The disextinction enterprise sets its next (first?) target: thylacine

The disextinction enterprise sets its next (first?) target: thylacine

Of all the species humanity has wiped off the face of the earth, the thylacine is perhaps the most tragic loss. A wolf-sized marsupial sometimes called the Tasmanian tiger, the thylacine went extinct in part because the government paid its citizens a bounty for each animal killed. This end came recently enough that we have photographs and film clips of the last thylacines ending their days in zoos. Late enough that in just a few decades countries will start writing laws to prevent other species from meeting the same fate.

On Tuesday, a company called Colossal, which has previously said it wants to bring the mammoth back, announced a partnership with an Australian lab it says will eradicate the thylacine with the aim of reintroducing it into the wild. A number of characteristics of marsupial biology make it a more realistic target than the mammoth, although there is still a lot of work to be done before the debate even begins on whether reintroduction of the species is an option. good idea.

To learn more about the company’s plans for thylacine, we spoke with Colossal founder Ben Lamm and the head of the lab he partners with, Andrew Pask.

Branching out

To some extent, Colossal is a way to organize and fund the ideas of Lamm’s partner, George Church. Church talks about the mammoth’s demise for a number of years, spurred in part by developments in gene editing. The company is structured like a startup, and Lamm said it’s very open to commercializing the technology it develops while pursuing its goals. “On our journey to de-extinction, Colossal is developing innovative new software, wet and hardware technologies that can have profound impacts on both conservation and human health care,” he told Ars. But fundamentally, it’s about developing products for which there is obviously no market: species that no longer exist.

The general approach prepare for the mammoth is simple, even if the details are extremely intricate. There are many mammoth tissue samples from which we can obtain at least partial genomes, which can then be compared to its closest relatives, elephants, to find key differences distinct from mammoth lineage. Using gene-editing technology, key differences can be edited into the genome of an elephant stem cell, essentially “mammothifying” the elephant cells. A little IVF later, and we’ll have a furry beast ready for the subarctic steppes.

Again, details matter. At the start of the plan, we had not created elephant stem cells, nor done gene editing, even at a fraction of the scale required. There are credible arguments that the peculiarities of the elephant reproductive system make the “little IVF” that is needed a practical impossibility; if this happens, it will involve a gestation period of nearly two years before the results can be assessed. Elephants are also intelligent and social creatures, and there is a reasonable debate to be had over whether it is appropriate to use them for this purpose.

Given these challenges, it might not be a coincidence that Lamm said Colossal was looking for a second species to extinguish. And their research resulted in a project that took an almost identical approach: the Thylacine Integrated Genomic Restoration Research Laboratory (TIGRR), based at the University of Melbourne and led by Andrew Pask.

In the pocket

As with the gigantic Colossal plans, TIGRR intends to obtain thylacine genomes, identify key differences between this genome and related lines (mainly quols), then modify those differences into marsupial stem cells, which would then be used for IVF. It also faces significant hurdles, in that no one has made marsupial stem cells yet, and no one has cloned a marsupial – two things that have at least been done in placental mammals (but not pachyderms). ).

But Pask and Lamm pointed out a number of ways the thylacine is a much more docile system than a mammoth. For one, the animal’s survival to recent years means there are plenty of museum specimens, and so Pask says we’re likely to get enough genomes to get a sense of the population genetic diversity – probably critical if we are to re-establish a stable breeding population.

Marsupial reproduction also makes things much easier. A marsupial embryo “places much less nutritional demand to get to the point of birth,” Pask told Ars. “The placenta doesn’t really invade the uterus.” Marsupials are also born at a stage that is about halfway through a mammal’s embryogenesis. the rest of the development takes place in the mother’s pouch. Unlike the in utero years needed for a mammoth, the thylacine may only need a few weeks. Marsupial embryos are also so small at birth that adoptive mothers can be considerably smaller than a thylacine; Pask said his group plans to work with a fat-tailed dunnartwhich is about the size of a small rat.

Even after birth, thylacines would fit in the dunnart’s pouch for a short time, and Lamm is excited about the prospect of developing an artificial pouch to get the animals from there to the point where they can be reared by hand. . Alternatively, some larger marsupials could act as adoptive parents.

The dunnart is not the ideal substitute, as its lineage diverged from that of the thylacines several million years ago (compared to well under a million for mammoths and elephants). This means that a lot more genome editing has to be done on the dunnart cells to bring them to a thylacine-like state. That’s one of the reasons Pask was excited about the opportunity to team up with Colossal, which is working to develop high-throughput genome editing methods.

None of this is to say that the thylacine is more or less likely to be revived. Colossal will always face challenges in identifying what changes are absolutely essential to produce a thylacine-like animal, and what other changes are needed to ensure that the genome survives all of these categories of changes (those compensating mutations may be essential for species to survive evolutionary change). Yet most of the risks involved seem to be more manageable in his case.

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