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

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• 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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The COVID lab leak theory is dead. Here’s how we know the virus came from a Wuhan market

ARC Australian Laureate Fellow and Professor, University of Sydney

Disclosure statement

Edward C Holmes receives funding from the Australian Research Council and the National Health and Medical Research Council. He has received consultancy fees from Pfizer Australia and has held honorary appointments (for which he has received no renumeration and performed no duties) at the China CDC in Beijing and the Shanghai Public Health Clinical Center (Fudan University)

University of Sydney provides funding as a member of The Conversation AU.

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My colleagues and I published the most detailed studies of the earliest events in the COVID-19 pandemic last month in the journal Science.

Together, these papers paint a coherent evidence-based picture of what took place in the city of Wuhan during the latter part of 2019.

The take-home message is the COVID pandemic probably did begin where the first cases were detected – at the Huanan Seafood Wholesale Market.

At the same time this lays to rest the idea that the virus escaped from a laboratory.

Huanan market was the pandemic epicentre

An analysis of the geographic locations of the earliest known COVID cases – dating to December 2019 – revealed a strong clustering around the Huanan market. This was true not only for people who worked at or visited the market, but also for those who had no links to it.

Although there will be many missing cases, there’s no evidence of widespread sampling bias: the first COVID cases were not identified simply because they were linked to the Huanan market.

The Huanan market was the pandemic epicentre. From its origin there, the SARS-CoV-2 virus rapidly spread to other locations in Wuhan in early 2020 and then to the rest of the world.

The Huanan market is an indoor space about the size of two soccer fields. The word “seafood” in its name leaves a misleading impression of its function. When I visited the market in 2014, a variety of live wildlife was for sale including raccoon dogs and muskrats.

At the time I suggested to my Chinese colleagues that we sample these market animals for viruses. Instead, they set up a virological surveillance study at the nearby Wuhan Central Hospital, which later cared for many of the earliest COVID patients.

Wildlife were also on sale in the Huanan market in 2019. After the Chinese authorities closed the market on January 1 2020, investigative teams swabbed surfaces, door handles, drains, frozen animals and so on.

Most of the samples that later tested positive for SARS-CoV-2 were from the south-western corner of the market. The wildlife I saw for sale on my visit in 2014 were in the south-western corner.

This establishes a simple and plausible pathway for the virus to jump from animals to humans.

Read more: How do viruses mutate and jump species? And why are 'spillovers' becoming more common?

Animal spillover

SARS-CoV-2 has evolved into an array of lineages, some familiar to us as the “variants of concern” (what we call Delta, Omicron and so on). The first split in the SARS-CoV-2 family tree – between the “A” and “B” lineages – occurred very early in the pandemic. Both lineages have an epicentre at the market and both were detected there.

Further analyses suggest the A and B lineages were the products of separate jumps from animals. This simply means there was a pool of infected animals in the Huanan market, fuelling multiple exposure events.

Reconstructing the history of mutations in the SARS-CoV-2 genome sequence through time showed the B lineage was the first to jump to humans. It was followed, perhaps a few weeks later, by the A lineage.

All these events are estimated to have occurred no earlier than late October 2019. Claims that the virus was spreading before this date can be dismissed.

What’s missing, of course, is that we don’t yet know exactly which animals were involved in the transfer of SARS-CoV-2 to humans. Live wildlife were removed from the Huanan market before the investigative team entered, increasing public safety but hampering origin hunting.

The opportunity to find the direct animal host has probably passed. As the virus likely rapidly spread through its animal reservoir, it’s overly optimistic to think it would still be circulating in these animals today.

The absence of a definitive animal source has been taken as tacit support for counter claims that SARS-CoV-2 in fact “leaked” from a scientific laboratory – the Wuhan Institute of Virology.

Death knell for the lab leak theory

The lab leak theory rests on an unfortunate coincidence: that SARS-CoV-2 emerged in a city with a laboratory that works on bat coronaviruses.

Some of these bat coronaviruses are closely related to SARS-CoV-2. But not close enough to be direct ancestors.

Sadly, the focus on the Wuhan Institute of Virology has distracted us from a far more important connection: that, like SARS-CoV-1 (which emerged in late 2002) before it, there’s a direct link between a coronavirus outbreak and a live animal market.

Consider the odds that a virus that leaked from a lab was first detected at the very place where you would expect it to emerge if it in fact had a natural animal origin – vanishingly low. And these odds drop further as we need to link both the A and B lineages to the market.

Was the market just the location of a super-spreading event? Nothing says so. It wasn’t a crowded location in the bustling and globally connected metropolis of Wuhan. It’s not even close to being the busiest market or shopping mall in the city.

For the lab leak theory to be true, SARS-CoV-2 must have been present in the Wuhan Institute of Virology before the pandemic started. This would convince me.

But the inconvenient truth is there’s not a single piece of data suggesting this. There’s no evidence for a genome sequence or isolate of a precursor virus at the Wuhan Institute of Virology. Not from gene sequence databases, scientific publications, annual reports, student theses, social media, or emails.

Even the intelligence community has found nothing. Nothing. And there was no reason to keep any work on a SARS-CoV-2 ancestor secret before the pandemic.

To assign the origin of SARS-CoV-2 to the Wuhan Institute of Virology requires a set of increasingly implausible “what if?” scenarios. These eventually lead to preposterous suggestions of clandestine bioweapon research.

The lab leak theory stands as an unfalsifiable allegation. If an investigation of the lab found no evidence of a leak, the scientists involved would simply be accused of hiding the relevant material. If not a conspiracy theory, it’s a theory requiring a conspiracy.

It provides a convenient vehicle for calls to limit, if not ban outright, gain-of-function research in which viruses with greatly different properties are created in labs. Whether or not SARS-CoV-2 originated in this manner is incidental.

Read more: We want to know where COVID came from. But it’s too soon to expect miracles

Wounds that may never be healed

The acrid stench of xenophobia lingers over much of this discussion. Fervent dismissals by the Chinese scientists of anything untoward are blithely cast as lies.

Yet during this crucial period these same scientists were going to international conferences and welcoming visitors. Do we honestly believe they would have such a pathological disdain for the consequences of their actions?

The debate over the origins of COVID has opened wounds that may never be healed. It has armed a distrust in science and fuelled divisive political opinion. Individual scientists have been assigned the sins of their governments.

The incessant blame game and finger pointing has reduced the chances of finding viral origins even further. History won’t judge this period kindly.

Global collaboration is the bedrock of effective pandemic prevention, but we’re in danger of destroying rather than building relationships. We may even be less prepared for a pandemic than in 2019. Despite political barriers and a salivating media, the evidence for a natural animal origin for SARS-CoV-2 has increased over the past two years. To deny it puts us all at risk.

• Coronavirus
• Wildlife trade
• Zoonotic viruses
• Wuhan lab theory
• Wuhan Institute of Virology
• Wuhan lab-leak hypothesis
• COVID-19 origin
• lab leak hypothesis

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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.

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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.

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.

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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• 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.

For Hungry Minds

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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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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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 .

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• 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

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The Lab-Leak Hypothesis

For decades, scientists have been hot-wiring viruses in hopes of preventing a pandemic, not causing one. but what if ….

This article was featured in One Great Story , New York’ s reading recommendation newsletter. Sign up here to get it nightly.

When Nicholson Baker published “The Lab-Leak Hypothesis” in early January, the subject itself was still deeply taboo across the American political and journalistic landscape. A year later, the hypothesis has been revived and reconsidered not just by major investigations by the New York  Times ,  The Wall Street Journal , the Washington  Post , and  The Atlantic , but also by the WHO and the U.S. Intelligence Community. Nearly everything that would later serve as the basis for this public reconsideration of pandemic origins was contained in Baker’s original story, the first of its kind to break the ice.

Flask Monsters

What happened was fairly simple, I’ve come to believe. It was an accident. A virus spent some time in a laboratory, and eventually it got out. 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. SARS-2 was not designed as a biological weapon. But it was, I think, designed. Many thoughtful people dismiss this notion , and they may be right. They sincerely believe that the coronavirus arose naturally, “zoonotically,” from animals, without having been previously studied, or hybridized, or sluiced through cell cultures, or otherwise worked on by trained professionals. They hold that a bat, carrying a coronavirus, infected some other creature, perhaps a pangolin, and that the pangolin may have already been sick with a different coronavirus disease, and out of the conjunction and commingling of those two diseases within the pangolin, a new disease, highly infectious to humans, evolved. Or they hypothesize that two coronaviruses recombined in a bat, and this new virus spread to other bats, and then the bats infected a person directly — in a rural setting, perhaps — and that this person caused a simmering undetected outbreak of respiratory disease, which over a period of months or years evolved to become virulent and highly transmissible but was not noticed until it appeared in Wuhan.

There is no direct evidence for these zoonotic possibilities, just as there is no direct evidence for an experimental mishap — no written confession, no incriminating notebook, no official accident report. Certainty craves detail, and detail requires an investigation. It has been a full year, 80 million people have been infected , and, surprisingly, no public investigation has taken place. We still know very little about the origins of this disease.

Nevertheless, I think it’s worth offering some historical context for our yearlong medical nightmare. We need to hear from the people who for years have contended that certain types of virus experimentation might lead to a disastrous pandemic like this one. And we need to stop hunting for new exotic diseases in the wild, shipping them back to laboratories, and hot-wiring their genomes to prove how dangerous to human life they might become.

Over the past few decades, scientists have developed ingenious methods of evolutionary acceleration and recombination, and they’ve learned how to trick viruses, coronaviruses in particular, those spiky hairballs of protein we now know so well, into moving quickly from one species of animal to another or from one type of cell culture to another. They’ve made machines that mix and mingle the viral code for bat diseases with the code for human diseases — diseases like SARS, severe acute respiratory syndrome, for example, which arose in China in 2003, and MERS, Middle East respiratory syndrome, which broke out a decade later and has to do with bats and camels. Some of the experiments — “gain of function” experiments — aimed to create new, more virulent, or more infectious strains of diseases in an effort to predict and therefore defend against threats that might conceivably arise in nature. The term gain of function is itself a euphemism; the Obama White House more accurately described this work as “experiments that may be reasonably anticipated to confer attributes to influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route.” The virologists who carried out these experiments have accomplished amazing feats of genetic transmutation, no question, and there have been very few publicized accidents over the years. But there have been some.

And we were warned, repeatedly. The intentional creation of new microbes that combine virulence with heightened transmissibility “poses extraordinary risks to the public,” wrote infectious-disease experts Marc Lipsitch and Thomas Inglesby in 2014. “A rigorous and transparent risk-assessment process for this work has not yet been established.” That’s still true today. In 2012, in Bulletin of the Atomic Scientists , Lynn Klotz warned that there was an 80 percent chance, given how many laboratories were then handling virulent viro-varietals, that a leak of a potential pandemic pathogen would occur sometime in the next 12 years.

A lab accident — a dropped flask, a needle prick, a mouse bite, an illegibly labeled bottle — is apolitical. Proposing that something unfortunate happened during a scientific experiment in Wuhan — where COVID-19 was first diagnosed and where there are three high-security virology labs, one of which held in its freezers the most comprehensive inventory of sampled bat viruses in the world — isn’t a conspiracy theory. It’s just a theory. It merits attention, I believe, alongside other reasoned attempts to explain the source of our current catastrophe.

“A Reasonable Chance”

From early 2020, the world was brooding over the origins of COVID-19. People were reading research papers, talking about what kinds of live animals were or were not sold at the Wuhan seafood market — wondering where the new virus had come from.

Meanwhile, things got strange all over the world. The Chinese government shut down transportation and built hospitals at high speed. There were video clips of people who’d suddenly dropped unconscious in the street. A doctor on YouTube told us how we were supposed to scrub down our produce when we got back from the supermarket. A scientist named Shi Zhengli of the Wuhan Institute of Virology published a paper saying that the novel coronavirus was 96 percent identical to a bat virus, RaTG13, found in Yunnan province in southern China. On March 13, I wrote in my journal that there seemed to be something oddly artificial about the disease: “It’s too airborne — too catching — it’s something that has been selected for infectivity. That’s what I suspect. No way to know so no reason to waste time thinking about it.”

This was just a note to self — at the time, I hadn’t interviewed scientists about SARS-2 or read their research papers. But I did know something about pathogens and laboratory accidents; I published a book last year, Baseless , that talks about some of them. The book is named after a Pentagon program, Project Baseless, whose goal, as of 1951, was to achieve “an Air Force–wide combat capability in biological and chemical warfare at the earliest possible date.”

A vast treasure was spent by the U.S. on the amplification and aerial delivery of diseases — some well known, others obscure and stealthy. America’s biological-weapons program in the ’50s had A1-priority status, as high as nuclear weapons. In preparation for a total war with a numerically superior communist foe, scientists bred germs to be resistant to antibiotics and other drug therapies, and they infected lab animals with them, using a technique called “serial passaging,” in order to make the germs more virulent and more catching.

And along the way, there were laboratory accidents. By 1960, hundreds of American scientists and technicians had been hospitalized, victims of the diseases they were trying to weaponize. Charles Armstrong, of the National Institutes of Health, one of the consulting founders of the American germ-warfare program, investigated Q fever three times, and all three times, scientists and staffers got sick. In the anthrax pilot plant at Camp Detrick, Maryland, in 1951, a microbiologist, attempting to perfect the “foaming process” of high-volume production, developed a fever and died. In 1964, veterinary worker Albert Nickel fell ill after being bitten by a lab animal. His wife wasn’t told that he had Machupo virus, or Bolivian hemorrhagic fever. “I watched him die through a little window to his quarantine room at the Detrick infirmary,” she said.

In 1977, a worldwide epidemic of influenza A began in Russia and China; it was eventually traced to a sample of an American strain of flu preserved in a laboratory freezer since 1950. In 1978, a hybrid strain of smallpox killed a medical photographer at a lab in Birmingham, England; in 2007, live foot-and-mouth disease leaked from a faulty drainpipe at the Institute for Animal Health in Surrey. In the U.S., “more than 1,100 laboratory incidents involving bacteria, viruses and toxins that pose significant or bioterror risks to people and agriculture were reported to federal regulators during 2008 through 2012,” reported USA Today in an exposé published in 2014. In 2015, the Department of Defense discovered that workers at a germ-warfare testing center in Utah had mistakenly sent close to 200 shipments of live anthrax to laboratories throughout the United States and also to Australia, Germany, Japan, South Korea, and several other countries over the past 12 years. In 2019, laboratories at Fort Detrick — where “defensive” research involves the creation of potential pathogens to defend against — were shut down for several months by the Centers for Disease Control and Prevention for “breaches of containment.” They reopened in December 2019.

High-containment laboratories have a whispered history of near misses. Scientists are people, and people have clumsy moments and poke themselves and get bitten by the enraged animals they are trying to nasally inoculate. Machines can create invisible aerosols, and cell solutions can become contaminated. Waste systems don’t always work properly. Things can go wrong in a hundred different ways.

Hold that human fallibility in your mind. And then consider the cautious words of Alina Chan, a scientist who works at the Broad Institute of MIT and Harvard. “There is a reasonable chance that what we are dealing with is the result of a lab accident,” Chan told me in July of last year. There was also, she added, a reasonable chance that the disease had evolved naturally — both were scientific possibilities. “I don’t know if we will ever find a smoking gun, especially if it was a lab accident. The stakes are so high now. It would be terrifying to be blamed for millions of cases of COVID-19 and possibly up to a million deaths by year end, if the pandemic continues to grow out of control. The Chinese government has also restricted their own scholars and scientists from looking into the origins of SARS-CoV-2. At this rate, the origin of SARS-CoV-2 may just be buried by the passage of time.”

