lab leak essay

Why the Pandemic Probably Started in a Lab, in 5 Key Points

By Alina Chan

Dr. Chan is a molecular biologist at the Broad Institute of M.I.T. and Harvard, and a co-author of “Viral: The Search for the Origin of Covid-19.”

This article has been updated to reflect news developments.

On Monday, Dr. Anthony Fauci returned to the halls of Congress and testified before the House subcommittee investigating the Covid-19 pandemic. He was questioned about several topics related to the government’s handling of Covid-19, including how the National Institute of Allergy and Infectious Diseases, which he directed until retiring in 2022, supported risky virus work at a Chinese institute whose research may have caused the pandemic.

For more than four years, reflexive partisan politics have derailed the search for the truth about a catastrophe that has touched us all. It has been estimated that at least 25 million people around the world have died because of Covid-19, with over a million of those deaths in the United States.

Although how the pandemic started has been hotly debated, a growing volume of evidence — gleaned from public records released under the Freedom of Information Act, digital sleuthing through online databases, scientific papers analyzing the virus and its spread, and leaks from within the U.S. government — suggests that the pandemic most likely occurred because a virus escaped from a research lab in Wuhan, China. If so, it would be the most costly accident in the history of science.

Here’s what we now know:

1 The SARS-like virus that caused the pandemic emerged in Wuhan, the city where the world’s foremost research lab for SARS-like viruses is located.

• At the Wuhan Institute of Virology, a team of scientists had been hunting for SARS-like viruses for over a decade, led by Shi Zhengli.
• Their research showed that the viruses most similar to SARS‑CoV‑2, the virus that caused the pandemic, circulate in bats that live r oughly 1,000 miles away from Wuhan. Scientists from Dr. Shi’s team traveled repeatedly to Yunnan province to collect these viruses and had expanded their search to Southeast Asia. Bats in other parts of China have not been found to carry viruses that are as closely related to SARS-CoV-2.

The closest known relatives to SARS-CoV-2 were found in southwestern China and in Laos.

Large cities

Mine in Yunnan province

Cave in Laos

South China Sea

The closest known relatives to SARS-CoV-2

were found in southwestern China and in Laos.

philippines

The closest known relatives to SARS-CoV-2 were found

in southwestern China and Laos.

Sources: Sarah Temmam et al., Nature; SimpleMaps

Note: Cities shown have a population of at least 200,000.

There are hundreds of large cities in China and Southeast Asia.

There are hundreds of large cities in China

and Southeast Asia.

The pandemic started roughly 1,000 miles away, in Wuhan, home to the world’s foremost SARS-like virus research lab.

The pandemic started roughly 1,000 miles away,

in Wuhan, home to the world’s foremost SARS-like virus research lab.

The pandemic started roughly 1,000 miles away, in Wuhan,

home to the world’s foremost SARS-like virus research lab.

• Even at hot spots where these viruses exist naturally near the cave bats of southwestern China and Southeast Asia, the scientists argued, as recently as 2019 , that bat coronavirus spillover into humans is rare .
• When the Covid-19 outbreak was detected, Dr. Shi initially wondered if the novel coronavirus had come from her laboratory , saying she had never expected such an outbreak to occur in Wuhan.
• The SARS‑CoV‑2 virus is exceptionally contagious and can jump from species to species like wildfire . Yet it left no known trace of infection at its source or anywhere along what would have been a thousand-mile journey before emerging in Wuhan.

2 The year before the outbreak, the Wuhan institute, working with U.S. partners, had proposed creating viruses with SARS‑CoV‑2’s defining feature.

• Dr. Shi’s group was fascinated by how coronaviruses jump from species to species. To find viruses, they took samples from bats and other animals , as well as from sick people living near animals carrying these viruses or associated with the wildlife trade. Much of this work was conducted in partnership with the EcoHealth Alliance, a U.S.-based scientific organization that, since 2002, has been awarded over $80 million in federal funding to research the risks of emerging infectious diseases.
• The laboratory pursued risky research that resulted in viruses becoming more infectious : Coronaviruses were grown from samples from infected animals and genetically reconstructed and recombined to create new viruses unknown in nature. These new viruses were passed through cells from bats, pigs, primates and humans and were used to infect civets and humanized mice (mice modified with human genes). In essence, this process forced these viruses to adapt to new host species, and the viruses with mutations that allowed them to thrive emerged as victors.
• By 2019, Dr. Shi’s group had published a database describing more than 22,000 collected wildlife samples. But external access was shut off in the fall of 2019, and the database was not shared with American collaborators even after the pandemic started , when such a rich virus collection would have been most useful in tracking the origin of SARS‑CoV‑2. It remains unclear whether the Wuhan institute possessed a precursor of the pandemic virus.
• In 2021, The Intercept published a leaked 2018 grant proposal for a research project named Defuse , which had been written as a collaboration between EcoHealth, the Wuhan institute and Ralph Baric at the University of North Carolina, who had been on the cutting edge of coronavirus research for years. The proposal described plans to create viruses strikingly similar to SARS‑CoV‑2.
• Coronaviruses bear their name because their surface is studded with protein spikes, like a spiky crown, which they use to enter animal cells. T he Defuse project proposed to search for and create SARS-like viruses carrying spikes with a unique feature: a furin cleavage site — the same feature that enhances SARS‑CoV‑2’s infectiousness in humans, making it capable of causing a pandemic. Defuse was never funded by the United States . However, in his testimony on Monday, Dr. Fauci explained that the Wuhan institute would not need to rely on U.S. funding to pursue research independently.

The Wuhan lab ran risky experiments to learn about how SARS-like viruses might infect humans.

1. Collect SARS-like viruses from bats and other wild animals, as well as from people exposed to them.

2. Identify high-risk viruses by screening for spike proteins that facilitate infection of human cells.

2. Identify high-risk viruses by screening for spike proteins that facilitate infection of

human cells.

In Defuse, the scientists proposed to add a furin cleavage site to the spike protein.

3. Create new coronaviruses by inserting spike proteins or other features that could make the viruses more infectious in humans.

4. Infect human cells, civets and humanized mice with the new coronaviruses, to determine how dangerous they might be.

• While it’s possible that the furin cleavage site could have evolved naturally (as seen in some distantly related coronaviruses), out of the hundreds of SARS-like viruses cataloged by scientists, SARS‑CoV‑2 is the only one known to possess a furin cleavage site in its spike. And the genetic data suggest that the virus had only recently gained the furin cleavage site before it started the pandemic.
• Ultimately, a never-before-seen SARS-like virus with a newly introduced furin cleavage site, matching the description in the Wuhan institute’s Defuse proposal, caused an outbreak in Wuhan less than two years after the proposal was drafted.
• When the Wuhan scientists published their seminal paper about Covid-19 as the pandemic roared to life in 2020, they did not mention the virus’s furin cleavage site — a feature they should have been on the lookout for, according to their own grant proposal, and a feature quickly recognized by other scientists.
• Worse still, as the pandemic raged, their American collaborators failed to publicly reveal the existence of the Defuse proposal. The president of EcoHealth, Peter Daszak, recently admitted to Congress that he doesn’t know about virus samples collected by the Wuhan institute after 2015 and never asked the lab’s scientists if they had started the work described in Defuse. In May, citing failures in EcoHealth’s monitoring of risky experiments conducted at the Wuhan lab, the Biden administration suspended all federal funding for the organization and Dr. Daszak, and initiated proceedings to bar them from receiving future grants. In his testimony on Monday, Dr. Fauci said that he supported the decision to suspend and bar EcoHealth.
• Separately, Dr. Baric described the competitive dynamic between his research group and the institute when he told Congress that the Wuhan scientists would probably not have shared their most interesting newly discovered viruses with him . Documents and email correspondence between the institute and Dr. Baric are still being withheld from the public while their release is fiercely contested in litigation.
• In the end, American partners very likely knew of only a fraction of the research done in Wuhan. According to U.S. intelligence sources, some of the institute’s virus research was classified or conducted with or on behalf of the Chinese military . In the congressional hearing on Monday, Dr. Fauci repeatedly acknowledged the lack of visibility into experiments conducted at the Wuhan institute, saying, “None of us can know everything that’s going on in China, or in Wuhan, or what have you. And that’s the reason why — I say today, and I’ve said at the T.I.,” referring to his transcribed interview with the subcommittee, “I keep an open mind as to what the origin is.”

3 The Wuhan lab pursued this type of work under low biosafety conditions that could not have contained an airborne virus as infectious as SARS‑CoV‑2.

• Labs working with live viruses generally operate at one of four biosafety levels (known in ascending order of stringency as BSL-1, 2, 3 and 4) that describe the work practices that are considered sufficiently safe depending on the characteristics of each pathogen. The Wuhan institute’s scientists worked with SARS-like viruses under inappropriately low biosafety conditions .

In the United States, virologists generally use stricter Biosafety Level 3 protocols when working with SARS-like viruses.

Biosafety cabinets prevent

viral particles from escaping.

Viral particles

Personal respirators provide

a second layer of defense against breathing in the virus.

DIRECT CONTACT

Gloves prevent skin contact.

Disposable wraparound

gowns cover much of the rest of the body.

Personal respirators provide a second layer of defense against breathing in the virus.

Disposable wraparound gowns

cover much of the rest of the body.

Note: ​​Biosafety levels are not internationally standardized, and some countries use more permissive protocols than others.

The Wuhan lab had been regularly working with SARS-like viruses under Biosafety Level 2 conditions, which could not prevent a highly infectious virus like SARS-CoV-2 from escaping.

Some work is done in the open air, and masks are not required.

Less protective equipment provides more opportunities

for contamination.

Some work is done in the open air,

and masks are not required.

Less protective equipment provides more opportunities for contamination.

• In one experiment, Dr. Shi’s group genetically engineered an unexpectedly deadly SARS-like virus (not closely related to SARS‑CoV‑2) that exhibited a 10,000-fold increase in the quantity of virus in the lungs and brains of humanized mice . Wuhan institute scientists handled these live viruses at low biosafet y levels , including BSL-2.
• Even the much more stringent containment at BSL-3 cannot fully prevent SARS‑CoV‑2 from escaping . Two years into the pandemic, the virus infected a scientist in a BSL-3 laboratory in Taiwan, which was, at the time, a zero-Covid country. The scientist had been vaccinated and was tested only after losing the sense of smell. By then, more than 100 close contacts had been exposed. Human error is a source of exposure even at the highest biosafety levels , and the risks are much greater for scientists working with infectious pathogens at low biosafety.
• An early draft of the Defuse proposal stated that the Wuhan lab would do their virus work at BSL-2 to make it “highly cost-effective.” Dr. Baric added a note to the draft highlighting the importance of using BSL-3 to contain SARS-like viruses that could infect human cells, writing that “U.S. researchers will likely freak out.” Years later, after SARS‑CoV‑2 had killed millions, Dr. Baric wrote to Dr. Daszak : “I have no doubt that they followed state determined rules and did the work under BSL-2. Yes China has the right to set their own policy. You believe this was appropriate containment if you want but don’t expect me to believe it. Moreover, don’t insult my intelligence by trying to feed me this load of BS.”
• SARS‑CoV‑2 is a stealthy virus that transmits effectively through the air, causes a range of symptoms similar to those of other common respiratory diseases and can be spread by infected people before symptoms even appear. If the virus had escaped from a BSL-2 laboratory in 2019, the leak most likely would have gone undetected until too late.
• One alarming detail — leaked to The Wall Street Journal and confirmed by current and former U.S. government officials — is that scientists on Dr. Shi’s team fell ill with Covid-like symptoms in the fall of 2019 . One of the scientists had been named in the Defuse proposal as the person in charge of virus discovery work. The scientists denied having been sick .

4 The hypothesis that Covid-19 came from an animal at the Huanan Seafood Market in Wuhan is not supported by strong evidence.

• In December 2019, Chinese investigators assumed the outbreak had started at a centrally located market frequented by thousands of visitors daily. This bias in their search for early cases meant that cases unlinked to or located far away from the market would very likely have been missed. To make things worse, the Chinese authorities blocked the reporting of early cases not linked to the market and, claiming biosafety precautions, ordered the destruction of patient samples on January 3, 2020, making it nearly impossible to see the complete picture of the earliest Covid-19 cases. Information about dozens of early cases from November and December 2019 remains inaccessible.
• A pair of papers published in Science in 2022 made the best case for SARS‑CoV‑2 having emerged naturally from human-animal contact at the Wuhan market by focusing on a map of the early cases and asserting that the virus had jumped from animals into humans twice at the market in 2019. More recently, the two papers have been countered by other virologists and scientists who convincingly demonstrate that the available market evidence does not distinguish between a human superspreader event and a natural spillover at the market.
• Furthermore, the existing genetic and early case data show that all known Covid-19 cases probably stem from a single introduction of SARS‑CoV‑2 into people, and the outbreak at the Wuhan market probably happened after the virus had already been circulating in humans.

An analysis of SARS-CoV-2’s evolutionary tree shows how the virus evolved as it started to spread through humans.

SARS-COV-2 Viruses closest

to bat coronaviruses

more mutations

Source: Lv et al., Virus Evolution (2024) , as reproduced by Jesse Bloom

The viruses that infected people linked to the market were most likely not the earliest form of the virus that started the pandemic.

• Not a single infected animal has ever been confirmed at the market or in its supply chain. Without good evidence that the pandemic started at the Huanan Seafood Market, the fact that the virus emerged in Wuhan points squarely at its unique SARS-like virus laboratory.

