The thylacine (Thylacinus cynocephalus), commonly known as the Tasmanian tiger, was a highly peculiar animal. It looked exactly like a dog or wolf and had the stripes of a tiger, but was a marsupial. It’s the kind of bizarre combination few places other than Australia can boast.

The story of the thylacine’s decline is inherently tied to that of humans. As soon as early hunter-gatherers entered the picture, the thylacine was in deep trouble. As humans expanded their reach across the continent, the range of the marsupial only declined. When humans introduced the dingo (Canis lupus dingo) to Australia several thousand years ago, the thylacine was almost wiped out by the competition. But an isolated population could still be found in Tasmania — it too wouldn’t last, though.

In the 19th century, European colonists saw the marsupial predators as a pest that harmed their sheep. They paid a bounty of £1 per carcass (good money at the time), which placed the thylacine on the cusp of extinction. In 1909, the bounties were dropped but it was already too late. Only a couple of individuals remained in the wild, which were seized by zoos. On September 7, 1936, the last Tasmanian tiger died in a zoo in Hobart, Australia.

And so the story of an entire species came to a sad and bitter end. Or has it?

Jurassic Park vibes

In 2021, Colossal Biosciences, a U.S. genetic engineering startup founded by tech entrepreneur Ben Lamm and Harvard genetics professor George Church, announced its lofty plan to de-extinct the woolly mammoth using cutting-edge gene-editing technology such as CRISPR. Earlier this year, the Dallas-based biotech company received a $60 million series A financing infusion led by Thomas Tull and At One Ventures. Now, the startup has announced it will embark on a second mission, that of bringing the thylacine back from the dead.

To this aim, Colossal has partnered with the University of Melbourne and its Thylacine Integrated Genetic Restoration Research Lab, headed up by Dr. Andrew Pask. In 2017, Pask and colleagues sequenced the thylacine genome for the first time from a thylacine pup who died in 1909 and has since been preserved in alcohol. This analysis showed that the extinct species is more related to the kangaroo than the dingo, among many other things such as a steep drop in genetic diversity corresponding to a drop in population that started some 70,000-120,000 years ago, well before humans arrived on the Australian continent.

But how does one go about resurrecting an extinct species? It’s no trivial task that’s for sure.

In the case of the woolly mammoth, the plan is to insert sequences of DNA from samples of mammoth tusks, bones, and other tissue into stem cells from its close extant relative, the Asian elephant. The Asian elephant only differs from the woolly mammoth by about 1.4 million DNA bases, corresponding to more than 1,600 protein-coding genes that would need to be edited. Among them are genes that encode for the mammoth’s dense hair and thick fat, which allow them to withstand the cold, along with their distinctively high-domed skulls.

After removing DNA from an elephant egg cell and replacing it with edited DNA from woolly mammoths using CRISPR, the next step would be to implant the embryo into an artificial uterus lined with uterine tissue grown from stem cells. If everything goes according to plan, the artificial womb would gestate a 200-pound baby woolly mammoth-elephant hybrid of some sort for two years. The resulting animal would be part elephant, part mammoth. Ultimately, these hybrids would be released into the wild in the melting Arctic tundra, where herds of quasi-mammoths would help knock down sunlight-absorbing trees and vegetation, thereby fostering grasslands that would help keep the ground colder and protect the permafrost from melting and releasing methane, a very potent greenhouse gas. The goal is to achieve all of this by 2027.

But let’s say all goes well. The resulting animal would be part elephant, part mammoth. Ultimately, these hybrids would be released into the wild in the melting Arctic tundra, where herds of quasi-mammoths would help knock down sunlight-absorbing trees and vegetation, thereby fostering grasslands that would help keep the ground colder and protect the permafrost from melting and releasing methane, a very potent greenhouse gas. The goal is to achieve all of this by 2027.

That’s mighty ambitious and a lot of things could and probably will go wrong. But resurrecting the thylacine sounds easier. The Tasmanian tiger has only been extinct for a hundred years, compared to the 10,000 years that have elapsed since the last woolly mammoth died stranded on Wrangler Island in the Arctic Ocean. This means it’s much easier to extract viable DNA from the thylacine compared to the woolly mammoth, whose genetic code is degraded and subject to all kinds of errors.

High risk, high reward

It’s not the first time someone has tried to resurrect the Tasmanian tiger. In 1999, Australian scientists wanted to clone the extinct animal using DNA extracted from specimens housed at the Australian Museum. However, the project was scrapped just a few years later after it became obvious the quality of the DNA was unworkable.

A lot of things have changed since then though. Scientists have much more advanced tools at their disposal, such as more sophisticated and reliable gene sequencing devices, CRISPR to cut and paste nucleotides (the basic building blocks of DNA), and machine learning algorithms that can identify regions of the genome that are supposed to serve particular functions.

It will still be highly challenging though. Just like the woolly mammoth needs elephant cells as a scaffold, Colossal plans on taking cells from thylacine’s closest living relative, a mouse-like marsupial known as the fat-tailed dunnart (Sminthopsis crassicaudata). Using sophisticated AI tools, scientists would identify all the regions where the dunnart and thylacine DNA differ from each other. It’s then a matter of replacing genes from the dunnart and inserting thylacine sequences in their stead using CRISPR to essentially build a thylacine cell and ultimately a thylacine embryo.

The embryo could be grown inside the pouch of a surrogate marsupial, such as the dunnart, or in a microfluidics chamber that artificially mimics the marsupial pouch. And just like the woolly mammoth, the plan is to rewild these thylacine hybrids, which could help restore ecosystems to an earlier, less disturbed state. Dozens of such animals would have to be bred in order for this rewilding to have a shot at success.

“This is a landmark moment for marsupial research and we’re proud to team up with Colossal to make this dream a reality,” Dr. Pask said in a statement. “The technology and key learnings from this project will also influence the next generation of marsupial conservation efforts. Additionally, rewilding the thylacine to the Tasmanian landscape can significantly curb the destruction of this natural habitat due to invasive species. The Tasmanian tiger is iconic in Australian culture. We’re excited to be part of this team in bringing back this unique, cornerstone species that mankind previously eradicated from the planet.”

If neither the woolly mammoth nor thylacine are revived, Colossal says that all their work won’t be futile. The technologies they are currently working on could be used to conserve currently living species that are on the brink of extinction, as well as allow for a more profound understanding of evolutionary change in countless critical species. For instance, these advances could help equip other species with genes that enable them to resist pathogens, or better withstand the heat and drought brought on by climate change.

One could argue that all the tens of millions of dollars funneled into these projects are going to waste when they could be used to fund more down-to-earth conservation. That’s certainly a valid point. Prevention is better than the cure, after all. Whenever you’re pushing the boundaries of science, you always stand the risk of hitting a dead end that leads nowhere. But the rewards may well be worth it.