I asked Jonathan A. King, a molecular biologist and biosafety advocate from MIT, whether he’d thought lab accident when he first heard about the epidemic. “Absolutely, absolutely,” King answered. Other scientists he knew were concerned as well. But scientists, he said, in general were cautious about speaking out. There were “very intense, very subtle pressures” on them not to push on issues of laboratory biohazards. Collecting lots of bat viruses, and passaging those viruses repeatedly through cell cultures, and making bat-human viral hybrids, King believes, “generates new threats and desperately needs to be reined in.”

“All possibilities should be on the table, including a lab leak,” a scientist from the NIH, Philip Murphy — chief of the Laboratory of Molecular Immunology — wrote me recently. Nikolai Petrovsky, a professor of endocrinology at Flinders University College of Medicine in Adelaide, Australia, said in an email, “There are indeed many unexplained features of this virus that are hard if not impossible to explain based on a completely natural origin.” Richard Ebright, a molecular biologist at Rutgers University, wrote that he’d been concerned for some years about the Wuhan laboratory and about the work being done there to create “chimeric” (i.e., hybrid) SARS-related bat coronaviruses “with enhanced human infectivity.” Ebright said, “In this context, the news of a novel coronavirus in Wuhan ***screamed*** lab release.”

“No Credible Evidence”

The new disease , as soon as it appeared, was intercepted — stolen and politicized by people with ulterior motives. The basic and extremely interesting scientific question of what happened was sucked up into an ideological sharknado.

Some Americans boycotted Chinese restaurants; others bullied and harassed Asian Americans . Steve Bannon, broadcasting from his living room, in a YouTube series called War Room , said that the Chinese Communist Party had made a biological weapon and intentionally released it. He called it the “CCP virus.” And his billionaire friend and backer, Miles Guo, a devoted Trump supporter, told a right-wing website that the communists’ goal was to “use the virus to infect selective people in Hong Kong, so that the Chinese Communist Party could use it as an excuse to impose martial law there and ultimately crush the Hong Kong pro-democracy movement. But it backfired terribly.”

In The Lancet , in February, a powerful counterstatement appeared, signed by 27 scientists. “We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin,” the statement said. “Scientists from multiple countries have published and analyzed genomes of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and they overwhelmingly conclude that this coronavirus originated in wildlife, as have so many other emerging pathogens.”

The behind-the-scenes organizer of this Lancet statement, Peter Daszak, is a zoologist and bat-virus sample collector and the head of a New York nonprofit called EcoHealth Alliance — a group that (as veteran science journalist Fred Guterl explained later in Newsweek ) has channeled money from the National Institutes of Health to Shi Zhengli’s laboratory in Wuhan, allowing the lab to carry on recombinant research into diseases of bats and humans. “We have a choice whether to stand up and support colleagues who are being attacked and threatened daily by conspiracy theorists or to just turn a blind eye,” Daszak said in February in Science magazine.

Vincent Racaniello, a professor at Columbia and a co-host of a podcast called This Week in Virology , said on February 9 that the idea of an accident in Wuhan was “complete bunk.” The coronavirus was 96 percent similar to a bat virus found in 2013, Racaniello said. “It’s not a man-made virus. It wasn’t released from a lab.”

Racaniello’s dismissal was seconded by a group of scientists from Ohio State, the University of Pennsylvania, and the University of North Carolina, who put out a paper in Emerging Microbes and Infections to quiet the “speculations, rumors, and conspiracy theories that SARS-CoV-2 is of laboratory origin.” There was “currently no credible evidence” that SARS-2 leaked from a lab, these scientists said, using a somewhat different argument from Racaniello’s. “Some people have alleged that the human SARS-CoV-2 was leaked directly from a laboratory in Wuhan where a bat CoV (RaTG13) was recently reported,” they said. But RaTG13 could not be the source because it differed from the human SARS-2 virus by more than a thousand nucleotides. One of the paper’s authors, Susan Weiss, told the Raleigh News & Observer , “The conspiracy theory is ridiculous.”

The most influential natural-origin paper , “The Proximal Origin of SARS-CoV-2,” by a group of biologists that included Kristian Andersen of Scripps Research, appeared online in a preliminary version in mid-February. “We do not believe any type of laboratory-based scenario is plausible,” the scientists said. Why? Because molecular-modeling software predicted that if you wanted to optimize an existing bat virus so that it would replicate well in human cells, you would arrange things a different way than how the SARS-2 virus actually does it — even though the SARS-2 virus does an extraordinarily good job of replicating in human cells. The laboratory-based scenario was implausible, the paper said, because, although it was true that the virus could conceivably have developed its unusual genetic features in a laboratory, a stronger and “more parsimonious” explanation was that the features came about through some kind of natural mutation or recombination. “What we think,” explained one of the authors, Robert F. Garry of Tulane University, on YouTube , “is that this virus is a recombinant. It probably came from a bat virus, plus perhaps one of these viruses from the pangolin.” Journalists, for the most part, echoed the authoritative pronouncements of Daszak, Racaniello, Weiss, Andersen, and other prominent natural-originists. “The balance of the scientific evidence strongly supports the conclusion that the new coronavirus emerged from nature — be it the Wuhan market or somewhere else,” said the Washington Post ’s “Fact Checker” column. “Dr. Fauci Again Dismisses Wuhan Lab As Source of Coronavirus,” said CBS News , posting a video interview of Anthony Fauci by National Geographic . “If you look at the evolution of the virus in bats, and what’s out there now,” Fauci said, “it’s very, very strongly leaning toward ‘This could not have been artificially or deliberately manipulated’ — the way the mutations have naturally evolved.”

Everyone took sides; everyone thought of the new disease as one more episode in an ongoing partisan struggle. Think of Mike Pompeo, that landmass of Cold War truculence; think of Donald Trump himself. They stood at their microphones saying, in a winking, I-know-something-you-don’t-know sort of way, that this disease escaped from a Chinese laboratory. Whatever they were saying must be wrong. It became impermissible, almost taboo, to admit that, of course, SARS-2 could have come from a lab accident. “The administration’s claim that the virus spread from a Wuhan lab has made the notion politically toxic, even among scientists who say it could have happened,” wrote science journalist Mara Hvistendahl in the Intercept .

“Is It a Complete Coincidence?”

Even so, in January and February of 2020, there were thoughtful people who were speaking up, formulating their perplexities.

One person was Sam Husseini, an independent journalist. He went to a CDC press conference at the National Press Club on February 11, 2020. By then, 42,000 people had gotten sick in China and more than a thousand had died. But there were only 13 confirmed cases in the U.S. Halfway through the Q&A period, Husseini went to the microphone and asked the CDC’s representative, Anne Schuchat, where the virus had come from. His head was spinning, he told me later.

“Obviously the main concern is how to stop the virus,” Husseini said; nonetheless, he wanted to know more about its source. “Is it the CDC’s contention,” he asked, “that there’s absolutely no relation to the BSL-4 lab in Wuhan? It’s my understanding that this is the only place in China with a BSL-4 lab. We in the United States have, I think, two dozen or so, and there have been problems and incidents.” (A BSL-4 laboratory is a maximum-security biosafety-level-four facility, used to house research on the most dangerous known pathogens. New York has confirmed there are at least 11 BSL-4 facilities currently operating in the U.S.) Husseini hastened to say that he wasn’t implying that what happened in Wuhan was in any way intentional. “I’m just asking, Is it a complete coincidence that this outbreak happened in the one city in China with a BSL-4 lab?”

Schuchat thanked Husseini for his questions and comments. Everything she’d seen was quite consistent with a natural, zoonotic origin for the disease, she said.

That same month, a group of French scientists from Aix-Marseille University posted a paper describing their investigation of a small insertion in the genome of the new SARS-2 virus. The virus’s spike protein contained a sequence of amino acids that formed what Etienne Decroly and colleagues called a “peculiar furin-like cleavage site” — a chemically sensitive region on the lobster claw of the spike protein that would react in the presence of an enzyme called furin, which is a type of protein found everywhere within the human body, but especially in the lungs. When the spike senses human furin, it shudders, chemically speaking, and the enzyme opens the protein, commencing the tiny morbid ballet whereby the virus burns a hole in a host cell’s outer membrane and finds its way inside.

The code for this particular molecular feature — not found in SARS or any SARS-like bat viruses, but present in a slightly different form in the more lethal MERS virus — is easy to remember because it’s a roar: “R-R-A-R.” The letter code stands for amino acids: arginine, arginine, alanine, and arginine. Its presence, so Decroly and his colleagues observed, may heighten the “pathogenicity” — that is, the god-awfulness — of a disease.

Botao Xiao, a professor at the South China University of Technology, posted a short paper on a preprint server titled “The Possible Origins of 2019-nCoV Coronavirus.” Two laboratories, the Wuhan Center for Disease Control and Prevention (WHCDC) and the Wuhan Institute of Virology, were not far from the seafood market, which was where the disease was said to have originated, Xiao wrote — in fact, the WHCDC was only a few hundred yards away from the market — whereas the horseshoe bats that hosted the disease were hundreds of miles to the south. (No bats were sold in the market, he pointed out.) It was unlikely, he wrote, that a bat would have flown to a densely populated metropolitan area of 15 million people. “The killer coronavirus probably originated from a laboratory in Wuhan,” Xiao believed. He urged the relocation of “biohazardous laboratories” away from densely populated places. His article disappeared from the server.

And late in the month, a professor at National Taiwan University, Fang Chi-tai, gave a lecture on the coronavirus in which he described the anomalous R-R-A-R furin cleavage site. The virus was “unlikely to have four amino acids added all at once,” Fang said — natural mutations were smaller and more haphazard, he argued. “From an academic point of view, it is indeed possible that the amino acids were added to COVID-19 in the lab by humans.” When the Taiwan News published an article about Fang’s talk, Fang disavowed his own comments, and the video copy of the talk disappeared from the website of the Taiwan Public Health Association. “It has been taken down for a certain reason,” the association explained. “Thank you for your understanding.”

“A Serious Shortage of Appropriately Trained Technicians”

In the spring , I did some reading on coronavirus history. Beginning in the 1970s, dogs, cows, and pigs were diagnosed with coronavirus infections; dog shows were canceled in 1978 after 25 collies died in Louisville, Kentucky. New varieties of coronaviruses didn’t start killing humans, though, until 2003 — that’s when restaurant chefs, food handlers, and people who lived near a live-animal market got sick in Guangzhou, in southern China, where the shredded meat of a short-legged raccoonlike creature, the palm civet, was served in a regional dish called “dragon-tiger-phoenix soup.” The new disease, SARS, spread alarmingly in hospitals, and it reached 30 countries and territories. More than 800 people died; the civet-borne virus was eventually traced to horseshoe bats .

Later, smaller outbreaks of SARS in Taiwan, Singapore, and China’s National Institute of Virology in Beijing were all caused by laboratory accidents. Of the Beijing Virology Institute, the World Health Organization’s safety investigators wrote , in May 2004, that they had “serious concerns about biosafety procedures.” By one account, a SARS storage room in the Beijing lab was so crowded that the refrigerator holding live virus was moved out to the hallway. “Scientists still do not fully understand exactly where or how SARS emerged 18 months ago,” wrote Washington Post reporter David Brown in June 2004. “But it is clear now that the most threatening source of the deadly virus today may be places they know intimately — their own laboratories.”

MERS arose in 2012, possibly spread by camels that had contracted the disease from bats or bat guano, then passed it to human drinkers of raw camel milk and butchers of camel meat. It was an acute sickness, with a high fatality rate, mostly confined to Saudi Arabia. Like SARS, MERS ebbed quickly — it all but disappeared outside the Middle East, except for an outbreak in 2015 at the Samsung Medical Center in South Korea, where a single case of MERS led to more than 180 infections, many involving hospital workers.

In January 2015, the brand-new BSL-4 lab in Wuhan, built by a French contractor, celebrated its opening, but full safety certification came slowly. According to State Department cables from 2018 leaked to the Washington Post , the new BSL-4 lab had some start-up problems, including “a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory.” The staff had gotten some training at a BSL-4 lab in Galveston, Texas, but they were doing potentially dangerous work with SARS-like viruses, the memo said, and they needed more help from the U.S.

In November or December of 2019, the novel coronavirus began to spread. Chinese scientists initially named it “Wuhan seafood market pneumonia virus,” but soon that idea went away. The market, closed and decontaminated by Chinese officials on January 1, 2020, was an amplifying hub, not the source of the outbreak, according to several studies by Chinese scientists. Forty-five percent of the earliest SARS-2 patients had no link with the market.

Now let’s take a step back. AIDS, fatal and terrifying and politically charged, brought on a new era in government-guided vaccine research, under the guidance of Anthony Fauci. A virologist at Rockefeller University, Stephen S. Morse, began giving talks on “emerging viruses” — other plagues that might be in the process of coming out of nature’s woodwork. In 1992, Richard Preston wrote a horrific account of one emergent virus, Ebola, in The New Yorker , which became a best-selling book in 1994; Laurie Garrett’s The Coming Plague: Newly Emerging Diseases in a World Out of Balance appeared that same year and was also a best seller. The idea seemed to be everywhere: We were on the verge of a wave of zoonotic, emergent plagues.

This new, useful term, emerging , began to glow in the research papers of some coronavirologists, who were out of the spotlight, working on common colds and livestock diseases. The term was useful because it was fluid. An emerging disease could be real and terrifying, as AIDS was — something that had just arrived on the medical scene and was confounding our efforts to combat it — or it could be a disease that hadn’t arrived, and might never arrive, but could be shown in a laboratory to be waiting in the wings, just a few mutations away from a human epidemic. It was real and unreal at the same time — a quality that was helpful when applying for research grants.

Take, for instance, this paper from 1995: “High Recombination and Mutation Rates in Mouse Hepatitis Viruses Suggest That Coronaviruses May Be Potentially Important Emerging Viruses.” It was written by Dr. Ralph Baric and his bench scientist, Boyd Yount, at the University of North Carolina. Baric, a gravelly voiced former swim champion, described in this early paper how his lab was able to train a coronavirus, MHV, which causes hepatitis in mice, to jump species, so that it could reliably infect BHK (baby-hamster kidney) cell cultures. They did it using serial passaging: repeatedly dosing a mixed solution of mouse cells and hamster cells with mouse-hepatitis virus, while each time decreasing the number of mouse cells and upping the concentration of hamster cells. At first, predictably, the mouse-hepatitis virus couldn’t do much with the hamster cells, which were left almost free of infection, floating in their world of fetal-calf serum. But by the end of the experiment, after dozens of passages through cell cultures, the virus had mutated: It had mastered the trick of parasitizing an unfamiliar rodent. A scourge of mice was transformed into a scourge of hamsters. And there was more: “It is clear that MHV can rapidly alter its species specificity and infect rats and primates,” Baric said. “The resulting virus variants are associated with demyelinating diseases in these alternative species.” (A demyelinating disease is a disease that damages nerve sheaths.) With steady prodding from laboratory science, along with some rhetorical exaggeration, a lowly mouse ailment was morphed into an emergent threat that might potentially cause nerve damage in primates. That is, nerve damage in us.

A few years later, in a further round of “interspecies transfer” experimentation, Baric’s scientists introduced their mouse coronavirus into flasks that held a suspension of African-green-monkey cells, human cells, and pig-testicle cells. Then, in 2002, they announced something even more impressive: They’d found a way to create a full-length infectious clone of the entire mouse-hepatitis genome. Their “infectious construct” replicated itself just like the real thing, they wrote .

Not only that, but they’d figured out how to perform their assembly seamlessly, without any signs of human handiwork. Nobody would know if the virus had been fabricated in a laboratory or grown in nature. Baric called this the “no-see’m method,” and he asserted that it had “broad and largely unappreciated molecular biology applications.” The method was named, he wrote, after a “very small biting insect that is occasionally found on North Carolina beaches.”

