新冠病毒源頭

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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.

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. 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.”

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.

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 letterto 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.”

共產檔

The Lab-Leak Hypothesis

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

Flask Monsters

“A Reasonable Chance”

“No Credible Evidence”

“Is It a Complete Coincidence?”

“A Serious Shortage of AppropriatelyTrained Technicians”

Emergence

“I Had Not Slept a Wink”

“ ‘Bug to Drug’ in 24 Hours”

“Weapons of Mass Disruption”

“Risky Areas for Spillover”

“Lab-Made?”

“A New, Non-Natural Risk”

“Proximity Is a Problem”

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