Inside the risky engineering of the bat virus that connects America to Wuhan

For Baric, this research began in the late 1990s. Coronaviruses were then considered low risk, but Baric’s studies of the genetics that allow viruses to enter human cells convinced him that some could be a few mutations away from crossing the species barrier.

This intuition was confirmed in 2002-2003, when SARS broke out in southern China, infecting 8,000 people. As bad as it was, says Baric, we dodged a bullet with SARS. The disease did not spread from person to person until about a day after the onset of severe symptoms, making quarantine and contact tracing easier. Only 774 people died in this outbreak, but if it had been transmitted as easily as SARS-CoV-2, “we would have had a pandemic with a death rate of 10%,” says Baric. “This is how humanity came together.”

As tempting as it is to view SARS as a one-time event, MERS emerged in 2012 and began infecting people in the Middle East. “For me personally, this has been a wake-up call that animal reservoirs have to have many, many more strains ready to move between species,” says Baric.

By that time, examples of such dangers had already been discovered by Shi’s team, who had spent years sampling bats in southern China to locate 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 which comes from government grants, has its office in New York but partners with local research groups in other countries to perform field and laboratory work. The WIV was his crown jewel, and Peter Daszak, President of the EcoHealth Alliance, co-authored with Shi on most of his key articles.

By taking thousands of samples of guano, fecal swabs, and bat tissue, and searching these samples for genetic sequences similar to SARS, Shi’s team began to discover many closely related viruses. In a cave in Yunnan province in 2011 or 2012, they discovered the two closest, which they named WIV1 and SHC014.

Shi managed to grow WIV1 in his lab from a fecal sample and show that it can directly infect human cells, proving that SARS-like viruses ready to pass directly from bats to humans were already lurking in the natural world. This showed, according to Daszak and Shi, that bat coronaviruses were a “substantial global threat.” Scientists, they said, had to find and study them before they found us.

Most of the other viruses could not be grown, but Baric’s system provided a way to quickly test their peaks by turning them into similar viruses. When the chimera he made using SHC014 was found capable of infecting human cells in a dish, Daszak told reporters that these revelations should “turn this virus into an emerging pathogen.” candidate for a clear and present danger ”.

For others, it was the perfect example of the unnecessary dangers of gain-of-office science. “The only impact of this work is the creation in a laboratory of a new, unnatural hazard,” Rutgers microbiologist Richard Ebright, a longtime critic of the research, told Nature.

For Baric, the situation was more nuanced. While his creation may be more dangerous than the original mouse-adapted virus he used as a backbone, it was still weak compared to SARS – certainly not the supervirus Senator Paul would later suggest.

Ultimately, the NIH crackdown never had teeth. It included a clause granting exceptions “if the head of the funding agency determines that the research is urgently needed to protect public health or national security.” Not only were Baric’s studies allowed to go ahead, but so were all studies that requested exemptions. Funding restrictions were lifted in 2017 and replaced with a more lenient system.

Tyvek suits and respirators

If the NIH was looking for a scientist to make regulators comfortable with gain-of-function research, Baric was the obvious choice. For years he had insisted on additional security measures, and he tried to highlight them in his 2015 article, as if he was modeling the way forward.

the CDC recognizes four levels of biosafety and recommends which pathogens should be investigated at which level. Biosafety level 1 concerns non-hazardous organisms and requires virtually no precautions: wear a lab coat and gloves if necessary. BSL-2 is intended for moderately dangerous pathogens that are already endemic in the region, and relatively gentle interventions are indicated: close the door, wear protective glasses, dispose of waste in an autoclave. BSL-3 is where things get serious. This is for pathogens that can cause serious illnesses through respiratory transmission, such as influenza and SARS, and associated protocols include multiple barriers to escape. The laboratories are surrounded by two sets of self-closing lockable doors; the air is filtered; staff wear full PPE and N95 masks and are under medical supervision. The BSL-4 is aimed at the wicked ones, like Ebola and Marburg: full moon suits and dedicated air systems are added to the arsenal.

“There are no binding standards on what you should and shouldn’t do. It depends on countries, institutions and individual scientists. “

Filippa Lentzos, King’s College London

In Baric’s lab, the chimeras were studied at BSL-3, enhanced by additional steps such as Tyvek suits, double gloves, and powered air respirators for all workers. Local first responder teams participated in regular exercises to familiarize themselves with the lab. All workers were monitored for infections, and local hospitals had procedures in place to handle new scientists. It was probably one of the safest BSL-3 installations in the world. It still wasn’t enough to prevent a handful of mistakes over the years: some scientists have even been bitten by mice carrying viruses. But no infection resulted.

New pathogens

In 2014, the NIH awarded a five-year, $ 3.75 million grant to the EcoHealth Alliance to study the risk of more bat-borne coronaviruses emerging in China, using the same type of techniques Baric had developed. Some of this work was to be contracted out to the Wuhan Institute of Virology.

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