In 2006, Baric, Yount, and two other scientists were granted a patent for their invisible method of fabricating a full-length infectious clone using the seamless, no-see’m method. But this time, it wasn’t a clone of the mouse-hepatitis virus — it was a clone of the entire deadly human SARS virus, the one that had emerged from Chinese bats, via civets, in 2002. The Baric Lab came to be known by some scientists as “the Wild Wild West.” In 2007, Baric said that we had entered “the golden age of coronavirus genetics.”

“I would be afraid to look in their freezers,” one virologist told me.

Baric and Shi Zhengli of the Wuhan Institute of Virology, the two top experts on the genetic interplay between bat and human coronaviruses, began collaborating in 2015.

“I Had Not Slept a Wink”

Early in the pandemic, Scientific American profiled Shi Zhengli, known in China as the “bat woman.” Shi trapped hundreds of bats in nets at the mouths of caves in southern China, sampled their saliva and their blood, swabbed their anuses, and gathered up their fecal pellets. Several times, she visited and sampled bats in a mine in Mojiang, in southern China, where, in 2012, six men set to work shoveling bat guano were sickened by a severe lung disease, three of them fatally. Shi’s team took the samples back to Wuhan and analyzed whatever fragments of bat virus she could find. In some cases, when she found a sequence that seemed particularly significant, she experimented with it in order to understand how it might potentially infect humans. Some of her work was funded by the National Institutes of Health and some of it by the U.S. Defense Threat Reduction Agency of the Department of Defense via Peter Daszak’s EcoHealth Alliance.

As Shi explained to Scientific American , late in December 2019, she heard from the director of the Wuhan Institute that there was an outbreak of a new disease in the city. Medical samples taken from hospital patients arrived at her lab for analysis. Shi determined that the new virus was related to SARS but even more closely related to a bat disease that her own team had found on a virus-hunting trip: the now-famous RaTG13. Shi was surprised that the outbreak was local, she said: “I had never expected this kind of thing to happen in Wuhan, in central China.” The bat hiding places that she’d been visiting were, after all, as far away as Orlando, Florida, is from New York City. Could this new virus, she wondered, have come from her own laboratory? She checked her records and found no exact matches. “That really took a load off my mind,” she said. “I had not slept a wink for days.”

If one of the first thoughts that goes through the head of a lab director at the Wuhan Institute of Virology is that the new coronavirus could have come from her lab, then we are obliged to entertain the scientific possibility that it could indeed have come from her lab. Right then, there should have been a comprehensive, pockets-inside-out, fully public investigation of the Virology Institute, along with the other important virus labs in Wuhan, including the one close by the seafood market, headquarters of the Wuhan CDC. There should have been interviews with scientists, interviews with biosafety teams, close parsings of laboratory notebooks, freezer and plumbing and decontamination systems checks — everything. It didn’t happen. The Wuhan Institute of Virology closed down its databases of viral genomes, and the Chinese Ministry of Education sent out a directive: “Any paper that traces the origin of the virus must be strictly and tightly managed.”

Shi made some WeChat posts early in 2020. “The novel 2019 coronavirus is nature punishing the human race for keeping uncivilized living habits,” she wrote. “I, Shi Zhengli, swear on my life that it has nothing to do with our laboratory.” She advised those who believed rumors, and gave credence to unreliable scientific papers, to “shut their stinking mouths.”

“ ‘Bug to Drug’ in 24 Hours”

It wasn’t only AIDS that changed the way the NIH funded research. The War on Terror also influenced which diseases got the most attention. In the late ’90s, under Bill Clinton and then George W. Bush, biodefense specialists became interested — again — in anthrax. The Defense Threat Reduction Agency built a small anthrax factory in Nevada, using simulants, to demonstrate how easy it would be for a terrorist to build a small anthrax factory. And in the first year of the Bush presidency, the Defense Intelligence Agency wrote up plans to create a vaccine-resistant form of anthrax using state-of-the-art gene-splicery. A front-page article describing these initiatives, “U.S. Germ Warfare Research Pushes Treaty Limits,” appeared in the New York Times on September 4, 2001, one week before 9/11. “Pentagon Says Projects Are Defense, Is Pressing Ahead,” was the subtitle.

After the 9/11 attacks, and the mysterious anthrax mailings that began a week later (which said, “TAKE PENACILIN [ sic ] NOW / DEATH TO AMERICA / DEATH TO ISRAEL / ALLAH IS GREAT”), the desire for biopreparedness became all consuming. Now there were emerging biothreats from humans as well as from the evolving natural world. Fauci’s anti-terror budget went from $53 million in 2001 to $1.7 billion in 2003. Setting aside his work toward an AIDS vaccine, which was taking longer than he’d foreseen, Fauci said he would be going all out to defend against a suite of known Cold War agents, all of which had been bred and perfected in American weapons programs many years before — brucellosis, anthrax, tularemia, and plague, for instance. “We are making this the highest priority,” Fauci said. “We are really marshaling all available resources.”

Vaccine development had to progress much faster, Fauci believed; he wanted to set up “vaccine systems” and “vaccine platforms,” which could be quickly tailored to defend against a particular emergent strain some terrorist with an advanced biochemistry degree might have thrown together in a laboratory. “Our goal within the next 20 years is ‘bug to drug’ in 24 hours,” Fauci said. “This would specifically meet the challenge of genetically engineered bioagents.” The first Project BioShield contract Fauci awarded was to VaxGen, a California pharmaceutical company, for $878 million worth of shots of anthrax vaccine.

By 2005, so much money was going toward biothreat reduction and preparedness that more than 750 scientists sent a protest letter to the NIH. Their claim was that grants to study canonical biowar diseases — anthrax, plague, brucellosis, and tularemia, all exceptionally rare in the U.S. — had increased by a factor of 15 since 2001, whereas funds for the study of widespread “normal” diseases, of high public-health importance, had decreased.

Fauci was firm in his reply: “The United States through its leaders made the decision that this money was going to be spent on biodefense,” he said. “We disagree with the notion that biodefense concerns are of ‘low public-health significance.’ ”

In 2010, by one count, there were 249 BSL-3 laboratories and seven BSL-4 laboratories in the U.S., and more than 11,000 scientists and staffers were authorized to handle the ultralethal germs on the government’s select pathogen list. And yet the sole bioterrorist in living memory who actually killed American citizens, according to the FBI — the man who sent the anthrax letters — turned out to be one of the government’s own researchers. Bruce Ivins , an eccentric, suicidal laboratory scientist from Ohio who worked in vaccine development at Fort Detrick, allegedly wanted to boost the fear level so as to persuade the government to buy more of the patented, genetically engineered anthrax VaxGen vaccine, of which he was a co-inventor. (See David Willman’s fascinating biography of Ivins, Mirage Man .) Fauci’s staff at NIH funded Ivins’s vaccine laboratory and gave $100 million to VaxGen to accelerate vaccine production. (The NIH’s $878 million contract with VaxGen, however, was quietly canceled in 2006; Ivins, who was never charged, killed himself in 2008.)

“The whole incident amounted to a snake eating its own tail,” wrote Wendy Orent in an August 2008 piece titled “Our Own Worst Bioenemy” in the Los Angeles Times . “No ingenious biowarrior from Al Qaeda sent the lethal envelopes through the U.S. postal system. An American scientist did.” What confirmed Ivins’s guilt, according to the FBI, was that there was a genetic match between the anthrax used in the killings and the strain held at Fort Detrick.

“Weapons of Mass Disruption”

After SARS appeared in 2003, Ralph Baric’s laboratory moved up the NIH funding ladder. SARS was a “dual use” organism — a security threat and a zoonotic threat at the same time. In 2006, Baric wrote a long, fairly creepy paper on the threat of “weaponizable” viruses. Synthetic biology had made possible new kinds of viral “weapons of mass disruption,” he wrote, involving, for example, “rapid production of numerous candidate bioweapons that can be simultaneously released,” a scattershot terror tactic Baric called the “ ‘survival of the fittest’ approach.”

Baric hoped to find a SARS vaccine, but he couldn’t; he kept looking for it, year after year, supported by the NIH, long after the disease itself had been contained. It wasn’t really gone, Baric believed. Like other epidemics that pop up and then disappear, as he told a university audience some years later, “they don’t go extinct. They are waiting to return.” What do you do if you run a well-funded laboratory, an NIH “center of excellence,” and your emergent virus is no longer actually making people sick? You start squeezing it and twisting it into different shapes. Making it stand on its hind legs and quack like a duck, or a bat. Or breathe like a person.

Baric’s safety record is good — although there was a minor mouse-bite incident in 2016, uncovered by ProPublica — and his motives are beyond reproach: “Safe, universal, vaccine platforms are needed that can be tailored to new pathogens as they emerge, quickly tested for safety, and then strategically used to control new disease outbreaks in human populations,” he wrote in a paper on public health. But the pioneering work he did over the past 15 years — generating tiny eager single-stranded flask monsters and pitting them against human cells, or bat cells, or gene-spliced somewhat-human cells, or monkey cells, or humanized mice — was not without risk, and it may have led others astray.

In 2006, for instance, Baric and his colleagues, hoping to come up with a “vaccine strategy” for SARS, produced noninfectious virus replicon particles (or VRPs) using the Venezuelan-equine-encephalitis virus (another American germ-warfare agent), which they fitted with various SARS spike proteins. Then, wearing Tyvek suits and two pairs of gloves each, and working in a biological safety cabinet in a BSL-3-certified laboratory, they cloned and grew recombinant versions of the original SARS virus in an incubator in a medium that held African-green-monkey cells. When they had grown enough virus, the scientists swapped out one kind of spike protein for a carefully chosen mutant, and they challenged their prototype vaccine with it in mice.

The scientists also tried their infectious SARS clones in something called an air-liquid interface, using a relatively new type of cell culture developed by Raymond Pickles of the University of North Carolina’s Cystic Fibrosis Center. Pickles had perfected a method of emulating the traits of human airway tissue by cultivating cells taken from lung-disease patients — nurturing the culture over four to six weeks in such a way that the cells differentiated and developed a crop of tiny moving hairs, or cilia, on top and goblet cells within that produced real human mucus. In fact, before infecting these HAE (human airway epithelial) cells with a virus, the lab worker must sometimes rinse off some of the accumulated mucus, as if helping the lab-grown tissue to clear its throat. So Baric was exposing and adapting his engineered viruses to an extraordinarily true-to-life environment — the juicy, sticky, hairy inner surface of our breathing apparatus.

SARS-2 seems almost perfectly calibrated to grab and ransack our breathing cells and choke the life out of them. “By the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission,” Alina Chan and her co-authors have written, whereas SARS, when it first appeared in 2003, underwent “numerous adaptive mutations” before settling down. Perhaps viral nature hit a bull’s-eye of airborne infectivity, with almost no mutational drift, no period of accommodation and adjustment, or perhaps some lab worker somewhere, inspired by Baric’s work with human airway tissue, took a spike protein that was specially groomed to colonize and thrive deep in the ciliated, mucosal tunnels of our inner core and cloned it onto some existing viral bat backbone. It could have happened in Wuhan, but — because anyone can now “print out” a fully infectious clone of any sequenced disease — it could also have happened at Fort Detrick, or in Texas, or in Italy, or in Rotterdam, or in Wisconsin, or in some other citadel of coronaviral inquiry. No conspiracy — just scientific ambition, and the urge to take exciting risks and make new things, and the fear of terrorism, and the fear of getting sick. Plus a whole lot of government money.

“Risky Areas for Spillover”

Project Bioshield began to fade by the end of the Bush administration, although the expensive high-containment laboratories, controversial preservers and incubators of past and future epidemics, remain. By 2010, some BioShield projects had dissolved into Obama’s Predict program, which paid for laboratories and staff in 60 “risky areas for spillover” around the world. Jonna Mazet, a veterinary scientist from the University of California, Davis, was in charge of Predict, which was a component of USAID’s “Emerging Pandemic Threats” program. Her far-flung teams collected samples from 164,000 animals and humans and claimed to have found “almost 1,200 potentially zoonotic viruses, among them 160 novel coronaviruses, including multiple SARS- and MERS-like coronaviruses.” The fruits of Predict’s exotic harvest were studied and circulated in laboratories worldwide, and their genetic sequences became part of GenBank , the NIH’s genome database, where any curious RNA wrangler anywhere could quickly synthesize snippets of code and test out a new disease on human cells.

Baric, Jonna Mazet, and Peter Daszak of EcoHealth worked together for years — and Daszak also routed Predict money to Shi Zhengli’s bat-surveillance team in Wuhan through his nonprofit, mingling it with NIH money and money from the U.S. Defense Threat Reduction Agency. In 2013, Mazet announced that Shi Zhengli’s virus hunters, with Predict’s support, had, for the first time, isolated and cultured a live SARS-like virus from bats and demonstrated that this virus could bind to the human ACE2, or “angiotensin-converting enzyme 2,” receptor, which Baric’s laboratory had determined to be the sine qua non of human infectivity. “This work shows that these viruses can directly infect humans and validates our assumption that we should be searching for viruses of pandemic potential before they spill over to people,” Mazet said .

Daszak, for his part, seems to have viewed his bat quests as part of an epic, quasi-religious death match. In a paper from 2008, Daszak and a co-author described Bruegel’s painting The Fall of the Rebel Angels and compared it to the contemporary human biological condition. The fallen angels could be seen as pathogenic organisms that had descended “through an evolutionary (not spiritual) pathway that takes them to a netherworld where they can feed only on our genes, our cells, our flesh,” Daszak wrote . “Will we succumb to the multitudinous horde? Are we to be cast downward into chthonic chaos represented here by the heaped up gibbering phantasmagory against which we rail and struggle?”

“Lab-Made?”

There are, in fact, some helpful points of agreement between zoonoticists — those who believe in a natural origin of the SARS-2 virus — and those who believe that it probably came from a laboratory. Both sides agree, when pressed, that a lab origin can’t be conclusively ruled out and a natural origin can’t be ruled out either — because nature, after all, is capable of improbable, teleological-seeming achievements. Both sides also agree, for the most part, that the spillover event that began the human outbreak probably happened only once, or a few times, quite recently, and not many times over a longer period. They agree that bat virus RaTG13 (named for the Rinolophus affinus bat, from Tongguan, in 2013) is the closest match to the human virus that has yet been found, and that although the two viruses are very similar, the spike protein of the bat virus lacks the features the human spike protein possesses that enable it to work efficiently with human tissue.

Zoonoticists hold that SARS-2’s crucial features — the furin cleavage site and the ACE2 receptor — are the result of a recombinant event involving a bat coronavirus (perhaps RaTG13 or a virus closely related to it) and another, unknown virus. Early on, researchers proposed that it could be a snake sold at the seafood market — a Chinese cobra or a banded krait — but no: Snakes don’t typically carry coronaviruses. Then there was a thought that the disease came from sick smuggled pangolins, because there existed a certain pangolin coronavirus that was, inexplicably, almost identical in its spike protein to the human coronavirus — but then, no: There turned out to be questions about the reliability of the genetic information in that diseased-pangolin data set, on top of which there were no pangolins for sale at the Wuhan market. Then a group from China’s government veterinary laboratory at Harbin tried infecting beagles, pigs, chickens, ducks, ferrets, and cats with SARS-2 to see if they could be carriers. (Cats and ferrets got sick; pigs, ducks, and most dogs did not.)

In September, some scientists at the University of Michigan, led by Yang Zhang, reported that they had created a “computational pipeline” to screen nearly a hundred possible intermediate hosts, including the Sumatran orangutan, the Western gorilla, the Olive baboon, the crab-eating macaque, and the bonobo. All these primates were “permissive” to the SARS-2 coronavirus and should undergo “further experimentational investigation,” the scientists proposed.

