The Lab-Leak Hypothesis For decades, scientists have been hot-wiring viruses in hopes of preventing a pandemic, not causing one. But what if …?
by Nicholson Baker
New York Magazine
January 4, 2021
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Illustration: Illustration by Robert Beatty for New York Magazine
I. 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.
-- A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic [W/Comments], by Jonathan Latham, PhD and Allison Wilson, PhD
-- 2019 Global Health Security Index: Building Collective Action and Accountability, by Nuclear Threat Initiative, Center for Health Security, Johns Hopkins Bloomberg School of Public Health, and The Economist Intelligence Unit
-- Is Considering a Genetic-Manipulation Origin for SARS-CoV-2 a Conspiracy Theory That Must Be Censored?, by Rossana Segreto, University of Innsbruck, and Yuri Deigrin, Youthereum Genetics Inc.
-- Laboratory Escapes and “Self-fulfilling prophecy” Epidemics, by Martin Furmanski MD, Scientist’s Working Group on Chemical and Biologic Weapons, Center for Arms Control and Nonproliferation, February 17, 2014
-- Master's Thesis: "The Analysis of Six Patients With Severe Pneumonia Caused By Unknown Viruses", by Li Xu, No. 1 School of Clinical Medicine, Kun Ming Medical University, May, 2013
-- Risk and Benefit Analysis of Gain of Function Research, Final Report, April 2016, by Gryphon Scientific
-- Did the SARS-CoV-2 virus arise from a bat coronavirus research program in a Chinese laboratory? Very possibly, by Milton Leitenberg
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. While the first documented case of SARS was in November 2002, it became a pandemic in 2003, and the WHO issued its first alert about the virus in March of that year, 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.
-- Danger of Potential-Pandemic-Pathogen Research Enterprises, by Lynn C. Klotz
-- Human error in high-biocontainment labs: a likely pandemic threat, by Lynn Klotz
-- Is there a Role for the States Parties to the BWC in Oversight of Lab-created Potential Pandemic Pathogens?, by Lynn C. Klotz, PhD
-- Letter to The NSABB Board [U.S. National Science Advisory Board for Biosecurity], by Lynn C. Klotz, Ph.D., Senior Science Fellow and member of the Scientist Working Group on Biological and Chemical Weapons Center for Arms Control and Non-proliferation, Washington, DC, USA
-- The consequences of a lab escape of a potential pandemic pathogen, by Lynn C. Klotz, The Center for Arms Control and Non-Proliferation, Washington, DC, USA; and Edward J. Sylvester, Science and Medical Journalism, Walter Cronkite School of Journalism and Mass Communication, Arizona State University, Phoenix, AZ, USA
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.
II. “A Reasonable Chance”
Seeking Ebola strains in Sierra Leone’s wild-animal population for USAID’s Predict project in 2018. Photo: Simon Townsley
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.
-- A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence, by Vineet D Menachery, Boyd L Yount Jr, Kari Debbink, Sudhakar Agnihothram, Lisa E Gralinski, Jessica A Plante, Rachel L Graham, Trevor Scobey, Xing-Yi Ge, Eric F Donaldson, Scott H Randell, Antonio Lanzavecchia, Wayne A Marasco, Zhengli-Li Shi & Ralph S Baric
-- Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response, by Lei-Ping Zeng, Yu-Tao Gao, Xing-Yi Ge, Qian Zhang, Cheng Peng, Xing-Lou Yang, Bing Tan, Jing Chen, Aleksei A. Chmura, Peter Daszak, and Zheng-Li Shi
-- Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus, by Ben Hu, Data curation, Formal analysis, Investigation, Validation, Visualization, Writing – original draft,#1 Lei-Ping Zeng, Investigation, Methodology, Xing-Lou Yang, Investigation, Resources, Xing-Yi Ge, Formal analysis, Resources, Wei Zhang, Investigation, Bei Li, Investigation, Jia-Zheng Xie, Investigation, Xu-Rui Shen, Investigation, Yun-Zhi Zhang, Resources, Ning Wang, Investigation,1 Dong-Sheng Luo, Investigation, Resources,1 Xiao-Shuang Zheng, Investigation, Mei-Niang Wang, Resources,1 Peter Daszak, Funding acquisition, Writing – review & editing, Lin-Fa Wang, Conceptualization, Funding acquisition, Writing – review & editing, Jie Cui, Conceptualization, Formal analysis, Funding acquisition, Software, Writing – review & editing, and Zheng-Li Shi, Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Visualization, Writing – review & editing
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 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.”
