A new report details how Chinese scientists at the Wuhan Institute of Virology copied techniques developed by a high-profile U.S. researcher to engineer bat coronaviruses under subpar lab safety conditions, doing so with funding from the National Institutes of Health via the nonprofit organization EcoHealth Alliance. The report includes statements from various scientists, including the U.S. researcher who developed these techniques, condemning funding for the Wuhan lab's work as a mistake.

The MIT Technology Review report, "Inside the risky bat-virus engineering that links America to Wuhan," describes how Dr. Ralph Baric, a world-renowned coronavirus expert and professor at the University of North Carolina, developed a technique to create chimera viruses in his North Carolina lab for the purposes of developing vaccines and treatments to potentially deadly SARS-like pathogens. His "gain-of-function" research involved a technique for "reverse genetics" in coronaviruses, which allowed him to mix and match parts of multiple viruses by studying the genetic codes of virus samples, creating new artificial viruses that could infect human beings.

Baric's goal was the development of a universal vaccine that would protect against all potential viruses that were related to SARS. By creating artificial SARS-like viruses, Baric's work could show how coronaviruses in the wild might evolve to attack human cells and potentially develop weaker versions of these viruses that could be used in a vaccine to teach human immune cells to fend off SARS-like diseases.

In 2013, Baric connected with Zhengli Shi, a researcher at the Wuhan lab who was leading a team that had been discovering new coronaviruses in bat caves. Baric asked Shi to share a sample of one of the viruses she discovered, named SHC014, which she agreed to do. He took that sample back to his lab and began conducting gain-of-function experiments with it.

While Baric was conducting his research, high-profile lab accidents involving anthrax and smallpox and media attention surrounding the Ebola outbreak caused the Obama administration's NIH to announce a moratorium on federal funding for gain-of-function research on SARS, MERS, and influenza viruses in 2014. Gain-of-function experiments had been deemed risky because of the possibility that a lab accident could result in an artificial deadly pathogen escaping into the wild and causing a pandemic. But Baric successfully argued to the NIH that his research was conducted under "extreme measures" of safety in his lab that "made his work categorically different from the high-risk influenza work the NIH had been targeting."

The NIH moratorium on gain-of-function research contained an exception "if head of funding agency determines research is urgently necessary to protect public health or national security." Baric's studies were exempted, and according to the Technology Review report, so were "all studies that applied for exemptions." In 2017, the moratorium was lifted and the Department of Health and Human Services was instructed to create a framework to review proposed gain-of-function research before approving funding for these projects.

Baric's study was published in 2015 and showed how bat coronaviruses occurring in nature were capable of leaping to humans. The MIT Technology Review notes that Baric emphasized the safety precautions he'd taken in his paper. "The potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens," Baric wrote. "Scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue."

The problem was these safety precautions were not necessarily shared by other labs around the world, most notably the Wuhan lab.

According to the MIT Technology Review report, after initially collaborating, Baric's lab at UNC and Zhengli Shi's at WIV became "more like competitors," with both "in a race to identify dangerous coronaviruses, assess the potential threat, and develop countermeasures like vaccines."

Shi's work sampling bat coronaviruses in Southern China is supported by EcoHealth Alliance, a global nonprofit led by Peter Daszak that reportedly receives over 90% of its $16 million in annual income from government grants. Between 2014 and 2019, EcoHealth Alliance sent the Wuhan Institute about $600,000 in NIH funding to study bat coronaviruses.

The research EcoHealth Alliance funded included work that was similar to Baric's studies, but was conducted in a lab that did not share his safety precautions:

In 2014, the NIH awarded a five-year, $3.75 million grant to EcoHealth Alliance to study the risk that more bat-borne coronaviruses would emerge in China, using the same kind of techniques Baric had pioneered. Some of that work was to be subcontracted to the Wuhan Institute of Virology.