Despite this wide-ranging effort, there is at the moment no animal host that zoonoticists can point to as the missing link. There’s also no single, agreed-upon hypothesis to explain how the disease may have traveled from the bat reservoirs of Yunnan all the way to Wuhan, seven hours by train, without leaving any sick people behind and without infecting anyone along the way.

The zoonoticists say that we shouldn’t find it troubling that virologists have been inserting and deleting furin cleavage sites and ACE2-receptor-binding domains in experimental viral spike proteins for years: The fact that virologists have been doing these things in laboratories, in advance of the pandemic, is to be taken as a sign of their prescience, not of their folly. But I keep returning to the basic, puzzling fact: This patchwork pathogen, which allegedly has evolved without human meddling, first came to notice in the only city in the world with a laboratory that was paid for years by the U.S. government to perform experiments on certain obscure and heretofore unpublicized strains of bat viruses — which bat viruses then turned out to be, out of all the organisms on the planet, the ones that are most closely related to the disease. What are the odds?

In July, I discovered a number of volunteer analysts who were doing a new kind of forensic, samizdat science, hunched over the letter code of the SARS-2 genome like scholars deciphering the cuneiform impressions in Linear B tablets. There were the anonymous authors of Project Evidence, on GitHub, who “disavow all racism and violent attacks, including those which are aimed at Asian or Chinese people,” and there was Yuri Deigin, a biotech entrepreneur from Canada, who wrote a massive, lucid paper on Medium, “Lab-Made?,” which illumined the mysteries of the spike protein. Jonathan Latham of the Bioscience Resource Project, with his co-author Allison Wilson, wrote two important papers: one a calm, unsparing overview of laboratory accidents and rash research and the other a close look at the small outbreak of an unexplained viral pneumonia in a bat-infested copper mine in 2012. I corresponded with Alina Chan (now the subject of a nicely turned piece in Boston magazine by Rowan Jacobsen) and with the pseudonymous Billy Bostickson, a tireless researcher whose Twitter photo is a cartoon of an injured experimental monkey, and Monali Rahalkar, of the Agharkar Research Institute in Pune, India, who wrote a paper with her husband, Rahul Bahulikar, that also sheds light on the story of the bat-guano-shoveling men whose virus was remarkably like SARS-2, except that it was not nearly as catching. I talked to Rossana Segreto, a molecular biologist at the University of Innsbruck, whose paper , “Is Considering a Genetic-Manipulation Origin for SARS-CoV-2 a Conspiracy Theory That Must Be Censored?,” co-authored with Yuri Deigin, was finally published in November under a milder title; it argued that SARS-2’s most notable features, the furin site and the human ACE2-binding domain, were unlikely to have arisen simultaneously and “might be the result of lab manipulation techniques such as site directed mutagenesis.” Segreto is also the person who first established that a bat-virus fragment named BtCoV/4991, identified in 2013, was 100 percent identical to the closest known cousin to SARS-CoV-2, the bat virus RaTG13, thereby proving that the virus closest to the SARS-2-pandemic virus was linked back not to a bat cave but to a mine shaft, and that this same virus had been stored and worked on in the Wuhan Institute for years. This made possible the first big investigative piece on SARS-2’s origins, in the Times of London, in July: “Nobody can deny the bravery of scientists who risked their lives harvesting the highly infectious virus,” the Times authors write. “But did their courageous detective work lead inadvertently to a global disaster?”

“A New, Non-Natural Risk”

In 2011, a tall , confident Dutch scientist, Ron Fouchier, using grant money from Fauci’s group at NIH, created a mutant form of highly pathogenic avian influenza, H5N1, and passaged it ten times through ferrets in order to prove that he could “force” (his word) this potentially fatal disease to infect mammals, including humans, “via aerosols or respiratory droplets.” Fouchier said his findings indicated that these avian influenza viruses, thus forced, “pose a risk of becoming pandemic in humans.”

This experiment was too much for some scientists: Why, out of a desire to prove that something extremely infectious could happen, would you make it happen? And why would the U.S. government feel compelled to pay for it to happen? Late in 2011, Marc Lipsitch of the Harvard School of Public Health got together with several other dismayed onlookers to ring the gong for caution. On January 8, 2012, the New York Times published a scorcher of an editorial , “An Engineered Doomsday.” “We cannot say there would be no benefits at all from studying the virus,” the Times said. “But the consequences, should the virus escape, are too devastating to risk.”

These gain-of-function experiments were an important part of the NIH’s approach to vaccine development, and Anthony Fauci was reluctant to stop funding them. He and Francis Collins, director of the National Institutes of Health, along with Gary Nabel, NIAID director of vaccine research, published an opinion piece in the Washington Post in which they contended that the ferret flu experiments, and others like them, were “a risk worth taking.” “Important information and insights can come from generating a potentially dangerous virus in the laboratory,” they wrote; the work can “help delineate the principles of virus transmission between species.” The work was safe because the viruses were stored in a high-security lab, they believed, and the work was necessary because nature was always coming up with new threats. “Nature is the worst bioterrorist,” Fauci told a reporter. “We know that through history.”

Soon afterward, there followed some distressing screwups in secure federal laboratories involving live anthrax, live smallpox, and live avian influenza. These got attention in the science press. Then Lipsitch’s activists (calling themselves the Cambridge Working Group) sent around a strong statement on the perils of research with “Potential Pandemic Pathogens,” signed by more than a hundred scientists. The work might “trigger outbreaks that would be difficult or impossible to control,” the signers said. Fauci reconsidered, and the White House in 2014 announced that there would be a “pause” in the funding of new influenza, SARS, and MERS gain-of-function research.

Baric, in North Carolina, was not happy. He had a number of gain-of-function experiments with pathogenic viruses in progress. “It took me ten seconds to realize that most of them were going to be affected,” he told NPR . Baric and a former colleague from Vanderbilt University wrote a long letter to an NIH review board expressing their “profound concerns.” “This decision will significantly inhibit our capacity to respond quickly and effectively to future outbreaks of SARS-like or MERS-like coronaviruses, which continue to circulate in bat populations and camels,” they wrote. The funding ban was itself dangerous, they argued. “Emerging coronaviruses in nature do not observe a mandated pause.”

Hoping to smooth over controversy by showing due diligence, the National Science Advisory Board for Biosecurity, founded in the BioShield era under President Bush, paid a consulting firm, Gryphon Scientific, to write a report on gain-of-function research, which by now was simply referred to as GoF. In chapter six of this thousand-page dissertation, published in April 2016, the consultants take up the question of coronaviruses. “Increasing the transmissibility of the coronaviruses could significantly increase the chance of a global pandemic due to a laboratory accident,” they wrote.

The Cambridge Working Group continued to write letters of protest and plead for restraint and sanity. Steven Salzberg, a professor of biomedical engineering at Johns Hopkins, said, “We have enough problems simply keeping up with the current flu outbreaks — and now with Ebola — without scientists creating incredibly deadly new viruses that might accidentally escape their labs.” David Relman of Stanford Medical School said, “It is unethical to place so many members of the public at risk and then consult only scientists — or, even worse, just a small subset of scientists — and exclude others from the decision-making and oversight process.” Richard Ebright wrote that creating and evaluating new threats very seldom increases security: “Doing so in biology — where the number of potential threats is nearly infinite, and where the asymmetry between the ease of creating threats and the difficulty of addressing threats is nearly absolute — is especially counterproductive.” Lynn Klotz wrote, “Awful as a pandemic brought on by the escape of a variant H5N1 virus might be, it is SARS that now presents the greatest risk. The worry is less about recurrence of a natural SARS outbreak than of yet another escape from a laboratory researching it to help protect against a natural outbreak.” Marc Lipsitch argued that gain-of-function experiments can mislead, “resulting in worse not better decisions,” and that the entire gain-of-function debate as overseen by the NIH was heavily weighted in favor of scientific insiders and “distinctly unwelcoming of public participation.”

Nariyoshi Shinomiya, a professor of physiology and nano-medicine at the National Defense Medical College in Japan, offered this warning: “Similar to nuclear or chemical weapons there is no going back once we get a thing in our hands.”

But in the end, Baric was allowed to proceed with his experiments, and the research papers that resulted, showered with money, became a sort of Anarchist’s Cookbook for the rest of the scientific world. In November 2015, Baric and colleagues published a collaboration paper with Shi Zhengli titled “A SARS-like Cluster of Circulating Bat Coronaviruses Shows Potential for Human Emergence.” Into a human SARS virus that they had adapted so that it would work in mice, Baric and Shi et al. inserted the spike protein of a bat virus, SHC014, discovered by Shi in southern China. They dabbed the mice nasally with virus and waited, looking for signs of sickness: “hunching, ruffled fur.” They also infected human airway cells with the mouse-adapted bat-spike-in-a-human-virus backbone. In both mice and human airway cells, the chimeric virus caused a “robust infection.”

This proved, Baric and Shi believed, that you did not need civets or other intermediate hosts in order for bats to cause an epidemic in humans and that therefore all the SARS-like viruses circulating in bat populations “may pose a future threat.” Peter Daszak, who had used Predict funds to pay Shi for her work on the paper, was impressed by this conclusion; the findings, he said, “move this virus from a candidate emerging pathogen to a clear and present danger.”

Richard Ebright was trenchantly unenthusiastic. “The only impact of this work,” he said , “is the creation, in a lab, of a new, non-natural risk.”

Early in 2016, Baric and Shi again collaborated. Shi sent Baric a fresh bat virus spike protein, and Baric inserted it into the backbone of a human SARS virus and then used that infectious clone to attack human airway cells. “The virus readily and efficiently replicated in cultured human airway tissues, suggesting an ability to potentially jump directly to humans,” reported the UNC’s website. This time, they also used the bat-human hybrid virus to infect transgenic humanized mice that grew human ACE2 protein. The mice, young and old, lost weight and died, proving, again, that this particular bat virus was potentially “poised to emerge in human populations.” It was “an ongoing threat,” Baric wrote. But was it? Civets and camels that are exposed to a lot of bat-guano dust may be an ongoing threat and a manageable one. But the bats themselves just want to hang in their caves and not be bothered by frowning sightseers in spacesuits who want to poke Q-tips in their bottoms. This 2016 “poised for human emergence” paper was supported by eight different NIH grants. In 2015, Baric’s lab received $8.3 million from the NIH; in 2016, it received $10.5 million.

Gain-of-function research came roaring back under Trump and Fauci. “The National Institutes of Health will again fund research that makes viruses more dangerous,” said an article in Nature in December 2017. Carrie Wolinetz of the NIH’s office of science policy defended the decision. “These experiments will help us get ahead of viruses that are already out there and pose a real and present danger to human health,” she told The Lancet . The NIH, Wolinetz said, was committed to a leadership role with gain-of-function research internationally. “If we are pursuing this research in an active way, we will be much better positioned to develop protection and countermeasures should something bad happen in another country.”

A reporter asked Marc Lipsitch what he thought of the resumption of NIH funding. Gain-of-function experiments “have done almost nothing to improve our preparedness for pandemics,” he said, “yet they risked creating an accidental pandemic.”

“Proximity Is a Problem”

In April , four months into the coronavirus emergency, a deputy director at the NIH wrote an email to EcoHealth Alliance. “You are instructed to cease providing any funds to Wuhan Institute of Virology,” it said. In response, Daszak and the chief scientific officer of New England Biolabs (a company that sells seamless gene-splicing products to laboratories, among other things) got 77 Nobel Prize winners to sign a statement saying that the cancellation deprived the “nation and the world of highly regarded science that could help control one of the greatest health crises in modern history and those that may arise in the future.” Later, as a condition of further funding, the NIH wrote to say it wanted Daszak to arrange an outside inspection of the Wuhan lab and to procure from Wuhan’s scientists a sample of whatever they’d used to sequence the SARS-2 virus. Daszak was outraged (“I am not trained as a private detective”), and again he fought back. He was reluctant to give up his own secrets, too. “Conspiracy-theory outlets and politically motivated organizations have made Freedom of Information Act requests on our grants and all of our letters and emails to the NIH,” he told Nature . “We don’t think it’s fair that we should have to reveal everything we do.”

But Daszak has survived — even prospered. Recently, The Lancet made him the lead investigator in its inquiry into the origins of the pandemic, and the World Health Organization named him to its ten-person origins investigation. (“We’re still close enough to the origin to really find out more details about where it has come from,” Daszak told Nature .)

The NIH has also set up an ambitious new international program, called CREID, which stands for Centers for Research in Emerging Infectious Diseases, and it has put Daszak’s EcoHealth in charge of trapping animals and looking for obscure bat viruses in Singapore, Malaysia, and Thailand. Baric is one of Daszak’s partners in CREID. The virus hunting and collecting, which Richard Ebright likens to “looking for a gas leak with a lighted match,” will continue and widen with U.S. funding. “We’re going to work in remote parts of Malaysia and Thailand to get to the front line of where the next pandemic is going to start,” Daszak told NPR.

In May, an interviewer from the People’s Pharmacy website asked Baric if he had any thoughts on whether the coronavirus began with a natural bat-to-human transfer. “Or was there something a little bit more, perhaps, insidious involved?”

“Well, of course the answers to those questions are in China,” Baric replied. “Exactly how they work in that facility is something that would be very difficult for a Westerner to know,” he said. “The main problems that the Institute of Virology has is that the outbreak occurred in close proximity to that Institute. That Institute has in essence the best collection of virologists in the world that have gone out and sought out, and isolated, and sampled bat species throughout Southeast Asia. So they have a very large collection of viruses in their laboratory. And so it’s — you know — proximity is a problem. It’s a problem.”

Over the course of the fall, and especially after the election muffled Donald Trump’s influence over the country’s public-health apparatus, that proximity problem — and the uncomfortable questions of origins it raised — began to grow somewhat more discussable. The BBC, Le Monde , and Italy’s RAI have all recently taken seriously the scientific possibility of a lab leak. In late October, the World Health Organization convened the first meeting of its second inquiry into the origins of the disease. The WHO’s effort is perhaps the world’s best chance to satisfy its curiosity about goings-on at the Wuhan Institute of Virology and at the Wuhan CDC’s virus lab near the Wuhan seafood market. But, as the New York Times has reported , the WHO’s information gathering has been hindered by Chinese secretiveness since February, when an initial investigative team sent to Beijing was told its members’ access to scientists would be restricted and that it couldn’t visit the seafood market, then considered a hub of the pandemic.

When a BBC video team tried to inspect the Yunnan mine shaft, they found the road to the mine blocked by a strategically parked truck that had “broken down” shortly before they arrived. Reporter John Sudworth asked Daszak, one of the ten members of the second WHO investigative team, whether he would push for access to the Wuhan Institute of Virology. “That’s not my job to do that,” Daszak replied.

In November, David Relman, the Stanford microbiologist, one of the most thoughtful of the voices warning against gain-of-function research, published a paper in Proceedings of the National Academy of Sciences on the urgent need to unravel the origins of COVID-19. “If SARS-CoV-2 escaped from a lab to cause the pandemic,” he wrote, “it will become critical to understand the chain of events and prevent this from happening again.” Conflicts of interest by researchers and administrators will need to be addressed, Relman wrote; to reach the truth, the investigation must be transparent, international, and, as much as possible, unpolitical. “A more complete understanding of the origins of COVID-19 clearly serves the interests of every person in every country on this planet.”

“The world is sitting on a precedent-setting decision right now,” wrote Alina Chan on December 8. “It is unclear if SARS2 is 100 percent natural or emerged due to lab/research activities. If we walk away from this, demonstrating that we cannot effectively investigate its origins, it will pave the way for future COVIDS.”

