On a foggy morning in early February last year, dozens of journalists from around the world gathered outside the Wuhan Institute of Virology. Some walked around to find the best camera position; others climbed a ladder to peer into the fenced-off compound, its tall red-brick buildings hidden behind a thick mist. Security guards in blue uniforms lined the winding driveway leading to the entrance.
The crowd was gathered because a team of international disease detectives selected by the World Health Organization (WHO) to hunt for the origins of covid-19 was on its way to visit.
“They will be here in a minute,” a journalist working for Japan’s Tokyo Broadcasting System Television said after checking her phone. Her voice was brisk and slightly shaken; her eyes sparkled with nervous excitement. “My colleagues just told me. They’re chasing the WHO cars.”
Soon enough, the motorcade burst through the fog. As it approached the institute’s main gate, a journalist in a blue down jacket and white face mask sprinted alongside as if he were running for his life, pointing a video camera toward the cars, his rucksack bouncing up and down on his back. A dozen photographers flocked to the lead car, pushing against one another and forcing the convoy to a stop. The guards tried herding them away to get the cars moving again. “Comments, please!” several journalists shouted.
Inside the car, Peter Daszak—a disease ecologist and president of the EcoHealth Alliance, a New York-based nonprofit that works with scientists around the world to study viruses in wildlife—was filming the scene on his cell phone.
He was a member of the WHO team, and when we’d spoken the week before, he’d cautioned that the Wuhan trip was just a first step in trying to figure out where covid-19 came from. “It can take years or even decades to find the cause of a new infectious disease,” said Daszak, who has collaborated with the Wuhan Institute of Virology for more than 15 years and is now himself caught up in the debate over the disease’s origins. “Sometimes we just never know.”
But the world wanted quick answers.
The institute holds a critical place in the story of the covid-19 pandemic. A leading center for coronavirus research, it was the first facility to isolate the new virus, and the first to sequence its genome. One of its labs, led by virologist Shi Zhengli, focuses on coronaviruses that live in bats, and has spent years sequencing viral genomes, isolating live viruses, and—through genetic mixing and matching—trying to understand how they may evolve to gain the ability to infect humans. Over the past 18 years, her team has collected more than 20,000 samples from bat colonies across China.
Shi’s work, which has earned her the nickname China’s bat woman, has been at the center of controversy. Some have suggested that her bat samples could be the source of the covid-19 virus, which scientists call SARS-CoV-2. They have claimed that the virus could have hitched a ride to Wuhan by infecting one of her team members in their fieldwork collecting samples from bats. Or, some speculate, the live viruses her team cultured in the lab, including—more worryingly—the ones they created by genetic tinkering, could be the source of the pandemic.
All eyes were on the WHO, the leading international public health agency, to probe covid-19’s origins. The team’s mission was to examine when and where the outbreak had started and how the new virus crossed over to humans. The report, which was released last March, concluded it was “extremely unlikely” that covid-19 could have been caused by a lab accident. The situation the team ranked most likely was that it had jumped from bats to humans via some intermediary animal. Their results, supported by research published in peer-reviewed journals and by ongoing studies, suggest that the pandemic probably started at the Huanan Seafood Wholesale Market in central Wuhan, where live mammals were sold and where most of the early covid-19 cases emerged.
Not everybody agrees, but the majority of virologists and infectious-disease experts, especially those working directly on the origins question, lean toward that theory, barring the emergence of new evidence that persuades them otherwise.
Spillover from animals to humans “was how almost every major epidemic got started in the past decades,” says Shi’s longtime collaborator Linfa Wang, an expert on emerging infectious diseases at the Duke–National University of Singapore Medical School and a member of the WHO team that in 2003 investigated the origins of SARS, a deadly infectious disease caused by a coronavirus now known as SARS-CoV-1. That illness sickened 8,000 people worldwide and killed nearly 800 between 2002 and 2004. “It’s a common and well-documented pathway,” he says.
But one year after the WHO’s visit to Wuhan, the disease detectives have yet to find the guilty animal or other indisputable evidence of natural origins. Critics also question the conclusion of the agency’s mission team partly because one of its members, Daszak, who is a prominent advocate of the natural origins theory, has potential conflicts of interest. Speculation over the possibility of a lab accident has surged. Inflaming the suspicions are concerns over biosafety procedures at the Wuhan lab, political tensions between China and the US, and a general sense that the Chinese government is not to be trusted.