5 Key evidence that would be expected if the virus had emerged from the wildlife trade is still missing.

In previous outbreaks of coronaviruses, scientists were able to demonstrate natural origin by collecting multiple pieces of evidence linking infected humans to infected animals.

Infected animals

Earliest known

cases exposed to

live animals

Antibody evidence

of animals and

animal traders having

been infected

Ancestral variants

of the virus found in

Documented trade

of host animals

between the area

where bats carry

closely related viruses

and the outbreak site

Infected animals found

Earliest known cases exposed to live animals

Antibody evidence of animals and animal

traders having been infected

Ancestral variants of the virus found in animals

Documented trade of host animals

between the area where bats carry closely

related viruses and the outbreak site

For SARS-CoV-2, these same key pieces of evidence are still missing , more than four years after the virus emerged.

For SARS-CoV-2, these same key pieces of evidence are still missing ,

more than four years after the virus emerged.

• Despite the intense search trained on the animal trade and people linked to the market, investigators have not reported finding any animals infected with SARS‑CoV‑2 that had not been infected by humans. Yet, infected animal sources and other connective pieces of evidence were found for the earlier SARS and MERS outbreaks as quickly as within a few days, despite the less advanced viral forensic technologies of two decades ago.
• Even though Wuhan is the home base of virus hunters with world-leading expertise in tracking novel SARS-like viruses, investigators have either failed to collect or report key evidence that would be expected if Covid-19 emerged from the wildlife trade . For example, investigators have not determined that the earliest known cases had exposure to intermediate host animals before falling ill. No antibody evidence shows that animal traders in Wuhan are regularly exposed to SARS-like viruses, as would be expected in such situations.
• With today’s technology, scientists can detect how respiratory viruses — including SARS, MERS and the flu — circulate in animals while making repeated attempts to jump across species . Thankfully, these variants usually fail to transmit well after crossing over to a new species and tend to die off after a small number of infections. In contrast, virologists and other scientists agree that SARS‑CoV‑2 required little to no adaptation to spread rapidly in humans and other animals . The virus appears to have succeeded in causing a pandemic upon its only detected jump into humans.

The pandemic could have been caused by any of hundreds of virus species, at any of tens of thousands of wildlife markets, in any of thousands of cities, and in any year. But it was a SARS-like coronavirus with a unique furin cleavage site that emerged in Wuhan, less than two years after scientists, sometimes working under inadequate biosafety conditions, proposed collecting and creating viruses of that same design.

While several natural spillover scenarios remain plausible, and we still don’t know enough about the full extent of virus research conducted at the Wuhan institute by Dr. Shi’s team and other researchers, a laboratory accident is the most parsimonious explanation of how the pandemic began.

Given what we now know, investigators should follow their strongest leads and subpoena all exchanges between the Wuhan scientists and their international partners, including unpublished research proposals, manuscripts, data and commercial orders. In particular, exchanges from 2018 and 2019 — the critical two years before the emergence of Covid-19 — are very likely to be illuminating (and require no cooperation from the Chinese government to acquire), yet they remain beyond the public’s view more than four years after the pandemic began.

Whether the pandemic started on a lab bench or in a market stall, it is undeniable that U.S. federal funding helped to build an unprecedented collection of SARS-like viruses at the Wuhan institute, as well as contributing to research that enhanced them . Advocates and funders of the institute’s research, including Dr. Fauci, should cooperate with the investigation to help identify and close the loopholes that allowed such dangerous work to occur. The world must not continue to bear the intolerable risks of research with the potential to cause pandemics .

A successful investigation of the pandemic’s root cause would have the power to break a decades-long scientific impasse on pathogen research safety, determining how governments will spend billions of dollars to prevent future pandemics. A credible investigation would also deter future acts of negligence and deceit by demonstrating that it is indeed possible to be held accountable for causing a viral pandemic. Last but not least, people of all nations need to see their leaders — and especially, their scientists — heading the charge to find out what caused this world-shaking event. Restoring public trust in science and government leadership requires it.

A thorough investigation by the U.S. government could unearth more evidence while spurring whistleblowers to find their courage and seek their moment of opportunity. It would also show the world that U.S. leaders and scientists are not afraid of what the truth behind the pandemic may be.

More on how the pandemic may have started

Where Did the Coronavirus Come From? What We Already Know Is Troubling.

Even if the coronavirus did not emerge from a lab, the groundwork for a potential disaster had been laid for years, and learning its lessons is essential to preventing others.

By Zeynep Tufekci

Why Does Bad Science on Covid’s Origin Get Hyped?

If the raccoon dog was a smoking gun, it fired blanks.

By David Wallace-Wells

A Plea for Making Virus Research Safer

A way forward for lab safety.

By Jesse Bloom

The Times is committed to publishing a diversity of letters to the editor. We’d like to hear what you think about this or any of our articles. Here are some tips . And here’s our email: [email protected] .

Follow the New York Times Opinion section on Facebook , Instagram , TikTok , WhatsApp , X and Threads .

Alina Chan ( @ayjchan ) is a molecular biologist at the Broad Institute of M.I.T. and Harvard, and a co-author of “ Viral : The Search for the Origin of Covid-19.” She was a member of the Pathogens Project , which the Bulletin of the Atomic Scientists organized to generate new thinking on responsible, high-risk pathogen research.

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• The covid-19 lab leak...

The covid-19 lab leak hypothesis: did the media fall victim to a misinformation campaign?

Read our latest coverage of the coronavirus pandemic.

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This article has a correction. Please see:

• The covid-19 lab leak hypothesis: did the media fall victim to a misinformation campaign? - July 12, 2021
• Paul D Thacker , investigative journalist
• thackerpd{at}gmail.com Twitter @thackerpd

The theory that SARS-CoV-2 may have originated in a lab was considered a debunked conspiracy theory, but some experts are revisiting it amid calls for a new, more thorough investigation. Paul Thacker explains the dramatic U turn and the role of contemporary science journalism

For most of 2020, the notion that SARS-CoV-2 may have originated in a lab in Wuhan, China, was treated as a thoroughly debunked conspiracy theory. Only conservative news media sympathetic to President Donald Trump and a few lonely reports dared suggest otherwise. But that all changed in the early months of 2021, and today most outlets across the political spectrum agree: the “lab leak” scenario deserves serious investigation.

Understanding this dramatic U turn on arguably the most important question for preventing a future pandemic, and why it took nearly a year to happen, involves understanding contemporary science journalism.

A conspiracy to label critics as conspiracy theorists

Scientists and reporters contacted by The BMJ say that objective consideration of covid-19’s origins went awry early in the pandemic, as researchers who were funded to study viruses with pandemic potential launched a campaign labelling the lab leak hypothesis as a “conspiracy theory.”

A leader in this campaign has been Peter Daszak, president of EcoHealth Alliance, a non-profit organisation given millions of dollars in grants by the US federal government to research viruses for pandemic preparedness. 1 Over the years EcoHealth Alliance has subcontracted out its federally supported research to various scientists and groups, including around $600 000 (£434 000; €504 000) to the Wuhan Institute of Virology. 1

Shortly after the pandemic began, Daszak effectively silenced debate over the possibility of a lab leak with a February 2020 statement in the Lancet . 2 “We stand together to strongly condemn conspiracy theories suggesting that covid-19 does not have a natural origin,” said the letter, which listed Daszak as one of 27 coauthors. Daszak did not respond to repeated requests for comment from The BMJ .

“It’s become a label you pin on something you don’t agree with,” says Nicholas Wade, a science writer who has worked at Nature , Science , and the New York Times . “It’s ridiculous, because the lab escape scenario invokes an accident, which is the opposite of a conspiracy.”

But the effort to brand serious consideration of a lab leak a “conspiracy theory” only ramped up. Filippa Lentzos, codirector of the Centre for Science and Security Studies at King’s College, London, told the Wall Street Journal , “Some of the scientists in this area very quickly closed ranks.” 3 She added, “There were people that did not talk about this, because they feared for their careers. They feared for their grants.”

Daszak had support. After he wrote an essay for the Guardian in June 2020 attacking the former head of MI6 for saying that the pandemic could have “started as an accident,” Jeremy Farrar, director of the Wellcome Trust and co-signer of the Lancet letter, promoted Daszak’s essay on Twitter, saying that Daszak was “always worth reading.” 4

Daszak’s behind-the-scenes role in orchestrating the statement in the Lancet came to light in November 2020 in emails obtained through freedom of information requests by the watchdog group US Right To Know.

“Please note that this statement will not have EcoHealth Alliance logo on it and will not be identifiable as coming from any one organization or person,” wrote Daszak in a February email, while sending around a draft of the statement for signatories. 5 In another email, Daszak considered removing his name from the statement “so it has some distance from us and therefore doesn’t work in a counterproductive way.” 6

Several of the 27 scientists who signed the letter Daszak circulated did so using other professional affiliations and omitted reporting their ties to EcoHealth Alliance. 3

For Richard Ebright, professor of molecular biology at Rutgers University in New Jersey and a biosafety expert, scientific journals were complicit in helping to shout down any mention of a lab leak. “That means Nature , Science , and the Lancet ,” he says. In recent months he and dozens of academics have signed several open letters rejecting conspiracy theory accusations and calling for an open investigation of the pandemic’s origins. 7 8 9

“It’s very clear at this time that the term ‘conspiracy theory’ is a useful term for defaming an idea you disagree with,” says Ebright, referring to scientists and journalists who have wielded the term. “They have been successful until recently in selling that narrative to many in the media.”

The Lancet ’s editor in chief, Richard Horton, did not respond to repeated requests for comment but, after The BMJ had sent him questions, the Lancet expanded Daszak’s conflicts of interest on the February statement and recused him from working on its task force looking into the pandemic’s origin. 10 11

The Lancet letter ultimately helped to guide almost a year of reporting, as journalists helped to amplify Daszak’s message and to silence scientific and public debate. “We’re in the midst of the social media misinformation age, and these rumours and conspiracy theories have real consequences,” Daszak told Science . 12 Months later in Nature , he again criticised “conspiracies” that the virus could have come from the Wuhan Institute of Virology and complained about “politically motivated organisations” requesting his emails. 13

That summer Scientific American , one of the oldest and best known popular science magazines in America, published a complimentary profile of Daszak’s colleague, Shi Zhengli, a centre director at the Wuhan Institute of Virology, which has been funded by EcoHealth Alliance. 14

EcoHealth Alliance and the Wuhan Institute of Virology earned additional sympathetic reporting after the US National Institutes of Health (NIH) cancelled its grant to EcoHealth Alliance in April last year—allegedly on President Trump’s order—because of its ties to Wuhan, a decision protested by 77 Nobel laureates and 31 scientific societies. 15 (The NIH has subsequently awarded EcoHealth Alliance new funding.)

Efforts to characterise the lab leak scenario as unworthy of serious consideration were far reaching, sometimes affecting reporting that had first appeared well before the covid-19 pandemic. For example, in March 2020 Nature Medicine added an editor’s note (“Scientists believe that an animal is the most likely source of the coronavirus”) to a 2015 paper on the creation of a hybrid version of a SARS virus, co-written by Shi. 16

Wade explains, “Science journalists differ a lot from other journalists in that they are far less sceptical of their sources and they see their main role as simply to explain science to the public.” This, he says, is why they began marching in unison behind Daszak.

By the end of 2020, just a handful of journalists had dared to seriously discuss the possibility of a lab leak. In September, Boston magazine reported on a preprint that found the virus unlikely to have come from the Wuhan seafood market, as Daszak has argued, and that it seemed too well adapted to humans to have arisen naturally. However, the story failed to garner much attention, similarly to a little noticed investigative report by the Associated Press in December that exposed how the Chinese government was clamping down on research into covid-19’s origins.

In January this year, New York magazine ran a sprawling story detailing how the pandemic could have started with a leak from the lab in Wuhan. The hypothetical scenario: “SARS-CoV-2, the virus that causes covid-19, began its existence inside a bat, then it learned how to infect people in a claustrophobic mine shaft, and then it was made more infectious in one or more laboratories, perhaps as part of a scientist’s well-intentioned but risky effort to create a broad-spectrum vaccine.” Scientists and their media allies swiftly criticised the article.

But mainstream outlets from the New York Times to the Washington Post are now treating the lab leak hypothesis as a worthy question, one to be answered with a serious investigation. In a recent interview with the New York Times , Shi denied that her lab was ever involved in “gain of function” experiments ( box 1 ) that enhance a virus’s virulence. But the newspaper reported that her lab had been involved in experiments that altered the transmissibility of viruses, alongside interviews with scientists who said that far more transparency was necessary to determine the truth of SARS-CoV-2’s origins. 17

What is “gain of function” research?

After two teams genetically tweaked the H5N1 avian flu virus in 2011 to make it more transmissible in mammals, biosafety experts voiced concerns about “gain of function” research—experimental research that involves altering microbes in ways that change their transmissibility, pathogenicity, or host range.

In the Bulletin of the Atomic Scientists in 2012, Lynn Klotz predicted an 80% chance that a leak of a potential pandemic pathogen would occur sometime in the next 12 years. Two years later a Harvard epidemiologist, Marc Lipsitch, founded the Cambridge Working Group to lobby against such experiments.

At that time, three safety lapses involving dangerous pathogens led to a safety crackdown at the US Centers for Disease Control and Prevention. Lipsitch later argued in 2018 that the release of such a pathogen would “lead to global spread of a virulent virus, a biosafety incident on a scale never before seen.”