Just before this issue of New York went to press, I reached Ralph Baric by phone and asked him where he now believed SARS-2 came from. (Anthony Fauci, Shi Zhengli, and Peter Daszak didn’t respond to emails, and Kristian Andersen said he was busy with other things.) Baric said he still thought the virus came from bats in southern China, perhaps directly, or possibly via an intermediate host, although the smuggled pangolins, in his view, were a red herring. The disease evolved in humans over time without being noticed, he suspected, becoming gradually more infectious, and eventually a person carried it to Wuhan “and the pandemic took off.” Then he said, “Can you rule out a laboratory escape? The answer in this case is probably not.”

Transmission

So how did we actually get this disease?

Here’s what I think happened. In April 2012, in a copper mine in Mojiang, China, three men were given an awful job — they were told to shovel bat guano out of a mine shaft. They went to work and shoveled guano for seven hours a day in the confined, insufficiently ventilated space of the mine shaft, and by the end of the week, they were sick with a viral pneumonia of unknown etiology. Three more, younger shovelers were hired to replace the ones who were out sick.

The viral load in their lungs was so huge, because of all the guano dust, that their lungs became a kind of accelerated laboratory passaging experiment, as Jonathan Latham and Allison Wilson have written, forcing the virus to switch its allegiance from bats to humans. SARS experts were consulted, and the disease was judged to be SARS-like but not SARS. It was something new. (Shi Zhengli told Scientific American that the guano shovelers had died of a fungal disease, but, as Monali Rahalkar pointed out, they were treated with antivirals, and their symptoms were consistent with viral pneumonia with attendant secondary fungal infections.)

Although it was a severe disease, and in the end three of the shovelers died, there was no resultant epidemic. It was actually a case of industrial overexposure to an infectious substance — what we might call a massive OSHA violation. The bat disease that the men encountered wasn’t necessarily all that dangerous except in an environment of immunosuppressive overload.

Peter Daszak and Shi Zhengli were interested, of course, because this unidentified coronavirus disease involved bats and people. Of the fragmentary bits of virus Shi retrieved from the mine shaft, one was SARS-like, and Shi sequenced it and called it BtCoV/4991 and published a paper about it. Several times — in 2016 and 2018 and 2019 — this most interesting sample, a portion of what we now know as RaTG13, was taken out of the freezers in Shi’s lab and worked on in undisclosed ways. (Peter Daszak claims that these samples have disintegrated and can’t be validated or studied.) Samples of the nameless human disease also traveled back to the Wuhan Institute of Virology — few specifics about these valuable specimens have been released by Chinese sources, however.

This is the period in the story that demands a very close investigation, when chimeric assemblages may have been created and serially passaged, using BtCoV/4991, a.k.a. RaTG13, and other bat viruses, perhaps along with forms of the human virus. It’s when Shi and Baric both published papers that were about what happened when you hot-swapped mutant spike proteins between bat viruses and human viruses.

The link, via the renamed sample BtCoV/4991, to the copper mine is of exceptional importance because of the one huge difference between the unnamed guano shovelers’ virus and the SARS-2 virus that is now ravaging, for example, California: transmissibility. Airborne human-to-human transmissibility — the kind of thing that gain-of-functioneers like Ron Fouchier and Ralph Baric were aiming at, in order to demonstrate what Baric called “lurking threats” — is COVID-19’s crucial distinguishing feature. If six men had gotten extremely sick with COVID-19 back in 2012 in southern China, doctors and nurses in the hospital where they lay dying would likely have gotten sick as well. There might have been hundreds or thousands of cases. Instead, only the shovelers themselves, who had breathed a heavy concentration of guano dust for days, got it.

The existence of bat virus RaTG13 is therefore not necessarily evidence of a natural bat origin. In fact, it seems to me to imply the opposite: New functional components may have been overlaid onto or inserted into the RaTG13 genome, new Tinkertoy intermolecular manipulations, especially to its spike protein, which have the effect of making it unprecedentedly infectious in human airways.

This is where the uniquely peculiar furin insert and/or the human-tuned ACE2-receptor-binding domain may come in — although it’s also possible that either of these elements could have evolved as part of some multistep zoonotic process. But in the climate of gonzo laboratory experimentation, at a time when all sorts of tweaked variants and amped-up substitutions were being tested on cell cultures and in the lungs of humanized mice and other experimental animals, isn’t it possible that somebody in Wuhan took the virus that had been isolated from human samples, or the RaTG13 bat virus sequence, or both (or other viruses from that same mine shaft that Shi Zhengli has recently mentioned in passing), and used them to create a challenge disease for vaccine research — a chopped-and-channeled version of RaTG13 or the miners’ virus that included elements that would make it thrive and even rampage in people? And then what if, during an experiment one afternoon, this new, virulent, human-infecting, furin-ready virus got out?

For more than 15 years, coronavirologists strove to prove that the threat of SARS was ever present and must be defended against, and they proved it by showing how they could doctor the viruses they stored in order to force them to jump species and go directly from bats to humans. More and more bat viruses came in from the field teams, and they were sequenced and synthesized and “rewired,” to use a term that Baric likes. In this international potluck supper of genetic cookery, hundreds of new variant diseases were invented and stored. And then one day, perhaps, somebody messed up. It’s at least a reasonable, “parsimonious” explanation of what might have happened.

This may be the great scientific meta-experiment of the 21st century. Could a world full of scientists do all kinds of reckless recombinant things with viral diseases for many years and successfully avoid a serious outbreak? The hypothesis was that, yes, it was doable. The risk was worth taking. There would be no pandemic.

I hope the vaccine works.

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Goats and Soda

• Infectious Disease
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• Women & Girls
• Coronavirus FAQ

What does the science say about the origin of the SARS-CoV-2 pandemic?

Michaeleen Doucleff

Security guards stand in front of the Huanan Seafood Wholesale Market in Wuhan, China, on Jan. 11, 2020, after the market had been closed following an outbreak of COVID-19 there. Two studies document samples of SARS-CoV-2 from stalls where live animals were sold. Noel Celis/AFP via Getty Images hide caption

Security guards stand in front of the Huanan Seafood Wholesale Market in Wuhan, China, on Jan. 11, 2020, after the market had been closed following an outbreak of COVID-19 there. Two studies document samples of SARS-CoV-2 from stalls where live animals were sold.

Since the SARS-CoV-2 pandemic began three years ago, its origin has been a topic of much scientific — and political — debate. Two main theories exist: The virus spilled over from an animal into people, most likely in a market in Wuhan, China, or the virus came from the Wuhan Institute of Virology and spread due to some type of laboratory accident.

The Wall Street Journal added to that debate this week when they reported that the U.S. Department of Energy has shifted its stance on the origin of COVID. It now concludes, with "low confidence," that the pandemic most likely arose from a laboratory leak in Wuhan, China.

The agency based its conclusion on classified evidence that isn't available to the public. According to the federal government, "low confidence" means "the information used in the analysis is scant, questionable, fragmented, or that solid analytical conclusions cannot be inferred from the information."

And at this point, the U.S. intelligence community still has no consensus about the origin of SARS-CoV-2. Four of the eight intelligence agencies lean toward a natural origin for the virus, with "low confidence," while two of them — the DOE and the Federal Bureau of Investigation — support a lab origin, with the latter having "moderate confidence" about its conclusion.

But it's a theory that the agencies are definitely bringing into the public eye. On Tuesday, FBI director Christopher A. Wray reiterated his belief that COVID-19 "most likely" sprang from "a potential lab incident" in Wuhan, China.

Staff members of the Wuhan Hygiene Emergency Response Team investigate the shuttered Huanan Seafood Wholesale Market on Jan. 11, 2020, after it was linked to cases of COVID-19. Noel Celis/AFP via Getty Images hide caption

Staff members of the Wuhan Hygiene Emergency Response Team investigate the shuttered Huanan Seafood Wholesale Market on Jan. 11, 2020, after it was linked to cases of COVID-19.

But at the end of the day, the origin of the pandemic is also a scientific question. Virologists who study pandemic origins are much less divided than the U.S. intelligence community. They say there is " very convincing " data and " overwhelming evidence " pointing to an animal origin.

In particular, scientists published two extensive, peer-reviewed papers in Science in July 2022, offering the strongest evidence to date that the COVID-19 pandemic originated in animals at a market in Wuhan, China. Specifically, they conclude that the coronavirus most likely jumped from a caged wild animal into people at the Huanan Seafood Wholesale Market, where a huge COVID-19 outbreak began in December 2019.

Virologist Angela Rasmussen , who contributed to one of the Science papers, says the DOE's "low confident" conclusion doesn't "negate the affirmative evidence for zoonotic [or animal] origin nor do they add any new information in support of lab origin."

"Many other [news] outlets are presenting this as new conclusive proof that the lab origin hypothesis is equally as plausible as the zoonotic origin hypothesis," Rasmussen wrote in an email to NPR, "and that is a misrepresentation of the evidence for either."

So just what is the scientific evidence that the pandemic began at the seafood market?

Neither of the Science papers provide the smoking gun — that is, an animal infected with the SARS-CoV-2 coronavirus at a market.

But they come close. They provide photographic evidence of wild animals such as raccoon dogs and a red fox, which can be infected with and shed SARS-CoV-2, sitting in cages in the market in late 2019. What's more, the caged animals are shown in or near a stall where scientists found SARS-CoV-2 virus on a number of surfaces, including on cages, carts and machines that process animals after they are slaughtered at the market.

The data in the 2022 studies paints an incredibly detailed picture of the early days of the pandemic. Photographic and genetic data pinpoint a specific stall at the market where the coronavirus likely was transmitted from an animal into people. And a genetic analysis estimates the time, within weeks, when not just one but two spillovers occurred. It calculates that the coronavirus jumped into people once in late November or early December and then again few weeks later.

At this exact same time, a huge COVID outbreak occurred at the market. Hundreds of people, working and shopping at the market, were likely infected. That outbreak is the first documented one of the pandemic, and it then spilled over into the community, as one of the Science papers shows.

At the same time, the Chinese Center for Disease Control and Prevention found two variants of the coronavirus inside the market. And an independent study, led by virologists at the University of California, San Diego, suggests these two variants didn't evolve in people, because throughout the entire pandemic, scientists have never detected a variant linking the two together. Altogether, the new studies suggest that, most likely, the two variants evolved inside animals.

Michael Worobey is a top virus sleuth. He has tracked the origins of the 1918 flu, HIV and now SARS-CoV-2. Worobey is a research professor in the Department of Ecology and Evolutionary Biology at the University of Arizona. University of Arizona hide caption

Evolutionary biologist Michael Worobey helped lead two of the studies and has been at the forefront of the search for the origins of the pandemic. He has spent his career tracking down the origins of pandemics, including the origin of HIV and the 1918 flu.

Back in May 2021, Worobey signed a letter calling for an investigation into the lab-leak theory. But then, through his own investigation, he quickly found data supporting an animal origin.

When the studies were first published online, NPR spoke to Worobey, who's at the University of Arizona, to understand what the data tells us about the origin of SARS-CoV-2; how, he believes, the data may shift the debate about the lab-leak theory; and the significance of photos taken five years before the pandemic. Here are key points from the conversation, which has been edited for clarity and length.

Live animals that are susceptible to COVID-19 were in the market in December 2019

It's clear-cut these wild, live animals, including raccoon dogs and red foxes, were in the market. We have photographic evidence from December 2019. A concerned customer evidently took these photos and videos of the market on Dec. 3 and posted them on Weibo [because it was illegal to sell certain live animals]. The photos were promptly scrubbed. But a CNN reporter had communicated directly with the person who took the photos. I was able to get in touch with this reporter, and they passed on those photos from the source. So we don't completely verify the photos.

An anonymous user on the Chinese social media platform Weibo posted pictures of live animals for sale in the southwest corner of the Huanan Seafood Market in Wuhan, China, in 2019. Researchers investigating the origins of the SAR-CoV-2 virus are including these images in a forthcoming academic paper that pinpoints the southwest corner as the most probable origin point of the pandemic. Worobey and Holmes et al. hide caption

An anonymous user on the Chinese social media platform Weibo posted pictures of live animals for sale in the southwest corner of the Huanan Seafood Market in Wuhan, China, in 2019. Researchers investigating the origins of the SAR-CoV-2 virus are including these images in a forthcoming academic paper that pinpoints the southwest corner as the most probable origin point of the pandemic.

Live susceptible animals were held in a stall where SARS-CoV-2 was later detected on a machine that processed animals in the market

We analyzed a leaked report from the Chinese CDC detailing the results of this environmental sampling. Virtually all of the findings in the report matched what was in the World Health Organization's report. But there was some extra information in the leaked report. For example, there was information not just on which stalls had virus in them — or had samples positive for SARS-CoV-2 — but also how many samples in a given stall yielded positive results.

We found out that one stall actually had five positive samples — five surfaces in that stall had virus on them. And even better, in that particular stall, the samples were very animal-y. For example, scientists found virus on a feather/hair remover, a cart of the sort that we see in photographs that are used for transporting cages and, best of all, a metal cage in a back room.

So now we know that when the national public health authorities shut down the market and then sampled the surfaces there, one of the surfaces positive for SARS-CoV-2 was a metal cage in a back room.

What's even weirder — it turns out that one of the co-authors of the study, Eddie Holmes , had been taken to the Huanan market several years before the pandemic and shown raccoon dogs in one of the stalls. He was told, "This is the kind of place that has the ingredients for cross-species transmission of dangerous pathogens."

So he clicks photos of the raccoon dogs. In one photo, the raccoon dogs are in a cage stacked on top of a cage with some birds in it.

And at the end of our sleuth work, we checked the GPS coordinates on his camera, and we find that he took the photo at the same stall, where five samples tested positive for SARS-CoV-2.

So we connected all sorts of bizarre kinds of data. Together the data are telling a strong story.

These two photos, taken in 2014 by scientist Edward Holmes, show raccoon dogs and unknown birds caged in the southwest corner of the Huanan Seafood Market in Wuhan, China. GPS coordinates of these images confirm that the animals were housed in the southwest corner of the market where researchers found evidence of the virus in January 2020. Edward Holmes hide caption

These two photos, taken in 2014 by scientist Edward Holmes, show raccoon dogs and unknown birds caged in the southwest corner of the Huanan Seafood Market in Wuhan, China. GPS coordinates of these images confirm that the animals were housed in the southwest corner of the market where researchers found evidence of the virus in January 2020.

Earliest known cases of COVID-19, even those not directly related to individuals who had been in the market, radiate out from the market

With a virus, such as SARS-CoV-2, that causes no symptoms or mild symptoms in most people, you don't have any chance of linking all the early cases to the site where the outbreak started. Because the virus is going to quickly spread to people outside of wherever it started.

And yet, from the clinical observations in Wuhan, around half of the earliest known COVID cases were people directly linked to the seafood market. And the other cases, which aren't linked through epidemiological data, have an even closer geographical association to the market. That's what we show in our paper.

It's absurd how strong the geographical association is [to the market].

NPR: Absurd? How? In the sense that the seafood market is so clearly bull's-eye center of this outbreak?

Yes. How could anyone not be moved, at least somewhat, by that data and then not take this idea [of an animal origin] seriously, especially given the other things we've found in these studies? That I don't understand.

The Huanan Seafood Wholesale Market on July 16, 2021. Getty Images/ Stringer hide caption

The Huanan Seafood Wholesale Market on July 16, 2021.

The virus jumped into people right before the outbreak in the market

For example, our new genetic analysis tells us that this virus was not around for very long when the cases occurred at the market. For example, the earliest known patient at the market had an onset of symptoms on Dec. 10, 2019. And we can estimate that at that point in time, there were only about 10 people infected with the virus in the world and probably fewer than 70.

