“I will tell you, more and more, we’re hearing the story [that the new coronavirus emerged from a Wuhan lab].”

— President Donald Trump, in a news conference, April 15, 2020

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President Donald Trump isn’t the only one hearing this tale. The political world, internet theorists, intelligence analysts and global public health officials are abuzz with a big question: Is it possible that the new coronavirus — which causes COVID-19 — leaked from a lab?

For months, Chinese authorities have pointed to the Huanan Seafood Wholesale Market in Wuhan as the virus’s likely origin. A cluster of early cases had contact with the market. It sold a wide variety of wildlife which, officials hypothesized, was critical to the virus’s formation and spread. Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which cause similar symptoms, were formed after a coronavirus from a bat transformed in another animal and then jumped to humans.

The logic seems straightforward. But a more complete analysis of early cases suggested locating the origin of the virus may not be so simple. A study published in the New England Journal of Medicine found that of the first 425 patients, only 45% had connections to the market. A separate Jan. 24 analysis published in the Lancet found that three of the first four cases — including the first known case — did not have market links.

Daniel Lucey, a pandemics expert at Georgetown University, put it simply: “In my opinion, the virus came into the market before it came out of the market.”

That tinge of uncertainty was bolstered after Washington Post columnist Josh Rogin revealed two 2018 cables in which State Department officials warned of safety issues at the Wuhan Institute of Virology, a laboratory studying bat coronaviruses. Renewed questions about the virus’s origin brought a rush of alternative theories. Some claimed the virus was a bioweapon. Others suggested it had been altered for a scientific experiment or was simply a viral sample that escaped from a lab.

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Let’s be clear: No scientist we spoke to thinks the new coronavirus was designed as a bioweapon. When asked, Milton Leitenberg, a biological weapons expert at the University of Maryland, responded with a flat, “No.”

Most experts say the new coronavirus was the product of a natural process. Still, the safety issues described in the 2018 cables, the Chinese government’s response and the proximity of the labs to the market have raised eyebrows.

As college professors are fond of saying, the absence of evidence is not the same as the evidence of absence. Let’s explore.

The facts

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The labs

In Wuhan, at least two labs study coronaviruses that originate in bats: the Wuhan Institute of Virology (WIV) and the Wuhan Center for Disease Control and Prevention (WHCDC). Both are close to the seafood market. WIV is about eight miles away. WHCDC is right around the corner.

Despite the overlap in research, what the two labs actually do is quite different. WIV is home to China’s first laboratory to receive the highest level of international bioresearch safety (known as BSL-4). In addition, it houses lower-level (BSL-3 and BSL-2) labs. WHCDC is home only to a BSL-2 lab.

“BSL-2 is what we normally think of when we think of a lab,” explained Angela Rasmussen, a virologist at Columbia University’s Mailman School of Public Health. It is a lab where “somebody is wearing a lab coat and gloves, they’re at a bench.” (BSL-4 is akin to what is seen in movies like “Contagion.”)

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She explained the seemingly relaxed security is because coronaviruses found in bats “don’t infect human cells very well, if at all. So often they’re not considered major potential pathogens because they just don’t grow very well in other species besides bats.” If scientists were being particularly cautious, she explained, they might work in a BSL-3 lab.

Researchers from both labs faced criticism in recent years that they have not followed appropriate safety protocols. A video published in December 2019 shows Tian Junhua, a prominent researcher based at WHCDC, conducting field research on bats without appropriate protective equipment.

Warnings from U.S. diplomats in 2018 appeared to refer to the BSL-4 lab at WIV. They reported: “During interactions with scientists at the WIV laboratory, they noted the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory.”

But Rasmussen cautioned against putting too much weight in these reports: “Without fail, every single BSL-4 lab in the U.S. gets some type of safety violation, some type of thing that they could do better.”

A 2019 paper written by WIV researchers about China’s effort to add more high-level bioresearch labs warned, “The experience of laboratory biosafety personnel training is relatively lacking … Insufficient training staff and training problems such as uneven standards require urgent improvement and improvement.” A separate 2019 paper by Yuan Zhiming, a chief scientist at Wuhan, described systemic deficiencies at high-security labs: “Maintenance cost is generally neglected; several high-level BSLs have insufficient operating funds for routine, yet vital processes.” Most laboratories “lack specialized biosafety managers and engineers,” he wrote.

