The conversation on thylacine resurrection
Dr Stephen Frankenberg, a member of Pask’s team, holds a dunnart. Credit: Paul Jeffers.
Liam Mannix, Hope, hype or madness? Inside the ‘crazy money’ bid to bring the Tasmanian tiger back from extinction, The Sydney Morning Herald, 26 August 2022
Andy Pask reaches his hands into the cage and pulls something out. He beckons me closer like a magician before the big reveal.
From his cupped hands out peeks a short brown nose that twitches as it sniffs the air. Two black globe-like eyes cautiously follow.
The creature that will save the Tasmanian tiger is, frankly, smaller than I expected. “It’s a fat-tailed dunnart,” says Pask, looking absolutely delighted.
The dunnart is no bigger than a mouse – and, to be honest, looks just like one.
Pask’s plan: use the genes of the dunnart as a genetic scaffold to rebuild the DNA of the Tasmanian tiger. Use those genes to create a thylacine embryo, and then place that embryo in the pouch of the dunnart to raise.
Backed by millions from a “tech genius”, Pask says he is “100 per cent” confident they will have a tiger within the decade.
But he is treading in the footsteps of failure. An effort to de-extinct the tiger collapsed almost 20 years ago amid allegations of sabotage. And the company funding Pask is about as far from the sober, serious world of science as you can imagine.
Pask wants to turn a mouse into a tiger. In his hands the tiny dunnart shivers, almost as though it knows what’s coming.
Every ecosystem has an apex predator. For about 30 million years Australia’s was Thylacinus cynocephalus. It reigned across the entire continent in its prime, hunting kangaroos and birds all the way up to New Guinea.
Thylacines look like striped dogs but genetically are nothing alike, having last shared a common ancestor 160 million years ago. They are marsupials, splitting off from dunnarts, kangaroos and koalas 30 million years ago.
The arrival of dingos led to their extinction on the mainland about 2000 years ago. A group on Tasmania survived, cut off by rising sea levels, until they were finally hunted to death by white settlers protecting spreading sheep herds.
The last thylacine died in a concrete pen at Hobart’s zoo in 1936, alone and freezing after somehow getting locked out of his backroom shelter. After discovering him in the morning, keepers tossed his corpse in a dumpster.
From a cramped office at the University of Melbourne, brick walls hung with thylacine paintings and shelves bulging under toothy skulls, Andy Pask dreams of bringing it back.
Professor Pask, a geneticist, publishes a dozen highly cited papers a year on reproduction and evolutionary biology. But he keeps coming back to the Tasmanian tiger, even managing to publish an entire sequenced genome in Nature in 2017.
“You think, this is something I’ve got to work on, on my own, struggle with it, believe in it,” he says.
And then, almost overnight, Pask had more money than he could dream of. First $5 million from a private donor in March, and then another $10 million from Colossal Biosciences in August. An “unimaginable budget” for an Australian science project, another researcher tells me.
“It’s crazy money,” says Pask. He shakes his head. “I just can’t believe it.”
The money will pay for a team of about 50 scientists across Melbourne and Texas, where Colossal’s labs are based. Melbourne University will move Pask out of his cramped office and into a custom-built new lab. And then the real work will begin.
It is a truism that every article on bringing back extinct species must quote Jeff Goldblum in Jurassic Park: “Your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should.”
This cliche sells readers short by diminishing how difficult it is to actually bring something back. “I still don’t believe we are even close to having the technology to genuinely re-create an extinct animal,” says Associate Professor Jeremy Austin from the Australian Centre for Ancient DNA.
To pull it off, Pask and Colossal have to make three genuine scientific breakthroughs. Fail at any step and the whole project falls over.
First they must assemble a complete copy of thylacine DNA. Pask says he has assembled 95 per cent of the DNA.
He has the remaining 150 million missing letters, he says, but needs to find where it fits. And regardless, it’s likely to be “junk DNA,” says Pask.
But we don’t know what each part of tiger DNA does. “We don’t even know how much of this stuff is important or if it’s just junk,” says Austin. “And any mistakes in that genome sequence might be fatal.”
Pask plans to fill the gaps either with DNA from other thylacine genomes they will find, or with DNA from the marsupial dunnart, who is – remarkably – the thylacine’s closest living relative. How close? About 30 million years of evolution. The gap is so big “you just can’t get to it by any kind of gene editing”, says Professor Kristofer Helgen, chief scientist at the Australian Museum.
