From an Australian frog that swallowed its own eggs to woolly mammoths, scientists are getting closer to resurrecting long-extinct species.
Thylacines, also known as Tasmanian tigers, were common throughout Australia millions of years ago. These dog-like creatures with stripes, about the size of an American coyote, vanished from the mainland around 2,000 years ago. They remained in Tasmania until the 1920s, when European colonists saw them as a threat to livestock and slaughtered them.
“It was a human-caused extinction – European settlers came to Australia and brutally obliterated this animal,” says geneticist Andrew Pask of the University of Melbourne.
Pask is leading a team of scientists who, in collaboration with the “de-extinction” company Colossal Biosciences, hope to recreate and reintroduce the wolf-like creature.
Because of recent advances in genetics, specifically the introduction of gene editing technology Crispr-Cas9, The thylacine is not the only extinct species that may reappear in the near future. How does the science of extinction work, and what ethical issues does it raise?
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In the case of the thylacine, the first step is to sequence the DNA of the extinct animal – the genetic blueprint found in every cell of the body. Pask accomplished this in 2017.
“The wonderful thing about the thylacine is that because it was such an important marsupial, every major museum wanted one in their collection, so there are hundreds of samples all over the world, some of which are exceptionally preserved,” says Pask.
“A baby was taken from its mother’s pouch as our sample. They shot the mother and immediately immersed the child in alcohol, which preserves DNA. That was the holy grail and the miracle specimen for us in terms of being able to truly build that genome.”
Despite being in good condition, The DNA isn’t entirely complete. UV light exposure and bacterial action break down DNA into short fragments over time. The older the sample, the smaller the fragments that remain, until eventually there aren’t enough left (there’s no way to bring back a dinosaur for this reason).
This leaves scientists with the seemingly impossible task of figuring out how the various pieces of DNA fit together – a task akin to completing a massive jigsaw puzzle without the helpful picture on the front of the box.
Fortunately, a small mouse-sized marsupial known as a dunnart provided a blueprint.
“We discovered the dunnart, which is the closest living relative to the thylacine,” Pask says.
Dunnarts and thylacines share 95% of their DNA, which is thought to be highly conserved, meaning it hasn’t changed much over time.
Nobody’s done it on this scale before because the DNA-editing technology wasn’t good enough or quick enough – Andrew Pask
“We sequenced the Dunnart’s genome and compared its genetic code to that of our extinct species, then overlapped them and found differences everywhere,” Pask says.
However, simply knowing an animal’s DNA is insufficient to bring it back. The next stage of the puzzle involves modifying the dunnart’s genes to match those of the thylacine. Crispr-Cas9, the Nobel Prize-winning genome editing method, can be used to accomplish this.
“We start with living cells from the dunnart and start editing all of those changes, so we essentially engineer or turn that dunnart cell into a living thylacine cell with thylacine chromosomes in it,” Pask explains.
Previously, Gene editing was not yet advanced enough to change all of the different sequences to thylacine DNA at once. With millions of edits required, it was assumed that researchers would prioritise the most important DNA sequences, resulting in an animal genome that was not identical to the extinct one. Pask believes that this will be unnecessary in the future.
“All of those technologies are in place, but no one has done it on this scale before because DNA-editing technology isn’t good or fast enough. But we’ve come a long way since then, and we’ve made significant investments to try to make this work.”
Once the researchers have a thylacine cell, they must convert it into a developing embryo before implanting it into the womb of a living close relative. If that sounds simple, it isn’t. “We have a lot of work ahead of us,” Pask says.
“It took us about five years to create marsupial stem cells. We’re now putting those stem cells into embryos to see if we can get them to develop into a full-fledged living creature.”
This method could be used to bring back more than just the thylacine. Woolly mammoth DNA fragments discovered frozen in Arctic tundra indicate that this large mammal may return. The majority of woolly mammoths died out around 10,000 years ago.
Colossal Laboratories and Bioscience scientists – Harvard University researchers are using Crispr to splice bits of mammoth DNA into the genome of the Asian elephant, the mammoth’s closest living relative. The resulting hybrid, known as a “mammophant,” would be adapted to the cold Siberian tundra and could help fill an ecological void left by the extinct mammoth. (Watch a BBC Reel video about how mammoths could be a surprising help in combating climate change, or watch it below.)
However, there are technological limitations and obstacles that must still be overcome.
“Many of the characteristics that we have as living animals require several different copies of genes, but it’s not easy to tell how many are required from looking at a reconstructed genome,” says Michael Archer, a palaeontologist at the University of New South Wales in Sydney, Australia.
“You cross your fingers that one copy will be enough to enable the feature you want, but there’s a big suck-it-and-see component to these projects.”
However, genome reconstruction is not the only method that scientists could use to bring extinct animals back to life.
The auroch, a type of prehistoric cow, is depicted in ancient cave paintings all over the world. It used to roam the plains of Europe, standing as tall as an elephant. It died out in the 1600s. Auroch genes can still be found in various cattle breeds across the continent, with descendants in Spain, Portugal, Italy, and the Balkans. Geneticists are now “back breeding” these species together to produce offspring with auroch-like characteristics.
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Another possibility is to clone the dead animal by transferring the nucleus from an intact cell into the egg of a close living relative in the hope that an embryo will form.