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A now-canceled grant from the National Institutes of Health allowed researchers associated with the EcoHealth Alliance to gather samples from bats, which can carry viruses that jump to other animals and humans.

ECOHEALTH ALLIANCE

NIH’s axing of bat coronavirus grant a ‘horrible precedent’ and might break rules, critics say

Sciences COVID-19 reporting is supported by the Pulitzer Center.

The research community is reacting with alarm and anger to the National Institutes of Health’s (NIH’s) abrupt and unusual termination of a grant supporting research in China on how coronaviruses—such as the one causing the current pandemic—move from bats to humans.

The agency axed the grant last week, after conservative U.S. politicians and media repeatedly suggested—without evidence—that the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escaped from a laboratory in Wuhan, China, that employs a Chinese virologist who had been receiving funding from the grant. The termination, which some analysts believe might violate regulations governing NIH, also came 7 days after President Donald Trump, asked about the project at a press conference, said: “We will end that grant very quickly.”

NIH declined to comment on why it canceled the grant, which was in its sixth year. But in emails reviewed by ScienceInsider, Michael Lauer, NIH’s deputy director for extramural research, suggested the Wuhan laboratory had not “taken all appropriate precautions to prevent the release of pathogens” that were the focus of the project. NIH offered no further support for that statement, however, and Lauer referred to the notion of the pandemic virus escaping the lab simply as “allegations.”

Researchers familiar with the laboratory are skeptical of claims of lax safety practices, and the Chinese virologist at the center of the allegation has asserted the virus did not escape from her laboratory. Trump administration officials have reportedly pressed U.S. intelligence agencies to produce firm evidence linking the virus to the lab, but key spy agencies have not confirmed any connection so far. Today, a U.S. intelligence assessment added that the U.S. intelligence community “concurs with the wide scientific consensus that the COVID-19 virus was not manmade or genetically modified.” The statement left open the possibility that an accidental release of a natural virus could have launched the pandemic. (Later today, Trump said he was confident the virus came from the Wuhan lab, but that he was “not allowed” to say why he believed that.)

NIH’s move, which was first reported by Politico, “is the most counterproductive thing I could imagine,” given the research’s relevance to understanding the current pandemic and avoiding future viral outbreaks, says Gerald Keusch, a former director of NIH’s Fogarty International Center who is now with the National Emerging Infectious Diseases Laboratory at Boston University. “This is a horrible precedent.” (Keusch recently partnered with the canceled grant’s principal investigator to apply for a different NIH grant; they were unsuccessful.)

Others fear the project has become a casualty of an overtly political attempt by the Trump administration to shift attention away from its own troubled response to the pandemic and blame China. “There’s a culture of attacking really critical science for cheap political gain,” says Dennis Carroll, who recently retired as director of the emerging threats division of the U.S. Agency for International Development (USAID).

A long-standing collaboration

NIH’s move disrupts a long-standing collaboration. For some 15 years, the grant’s principal investigator, Peter Daszak, president of EcoHealth Alliance, a New York City nonprofit, and his colleagues have collaborated with a leading Chinese virologist who studies coronaviruses that infect bats. The virologist, Shi Zhengli, is based at the Wuhan Institute of Virology (WIV), located in the city where researchers first identified SARS-CoV-2.

The team has worked to understand how dangerous viruses jump from bats to humans, and to develop tools that could help researchers create diagnostics, treatments, and vaccines for human outbreaks. Bat viruses are believed to be the ancestral source of both the virus that jumped to civets and then to humans, sparking SARS and the camel virus that led to Middle East respiratory syndrome. The exact path SARS-CoV-2 might have taken from bats to humans remains a mystery. EcoHealth Alliance researchers have long collected blood, urine, feces, and oral and anal swabs from wild bats in China and elsewhere in an effort to solve such puzzles.

The alliance’s grant from the National Institute of Allergy and Infectious Diseases, titled “Understanding the risk of bat coronavirus emergence,” was launched in 2014 and renewed for 5 years in 2019 after receiving an outstanding peer-review score. During the first 5 years, Daszak, with NIH vetting and approval, provided Shi with $599,000 out of a total of $3.1 million in grant funding to use lab sequencing techniques to identify bat coronaviruses that were at high risk of jumping to humans. The grant has also supported blood testing of people who live near bat caves in southern China to see whether they carried antibodies indicating they had been infected with a bat coronavirus. In the grant’s next term, through 2024, the researchers were planning to do more human, wildlife, and lab-based studies to pinpoint hot spots in southern China where the risk is highest for a bat coronavirus to jump to humans.

Supported by a now-defunct National Institutes of Health grant, researchers entered this limestone cave in southern China to capture bats, which they put in cloth bags and then released after taking biological samples from them.

ECOHEALTH ALLIANCE

I“The reason our grant was renewed for 5 years is because our work is so important in helping prevent pandemics,” Daszak says. In its first 5 years, the grant produced a score of papers and advances, including genetic sequences of two bat coronaviruses that have now been used as lab tools to test the antiviral drug remdesivir, which has shown some promise as a treatment for COVID-19.

“I am shocked by this,” says Mark Denison, a Vanderbilt University virologist who launched the lab studies that led to remdesivir’s deployment in the current pandemic. “There is no more important research than what EcoHealth Alliance is doing. Our work on remdesivir absolutely would not have moved forward without it.”

Shi’s participation in the grant recently drew attention because she works at WIV, a sprawling campus that includes one of China’s two biosafety level 4 (BSL-4) laboratories, which handle the most dangerous pathogens. Shi and colleagues have collected some 15,000 biological samples in the field from bats, some of which harbor coronaviruses. In January, her team published the genetic sequence of a bat virus that shares 96.2% of its genome with SARS-CoV-2—the closest relative of today’s pandemic virus yet found.

