For Barrick, this research began in the late 1990s. Coronaviruses were then considered low-risk, but Barrick’s studies of the genes that allowed the viruses to enter human cells convinced him that some of them might be a few mutations away from jumping the species barrier.
This conjecture was confirmed in 2002-2003, when SARS broke out in southern China, infecting 8,000 people. Although that was bad, says Barrick, we dodged a bullet with Sars. The disease did not spread from person to person until about a day after severe symptoms appeared, making it easier to tolerate through quarantine and contact tracing. Only 774 people died in that outbreak, but if it were transmitted as easily as SARS-CoV-2, “we would have a pandemic with a 10% mortality rate,” Barrick says. “That’s how close humanity is.”
Despite the temptation to write off SARS as a one-time event, in 2012 Middle East Respiratory Syndrome emerged and began infecting people in the Middle East. “For me personally, that was a wake-up call that animal reservoirs should contain many, many subspecies adapted for movement across species,” Barrick says.
By then, Shi’s team had already discovered examples of such dangers, spending years sampling bats in southern China to determine the origin of SARS. The project was part of a global viral surveillance effort led by the US nonprofit EcoHealth Alliance. The nonprofit—which has an annual income of more than $16 million, more than 90% of government grants—has an office in New York but partners with local research groups in other countries to do field and laboratory work. WIV was its crown jewel, and Peter Daszak, president of EcoHealth Alliance, was a co-author with Shi on most of its major papers.
By taking thousands of samples from guano, fecal swabs and bat tissue, and searching those samples for genetic sequences similar to SARS, Shi’s team is beginning to discover several closely related viruses. In a cave in Yunnan province in 2011 or 2012, they discovered the closest, and named it WIV1 and SHC014.
Shi was able to culture WIV1 in her lab from a fecal sample and showed that it can directly infect human cells, proving that SARS-like viruses are ready to jump directly from bats to humans already lurking in the natural world. This showed, as Daszak and Shi said, that bat viruses pose a “significant global threat.” They said that scientists need to find and study them before they find us.
Many other viruses cannot be cultured, but Baric’s system provided a way to quickly test their mutations by engineering them into similar viruses. When the illusion he made using SHC014 proved capable of infecting human cells in a dish, Daszak told the press that these discoveries should “transfer this virus from an emerging candidate pathogen to a clear and present danger.”
For others, it was the perfect example of the unnecessary dangers of job-gain science. “The only effect of this work is to create a new abnormal hazard in the lab,” Rutgers microbiologist Richard Ebright, a longtime critic of such research, told Nature.
For Barrick, the situation was more subtle. Although creating it may have been more dangerous than the original mouse-adapted virus that used it as a backbone, it was weak compared to the SARS virus — certainly not the supervirus that Senator Paul later proposed.
In the end, the NIH campaign had no teeth. It included a provision granting exceptions “if the head of the funding agency determines that the research is urgently necessary to protect public health or national security.” Not only Barrick’s studies were allowed to proceed, but also all studies that had applied for exemptions. Funding restrictions were lifted in 2017 and replaced with a more lenient system.
Tyvek suits and respirators
If the National Institutes of Health were looking for a scientist who would make regulators comfortable with gain-of-function research, Barrick was the obvious choice. For years, he’s been adamant about taking extra safety steps, and he made an effort to reference these steps in his 2015 research paper, as if they were a model for the way forward.
The CDC recognizes Four Biosafety Levels Recommended pathogens at which level should be studied. Biosafety Level 1 is intended for non-hazardous organisms and requires virtually no precautions: wear lab coat and gloves as needed. BSL-2 is intended for pathogens of medium severity that are already endemic to the area, Relatively mild interventions are indicated: close the door, wear eye protection, and dispose of waste in an autoclave. BSL-3 is where things get serious. It is intended for pathogens that can cause serious illness through respiratory transmission, such as influenza and SARS, and its associated protocols include multiple barriers to escape. The labs are covered with two sets of self-closing doors; The air is filtered. Staff are using full PPE and N95 masks and are under medical observation. BSL-4 is for super bad guys, like Ebola and Marburg: Full Moon suits and custom air systems have been added to the arsenal.
There are no enforceable standards for what you should and should not do. It is up to individual states, institutions and scholars.”
Philippa Lentzos, King’s College London
In Baric’s lab, the chimeras in BSL-3 were studied, augmented with additional steps such as Tyvek suits, double gloves, and powered respirators for all workers. Local first responder teams participated in regular exercises to increase their knowledge of the lab. All workers were monitored for infection, and local hospitals had procedures in place to deal with incoming scientists. It was probably one of the safest BSL-3 facilities in the world. This is still not enough to stop him a bunch of mistakes Over the years: some scientists have been bitten by virus-carrying mice. But there were no injuries.
Brand new nurses
In 2014, the National Institutes of Health awarded a five-year, $3.75 million grant to EcoHealth Alliance to study the risk of more bat-borne coronaviruses emerging in China, using the same kind of technologies Baric pioneered. Some of this work was to be subcontracted to the Wuhan Institute of Virology.