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Can genetically modifying a rare marsupial save it from extinction?

Researchers are aiming to make the northern quoll resistant to the toxic cane toads wiping it out in Australia, but little progress has been made
Northern quolls are poisoned by eating cane toads
Jurgen Freund/Nature Picture Library/Alamy

The US-based “de-extinction” company Colossal Biosciences claims a team it funds in Australia has taken “a major step” towards saving an endangered marsupial called the northern quoll.

The plan is to genetically modify the animals to make them resistant to the toxin of the invasive cane toad, but so far the team has only edited the cells of another marsupial.

The northern quoll (Dasyurus hallucatus) is a small, mostly carnivorous marsupial found in northern regions of Australia. Very unusually for a mammal, .

Populations have been devastated by introduced predators such as cats and the loss of habitat. But the single biggest threat is the invasive cane toad (Rhinella marina), which secretes a toxin that kills many would-be predators in Australia.

This works by inhibiting a protein that pumps sodium out of cells, which means sodium levels can rise to dangerous levels. Outside of Australia, small changes in the pump protein that confer resistance in a range of predators, from insects to hedgehogs.

at the University of Melbourne, Australia, and his colleagues want to edit the genome of the northern quoll to make it resistant too.

“Our toxin-resistance edit only changes a couple of DNA bases, which would probably arise by natural spontaneous mutation eventually anyway if quolls were to live with toads for the next few thousand years,” says Frankenberg. “We’re just speeding up the process so they don’t go extinct before resistance can evolve naturally.”

His team is far from the first to propose using genetic engineering to help save endangered species. In the US, for instance, American chestnut trees have been genetically modified to resist the fungus that wiped out most of them.

Engineering northern quolls could help save these animals, says at the University of Technology Sydney, Australia, who isn’t part of the team.

“If the genetically engineered quolls had sufficient toxin resistance, then they would have a high chance of surviving a predatory attack on a cane toad,” says Webb. “Thereafter, they’d either learn to avoid toads, or they might exploit the toads as food, which could help turn the tide on cane toads.”

Other approaches have failed, says Webb. For instance, his team tried to develop baits that would teach northern quolls to avoid cane toads, but this didn’t prove feasible on a large scale.

But not much progress has been made towards genetically modifying northern quolls. In 2020, Frankenberg that the team had used CRISPR gene editing to introduce toxin resistance into cells growing in a dish of another marsupial known as the dunnart. It is in the same family as quolls, but is easier to work with.

Now, the team is about to release a study showing that the edited dunnart cells are 45 times more resistant to cane toad toxin than unaltered ones.

Only one of the two copies of the sodium-pump gene has been altered, the paper says. If both were altered, the resistance would be even higher, it states.

“This is like someone climbing the first rung on a ladder and proclaiming, ‘look, this first step proves I can reach the moon’,” says at the University of New South Wales in Sydney.

The thing is, the real challenge isn’t editing cells in a dish. To genetically modify mammals, scientists must extract and manipulate egg cells, and then implant embryos in receptive females.

This is easy to do in some well-studied animals such as mice, but often fails when attempted in new species. Getting it to work can take a lot of effort and a lot of individuals to practise on. That is costly and especially difficult with endangered species.

What’s more, no team in the world had managed to genetically engineer any marsupial. A major issue is that their eggs develop a hard shell soon after fertilisation that prevents the injection of things such as CRISPR gene editing machinery.

Even if Frankenberg succeeds in engineering toxin-resistant quolls, his team will still need to generate large enough numbers to release into the wild to spread the resistance gene, not to mention getting permission to release them.

“I like the idea and think it is worth exploring,” says Crossley. But the hard part is still to come, he says.

Topics: Conservation / Extinction / Genetic modification