So if the pandemic didn't start at the market, one of the first five or 10 people infected in the world was at the market. And how do you explain that?

You have to remember: Wuhan is a city of 11 million people. And the Huanan market is only 1 of 4 places in Wuhan that sold live animals susceptible to SARS-CoV-2, such as raccoon dogs.

It's highly unlikely that the first COVID-19 outbreak would occur at the market if there weren't a source of the virus there

Step back and think, "Where is the first cluster of a new respiratory infection going to appear in this city?" It could appear at a market. But it could also appear at a school, a university or a meatpacking plant.

NPR: Or a biotech conference?

Yes. In Washington state, SARS-CoV-2 first appeared in a man who had traveled back from China. In Germany, it was at an auto-parts supplier.

There are thousands, perhaps 10,000, other places at least as likely, or even more likely, to be the place where a new pathogen shows up. And yet, in Wuhan, the first cluster of cases happens to be one of the four places that sells live animals, out of 10,000 other places. If you're not surprised by that, then I don't think you're understanding the unlikelihood that that presents.

NPR: So what is the likelihood of that coincidence happening — that the first cluster of cases occurs at a market that sells animals known to be susceptible to SARS-CoV-2, but the virus didn't actually come from the market?

I would put the odds at 1 in 10,000. But it's interesting. We do have one analysis where we show essentially that the chance of having this pattern of cases [clustered around the market] is 1 in 10 million [if the market isn't a source of the virus]. We consider that strong evidence in science.

The analyses that we've done are telling a very strong story.

The evidence is amongst the best we have for any emerging virus.

NPR: Really?

It's important to note we haven't found a related virus from the intermediate host. But we have a bunch of other evidence.

And the data zeroing in on the Huanan market, to me, is as compelling as the data that indicated to John Snow that the water pump was poisoning people who used it. [ John Snow was a doctor in London who helped launch the field of outbreak investigations by figuring out the source of a cholera outbreak in the city in the mid-19th century.]

Making these findings brought tears

Sometimes you have these rare moments where you're maybe the only person on Earth who has access to this kind of crucial information. As I just started to figure out that there were more cases around the market than you can expect randomly — I felt that way. And no exaggeration, that moment — those kinds of moments — bring a tear to your eye.

Correction Feb. 28, 2023

An earlier version of this story misstated the Federal Bureau of Investigation as the Federal Bureau of Information.

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COVID-19 Pandemic Origins: Bioweapons and the History of Laboratory Leaks

To date, the coronavirus disease 2019 (COVID-19) pandemic has taken more than 3.5 million lives. Many of these deaths have been attributed to misleading information that fragmented a coordinated effort to mitigate loss of life. Future pandemics will continue to be a threat, so it is important to lay bare the true cause of this devastation. From the beginning, the origins of the pandemic have been debated, even though a natural zoonotic transfer to humans has been determined as the likely cause; however, speculation around a viral bioweapon and laboratory leaks remains. The evidence for the origins of this current pandemic can be found in the science and history behind biological outbreaks and the signs of bioweapon use. This knowledge will help minimize the harm of future pandemics.

One microbe has just devastated our world. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the cause of COVID-19, has shattered economies, upended patterns of life globally, and already killed >3.5 million people. More than 85 million cases were documented worldwide in <1 year, 1 and many people want to know how this happened and where the virus originated. The first reports in late 2019 indicated that an epidemic caused by a zoonotic virus was spreading from Wuhan, China, believed to have been transmitted from an animal reservoir at a live-animal market. Speculation remains that the blame lies elsewhere, however, which seems surprising to scientists. For the public, the truth is easy to question because of the vast amounts of circulating misinformation.

From the early stages, wild speculation existed regarding the origins of the virus. In March 2020, the US Department of State summoned the Chinese ambassador to protest statements of a Chinese spokesperson, who suggested that the virus was brought to Wuhan by the US military, allegedly as a bioweapon. 2 Then, a US senator suggested that the virus resulted from a botched Chinese bioweapons program. 3 Palestinian media argued that SARS-CoV-2 was a biological weapon being used by the US and Israel against China and Iran. 4 Other US officials suspected that the virus came from a Wuhan laboratory that was performing legitimate viral research because safety concerns had been previously identified at this laboratory. 5 As time went on, concern grew because China was found to be censoring the results of research into the origins of the pandemic. 6 It would not be the first time that modern research in China drew attack. In late 2018, the announcement of gene editing of babies resulted in criminal charges against a Chinese biophysicist and his two colleagues. 7 These issues have served to maintain alternative possibilities for the origin of COVID-19, based mostly on conspiracy theories and rumors that spread quickly through social media and remain difficult to stop. The virus as a bioweapon and the possible laboratory leak from legitimate research are the two most common remaining theories about the origins of SARS-CoV-2. The aim of this perspective is to show that the current pandemic is unlikely to have resulted from either bioweapons or a laboratory leak.

Bioweapons and Natural Disease Outbreaks

On the surface, similarities exist between bioweapons and viral pandemics that may have allowed this conspiracy theory to seem plausible. As nonconventional, nonkinetic weapons of mass destruction, bioweapons can create the same havoc as pandemics. As with a pandemic, if a bioweapon attack spreads widely, healthcare systems could be overwhelmed, perpetuating societal panic as well as frustration, despair, and psychological casualties among healthcare workers, adding to the panic. This cycle would only change when a pathogen weakens or natural immunity is strengthened.

Natural outbreaks and bioweapons can affect animal populations in ways similar to that for humans. Rabinowitz et al showed that for certain bioweapons, animals stricken with disease could help identify exposure risks to humans—so much so that the authors implored public health officials to transition from passive to active surveillance of animal populations for biosecurity. 7 , 8 Worldwide during this pandemic, animals of various species have been infected with SARS-CoV-2, including animals at the Bronx Zoo in New York City. 8 – 11

Throughout history, viral agents have been studied for use as weapons of disease. Dr Ken Alibek, former director of the bioweapons program of the Union of Soviet Socialist Republics, provides insight in his memoir 10 regarding the most highly developed bioweapons program in history. He described the production of a Marburg viral weapon that was ready to be manufactured in large amounts and placed into missile payloads with several warheads. Fortunately, Marburg missiles were never used, but other bioweapons have been used, such as ceramic bombs filled with plague-infested fleas that were used by Japan against a Chinese city during World War II and Salmonella used in the Rajneeshee bioterror attack in 1984 that contaminated Oregon salad bars. 12 The effects of such attacks are fatal at worst and drive panic at best.

Despite similarities between bioweapons and natural outbreaks of viral diseases, the bioweapon conspiracy theories are easily invalidated. Biowarfare as imagined by the public is different from biowarfare that has been deployed in real life. Casualty from a successfully deployed bioweapon has never been remotely close to the devastation caused by this pandemic, and most likely, never will. International laws have limited all known bioweapons production, and developing a weaponized form of a virus would require months of complete secrecy using gene-editing technology. With advanced CRISPR-Cas systems, weapons development could be shortened to weeks, but this is virtually impossible with the current controls in place. The Biological Weapons Convention of 1972 declared the development, production, and stockpiling of bioweapons a war crime. As of August 2019, 183 countries ratified or acceded to the treaty, including China, Russia, Iran, and the United States. Some countries have expressed reservations because the Biological Weapons Convention allows for stockpiling of biological agents and toxins for “prophylactic, protective, or other peaceful purposes.” 13 , 14 For example, smallpox virus is still stored for these reasons at the Centers for Disease Control and Prevention in Atlanta, Georgia, and the Vector Institute in Russia.

Although the United States, Russia, United Kingdom, Syria, Japan, and Iraq have had bioweapon programs in the past, China and Iran have never admitted to a developed program, 12 , 13 , 15 although small-scale production is certainly possible. The US Department of State’s 2020 Compliance Report notes, “The United States does not have sufficient information to determine whether China eliminated its assessed biological warfare program, as required under Article II of the Convention.” 14 Still, the historical effect of bioweapons pales in comparison to the devastation of COVID-19.

Epidemiologic indicators can be used to differentiate between bioweapon attacks and natural outbreaks of disease. The clues include exceptions to geographic or seasonal distribution and unusual presentation of illness for certain populations or age groups. Influenza outbreaks during winter months in northern latitudes are not unusual, but pulmonary anthrax in populated areas of the US East Coast is alarming. COVID-19 does not fit any unnatural indicators. Coronaviruses (and all respiratory viruses) are most common in winter months, as was the case in China in late 2019. Mostly, this results from large numbers of people gathering in enclosed spaces, breathing the same air. In addition, coronaviruses are common in China and derive from animal reservoirs. For SARS-CoV-2, the virus most likely evolved from bats, a finding reported in Nature Medicine . 16 In western China, horseshoe bats are abundant, and consumption of wild animals—part of the region’s culture—is a $76 billion industry; 17 therefore, finding zoonotic diseases is not unusual, as the population interacts regularly with wildlife.

Laboratory Leaks

The second major theory on the origin of the pandemic is that it resulted from a leak at a laboratory performing legitimate research. Considering China’s lack of transparency, concerns about an accidental release of a deadly microbe are understandable, and it has happened before. In 1977, the H1N1 virus was thought to have leaked from a Chinese laboratory. 18 During the first outbreak of SARS in 2004, two accidental releases from a Beijing laboratory were reported to have occurred. 19 In 1979, anthrax spores were released accidentally from a Soviet research facility near Sverdlovsk, Russia. 20 These events provide some background for accidental-release theories for SARS-CoV-2. As reported in Nature Medicine, had there been genetic manipulation, it would have been done with a reverse-genetic system used for betacoronaviruses. 16 The study conclusively showed from genetic data, however, that SARS-CoV-2 did not derive from any previously used viral framework. The authors proposed two explanations for the origin of SARS-CoV-2: “natural selection occurred in an animal host before zoonotic transfer; and natural selection in humans occurred after zoonotic transfer.” Either way, the results effectively eliminated the possibility of a laboratory leak with a genetically manipulated or “enhanced” virus. With an evidence-based approach, the authors described that if this virus came from a laboratory, then it would have signs of human manipulation; however, this virus does not.

Conclusions

From the beginning, the COVID-19 epidemic quickly became a pandemic. The damage still has no end in sight, but there is hope from the early successes of vaccination programs. Ironically, vaccine development received a head start from the same laboratory studying coronaviruses in Wuhan that was suspected of leaking the virus. This laboratory had already sequenced the viral genome and shared its code, thus eliminating months of standard vaccine research. 21 Ultimately, the country where the pandemic started could help to end it. 22 More than ever, experts—physicians, healthcare workers, and community leaders—must continue to acknowledge the threat and encourage calm until the vaccine is available to everyone. Science must guide in a manner that maintains hope and attains the shortest path to normalcy. This will permit coordinated efforts to minimize the current devastation and, in establishing where this pandemic came from, allow for the first step toward preventing such a pandemic from occurring again.

Acknowledgment

The author expresses his sincere gratitude to Marianne Mallia, ELS, MWC, of Scientific Publications at Mayo Clinic for editing support.

Opinions expressed by the author are his own and not necessarily those of the Mayo Clinic, the Southern Medical Association, the Publisher, the Editor, or the editorial staff. These entities are not responsible for the authenticity of the opinions or statements made by the author; only the author is entirely responsible. These entities do not guarantee, warrant, or endorse any product, service, or claim made or advertised in this publication.

The author did not report any financial relationships or conflicts of interest.

The Peer-Review Dilemma

Scientific publication can be a constraining, flattening, and maddening process—but that’s not necessarily a bad thing.

Updated at 11:06 a.m. ET on October 3, 2023

In recent months, two loud public discussions have taken up the question of what scientists really think of their research. “I left out the full truth to get my climate change paper published,” the climatologist Patrick Brown wrote in an essay posted earlier this month, just days after his research had appeared in the journal Nature . The paper’s main finding, that global warming makes extreme wildfires more common, was based on a willful oversimplification of reality, he confessed—and it did not represent his private view that other factors are as or more important.

Another story came out this summer, during the congressional inquiry into COVID’s origins. In this case, House Republicans accused the virologist Kristian Andersen and his colleagues of downplaying the possibility that the coronavirus had leaked out of a lab. A House subcommittee found that the language of a crucial, early paper written by this group that ruled out the “lab-leak theory” had been altered during peer review to make its conclusions “stronger.” Andersen acknowledged that the paper’s blanket dismissal of “any type of laboratory-based scenario” was added in response to comments by the journal’s editor and peer reviewers. But he said this was just part of the normal, iterative scientific process, and that the updated text reflected his beliefs at the time. “The process of peer review means that you incorporate changes, you shorten it down, you make some of the language punchier because you don’t have three sentences to write the same thing, you only have one,” Andersen told investigators. “That’s just part of peer review, scientific publishing.” House Republicans described the publication process differently: as a cover-up . (Of course, some Republicans have seized on the COVID-origins debate for their own political gain.)

Each of these incidents brought demands that the affected papers be retracted —not because they contained fraudulent data or false facts but rather on the grounds that their authors had supposedly been hiding doubts about their own conclusions. Neither paper has been taken down. The editor in chief of Nature did call out Brown’s “poor research practices” and say that the journal is “carefully considering the implications of his stated actions.” (Brown has said that he stands by his research and that “there is nothing explicitly wrong with the paper,” but that “molding the presentation of the research for a high-impact journal made it less useful than it could have been.”) The editor of Nature Medicine , the journal that published Andersen’s paper, said that retraction was unwarranted.

Researchers tend to get into trouble when their published numbers have been faked, or when their math is incorrect. Other matters of dubious judgment—whether pertaining to a study’s design or its interpretation—would fall under the more permissive auspices of scholarly debate. The accusations against Brown and Andersen, however, propose a novel form of misbehavior: the crime of insincerity.

This newly prominent offense aligns with the nation’s mood. In today’s skeptical environment , any outside influence on the work of scientists may be cast as covert manipulation, if not censorship. Brown publicly confessed that he held back his true feelings in order to get the work published in a top journal—that sort of publication is a near-requirement for academic scientists. Prestige periodicals, he claimed, demand obsequious devotion to the most alarming possible narrative about climate change. If he’s right, then peer review—once a means of making scientific work balanced and consensus-driven—now serves to stifle disagreements, and deferring to it would be a form of surrender to establishment elites. The most important aspect of an article would be whether it is heartfelt.

But that is far too simple—and cynical—a way to look at science, which is a muddy, human endeavor. Every study is strategic. Each requires choices about how to design the analysis and explain the results. Yes, Brown made his choices with a particular conclusion in mind, one he thought would be acceptable to scientific gatekeepers. And while Andersen’s COVID-origins paper was in progress, the authors were clearly attuned (like all of us were) to the political environment of early 2020. But their stories are not exceptional . As an academic physician, I’ve contributed to papers for medical journals and fielded the demands of peer reviewers, however parochial they may be. I can’t say that I’ve always held the line on my every belief or conviction. I’ve toned down criticism of professional colleagues. I’ve hewed to the preferred phrasing of my editors. (I’ve also played the part of narrow-minded reviewer myself.)

The academic half of me feels that this represents at most a minor breach of principles: Getting useful data or an interesting idea into the literature is worth a few compromises around the edges. But the physician half becomes indignant at the prospect of insincerity. The framing of a paper helps determine how research is received and understood. Subtle choices in its assumptions, figures, and conclusion may, for instance, encourage readers to believe that the most apocalyptic predictions about climate change are inevitable, or that the lab-leak hypothesis has never been more than a conspiracy theory. Anti-vaccine ideas also gain traction in this way. By tempering their rhetoric and zooming in on discrete claims, vaccine doubters can transform a questionable ideology into a facsimile of healthy skepticism, and publish watered-down versions of their core theories in peer-reviewed medical journals.