Gain of function research was briefly paused because of these concerns, although critics debate as to when it restarted. For more than a decade, scientists at the Wuhan Institute of Virology have been discovering coronaviruses in bats in southern China and bringing them back to their lab for gain of function research, to learn how to deal with such a deadly virus should it arise in nature.

The closest known relative of the SARS-CoV-2 virus was found in a region of China almost 1000 miles from the Wuhan Institute of Virology—yet the pandemic apparently started in Wuhan. Biosafety experts have noted that lab leaks are common but rarely reported, as hundreds of lab accidents had happened in the US alone. 27

Two major events are probably responsible for the media’s change in tune. First, Trump was no longer president. Because Trump had said that the virus could have come from a Wuhan lab, Daszak and others used him as a convenient foil to attack their critics. But the framing of the lab leak hypothesis as a partisan issue was harder to sustain after Trump left the White House.

Second, after months of negotiation the Chinese government finally allowed the World Health Organization to come to Wuhan and investigate the pandemic’s origin. But in January 2021 WHO, which included Daszak on the team, returned with no evidence that the virus had arisen through natural spill-over. 18 More worryingly, members were allowed only a few hours of supervised access to the Wuhan Institute of Virology.

The White House then released a statement making clear that it did not trust China’s propaganda denying that the virus could have come from one of the country’s labs. “We have deep concerns about the way in which the early findings of the covid-19 investigation were communicated and questions about the process used to reach them,” said the statement. “It is imperative that this report be independent, with expert findings free from intervention or alteration by the Chinese government.”

The following month the Washington Post editorial board called for an open and transparent investigation of the virus’s origins, highlighting Shi’s experiments with bat coronaviruses that were genetically very similar to the one that caused the pandemic. 19 It asked, “Could a worker have gotten infected or inadvertent leakage have touched off the outbreak in Wuhan?” The Wall Street Journal , citing a US intelligence document, recently reported that three Wuhan Institute of Virology researchers were admitted to hospital in November 2019. 20

To follow any US financial ties and to better understand how the pandemic started, Republicans have launched investigations of government agencies that fund coronavirus research, and one investigative committee has sent a letter to Daszak at EcoHealth Alliance demanding that he turn over documents. Meanwhile, Senate Republicans and Democrats have started to discuss an independent investigation of the virus’s origins.

A hard truth to swallow

The growing tendency to treat the lab leak scenario as worthy of serious investigation has put some reporters on the defensive. After Robert Redfield, former director of the Centers for Disease Control and Prevention, appeared on CNN in March, Scientific American ’s editor in chief, Laura Helmuth, tweeted, “On CNN, former CDC director Robert Redfield shared the conspiracy theory that the virus came from the Wuhan lab.” The following day, Scientific American ran an essay calling the lab leak theory “evidence free.” And a week later a Nature reporter, Amy Maxmen, labelled the idea that the virus could have leaked from a lab as “conjecture.”

Helmuth did not respond to questions from The BMJ .

Some media outlets have attempted to justify their past reporting about the lab leak hypothesis as simply a matter of tracking a “scientific consensus” which, they say, has now changed. Vox posted an erratum noting, “Since this piece was originally published in March 2020, scientific consensus has shifted.”

The “scientific consensus” argument does not sit well with David Relman, a microbiologist at Stanford University, California. “We can’t even begin to talk about a consensus other than a consensus that we don’t know [the origins of SARS-CoV-2],” he recently told the Washington Post . 21

A year lost

While the narrative took months to change in the media, several high profile intelligence sources had treated the lab leak theory seriously from early on. In April 2020, Avril Haines joined two other former deputy directors of the Central Intelligence Agency to write an essay in Foreign Policy asking, “To what extent did the Chinese government misrepresent the scope and scale of the epidemic?” 22 A week later, one of the former intelligence officials who wrote that essay gave similar quotes to Politico .

Ignoring these early warnings led to a year of biased, failed reporting, says Wade. “They didn’t question what their sources were saying,” he says of the reporters who helped to sell the conspiracy theory narrative to the public. “That is the simple explanation for this phenomenon.”

An impartial, credible investigation?

As the news media scramble to correct and reflect on what went wrong with nearly a year of reporting, the episode has also highlighted quality control issues at the ubiquitous “fact checking” services.

Prominent outlets such as PolitiFact 23 and FactCheck.org 24 have added editor’s notes to pieces that previously “debunked” the idea that the virus was created in a lab or could have been bioengineered—softening their position to one of an open question that is “in dispute.” For almost a year Facebook sought to control misinformation by banning stories suggesting that the coronavirus was man made. After renewed interest in the virus’s origin, Facebook lifted the ban. 25

Whether a credible investigation will be made into the lab leak scenario remains to be seen. WHO and the Lancet both launched investigations last year ( box 2 ), but Daszak was involved in both, and neither has made significant progress.

September Weeks before the pandemic erupts, Jeremy Farrar (Wellcome Trust) and Anthony Fauci (US National Institutes of Health; NIH) help oversee a World Health Organization report highlighting an “increasing risk of global pandemic from a pathogen escaping after being engineered in a lab”

November Three researchers from the Wuhan Institute of Virology are admitted to hospital, says a previously undisclosed US intelligence document reported by the Wall Street Journal on 23 May 2021

31 December WHO is notified of cases of pneumonia of unknown aetiology in Wuhan City

1 February Jeremy Farrar holds a teleconference with Anthony Fauci and others to discuss the outbreak’s origins

6 February A commentary from Chinese researchers based in Wuhan, arguing that “the killer coronavirus probably originated from a laboratory in Wuhan,” is posted and later removed from ResearchGate (the user account “Botao Xiao” is also deleted)

19 February An open letter is published in the Lancet from 27 scientists including Peter Daszak and Jeremy Farrar, who “strongly condemn conspiracy theories suggesting that covid-19 does not have a natural origin”

19 February Science magazine reports: “Scientists ‘strongly condemn’ rumors and conspiracy theories about origin of coronavirus outbreak,” quoting Daszak as saying, “We’re in the midst of the social media misinformation age, and these rumors and conspiracy theories have real consequences, including threats of violence that have occurred to our colleagues in China.”

22 February New York Post publishes an article by a China scholar arguing that “coronavirus may have leaked from a lab”—subsequently censored by Facebook

6 March Kristian Andersen (Scripps Research Institute) thanks Jeremy Farrar (Wellcome), Anthony Fauci (NIH), and Francis Collins (NIH) “for your advice and leadership as we have been working through the SARS-CoV-2 ‘origins’ paper.” The paper is published on 17 March in Nature Medicine and states, “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.”

24 April NIH abruptly cuts funding to EcoHealth Alliance, allegedly on President Trump’s order

28 April Three former US intelligence agents write in Foreign Policy asking whether the virus emerged from nature or escaped from a Chinese lab

21 May New York Times depicts the Wuhan Institute of Virology as a victim of “conspiracy theories”

27 May Nature reports the lab leak hypothesis as “coronavirus misinformation” and “false information”

8 June The science magazine Undark reports that the lab leak is a conspiracy theory “that’s been broadly discredited”

30 December Associated Press investigation finds documents from March 2020 showing how Beijing has shaped and censored research into the origins of SARS-CoV-2

February Facebook places warning on an article by Ian Birrell about the origins of covid-19. Facebook says that these warnings reduce article viewership by 95%

13 February Jake Sullivan, US national security adviser, expresses “deep concerns” about WHO’s covid-19 investigation, calling on China to be more transparent

March Washington Post calls for serious investigations of the lab leak hypothesis

30 March WHO releases a report on its investigation into the origins of covid-19, listing the lab leak as least likely of the possible scenarios considered. Hours earlier, WHO’s director general, Tedros Adhanom Ghebreyesus, acknowledged that the lab leak hypothesis should “remain on the table” and called for a more extensive probe

30 March The US, Australian, Japanese, Canadian, UK, and other governments express concern over WHO’s investigation and call for “transparent and independent analysis and evaluation, free from interference and undue influence”

26 May Facebook lifts its ban on posts referencing the lab leak hypothesis

In recent weeks, several high profile scientists who once denigrated the idea that the virus could have come from a lab have made small steps into demanding an open investigation of the pandemic’s origin.

The NIH’s director, Francis Collins, said in a recent interview, “The Chinese government should be on notice that we have to have answers to questions that have not been answered about those people who got sick in November who worked in the lab and about those lab notebooks that have not been examined.” He added, “If they really want to be exonerated from this claim of culpability, then they have got to be transparent.” 26

But the nature of this investigation has still not been decided.

Competing interests: I am paid by various media outlets for journalism stories and consult part time for a non-profit institute focused on brain disorders. I run a newsletter called the Disinformation Chronicle .

Provenance and peer review: Commissioned, not externally peer reviewed.

This article is made freely available for use in accordance with BMJ's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

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Science-Based Medicine

Exploring issues and controversies in the relationship between science and medicine

The rise and fall of the lab leak hypothesis for the origin of SARS-CoV-2

Two new studies were published last week that strongly support a natural zoonotic origin for COVID-19 centered at the wet market in Wuhan, China. Naturally, lab leak proponents soberly considered this new evidence and thought about changing their minds. Just kidding! They doubled down on the conspiracy mongering, because of course they did.

Ever since the coronavirus now known as SARS-CoV-2 was first identified as the cause of an outbreak of a mysterious severe viral pneumonia in Wuhan, China two and a half years ago, a disease that later spread to the rest of the world as the COVID-19 pandemic, there has been intense curiosity about the origins of the virus. The most plausible hypothesis was that, like many diseases before, SARS-CoV-2 had a zoonotic origin; i.e., it developed the ability to “jump” from an animal reservoir to humans. Far less plausible, albeit not impossible, was the hypothesis that the novel coronavirus was created in a laboratory and then escaped, either through incompetence or malfeasance, a hypothesis that became more colloquially known as the “lab leak” hypothesis. Last week, two papers were finally published in Science that, under normal circumstances, would be, if not the final nails in the coffin of the lab leak hypothesis, getting very close. One examined the molecular epidemiology of SARS-CoV-2 and the other demonstrated that the wet market in Wuhan was indeed an early epicenter of the pandemic . Steve Novella has already discussed the studies , but that’s never stopped me before, given that having a few days to look at them allowed me also to judge reactions. Let’s just say that, contrary to the assertions of some optimists, these studies haven’t made much of an impact on conspiracy theorists, other than to provide them with targets to try to discredit.

Before I get to the studies, though, let’s look at some background on the lab leak hypothesis and conspiracy theories. I do this for two reasons. First, I want to show what these studies add to what we know about the origin of SARS-CoV-2. Second, it’s been a long time since I’ve written about this issue, and I think a recap is overdue.

A brief history of the lab leak hypothesis/conspiracy theory

Since the early days of the pandemic, there has been a question of whether SARS-CoV-2 arose naturally or had escaped from a lab. The latter hypothesis didn’t start out as a conspiracy theory, as lab leaks have happened before—although none had ever caused a pandemic that caused millions of deaths worldwide, over a million in the US alone. However, it rapidly took on the characteristics of a conspiracy theory such that even those advocating the “lab leak” hypothesis often had difficulty not interspersing more serious scientific arguments with what can be only described as a dollop of conspiratorial thinking. As time went on, if anything, the lab leak hypothesis drifted further and further from legitimate science and deeper and deeper into conspiracyland, such that, try as I might, I now have a difficult time finding examples of lab leak advocates who don’t add conspiracy mongering narratives to their arguments.

Here’s what I mean. By by May 2021 it clearly had developed all the hallmarks of a conspiracy theory, complete with a coverup narrative in which China and powerful forces in the US were “suppressing” all mention of a lab leak as a “conspiracy theory”, attacks on funding sources of investigators doing research on coronaviruses, bad science in the form of anomaly hunting ( Nicholas Wade and furin cleavage sites or Steven Quay and Richard Muller and CGGCGG , anyone?) in which any observed oddity in the nucleotide sequence of the virus was portrayed as clear-cut evidence of lab manipulation by scientists doing gain-of-function research (which, apparently, went very wrong), all coupled with an utter resistance to disconfirming evidence. It didn’t help, of course, that the Wuhan Institute of Virology (WIV) was not far from the wet markets that were first identified as likely sources of the outbreak and that the WIV was studying coronaviruses and thus had them on premises. Lab leak proponents are also fond of other kinds of conspiratorial thinking , such as attribution errors, weaponization of disagreements within a general consensus, shifting the burden of proof, moving the goalposts in response to disconfirming evidence, and others, all accompanied by an intense belief in a coverup at the highest levels of multiple governments.

Of course, conspiracy theories about a lab origin for a new pathogen (often as a “bioweapon” that somehow “leaked” from a biowarfare research lab) are nothing new. They inevitably arise whenever a deadly new pathogen appears to cause major outbreaks or, as in the case of SARS-CoV-2, a pandemic. It happened with HIV/AIDS, Ebola , and H1N1 . For instance, there was a major conspiracy theory about HIV/AIDS that involved its creation at Fort Detrick when scientists supposedly spliced together two other viruses, Visna and HTLV-1 and then tested the results on prison inmates. (Interestingly, this turned out to be a Russian propaganda operation codename Operation INFEKTION designed to blame the AIDS pandemic on the US biological warfare program.) Other conspiracy theories include claims that HIV had contaminated various vaccines (smallpox, hepatitis B, etc., depending on the specific version of the conspiracy theory) and thereby gotten into the population. It’s therefore no surprise that almost as soon as SARS-CoV-2 was identified as the source of the initial outbreak in Wuhan, China so did conspiracy theories about a lab origin for the virus, among other things.