Months after the new coronavirus was discovered, Global Times, a state-run news site, published an article outlining new government guidelines aimed at fixing “chronic management loopholes at virus labs.” The article noted some labs have paid “insufficient attention to biological disposal.”

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Could a safety lapse have opened the door for the new coronavirus to escape one of these labs, just as SARS had? (To be clear, SARS escaped after it had been identified. The initial outbreak did not begin this way.) Accidents happen. Records reveal multiple accidents have led to the escape of dangerous pathogens and inadvertent infections at U.S. laboratories.

While no comparable records exist in China, one of the world’s foremost experts on these viruses, Shi Zhengli, based at WIV, thought it was possible. In March, Shi told the Scientific American that in the early days of the outbreak, even she wondered whether coronaviruses were to blame. “Could they have come from our lab?” After all, her lab had collected and sequenced tens of thousands of coronaviruses over the past decade. (She has since adamantly denied that the new coronavirus could have emerged from her lab. Her boss and WIV issued similar denials.)

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The virus

Safety protocols aren’t a virus’s only barrier between a life in a test tube and one infecting millions. The virus would need to be able to infect humans (or another animal that can then infect humans), and that infection needs to be strong enough that it isn’t immediately beaten by the immune system, allowing it to spread among people.

Most known bat coronaviruses can’t do either of these things. The novel coronavirus, however, can do both. That said, it is called “novel” for a reason: It had never before appeared in scientific research.

Viruses — like people — have distinct genetic sequences that give scientists clues to their origin. Research published in the journal Nature on Feb. 3 found that this virus falls within a family of known coronaviruses that come from bats. It shares nearly 80% of the genome as the original SARS-CoV and 96% of the genome of a virus (RaTG13) that Shi’s team had previously sampled.

While 96% may sound like a big overlap to nonscientists, the 4% difference is found in the part of the virus that binds to human cells. Without that adaptation, Lucey, the Georgetown professor, put it simply: “It’s interesting, but it’s not going to cause any outbreaks in people.”

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Moreover, the two viruses are generations apart. Edward Holmes, an evolutionary virologist from the University of Sydney who has written about the origin of the new virus, explained via email that the two viruses “shared a common ancestor that lived a long time ago. What this means is that [the new coronavirus] is NOT derived from RaTG13.” Holmes noted another virus that — like RaTG13 — was sampled 1,000 miles from Wuhan in a cave in Yunnan is a closer relative to the new virus, but “not close enough to be the direct ancestor.” And critically, he said, this other virus, “is not from the Wuhan Institute of Virology, nor from anywhere else in Wuhan.”

So how did this virus end up 1,000 miles from the nearest known relative? There are any number of potential explanations. A wildlife trafficker might have brought an infected bat into the city. Another animal might have picked up the virus from bats years ago, allowing it to transform in just the right way to infect humans. There are thousands of bat viruses scientists have not sampled and even more coronaviruses that circulate in other species, so there’s no guarantee it actually came from thousands of miles away.

But even if that virus from Shi’s lab is not the source for the virus, her lab is full of bat coronavirus variants. That left us wondering: Could this virus have been the accidental product of an experiment gone awry? A 2015 paper cautioned against the “gain of function” experiments with which Shi’s team was involved. In this kind of experiment, the researchers mutate virus strain to enhance a pathogen’s natural traits. Even though the most dangerous part of that experiment was not conducted at WIV, the 2018 State Department cables referenced similar research by Shi and her team.

In 2017, Shi and her team published a study revealing that they had found a coronavirus from a bat that could be transmitted directly to humans. After reviewing the study, Rasmussen said via email that just because these viruses could attach to human cells, it “does not show that they are particularly effective at doing so.” Binding is only one part of the process. “It is not the sole determinant of viral fitness (the ability of the virus to replicate robustly in a given host) or pathogenicity (the ability of the virus to cause disease).” Moreover, genomic analysis reveals none of the virus samples used to conduct these experiments were or could have been transformed to be the new coronavirus that causes COVID-19.

That, however, is just one study. Shi’s lab published dozens of academic papers researching bat coronaviruses. The Washington Post reviewed academic studies that described “scores of encounters with animals that are known hosts to deadly viruses, including strains closely related to the pathogen behind the COVID-19 outbreak.”

