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Amid the devastating Covid-19 pandemic, two researchers are proposing a drastic way to stop future pandemics: using a technology called a gene drive to rewrite the DNA of bats to prevent them from becoming infected with coronaviruses.

The scientists aim to block spillover events, in which viruses jump from infected bats to humans — one suspected source of the coronavirus that causes Covid. Spillover events are thought to have sparked other coronavirus outbreaks as well, including SARS-1 in the early 2000s and Middle East respiratory syndrome (MERS).

This appears to be the first time that scientists have proposed using the still-nascent gene drive technology to stop outbreaks by rendering bats immune to coronaviruses, though other teams are investigating its use to stop mosquitoes and mice from spreading malaria and Lyme disease.

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The scientists behind the proposal realize they face enormous technical, societal, and political obstacles, but want to spark a fresh conversation about additional ways to control diseases that are emerging with growing frequency.

“With a very high probability, we are going to see this over and over again,” argues entrepreneur and computational geneticist Yaniv Erlich of the Interdisciplinary Center Herzliya in Israel, who is one of two authors of the proposal, titled “Preventing COVID-59.”

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“Maybe our kids will not benefit, maybe our grandchildren will benefit, but if this approach works, we could deploy the same strategy against many types of viruses,” Erlich told STAT.

As the Covid-19 pandemic has killed more than 3.9 million people and triggered $16 trillion in economic losses, scientists, public health officials, ecologists, and many others have called for deeper investments in longstanding pandemic prevention measures.

Such measures include boosting global health funding, reducing poverty and health inequity, strengthening disease surveillance networks and community education, preventing deforestation, controlling the wildlife trade, and beefing up investments in infectious disease diagnostics, treatments, and vaccines.

Erlich and his co-author, immunologist Daniel Douek at the U.S. National Institute of Allergy and Infectious Diseases, now propose an additional measure: creating a gene drive to render wild horseshoe bats immune to the types of coronavirus infections that are thought to have triggered the SARS, MERS, and Covid-19 pandemics. They shared the proposal Wednesday on the Github publishing and code-sharing platform.

Though there is heated debate about whether the Covid-19 virus originated in a lab, most scientists say the virus is most likely to have originated in wild animals. There is strong evidence, for instance, that horseshoe bats carry the coronavirus that caused the SARS outbreak.

A gene drive is a technique for turbocharging evolution and spreading new traits throughout a species faster than they would spread through natural selection. It involves using a gene editing technology such as CRISPR to modify an organism’s genome so that it passes a new trait to its offspring and throughout the species.

The idea of making a gene drive in bats faces such enormous scientific, technical, social, and economic obstacles that scientists interviewed by STAT called it “folly,” “far-fetched,” and “concerning.” Among other objections, they worried about unintended consequences with so radically tampering with nature.

“We have other ways of preventing future Covid-19 outbreaks,” argued Natalie Kofler, a trained molecular biologist and bioethicist and founder of Editing Nature, a group focused on inclusive decision-making about genetic technologies.

“We need to be thinking about changing the unhealthy relationship of humans and nature, not to gene drive a wild animal so that we can continue our irresponsible and unsustainable behavior that is going to come back to bite us in the ass in the future.”

Coming from anyone else, the idea might be laughed off.

But Erlich has a reputation as a visionary. In 2014, for instance, he and another scientist predicted that genetic genealogy databases might one day be used to reveal people’s identities. Four years later, that happened, when law enforcement officials used the method to identify a former California police officer as the notorious Golden State Killer. Erlich has since become chief scientific officer of the genetic genealogy company MyHeritage and he is also founder of a biotech startup, Eleven Therapeutics.

Now, Erlich says, it’s worth thinking about how a gene drive could work in bats.

Erlich proposes to modify bat genomes so that they would block coronavirus infections. He would create a genetic element, called a shRNA, that targets and destroys coronaviruses. He would then use CRISPR to insert this element into the bat genome. The insertion would also contain a component that pushes bats to preferentially pass the shRNA to their offspring, so that entire bat populations would soon resist coronavirus infection.

“It’s almost like creating a self-propagating vaccine in these bats,” Erlich said.

The idea is intriguing, said geneticist and molecular engineer George Church of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

“Most of the proposals I’ve heard involving gene drives have seemed quite attractive, and this is probably the most attractive,” he said.

Creating a gene drive in bats would be enormously difficult, and perhaps impossible, other scientists say. Researchers have created gene drives in mosquitoes and mice in the lab, but none has been released in the wild. The most advanced gene drive projects intended for field use involve modifying mosquitoes to prevent the spread of malaria and attempting to engineer mice to stop them from causing ecological damage.

