenate the forests and enriching the soil with their droppings. The birds were very appreciated for their meat; the hunters could see the herds approaching from miles away. The population entered a sharp decline at the end of the 19th century and never recovered.


The last known passenger pigeon, a bird named Martha, died in captivity at a Cincinnati zoo in 1914. His death prompted the adoption of modern conservation laws to protect other endangered species in the United States. Shortly after her death, Martha was frozen and sent to the Smithsonian Institution in Washington, DC, for refilling. It is no longer on display, but Novak has seen it, of course. "Martha is in bad shape," he says. Written history and degraded taxidermy intensified Novak's desire to revive the species. "Nobody can tell me what a migratory pigeon was like in real life," he says. "I feel stolen from history."




The genetically edited beef could come to dinners around the world. In this episode of Moving Upstream, WSJ's Jason Bellini travels to Brazil to meet the world's first cow designed for warmer climates. Photo: Brian Wengrofsky



The first step was to sequence the genome of the passenger pigeon. The project was led by Beth Shapiro, professor of ecology and evolutionary biology at the University of California, Santa Cruz and author of the book "How to clone a mammoth." Shapiro's lab studies the DNA of extinct animals, extracting fragments of bones. And other remains, some dating back hundreds of thousands of years. Novak joined the laboratory in 2013 to work on the migratory pigeon project; Revive & Restore financed their work.


Sequencing the genome of an extinct species is not an easy task. When an organism dies, the DNA in its cells begins to degrade, leaving scientists with what Shapiro describes as "a soup of billions of tiny fragments" that require reassembly. For the passenger pigeon project, Shapiro and his team took tissue samples from the toes of birds dissected in the museum's collections. The DNA in the dead tissue left them with tempting clues but with an incomplete image. To fill in the gaps, they sequenced the genome of the band-tailed pigeon, the closest living relative of the passenger pigeon.


By comparing the genomes of the two birds, the researchers began to understand what features distinguished the migratory pigeon. In an article published last year in "Science", they reported finding 32 genes that make the species unique. Some of these allowed birds to withstand stress and disease, essential traits for a species that lived in large flocks. They did not find genes that could have led to extinction. "The passenger pigeons became extinct because people hunted them to death," says Shapiro.





In a Harvard lab, Asian elephant cells are being edited with DNA from the extinct woolly mammoth.



In a Harvard lab, Asian elephant cells are being edited with DNA from the extinct woolly mammoth.


Illustration:
Sagmeister and Walsh




In 2014, Shapiro taught a graduate class on extinction and asked each student to defend the return of an animal from the dead. The extinct birds that do not fly, the New Zealand moa and the dodo, were the favorites, along with the Yangtze river dolphin. Some students cited the importance or ecological value of an animal for tourism. Others mentioned the role humans played in the extinction of a species, a cornerstone of Stewart Brand's argument for reviving the migratory pigeon.


According to Shapiro, none of these arguments justifies the extinction. "What is the point of bringing something back if we do not know why it went extinct?" He asks. "Or do we know why it went extinct but we have not solved the problem?"


The dodo, she says, exemplifies the last question. The non-flying bird, originally from the island of Mauritius, in the Indian Ocean, nested on the ground and laid only one egg at a time. The settlers who arrived in 1638 brought cats, rats and pigs that devoured dodo eggs. "There's no point in bringing back the dodo," says Shapiro. "Their eggs will be eaten the same way they were extinguished the first time."


The revived passenger pigeons could also face extinction. The species thrived in the years before the European settlement of North America, when vast forests supported billions of birds. Those forests have been replaced by cities and farmland. "The habitat that passenger pigeons need to survive is also extinct," says Shapiro.


His interest in the bird was rooted in conservation rather than extinction. Understanding the exact cause of species extinction can help scientists protect living animals and ecosystems. Shapiro argues that the genes of the migratory pigeon related to immunity could help today's endangered birds survive. "I wanted to study the migratory pigeon," says Shapiro. "Ben wanted to give life back to the migratory pigeon."


But what does it mean to bring back an extinct species? Andre E. R. Soares, a scientist who helped sequence the genome of the migratory pigeon, says that most people will accept a similar aspect as evidence of extinction. "If it looks like a passing pigeon and flies like a passing pigeon, if it has the same shape and color, it will be considered a passing pigeon," says Soares.


Shapiro says that is not enough. Finally, he says, gene editing tools can create a genetic copy of an extinct species, "but that does not mean you're going to end up with an animal that behaves like a migratory pigeon or a woolly mammoth." We can understand the nature of an extinct species through its genome, but breeding is another matter. Without living shaggy mammoths or passing pigeons to model social behavior, who will teach these genetic replicates how to behave as their class?


"We are going to need a new biology and new names for all this," says Soares.


The church admits that there are obstacles to extinction, among which public apprehension stands out. But the history of science, he says, is full of ideas that start to sound crazy, pose complex ethical questions and eventually move towards social acceptance. "The more unknowns there are, the more intense the disagreement will be," he says. It points to in vitro fertilization, now a routine reproductive technology that has led to the birth of millions of children. When IVF was proposed for the first time, people were concerned about ethics, repercussions and possible risks. "As soon as Louise Brown was born in 1978 and it was completely normal, the disagreement disappeared," says Church.


In almost all countries, the process of extinction requires the approval of governments, academic committees and the public along the way. To inject the Cas9 gene into their birds, Novak needed permission from the Genetic Technology Regulator's Office in Australia, as well as ethics and animal welfare committees. You will need another round of approvals to breed and edit the next generation of your pigeons.


Meanwhile, Novak is constantly building the flock. In May he injected 19 eggs with the Cas9 gene, but only two pigeons survived hatching. In August, 11 eggs of 46 eggs survived. Novak and a small team of scientists plan to repeat the process until they have 22 pairs of birds for breeding. They are considering what traits of passenger pigeon to add first, combining the sequence data for the genes associated with the distinctive color of the extinct bird and the preference for life in large flocks. After determining how the dove DNA is manifested in rock pigeons, Novak hopes to edit the band-tailed pigeon, the closest living relative of the passenger pigeon, with as many defining features of extinct birds as may be possible. Eventually, he says, he will have a hybrid creature that looks and acts like a passing pigeon (although without parental training) but still contains dovetail pigeon DNA. These new and old birds will need a name, which their human creator has already chosen: Patagioenas neoectopistas, or "new wandering dove of America".


Write to Amy Dockser Marcus in amy.marcus@wsj.com


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