By trying to understand the process and context of Shi’s work—and to find out who she was—I wanted to learn what role, if any, China’s bat woman had in the origins of covid-19.
Scientists like David Relman, an expert on microbiology and biosecurity at Stanford University, are dismayed at the way the lab leak theory has been dismissed. He helped organize a group of 18 scientists to sign a letter published in Science last May calling for further investigation of a possible accident. (At least two of those involved later sought to distance themselves from the letter after seeing how it had been used to promote the lab leak theory.) Soon afterwards, President Joe Biden directed the US intelligence community to intensify its probe into the pandemic’s origins. The declassified report released in October shows that it reached no firm conclusion.
In December 2020, a month before the WHO visit, I too embarked on a search for answers. I talked to dozens of top scientists and biosafety experts worldwide. I spent six weeks in Wuhan, where I interviewed Shi and her team for a total of more than 40 hours. I had a private meeting with three members of the WHO mission. I visited the Wuhan Institute of Virology half a dozen times, often on the spur of the moment, and went with the scientists on a virus-sampling trip to a bat cave. By trying to understand the process and context of Shi’s work—and to find out who she was—I wanted to learn what role, if any, China’s bat woman had in the origins of covid-19.
Probing covid-19’s origins will not only help us understand how coronaviruses work but shine a bright light on the human behaviors—including the types of scientific research—that risk causing a pandemic in the future.
Like the WHO team, I have not gone through Shi’s freezers or lab books, and therefore I cannot prove or disprove whether activities associated with her research caused the pandemic. It’s more about providing additional perspectives—having Shi and her team tell their side of the story on the record, and in the most detail to date, so that the world can better understand how this deeply entrenched controversy has come about and how we can move forward.
Meeting China’s bat woman
I met Shi Zhengli in person for the first time on a cold afternoon in December 2020. We had spoken earlier that year for an article published in Scientific American. The level of access she has given me is unparalleled. She rarely speaks with the press, and her interaction with journalists writing for the Western media has been largely confined to emails and texts. She told me she spoke to me because my strong science background allows me to grasp the nuances and complexity of her work, because I understand China, and because we can communicate in Chinese, our native tongue, in which I conducted the interviews.
We met for lunch and then went for a walk in a nearby park. A few days later, I visited the institute’s city campus in central Wuhan—approximately 12 miles from the suburban site that the WHO team later toured. Her lab was on the second floor of a solemn-looking cream-colored building. The main room had rows of benches with weighing machines, polystyrene ice boxes, and desktop centrifuges. Bottles of chemicals and solutions were tightly packed on the shelves. One student was typing away on a computer, while another was pipetting a tiny amount of colorless liquid from one test tube to another. The scene gave me a sense of déjà vu—I’d spent a decade working as a molecular biologist, including six years as a postdoc. It reminded me of my days in the lab.
“It’s probably not that different from where you worked,” said Shi, as if she could read my mind.
Shi is petite, with short wavy hair that is neatly combed. Her voice is high and light, with the sparkle of a soprano (she is an amateur folksinger). That day she wore a beige sweater and blue jeans. As we went on to other parts of her lab—the deep freezers that held bat samples, and the rooms for culturing cells in petri dishes—she explained that her team had about three dozen researchers. That’s a lot for a Chinese lab, but it’s not the gigantic operation that many outsiders imagine. “I do not have an army of researchers and unlimited resources,” she said. Until the pandemic hit, coronavirus research was not a trendy subject and could not easily attract funding.
Shi is one of the rare breed of virologists who are just as comfortable in the field as in the lab. She grew up in a small village in central China’s Henan province and spent most of her childhood roaming the hills. She doesn’t regard herself as ambitious. When she graduated from the prestigious Wuhan University in late 1987, she told me, “I thought I had achieved my career goal and the next stage was to get married and have kids.” The main reason she went on to study at the Wuhan Institute of Virology was to stay in the same city as her then boyfriend. But as China invested in sending promising young scientists abroad to pursue doctoral degrees, Shi grabbed the opportunity.
In 2000, she got her PhD at Université Montpellier 2 in France. Studying there was an unusual decision since she didn’t speak French, and a difficult one because it meant leaving her young son behind in China; the stipend was not enough to support a young family. But the experience left a positive imprint; she particularly appreciated the Western culture that prized “critical thinking, independent-mindedness, and not following the crowd,” she told me. “You can’t do great science without any of these. This is what China really needs to get better at.”
