Rewriting Life

First Gene Drive in Mammals Could Aid Vast New Zealand Eradication Plan

Evolution-warping technology applied to mice is a step toward “synthetic” species conservation.

Fluorescent mice as seen in a archive photo.

Scientists working in coördination with a U.S. conservation group say they’ve established an evolution-warping technology called a “gene drive” in mammals for the first time and could use it to stamp out invasive rodents ravaging seabirds on islands.

Gene-drive technology, so far demonstrated only in insects and yeast, is a powerful way of biasing the inheritance of DNA such that wild animals can be genetically altered as they reproduce, including to cause a population crash.

Now two scientific teams—one in Australia and one in Texas—say they’ve genetically engineered the house mouse, Mus musculus, so that its genome also harbors 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 coördinated 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. Its motto is “preventing extinctions.”

But poison doesn’t work to extirpate rodents on larger islands or heavily populated ones. That’s why the group thinks gene drives could be the “transformative technology” that allows it to extend its campaign to thousands more islands it says are infested. “We were looking for something really out of the box,” says Karl Campbell, a program director at the nonprofit, 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, due to a gene drive, are only able to have 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 ravaging native plants and animals.

And rodents are high on the list of troublemakers. Brought by shipwrecks or sailors, they swarm over oceanic islands, imperiling native seabirds. While rats are the bigger problem, mice cause havoc, too. On Pacific islands, mice have been filmed gnawing on albatross chicks, which are defenseless against them.

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 reëngineering 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. Last year, the U.S. 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.

“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.

Daughterless mice

A man-made gene drive was first demonstrated in fruit flies only in 2015. Within a few months the concept had been extended to mosquitoes, and already the technology is viewed as promising enough to have landed $75 million from Bill Gates, whose foundation is betting that extinguishing mosquitoes could eradicate malaria from Africa

So it was only a matter of time—less than two years, it turned out—before the technique was adapted to mammals.

The two groups of scientists coördinating their work with Island Conservation agreed to reveal the extent of their technical progress to MIT Technology Review, 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 his lab has taken precautions to prevent a mishap, including designing safety features so the drive can’t yet be transmitted to wild mice. When I spoke to him in January, Thomas said he was about to start breeding the first set of lab animals to determine if the drive works as predicted. This step, carried over a few generations, will take several months. 

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.

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 favoring 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 to the t-complex an extra copy of Sry, a gene that is normally found on the Y chromosome and which determines whether a mammal turns out to be male. 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 have male sex organs. 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. 

Rat Island

Island Conservation was formed in the 1990s, and its early exploits removing cats, goats, and even feral donkeys from Baja California are recounted in Rat Island, a book-length account of global island-clearing efforts, which by now have eradicated rodents from 500 islands.

The drawback is how conservation groups have 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. So do any bald eagles and gulls unlucky enough to chomp the poisoned prey.

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 ambitious plan to kill every rat, possum, and weasel across its 103,483-square-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.  

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.” Cummings, who has listened to Island Conservation’s arguments, says she’s come to the conclusion that saving seabirds from rats is being used to “whitewash this technology, give it moral cover, when it might be the world’s most dangerous bioweapon.”

The two sides debated several times last year, most recently in December, at a meeting in Cancun of the UN Convention on Biodiversity, where activists including Friends of the Earth and ETC Group rallied about 170 civil society groups calling for a moratorium on gene drives. A letter signed by luminaries including the primatologist Jane Goodall warned that “genocidal genes” could have “consequences beyond our comprehension.” 

The effort to compel a ban fell short.

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