Of all the species that humanity has wiped off the face of the earth, the thylacine is possibly the most tragic loss. A wolf-sized marsupial, sometimes called the Tasmanian tiger, the thylacine died in part because the government paid its citizens a bounty for every animal killed. That end came recently enough that we have photos and movie clips of the last thylacines ending their days in zoos. So late that in a few decades countries would start writing laws to prevent other species from seeing the same fate.
On Tuesday, a company called Colossal, which has already said it wants to bring the mammoth back, announced a partnership with an Australian lab that it says will extinct the thylacine with the aim of reintroducing it to the wild. Some features of the marsupial biology make this a more realistic goal than the mammoth, though there’s still a lot of work to do before we even begin the debate about whether reintroducing the species is a good idea.
To learn more about the company’s plans for the thylacine, we spoke with Colossal founder Ben Lamm and the head of the lab he works with, Andrew Pask.
To some extent, Colossal is a way to organize and fund the ideas of Lamm’s partner, George Church. The church has been talking about mammoth extinction for several years, spurred in part by advances in gene editing. The company is structured as a startup and Lamm said it is very open to commercializing technology it develops while pursuing its goals. “On our path to de-extinction, Colossal is developing new software, wetware and hardware innovative technologies that could have profound implications for both conservation and human health care,” he told Ars. But essentially it’s about developing products for which there is clearly no market: species that no longer exist.
The general approach it describes for the mammoth is simple, even if the details are extremely complex. There are numerous samples of mammoth tissue from which we can obtain at least partial genomes, which can then be compared with its closest relatives, the elephants, to find key differences that differ from the mammoth lineage. Gene-editing technology makes it possible to edit key differences in the genome of an elephant stem cell, essentially making the elephant cells ‘mammoth’. A little IVF later, and we have a shaggy beast ready for the subarctic steppes.
Again, the details are important. At the start of the plan, we hadn’t made elephant stem cells, nor had we done any gene editing at even a fraction of the required scale. There are credible arguments that the idiosyncrasies of elephants’ reproductive system make the “little bit of IVF” necessary practically impossible; when it happens, it takes nearly two years of pregnancy before the results can be evaluated. Elephants are also intelligent, social creatures, and there is a fair amount of debate as to whether it is appropriate to use them for this purpose.
Given these challenges, it may not be a coincidence that Lamm said Colossal was looking for a second species to go extinct. And their search yielded a project with an almost identical approach: the Thylacine Integrated Genomic Restoration Research Lab (TIGRR), located at the University of Melbourne and led by Andrew Pask.
In the pouch
Similar to Colossal’s mammoth plans, TIGRR plans to obtain thylacine genomes, identify key differences between that genome and related lineages (usually quolls), and then edit those differences into marsupial stem cells, which would then be used for IVF. It also faces some significant hurdles, in that no one has yet made marsupial stem cells, nor has anyone cloned a marsupial—two things that have been done, at least, in placental mammals (though not pachyderms).
But Pask and Lamm pointed out a number of ways that the thylacine is a much more tractable system than a mammoth. First, the animal’s survival into recent years means there are a lot of museum specimens, and so Pask says we’ll probably get enough genomes to get a sense of the population’s genetic diversity — probably critical if we do. a new stable breeding population.
The reproduction of marsupials also makes things considerably easier. A marsupial embryo “poses much less of a nutrient requirement to reach the point of birth,” Pask told Ars. “The placenta doesn’t actually invade the uterus.” Marsupials are also born at a stage that is about halfway through embryogenesis for a mammal; the rest of the development takes place in the mother’s pouch. Unlike in the womb years it takes a mammoth, the thylacine may only need a few weeks. The marsupial embryos are also so small at birth that the foster mothers can be significantly smaller than a thylacine; Pask said his group plans to work with a thick-tailed dunnart, which is about the size of a small rat.
Even after birth, the thylacines would fit into the dunnart’s sac for a short time, and Lamm is excited by the prospect of developing an artificial sac to transport the animals from there to the point where they can be hand-reared. If not, some larger marsupials could act as foster parents.
The dunnart is not the ideal surrogate, as its lineage diverged from that of thylacines several million years ago (compared to well under a million for mammoths and elephants). That means a lot more genome editing needs to be done to thin cells to get them into a thylacine-like state. That’s one of the reasons Pask was excited about the opportunity to partner with Colossal, which is developing high-throughput genome editing methods.
None of this is to say that the thylacine is more or less likely to be revived. Colossal will still face challenges in determining which changes are absolutely essential to produce a thylacine-like animal, and what other changes are necessary for the genome to survive all those category of changes (these compensatory mutations may be essential to enable species to survive evolutionary changes). Still, most risks seem more manageable in this case.