One of the earliest conspiracy theories had arisen by February 2020, when James Lyons-Weiler claimed to have “ broken the coronavirus code “, claiming the novel coronavirus whose nucleotide sequence had been published a week or two before, was actually the result of a failed attempt to develop a vaccine for SARS, the coronavirus-caused disease that nearly became a pandemic in 2002-2003. Hilariously, he tried to claim that the novel coronavirus showed evidence of containing nucleotide sequences from a plasmid (a circular DNA construct into which scientists insert genes that can then be introduced into cells to get them to make the protein products of those genes), which, if true, certainly would have been slam-dunk evidence that SARS-CoV-2 had been created in a laboratory. Let’s just say that Lyons-Weiler, for all his claims of molecular biology expertise, made some rather glaring errors. Another variation on this theme was the claim that there were HIV sequences in the virus that indicated that the pandemic had come about as the result of a failed attempt to develop a vaccine against AIDS .

By March 2020, direct examination of the nucleotide sequence of SARS-CoV-2 had led scientists to conclude that the virus was highly unlikely to have been engineered in a laboratory. Predictably, that revelation didn’t stop the conspiracy theories claiming that the virus had been created in a lab and escaped, at least not right away. It took time and more accumulating evidence. In the meantime, distorted claims about the rarity of certain base combinations in the virus and its furin cleavage site had proliferated. Still, by late last year, it had become pretty clear that these narratives were not consistent with scientific data; so, as Steve noted, the goalposts shift (as they often do when conspiracy theories run headlong into disconfirming evidence). The “bioweapon” or lab-engineered version of the lab leak hypothesis then, as conspiracy theories tend to do, morphed into a version that was much harder to falsify, namely that the origin of SARS-CoV-2 was indeed a lab leak, just of a naturally occurring coronavirus that had been collected from bats or pangolins and stored for study at the Wuhan Institute of Virology, such as the bat virus RaTG13 , which was incorrectly claimed to be a direct precursor to SARS-CoV-2. Then, of course, there were claims that workers at WIV were infected with SARS-COV-2 in November 2019, but exhaustive contact tracing failed to find these cases .

None of this is to say that the lab leak hypothesis is impossible, or even homeopathy-level improbable. As I mentioned once, lab leaks of pathogens have occurred before, although none have led to a global pandemic. Rather, conspiracy theorists simply tended to assume that because lab leak was possible that implied that it was equally likely as a natural origin, when the preponderance of evidence has long suggested the conclusion that a lab leak origin for this pandemic is incredibly unlikely. Before I move on to the studies and the reaction to them, I’ll quote Dan Samorodnitsky from over a year ago :

If the question is “are both hypotheses possible?” the answer is yes. Both are possible. If the question is “are they equally likely?” the answer is absolutely not. One hypothesis requires a colossal cover-up and the silent, unswerving, leak-proof compliance of a vast network of scientists, civilians, and government officials for over a year. The other requires only for biology to behave as it always has, for a family of viruses that have done this before to do it again. The zoonotic spillover hypothesis is simple and explains everything. It’s scientific malpractice to pretend that one idea is equally as meritorious as the other. The lab-leak hypothesis is a scientific deus ex machina , a narrative shortcut that points a finger at a specific set of bad actors. I would be embarrassed to stand up in front of a room of scientists, lay out both hypotheses, and then pretend that one isn’t clearly, obviously better than the other.

Change that to lab leak requiring a “colossal cover-up and the silent, unswerving, leak-proof compliance of a vast network of scientists, civilians, and government officials” to over two years now, and the two studies published last week just add to the difference. As was noted last year , there are a number of coronaviruses that routinely infect humans and are known to have had an animal origin and “there is no data to suggest that the WIV—or any other laboratory—was working on SARS-CoV-2, or any virus close enough to be the progenitor, prior to the COVID-19 pandemic”.

Molecular epidemiology: Two lineages likely jumped to humans

The first study comes from Joel O. Wertheim at the University of California at San Diego (UCSD) and was first authored by Jonathan E. Pekar. As is often the case with papers of this sort, the list of authors is long, with multiple labs contributing, because studies of this sort require a lot of expertise and materials and single institutions rarely have everything needed to do them.

I read the whole paper, as well as its very copious supplementary materials and figures (all 31 supplemental figures!), and although my knowledge of bioinformatics and molecular biology is not sophisticated enough to understand the finer details of the analysis, I can help to summarize the overall findings. In brief, the authors queried several large nucleotide sequence databases maintained by different countries, including the GISAID database, GenBank, and National Genomics Data Center of the China National Center for Bioinformatics (CNCB), for complete high-coverage SARS-CoV-2 genomes collected early in the pandemic, specifically by February 14, 2020. They then analyzed the sequences by computer to reconstruct the likely origin and evolution of different viral lineages and used epidemic modeling to surmise when the virus was likely introduced into the human population, as well as to reconstruct the sequence of a probable common ancestor.

The first clear finding is that it is highly unlikely that SARS-CoV-2 circulated widely in humans before November 2019. Indeed, the authors were able to use their phylogenetic analysis to estimate that the first zoonotic transfer from animals to humans likely occurred sometime around November 19, 2019, with a range from October 23- December 8. Interestingly, a news story cites Chinese government data finding that the earliest confirmed case of COVID-19 in China could be traced back to November 17, 2019 , which is pretty close to the date of zoonotic transmission that this study found. On that date a 55-year-old man from Hubei province might have been the first person to have contracted COVID-19. Every day after that, one to five new cases were reported each day, and by December 15 the total number of infections stood at 27. By December 20, the total number of confirmed cases had reached 60, and then it was off to the races for the outbreak.

The second clear finding is that a single zoonotic event can’t explain the data, but rather required two such events from two different lineages, dubbed Lineage A and Lineage B by the scientists. The study found that Lineage B was the first to make the jump to humans. Tellingly, it was only found in people who had a direct connection to the Wuhan wet market. Lineage A appears to have made the jump within weeks—or even days—of when Lineage B did; it was found only in samples from humans who lived near or stayed close to the market. From the paper:

Therefore, our results indicate that lineage B was introduced into humans no earlier than late-October and likely in mid-November 2019, and the introduction of lineage A occurred within days to weeks of this event.

The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October–8 December), while the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

Now, I know what lab leak proponents are thinking. Two zoonotic events introducing this novel coronavirus into the human population? Isn’t that highly unlikely?

Yes and no :

The likelihood that such a virus would emerge from two different events is low, acknowledged co-author Joel Wertheim, an associate adjunct professor of medicine at the University of California, San Diego. “Now, I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare, but once all the conditions are in place — that is a zoonotic virus capable of both human infection and human transmission that is in close proximity to humans — the barriers to spillover have been lowered such that multiple introductions, we believe, should actually be expected,” Wertheim said.

Also, as the authors noted in their discussion:

Successful transmission of both lineage A and B viruses after independent zoonotic events indicates that evolutionary adaptation within humans was not needed for SARS-CoV-2 to spread (49). We now know that SARS-CoV-2 can readily spread after reverse-zoonosis to Syrian hamsters (Mesocricetus auratus), American mink (Neovison vison), and white-tailed deer (Odocoileus virginianus), indicating its host generalist capacity (50–55). Furthermore, once an animal virus acquires the capacity for human infection and transmission, the only remaining barrier to spillover is contact between humans and the pathogen. Thereafter, a single zoonotic transmission event indicates the conditions necessary for spillovers have been met, which portends additional jumps. For example, there were at least two zoonotic jumps of SARS-CoV-2 into humans from pet hamsters in Hong Kong (56) and dozens from minks to humans on Dutch fur farms (52, 53).

In other words, if SARS-CoV-2 was already able to infect humans, it shouldn’t be surprising that more than one introduction occurred. In any case, this study is robust evidence that the most likely origin of SARS-CoV-2 was in an animal reservoir and that it very likely it first made the jump to humans in the wet market at Wuhan in November 2019. The study did not successfully identify the intermediary animal and is observational. It is, however, powerful.

But what about the second study?

Early cases clustered

The second study has a similarly large list of authors from different institutions, with the corresponding author being Kristian Andersen. It’s a correlative study that can’t prove the origin of the pandemic by itself, but when coupled with the first study is highly suggestive that COVID-19 arose in late 2019 in Wuhan as a result of zoonotic transfer from an animal at the market to humans.

The authors examined a number of data sources for their analysis

COVID-19 case data from December 2019 was obtained from the WHO mission report (7) and our previous analyses (5). Location information was extracted and sensitivity analyses performed to confirm accuracy and assess potential ascertainment bias. Geotagged January/February 2020 data from Weibo COVID-19 help seekers was obtained from the authors (26). Population density data was obtained from worldpop.org (27). Sequencing- or qPCR-based environmental sample SARS-CoV-2 positivity from the Huanan market was obtained from a January 2020 China CDC report (data S1) (24).

To estimate the relative amount of intra-urban human traffic to the Huanan market compared to other locations within the city of Wuhan, we utilized a location-specific dataset of social media check-ins in the Sina Visitor System as shared by Li et al. 2015 (33). This dataset is based on 1,491,499 individual check-in events across the city of Wuhan from the years 2013-2014 (5-6 years before the start of the COVID-19 pandemic), and 770,521 visits are associated with 312,190 unique user identifiers. Location names and categories were translated using a Python API for Google Translate.

So what did the investigators find? I think a picture, specifically the spatial analyses in Figure 2, is worth a thousand words:

Fig. 2. Spatial analyses. (A) Inset: map of Wuhan, with gray dots indicating 1000 random samples from worldpop.com null distribution. Main panel: median distance between Huanan market and (1) worldpop.org null distribution shown with a black circle and (2) December cases shown by red circles (distance to Huanan market depicted in purple boxes). Center-point of Wuhan population density data shown by blue dot. Center-points of December case locations shown by red dots (‘all’, ‘linked’ and ‘unlinked’ cases); dark blue dot (lineage A cases); and yellow dot (lineage B cases). Distance from center-points to Huanan market depicted in orange boxes. (B) Schematic showing how cases can be near to, but not centered on, a specific location. We hypothesized that if the Huanan market epicenter of the pandemic then early cases should fall not just unexpectedly near to it but should also be unexpectedly centered on it (see Methods). The blue cases show how cases quite near the Huanan market could nevertheless not be centered on it. (C) Tolerance contours based on relative risk of COVID-19 cases in December, 2019 versus data from January-February 2020. The dots show the December case locations. The contours represent the probability of observing that density of December cases within the bounds of the given contour if the December cases had been drawn from the same spatial distribution as the January-February data.

Leading to the conclusions:

Several lines of evidence support the hypothesis that the Huanan market was the epicenter of the COVID-19 pandemic and that SARS-CoV-2 emerged from activities associated with live wildlife trade. Spatial analyses within the market show that SARS-CoV-2-positive environmental samples, including cages, carts, and freezers, were associated with activities concentrated in the southwest corner of the market. This is the same section where vendors were selling live mammals, including raccoon dogs, hog badgers, and red foxes, immediately prior to the COVID-19 pandemic. Multiple positive samples were taken from one stall known to have sold live mammals, and the water drain proximal to this stall, as well as other sewerages and a nearby wildlife stall on the southwest side of the market, tested positive for SARS-CoV-2 (24). These findings suggest that infected animals were present at the Huanan market at the beginning of the COVID-19 pandemic; however, we do not have access to any live animal samples from relevant species. Additional information, including sequencing data and detailed sampling strategy, would be invaluable to test this hypothesis comprehensively.

And the answer to one major criticism of the hypothesis that zoonotic transfer first occurred at the Huanan market in Wuhan:

One of the key findings of our study is that ‘unlinked’ early COVID-19 patients, those who neither worked at the market or knew someone who did, nor had recently visited the market, resided significantly closer to the market than patients with a direct link to the market. The observation that a substantial proportion of early cases had no known epidemiological link had previously been used as an argument against a Huanan market epicenter of the pandemic. However, this group of cases resided significantly closer to the market than those who worked there, indicating that they had been exposed to the virus at, or near, the Huanan market. For market workers, the exposure risk was their place of work not their residential locations, which were significantly further afield than those cases not formally linked to the market.

The authors also note that the “live animal trade and live animal markets are a common theme in virus spillover events” and that markets like the Huanan market “selling live mammals being in the highest risk category,” comparing SARS-CoV-2 to SARS-CoV-1 outbreaks from 2002-2004, which were “traced to infected animals in Guangdong, Jiangxi, Henan, Hunan, and Hubei provinces in China”.

Again, is this one study slam-dunk evidence in and of itself for zoonotic transfer? No. However, the two studies together constitute powerful evidence that SARS-CoV-2 was not introduced into the human population from a laboratory, but rather transferred from animals to human, almost certainly in the Huanan market, from which is spread to the rest of Wuhan province, to China, and then to the world.

Indeed, the combination of studies was so powerful that it convinced a couple of the scientists doing the studies that lab leak is no longer a viable hypothesis to explain the origin of SARS-CoV-2:

Andersen said the studies don’t definitively disprove the lab leak theory but are extremely persuasive, so much so that he changed his mind about the virus’ origins. “I was quite convinced of the lab leak myself, until we dove into this very carefully and looked at it much closer,” Andersen said. “Based on data and analysis I’ve done over the last decade on many other viruses, I’ve convinced myself that actually the data points to this particular market.” Worobey said he too thought the lab leak was possible, but the epidemiological preponderance of cases linked to the market is “not a mirage.” “It’s a real thing,” he said. “It’s just not plausible that this virus was introduced any other way than through the wildlife trade.”

