May 30, 2024

Ilab in the University of Melbourne earlier this year, PhD student Pierre Ibri conducted an experiment that could be a critical step in a bold plan to save Australia’s endangered northern quoll.

In plastic bowls were groups of tissue cells from another Australian marsupial – the common and mouse-like fat-tailed dunnart – which he had subjected to the toxin of the cane toad, an invasive amphibian that is cutting through populations of native animals in Australia’s north.

Except some of these cells were different.

They have been genetically modified by a team of scientists at the University of Melbourne and Colossal Biosciences to have the same resistance to the frog’s bufotoxin that other mammals elsewhere in the world have managed to develop over millions of years of evolution.

“We tried to show that the cells have this resistance,” says Dr Stephen Frankenberg, a synthetic biologist and Ibri’s supervisor. “They have – something on the order of 45 times more resistance.”

What happens next, the team hopes, could lead to a revolution for conservation – the creation of a mammal that has been genetically modified to deal with a threat that is now helping to send it to extinction.

Frankenberg believes the technical hurdles to creating a road-resistant quoll are small and the team could have them living in captivity within five years.

Dr. Stephen Frankenberg. Photo: Colossal Biosciences

One native Australian species that can eat cane toads is the rakali – or water rat – and Frankenberg says that although the species is unique to Australia, it has probably retained some resistance to cane toads from its ancestors in other parts of the world.

If the northern quoll were to live alongside cane toads for many thousands of years, it is likely, he says, that they too would evolve to resist the toxin.

“That resistance would arise like for other species,” he says, “but the quolls just don’t have enough time.”

Like most Australian native species, the carnivorous northern quoll evolved in a landscape absent of the bufotoxin. That is, until the cane toad was introduced in 1935 in a futile attempt by Queensland’s sugar cane industry to control bugs that were eating their crops.

Since then, the frogs have spread across the northern parts of Australia. Prof John Woinarski, a leading conservation biologist at Charles Darwin University, says cane toads were – along with feral cats and habitat clearing – a major factor in pushing the northern toad to endangered status.

“Quolls are very effective predators,” he says. “They are the largest marsupial predator in much of northern Australia.

“But when they try to kill a cane toad, they grab them by the back of the head right where the poison glands are mostly concentrated. They die remarkably quickly and it’s a terrifying death.”

Woinarski, who is not involved in the genetic research in Melbourne, says efforts to save species of cane toads have had only limited success.

“New blue sky thinking is now possibly the only hope we have,” he says. “If this genetic engineering can be proven, then it’s a great innovation, I think. Genetic manipulation of a quoll is unlikely to have an effect on other species.”

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Woinarski says because quolls have up to 10 young each year but only live for a few years, a theoretical release of frog-resistant quolls could spread quickly through the population.

The team behind the quoll project is the same group, backed by US-based “de-extinction company” Colossal Biosciences, which is looking for genetic techniques to bring back the woolly mammoth and the thylacine – Tasmania’s dog-like marsupial predator that until was hunted to extinction in the early 20th century.

The next step for Frankenberg and the team will be to take a type of stem cell from the northern quoll and modify its genome to introduce the same resistance to the bufotoxin that they successfully put into the tissue cells of the quoll.

Next will come approaches to breeding a living animal with the reed pad resistant traits, starting with a dunnart and then, hopefully, a northern quoll. One approach would be similar to that in cloning of the famous Dolly the sheep. Dunnarts are close relatives of the quoll and the thylacine.

If they can then breed a quoll using those stem cells, the team says the offspring of those animals should also inherit the resistance.

Prof Andrew Pask, who leads the Thilacine Integrated Genomic Restoration Research Laboratory at the University of Melbourne, says cloning has not yet been perfected for marsupials. But he is confident it can be done.

“It’s a simple one [genetic] modification that would naturally have developed. We add a natural resistance and it gives the quoll a fighting chance,” he says.

Pask says a frog-resistant quoll can have a double-whammy effect. “They can then use the frogs as a viable food source. Not only does this save the quoll, but hopefully it can arm our native wildlife [against the cane toad].”

In the future, the technique could be used to genetically engineer other Australian species such as goannas, freshwater crocodiles and various snakes for whom cane toads can also be a deadly meal.

Frankenberg says what may take longer than creating the super-quoll is getting regulatory approval to release them into the wild.

Prof Euan Ritchie, a wildlife ecologist at Deakin University, says: “If northern quolls and other species can one day become resistant to frogs, this could have a dramatic positive effect as it ripples through food webs and ecosystems.

“Innovation like this is just what is needed to help turn around Australia’s dire conservation record and better protect endangered species.”

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