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An extinction gene and glowing mice help scientists eradicate invasive species

WHY THIS MATTERS IN BRIEF

The question of whether or not to use gene drives, an extinction technology, to eradicate pests and invasive species is divisive but it looks set to get the go ahead.

 

Scientists working with US conservation group Island Conservation say they’ve managed to establish an evolution defying technology called a “gene drive,” also known as the “extinction gene,” in mammals, in what’s a world first for the technology which, up until now, has been constrained to being used on insects such as fruit flies and mosquitos. The team want to unleash the technology to help eradicate the invasive rodents that are ravaging seabirds on remote islands.

 

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Gene drives are a form of genetic technology that lets scientists use genetic engineering techniques to override nature’s natural reproduction process and introduce new genetic traits – everything from a new eye colour to infertility – into an entire species, and it’s applicable to every DNA based organism. That’s every animal, every plant – and every human, which is one of the reasons why the UN debated the technology last year.

On the one hand though, while the technology can be used to do great good, such as eliminate hereditary disease, in the wrong hands it can also be personalised to target specific groups of people based on specific genetic markers, such as the markers for brown hair, or hereditary origin, many of which were indexed in the Human Genome Project. As a consequence, it could be used to create the ultimate bioweapon – silent, almost undetectable, and 100 percent deadly.

Now two scientific teams, one based in Australia and one in Texas, say they’ve genetically engineered the House Mouse, Mus musculus, so that its genome harbours “genetic surprises” that could be unleashed on wild populations. The modified rodents were born in the last two months and the results are still preliminary.

The effort to establish gene drives in mammals is being coordinated by Island Conservation, a hard charging conservation group based in Santa Cruz, California, whose specialty is bombing small islands with rat poison in order to save endangered seabirds, and ironically its motto is “Preventing extinctions.”

 

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But poison doesn’t work on larger islands or heavily populated ones, and that’s why the group thinks gene drives could be the “transformative technology” that allows them to extend their campaign of eradication to thousands more rodent infested islands.

“We were looking for something really out of the box,” says Karl Campbell, a program director at the non profit, which has plans to spent about $7 million a year to speed the technique toward an initial test on a remote island surrounded by miles of ocean, if authorities allow it.

Campbell says they are pursuing the creation of “daughterless” mice, which, using a gene drive, will only be capable of having male offspring. The gender-biasing effect would drive down mouse populations on an island, possibly to zero if it proves effective.

The mice are an early glimpse of an idea being called “Synthetic conservation,” in which genetic engineering is viewed as a means to revive extinct animals, offer genetic refills for endangered species with shallow gene pools, or knock out invasive pests, such as lionfish and Crown of Thorns starfish which up until know are being eliminated using hunter killer robots ravaging native plants and animals.

And rodents – not surprisingly – are high on the list of troublemakers. Brought by shipwrecks or sailors, they swarm over oceanic islands, wiping out the native seabirds, and while rats are the bigger problem, mice cause havoc, too. On Pacific islands, for example, mice have been filmed gnawing on albatross chicks, which are defenseless against them.

 

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The group’s plans have divided ecologists, however, some of whom see a devil’s bargain in the dizzying new power to modify nature.

“Conservation means caring for the natural world, not re-engineering it,” says Claire Hope Cummings, an environmental lawyer who says she dropped her support for Island Conservation over its gene-drive work.

Even proponents of gene drive technology say it needs to be carefully studied and cautiously deployed, and also say it may not work as advertised – which loosely translates into we have no idea what the broader impact will be if genetically modified, extinction gene carrying animals are released into the wild.

Last year, the US National Academies advised a go-slow approach noting that “proof of concept in a few laboratories” isn’t enough to “support a decision to release gene-drive organisms into the environment.”

But it’s hard not to see the potential. New Zealand, whose flightless birds were overrun starting in the 19th century by species brought by Westerners, this year announced plans to become “predator free” within 30 years by eliminating hundreds of millions of rats, possums, and weasels. The country’s parliament has said that gene drives could be the very “breakthrough” that lets them achieve the goal, and then across the water in Australia it could also be used to eliminate Cane toads – another invasive species.

 

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“No holds barred? That’s what we’d do. That would be phenomenal,” says Campbell of clearing invasive predator species off New Zealand, “then once we got through those, I don’t see why you wouldn’t be thinking about mainland areas like slums or ecosystems which rats have also invaded,” he says.