That’s what real scientists (and skeptics) do. When the evidence becomes overwhelming, even if not absolutely 100% definitive, they change their minds. But will it make a difference to lab leak proponents? I think you know the answer.

Lab leak proponents react

If there’s one thing that’s true about conspiracy theorists, it’s that evidence that would tend to refute their hypotheses doesn’t persuade them to question their beliefs. Instead, it tends to make them double down. I can’t help but quote a comment after Steve’s post last Wednesday as an example, in which one of our commenters dismisses the studies solely based on this:

Anything to exculpate the elites who foisted this on us. But there’s a lot of money going back and forth between the NIH, Big Pharma, and their CCP buddies. To appropriate a public metaphor, one hand washes the other. Truly a clown world that we live in.

And then on Twitter the other day:

The US-funded scientists spiking the football w/ their NIH-funded paper based on public & self-edited Chinese data, is a thing to behold. The “Funding” section of the Wuhan wet market epicenter paper has so many NIH grants, needed 2 screen shots.🧐 https://t.co/wTlXgdQhMz pic.twitter.com/6suwYPhAB7 — sheila (@capitolsheila) July 30, 2022

Despicable Fauci trying to cover his Arse again.Funding: This project funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) https://t.co/2PXLi9ASCj — Ocular Deliberation (@ODeliberation) July 26, 2022

Note the conspiratorial thinking that because the NIH funded these studies that must mean they are hopelessly biased and that “Fauci is trying to cover his Arse”. This is a frequent narrative among conspiracy theorists, to personalize decisions by government agencies to a preferred bogeyman who can be attacked and to be unable to imagine that any government institution would provide research money to any group opposed to its messaging or to fund any research whose results might not line up with the message it wants to promote. I’ve discussed this issue many times before; whatever its flaws in funding mechanisms , the NIH peer review process for funding grants is arguably about as close to a true meritocracy as you will ever find in a government agency. Scientists on study sections review each grant for merit based on science, if the preliminary evidence supports their hypotheses, whether the proposed methodology is appropriate to address the scientific questions asked, if the investigators and institution are capable of carrying out the proposed research with, and the appropriateness of the budget requested. A priority score (lower is better) is assigned by the study section, and then in the best scoring grants are funded until the money runs out.

Then, just yesterday, I came across this:

I'm also looking forward to what promises to be a highly nuanced and non-conspiratorial analysis of the the recent papers ( https://t.co/DBEOGUxbhN , https://t.co/QV3w210Xk3 ) finding lab leak to be increasingly implausible pic.twitter.com/XxiYQ5HbfD — bad_stats 🕜💵🖨️🕣 (@thebadstats) July 31, 2022

That’s evolutionary biologist Heather Heying on the podcast that she does with her husband, biologist Bret Weinstein , claiming that it’s a conspiracy to “definitely” show that it was “those people” who caused the pandemic, not a lab leak. In a massive exercise in projection, she calls claims that the pandemic started at the Huanan market “racist,” apparently ignoring the blatant anti-Chinese racism and xenophobia behind lab leak, whose proponents often ascribe a nefarious coverup to the Chinese government, or:

Yah that was weird. I'm guessing she was trying squeeze in a talking point about how "they" would call *other* people racist for saying the virus came from the wet market, but she didn't think through it and accidentally just became an antiracist fanatic for a second — bad_stats 🕜💵🖨️🕣 (@thebadstats) July 31, 2022

At the end, Weinstein promises to discuss these studies more in the future. Given his previous promotion of ivermectin as a cure-all for COVID-19 based on misunderstood meta-analyses , I’m sure his discussions will be as nuanced as his wife’s ascribing racism to the investigators.

Then there’s the appeal to personal incredulity:

4/ Did: 1. A pangolin kiss a Turtle? 2. A bat fly into the cloaca of a turkey and sneeze into chili. No. But Stuart’s bit tapped into the obvious: 1. The proximity of the lab to the market. 2. The nature of the work and the virus’ at the lab. https://t.co/iHYLaeG3ta — Brent Carpenter (@BrentCa24718741) July 31, 2022

As I like to say, just because you personally find it difficult to believe that zoonosis is the much more likely explanation for SARS-CoV-2 than lab leak does not mean that lab leak is the more viable hypothesis. Also, in that interview from last year Jon Stewart disappointed me in the extreme by sounding very much like the sort of conspiracy theorists that he used to mock on The Daily Show .

Another favorite conspiracist narrative is that the wording of the conclusions of the Science papers is less definitive than it was in the preprint versions published in February . Specifically, they’ve homed in on this sentence in the second study :

While there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, and show that the Huanan market was the epicenter of the COVID-19 pandemic.

Twice now I've seen people tweet the following sentence from the introduction of our recent paper out of context: "However, the observation that the preponderance of early cases were linked to the Huanan market does not establish that the pandemic originated there." — Michael Worobey (@MichaelWorobey) July 27, 2022

With one conspiracy theorist from US Right to Know going on about:

A COVID origins preprint that made splashy headlines a few months ago has now been published in a scientific journal. But the words "dispositive evidence" appear to have not survived peer review. https://t.co/fDPy4gqVZI — Emily Kopp (@emilyakopp) July 26, 2022

And another:

Those preprints from a while ago, arguing for wet market spillover (against e.g. lab leak followed by market super-spreading), are now published. Idk when I'll get to them but at least they don't say "dispositive" anymore. https://t.co/nXAvtTN5PT https://t.co/zyXaHuGIaP — David Bahry (@DavidBahry) July 26, 2022

The editors wanted to push this narrative. — Florian (@Florian_Hanover) July 26, 2022

You get the idea. Lab leak conspiracy theorists seem to be perseverating on how the word “dispositive,” which was apparently used in the preprints to describe this evidence but was removed from the final versions of the studies as published in Science . To be honest, it was a mistake on the part of the authors to use a word like that, given that it is a legal term, not scientific one, meaning something that resolves a legal issue, claim or controversy. If there’s one thing I’ve learned over the years, it’s that science deniers love to substitute legal reasoning for scientific reasoning; a favorite example that I like to cite is falsus in uno, falsus in omnibus , meaning “false in one thing, false in all.” Cranks love to imaging that interrogating science is like interrogating a witness, where this legal principle allows the jury to assume that if the witness is incorrect or lies about one thing they can discount everything that witness says. Science doesn’t work like that, because the path to a scientific consensus is almost never straight and there is almost always something “false” to find if you look hard enough.

In fact, the toning down of the language in the conclusions and discussion sections of a scientific paper is a feature, not a bug, of peer review. I could point to a number of examples that I’ve personally experienced getting papers published over the last 30 years. That the final versions of the paper include more carefully nuanced language than the initial versions is not a conspiracy. It’s something that very frequently happens with peer review. Think of it this way. Scientists like to state their conclusions as clearly as possible; however peer-reviewers often see the caveats more strikingly and require toned down language. It’s normal.

Failing that, conspiracy theorists attack peer review itself:

Lab leakers will disparage any evidence that counters their theory. — Sense Strand (@sense_strand) July 31, 2022

No one ever said, though, that peer review is anything magical. It does, however, mean that scientists carefully examined the submitted manuscript, its data, and its supplementary data and figures and decided that the data did support the hypothesis being tested and was therefore worthy of publication in the journal for which the manuscript was being considered. Again, note the conspiratorial thinking in all the criticisms:

• It’s a coverup by Anthony Fauci and the NIH (and big pharma and who knows who else).
• Anomaly hunting, in which minor issues with the papers are portrayed as fatal flaws.
• Arguments based on personal incredulity of the results.
• Cherry picking of opposing studies.
• Failure to consider the totality of the evidence and perseveration about bits of evidence that appear to support your view.

Science is a process, and definitive scientific conclusions rarely flow from a single study. The rejection of the lab leak hypothesis and conclusion that a zoonotic origin for SARS-CoV-2 is far more likely derive not from any single study—or even from these two studies—but from an accumulation of evidence obtained using different methodologies that all converge on the same conclusion. While lab leak proponents are correct that these studies don’t absolutely rule out a lab leak hypothesis, when they are taken together with existing evidence, they do deliver blows to lab leak so devastating that the hypothesis should be considered dead until and unless proponents can produce evidence sufficiently compelling to persuade scientists to resurrect it.

At this point, I can’t help but think that lab leak hypothesis has become the parrot in a classic Monty Python sketch , pining for the fjords.

Dr. Gorski's full information can be found here , along with information for patients. David H. Gorski, MD, PhD, FACS is a surgical oncologist at the Barbara Ann Karmanos Cancer Institute specializing in breast cancer surgery, where he also serves as the American College of Surgeons Committee on Cancer Liaison Physician as well as an Associate Professor of Surgery and member of the faculty of the Graduate Program in Cancer Biology at Wayne State University. If you are a potential patient and found this page through a Google search, please check out Dr. Gorski's biographical information, disclaimers regarding his writings, and notice to patients here .

• Posted in: Basic Science , Epidemiology , Politics and Regulation , Public Health , Science and Medicine
• Tagged in: antivaccine , bats , coronavirus , COVID-19 , Huanan Market , lab leak , pangolin , SARS-CoV-2 , vaccines , Wuhan , Wuhan Institute of Virology , zoonosis

Posted by David Gorski

• CORONAVIRUS COVERAGE

What you need to know about the COVID-19 lab-leak hypothesis

Newly reported information has revived scrutiny of this possible origin for the coronavirus, which experts still call unlikely though worth investigating.

Months after a World Health Organization investigation deemed it “extremely unlikely” that the novel coronavirus escaped accidentally from a laboratory in Wuhan, China, the idea is back in the news, giving new momentum to a hypothesis that many scientists believe is unlikely, and some have dismissed as a conspiracy theory .

The renewed attention comes on the heels of President Joe Biden’s ordering U.S. intelligence agencies on May 26 to “ redouble their efforts ” to investigate the origins of the coronavirus. On May 11, Biden’s chief medical adviser, Anthony Fauci, acknowledged he’s now “ not convinced ” the virus developed naturally—an apparent pivot from what he told National Geographic in an interview last year.  

Also last month, more than a dozen scientists—top epidemiologists, immunologists, and biologists—wrote a letter published in the journal Science calling for a thorough investigation into two viable origin stories: natural spillover from animal to human, or an accident in which a wild laboratory sample containing SARS-CoV-2 was accidentally released. They urged that both hypotheses “be taken seriously until we have sufficient data,” writing that a proper investigation would be “transparent, objective, data-driven, inclusive of broad expertise, subject to independent oversight,” with conflicts of interest minimized, if possible.

“Anytime there is an infectious disease outbreak it is important to investigate its origin,” says Amesh Adalja, an infectious disease physician and senior scholar at the Johns Hopkins University Center for Health Security who did not contribute to the letter in Science . “The lab-leak hypothesis is possible—as is an animal spillover,” he says, “and I think that a thorough, independent investigation of its origins should be conducted.”

Unanswered questions

The origins of SARS-CoV-2, the virus that causes COVID-19 and has infected more than 171 million people, killing close to 3.7 million worldwide as of June   4, remain unclear. Many scientists, including those that participated in the WHO’s months-long investigation, believe the most likely explanation is that that it jumped from an animal to a person—potentially from a bat directly to a human, or through an intermediate host. Animal-to-human transmission is a common route for many viruses; at least two other coronaviruses, SARS and MERS , were spread through such zoonotic spillover.

Other scientists insist it’s worth investigating whether SARS-CoV-2 escaped from the Wuhan Institute of Virology, a laboratory that has studied coronaviruses in bats for more than a decade.

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The WHO investigation —a joint effort between WHO-appointed scientists and Chinese officials—concluded it was “extremely unlikely” the highly transmissible virus escaped from a laboratory. But the WHO team suffered roadblocks that led some to question its conclusions; the scientists were not permitted to conduct an independent investigation and were denied access to any raw data. ( We still don’t know the origins of the coronavirus. Here are 4 scenarios .)

On March 30, when the WHO released its report, its director-general, Tedros Adhanom Ghebreyesus, called for further studies . “All hypotheses remain on the table,” he said at the time.

Then on May 11, Fauci told PolitiFact that while the virus most likely emerged via animal-to-human transmission, “it could have been something else, and we need to find that out.”

Recently disclosed evidence, first reported by the Wall Street Journal , has added fuel to the fire: Three researchers from the Wuhan Institute of Virology fell sick in November 2019 and sought hospital care, according to a U.S. intelligence report. In the final days of the Trump administration, the State Department released a statement that researchers at the institute had become ill with “symptoms consistent with both COVID-19 and common seasonal illness.”

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Seeking the Source of Ebola

Most epidemiologists and virologists who have studied the novel coronavirus believe that it began spreading in November 2019. China says the first confirmed case was on December 8, 2019. During a briefing in Beijing this week, China’s foreign ministry spokesperson, Zhao Lijian, accused the U.S. of “ hyping up the theory of a lab leak ,” and asked, “does it really care about the study of origin tracing, or is it trying to divert attention?” Zhao also denied the Wall Street Journal   report that three people had gotten sick.

Lab leak still ‘unlikely’

Some conservative politicians and commentators have embraced the lab-leak theory, while liberals more readily rejected it, especially early in the pandemic. The speculation has also heightened ongoing tensions between the U.S. and China.

On May 26, as the U.S. Senate passed a bill to declassify intelligence related to potential links between the Wuhan laboratory and COVID-19, Missouri Senator Josh Hawley, a Republican who sponsored the bill, said, “the world needs to know if this pandemic was the product of negligence at the Wuhan lab,” and lamented that “for over a year, anyone asking questions about the Wuhan Institute of Virology has been branded as a conspiracy theorist.”