Afterwards, she returned to the Wuhan institute, where she focused mainly on aquaculture pests until 2004. At that time, the world was still reeling from SARS, and Wang, the Duke-NUS infectious-disease specialist, was working in Australia and looking for a virologist in China to help hunt for the origins of the new disease. Shi jumped at the opportunity, joining an international team to collect blood, urine, saliva, and feces from bat colonies in mountainous areas across China. They found SARS-like coronaviruses in bats within a year, but it took nearly a decade to prove that bats were the source of the contagion. Through their collaboration, Shi and Wang became friends; colleagues knew them for their karaoke duets, and they earned the nicknames “bat woman” and “bat man,” respectively.
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As Shi showed me around her lab, she pointed to the deep freezers where the team kept tens of thousands of bat samples in chemical soups. She told me how virus-containing samples are kept frozen in the field, either on dry ice or in liquid nitrogen, before being transferred to dedicated, double-locked deep freezers in the Wuhan lab. Only designated personnel can access those samples; they need approval from two senior staff members, each of whom is in charge of a separate key to the two locks. All access to the samples is logged.
The core of her research over the past 18 years, she explained, has been to look for bat viruses that are closely related to SARS-CoV-1, and to understand how they could evolve new features that allow them to infect humans. She talked me through that process, which begins with testing each bat sample to see if it contains a coronavirus—using the same PCR-based technique as many covid-19 tests. All coronaviruses contain a gene that encodes an enzyme called RNA-dependent RNA polymerase, or RdRp, which helps viruses replicate by making more copies of their genomes. If the characteristic RdRp shows up in a bat sample, it’s a telltale sign that a coronavirus is present.
At first glance I was concerned by the sheer size of Shi’s collection of more than 20,000 bat samples. But she explained that on average only 10% contain coronaviruses, and only 10% of those are closely related to SARS-CoV-1: in all its years, the team has identified approximately 220 such viruses. The findings, say virologists such as Edward Holmes of the University of Sydney, have provided valuable insight into the evolutionary history of coronaviruses and the way they generate genetic variants.
Whenever the team found a bat relative of SARS-CoV-1, Shi says, she asked the same questions: How threatening is it to other animal species, including humans? What would it take for the virus to become one that, like SARS-CoV-1, can cause major epidemics?
The real thing
An important way to test if a coronavirus can evolve into something more threatening is to see whether its spike proteins—the weapons of invasion that give the virus a crown-like appearance—can latch onto a molecule called angiotensin-converting enzyme 2, or ACE2, which is present on the surface of cells in most vertebrates. To find out about a virus’s potential to infect people, Shi’s team would sequence its spike gene, compare it with that of SARS-CoV-1, and study on a computer its structure and ability to bind to ACE2.
The researchers also used pseudoviruses—viruses whose ability to copy their genomes is disabled—to test whether the spikes could help them enter cells from various animals. Scientists all over the world use this approach to study new pathogens without resorting to live viruses. It can be conducted with relatively inexpensive biocontainment precautions at what’s known as biosafety level 2, or BSL-2: researchers wear gloves and lab coats, and they work in cabinets that have air filtration and are under negative pressure to keep pathogens inside.
The first step for this type of work is to extract genetic material for genomic sequencing, which would inactivate all the microbes in the sample. This and subsequent cell-entry studies using pseudoviruses are well-established, safe methods.
But while pseudoviruses are a great tool, spikes—it’s become increasingly clear—are not the only factor that determines a virus’s ability to infect cells. The approach also can’t show, for instance, how exactly a virus makes cells sick, how it spreads from one cell to another, or how a pathogen might evade the body’s immune response. Those questions, which are critical for the development of drugs and vaccines, can be addressed only by using the real thing—a fully functional virus. And it’s this more dangerous work that has become the center of the controversy around Shi.
Isolating live coronaviruses from bat samples is notoriously tricky—mostly because only a small fraction of samples contain even a whiff of the viruses (whereas specimens from people with SARS or covid-19 are often teeming with coronaviruses). The process of culturing viruses involves providing them with cells they can infect. Several labs around the world have tried to get live bat coronaviruses and failed. Until January 2021, the Wuhan lab was the only one that had managed the feat, according to Stephen Goldstein, a coronavirus expert at the University of Utah in Salt Lake City. And the person with the green thumb was Yang Xinglou, a senior research scientist on Shi’s team.
