Medical Examiner

A Very Calm Guide to the Lab Leak Theory

How could it happen? What are the chances? What on earth is “gain of function” research?

A side-by-side of test tubes and a bat
Photo illustration by Slate. Photos by DoroO/iStock/Getty Images Plus and serikbaib/iStock/Getty Images Plus.

More than a year into the COVID-19 pandemic, scientists still aren’t sure where exactly the virus that caused this mess came from, and how it was able to spread so rapidly among humans. With the origins of the coronavirus still up in the air, there’s been a lot of talk of the so-called lab leak theory—the idea that the virus spread to people in a laboratory accident, rather than jumping from a wild animal to a human.

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In recent days, there’s been a flurry of speculation, and it can be hard to parse what the lab leak theory is all about, how likely it is, and why it matters at all. Here’s our attempt to sort some of that out.

OK, for starters: I thought this was all a conspiracy theory.

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Well, sort of. Near the beginning of the pandemic, President Donald Trump blamed China for the virus and suggested it originated in a lab. He didn’t have evidence, and he wasn’t taking his cues from scientists (who were saying that the virus most likely came from animals, as many viruses do). So, yes, shouting that the virus came from a lab in that context was unwarranted.

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Some researchers published letters in prominent journals that dismissed those unfounded statements. “We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin,” read a letter in the Lancet. “We were just saying, hey, time out, let’s not draw conclusions until we have data,” says Charles Calisher, an emeritus professor of microbiology and immunology at Colorado State University and a co-author of the Lancet letter.

So how is this no longer a conspiracy theory? Is there new data?

There is currently no direct evidence for either a natural origin or a lab leak. That is, no one has found the smoking gun—the virus hanging out in a lab, or in nature. Genetically, the virus is similar to coronaviruses found in bats and in pangolins, which are a type of anteaterlike mammal. But scientists haven’t found the virus’s exact sequence in an animal.

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That seems like good evidence for the lab leak theory!

Not really. It can take years to identify a virus’s source. It’s also not a unique situation—scientists also aren’t exactly sure where Ebola came from, either. Also, almost every vertebrate gets infected by coronaviruses, says Shangxin Yang, assistant medical director of the Clinical Microbiology Laboratory at UCLA Health. It’s really no surprise we haven’t found this one yet.

OK, but what about that Wall Street Journal article about the researchers who got sick?

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In May, the Wall Street Journal reported that in November 2019, three researchers at the Wuhan Institute of Virology were sick enough that they sought hospital treatment for respiratory illness. They had symptoms that were similar to those of COVID-19—but also to those of other illnesses, like the flu.

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Although some saw the report as supporting the lab leak theory, Yang notes that there was already some evidence that COVID-19 could have begun spreading in Wuhan as early as October. “I don’t really see that as evidence [of a lab leak],” Yang says, because even if the researchers did have COVID-19, they wouldn’t have had to have gotten it from a lab. “Those three could be only three out of hundreds or thousands of people who already got it.”

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Got it. OK, so that sounds pretty shaky. Hasn’t there been an actual investigation into the lab leak?

Yes. In March 2021, a joint study between World Health Organization and Chinese scientists looked at some of the ways the virus might have spread. They visited hospitals and government labs and interviewed Chinese scientists, doctors, and officials about the start of the pandemic. The report concluded that a lab origin of the virus was “extremely unlikely.” Researchers in the Wuhan Institute of Virology’s coronavirus lab—which is where the leak would have potentially come from—said none of them had antibodies for the virus, and no coronavirus sample matching Sars-CoV-2 exists in their lab. Plus, viruses similar to Sars-CoV-2 exist in nature.

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Why not just trust that conclusion, then?

Well, some scientists do. But it was far from a transparent investigation, says Alina Chan, a molecular biologist at the Broad Institute of the Massachusetts Institute of Technology and Harvard. Chan has previously argued that a lab origin of the virus is possible in part because, unlike the original SARS virus, this new virus didn’t change and mutate constantly to adapt to human hosts in the pandemic’s first months. The WHO scientists, she says, “had to be chaperoned everywhere” by Chinese government officials and weren’t allowed to see raw data on early COVID-19 patients, limiting their ability to draw conclusions about the virus’s early spread. Chan also said that scientists’ early efforts to distance themselves from the theory, back when Trump was shouting about it, only made it harder for other scientists to voice concerns over the real possibility of a lab leak.