Peter Navarro, Donald Trump’s former trade adviser, asserted in April 2020 that SARS-CoV-2 could have been engineered as a bioweapon, without citing any evidence.

The theory that SARS-CoV-2 was created as a bioweapon is “completely unlikely,” says William Schaffner, a professor of infectious diseases at Vanderbilt University Medical Center. For one thing, he explains, for a bioweapon to be successful, it must target an adversarial population without affecting one’s own. In contrast, SARS-CoV-2 “cannot be controlled,” he says. “It will spread, including back on your own population,” making it an extremely “counterproductive biowarfare agent.”

The more plausible lab-leak hypothesis, scientists say, is that the Wuhan laboratory isolated the novel coronavirus from an animal and was studying it when it accidentally escaped. “Not knowing the extent of its virulence and transmissibility, a lack of protective measures [could have] resulted in laboratory workers becoming infected,” initiating the transmission chain that ultimately resulted in the pandemic, says Rossi Hassad, an epidemiologist at Mercy College.

But Hassad adds he believes that this lab-leak theory is on the “extreme low end” of possibilities, and it “will quite likely remain only theoretical following any proper scientific investigation,” he says.

Biden ordered U.S. intelligence agencies to report back with their findings in 90 days, which would be August 26.

Based on the available information, Eyal Oren, an epidemiologist at San Diego State University, says it’s apparent why the most accepted hypothesis is that this virus originated in an animal and jumped to a human: “What is clear is that the genetic sequence of the COVID-19 virus is similar to other coronaviruses found in bats,” he says.

Some scientists remain skeptical that concrete conclusions can be drawn. “At the end, I anticipate that the question” of SARS-CoV-2’s origins “will remain unresolved,” Schaffner says.

In the meantime, science “moves much more slowly than the media and news cycles,” Oren says.

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March 1, 2022

13 min read

The Lab-Leak Hypothesis Made It Harder for Scientists to Seek the Truth

Virus origin stories have always been prone to conspiracy theories. COVID disinformation has threatened research—and lives

By Stephan Lewandowsky , Peter Jacobs & Stuart Neil

Greater horseshoe bat ( Rhinolophus ferrumequinum ). Research shows a clear zoonotic path between bats and the SARS-CoV-2 virus.

Stephen Dalton/Minden Pictures

W henever scientific findings threaten people’s sense of control over their lives, conspiracy theories are never far behind. The emergence of novel viruses is no exception. New pathogens have always been accompanied by conspiracy theories about their origin. These claims are often exploited and amplified—and sometimes even created—by political actors. In the 1980s the Soviet KGB mounted a massive disinformation campaign about AIDS, claiming that the U.S. Central Intelligence Agency had created HIV as part of a biological weapons research program. This campaign benefited from a “scientific” article written by two East German scientists that ostensibly ruled out a natural, African origin of the virus, an explanation favored by Western scientists that has since been unambiguously established . In African countries, where many scientists and politicians considered the hypothesis of an African origin of AIDS to be racist , the disinformation campaign fell on fertile ground. Ultimately the conspiracy theory was picked up by Western media and became firmly entrenched in the U.S. Similarly, when the Zika virus was spreading in 2016 and 2017, social media was awash in claims that it had been designed as a bioweapon .

From the beginning, the genomic evidence led most virologists who were investigating SARS-CoV-2 to favor a zoonotic origin involving a jump of the virus from bats to humans, possibly with the help of an intermediate host animal. But considering the anxiety-provoking upheavals of the pandemic, it came as no surprise that the virus inspired conspiratorial thinking. Some of these theories—such as the idea that 5G broadband rather than a virus causes COVID or that the pandemic is a hoax—are so absurd that they are easily dismissed. But some theories came with a patina of plausibility. Speculation that the SARS-CoV-2 virus was engineered in the Wuhan Institute of Virology (WIV) in China was facilitated by the physical location of the institute: it is right across the Yangtze River from the Huanan market where many of the earliest cases of COVID were detected. The Chinese government’s denial that markets sold live wild animals also roused suspicion, even though such wares were always suspected and have since been confirmed .

The so-called lab-leak hypothesis gained sufficient rhetorical and political force that President Joe Biden instructed the U.S. intelligence services to investigate it. Although the interagency intelligence report update , declassified in October 2021, dismissed several popular laboratory-origin claims—including that the virus was a bioweapon and that the Chinese government knew about the virus before the pandemic—it was unable to unequivocally resolve the origin question.

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Does this mean that proponents of the lab-leak hypothesis uncovered a genuine conspiracy that will be revealed by persistent examination? Or is the lab-leak rhetoric rooted in conspiracy theories fueled by anxiety over China’s increasing prominence on the world stage or in preexisting hostility to biotechnology and fear over biosecurity? And what is it about the conditions of the past two years that made it so difficult to know?

Zoonotic Origins

The ostensible lab-leak hypothesis is not a single identifiable theory but a loose constellation of diverse possibilities held together by the common theme that Chinese science institutions—be it the WIV or some other arm of the Chinese government—are to blame for the pandemic. At one end is the straightforward possibility of WIV lab personnel being infected during fieldwork or while culturing viruses in the lab. Scientifically, this possibility is challenging to disentangle from a zoonotic origin that followed other pathways and is therefore difficult to rule out or confirm. At the other extreme are the assertions that SARS-CoV-2 was designed and engineered by the WIV, perhaps as a bioweapon, and was released either accidentally or as a biological attack. This possibility necessarily entails a conspiracy among WIV scientists—and potentially many others—to first engineer a virus and then cover up its release. Scientific investigation of the genomic and phylogenetic evidence can help us determine whether SARS-CoV-2 was genetically engineered.

Fear and blame: A table of T-shirts with antimask slogans accompanied a protest outside the Jet Blue headquarters in Queens, N.Y., on October 27, 2021. Protesters were pushing back against the airline's COVID vaccine mandate and mask policies. The instability created by the pandemic is fertile ground for conspiracy theories. Credit: Mark Peterson/Redux Pictures

SARS-CoV-2 is a member of a subgenus of the betacoronaviruses called the sarbecoviruses, named after their prototype member, SARS-CoV-1, which caused the SARS epidemic in 2002 and 2003. The zoonotic origin of SARS-CoV-1 has been firmly established by research that also showed that the bat sarbecoviruses pose a clear and present danger of pandemic overspill from bats to humans.

One key feature of sarbecoviruses is that they undergo extensive amounts of recombination. Parts of their genomes are being regularly swapped at a rate that implies a vast ecosystem of these viruses is circulating, most of which have not been discovered. The area of the genome that is most likely to recombine is also the area that encodes the “spike” proteins—the very proteins that play a crucial role in initiating an infection. Many sarbecoviruses encode spike proteins that can bind to a wide range of mammalian cells, suggesting that these viruses can easily move back and forth between different species of mammals, including humans.

SARS-CoV-2 is not as virulent as SARS-CoV-1, but it is transmitted far more easily between people. Two of the most prominent features of the SARS-CoV-2 spike are its receptor-binding domain (RBD), which binds very tightly to human ACE2, the protein that allows it to enter lung cells, and the so-called furin cleavage site (FCS). This site divides the spike protein into subunits. The FCS is present in many other coronaviruses, but so far SARS-CoV-2 is the only sarbecovirus known to include it. It allows the viral spike protein to be cut in half during its release from an infected cell, priming the virus to spread to new cells more efficiently.

The RBD and FCS are central to initial virological arguments by expert proponents of the lab-leak hypothesis. Such arguments are based on the supposition that neither the RBD nor the FCS “appears natural” and therefore that they can only be the product of lab-based engineering or selection. Nobel laureate David Baltimore, an early proponent of the lab-leak hypothesis, referred to the FCS as a “smoking gun” that points to a lab origin.

Although an unusual feature of a virus can legitimately stimulate further inquiry, this argument is reminiscent of the creationist claim that humans must have been “intelligently designed” because we are seemingly too complex to have evolved by natural selection alone. This logic is fundamentally flawed because complexity does not license dismissal of the overwhelming evidence for natural selection and, by itself, does not mandate any design, intelligent or otherwise. Likewise, labeling the RBD or the FCS “unnatural” does not mandate lab-based engineering, and, critically, it does not license the dismissal of the growing evidence for a zoonotic origin.

Recently, for example, bat colonies on the border between Laos and China were discovered to carry sarbecoviruses that have RBDs almost identical to those of SARS-CoV-2 in both sequence and ability to enter human cells. This finding refutes the claim that SARS-CoV-2’s binding affinity in humans is unlikely to have a natural origin .

Similarly, although some lab-leak proponents contend that the lack of an FCS in the closest relatives of SARS-CoV-2 is indicative of its manual insertion in a lab, very recent evidence from SARS-CoV-2 population sequencing suggests that the insertion of new sequences from human genes next to the FCS can be detected. Moreover, the closest relative of the SARS-CoV-2 spike in the Laotian bat viruses would require the addition of only a single amino acid to generate a putative FCS. Thus, in a species where it would have a major selective advantage, it would probably be very easy for some of these bat coronaviruses to rapidly evolve an FCS.

This research sketches a clear zoonotic path to the emergence of the RBD and FCS. Although some evolutionary gaps along this path persist, their number and size have been dwindling. A detailed analysis in late 2021 further strengthened the link to the Huanan markets as the point of origin of the virus and the initial source of community transmission. This rapidly growing body of evidence for a zoonotic origin of SARS-CoV-2 creates increasing difficulties for the lab-engineering hypothesis.

Conspiratorial Cognition

In normal scientific inquiry, as evidence emerges, the remaining space for plausible hypotheses narrows. Some facets continue to be supported, and others are contradicted and eventually precluded altogether. Some of the strongest advocates for a lab origin for SARS-CoV-2 changed their views as they learned more. Baltimore, for instance, withdrew his “smoking gun” comment when challenged by additional evidence, conceding that a natural origin was also possible . Revising or rejecting failed hypotheses in light of refuting evidence is central to the scientific process. Not so with conspiracy theories and pseudoscience. One of their hallmarks is that they are self-sealing: as more evidence against the conspiracy emerges, adherents keep the theory alive by dismissing contrary evidence as further proof of the conspiracy, creating an ever more elaborate and complicated theory.

There is perhaps no better example of self-sealing cognition than the contortions of climate change denial that erupted after the 2009 “Climategate” controversy. At that time thousands of documents and e-mails were stolen from the Climatic Research Unit of the University of East Anglia in England and made public right before the United Nations climate conference in Copenhagen. The e-mails were cherry-picked by deniers for sound bites that, when taken out of context, seemed to point to malfeasance by scientists. Ultimately nine independent inquiries around the world cleared the scientists of misconduct, and nine of the warmest years ever measured have occurred in the 11 years since Climategate.

Undeterred by the exonerations, climate deniers—including at least one U.S. congressperson—branded the inquiries as a “ whitewash .” The volume of activity on skeptics’ Web sites relating to the hacked e-mails continued to increase for at least four years , long after the public had lost all interest in the confected scandal. It was only in late 2021 that one of the principals making unfounded accusations against the scientists apologized for his role .

The e-mails were publicly misrepresented as a result of an unsolved hack, but top scientists and health officials also have seen their correspondence become public through Freedom of Information Act (FOIA) requests by groups with long histories of attacking scientists. The organization U.S. Right to Know honed its FOIA tactics against food scientists before turning its sights on virologists.* Despite e-mails clearly showing virologists considering but ultimately rejecting various claims about SARS-CoV-2 being engineered, lab-leak proponents tend to selectively quote messages. They cast virologists as either never having given lab scenarios fair consideration or—on the other extreme—believing in a lab origin all along and deliberately lying about it. People who push conspiracy theories often toggle between opposing claims as the rhetorical need arises.

In the lab: The Wuhan Institute of Virology in China, shown here in a 2017 photograph, has been a leader in infectious disease research for many years. Some scientists identified with COVID research have been harassed by proponents of SARS-CoV-2 conspiracy theories. Credit: Feature China/Barcroft Media via Getty Images

Another e-mail-centered theory turned on the idea that the WIV had originally housed viruses closely related to SARS-CoV-2, presumably including the natural virus from which it had been engineered . The theory further held that the WIV suspiciously delayed publication of a paper that had been submitted in October 2019 until 2020 . At some point after the paper’s submission with the “true” sequences, the argument went, the WIV halted its publication and altered the sequence information in furtherance of the cover-up.

Another FOIA effort was marshaled to reveal the discrepancy between the “real” sequences submitted to the journal and those that were pawned off on the unsuspecting public. Unfortunately for this conspiracy claim, the FOIA results revealed that the submitted paper’s sequences were exactly what the scientists publicly said they were. The self-sealing nature of conspiratorial reasoning being what it is, however, some proponents of the lab-leak hypothesis remain undeterred and believe the “real” sequences must exist in some as yet undocumented draft created before the submitted version.

The self-sealing dynamic can produce even more elaborate epicycles to resist falsification. Until earlier this year, the closest known relative of SARS-CoV-2 was a virus called RaTG13, which is known to have been held by the WIV in a collection of bat swab samples. RaTG13 is more than 96 percent identical to SARS-CoV-2. It is likely that this virus genome was sequenced from a swab taken in 2013 from bats in an abandoned mine shaft in Mojiang, a county in China’s Yunnan province. RaTG13’s centrality to many lab-leak claims stemmed from its putative role as the “ backbone ” from which SARS-CoV-2 was allegedly engineered.