I met Yang at the institute’s maximum-biocontainment campus on the outskirts of Wuhan on a muggy afternoon last May. He came to pick me up at the main gate wearing a turquoise-colored T-shirt and jeans. In his mid-30s, Yang was slim and of medium height. His hair was neatly trimmed, but in a sudden breeze, his bangs danced over a forehead dominated by thick brows. I filled out a registration form and showed the security guards my national identity card, and we walked to his office across the neatly manicured campus.
Instead of walking along the winding, camera-lined driveway meant for cars, we stepped onto a narrow path that ran by a small lake. On the far side I could see an austere-looking square building, about four floors high, sturdy, with silver siding and few windows. Inside it was China’s flagship BSL-4 lab—the crown jewel of the country’s microbiology work.
I did not go inside the BSL-4 facility: there are strict protocols that make it difficult for any visitors to get in, let alone the press. I did, however, visit the nearby BSL-3 lab, which handles less deadly pathogens. After undergoing further security checks, we entered its control room, where large screens revealed what was inside: a preparatory room, three rooms for culturing cells, a room for working with small animals such as mice and rats, a dedicated space for disinfection, and the entrances to both the lab and the control room itself. While I watched, one researcher put materials into a decontamination chamber, and two scientists in white full-body protective suits sat in front of a biosafety cabinet, working with rows of small vials behind a glass screen. A black tube on the back of their suits delivered filtered air to their face masks.
It was here, on January 5, 2020, that Yang first successfully isolated SARS-CoV-2 from a patient sample—the first isolate of the new coronavirus. “Which room did you use?” I asked. “Cell culture room 3,” he told me, pointing at one of the screens. “It was in that cabinet.”
It was just an ordinary cabinet in an ordinary room, with two bottles of disinfectant and two biohazard garbage bins behind the glass screen—but it’s now a landmark in the battle against the biggest pandemic in a century.
It was here, on January 5, 2020, that Yang first successfully isolated SARS-CoV-2 from a patient sample—the first isolate of the new coronavirus.
Yang has worked at the institute with pathogens in bats and rodents since 2008, developing and refining virus-catching techniques. There were lots of failures along the way, but in 2012, he hit the jackpot: a sample his team retrieved from a bat cave near Kunming successfully infected a type of monkey kidney cells called Vero E6, which has high levels of ACE2 on its surface. Once a live virus was at their disposal, the scientists could test directly whether it posed a potential threat.
It was a major breakthrough: for the first time researchers were able to demonstrate that bat coronaviruses in a petri dish could also infect cells from other species, including pigs and humans, by binding to their ACE2 receptors. The virus was 95% identical to SARS-CoV-1. The team named it WIV1 to indicate that it was isolated at the Wuhan Institute of Virology. Their study, published in Nature in 2013, provided strong evidence that SARS-CoV-1 originated in bats.
In all his years of work, Yang has managed to isolate only three bat coronaviruses—all of them close relatives of SARS-CoV-1. More recently, the team managed to synthesize three bat coronaviruses from their genomic sequences. All six are close relatives of SARS-CoV-1. None of them, said virologists MIT Technology Review spoke to, could have been the source of SARS-CoV-2: they’re just too different.
There was, however, one other virus in a bat sample that is a lot closer to SARS-CoV-2—96% identical. It has its own curious origin story, and in some parts of the scientific community and beyond, it’s become a prime suspect in the hunt for the pandemic’s origins. It’s called RaTG13.
Mine mystery
In late April 2012, a strange disease emerged from an abandoned copper mine near the town of Tongguan in Mojiang county, a region in China’s southwestern province of Yunnan. Six workers who had been cleaning up bat guano in the mine fell ill with pneumonia-like symptoms—coughs, headaches, fevers, and aching limbs—and were admitted to a hospital in Kunming, the provincial capital. One died in 12 days, and two recovered in a month, followed by another death on June 12.
A week later, the country’s leading respiratory clinician, Zhong Nanshan, joined a clinical consultation remotely with colleagues at the Kunming hospital to determine how to treat the remaining two Mojiang patients. Zhong, the former director of the Guangzhou Institute of Respiratory Diseases, had played an instrumental role in the fight against SARS. He noted that the miners’ lab tests and CT scans were uncannily similar to those of patients with SARS, which hadn’t been seen since 2004. The clinicians in Kunming, he told me, suspected that a fungus had caused their illness—because cave-associated fungal infections happen in Yunnan every now and then—but Zhong thought a virus might be involved. He asked Shi’s team to test the patient samples for viral infections, but they couldn’t find any evidence of infection by coronaviruses or other known viruses.
