Innovative technology mimics nature, providing
the northern quoll a chance to avoid extinction in the fight
against the invasive cane toad.
Today scientists from Colossal Biosciences, the world’s first
de-extinction company, and the University of Melbourne announce a
major step forward in the effort to save Australia’s endangered
northern quoll (Dasyurus hallucatus) from the invasive cane toad.
The two organizations have performed genetic engineering with
proprietary tools, to introduce genetic resistance in marsupial
cells against the cane toad toxin. This is a crucial step towards a
world-first application of gene-editing technologies for conserving
a threatened species.
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Colossal Biosciences and the University
of Melbourne take steps forward in effort to save the endangered
northern quoll (right) from the invasive cane toad (left) (Graphic:
Business Wire)
To achieve the world-first, the team will next derive induced
pluripotent stem cells (iPSCs) from northern quolls, which can be
CRISPR-edited to introduce the same genetic resistance, ultimately
producing offspring who are cane toad toxin resistant. The
offspring of these quolls will inherit this resistance and can then
be released to rescue the threatened wild population. That
heritable resistance will mean that no further intervention will be
necessary to protect the species from the devastating impacts of
the cane toad.
Quolls are carnivorous marsupials that play a crucial role in
the Australian ecosystem as both a scavenger and a primary
carnivore. They feed on invertebrates and vertebrates, while also
consuming fruits (figs). Since the introduction of invasive cane
toads (Rhinella marina) in Queensland in the 1930s, the northern
quolls have seen their populations plummet by 75%. Cane toads have
now become an attractive food source for the northern quoll, which
is especially vulnerable to the toad’s neurotoxins. The toad is
poisonous at all stages of its life cycle: eggs, tadpoles, toadlets
and adult toads. As adults, the cane toad has venom-secreting
poison glands (parotoid glands) on each shoulder that store and
release poison. When ingested, victims experience rapid heartbeat,
excessive salivation, convulsions and paralysis which results in
death for the quoll and other native animals. Cane toads have
spread well beyond Queensland into coastal New South Wales, the
Northern Territory's Top End and the Kimberley region of Western
Australia and are rapidly moving westward. Their expansion
threatens a complete extinction of the quoll species.
“We need northern quolls to have a balanced ecosystem in
mainland Australia,” shared Professor Andrew Pask, who leads the
Thylacine Integrated Genomic Restoration Research Laboratory at the
School of BioSciences at the University of Melbourne. “By using
Colossal’s technology we’re giving our conservation partners a
fighting chance of succeeding in restoring that balance.”
“We discovered that select gene edits to the quoll could confer
natural resistance,” said Dr. Stephen Frankenberg who heads up the
quoll bufotoxin-resistance research team in Professor Pask’s lab,
which includes PhD student Mr. Pierre Ibri. “That’s why we have
dedicated our efforts to finding out how to save it.”
Dr. Stephen Frankenberg’s observations of other genetically
resistant species led the team to hypothesize that the 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 (in the family Dasyuridae) and serves as a useful
model species, the combined teams successfully engineered
resistance in dunnart cells (which Colossal has used for its
research in Thylacine de-extinction, and is closely related to the
quoll) 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. The team predicts this
resistance will extend to the context of the whole animal. This is
a substantial breakthrough in creating toxin resistance in all
susceptible native animals, and proves that the vision set forth to
create hereditary defense by Frankenberg, Pask and team is
achievable.
“Colossal has been an invaluable partner in this project,” said
Frankenberg. “With their expertise in the gene editing technologies
that will ultimately lead to the de-extinction of entire species,
we know we could be the first to use gene editing for the
conservation of a threatened species.”
A preprint manuscript describing the initial CRISPR editing and
demonstration of toxin resistance has been submitted to bioRxiv,
prior to submission to a peer reviewed journal later this year. The
team hopes that not only will the quolls become resistant but that
they could become a primary predator of cane toads and help to slow
and eventually reverse the cane toads growing population.
“This is cutting edge work in conservation, and an exciting
idea. While there is still a way to go, this is an important
development,” said Professor Ben Phillips, the Premier’s Science
Fellow at Curtin University.
The team hopes 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. Because
cane toads are indiscriminate feeders, they out-compete native
species, moving at an estimated 40-60 km per year. With the cane
toad’s expansion into coastal New South Wales, the Northern
Territory's Top End and the Kimberley region of Western Australia,
they put numerous predatory species at significant risk.
“One of the greatest threats that Australia’s wildlife faces is
invasive species. Toxic prey, such as cane toads, have had
devastating impacts on northern quolls, freshwater crocodiles,
goannas, snakes, and many other native species. This advance, by
Frankenberg and colleagues, is a crucial step towards a future that
might give native wildlife a potential leg up over toads, and maybe
even turn them from a deadly last meal to an abundant food supply,”
said Euan G Ritchie, Professor of Wildlife Ecology and Conservation
at Deakin University. “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.”
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 and thereby ensure hereditary resistance, which will give the
northern quoll a fighting chance at survival. Colossal’s recent
groundbreaking achievement with elephant iPSCs has shed additional
light on the full potential of iPSC edits.
“Innovations like these are desperately needed for conservation
today,” said the Chief Science Officer of Colossal, Beth Shapiro.
“This is precisely why I joined Colossal - to leverage cutting-edge
de-extinction and genetic rescue technologies to accelerate
conservation efforts and restore and preserve at-risk ecosystems
around the world. In this case, 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.”
As this work expands, it will have a dramatic impact on
conservation practices in Australia but could also be extended to
other species affected by toads, such as some reptiles.
“It’s thrilling to see our de-extinction work for the Thylacine
providing technology solutions for living endangered marsupials,”
said Sara Ord, Director of Species Restoration at Colossal. “I
expect we will be able to share many more of these breakthroughs as
we continue our efforts.”
ABOUT COLOSSAL
Colossal was founded by emerging technology and software
entrepreneur Ben Lamm and world-renowned geneticist and serial
biotech entrepreneur George Church, Ph.D., and is the first to
apply CRISPR technology for the purposes of species de-extinction.
Colossal creates innovative technologies for species restoration,
critically endangered species protection and the repopulation of
critical ecosystems that support the continuation of life on Earth.
Colossal is accepting humanity's duty to restore Earth to a
healthier state, while also solving for the future economies and
biological necessities of the human condition through cutting-edge
science and technologies. To follow along, please visit:
www.colossal.com
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