In a laboratory in the University of Melbourne earlier this year, PhD student Pierre Ibri was running an experiment that could prove to be a critical step in an audacious plan to save Australia’s endangered northern quoll.
In plastic trays were groups of tissue cells of another Australian marsupial – the common and mouse-like fat-tailed dunnart – that he was subjecting to the toxin of the cane toad, an invasive amphibian that has cut a swathe through populations of native animals in Australia’s north.
Except some of these cells were different.
They had been genetically tweaked by a team of scientists at the University of Melbourne and Colossal Biosciences to have the same resistance to the toad’s bufotoxin that other mammals elsewhere in the world have managed to develop over millions of years of evolution.
“We were trying to demonstrate the cells had this resistance,” says Dr Stephen Frankenberg, a synthetic biologist and Ibri’s supervisor. “They did – something in the order of 45 times more resistant.”
What happens next could, the team hopes, lead to a revolution for conservation – the creation of a mammal genetically modified to deal with a threat that is now helping send it towards extinction.
Frankenberg believes the technical barriers to creating a toad-resistant quoll are small and the team could have them living in captivity within five years.
One native Australian species that can eat cane toads is the rakali – or water rat – and Frankenberg says even though 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 beside 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 as it has for other species,” he says, “but the quolls just don’t have enough time.”
Like most Australian native species, the carnivorous northern quoll has 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 eating their crops.
Since then, the toads have spread across the northern parts of Australia. Prof John Woinarski, a leading conservation biologist at Charles Darwin University, says cane toads have – alongside feral cats and habitat clearing – been a major factor in pushing the northern quoll to endangered status.
“Quolls are very effective predators,” he says. “They’re the largest marsupial predator across much of the north of Australia.
“But when they try and kill a cane toad, they grab them by the back of the head just where the toxin glands are mostly concentrated. They die remarkably quickly and it’s an agonising death.”
Woinarski, who is not involved in the genetic research in Melbourne, says attempts to save species from cane toads have had only limited success.
“New blue-sky thinking are now possibly the only hope that we’ve got,” he says. “If this genetic engineering can be proven, then that is a great innovation, I think. It’s unlikely that genetically engineering a quoll would have an effect on other species.”
Woinarski says because quolls have up to 10 young each year but only live for a couple of years, a theoretical release of toad-resistant quolls could quickly spread through the population.
The team behind the quoll project is the same group, backed by US-based “de-extinction company” Colossal Biosciences, looking to genetic techniques to bring back the woolly mammoth and the thylacine – Tasmania’s dog-like marsupial predator that 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 edit its genome to introduce the same resistance to the bufotoxin they successfully placed into the tissue cells of the dunnart.
Next would come testing approaches of breeding a live animal with the cane toad-resistant traits, starting with a dunnart and then, hopefully, a northern quoll. One approach would be similar to that used in cloning 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 is leading the Thylacine Integrated Genomic Restoration Research Laboratory at the University of Melbourne, says cloning has not been perfected yet for marsupials. But he is confident it could be done.
“This is a simple [genetic] edit that would have evolved naturally. We’re adding a naturally occurring resistance and it gives the quoll a fighting chance,” he says.
Pask says a toad-resistant quoll could have a double-whammy effect. “They can then use the toads as a viable food source. Not only does this save the quoll, but hopefully it could weaponise our native wildlife [against the cane toad].”
In the future, the technique could be used to genetically engineer other Australian species like goannas, freshwater crocodiles and several snakes for whom cane toads can also be a deadly meal.
Frankenberg says what could take longer than creating the super-quoll is gaining regulatory approval to release them into the wild.
Prof Euan Ritchie, a wildlife ecologist at Deakin University, says: “If northern quolls and other species could one day be resistant to toads, this could have a dramatic positive effect as it ripples through food webs and ecosystems.
“Innovation such as this is just what’s needed to help turn around Australia’s dire conservation record and better protect threatened species.”