III. “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.”
You know Ralph, I think the public has not been in on this debate. It has been a secret debate with the NIH and other people who funded it. I think COVID-19 is a product of this. And I know Trump wants to call it the China virus. Well, the money that went into the creation and the genetic engineering of these coronaviruses in Wuhan was supported by the NIH and the USAID. So why wouldn't it be the NIH virus, or the USAID virus?
-- Interview with Andrew Kimball on the Ralph Nader Radio Show
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.
[O]n April 16th Peter Daszak, who is the President of the EcoHealth Alliance, told Democracy Now! in a lengthy interview that the lab escape thesis was “Pure baloney”. He told listeners:
“There was no viral isolate in the lab. There was no cultured virus that’s anything related to SARS coronavirus 2. So it’s just not possible...”
Daszak is the named principal investigator on multiple US grants that went to the Shi lab at WIV. He is also a co-author on numerous papers with Zheng-Li Shi, including the 2013 Nature paper announcing the isolation of coronavirus WIV-1 through passaging (Ge et al., 2013). One of his co-authorships is on the collecting paper in which his WIV colleagues placed the four fully functional bat coronaviruses into human cells containing the ACE2 receptor (Hu et al. 2017). That is, Daszak and Shi together are collaborators and co-responsible for most of the published high-risk collecting and experimentation at the WIV.
If the Shi lab has anything to hide, it is not only the Chinese Government that will be reluctant to see an impartial investigation proceed. Much of the work was funded by the US taxpayer, channeled there by Peter Daszak and the EcoHealth Alliance. Virtually every credible international organisation that might in principle carry out such an investigation, the WHO, the US CDC, the FAO, the US NIH, including the Gates Foundation, is either an advisor to, or a partner of, the EcoHealth Alliance. If the Sars-CoV-2 outbreak originated from the bat coronavirus work at the WIV then just about every major institution in the global public health community is implicated.
-- The Case Is Building That COVID-19 Had a Lab Origin, by Jonathan Latham, PhD and Allison Wilson, PhD
From 2004 on, the WIV published many dozens of partial or full genome sequences of coronaviruses in their collection. On June 1, Daszak and Shi published partial genetic sequences of 781 Chinese bat coronaviruses, more than one-third of which had never been published previously.36 There are also multiple published records of animal infection research with bat coronaviruses at the WIV. In order to carry out the research program described above, the WIV laboratory needs to use live viruses, and not just RNA fragments. This contradicts two of the assertions, made by some commentators, that Shi worked only with RNA fragments and that her laboratory did not maintain live viruses. On May 24, 2020, the director of the WIV acknowledged that the laboratory did have “three live strains of bat corona viruses on site,” but implied only three.37 Knowledgeable virologists assume that the number must be much higher, probably hundreds of live viral isolates.38
It is precisely in the course of the kind of gain of function research that the WIV conducted that there would be the greatest likelihood of infection of a laboratory researcher.
-- Did the SARS-CoV-2 virus arise from a bat coronavirus research program in a Chinese laboratory? Very possibly, by Milton Leitenberg
How Did It Get Out? 1. The Tongguan Mine Shaft in Mojiang, Yunnan, where, in 2013, fragments of RaTG13, the closest known relative of SARSCoV-2, were recovered and transported to the Wuhan Institute of Virology; 2. The Wuhan Institute of Virology, where Shi Zhengli’s team brought the RaTG13 sample, sequenced its genome, then took it out of the freezer several times in recent years; 3. The Wuhan Center for Disease Control and Prevention, which first reported signs of the novel coronavirus in hospital patients; 4. The Huanan Seafood Wholesale Market, an early suspected origin of the pandemic, where the first major outbreak occurred. Illustration: Map by Jason Lee
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.”
At first glance RaTG13 is unlikely to have evolved into SARS-CoV-2 since RaTG13 is approximately 1,200 nucleotides (3.8%) different from SARS-CoV-2. Although RaTG13 is the most closely related virus to SARS-CoV-2, this sequence difference still represents a considerable gap. In a media statement evolutionary virologist Edward Holmes has suggested this gap represents 20-50 years of evolution and others have suggested similar figures.
We agree that ordinary rates of evolution would not allow RaTG13 to evolve into SARS-CoV-2 but we also believe that conditions inside the lungs of the miners were far from ordinary. Five major factors specific to the hospitalised miners favoured a very high rate of evolution inside them.
i) When viruses infect new species they typically undergo a period of very rapid evolution because the selection pressure on the invading pathogen is high. The phenomenon of rapid evolution in new hosts is well attested among corona- and other viruses (Makino et al., 1986; Baric et al., 1997; Dudas and Rambaut 2016; Forni et al., 2017).
ii) Judging by their clinical symptoms such as the CT scans, all the miner’s infections were primarily of the lungs. This localisation likely occurred initially because the miners were exerting themselves and therefore inhaling the disturbed bat guano deeply. As miners, they may already have had damaged lung tissues (patient 3 had suspected pneumoconiosis) and/or particulate matter was present that irritated the tissues and may have facilitated initial viral entry.