Being closely related to SARS-CoV-2 and being present in the lab at the WIV made RaTG13 a perfect candidate for a precursor that was engineered into SARS-CoV-2. In the short time since the pandemic took hold, however, several related viruses have been discovered that are closer in sequence to SARS-CoV-2 over much of the genome. Moreover, despite being related to SARS-CoV-2, RaTG13 has been found to occupy a separate phylogenetic branch. SARS-CoV-2 is not descended from RaTG13; rather the viruses share a common ancestor from which they diverged an estimated 40 to 70 years ago, meaning it could not have served as a backbone for an engineered SARS-CoV-2.

Rather than accepting this contrary evidence, some lab-leak advocates resorted to self-sealing reasoning that deviates from standard scientific practice: They began to argue that RaTG13 was not a natural virus itself but rather had been edited or in some way fabricated in an effort to hide the “true” backbone of SARS-CoV-2 and thus its engineered nature. The virus from Laos showing that SARS-CoV-2’s RBD and the efficiency of its binding to human receptors are not unique—providing strong support for a zoonotic origin—is thus reinterpreted to mean that the WIV obtained and used a similar but so far secret virus from Laos to design SARS-CoV-2. This ad hoc hypothesis is accompanied by the expectation that the burden is on the WIV to prove it did not have that secret virus—a reversal of the expected burden of proof that runs counter to conventional scientific reasoning.

Such pivots are potentially immune to further evidence. Just as there are effectively unlimited “gaps” between transitional fossils that are exploited by creationists, so, too, are there effectively unlimited potential natural viruses from which SARS-CoV-2 must have been engineered that have been kept hidden by the WIV. Or else unnatural viruses the WIV might have engineered to make SARS-CoV-2’s features seem naturally evolved.

More and more relatives and antecedents of SARS-CoV-2 are bound to be discovered, and adherents of the lab-leak hypothesis will face a stark choice. They can abandon, or at least qualify, their belief in genetic engineering, or they must generate an ever increasing number of claims that these relatives and antecedents, too, have been fabricated or engineered. It is likely that at least some people will follow the latter path of motivated reasoning, insisting that secretive Chinese machinations or an unnatural manipulation of biology is responsible for the virus’s origin.

Motivated reasoning based on blaming an “other” is a powerful force against scientific evidence. Some politicians—most notably former President Donald Trump and his entourage—still push the lab-leak hypothesis and blame China in broad daylight. When Trump baldly pointed the finger at China in the earliest days of the pandemic, unfortunate consequences followed. The proliferation of xenophobic rhetoric has been linked to a striking increase in anti-Asian hate crimes . It has also led to a vilification of the WIV and some of its Western collaborators, as well as partisan attempts to defund certain types of research (such as “gain of function” research) that are linked with the presumed engineering of SARS-CoV-2. There are legitimate arguments about the regulation, acceptability and safety of doing gain-of-function research with pathogens. But conflating these concerns with the fevered discussion of the origins of SARS-CoV-2 is unhelpful. These examples show how a relatively narrow conspiracy theory can expand to endanger entire groups of people and categories of scientific research—jeopardizing both lives and lifesaving science .

A Long Tail

Scientists no longer debate the fact that greenhouse gas emissions from the burning of fossil fuels are changing Earth’s climate. Although this scientific consensus on climate change was established 20 years ago, it has never stopped influential politicians from calling climate change a hoax . Climate denial is a well-organized disinformation campaign to confuse the public in pursuit of a clear policy goal—namely, to delay climate mitigation.

The markers of conspiratorial cognition are universal, whether the subject is climate denial, antivaccination propaganda or conspiracies surrounding the origin of SARS-CoV-2. It is critical to help the media and the public identify those markers. Unlike the overwhelming evidence for climate change, however, a zoonotic origin of SARS-CoV-2 is likely but not yet conclusive. This is not a sign of nefarious activity and is, in fact, entirely unsurprising: It took 10 years to pin down the zoonotic source of SARS-CoV-1. The Zaire Ebola virus has never been isolated from bats, despite strong serological evidence that they are the likely reservoir.

Plausible routes for a lab origin do exist—but they differ from the engineering-based hypotheses that most lab-leak rhetoric relies on. The lab in Wuhan could be a relay point in a zoonotic chain in which a worker became infected while sampling in the field or being accidentally contaminated during an attempt to isolate the virus from a sample. Evidence for these possibilities may yet emerge and represents a legitimate line of inquiry that proponents of a natural origin and lab-leak theorists should be able to agree on. But support for those claims will not be found in self-sealing reasoning, quote mining of e-mails or baseless suggestions. Ironically the xenophobic instrumentalization of the lab-leak hypothesis may have made it harder for reasonable scientific voices to suggest and explore theories because so much time and effort has gone into containing the fallout from conspiratorial rhetoric.

Lessons from climate science show that failure to demarcate conspiratorial reasoning from scientific investigation results in public confusion, insufficient action from leadership, and the harassment of scientists. It even has the potential to impact research itself, as scientists are diverted into knocking back incorrect claims and, in the process, potentially ceding them more legitimacy than warranted.

We must anticipate that this type of dangerous distraction will continue. Scientists identified with COVID research are suffering abuse , including death threats . When the Omicron variant emerged, so did nonsensical conspiracy theories that it, too, was an escaped, human-altered virus, originating from the lab in South Africa that first reported it. One can only assume that further variants may likewise be blamed on whichever research lab is closest to the location of discovery. We are not doomed to keep repeating the mistakes of past intersections of science and conspiracy should we choose to learn from them instead.

*Editor’s Note (2/18/22): This sentence was edited after posting. It originally described U.S. Right to Know as an anti-GMO organization.

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The lab leak hypothesis, explained

We may never know for sure if the virus that causes Covid-19 leaked from a lab. But that won’t stop the debate.

by Umair Irfan

Where did the virus that causes Covid-19 come from?

It’s one of the most persistent mysteries of the pandemic. The debate about it among scientists, policymakers, journalists, amateur internet sleuths, and the general public has reignited with new revelations and new voices in the mix.

Most recently, emails obtained by the Washington Post and BuzzFeed showed that National Institute of Allergy and Infectious Diseases Director Anthony Fauci was corresponding with a scientist as early as January 2020 investigating the possibility that SARS-CoV-2, the virus that causes Covid-19, may have been engineered in a lab. An article in Vanity Fair highlighted how efforts to probe a lab leak were suppressed within parts of the US government as some officials worried that a lab in Wuhan, China, that received US funding may have been the source.

Scientists last year argued that the most plausible explanation is the “natural emergence” of the SARS-CoV-2 virus: It jumped from bats, or an intermediary species, to humans in a random event sometime in 2019. Many still hold this view, and some have become even more confident in this pathway.

Several media outlets, including Vox, also downplayed in 2020 the possibility that human error launched the virus, after many scientists with relevant experience described the idea as extremely unlikely. In February 2020, 27 scientists co-signed a letter in The Lancet affirming their belief in a natural origin of the virus and decrying efforts to pin the blame for the outbreak on Chinese scientists.

But in recent weeks, more scientists — including some who had not weighed in until now — have spoken up about the possibility that the virus may have escaped a laboratory in China, and argued that this scenario has not been adequately investigated.

The Covid-19 pandemic has illustrated that science is essential for grappling with the disease, but also that experts can get things wrong. For example, the World Health Organization in January 2020 said that there was “ no clear evidence ” of transmission of SARS-CoV-2 between people. The US surgeon general told Americans in February 2020 that face masks were not effective in slowing the spread of the disease. It could be possible, then, that the dismissal of a laboratory origin of the virus was premature among some experts amid the flurry of developments in the early stages of a global outbreak.

“We must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data,” reads a letter published in the journal Science in May 2021, co-authored by 18 researchers.

Some scientists had been reluctant to publicly broach the “lab leak” hypothesis in part because the Trump administration had asserted, without clear evidence, its confidence in the theory, as it tried to find ways to blame China for the pandemic and deflect scrutiny from the White House’s mishandling of the crisis. The idea also collapsed into conspiracy theories, like the notion that the virus was deliberately released as a bioweapon .

The lab leak hypothesis “really is not a fringe theory,” Marc Lipsitch , an epidemiology professor at the Harvard School of Public Health and a co-signer of the letter, told CNN . “It had been viewed as a fringe theory because it was espoused in fringe ways by some people with political agendas.”

Lipsitch and other researchers pushing for further investigation say that the Chinese government hasn’t been forthcoming with critical details about its research on coronaviruses; it also ordered some early lab specimens of the virus to be destroyed and censored reporting around the outbreak . The calls for more transparency from scientists prompted the Biden administration to order US intelligence agencies to investigate the possibility of an accidental lab leak. The answer to the question of how the virus originated has as much political import as it does scientific.

At the most basic level, the case for the natural origins of the virus rests on incomplete evidence, while the lab leak hypothesis rests on the gaps in that very evidence.

A natural exposure route for SARS-CoV-2 still seems far more likely to many scientists, but a satisfying answer one way or another may never coalesce as the initial infections recede into history and China continues to withhold data and records from those early days. Scientists still haven’t determined from which animal the virus hopped into humans, but neither have they found any trace of SARS-CoV-2 in a laboratory prior to its emergence. All the while, the tense US-China relationship looms over the investigation, threatening to throttle the search for answers.

Many prominent voices in science, politics, and national security are now deeply invested in seeing this investigation through. Here’s how some of the researchers currently engaged in the conversation are parsing the evidence, what they see as some of the most important lines of inquiry going forward, and what they say we may never know.

Why some scientists say that a lab origin deserves a closer look

The term “lab leak” refers to the possibility that the SARS-CoV-2 virus or a close relative was at some point being studied at a laboratory in China prior to the Covid-19 pandemic and then later escaped. In particular, investigation proponents are interested in the Wuhan Institute of Virology near the original epicenter of the Covid-19 outbreak. After the 2003 SARS outbreak , the facility increased its focus on emerging diseases, including respiratory infections caused by coronaviruses.

The possibility of a lab leak crossed the mind of Shi Zhengli , a renowned virologist at the Wuhan lab. She told Scientific American last year that she recalled being told in December 2019 about a mysterious pneumonia caused by a coronavirus spreading in the city of Wuhan and wondering if the pathogen came from her lab.

There have been reports that researchers at the institute were performing gain-of-function experiments , where a natural virus is modified to become more virulent or to better infect humans. This research tries to map potential ways a virus could mutate and lead to an outbreak, allowing scientists to get a head start on countering a potentially dangerous pathogen. But such research is dangerous and controversial. The National Institutes of Health declared a moratorium on funding gain-of-function research in 2014, lifting it in 2017 for experiments that undergo review by an expert panel.

US officials have been adamant that US funding did not support any gain-of-function research at the Wuhan Institute, or anywhere in the world. NIH Director Francis Collins said in a May statement that US federal health research agencies have never “approved any grant that would have supported ‘gain-of-function’ research on coronaviruses that would have increased their transmissibility or lethality for humans.”

Scientists at the Wuhan lab were known to be working with an international team on creating chimeric versions of different coronaviruses to study the potential of a human outbreak, though they say that these chimeric viruses did not increase in pathogenicity and therefore do not constitute gain of function. The chimeras in the experiment were also created in the US, not China. Wuhan Institute researchers also published a paper in 2017 reporting on a bat coronavirus that could be transmitted directly to humans, with researchers creating chimeras of the wild virus to see if they could infect human cells. That study had funding from the US National Institutes of Health.

Looking at these studies, there are scientists who say such experiments meet the definition. “The research was — unequivocally — gain-of-function research,” Richard Ebright , a microbiology researcher at Rutgers University, told the Washington Post .

There is also a possibility that other, more direct gain-of-function experiments were conducted with other funding sources, but no evidence has emerged for this.

The lab leak hypothesis “had been viewed as a fringe theory because it was espoused in fringe ways by some people with political agendas” —Marc Lipsitch, epidemiologist

That said, the lab leak hypothesis doesn’t hinge on risky gain-of-function research being conducted at the lab, explained Alina Chan, a researcher at the Broad Institute and a co-signer of the Science letter.

“Maybe a few people think that there could’ve been some gain-of-function research, but I’d say that a lot of scientists who are asking for an investigation say that this was a lab accident of a mostly natural, or completely natural, virus,” Chan said.

She and other scientists want to investigate the possibility that SARS-CoV-2 or a very closely related virus escaped during normal laboratory operations. The two strongest possibilities, according to Chan, are, one, that a researcher at the Wuhan Institute of Virology was exposed to a bat coronavirus while collecting samples in the field and inadvertently brought the infection back to Wuhan. The field, in this case, is the native habitat of the bats in the southeastern provinces of China, more than 1,000 miles from Wuhan. And two, scientists at the lab could have been exposed to a sample of SARS-CoV-2 that was under study and then spread the virus to others.

Indeed, dangerous pathogens have leaked out of laboratories several times before, and human error is a constant risk in any research institution. “The only labs that don’t have accidents are labs that are not functional,” Chan said.

She pointed out that someone unwittingly falling sick with a virus under study in a lab has happened before in China. In 2004, a researcher contracted SARS after a stint working at the Chinese National Institute of Virology in Beijing. The researcher went on to infect her mother and a nurse at the hospital who went on to infect others, leading to 1,000 placed under quarantine or medical supervision.

Another concern was that the Wuhan Institute of Virology was handling coronavirus samples at biosafety level 2 precautions when most other labs recommend a biosafety level of 3 or higher. At biosafety level 2, lab access is restricted, researchers must wear personal protective equipment like gloves, lab coats, and eye protection, and much of the experimental work is conducted in biosafety cabinets that filter air rather than open lab benches.

