It might have been professional suicide for scientists to raise suspicions about a possible lab leak, Metzl says, especially when there was already a long history of viral disease outbreaks originating in nature. Alina Chan, a postdoctoral researcher specializing in gene therapy and cell engineering at the Broad Institute in Cambridge, Massachusetts, echoes this view. Chan says the risk of challenging the orthodoxy that SARS-CoV-2 has natural origins – a highly plausible hypothesis, she argues – is greatest for established infectious disease scientists with supervisory and staff roles to be supported. She herself has spent much of the past year asking for a more in-depth examination of a potential lab leak, saying that as a post-doc she has less to lose.
The vitriol also obscures a larger imperative, says Relman, which is that finding the origins of the virus is crucial to stopping the next pandemic. Threats from both laboratory accidents and natural fallout are increasing simultaneously, as humans regularly move through wild places and new biosafety labs proliferate around the world. “That’s why the question of origins is so important,” says Relman.
“We need a much better idea of where to put our resources and efforts,” he adds. And if a lab version for SARS-CoV-2 sounds plausible, says Relman, “then it absolutely deserves a lot more attention.”
If SARS-CoV-2 has spread to humans from nature, how and where did it happen? A year after the start of the pandemic, these questions remain open. Scientists still wonder if the virus is transmitted directly to humans from infected bats (known reservoirs for hundreds of different coronaviruses), or via an intermediate animal species. The Huanan Seafood Wholesale Market in Wuhan was initially believed to be the original site of a potential spread, as this is where the first cluster of Covid-19 – the disease caused by the virus – was detected. But new evidence suggests animal or human infections may have circulated elsewhere for months before, and attention has since widened to other markets in the city, wildlife farms in southern Chinaand other possible scenarios, such as eating frozen meat contaminated with viruses from other provinces.
Importantly, the immediate ancestors of the virus have not yet been identified. The closest known relative, a coronavirus called RaTG13, is 96% genetically similar to SARS-CoV-2.
A virus that escaped the laboratory, meanwhile, would have been introduced into the world by a researcher or technician who was infected with it. These kinds of lab leaks have happened before and have been implicated in several cases transmission during the SARS outbreaks in the early 2000s. In 2017, the Wuhan Institute of Virology became the first laboratory in mainland China to receive biosafety level 4 (BSL-4) designation, the status of highest security for a search space. But the institute also has a history of questionable security practices. Scientists at the lab reported a lack of trained technicians and investigators at the facility, prompting U.S. diplomats who visited in 2017 and 2018 to alert the State Department. At the same time, many scientists have pointed out, especially as a result of a recent and for some people, litigation, examination of the laboratory leak hypothesis New York Magazine, that coronaviruses have generally been treated at BSL-2 or BSL-3 – lower safety levels.
These caveats aside, a dominant theory among proponents of lab leaks is that SARS-CoV-2 was not just introduced into the Wuhan lab, but was somehow engineered there, given that many of its scientists regularly conduct genetic research on coronaviruses and may also have “collaborated on secret publications and projects with the Chinese military,” according to a US State Department fact sheet released during the last week of the Trump administration. On March 9, a Washington Post columnist, citing an anonymous State Department official, suggested that the Biden administration – while stopping long before endorsing a particular theory regarding the origin of the virus – did not dispute many of the points made in this fact sheet.
Still, skeptics who doubt the lab leak hypothesis say SARS-CoV-2 looks nothing like an artificial virus. Instead of appearing in discrete chunks, as one would expect with a genetically modified microbe, the differences with RaTg13 are distributed randomly throughout the viral genome. In an email to Undark, University of Chicago Emeritus Professor of Virology Bernard Roizman wrote that “we are many years away from a full understanding of the functions and regulation of viral genes – the elements keys essential for the construction of deadly viruses “.
The virus has an inexplicable feature: a so-called “furin cleavage site” in the spike protein that helps SARS-CoV-2 find its way into human cells. Although such sites are present in some coronaviruses, they have not been found in any of the known closest relatives of SARS-CoV-2. “We don’t know where the furin site came from,” says Susan Weiss, a microbiologist who co-directs the Penn Center for Research on Coronaviruses and Other Emerging Pathogens at the Perelman School of Medicine at the University of Pennsylvania. “It’s a mystery. Although Weiss says SARS-CoV-2 was probably not designed, she adds that the possibility that it escaped from a lab cannot be ruled out.
ALBERTO E. RODRIGUEZ / GETTY IMAGES
Relman says it is also possible that scientists working with undisclosed and even more closely related coronaviruses – perhaps one with a furin cleavage site and another with the backbone of the SARS-CoV-2 gene – may have been tempted to create a recombinant virus so that they can study its properties. Indeed, researchers from the Wuhan Institute of Virology initially failed to disclose that eight other SARS-like coronaviruses had been detected in samples taken from the same mining cave where RaTG13 was found. Workers who cleaned up bat droppings in this cave, located in Yunnan Province near the border with Laos, developed severe respiratory illness and one died.
Petrovsky leans towards another potential scenario, which is that SARS-CoV-2 could be evolved from coronaviruses that have crept into lab cultures. Related viruses in the same culture, he explains, such as one optimized for human ACE2 binding and the other not, can exchange genetic material to create new strains. “We’ve had this stuff in our own lab,” he says. “One day you grow the flu, then one day you sequence it, and you say ‘Holy shit, where did this other virus in our culture come from?’ Viruses evolve all the time, and it’s easy for a virus to enter your crop without you knowing it. “Petrovsky and several co-authors speculated in an article published as an unpaired preprint in May of last year on whether the virus was “completely natural” or whether it was from a “recombination event that occurred inadvertently or intentionally in a laboratory handling coronaviruses.” ” The team did not “say it was a laboratory virus”, emphasizes Petrovsky, but rather “simply presented our data”.
But at the end of April 2020, as Petrovsky’s group wondered where to publish their work, “Trump blurted out” that he had reason to believe the virus came from a Chinese lab, says Petrovsky. . And at that point, he adds, much “of the left-wing media decided they were going to portray the whole lab as a conspiracy theory to bring down Trump.” When Petrovsky approached the administrators of the bioRxiv preprint server, the article was refused. BioRxiv staff responded that it would be best distributed after peer review, “which blew us away,” says Petrovksy. “We thought the purpose of pre-printing was to get important information out quickly.”
The paper was posted later on another preprint server called arXiv.org, based at Cornell University. Soon reporters came calling, but most were from right-wing media representing what Petrovsky calls “the Murdoch press”. Petrovsky says he had to work to prevent some biased journalists from distorting the findings of his article to shape a narrative that SARS-CoV-2 was unequivocally fabricated. And at the same time, he says, other media have tried to “mock the possibility of the lab.”