In contrast, standard coronavirus infections are confined to the throat and upper respiratory tract. They do not normally reach the lungs (Perlman and Netland, 2009). Lungs are far larger tissues by weight (kilos vs grammes) than the upper respiratory tract. There was therefore likely a much larger quantity of virus inside the miners than would be the case in an ordinary coronavirus infection.
Comparing a typical coronavirus respiratory tract infection with the extent of infected lungs in the miners from a purely mathematical point of view indicates the potential scale of this quantitative difference. The human aerodigestive tract is approximately 20cm in length and 5cm in circumference, i.e. approximately 100 cm2 in surface area. The surface area of a human lung ranges from 260,000-680,000 cm2(Hasleton, 1972). The amount of potentially infected tissue in an average lung is therefore approximately 4500-fold greater than that available to a normal coronavirus infection. The amount of virus present in the infected miners, sufficient to hospitalise all of them and kill half of them, was thus proportionately very large.
Evolutionary change is in large part a function of the population size. The lungs of the miners, we suggest, supported a very high viral load leading to proportionately rapid viral evolution.
Furthermore, according to the Master’s thesis, the immune systems of the miners were compromised and remained so even for those discharged. This weakness on the part of the miners may also have encouraged evolution of the virus.
iii) The length of infection experienced by the miners (especially patients 2, 3 and 4) far exceeded that of an ordinary coronavirus infection. From first becoming too sick to work in the mine, patient 2 survived 57 days until he died. Patient 3 survived 120 days after stopping work. Patient 4 survived 117 days and then was discharged as cured. Each had been exposed in the mine for 14 days prior to the onset of severe symptoms; thus each presumably had nascent infections for some time before calling in sick (See Table 2 of the thesis).
In contrast, in ordinary coronavirus infections the viral infection is cleared within about ten to fourteen days after being acquired (Tay et al., 2020). Thus, unlike most sufferers from coronavirus infection, the hospitalised miners had very long-term bouts of disease characterised by a continuous high load of virus. In the cases of patients 3 and 4 their illnesses lasted over 4 months.
iv) Coronaviruses are well known to recombine at very high rates: 10% of all progeny in a cell can be recombinants (Makino et al., 1986; Banner and Lai, 1991; Dudas and Rambaut, 2016). In normal virus evolution the mutation rate and the selection pressure are the main foci of attention. But in the case of a coronavirus adapting to a new host where many mutations distributed all over the genome are required to fully adapt to the new host, the recombination rate is likely to be highly influential in determining the overall speed of adaptation by the virus population (Baric et al., 1997).
Inside the miners a large tissue was simultaneously infected by a population of poorly-adapted viruses, with each therefore under pressure to adapt. Even if the starting population of virus lacked any diversity, many individual viruses would have acquired mutations independently but only recombination would have allowed these mutations to unite in the same genome. To recombine, viruses must be present in the same cell. In such a situation the particularities of lung tissues become potentially important because the existence of airways (bronchial tubes, etc.) allows partially-adapted viruses from independent viral populations to travel to distal parts of the lung (or even the other lung) and encounter other such partially-adapted viruses and populations. This movement around the lungs would likely have resulted in what amounted to a passaging effect without the need for a researcher to infect new tissues. Indeed, in the Master’s thesis the observation is several times made that areas of the lungs of a specific patient would appear to heal even while other parts of the lungs would become infected.
v) There were also a number of unusual things about the bat coronaviruses in the mine. They were abnormally abundant but also there were many different kinds, often causing co-infections of the bats (Ge et al., 2016). Viral co-infections are often more infectious or more pathogenic (Latham and Wilson, 2007).
As the WIV researchers remarked about the bats in the mine:“we observed a high rate of co-infection with two coronavirus species and interspecies infection with the same coronavirus species within or across bat families. These phenomena may be owing to the diversity and high density of bat populations in the same cave, facilitating coronavirus intra- and interspecies transmissions, which may result in recombination and acceleration of coronavirus evolution.” (Ge et al., 2016).
The diversity of coronaviruses in the mine suggests that the miners were similarly exposed and that their illness may potentially have begun as co-infections.
Combining these observations, we propose that the miners’ lungs offered an unprecedented opportunity for accelerated evolution of a highly bat-adapted coronavirus into a highly human-adapted coronavirus and that decades of ordinary coronavirus evolution could easily have been condensed into months. However, we acknowledge that these conditions were unique.
