There was a lot of hype about an American company’s “de-extinction” of dire wolves this week, but the significance of the achievement has been polarising.
The company said they were “dire wolf” pups.
Other geneticists said they were essentially grey wolves with slightly modified genes.
It prompted debate about the difference of resurrecting an extinct species and genetically modifying an existing one.
And it raises questions about whether we are now any closer to resurrecting Australia’s own extinct “wolf”, the Tasmanian tiger.
What happened with dire wolves?
A company called Colossal Laboratories and Biosciences said it “successfully de-extincted” dire wolves, saying three dire wolf pups had been born in the past six months.
The story was seemingly everywhere, with major outlets like Time Magazine running it as a cover story:
One of the company’s wolves was the cover star for Time Magazine. (Time Magazine)
It was made possible by pulling together most of the dire wolf’s genome, the complete set of genes that make up an organism, from ancient DNA.
According to Colossal the grey wolf shares 99.5 per cent of the same DNA as the dire wolf.
But you can’t clone an animal without living tissue.
So Colossal scientists modified grey wolf genes, which they used to create embryos that were implanted into surrogate dog mothers that gave birth to pups.
They made 20 targeted changes to 15 different grey wolf genes, based on analysis of deoxyribonucleic acid (DNA) extracted from dire wolf bones.
Colossal said this means they have “functionally de-extincted” the dire wolf.
And that the pups had a “close resemblance and significant genetic similarity to dire wolves of the past”.
A pack of reddish-brown dire wolves feast on a bison kill while fending off grey wolves. (Illustration: Mauricio Antón/Nature)
Other geneticists like Emily Roycroft, from Monash University’s Evolutionary and Conservation Genomics Research Group aren’t convinced.
“This is a grey wolf with an edited genome, not a dire wolf,” she said.
Mark Eldridge, the Australian Museum’s principal research scientist of land-based vertebrates, thought the de-extinction claim was far fetched and had overshadowed other aspects of the research.
“Editing the grey wolf genome and producing viable pups, cloning viable pups, is an achievement,” he said.
Colossal has only released the research behind mapping the dire wolf genome but not how the pups were created.
What does that mean for the Tasmanian tiger?
Colossal is also working on a project dedicated to the thylacine, better known as the Tasmanian tiger.
Tasmanian tigers capture the imagination of many Australians — culturally, there’s a mythical quality about them that blurs the lines between science fiction and fantasy.
And there’s been much fanfare about the quest to bring them back from extinction.
But bringing back a Tasmanian tiger compared to a dire wolf is a whole new level of difficulty.
“They’re really, really quite different,” Andrew Pask says.
Dr Pask is the head of the University of Melbourne’s Thylacine Integrated Genomic Restoration Research group, which has teamed up with Colossal on the project.
Andrew Pask is hopeful his team will achieve de-exctinction of the thylacine in a decade. (Supplied: Colossal Biosciences)
He’s been championing the project for years, but it has its critics.
Dr Roycroft said unlike dire wolves and grey wolves, the thylacine’s closest relatives had been genetically separated for much longer.
“There’s a lot more genetic differences that would need to be induced in a relative of a thylacine to get anywhere near this,” she said.
Dr Pask acknowledges the gap.
He says while the dire wolf project took a few months, his project will take 10 years.
That’s because the dire wolf project edited 15 genes, while the Tasmanian tiger project aims to make “hundreds of thousands of edits”.
Just like the dire wolf, you can’t clone a thylacine but Dr Pask said the plan was to replicate 100 per cent of its DNA.
So far Dr Pask’s team has reconstructed a genome they claim to be 99.9 per cent accurate, with a peer-reviewed study on how they did it expected in a few months.
Even with the genome, bringing back the Tasmanian tiger is going to require some help from one of its distant relatives.
What’s the nearest relative to the Tasmanian tiger?
While the Tasmanian tiger was also known as the “marsupial wolf” it actually comes from a completely different part of the animal kingdom to canids.
This group of meat-eating marsupials, known as Dasyuromorphia, include numbats, Tasmanian devils, quolls and fierce mouse-like critters called dunnarts.
Colossal has singled out the fat-tailed dunnart as the candidate for helping “de-extinct” the thylacine.
Here’s what a dunnart looks like:
The fat-tailed dunnart is a nocturnal mouse-like marsupial that spends its evenings eating its own body weight in food. (iNaturalist: Antoni Camozatto, Fat-tailed dunnart, CC BY-NC 4.0)
And here’s what a thylacine looked like:
The last-known surviving Tasmanian tiger, or thylacine, which died in 1936. (Supplied: NFSA)
The Tasmanian tiger was about 50 to 70 centimetres tall — think a medium dog like a kelpie — while the fat-tailed dunnart is about the size of a mouse.