“While the scientists wore gloves and masks and took other protective measures, U.S. experts who reviewed the experiments say the precautions would not necessarily protect the researchers from harmful exposures, in caves or in the lab,” The Post reported.

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This kind of research filled in critical gaps in scientific understanding of SARS-like coronaviruses. It also increased the risk of accidental exposure and lab accidents. But many scientists are still dubious.

Kristian G. Andersen, an immunology and microbiology professor at Scripps Research, alongside Holmes and other researchers, stated firmly, “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.” Trevor Bedford, a researcher in computational biology and infectious diseases at the University of Washington, was more specific. “You don’t see kind of large chunks of genomic material that are somehow inserted or absent,” he said. Rather, it is the opposite. “The differences are these small mutations, as you’d expect from nature.”

(Shi did not return our emails. None of her current collaborators we spoke to could precisely speak to her current research.)

Still, no scientist was willing to completely dismiss the idea — and only said that it was highly unlikely. After all, we neither know what either lab was specifically working on, nor do we have an archive of every animal in the lab and virus sequence in their freezer. Without identifying the earliest case and the evolution of the virus, everything is a hypothesis.

Richard H. Ebright, a microbiologist and biosafety expert at Rutgers University, said: “The question whether the outbreak virus entered humans through an accidental infection of a lab worker is a question of historical fact, not a question of scientific fact. The question can be answered only through a forensic investigation, not through a scientific investigation.”

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The Chinese response

The actions of Chinese officials have done little to quash suspicion of lab leak. Before the government had even alerted the World Health Organization to the growing epidemic, scientists were told to destroy early samples of the virus, according to the Straits Times.

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Then, in an unusual move for the government, officials quickly pinned the outbreak on the market. But they have done little to provide supporting evidence for this theory. Officials reported 33 of 585 environmental samples from the market contained the new coronavirus. Thirty-one of the positive samples were located in the area of the market known to sell wildlife. But where exactly these samples were taken is not clear. They could just as well have been taken from animal cages or a bathroom. Moreover, China has not divulged the results of any tests done on any animals that were recovered from the market before it was cleaned.

Several doctors, journalists and researchers based in China appear to have suddenly gone quiet over this issue. The New York Times reported by mid-January — shortly after the sequence of the virus was made public — that “Chinese scientists cut off official communications” with their American counterparts.

On Feb. 6, Botao Xiao, a molecular biomechanics researcher at South China University of Technology, published a paper arguing that “the killer coronavirus probably originated from a laboratory in Wuhan.” He pointed to the previous safety mishaps and the kind of research both labs undertake as evidence. After the paper gained international attention, Chinese authorities flatly denied that an accident happened. Xiao later withdrew the paper, explaining in a brief email to the Wall Street Journal on Feb. 26: “The speculation about the possible origins in the post was based on published papers and media, and was not supported by direct proofs.”

The Chinese government’s actions have inhibited the scientific community’s ability to trace the origin of the virus and only serve to raise suspicions.

“It just seems like such a remarkable coincidence that you have an outbreak of a coronavirus in theory from a bat in the same city where there is this high-level BSL-4 laboratory, where not only are there foreign concerns about its safety, but there are Chinese articles about the safety protocols not being sufficient. And obviously there’s no smoking gun,” said Emily de La Bruyère, a China expert with Horizon Advisory. “It’s all circumstantial, but it’s pretty remarkable.”

In a statement via email, the Chinese Embassy in Washington told The Fact Checker: “The source of the virus is a serious and complex matter of science that must be studied by scientists and medical experts. Many scientists have already pointed out that COVID-19 has a natural origin.”

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But the U.S. government is not convinced. The intelligence community “will continue to rigorously examine emerging information and intelligence to determine whether the outbreak began through contact with infected animals or if it was the result of an accident at a laboratory in Wuhan,” the director of national intelligence said in a statement on April 30.

The bottom line

The balance of the scientific evidence strongly supports the conclusion that the new coronavirus emerged from nature — be it the Wuhan market or somewhere else. Too many unexpected coincidences would have had to take place for it to have escaped from a lab. But the Chinese government has not been willing or able to provide information that would clarify lingering questions about any possible role played by either Wuhan lab.

That’s why intelligence agencies are still exploring that possibility, no matter how remote it may be. And even then, it’s unclear when or if we will ever know the origin story of this new virus that is causing death and economic turmoil around the globe.

(Anika Varty / The Seattle Times)