Joseph Ladapo, the vaccine-skeptical surgeon general of Florida, has been a prominent user of this motte-and-bailey strategy. He has consistently been a vocal detractor of the COVID shots. He’s called them an “ unsafe medication ” and said he’s not sure that anyone should be getting inoculated this far into the pandemic—yet when his department released a scientific analysis last year suggesting that vaccination may increase the risk of cardiac death, its conclusion was presented with the mealymouthed restraint of formal scientific inquiry: “The risk associated with mRNA vaccination should be weighed against the risk associated with COVID-19 infection,” it said, then cautioned that the results were preliminary. But shortly after putting out these data, Ladapo recommended that all men under 40 avoid the vaccine. If the language in Andersen’s paper was punched up for publication, the language in the surgeon general’s must have been tamped down. (Ladapo’s office did not respond to inquiries.)

Ladapo has faced more scrutiny than other vaccine skeptics because of his influential public post and affiliation with Governor Ron DeSantis. Numerous media outlets have run stories undermining the validity of Florida’s vaccine study, and the Tampa Bay Times obtained draft versions of the paper revealing that, prior to release, results showing that COVID infection posed a greater risk of cardiac death than the vaccines did were removed. Ladapo also cut an analysis showing that the risk of cardiac death to young men from vaccination was not significant. Critics called the changes a “ lie by omission .” A review by a faculty committee at the University of Florida, where Ladapo is a tenured professor, found that he may have violated the school’s research-integrity standards. The committee report did not allege that he had committed “research misconduct” in the classic sense. Instead, it raised the squishier concern that he had engaged in “careless, irregular, and contentious” research practices. (The university declined to investigate, saying that Ladapo’s work as surgeon general was outside their purview.)

Ladapo brushed off the criticism, saying that he had revised the paper based on his scientific expertise. He was simply making choices about how to present his research, and those choices happened to support the conclusion that would be most amenable to a specific audience. Truthfully, his behavior may be dangerous, but it is not all that unusual. A large swath of academic literature could reasonably be described as “careless” or “contentious.” In 2019, I published an article describing how poor methodology in my own field of pathology commonly leads to some of the very same questionable scientific behaviors that the faculty report accused Ladapo of committing. The blowback to Ladapo’s paper—and to Andersen’s and Brown’s—has more to do with ongoing political conflicts than any specific, egregious details of its presentation. No researcher is immune to bias or the impulse to spin their findings in order to advance their private goals. Some are just better at keeping themselves out of the spotlight.

Is scientific insincerity really a problem? Facts, as the saying goes, don’t care about our feelings; science is supposed to be the land of facts. Data are presented, discussed, confirmed, or discredited—all on their own terms. Belief has nothing to do with it, and forensically dissecting an author’s motivations has little practical value. But the public’s skepticism of science remains significant . People want to know what the research community might be keeping from them. Brown’s essay, which accused scientific journals of bias, was published by The Free Press , an outlet devoted to “stories that are ignored or misconstrued in the service of an ideological narrative.” The Free Press ’s science section is awash in references to censorship, deception, and lies. Only bad news is newsworthy in some corners of the media; shady science has become a dominant narrative in its own right.

The Andersen, Brown, and Ladapo controversies suggest that scientists’ personal views—and the way they get run through the publication meat grinder—are likely to remain a source of scandal. When an unpalatable result cannot be dismissed out of hand, we turn to a simpler explanation: human nature. The science is wrong because the scientists are being insincere. It’s too easy to assume that if they’d only tell us what they really think, the facts would be on our side.

The Covid Wuhan lab leak theory is being twisted to validate conspiracy theories

We are hearing a lot about how science and scientists got the lab leak theory wrong . This (mostly) partisan narrative , especially powerful among conservatives , is being used to discredit both science and science-informed public health officials. And it's both misinformed and shortsighted.

This (mostly) partisan narrative is being used to discredit both science and science-informed public health officials.

Unlike what people like Sean Hannity , Tucker Carlson and Alex Jones may lead you to believe, the lab leak theory isn't an I-told-you-so movement. An admission of uncertainty isn't a condemnation of science or a validation of conspiracy theorists . In fact, it is how science works . There are ambiguity, the emergence of new evidence and the shifting of individual and collective perspectives.

Let's start with the reality. Despite both the recognition that a lab leak is theoretically possible and pleas from many world leaders for more transparency from China, it is still far more likely that the coronavirus came from an animal. At this point , we simply don't know the actual source. And we may never know. But more knowledge about the origins (and possible lab safety issues — or lack thereof ) would be valuable to our efforts to address, or perhaps stop, future pandemics. That's why it's sensible to continue to investigate — not because anything has changed from an investigative perspective.

A past position that turns out to be wrong (and we don't know, yet, whether the animal source position is wrong) can still be the correct position to have adopted, given the available evidence, at that time. And a fringe position deemed wrong in the past that turns out to be possibly true doesn't make the postulator of the fringe-y position an all-knowing soothsayer who should be trusted with future decisions. This type of thinking is what steers people toward conspiracy theories.

Let's say a renowned meteorologist uses all the available evidence — satellite imagery, barometric and temperature trends, computer modeling, years of training and experience — to inform a prediction that there is a 95 percent chance of rain tomorrow. Your neighbor thinks that the weather is controlled by a "Big Weather" satellite and that rainy days are a political plot to make us stay inside to work, and his favorite YouTuber says it will be sunny. It turns out to be sunny. Do we give up on meteorology and go with the anti-Big Weather YouTuber?

Part of the problem is that our thinking can be distorted by a kind of hindsight bias ­— that is, our tendency to misremember earlier positions (and why they were held) or that we could have foreseen an event or a conclusion. This is also known as the knew-it-all-along phenomenon. But given the available evidence at the relevant time, you really didn't. It's likely that no one did.

Another problem is that, yes, many public health officials and journalists did a less-than-ideal job talking about the possible causes of the pandemic. The language was often definitive , when it should have reflected the fact that there were (and are) many unknowns. Indeed, both the scientific community and the popular press need to do better jobs generally representing uncertainty and science as a process. Covid-19 should be an important teachable moment for the scientific community and for journalists covering these kinds of science-based stories.

In addition, when a scientific position is altered, that is too often portrayed as some kind of a failure. A recent study found that these science-got-it-wrong representations can erode public trust. On the other hand, portraying science accurately — that is, as a self-correcting problem-solving process that often involves false starts and dead ends — can bolster confidence and increase understanding.

Indeed, representing science better may also help to lessen the chance that a reversal in a scientific position (e.g., about the usefulness of masks) can be weaponized by those who seek to polarize public discourse and discredit science-informed experts.

Representing science better may also help to lessen the chance that a reversal in a scientific position (e.g., about the usefulness of masks) can be weaponized.

It is worth noting that there is a deep irony to conspiracy theorists' pointing to new scientific positions to support their views. Studies have shown that those who believe in conspiracy theories have reduced tendencies to "revise beliefs in the face of disconfirmatory evidence." In other words, they won't alter their positions based on evidence, but they want you to. The truth may be out there, but they aren't changing their minds.

So yes, we absolutely need to keep open minds and constantly question. We do need to make sure that the science is communicated effectively (dogmatic pronouncements one way or another are almost always a mistake). And we do need to make sure science is done well and in a trustworthy manner, including being transparent about conflicts of interest and political pressures that may twist its representation.

Opinion We want to hear what you THINK. Please submit a letter to the editor.

Let me be crystal clear: Early on, the lab leak theory was not handled well. Continued investigation (minus racist overtones , please) is warranted. But public health positions should still be informed by science, not fearmongering or ideologically driven speculation, even if the science-informed decision turns out to be wrong because the science evolves. And even if some outlandish ideologically driven speculation turns out to be true, that doesn't mean giving in to conspiracy theory rants is a rational way to make future decisions.

The truth is out there. And science can nudge us closer.

Timothy Caulfield is a Canada Research Chair in Health Law and Policy at the University of Alberta and author of the  new book  “Your Day, Your Way: The Fact and Fiction Behind Your Daily Decisions” (Running Press, 2020).

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U.S. Intelligence Report Finds No Clear Evidence of Covid Origins in Wuhan Lab

A declassified report says that the illnesses of three laboratory researchers in 2019 do not support or refute the theory that the virus that causes Covid could have slipped out of a lab.

By Julian E. Barnes

Reporting from Washington

Intelligence agencies do not believe the case of three workers from a laboratory in Wuhan, China, who became ill in 2019 can help shed light on whether the Covid-19 pandemic originated from an accidental lab leak, according to a report made public Friday.

The Office of the Director of National Intelligence released a long-awaited declassified report, which included spy agencies’ findings on the so-called lab leak theory, but the material is unlikely to satisfy many people who have been wrestling with the unanswered questions on the origins of the Covid outbreak.

The 10-page report said scientists at the Wuhan Institute of Virology did conduct research on coronaviruses, in some cases had inadequate safety measures and had genetically engineered coronaviruses. But the intelligence agencies said they have found nothing that tells them that work at the laboratory caused the pandemic.

“The I.C. has no information, however, indicating that any W.I.V. genetic engineering work has involved SARS-CoV-2, a close progenitor, or a backbone virus that is closely related enough to have been the source of the pandemic,” the report said, referring to the intelligence agencies’ findings.

The country’s intelligence community, which includes more than a dozen organizations across the government, has been divided over Covid’s origins: Two agencies believe a lab leak was more likely while five others favor natural transmission from an animal market as the most likely cause of the original Covid outbreak. The C.I.A. and another agency remain unable to determine the precise origin of the pandemic, given conflicting intelligence, the report said.

“All agencies continue to assess that both a natural and laboratory-associated origin remain plausible hypotheses to explain the first human infection,” the report said.

The illnesses of the three workers, first made public by the State Department at the end of the Trump administration, has been a focus of researchers, journalists and the intelligence agencies.

In August last year, intelligence agencies concluded that the case of the workers could not help analysts determine whether the lab leak or natural transmission was more likely.

Nevertheless, the case of the three workers has received additional attention in recent days. A Chinese scientist at the Wuhan Institute of Virology worked on coronavirus projects that were funded by the U.S. government and was one of three researchers who became sick in November 2019. However, U.S. intelligence agencies have not determined if the researchers had Covid or another illness with similar symptoms.

The report released on Friday reinforced the intelligence agencies’ views that the workers’ illness could not help shed light on the origins of the pandemic.

The workers fell mildly ill, but the report cast some doubt on Covid as the cause. The report cites findings from the World Health Organization that said investigators with China’s National Security Commission reported blood samples from the sick workers for Covid were negative. It is not clear from the report if intelligence agencies believe the work of the Chinese investigators, but the spy agencies do not believe the workers’ illness can help resolve questions of the pandemic’s origins.

“The I.C. continues to assess that this information neither supports nor refutes either hypothesis of the pandemic’s origins because the researchers’ symptoms could have been caused by a number of diseases and some of the symptoms were not consistent with Covid-19,” the report says.

Both the Trump and Biden administration ordered investigations of Covid’s origins, and intelligence agencies generated hundreds of pages of material. But

After three years of study, some senior U.S. officials have said that the spy agencies are unlikely to come to any satisfactory conclusion , in large measure because China has not cooperated with international inquiries and some officials in Beijing are not interested in digging deeper into the cause of the pandemic.

The new report is the result of a bipartisan law that ordered intelligence agencies to release a declassified version of what they know about whether Covid might have been created inside the Wuhan Institute of Virology and then accidentally escaped from the laboratory.

The report was released on a Friday evening, traditionally a time when administrations put out news they want buried or ignored. Conservatives had criticized the government for failing to meet a deadline of the beginning of the week, though few congressionally mandated reports are delivered precisely on time.

While Biden administration officials have said they have ordered investigations without favoring one theory over another, Republicans have harshly criticized how the White House and its intelligence agencies have investigated Covid’s origins.

“The lab leak is the only theory supported by science, intelligence and common sense,” John Ratcliffe, who served as the director of national intelligence in the Trump administration, said as the report was released Friday, adding: “The Biden administration’s continued obfuscation of Covid origins is a disservice to the intelligence community.”

Julian E. Barnes is a national security reporter based in Washington, covering the intelligence agencies. Before joining The Times in 2018, he wrote about security matters for The Wall Street Journal. More about Julian E. Barnes

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• 25 August 2021

Origins of SARS-CoV-2: window is closing for key scientific studies

• Marion Koopmans 0 ,
• Peter Daszak 1 ,
• Vladimir G. Dedkov 2 ,
• Dominic E. Dwyer 3 ,
• Elmoubasher Farag 4 ,
• Thea K. Fischer 5 ,
• David T. S. Hayman 6 ,
• Fabian Leendertz 7 ,
• Ken Maeda 8 ,
• Hung Nguyen-Viet 9 &
• John Watson 10

Marion Koopmans is head of the Department of Viroscience at Erasmus Medical Center, Rotterdam, the Netherlands.

You can also search for this author in PubMed   Google Scholar

Peter Daszak is president of EcoHealth Alliance, New York City, New York, USA.

Vladimir G. Dedkov is deputy director-general for research at the Pasteur Institute, St Petersburg, Russia.

Dominic E. Dwyer is director of New South Wales Health Pathology’s Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.

Elmoubasher Farag is acting head of communicable-disease control programmes in the Public Health Department, Ministry of Public Health, Doha, Qatar.

Thea K. Fischer is director of clinical research at Nordsjællands University Hospital, Hillerød, Denmark.

David T. S. Hayman is co-director of the Molecular Epidemiology and Public Health Laboratory, Massey University, Palmerston North, New Zealand.

Fabian Leendertz is head of the Epidemiology of Highly Pathogenic Microorganisms group at the Robert Koch Institute, Berlin, Germany.

Ken Maeda is director of the Department of Veterinary Science at the National Institute of Infectious Diseases, Tokyo, Japan.

Hung Nguyen-Viet is co-leader of the Animal and Human Health Programme at the International Livestock Research Institute, Nairobi, Kenya.

John Watson is the former senior medical adviser for Public Health England, UK.

The World Health Organization assembled a team of staff and independent experts tasked with understanding the origins of SARS-CoV-2. Credit: Aly Song/Reuters/Alamy

You have full access to this article via your institution.

Our group was convened by the World Health Organization (WHO) in October 2020. We have been the designated independent international members of a joint WHO–China team tasked with understanding the origins of SARS-CoV-2. Our report was published this March 1 . It was meant to be the first step in a process that has stalled. Here we summarize the scientific process so far, and call for action to fast-track the follow-up scientific work required to identify how COVID-19 emerged, which we set out in this article.

The window of opportunity for conducting this crucial inquiry is closing fast: any delay will render some of the studies biologically impossible. Understanding the origins of a devastating pandemic is a global priority, grounded in science.

The mandate

We, all the members of the international expert team, each submitted detailed, confidential statements to the WHO on potential conflicts of interest, including funding, collaborative studies, public statements and other issues around the origins of COVID-19 that could be perceived as conflicts. After the WHO had reviewed these, team members were appointed in their individual capacity, not as representatives of their employers.

So far, our mission has been guided by terms of reference agreed between the WHO and China in 2020, before our involvement 1 . These terms tasked us with making a detailed reconstruction of the early phase of the pandemic, beginning in Wuhan, China, where the first known cases were reported. Our mandate was to conduct a collaborative study with leading scientists in China to review data they had generated on the basis of initial questions from the WHO. We refined the generic list of questions described in the mandate into a detailed workplan described in the mission report 1 (see also Annex A; go.nature.com/3k26jzx ).