Two years later, Daszak and Shi published a paper reporting how the Chinese lab had engineered different versions of WIV1 and tested their infectiousness in human cells. The paper announced that the WIV had developed its own reverse-genetics system, following the Americans' lead. It also included a troubling detail: the work, which was funded in part by the NIH grant, had been done in a BSL-2 lab. That meant the same viruses that Daszak was holding up as a clear and present danger to the world were being studied under conditions that, according to [Rutgers University professor] Richard Ebright, matched "the biosafety level of a US dentist's office."

Baric's lab is recognized by the CDC as a biosafety level 3 lab, where "pathogens that can cause serious disease through respiratory transmission, such as influenza and SARS" are studied "and the associated protocols include multiple barriers to escape." Such protocols include labs walled off by two sets of self-closing, locking doors; filtered air; and lab personnel equipped with full PPE and N95 masks under medical surveillance. Baric also implements additional safety precautions like Tyvek suits, double gloves, and powered-air respirators for all workers.

The Wuhan lab where Shi emulated Baric's experiments operated at biosafety level 2, which is reserved for "moderately hazardous pathogens that are already endemic in the area, and relatively mild interventions are indicated: close the door, wear eye protection, dispose of waste materials in an autoclave."

Rutgers University microbiologist Richard Ebright, a longtime critic of gain-of-function research, told the MIT Technology Review that the high-containment conditions Baric used in his lab imposed a cost and inconvenience the Chinese would have avoided by working under less restrictive conditions. He explained that the Wuhan lab's decision to work at BSL-2 would have "effectively increas[ed] rates of progress, all else being equal, by a factor of 10 to 20," giving the Chinese researchers an advantage over their American competition.

But the competitive advantage came at the cost of increasing the risk that a lab accident could leak a potentially deadly artificial pathogen onto an unsuspecting world.

The MIT Technology Review report does not disclose new evidence to suggest that the COVID-19 pandemic originated in the Wuhan lab and was leaked, as some observers have hypothesized. Shi claims her researchers never encountered the SARS-CoV-2 virus before the Wuhan outbreak, and an Australian scientist who worked at the Wuhan lab in 2019 recently defended the lab's security measures and said she never heard of anyone at the lab falling ill with COVID-like symptoms toward the end of 2019.

Still, that the American government funded gain-of-function-type experiments in a comparatively lax safety environment at the Wuhan lab is "an actual scandal," Stanford University bioengineer Michael Lin said.

Columbia University virologist Ian Lipkin, who co-authored an influential paper arguing that the SARS-CoV-2 virus had natural origins, told journalist Donald McNeil Jr. that the Wuhan lab operating at BSL-2 conditions was "screwed up." He explained that when he wrote the paper criticizing the lab-leak hypothesis, he was under the impression that the Wuhan lab was conducting its research under BSL-4 conditions, the highest level of security.

"It shouldn't have happened. People should not be looking at bat viruses in BSL-2 labs. My view has changed," he said, reassessing the lab-leak hypothesis.

Importantly, biosecurity expert Filippa Lentzos noted that the WIV did not violate any laws by operating under BSL-2 conditions. "There are no enforceable standards of what you should and shouldn't do. It's up to the individual countries, institutions, and scientists," she told MIT Technology Review.

But Baric, who invented the research Shi's team replicated, argues there should be. "I would never argue that WIV1 or SHC014 should be studied at BSL-2, because they can grow in primary human cells," he said. "There's some risk associated with those viruses. We have no idea whether they could actually cause severe disease in a human, but you want to err on the side of caution. ... If you study a hundred different bat viruses, your luck may run out."

MIT Technology Review reports that the NIH did not reply to questions on its decision to approve research conducted at the Wuhan Institute of Virology, nor has it released details on deliberations under its framework for reviewing gain-of-function research requests.

Under President Donald Trump's direction, the NIH terminated its funding for EcoHealth Alliance for bat coronavirus research in April 2020, citing concerns with lab safety at the Wuhan Institute of Virology. Months later, the NIH reversed its decision after outcry against what was called "political interference" by Trump, who was accused of promoting a "conspiracy theory" that the SARS-CoV-2 virus was leaked from the Wuhan lab.

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