As this graphic illustrates, those are very different sizes:
Fat-tailed dunnarts reach up to 15 centimetres in length including their tail while the thylacine’s shoulder height was about 60cm. (Illustration: ABC Science/Peter de Kruijff)
Dr Pask said 99.5 per cent of the fat-tailed dunnart’s genome is the same as the thylacine — this figure is based on data he says will be published later this year.
Researchers are hoping to fuse modified cells that resemble a thylacine profile with an empty dunnart egg to create an embryo.
Because marsupials are born so soon after insemination, as tiny little pink jelly beans doing most of their growing in the pouch, Colossal aims to use one of the thylacine’s (distant) relatives as a surrogate mother.
The first 35 days of pouch development for a fat-tailed dunnart sees it gain size and features after starting as a small fleshy jellybean. (Supplied: Communications Biology)
In the past, Colossal has indicated it would rear the joeys in an “artificial pouch environment”.
Given the genomic data Dr Pask mentioned hasn’t been published yet, there’s scepticism about using the dunnart as a host.
“If we assume that percentage is correct, we would be talking about more than 17 million genetic differences, Dr Roycroft said.
“These genetic variants interact with each other, and with the genomic backgrounds they occur on, to create the unique features we see in different evolutionary lineages.
“Understanding these complex genomic interactions in the absence of a living animal would be a huge challenge.”
Dr Pask says Colossal would closely monitor genetic edits in the embryonic stage for issues before any animals are born.
“There’s no plan to create half thylacine dunnarts,” he said.
Do we have complete DNA from Tasmanian tiger?
To try and make a Tasmanian tiger you need a blueprint.
And in genetics that blueprint is a genome which you usually get by sampling DNA from a freshly deceased animal.
Dr Roycroft said no sequenced genome was perfect, and even the best genomes in modern biology often have areas that are very difficult to decode.
So trying to get full genomes from long dead thylacine samples is a challenge.
But Dr Pask said there was new technology that makes complete sequencing possible.
He pointed to Telomere-to-Telomere (T2T) technology, which he said meant the team has “an exceptional genome resource”.
“We’re lucky, because we have very good, well-preserved specimens for the thylacine,” Dr Pask said.
“That’s not going to be possible for every extinct animal.”
Marsupials’ uniqueness adds to the challenge
But genetics aren’t the only barrier to bringing back a thylacine.
Trying to raise a thylacine joey without a mother would raise animal husbandry challenges. (Museums Victoria: Rodney Start, CC BY 4.0)
Dr Eldridge said marsupials were fundamentally different to dogs when it comes to breeding.
“We know a lot less about marsupial physiology and reproduction compared to well-studied organisms like dogs,” he said.
“Marsupials are usually born in an undeveloped stage and raised in a mother’s pouch.
“We don’t have a system yet artificially to raise marsupial young outside of the pouch.”
Artificial fertilisation of marsupials is also tricky.
“Marsupial IVF has struggled years and years to get working, and still haven’t got it working routinely in anything,” Dr Eldridge said.
“That’s because of the differences in reproduction.”
Would a ‘de-extincted’ Tasmanian tiger be introduced into the wild?
That’s Colossal’s plan.
Dr Pask says it wants to create an exact copy of the thylacine to reintroduce it into the wild.
He says Tasmania’s environment has suffered without an apex predator.
“Rewilding” has become a common practice in Australian conservation circles where native species are reintroduced to parts of their former range.
Predators can have major impacts on ecosystems so there’s even a belief you could put Tasmanian tigers back out into nature to regulate herbivores.
Alongside the genetic work on thylacines, there are ongoing studies as to whether wallabies in Tasmania would still respond with fear to the sight or smells of the predator.
The thylacine once roamed across most of Tasmania where its population was about 2,000 to 4,000 individuals. (Wikimedia: John Lewin/Linnean Society of London)
But Dr Eldridge said even if you revived the thylacine, there was the matter of finding it a home.
“The main habitat in Tasmania is well and truly human modified and broken up,” he said.
“Carnivores need large areas because they have big home ranges and you need big areas for big populations.
“It’s not like you could just let them loose on someone’s sheep farm in Tassie or the small reserves where they can hunt wallabies and do what they normally used to do.”
Dr Roycroft said it would be hard to predict whether a resurrected thylacine could survive in the wild with other threats like climate change and introduced species.
“It’s very unlikely that the thylacine will ever be brought back from extinction in a meaningful way,” she said.
Dr Pask acknowledges that bringing back an extinct animal is a big task.
But while he says “it will take a long time to get this right,” Colossal and Dr Pask clearly believe the project is worth the effort.
“De-extinction science is conservation biology,” he says.
“The tools that we need to deliver the de-extinction of a thylacine are really critical tools that we need right now for marsupials on the brink of extinction.”