Biosafety level 3 includes all the precautions of lower levels and adds medical surveillance for lab workers, the use of respirator masks, and lab access controlled with two sets of self-closing and locking doors. The biosafety level 3 measures are aimed at controlling potentially lethal respiratory pathogens that spread through the air, while biosafety level 2 is meant for pathogens that pose a “moderate hazard.”

So seeing that the Wuhan lab was handling viruses that can travel through the air at a safety level not designed for it alarmed some observers. “When scientists hear about this, they get really freaked out,” Chan said.

W. Ian Lipkin , a virologist at Columbia University, co-authored a Nature Medicine paper in March 2020 that reported the most likely origin of the virus in humans was a natural spillover from animals. But he told the journalist Donald McNeil in May 2021 that he was alarmed when he learned that the Wuhan Institute of Virology was conducting research on similar viruses at a lower level of protection.

“People should not be looking at bat viruses in BSL-2 labs,” Lipkin said. “My view has changed.”

Chan also noted that the Huanan Seafood Wholesale Market in Wuhan was initially suspected as the location where a SARS-CoV-2 spillover from animals to humans occurred, but to date, no infected animal has been identified and Chinese researchers have ruled it out as the origin of the virus. The initial outbreak could have occurred because so many people were in close proximity at the bustling market, but the virus may have made the leap to humans elsewhere.

There are also allegations that the Chinese government hasn’t been forthright about the early days of the pandemic and has withheld critical information from investigators, making it hard to eliminate a lab leak as a possibility. “I can also be convinced of a natural origin if that is properly investigated too,” Chan said in an email. “The problem is that the most definitive pieces of evidence would be inside of China where we currently have no access.”

A team from the World Health Organization that visited China in January and February of this year reported that they had difficulty getting all the information they wanted about the origins of SARS-CoV-2.

“In my discussions with the team, they expressed the difficulties they encountered in accessing raw data,” WHO Director-General Tedros Adhanom Ghebreyesus said during a briefing in March . “I expect future collaborative studies to include more timely and comprehensive data sharing.”

Properly investigating the possibility of a laboratory leak, if only to rule it out, would help answer critical scientific questions while also bolstering public confidence in the process, proponents argue. “We have to show that we have the will to investigate whenever something like this happens and that we have a system in place,” Chan said.

Why the lab leak theory is getting so much attention now

Questions about whether SARS-CoV-2 may have escaped from a lab have been simmering since the beginning of the pandemic, but several recent developments catapulted the debate back into the news, and even into Congress .

At the beginning of the year, New York Magazine (which is owned by Vox Media) published a long article by the novelist Nicholson Baker making the case that the virus may have leaked from a lab in China. Journalist Nicholas Wade made a similar case in an article published on Medium in May. The letter published by Science in May, which called for a more thorough investigation into the hypothesis, was another driver of the conversation. A few days after the letter, an article in the Wall Street Journal resurfaced US intelligence reports about three researchers at the Wuhan Institute of Virology who sought medical care for influenza-like symptoms in November 2019. That’s earlier than the first confirmed case of Covid-19 , which occurred on December 8, 2019, according to Chinese officials. (There’s no evidence that the researchers had Covid-19, however.)

Shortly thereafter, the Wall Street Journal highlighted the case of six miners in China who fell ill in 2012 after being hired to clear a cave of bat guano. The Wuhan Institute of Virology was called in to investigate. Researchers from the lab tested bats from the mine for coronaviruses and found an unidentified strain resembling SARS; several bats were infected with more than one virus. That created opportunities for recombination, in which viruses undergo rapid, large-scale mutations that create new pathogens.

“The problem is that the most definitive pieces of evidence would be inside of China, where we currently have no access” —Alina Chan, molecular biologist

One of the unidentified viruses, called RaTG13, was later found to have 96.2 percent genetic overlap with SARS-CoV-2, hinting that it may have been a predecessor. A WHO team reported that the lab wasn’t able to culture the virus, and was only in possession of its genetic sequence. If these reports are to be believed, that means the institute didn’t have an infectious ancestor to SARS-CoV-2 in its custody.

In the wake of these media reports and rising public interest, President Biden ordered US intelligence agencies last month to increase their efforts in investigating the potential of a laboratory origin of SARS-CoV-2 and report back in 90 days.

For some scientists, the resurgent interest in a lab leak has been frustrating, rather than illuminating. “Quite frankly, over the last number of days, we’ve seen more and more and more discourse in the media with terribly little actual news, evidence, or new material,” said Michael Ryan , executive director of the World Health Organization’s health emergencies program, during a May 28 press conference.

But for others, it has been validating. Former US Centers for Disease Control and Prevention Director Robert Redfield told Vanity Fair that he received death threats last year after stating publicly that he thought the virus originated in a lab.

And for still other researchers, the issue remains too contentious to discuss publicly. One scientist contacted for this article declined to comment on the record in part out of fear of harassment. Nonetheless, this renewed attention seems unlikely to go away anytime soon.

Why other scientists remain skeptical of the lab leak hypothesis

Despite the concerns and unknowns around the activities at the Wuhan Institute of Virology, there is no evidence SARS-CoV-2 ever passed through the laboratory; rather, the circumstances only indicate that a lab leak was possible.

Some scientists in the US were already looking into this possibility in the early days of the pandemic. Kristian Andersen, a professor at the Scripps Research Institute, exchanged emails with Fauci in January 2020 about his suspicions that the SARS-CoV-2 virus was engineered because its genetics didn’t resemble what he thought would occur in nature, according to documents obtained by BuzzFeed and the Washington Post. “I should mention that after discussions earlier today, Eddie, Bob, Mike, and myself all find the genome inconsistent with expectations from evolutionary theory,” Andersen wrote to Fauci.

Andersen then investigated the possibility, and co-authored the March 2020 Nature Medicine paper on the origins of the SARS-CoV-2 virus with Lipkin that reported the most likely origin of the virus was a spillover from an animal. Unlike Lipkin, Andersen has only become more convinced the virus came into humans via a natural exposure route.

“We cannot categorically say that SARS-CoV-2 has a natural origin but, based on available scientific data, the most likely scenario by far is that SARS-CoV-2 came from nature,” Andersen told Vox in an email. “No credible evidence has been presented to support the hypothesis that the virus was engineered in, or leaked from, a lab — such statements are based on pure speculation.”

Then what would it take to demonstrate that the virus escaped a lab?

“Evidence that [the Wuhan Institute of Virology] or another Wuhan virology lab had SARS-CoV-2 or something 99% similar would be the smoking gun,” Robert Garry , a virologist at Tulane University and another co-author of the Nature Medicine paper, said in an email. “There is no evidence that SARS-CoV-2 or an immediate progenitor virus existed in any laboratory before the pandemic.”

He, too, has become more convinced that the virus jumped to humans somewhere outside the lab. “The only change since we wrote our manuscript on the Proximal Origins of SARS-CoV-2 is that I now consider any of the lab leak hypotheses to be extremely unlikely,” he said.

Shi Zhengli at the Wuhan Institute of Virology told Scientific American she instructed her team to sequence the genomes of all the viruses they were studying in their laboratory and compare them to sequences obtained from Covid-19 patients. None matched. “That really took a load off my mind,” she said. (Shi did not respond to a Vox request for comment.)

Several other factors point toward a natural origin of SARS-CoV-2, according to Vincent Racaniello , a virologist at Columbia University. Among them is that the 2003 SARS virus outbreak established a precedent for a coronavirus jumping from bats to an intermediary species to humans. In that case, the intermediary — civet cats — was identified; scientists have been warning for years that a similar scenario could easily occur again.

Further animal investigations showed that there are a number of viruses like SARS-CoV-2 in bats, not just in China but also in Thailand, Cambodia, and Japan. These viruses are not direct ancestors of SARS-CoV-2, but they are closely related. Viruses mutate all the time, and the more widespread they are, the more changes can occur. Seeing a related virus over such a wide area shows there was ample opportunity for it to spread and mutate in nature before it made the final jump into humans.

The WHO also found that in the earliest days of the pandemic, during the outbreak in Wuhan, China, in 2019, there were two distinct lineages of the virus with different transmission patterns through the region. “That tells us that there were either two wildlife sources or that, early on, the virus switched from one animal to another,” Racaniello said. “That’s very difficult to make sense of with a lab origin. In my opinion, that’s really strong evidence this came from nature, because it’s a simpler scenario.”

He also pointed out that while there have been leaks of pathogens from laboratories in the past, those were known diseases at the time: “There has never been a new virus to come out of a lab.”

As for the circumstances that hint at a lab leak, some scientists still don’t find them compelling. For instance, while the Wuhan Institute of Virology was handling coronaviruses at biosafety level 2, none of the viruses the lab was known to be studying have leaked, and, again, there is no evidence the lab had any contact with SARS-CoV-2.

“It’s not actually news that the Wuhan Institute was handling these viruses at BSL-2. It’s in the methods of their papers going back years,” said Stephen Goldstein , a virologist at the University of Utah. “I don’t see how people can hold that up as a specific piece of evidence for any given scenario.”

Similarly, investigators say they were aware for months of reports that scientists at the Wuhan Institute of Virology sought treatment for an unknown illness. Virologist Marion Koopmans , a member of the WHO investigation team that visited China earlier this year, told NBC News they investigated and had already ruled out those infections as early cases of Covid-19. “There were occasional illnesses because that’s normal,” she said. “There was nothing that stood out.”

China’s reluctance to cooperate with outside investigators and share information could be a sign of a cover-up of a lab leak. But it could also stem from reasons that have nothing to do with the virus, perhaps a consequence of broader international tensions.

And while the WHO’s initial investigation was not comprehensive, researchers are in the planning stages of another trip to China to study the origins of the virus. This time, the team wants to look at blood samples going back two years and screen them for antibodies to SARS-CoV-2. That could allow scientists to map previously unknown chains of transmission of the virus and narrow the scope of possible origins.

We can take steps to stop a future pandemic without knowing where this one came from

If SARS-CoV-2 did escape via a laboratory accident, it’s urgent to try to figure out exactly how it happened and to take precautions, especially given that there are other laboratories conducting research on dangerous pathogens around the world. “If the lab-leak hypothesis is put aside because it is too contentious, laboratory safety and especially risky research will continue to be ignored,” David Relman , an infectious disease researcher at Stanford University and a co-signer of the Science letter, wrote Wednesday in the Washington Post . “We cannot afford to bury our heads in the sand about one possible cause of the origins of Covid-19 simply because it is politically sensitive.”

On the other hand, there is no reason why laboratories would need to wait on the outcome of such an investigation to take steps to prevent future accidents. They could conduct safety audits and ensure experiments are conducted under the proper biosafety levels. Over the long term, facilities researching viruses like the one in Wuhan could even be relocated away from major population centers.

Similarly, policymakers could take steps to prevent natural spillovers. As humans venture further into wilderness areas to cultivate land and resources, the chances grow of a previously unknown virus crossing over from animals into people. The wildlife trade and venues like wet markets certainly aren’t helping. In a sense, even a “natural origin” of SARS-CoV-2 stems from human causes. “All these spillovers, wherever they are, it’s because human activity is encroaching upon animal activity,” Racaniello said.

While it would be ideal to investigate all possible origins of a deadly global disease, it may not be practical. Given that one pathway has evidence for it and another does not, some scientists say it’s better to focus on the likelier routes.

“It is a mistake to weight these possibilities equally, and it risks underresourcing the investigations into animal sources of this virus that we really need so we can understand the pathways of emergence and cut them off before this happens again,” Goldstein said.

Tracing the animal origins of SARS-CoV-2 is already poised to be a monumental and tedious task for scientists. It will require immense resources as well as cooperation with authorities in China, which may be jeopardized if an investigation into a lab leak isn’t handled with tact.

“Sure ‘investigate’ the lab. But, arm-waving about an often mentioned ‘forensic’ investigation (whatever that means) is not helpful,” Garry said in an email.

More answers about the roots of the pandemic may emerge in the coming months, but it’s likely that further inquiries won’t be enough to satisfy everyone. Even after the pandemic fades away, the virus that caused it may long frustrate and confound.

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• 08 June 2021

The COVID lab-leak hypothesis: what scientists do and don’t know

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Debate over the idea that the SARS-CoV-2 coronavirus emerged from a laboratory has escalated over the past few weeks, coinciding with the annual World Health Assembly, at which the World Health Organization (WHO) and officials from nearly 200 countries discussed the COVID-19 pandemic. After last year’s assembly, the WHO agreed to sponsor the first phase of an investigation into the pandemic’s origins, which took place in China in early 2021 .

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Dongguan, Guangdong, China

City University of Hong Kong (Dongguan)

Alzheimer's Disease (AD) Researcher/Associate Researcher

Xiaoliang Sunney XIE’s Group is recruiting researchers specializing in Alzheimer's disease (AD).

Beijing, China

Changping Laboratory

Scientist / Postdoc (m/f/d): Analysis of Microscopic BIOMedical Images (AMBIOM)

The Leibniz-Institut für Analytische Wissenschaften - ISAS - e. V. develops efficient analytical methods for health research. Thus, it contributes ...

Dortmund, Nordrhein-Westfalen (DE)

Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V.

Postdoctoral Fellow (all genders) with focus on Thromboinflammation

Postdoctoral Fellow (all genders) with focus on Thromboinflammation Fulltime/Parttime | Temporary | Arbeitsort: Hamburg- Eppendorf UKE_Zentrum für ...

Hamburg (DE)

Universitätsklinikum Hamburg-Eppendorf

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