In 2020, with the pandemic raging, some scientists—including Stanford’s Relman—wondered if Shi had been wrong. Perhaps, they say, a SARS-like coronavirus was to blame. Perhaps there was even a link between the disease that affected the Mojiang miners and covid-19.
That suspicion was bolstered in May 2020, when the anonymous owner of the Twitter handle @TheSeeker268—who claimed to me in Twitter texts that he is a 30-year-old man trained in architecture and filmmaking and lives in the Indian city of Bhubaneswar—dug up a 2016 PhD thesis by Huang Canping from the Chinese internet. Huang was a student of George Gao, director-general of the Chinese Center for Disease Control and Prevention in Beijing, and his thesis cited the Wuhan Institute of Virology as claiming that four of the Mojiang miners had antibodies against SARS-CoV-1. Scientists like Monali Rahalkar, a microbial ecologist at the MACS Agharkar Research Institute in Pune, India, and a strong proponent of the lab leak theory, said that this suggests the miners were infected by a SARS-like coronavirus. Social media and the press teemed with suspicion that Shi tried to hide the fact.
The scientists directly involved in the work deny that speculation. Shi said her team did not find such antibodies, although she said some early tests did produce false positives that were corrected when the assays were fully validated. MIT Technology Review has been unable to locate Huang, but Gao said his lab never analyzed the miners’ antibody status, and that Huang’s statement—possibly based on the false-positive results, which Shi discussed at an internal meeting in 2012—was erroneous. After covid-19 struck, Shi’s team went back to the Mojiang samples to look for traces of SARS-CoV-2 proteins and found none.
“Many pathogens can cause pneumonia-like symptoms similar to SARS and covid-19,” Zhong told me. Some local clinicians, he adds, still suspect it was a fungus that had sickened the miners. “It remains a mystery to this day.”
It’s not unusual for respiratory illnesses to have an unknown cause, but even though Shi couldn’t figure out what had sickened the Mojiang miners, her instinct told her that something interesting might be going on. “What viruses were lurking in the cave?” she remembers wondering. Between 2012 and 2015, her team undertook more than half a dozen trips to the mine shaft, about 1,100 miles from Wuhan, and collected 1,322 bat samples.
They looked for the coronavirus-specific RdRp gene, and when they found it, they investigated further. In the end, the bat samples turned out to contain nearly 300 coronaviruses. Nine belonged to the same group of viruses as SARS-CoV-1—known as beta-coronaviruses—even though their RdRp genes were quite different: they were “distant cousins,” Shi told me.
“Why are you so different?” Shi wondered, but eventually she put the sample back in the freezer.
Eight of the nine were closely related to each other, but one—from a single fecal sample labeled “4991”—had a very distinct genomic signature. “Why are you so different?” Shi wondered, but eventually she put the sample back in the freezer. Her work was to look for bat viruses that could potentially cause SARS-like epidemics, and none of the Mojiang sequences appeared to be “directly relevant to our inquiry,” she told me. “So they were not the focus of our research.”
In 2018, though, 4991 was brought back out again. The Wuhan Institute of Virology had bought a new desktop sequencing machine, which made it much faster and cheaper to get a complete view of a virus’s genomic secrets, and 4991 was among the first batch of samples to be sequenced with the new device. The analysis confirmed that the virus residing in the sample was very different from SARS-CoV-1; they are 80% identical to each other across the genome. (The genomes of the other eight Mojiang viruses, which were sequenced after the pandemic, show they are only about three quarters identical to both SARS and covid-19 viruses across the genome.) It was always interesting to find new viruses, but there didn’t seem to be anything special for the researchers to write up, Shi said: “It didn’t seem to be a remarkable virus.”
It was so unremarkable, in fact, that it was expendable: In their attempts to piece together its genomic makeup, the scientists used up all the sample. By 2018 the virus existed only as a sequence in the Wuhan institute’s database.
In most cases, that would be the end of the story: the obscure, irrelevant virus would fade into oblivion. Except that it didn’t.