-- A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic, by Jonathan Latham, PhD and Allison Wilson, PhD
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.”
U.S. intelligence, after originally asserting that the coronavirus had occurred naturally, conceded last month that the pandemic may have originated in a leak from the Wuhan lab.
-- Dr. Fauci Backed Controversial Wuhan Lab with U.S. Dollars for Risky Coronavirus Research, by Fred Guterl, Newsweek
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.
IV. “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.”
V. “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.”
I’m just asking, Is it a complete coincidence that this outbreak happened in the one city in China with a BSL-4 lab?
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.
Two years before the novel coronavirus pandemic upended the world, U.S. Embassy officials visited a Chinese research facility in the city of Wuhan several times and sent two official warnings back to Washington about inadequate safety at the lab, which was conducting risky studies on coronaviruses from bats...
What the U.S. officials learned during their visits concerned them so much that they dispatched two diplomatic cables categorized as Sensitive But Unclassified back to Washington. The cables warned about safety and management weaknesses at the WIV lab and proposed more attention and help. The first cable, which I obtained, also warns that the lab’s work on bat coronaviruses and their potential human transmission represented a risk of a new SARS-like pandemic.
“During interactions with scientists at the WIV laboratory, they noted the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory,” states the Jan. 19, 2018, cable, which was drafted by two officials from the embassy’s environment, science and health sections who met with the WIV scientists. (The State Department declined to comment on this and other details of the story.)
The Chinese researchers at WIV were receiving assistance from the Galveston National Laboratory at the University of Texas Medical Branch and other U.S. organizations, but the Chinese requested additional help. The cables argued that the United States should give the Wuhan lab further support, mainly because its research on bat coronaviruses was important but also dangerous.
As the cable noted, the U.S. visitors met with Shi Zhengli, the head of the research project, who had been publishing studies related to bat coronaviruses for many years. In November 2017, just before the U.S. officials’ visit, Shi’s team had published research showing that horseshoe bats they had collected from a cave in Yunnan province were very likely from the same bat population that spawned the SARS coronavirus in 2003.
“Most importantly,” the cable states, “the researchers also showed that various SARS-like coronaviruses can interact with ACE2, the human receptor identified for SARS-coronavirus. This finding strongly suggests that SARS-like coronaviruses from bats can be transmitted to humans to cause SARS-like diseases. From a public health perspective, this makes the continued surveillance of SARS-like coronaviruses in bats and study of the animal-human interface critical to future emerging coronavirus outbreak prediction and prevention.”
The research was designed to prevent the next SARS-like pandemic by anticipating how it might emerge. But even in 2015, other scientists questioned whether Shi’s team was taking unnecessary risks. In October 2014, the U.S. government had imposed a moratorium on funding of any research that makes a virus more deadly or contagious, known as “gain-of-function” experiments...
“The cable tells us that there have long been concerns about the possibility of the threat to public health that came from this lab’s research, if it was not being adequately conducted and protected,” he said.
There are similar concerns about the nearby Wuhan Center for Disease Control and Prevention lab, which operates at biosecurity level 2, a level significantly less secure than the level-4 standard claimed by the Wuhan Insititute of Virology lab, Xiao said. That’s important because the Chinese government still refuses to answer basic questions about the origin of the novel coronavirus while suppressing any attempts to examine whether either lab was involved.
Sources familiar with the cables said they were meant to sound an alarm about the grave safety concerns at the WIV lab, especially regarding its work with bat coronaviruses. The embassy officials were calling for more U.S. attention to this lab and more support for it, to help it fix its problems.
“The cable was a warning shot,” one U.S. official said. “They were begging people to pay attention to what was going on.”
No extra assistance to the labs was provided by the U.S. government in response to these cables. The cables began to circulate again inside the administration over the past two months as officials debated whether the lab could be the origin of the pandemic and what the implications would be for the U.S. pandemic response and relations with China.
Inside the Trump administration, many national security officials have long suspected either the WIV or the Wuhan Center for Disease Control and Prevention lab was the source of the novel coronavirus outbreak. According to the New York Times, the intelligence community has provided no evidence to confirm this. But one senior administration official told me that the cables provide one more piece of evidence to support the possibility that the pandemic is the result of a lab accident in Wuhan.
“The idea that it was just a totally natural occurrence is circumstantial. The evidence it leaked from the lab is circumstantial. Right now, the ledger on the side of it leaking from the lab is packed with bullet points and there’s almost nothing on the other side,” the official said.
-- State Department cables warned of safety issues at Wuhan lab studying bat coronaviruses, by Josh Rogin, The Washington Post, April 14, 2020
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.