The United States does not require BSL-4 containment for the coronaviruses Shi works with, and she did her grant-funded research at WIV in a BSL-3 lab. Still, concerns about WIV were fueled by a 14 April column in The Washington Post reporting that U.S. Department of State officials had, in 2018, raised concerns about safety and staffing at WIV’s thenbrand-new BSL-4 lab.

Ten days after that column appeared, Lauer wrote to Daszak, to announce that NIH was ending his institute’s grant “for convenience.” Asked to explain the phrase, NIH did not elaborate, but quoted its Grants Policy Statement’s termination section; it notes the agency can cancel a grant “to protect the public health and welfare from the effects of a serious deficiency.”

That explanation has left Daszak befuddled. “I can’t imagine that a grant titled ‘Understanding the risk of bat coronavirus emergence’ could in any way be a danger to public health,” he says. “I would expect it to be entirely the opposite.”

Wuhan lab safety questions

NIH has not responded to an email asking how the grant’s funding posed a danger to public health and welfare. But in a 19 April email to Daszak, Lauer wrote of WIV: “It is in the public interest that NIH ensure that a [grant] sub-recipient has taken all appropriate precautions to prevent the release of pathogens that it is studying.”

There is no scientific evidence that SARS-CoV-2 originated in Shi’s collection of bat viruses at WIV, though researchers concede that such an escape can’t be unequivocally ruled out. The known bat virus closest to SARS-CoV-2, although 96.2% similar, is at least 20 years removed from the pandemic virus in evolutionary time—meaning that if it escaped from a laboratory, it would have taken decades for it to evolve into the virus that has now killed more than 230,000 people to date. One Nature Medicine paper further indicated that the pandemic virus shows no signs of having been engineered by scientists, another contention of conspiracy theorists. For one thing, although the researchers note that though the virus binds to a human cellular receptor to initiate an infection, that interaction is not optimal, “strong evidence that SARS-CoV-2 is not the product of purposeful manipulation,” they write.

James Le Duc, director of Galveston National Laboratory, where he runs a BSL-4 lab, trains scientists in biosafety from around the world—including one who came from Shi’s lab. He says he visited WIV shortly before its BSL-4 laboratory opened in 2018, and has known Shi for several years and holds her in high regard. “I just hate to see a world-class coronavirologist, who’s dedicated her life working with this, being scrutinized as the possible source,” says Le Duc, who sees no evidence for a lab spillover but does not rule out the possibility. Other researchers familiar with WIV and Shi’s work also are skeptical of claims that WIV was unsafe. “You can never eliminate anything 100%, but everything that we know—and everything that we know has happened in nature about emergence—says this came out of nature,” Keusch says.

On 18 April, before NIH moved to cancel the EcoHealth grant, Shi told ScienceInsider that “the closest progenitor of COVID-19 virus is still mysterious and its definitely not from my lab or any other labs. … It’s a shame to make the science so complicated.

Carroll says he saw State Department cables discussing the lab when he was at the U.S. Embassy in Beijing, working for USAID. He notes that they were written after a diplomatic visit by nonscientists. “I didn’t place an enormous amount of weight on the observations that were made because they were not part of a critical, standardized evaluation,” says Carroll, a virologist. “If those observations were of substance … NIH would … have needed to take serious steps, because they had authorized [grant] funding [for] work in this laboratory.” (There is no public indication that NIH took any action based on the cables.)

Still, Le Duc says he’s concerned about the Chinese government’s lack of openness about research into the origins of the pandemic—and the extra restrictions it has placed on scientists in China who are studying the question. “They’re not helping themselves,” he says, adding the U.S. government is also “throwing rocks at them.” And he worries the tensions will come at a high price when it comes to responding to COVID-19. “We would know a lot less were it not for the fact that we’ve been working with these guys in Wuhan for years,” he says. “We were personal friends with them—you know, you pick up the phone and talk to them. And this kind of dialogue is just critically important, especially now that there’s this hostile government attitude.”

NIH on shaky legal ground?

Even as the debate continues over the origins of the pandemic virus, some experts are questioning whether NIH has the legal authority to unilaterally cancel an already funded grant in the absence of wrongdoing by the investigators.

In cases of scientific misconduct or conflict of interest, NIH has wide latitude to cancel grant awards, notes Heather Pierce, senior director and regulatory counsel at the Association of American Medical Colleges. But NIH officials did not charge Daszak with any wrongdoing in their email exchanges, and at one point they stated that he could continue all of the grant’s work except for pieces planned for WIV. (Lauer later abruptly reversed that and told Daszak that NIH had canceled the entire grant.)

What’s more, the language that NIH provided to ScienceInsider from its Grants Policy Statement, citing the need “to protect the public health and welfare from the effects of a serious deficiency,” is superseded by a different regulation, says one longtime university research administrator who asked not to be identified. That regulation allows NIH to cancel an award midstream only in four situations, none of which appears to pertain in the current case, she says. “If this was my institution I would be talking to our counsel about pushing back on NIH hard.”

Keusch says he is trying to mobilize colleagues to contest NIH’s action. “This is cutting off your face to spite your nose,” he says. “This is the worst kind of thing that political interference can cause in a democracy.”

Daszak, meanwhile, says he is trying to engage NIH in hopes of charting a path forward. He says he asked on 27 April to speak with Lauer. Lauer has not responded.

With reporting by Dennis Normile.

*Update, 4 May, 8:40 a.m.: An 18 April comment from Shi, asserting the coronavirus did not escape from her laboratory, has been added to the story.