You could be forgiven for wondering how a disease as fast-moving and deadly as COVID-19 could just appear naturally, out of nowhere, seemingly overnight. President Trump expressed doubt, saying that “a lot of people” were looking at the possibility that a Chinese lab was responsible for the COVID-19 pandemic. Earlier that week, Fox News ran a story in which unnamed sources suggested that the COVID-19 outbreak originated in a Wuhan laboratory — the Wuhan Institute of Virology, which studies coronaviruses with a number of international collaborators. The New York Times reported that spy agencies are being pressured to find evidence blaming the lab, and at the end of April, the National Institutes of Health withdrew funding from a research consortium that had collaborated with the lab. As recently as this weekend, Secretary of State Mike Pompeo, despite saying there was no reason to disbelieve the intelligence community’s assessment that the virus was neither manmade nor genetically modified, claimed there was “enormous evidence” connecting the virus to the WIV.
But the truth is almost certainly not that salacious. Robert Garry, a professor of microbiology and immunology at the Tulane University School of Medicine, said this dynamic is familiar. “Every time there’s an outbreak, people say, oh, there’s a lab close by.” He should know: In 2014, during the Ebola epidemic in West Africa, conspiracy theorists alleged his team’s lab in Sierra Leone, not far from the origin of the outbreak, was a George Soros-funded bioweapons site.
According to a growing body of research, SARS-CoV-2 (the virus that causes COVID-19) is almost certainly a naturally occurring virus that initially circulated in bats then spilled into humans. But that hasn’t stopped some from trying to find a more sinister origin. “It seems like such an extreme event that people are looking for an extraordinary explanation for it,” said Stephen Goldstein, a postdoctoral researcher at the University of Utah who studies coronaviruses. No single piece of evidence has yet confirmed the virus’ origin. But according to scientists, the evidence that does exist paints a consistent picture of a wild virus, not one that sprang from a lab.
Why do scientists think it wasn’t genetically engineered?
To genetically engineer a new virus, scientists can combine pieces of viruses they’ve seen before. In the case of a genetically engineered coronavirus that was designed to infect humans, the bulk of its genetic material — its “backbone” — would come from SARS or a close relative, while the tools it used to infect cells would be grafted on. But the backbone doesn’t look like any disease-causing virus, and other key parts of the virus are new to science.
In SARS-CoV-2’s case, scientists thought they knew how to optimize SARS to infect human hosts. Coronaviruses enter host cells using protein “spikes” that cover their outer surface. At the tip of each spike is a cluster of amino acids that can bind to a certain receptor on a host cell, like a pick designed to open a particular cellular lock. In the case of SARS-CoV-2, the spike binds to human ACE2 receptors, which coat lung cells.
The original SARS coronavirus targeted the same receptors, and after the 2002 SARS epidemic, experiments tinkered with its spike to determine the structure of an “optimized” version of the SARS lock pick. Many factors influence the success of a virus, but its binding ability is thought to be important, so “if you were going to make a new virus, and make it even more infectious than SARS,” said Goldstein, you would give it that optimized tip.
But, Garry said, the tip of the SARS-CoV-2 spike is unlike anything scientists have seen before, sharing only a single key amino acid with SARS. Modeling suggests that it shouldn’t be able to bind to human lungs well, but the new configuration is about as effective as the optimized SARS.
How SARS-CoV-2 acquired this unusual tip is still a mystery. But blaming it on genetic engineering overstates the abilities of scientists, Garry said. Guessing that these particular amino acids can bind to ACE2 so effectively is nearly impossible— there are 20 common types of amino acids, and tens of millions of ways to arrange them into a binding tip. It would be like if you looked out over the proverbial infinite monkeys with their infinite typewriters, guessed that a specific macaque would type out King Lear, and then picked the right animal.
“Nobody has that kind of insight into how the viruses evolve or cause disease,” said Garry. “You could randomly try to make changes, but we’re talking about thousands of years of trying pathogens out. I’ve been really lucky to know a lot of talented virologists, and they’re not clever enough to come up with a virus that’s quite this good at spreading.”
What if it was in a petri dish and got out?
Another theory suggests a researcher at the WIV studying a precursor to SARS-CoV-2 was accidentally infected.
But the researchers I spoke to threw cold water on that. “I think it’s not unreasonable to ask these questions and examine all sources of the outbreak,” said Gregory Koblentz, a professor at George Mason University who studies biosecurity. “But based on what we know of the biology of the virus, a natural source of the outbreak is the most likely explanation.”
The virus’s spike has a hinge-like structure, allowing the spike to change shape as the virus enters the host cell. Like the spike tip, the hinge on SARS-CoV-2 is markedly different from anything seen in its close relatives. New research suggests that the hinge loses its unique characteristics when cultured in a lab, said Garry. The spike also appears to be able to shield itself from antibodies—another hint that it evolved in the presence of host immune systems.
Most importantly, there’s no smoking gun connecting the lab to an ancestor of the virus. There’s “no bat virus that’s close enough to be the progenitor,” said Garry. The closest known relative to SARS-CoV-2 is a cousin that diverged decades ago in bats.
And while critics suggest that the WIV might have concealed the ancestral virus, 27 scientists who have collaborated with the WIV, including former U.S. officials, rejected the idea in a letter to The Lancet.
Koblentz agrees there’s not much evidence to suggest a cover-up. “If the Chinese government suspected that the outbreak was the result of a biosafety breach in Wuhan, I would have expected them to come down very hard on that lab, not letting them talk to foreigners,” he said. But in March, a lead researcher at the WIV talked to Scientific American about her search for the ancestral strain.
The WIV has released sequences of bat coronavirus in the months since the epidemic started, giving other scientists insight into the origins of the virus that causes COVID-19. Several of the early virus genome sequences in an open-source international database were submitted by the WIV, which allowed other countries to begin developing diagnostic tools. That willingness to release data, Koblentz said, could be evidence that weights “the scale towards [the WIV] being transparent and cooperative.”
Then how’d it get here at all?
There’s a simpler, if less flashy, explanation for the emergence of a new SARS. A study, published in 2018, of four rural villages in Yunnan province located near caves containing bats known to carry coronaviruses found that 2.7 percent of those surveyed had antibodies for close relatives of SARS. Thousands, if not millions, of people are exposed to wild coronaviruses every year. Most of them aren’t dangerous, but “if you roll the dice enough times,” Goldstein said, you’ll see a bad one.
Critics have raised concerns over biosafety protocols at the WIV, but Angela Rasmussen, a virologist at Columbia University, said the criticisms are based on evidence taken out of context. The reports of biosafety issues, she said, are “like having the health inspector come to your restaurant. It could just be, ‘Oh, you need to keep your chemical showers better stocked.’ It doesn’t suggest, however, that there are tremendous problems.”
And Garry reiterated that it’s incredibly unlikely SARS-CoV-2 is the result of a “bad” roll of the dice at the WIV. “All the natural exposures dwarf the possibility that it was some lab guy that was out catching bats and infected himself. That’s one little thing among millions of encounters.”
It’s impossible to totally rule out a lab accident, Rasmussen said, but she worries that unilateral, politically charged investigations will permanently damage international scientific collaboration.
“We live in a global world,” said Rasmussen. “It would hurt us tremendously if we were to stop collaborating with Chinese scientists.” The next pandemic is unlikely to come from a lab, just as Ebola, SARS, Zika and avian flu did not, she said. And the U.S. will be much more vulnerable if our epidemiologists face it alone.