But it’s been difficult to engineer effective gene drives in mammals. Developmental geneticist Kim Cooper and her team at the University of California, San Diego, engineered a gene drive that spread a genetic variant through 72% of mouse offspring in her lab. That isn’t efficient enough to quickly spread the desired trait in the wild.

What’s more, creating a gene drive in bats would be much harder than it is in mice, because bat researchers lack the genetic tools available in mice, said Paul Thomas, a developmental geneticist at the University of Adelaide in Australia, who is trying to engineer mouse gene drives.

And unlike mice, which can breed at 6 to 8 weeks of age, bats take two years to reach sexual maturity, so it would take much longer for a trait to spread throughout wild bat populations than in lab mouse populations.

“They say the proposal is not an easy feat from a technical standpoint, and I think that underplays how hard it might be,” Cooper said.

Biologists also say that Erlich’s proposal is unlikely to work in the wild — even if researchers get bat gene drives to work in a lab — because bats are incredibly diverse.

There are 1,432 bat species, including multiple horseshoe bat species that carry coronaviruses and pass them among each other.

Wild viruses similar to the human Covid-19 virus have been found in bats across Asia, and in pangolins. And in June, Weifeng Shi of the Shandong First Medical University & Shandong Academy of Medical Sciences in Taian, China, found 24 coronavirus genomes in bat samples taken from in and around a botanical garden in Yunnan province, in southern China.

Engineering one gene drive in just one bat species would not solve the problem, biologists say.

“You’d have to develop systems for entire bat communities,” said evolutionary biologist Liliana Dávalos of Stony Brook University. “It’s the job of visionaries to come up with creative ideas, but this is a giant blind spot in their thinking.”

Biologists are also concerned about focusing on bats themselves, because they may not be the most important source of human epidemics. No one has found the exact bat analog to the human Covid-19 virus, or definitively proven that spillover from bats did start the pandemic. Coronaviruses have also been found in other species, including palm civets, pangolins, and camels.

Further, nobody knows how eliminating coronaviruses might affect bats.

“We don’t know the implications of wiping out coronaviruses in bat populations, because we don’t know how bats have evolved to coexist with these viruses,” said virologist Arinjay Banerjee of the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Saskatoon, Canada.

Some scientists, though, welcomed Erlich’s proposal, hoping that it will focus attention on what it would take to create successful mammalian gene drive systems.

Royden Saah, for instance, coordinates the Genetic Biocontrol of Invasive Rodents (GBIRd) program, which is trying to engineer gene drives in mice to prevent island bird extinctions. He wants to see more funding to help scientists solve the technical obstacles to such projects, and involve more communities in discussions about these ideas.

“I would be concerned if this proposal detracted from the need to fund public health infrastructure,” said Saah. But with that caveat, he added, “I think this proposal could make people think, ‘OK, if we were to use this technology in this animal in this system, what would we need to do?’ There would need to be a foundation of ethical development, of clear understanding, of social systems and trust, and technology built in a stepwise manner.”

Virologist Jason Kindrachuk of the University of Manitoba said that there are numerous technical and political challenges to a bat gene drive project, and that preventing future outbreaks should mainly involve tackling the challenges that drive spillover events, such as underfunded public health systems, poverty, food insecurity and climate-change-driven ecological disruption. But, he said, given the enormous economic and human toll of Covid-19 and other recent outbreaks, scientists and public health officials might also need to consider new approaches.

“In the past, maybe we were blinded a little bit by our belief that we would just be able to increase surveillance and identify these pathogens prior to them spilling over,” Kindrachuk said. “We now realize that this is going to take a lot of different efforts, so there’s an aspect from a research standpoint where we continue to look at things like this, and say, what are the top 5 to 10 things we should invest in.”

Erlich acknowledges the obstacles to his proposal, but thinks they aren’t insurmountable. He thinks the project would require an international investment involving a multidisciplinary consortium.

“While we totally agree about the technical complexities, technology advances at exponential rates,” Erlich said. “Things that are nearly impossible now can be totally reachable within a decade or so.”

He also thinks a gene drive could be a better alternative than culling bats, which has been tried (unsuccessfully) in communities around the world, and that scientists could monitor for negative impacts on bat populations.

“Let’s discuss the idea and think about what we can do to identify a very rigorous and cautious way to test this approach,” Erlich said. “We don’t like to mess with nature, but the current situation is not sustainable.”

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