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In May, a group of dissatisfied scientists, including Chan and many prominent virologists, epidemiologists, and public health researchers, published a letter in the journal Science in support of a more transparent investigation and serious consideration of the “lab leak” theory. Soon after, President Joe Biden asked U.S. intelligence agencies to redouble their investigation into the virus’s origins, which had been inconclusive. The agencies are to update Congress on the results within 90 days.

It’s important to acknowledge that scientists pushing for further investigation are not saying that the virus could have been engineered for use as a bioweapon or released on purpose. “That’s where the conspiracy line is very clear,” says Chan.

OK, so the “lab leak”—if it happened—wasn’t purposeful. How could it have happened?

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There are a few ways, says Chan. Researchers travel to remote areas to collect virus samples, she says, and “during that fieldwork, a researcher could get reasonably infected,” she says. Scientists going into remote caves and old mines to collect, for example, bat guano from infected animals sometimes wear full protective equipment but sometimes do not, as science writer David Quammen describes in his book on disease outbreaks from animals. Yes, this would effectively be an instance of “spillover” of a virus from an animal to a human—but in the course of doing research. Researchers could also have become infected if they were working with a virus in the lab and not wearing proper gear or following safety procedures, says Chan.

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Why would scientists in Wuhan be working with a dangerous virus in the first place?

In part, to try to prevent a pandemic like this one from happening. A type of research called “gain of function” research examines how a virus might evolve—or gain—different ways of spreading, including the ability to reach humans. Scientists try to mimic this process themselves, by altering parts of a virus’s structure or genome, then infecting human cells grown in the lab. “The reason for doing it [is] so in case an epidemic appeared, we want to be better prepared by understanding it better,” says Robert Gallo, co-founder and director of the Institute of Human Virology at the University of Maryland School of Medicine, and co-founder and international scientific adviser of the Global Virus Network.

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According to National Institutes of Health grants examined by journalist Nicholas Wade, gain of function research was being done at the Wuhan Institute of Virology at some point. (Confusingly, Anthony Fauci has claimed that the NIH did not fund gain of function research, but Chan points out that his definition of “gain of function research” is a bit narrow).

Does that mean scientists could have created Sars-CoV-2?

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Not quite. The virus’s genetic code shows that its genome has not been extensively altered by humans, says Chan. But she argues that it’s possible humans made small changes to it. Those are harder to detect.

Other scientists argue that humans simply wouldn’t be able to intentionally create (or tweak) a virus that spreads so efficiently. “Humans are not smart enough to do that,” says Yang. For proof, Yang says, just look to recent disease outbreaks—Ebola, SARS, and MERS are all caused by viruses that originated in animals. Gain of function research, in that line of thinking, would have to be very, very sophisticated in order to mimic that.

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OK, so it sounds like the jury is still out.

Most experts still tend to think the virus has a natural origin. Yang explains that a lab leak is theoretically possible but extremely unlikely. So many other infectious diseases have originated from animals, including the MERS and SARS outbreaks caused by coronaviruses. Because humans live increasingly close to animals, diseases that originate from animals have also long been predicted to become more prevalent.

But yes, without more data, it’s impossible to know for sure. Chan thinks scientists shouldn’t be asked to constantly make public judgment on the likelihood of one scenario versus another—if new evidence emerges, they might feel like they can’t change their mind. She also thinks it’s just impossible to really nail down the probability of a lab leak without a transparent understanding of what was happening in the lab. “It would be like trying to guess what’s the likelihood of rolling a six without knowing how many sides of the dice there are,” says Chan.

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That all makes sense, but, as someone who is not a doctor or a scientist, do I need to care about it?

Probably not. “If it was ever a lab leak, WHO would want to know and make sure it never happens again,” says Gallo. But “you’re not going to gain anything out of knowing one way or another.” And regardless of the origin of this virus, we know that viruses jump from animals all the time. That kind of transmission definitely poses an ongoing threat. Yang says it will be important to identify regional outbreaks of diseases from animals before they spread very far. But if history is any lesson, says Yang, there is no way to entirely prevent diseases from spreading this way. “The reality is, unfortunately, that COVID will not be the last one,” he says.

Others argue that everyone has a right to know how this pandemic started, especially if a safety lapse ended up causing a lab leak. As Chan explains, “If we’re aware that these labs are doing very high-risk pathogen research on the sources of pandemics, people in America and most of the world can write to their governments and say, ‘Let’s not have that happen in my city.’ ”

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