WHO report into COVID pandemic origins zeroes in on animal markets, not labs

The workplan specified eight items: specific retrospective studies detailing the profile of respiratory illness in the general community and hospitalized people in Wuhan and Hubei in the second half of 2019; a review of patient files for 76,000 cases in the same time period that had been notified by 233 Wuhan health centres; a review of death certificates and analysis of those data for possible clusters; and a detailed reconstruction of the investigation into the early outbreak, combining all data and findings from the various groups involved in human, animal and environmental studies (a One Health approach; see go.nature.com/3jy7ekh ). The other four items were: extensive mapping and trace-back of the supply chain of products sold at the Huanan seafood market in Wuhan; testing of a wide range of livestock, wildlife, pets and zoo animals for evidence of infection with SARS-CoV-2; analysis of published and unpublished viral genomic data and linking them with metadata for reconstruction of initial clusters; and a review of relevant literature related to the origins mission.

The possibility of a laboratory origin for the virus’s introduction into the local human population — what has come to be called the lab-leak hypothesis — was not part of the WHO’s original terms of reference for the team.

The mission

This January, we undertook a 28-day mission to Wuhan to interview clinical, laboratory and public-health professionals and visit institutions involved in the early epidemic response and subsequent investigations. Our work was supported by a team of staff from the WHO China office and from WHO headquarters in Geneva, Switzerland; staff from the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE); and a WHO-appointed team leader 1 . The huge burden of preparatory work was shouldered by the team in China, including more than 1,000 health-care professionals who collected, analysed, presented and discussed data and study outcomes during our joint mission.

Scientific discussions between the international and Chinese teams during this mission were lively. Large amounts of information were exchanged on the basis of the work carried out. It took days of discussion to develop recommendations on essential further work and ongoing data sharing. We drafted a model of the potential ‘pathways of emergence’ to structure our thoughts. We listed current evidence for and against these pathways (see Fig. 1 of ref. 1).

We found the laboratory origin hypothesis too important to ignore, so brought it into the discussions with our Chinese counterparts. And we included it as one of the hypotheses for SARS-CoV-2 origin in our report.

Officials collect COVID-19 test samples in a fresh market in China’s Shanxi province in January. Credit: Wei Liang/China News Service/Getty

We had limited time on the ground in Wuhan and a limited mandate. So we prioritized understanding the role of labs in the early days of the epidemic, the overall lab biosafety procedures and potential staff illness or absenteeism owing to respiratory disease in the late part of 2019. We spoke to the leadership and staff at the three Wuhan labs handling coronaviruses: the Wuhan Institute of Virology, the Chinese Center for Disease Control and Prevention (CDC) in Wuhan, and the Hubei provincial CDC. We reviewed published work from these labs to assess their scientific history of working with coronaviruses related to severe acute respiratory syndrome (SARS).

The Chinese team was and still is reluctant to share raw data (for instance, on the 174 cases identified in December 2019), citing concerns over patient confidentiality. Access to data on these cases was not specified in the mandate, although the WHO had demanded it during the investigation, and has done so since . The legal and possible other barriers could not be addressed in the short time frame of our visit. Also, by then, it was clear that the 174 cases were not likely to be the earliest ones, so we considered them less urgent for understanding origins.

It was therefore agreed that a second phase of studies would address these concerns and review these data.

In our joint report 1 , members of both teams concluded unanimously that there was clear evidence of widespread SARS-CoV-2 circulation in Wuhan during December 2019. We reported evidence for earlier emergence but reached no resolution on when, where and how that occurred. We concluded that the Huanan seafood market had a significant role in the early part of the pandemic, and that there were credible links to wild-animal markets to follow up. We agreed that the earliest cases of COVID-19 had probably been missed, as is common for outbreaks of new diseases 2 .

Divisive COVID ‘lab leak’ debate prompts dire warnings from researchers

Our joint report summarized the evidence base that was generated during this first phase of origin tracing. It concluded that there was no definitive proof for or against any of the four proposed pathways: direct zoonotic introduction (through a spillover from wild animals) and three indirect routes of introduction (see Fig. 1 of ref. 1 ). These three are: zoonotic infection from handling infected farmed animals; zoonotic introduction through the consumption of contaminated food or food from infected animals; or introduction through escape from a laboratory working with animal viruses. The report noted that we considered direct introduction or indirect zoonotic introduction through an intermediate host the most plausible.

As laid out in our terms of reference, this initial study was not expected to provide definitive answers to the origin of SARS-CoV-2. Rather, phase 1 was always intended to form the foundation of a longer process of scientific investigation that could last for months or years. Therefore, the report put forward recommendations for phase 2 studies that would follow the evidence and trace back further along the most likely pathways. As a joint WHO–China study report, these recommendations were agreed on by members of both the international and the Chinese team. The report also stated that this assessment could be revised if new evidence became available.

The response

Before the report was released, formal statements to the WHO from some governments were circulated in February, with three contentions: that China had not shared data adequately; that we had paid insufficient attention to the lab-leak hypothesis; and that our scientific conclusions were influenced by China’s political stance regarding transmission through the food chain.

Since its release, our report has received extensive coverage in the popular and scientific press and on social media. Much of this has focused on how we conducted the work, and has critiqued us, our methods and results. Five months on, criticisms of the WHO–China joint study continue to emerge.

When asked, our team has emphasized that much new information was shared by the Chinese team as a result of the agreed studies, and that even more was shared as part of the iterative process between the international and Chinese teams.

A woman pushes a cart at the closed wholesale seafood market in Wuhan, China, last January. Credit: Getty

Our critics have also suggested that the report dismisses the possibility of a lab leak. A laboratory origin hypothesis is presented in the pathway model in Figure 5 on page 119 of the report; we explicitly state in the report that it is possible. We held frank discussions with key scientists in the relevant Wuhan institutions — a line of inquiry that exceeded our original mandate. When we reviewed the responses to our questions on this issue, and all other available data, we found no evidence for leads to follow up; we reported this fact.

In our report, we state that if evidence supporting any of the hypotheses becomes known following publication, phase 2 studies should carefully examine this. For instance, we described that there was evidence of the presence of live animals in the market at the end of December 2019, but that the data presented to the team did not show definitive evidence of live mammals. This evidence came to light after publication 3 (as we discuss in more detail later in this article).

Another criticism was that the potential for introduction of SARS-CoV-2 through frozen food was included owing to pressure from China. The report addressed this hypothesis for three reasons: analysis showed that frozen food imported from all over the world was sold at the Wuhan market, including frozen wild-animal meat; foodborne viral-disease outbreaks are widely documented, including occasionally from frozen foods; and SARS-CoV-2 can remain infectious when frozen 4 . Therefore, the team felt it could not rule out introduction from undercooked meat from infected animals.

Some of the public discourse around the report probably originates from miscommunication and misunderstanding about the nature of the work. Although the published report correctly calls it a joint study to reflect what was laid out in the World Health Assembly resolution and terms of reference, it was publicly called an investigation by journalists, by representatives from some member states and, on occasion, by representatives of the WHO. This might have led to expectations that the report would provide watertight evidence based on formal audits of the institutes involved in the studies.

There have been calls from scientists for further investigation of the lab-leak hypothesis 5 . And there has been a wave of media items that give equivalence to the weight of evidence for a lab leak and for emergence through an intermediate host — an equivalence that the currently available data do not support, in our view.

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

The arguments and data for a zoonotic spillover event were summarized in a review published as a July preprint by a group of scientists who were not part of the international team 6 . That review includes new data released since the report, on SARS-CoV-2-related coronaviruses in bats in China’s Yunnan province 7 , 8 and an inventory of live mammals for sale in Wuhan markets up until November 2019, some of which could have theoretically been able to harbour SARS-related coronaviruses 3 . This inventory, compiled by scientists from the United Kingdom, Canada and China, would have been welcomed by the team had it been available earlier; it needs to be taken up in the phase 2 studies.

In June, a preprint 9 was published analysing genomic data that had been deleted after March 2020 from the database of the US National Center for Biotechnology Information at the request of the scientists from China who generated the information (that team had published its findings based on the raw data in June 2020 10 ). Our colleagues in China contacted the authors of the June 2020 paper, retrieved the data and added them to the SARS-CoV-2 genome phylogenetic data published in our report. The data were from people who had an onset of illness in January, so they did not contribute any new information to the origins question.

In the report, and since, we have publicly called for any data supporting the lab-leak hypothesis to be published and submitted to the WHO. None has, so far.

Six priorities

To keep up the momentum for phase 2 studies, our team has met weekly since the publication of the joint report. We have continued collaboration with our Chinese co-authors, including work on a list of corrections to the phase 1 report. Both the international team and the Chinese team have now put forward to the WHO priorities for phase 2 studies, developed from the recommendations in the joint report.

The international team listed the following priorities:

Further trace-back studies. On the basis of disease reporting, look for early COVID-19 cases in all regions inside and outside China that have the earliest evidence for SARS-CoV-2 circulation.

Antibody surveys. Use standardized methods in the regions that have the earliest evidence for SARS-CoV-2 circulation (inside and outside China) to identify any places where infections occurred that were not observed through disease reporting.

Trace-back and community surveys. These will need to be conducted at sites of wildlife farms that supplied animals to markets in Wuhan in the months before human cases were recognized (inside and outside China, depending on supply-chain analysis).

Risk-targeted surveys of possible hosts. Assess wild bats and other potential reservoirs or intermediate hosts in China and neighbouring countries, and selected high-risk farmed animals (including those farmed for fur), for evidence of exposure.

Detailed risk-factor analysis. Analyse pockets of earlier cases evidenced from the antibody surveys or other studies, and conduct an assessment of all possible exposures.

Follow-up. Investigate any credible new leads.

The search for the origins of SARS-CoV-2 is at a critical juncture. There is willingness to move forward from both the WHO international team and the Chinese team.

Crucially, the window is rapidly closing on the biological feasibility of conducting the critical trace-back of people and animals inside and outside China. SARS-CoV-2 antibodies wane, so collecting further samples and testing people who might have been exposed before December 2019 will yield diminishing returns. Chinese wildlife farms employ millions of people (14 million, according to a 2016 census 11 ) and supplied live mammals to cities across China, including Wuhan 3 . In response to the SARS-CoV-2 pandemic, many of these farms are now closed and the animals have been culled, making any evidence of early coronavirus spillover increasingly difficult to find.

In July, four months after the full report and five months after our debriefing, the WHO informed member states of plans to create a committee that will oversee future origins studies. We are pleased to see both this and its implication that outbreak investigations will be conducted routinely, rather than in an ad hoc manner that could be perceived as politically motivated or with potentially punitive goals.

However, applying this new process to the continuing SARS-CoV-2 origins mission runs the risk of adding several months of delay. Member-state representatives would need to negotiate detailed terms around the sensitive issue of investigating laboratory practices, then nominate and select team members, who would then have to develop a work plan.

Therefore, we call on the scientific community and country leaders to join forces to expedite the phase 2 studies detailed here, while there is still time.

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Competing Interests

M.K. has received funding from the WHO for a specific study on infections in animals, and has had collaboration with CDC Guangdong in her role as an unpaid adviser on public health surveillance for emerging diseases. P.D. has conducted collaborative studies with a range of organizations in China listed in published papers, including the Wuhan Institute of Virology, and this work was funded by the NIH and USAID. K.M. has received funding from the Japanese Agency for Medical Research and Development for collaboration on infectious-diseases research with the Chinese Academy of Sciences. P.D. is a member of the Lancet COVID-19 Commission Task Force on Origins, Early Spread, and One Health Implications of COVID-19. D.E.D. and M.K. have consulted with the WHO in China as part of GOARN activities for SARS.

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US shared ‘gobsmacking’ Covid lab leak file with UK

T he US shared “gobsmacking” evidence with Britain at the height of the Covid pandemic suggesting a “high likelihood” that the virus had leaked from a Chinese lab , The Telegraph can reveal.

In January 2021, Five Eyes intelligence-sharing nations were convened to discuss the possibility of a lab leak as the US warned that China had covered up research on coronaviruses and military activity at a laboratory in Wuhan .

In a previously unreported phone call that month, Mike Pompeo, the former US secretary of state, presented evidence that supported the lab leak theory to Dominic Raab, then the Foreign Secretary, and representatives from Canada, New Zealand and Australia.

Speaking to The Telegraph, two Trump administration officials accused Mr Raab and the UK Government of ignoring the lab leak theory because of resistance from government scientists who supported the explanation that the virus had jumped between animals and humans .

Mr Pompeo presented a summary of classified American intelligence reports collected in the early days of the pandemic and compiled by the State Department. The intelligence reports themselves are understood to have been shared separately with the UK via the Five Eyes network between October and December 2020.

“We saw several pieces of information and thought that they were, frankly, gobsmacking,” said one former official who worked on the intelligence that informed Mr Pompeo’s report. “They obviously pointed to the high likelihood that this was indeed a lab leak.”

In one document, which has since been released by the State Department under Freedom of Information laws, US officials warned of “consistent stonewalling” by China after the virus was first discovered and accused local officials of “gross corruption and ineptitude”.

The research revealed for the first time that Chinese military officials had worked with the Wuhan Institute of Virology in the years leading up to the pandemic, and that some researchers at the lab had become ill shortly before the virus was first recorded nearby.

It also showed that Chinese scientists had carried out “gain of function” research at the institute, which has since become a key piece of evidence for the lab leak theory .

The theory has become a divisive topic among scientists and government officials in the years following the pandemic and has prompted two investigations by the World Health Organisation, which China has been accused of obstructing .

British government ministers including Boris Johnson initially dismissed the possibility that Covid had been created by scientists, arguing in June 2021 that “the advice that we have had is that it doesn’t look as though this particular disease of zoonotic origin came from a lab”.

Two former officials claimed the UK had ignored the evidence presented by the US because ministers saw the lab leak claims as a “radioactive American political issue” fuelled by public disagreement between government scientists and Donald Trump.

“Once the thing became fundamentally political, the ability to pursue it internationally really just collapsed because no one else was interested in touching it,” said one of the officials. “I think [Five Eyes] were kind of annoyed by the way the issue had become treated in US politics.”

Both separately named Sir Jeremy Farrar , a member of the Government’s Scientific Advisory Group for Emergencies as one of the leading opponents of the lab leak theory within the British government.

A majority of scientific experts have long said that they believe an animal to human interaction was the most likely cause of the first infection.

However, some Government figures, including Michael Gove, have since said that they believe the virus was “man-made” .

In November, Mr Gove told the Covid Inquiry that there was a “significant body of judgment that believes that the virus itself was man-made – and that presents its own set of challenges”.

Both the FBI and US Department of Energy have said they believe a lab leak is the most likely cause of Covid, while other agencies have said they think it occurred naturally.

Joe Biden, the US president, has said he does not know where the virus started, while the US National Intelligence Council said last year it “probably emerged and infected humans through an initial small-scale exposure”.

UK ministers are now facing calls to expand the terms of the Covid Inquiry to include an investigation into the origin of the virus .

The Telegraph understands that the call in Jan 2021 was deliberately held on an “open line” without security encryption in the hope that Chinese intelligence agencies would hear that Western countries were aware of military activity in Wuhan.

“We did that deliberately…we wanted to put pressure on the bad guys,” said a State Department source.

Ten days after the call, in which officials said the UK was unwilling to assist with a US-led lab leak investigation or share its own research, the summary compiled by Mr Pompeo’s officials was released to the public in a “fact sheet”.

Those involved in the release said they took care to avoid revealing the sources or methods of US spy agencies, and that it was just the “tip of the iceberg” of the underlying intelligence that had been gathered.

A UK government spokesman said: “There are still questions that need to be answered about the origin and spread of Covid-19, not least so we can ensure we are better prepared for future pandemics. 

“The UK continues to support the World Health Organisation in its expert study of the origins of Covid-19. It is important that China and other countries cooperate fully with the researchers.”

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