At the moment we can do about 10,000 edits to a genome. Editing a dunnart into a thylacine will require an order of magnitude more. It’s possible “if you have a billion dollars”, says Professor Ian Paulsen, director of the Centre of Excellence in Synthetic Biology.
Two, Pask must replace the DNA in a fertilised dunnart egg with his new tiger DNA.
This is scientifically possible. Professor Michael Archer, who is working on de-extincting the gastric-brooding frog at the University of Newcastle, has managed to insert a whole copy of the frog’s DNA into a cell from another frog. But we have not yet successfully replaced an animal cell’s genome with the genome of a completely different species.
Finally, Pask must guide the embryo through to a fetus and then to birth. “We think you could culture these embryos in a flask in the lab, without using a surrogate mum,” says Pask. Or you could grow them in a dunnart’s pouch.
But embryos aren’t just seeds that grow by themselves. They must be carefully prompted with varying levels of oxygen, bloodflow and nutrients; the cells need to rotate just so. Science has no idea how that process worked in a thylacine’s body.
Archer should be a few steps ahead of the project. He has a complete copy of his frog’s DNA and can even make embryos.
But, for reasons he does not fully understand, the embryo stubbornly refuses to develop much further.
For now, creating new life remains the preserve of mothers and gods, not scientists.
“There are some problems there,” says the Australian Museum’s Helgen, “and these are the problems we ran into 20 years ago.”
In 1990, Michael Archer was roaming through one of the dusty warehouses that hold the Australian Museum’s vast collection when his eyes caught upon a glass jar. Inside: a thylacine pup, eyes closed, face peaceful, floating in eternal repose.
Archer became the museum’s director in 1999, and almost immediately announced a bold new project: the museum would bring the thylacine back from the dead, using “perfectly preserved” DNA from the pickled pup. Within 50 years people would own thylacines as pets, he predicted. “We’ve discovered the miracle bottle in which this time capsule is just waiting to pop back into life.”
The announcement ignited a media circus. Archer’s magnetic personality helped. “Mike is amazing. He is larger than life. He’s got an amazing out-there personality, pushing boundaries. He’s visionary,” says Dr Karen Firestone, who soon came on board as the project’s geneticist.
Together they extracted “high quality” DNA from the bottled pup, which the team described as “the biological equivalent of man walking on the moon”. “Nobody has ever done what we have just done,” Archer told journalists.
But the DNA soon turned out to be contaminated with human DNA from its handlers, Archer now tells The Age.
A second effort to get dental DNA from a thylacine skull was more successful. But all up, by 2003, the team had recovered only a few of the thylacine’s 30,000-odd genes.
As with Pask’s project, the whole thing was done in the face of enormous public opposition from the scientific community – and, Archer alleges, sabotage. He tried to recruit a world-leading American geneticist to the project. But a local geneticist got wind of the invitation, called the American and told him “he would not be welcome in Australia”, says Archer. “I was staggered.”
Archer’s contract as head of the museum expired in 2003. His replacement, Frank Howarth, publicly ended the project in 2005, claiming the degraded DNA meant the project had no chance of success.
“That’s simply not true,” says Archer, pointing out Pask is using similarly degraded DNA. “But this is the reality of life. What happens when a new lion moves into the old lion’s pride? He kills off all the juveniles.”
Pask’s project has many similarities to Archer’s.
Both are headed by larger-than-life figures: Pask glows with barely contained boyish enthusiasm. Both make huge claims. Both face a storm of opposition from independent scientists. And both are surrounded by extraordinary media hype (indeed, both projects are the subject of documentaries).
Archer told The Age he never sought media attention. But he was never shy of using it to make big claims. “We have the whole genome,” he boasted in 2002 (he later discovered he did not). “Before we thought extinct was forever. Suddenly, maybe not.”
Karen Firestone, Archer’s geneticist, had a different idea of what was happening. The project was about doing interesting ancient DNA work, she told The Age. “We weren’t capable of recreating the thylacine.
“The science behind it was very different from the public perception – and perhaps, as well, some of what the media put out there.”
Pask’s claims are just as big. “We will bring something back, 100 per cent,” says Pask. “There is nothing in the science that is insurmountable.”