As far as Island Conservations and the two international teams go though they’ve agreed to speak out and reveal the extent of their technical progress citing the need to develop powerful gene drive technology in the open rather than behind closed doors.

“It’s the perfect time to discuss the risks of the technology,” says Paul Thomas, a mouse geneticist at the University of Adelaide, in South Australia, “we still have to see if it works at all. And it’s not just showing it works, but how efficient and stable it is.”

Thomas says he and his students created gene drive mice using CRISPR, the powerful DNA editing technology. To do it, Australians fashioned CRISPR into a “selfish gene” designed to transmit itself to nearly all of a mouse’s offspring, rather than just half, as would be expected. To track its spread, they have also attached a fluorescent protein so mice who inherit it will glow red when you shine a black light on them.

With critics fretting over the possibility that a gene drive organism could escape from the lab, Thomas says they’ve taken precautions to prevent a mishap, including designing safety features so the drive can’t yet be transmitted to wild mice.

 

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The other team is based at Texas A&M University and led by mouse geneticist David Threadgill, who says his lab has engineered first generation “daughterless” mice. Some are now being bred to determine if the male only trait is passed to future generations, as is hoped. But instead of CRISPR, Threadgill’s lab used a different strategy, harnessing a naturally occurring group of genes called the “t-complex.” This genetic element also manages to spread itself selfishly by harming sperm that don’t have it, and favouring those that do, so they end up fertilizing eggs and making more mouse pups. Versions of the t-complex are already present in many wild mice.

In order to make the mice daughterless, Threadgill’s team introduced an additional modification. They attached Sry, a gene that is normally found on the Y chromosome and which determines whether a mammal turns out to be male, to the t-complex. If the drive operates as intended – something that should be clear inside of a few weeks – more than nine in 10 mouse pups could inherit Sry and turn out male. Released in large enough numbers on an island, the daughterless rodents could, over the course of several months to a few years, result in a mouse population that is, so to speak, all Mickey and no Minnie. Then the mice would die out.

Formed in the 1990’s Island Conservation started out removing cats, goats, and even feral donkeys from Baja California but they relied on brodifacoum, a toxin said to be 100 times as potent as the rat poison warfarin. Rodents bleed to death after they eat it, as do any bald eagles and gulls unlucky enough to chow down on the poisoned prey.

 

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In theory, a gene drive is the perfect solution. It would affect only one species, and it is entirely painless. But some scientists caution that the technology may never work as planned. Coddled lab mice put on an island would be the first to get grabbed by a raptor. And females might be able to sniff out the gene drive, shunning certain males, or even develop resistance to it.

“I think there are actually a hell of a lot of things that could go wrong,” says Neill Gemmell, a researcher at the University of Otago in New Zealand, “if you think you are just going to release things and they are going to eradicate for you, it’s a big mistake.”

Island Conservation, which initially said it planned to try an offshore test by 2020, has since backed away from that prediction, citing open-ended technical and regulatory questions.

That’s not to say Gemmell isn’t interested. In 2016, New Zealand’s government formally launched “Predator Free 2050”- its own ambitious plan to kill every rat, possum, and weasel across its 103,483sq mile territory. Program documents call gene drives a “realistic prospect,” and Gemmell is a part of a committee looking at the options.

Using a genetic assault along with poison and traps is probably the only way to ensure the eradication comes off “cheaply and quickly,” says Gemmell, but the hurdles look daunting. Even if the drives work in mice, no one has ever before genetically engineered an opossum or a weasel. And what would a breeding center able to turn out thousands of GM possums a week even look like? What’s more, because possums breed only once a year, it could take many years, or decades, for a gene drive to have its lethal effect.

 

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The use of gene drives won’t be able to move forward without wide public support. And that could be difficult to win given how it is already dividing conservationists. Some groups, like Friends of the Earth, are deeply suspicious of any genetic engineering and call genes drives a “false solution to the real problem of biodiversity loss.”

Cummings, the environmental lawyer who is also the author of a book critical of GMOs, says she’s also alarmed by the plans to target female mice.

“Daughterless anything is a problem,” she says, “the whole ‘eliminate the female’ concept needs to be looked at philosophically and ethically,” says Cummings, who says she’s listened to Island Conservation’s arguments and come to the conclusion that saving seabirds from rats is being used to “whitewash this technology and give it moral cover, when it might be the world’s most dangerous bioweapon.”

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