Gene editing could make quolls resistant to cane toad toxin

Scientists from de-extinction company Colossal Biosciences and The University of Melbourne have announced a major step forward in their quest to save the endangered northern quoll from the invasive cane toad, using proprietary tools to introduce genetic resistance against the cane toad toxin into marsupial cells.

Quolls are carnivorous marsupials that play a crucial role in the Australian ecosystem as both a scavenger and a primary carnivore. But since the introduction of invasive cane toads to Queensland in the 1930s, northern quolls have seen their populations plummet by 75%. This is because the toads — which have since spread well beyond Queensland into coastal NSW, the Northern Territory’s Top End and the Kimberley region of Western Australia — are an attractive food source for the northern quoll, which is especially vulnerable to the toad’s neurotoxins.

“We need northern quolls to have a balanced ecosystem in mainland Australia,” said Professor Andrew Pask, who leads Melbourne’s Thylacine Integrated Genetic Restoration Research (TIGRR) Lab. “By using Colossal’s technology, we’re giving our conservation partners a fighting chance of succeeding in restoring that balance.”

Observations of other genetically resistant species by Dr Stephen Frankenberg, a member of Pask’s lab, led the researchers to hypothesise that northern quolls could become genetically resistant with a very small genetic intervention. After several years of building resources from northern quoll tissue samples and introducing different genetic edits to the cells of a dunnart, which is closely related to the northern quoll and serves as a useful model species, the combined teams successfully engineered resistance in dunnart cells (which Colossal has used for its research into thylacine de-extinction) by introducing genetic features found in other natural predators of toads. The edited cells are 10-fold more toxin-resistant in the context of cell culture, with the team predicting this resistance will extend to the context of the whole animal.

As a next step in introducing toxin resistance to the northern quoll, the combined Colossal and University of Melbourne team has established eight northern quoll cell lines from pouch young. They are now working to reprogram those quoll fibroblasts into induced pluripotent stem cells (iPSCs); once the iPSCs are generated, the scientists can correct the toxin susceptibility at the cellular level. The offspring of these quolls, and their offspring again, should inherit this resistance against cane toad toxins, which theoretically means that no further intervention will be necessary to protect the species.

The team not only hopes that the quolls will become toxin-resistant, but that they will become a primary predator of cane toads and so help to slow the cane toads’ growing population. The researchers also hope to save other threatened species — like goannas, freshwater crocodiles, tiger snakes, red-bellied black snakes and death adders — who also consume and can die from cane toads.

“Innovations like these are desperately needed for conservation today,” said Colossal’s Chief Science Officer, Beth Shapiro.

“Saving the northern quoll both sets a precedent for what is possible using these technologies and creates an opportunity for ecological feedbacks that will allow other Australian species to flourish.”