Gain Of Function
New York magazine|January 4-17, 2021
How much risk of an accidental pandemic is too much?
By Nicholson Baker

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 broadspectrum 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.

II.

“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.”

Accidents Do Happen

A sampling of lab leaks over the decades.

1951

ANTHRAX | Fort Detrick, Maryland

An Army microbiologist became infected while performing research with anthrax and died. The Army gave “acute bronchial pneumonia” as his cause of death, later revealed to have been an anthrax infection.

1958

ANTHRAX | Fort Detrick

An electrician became sick with and died of what the Army described as “respiratory disease.” Later reporting by the New York Times disclosed that his death certificate read “Myocardial failure with antecedent visceral anthrax.”

1964

BOLIVIAN HEMORRHAGIC FEVER | Fort Detrick

An animal caretaker died after a two-week struggle with “an illness” later revealed to have been Bolivian hemorrhagic fever.

1978

SMALLPOX | Birmingham, England

A photographer at Birmingham Medical School contracted smallpox from a lab on campus studying the recently eradicated virus. Days before the photographer died from the disease, the lab director died by suicide.

2003

SARS | Singapore

A Ph.D. student studying West Nile virus became ill after being left to work unsupervised in a BSL-3 laboratory. The student tested positive for a mild case of SARS, and no one else was infected.

2003

SARS | Taipei, Taiwan

A researcher in a BSL-4 laboratory at the National Defense University developed a respiratory illness after cleaning up a spill without full protective equipment. He traveled to Singapore and back before becoming sick, then tested positive for SARS six days after returning to Taiwan.

2004

SARS-CoV | Beijing, China

Two researchers at China’s CDC became sick after working with a SARS antigen. The antigen had not been properly inactivated, and two other staff members contracted the virus, as did seven external contacts, one of whom died.

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 rightwing 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.”

How Did It Get Out?

1.The Tongguan Mine Shaft in Mojiang, Yunnan, where, in 2013, fragments of RaTG13, the closest known relative of SARS- CoV-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 for unspecified reasons.

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.

MAP BY JASON LEE

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.

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, who works for Consortium News. 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?”

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