Other scientists don’t agree. “De-extinction is a fairytale science. It preys upon peoples’ desire to see ‘curiosities’ returned to life,” says the Australian Centre for Ancient DNA’s Jeremy Austin. “It’s pretty clear to people like me that thylacine or mammoth de-extinction is more about media attention for the scientists and less about doing serious science.”
The Australian Museum’s Helgen worries Pask is at risk of falling victim to the project’s hype. “With all due respect to Andrew Pask … in science sometimes, scientists can get a little swept away with what they are promising, especially when tens of millions of dollars start to float around.”
Certainly the actions of Pask’s funder Colossal Biosciences are doing nothing to quell that hype.
In an extremely unusual move for a scientific project, Colossal paid several social media influencers – among them a former US Bachelorette contestant – to post about Pask’s project on Instagram the day it was announced.
“Funding this education on next-gen social channels is critical to reach younger audiences,” Colossal’s co-founder and CEO Ben Lamm tells The Age.
“This is not normal in our fields of science,” replies Kristofer Helgen. “It is a complication of science performed in a corporate culture. This is a new dynamic I don’t think is necessarily a welcome one.”
Colossal’s investors reportedly include Paris Hilton, Tony Robbins and Chris Hemsworth. They rub shoulders with a company making NFTs and another making a “metaverse” in which players can protect the environment while … collecting NFTs.
Pask describes Ben Lamm as a “tech genius”, and he’s almost as excited about the project as Pask is. “I would say our success chances are 100 per cent, because we have all the technologies,” he tells The Age. “It’s really a function of focus and funding.”
The company’s other co-founder is Harvard University’s George Church – one of the fathers of the Human Genome Project and an inventor of several key genetic engineering technologies.
Prior to Colossal’s founding, Church had spent nearly a decade on his own lonely journey to try to de-extinct the woolly mammoth.
The mammoth’s nearest living ancestor is the Asian elephant – the species only diverged about six million years ago. Modifying an elephant genome and then using an elephant womb to carry the embryo seems tantalisingly possible, at least compared to the thylacine project.
The company has raised $A105 million from investors to realise Church’s dream. Some investors are there for conservation, says Lamm. Others want to make money.
Some researchers think woolly mammoths played a key role in the ecosystem of Siberia and North America, knocking down trees and fertilising the land with their poo. Restoring the ecosystem might lock carbon-dioxide into the soil, Church has argued. “Long-term, we have applications for carbon credits,” says Lamm. “It’s a $200 billion market.” The technologies invented along the way are likely to be valuable, he says. Eco-tourism is another possibility.
Pask imagines the technology they develop could be used to create a sort of Noah’s ark for threatened species – like a population of koalas wiped out by a bushfire.
“As long as we have biobanked and frozen tissue from that particular species, we should be able to recreate and grow up 100 koalas. And that has commercialisation potential, if you could repopulate large amounts of animals to an ecosystem.”
In the dying days of Michael Archer’s project to bring back the thylacine, he made one final hail-Mary effort to keep the project alive.
In 2002, the Tasmanian government was locked in a high-profile battle with conservationists over plans to continue to log the ancient giant ash rainforest of the Styx Valley. Archer dashed to Tasmania with an extraordinary offer: stop logging the Styx and we’ll give you the first cache of reborn thylacines.
The baffled state government turned him down.
But it’s worth thinking about because this is Andy Pask’s long game. “Of course, you can release this animal across Tasmania,” he says.
Survey data suggests almost half of Australians still don’t support using gene technology in food, despite the fact the cotton we wear and the canola in our margarine come from gene-edited crops.
How are we going to handle dunnarts that have been genetically modified to become thylacines roaming the forest?
“Would we be comfortable with the ethics of taking a horse and editing it into a rhino? These things sound preposterous because they are preposterous,” says Helgen.
But if the critique is the hoary “human’s shouldn’t play god”, well, haven’t humans spent a few hundred years playing the devil?
Pask – like Archer before him – isn’t deterred by the scepticism.
“We’re not protecting any environment. We’re losing animals at increasing rate across the globe,” he says. “We’ve got a choice. We can step in and do some of this technology to save these species or we can lose them forever.”
“If we have the technology to bring it back, we absolutely owe it to that species to bring it back.”