“I didn’t want to screw up”
At 5:30 in the morning on January 2, 2020, Si Haorui, a student on Shi’s team, headed toward the institute to start his day’s work. It was cold, and the white cloud of his breath danced around as he walked on the dark, empty street.
Si is not a morning person. He rarely emerges before 10:30. But on that frigid January morning, he had a battle to fight. Two and half days earlier, clinicians at Wuhan Jinyintan Hospital, the city’s infectious-disease center, had sent samples to the virology institute for urgent analysis.
They were from seven patients in serious condition who had been recently hospitalized for a mysterious pneumonia.
The following day, December 31, the Wuhan Municipal Health Commission issued its first public statement about the outbreak, saying it was probing the cause of 27 pneumonia cases. Shi’s lab was among the first to officially investigate the illness, and Si was part of the team racing to pinpoint the cause. Working around the clock, team members had found coronavirus RdRp genes in five out of the seven patients’ samples; their next step was to sequence the viral genome. “That’s my specialty,” said Si, a slim man in his mid-20s whose eyes curve into two arcs when he smiles, the day we met at the institute’s sequencing facility. “I knew the stakes were high. I didn’t want to screw up.”
(Shi’s lab was one of the four teams designated by China’s National Health Commission to work in parallel to pin down the cause of the new disease. This was a high-profile assignment, and only the commission had the authority to declare outbreaks of an emerging infectious disease and to release the relevant information.)
Stepping into the sequencing room felt like being a soldier stepping onto the battlefield, Si recalled. He had laid out his weapons the night before—the software he had tweaked for piecing together the genomic sequence of unknown pathogens. The machine was still running, busy reading short fragments of the genetic material from the bugs in those patients’ samples. The low humming sound of the machine filled the room. Si’s eyes were fixated on the sequencer. It reached the final stage of sequencing. It began processing the files. It took forever. Time seemed to stand still. Eventually it was done, and with a slightly shaky hand, he inserted a flash disk and copied the files over. He bolted upstairs to his office, where he could link to the institute’s supercomputer for the analysis.
By 8:30 a.m., the genomic makeup had emerged. One sequence, now known as WIV04, was almost complete and of high quality: it was a coronavirus.
Shi entered the sequence into the institutional and international databases to see if it was new. The closest match was the sequence from sample 4991, which the team had taken from Mojiang in 2013. The virus, no longer obscure or irrelevant, now deserved an official name. The team called it RaTG13—Ra for the bat species it was found in, Rhinolophus affinis; TG for Tongguan, the town where it was found; and 13 for the year of its discovery. It was, as they reported in Nature a month later, 96% identical to the coronavirus found in the new patients.
The fact that RaTG13 is so similar to SARS-CoV-2 has aroused suspicion. Critics like Alina Chan—a molecular biologist specializing in gene therapy at the Broad Institute of MIT and Harvard University in Cambridge, Massachusetts—wonder why Shi’s Nature paper published in February 2020 didn’t mention that RaTG13 came from the Mojiang mine where people had come down with the mysterious pneumonia. Chan, who leans strongly towards the lab leak theory, has helped it spread far and wide, and signed the Science letter calling for further investigation of the possibility. She said in Viral, a book she co-authored with the British science writer Matt Ridley, that the Wuhan institute had been “economical with the truth” about this.
Shi attempted to head off this kind of suspicion by publishing an addendum detailing her Mojiang studies in Nature in November 2020 to show that the team had not detected any sign of coronavirus infection in the miners’ samples. But that didn’t help squelch the speculation.
The overall similarity between the two viruses, however, is not evidence that RaTG13 is the source of covid-19, according to an article published in Cell last September, authored by two dozen or so leading virologists and infectious-disease experts. The two viruses may be related, but they sit on different evolutionary branches that diverged half a century ago, says David Robertson, a virologist at the University of Glasgow in the UK. “RaTG13 couldn’t have naturally morphed into SARS-CoV-2,” he says. Neither could anybody have used RaTG13 as the backbone to engineer SARS-CoV-2, as some proponents of the lab leak theory have argued: the two viruses are different in 1,100 or so nucleotides spread across their whole genomes—a gap too large for any realistic effort. Making SARS-CoV-2 from RaTG13, says virologist Angela Rasmussen of the University of Saskatchewan in Canada, “would have required a feat of unprecedented genetic engineering.”
Meanwhile, evidence for the natural origins theory continues to mount. In the past year, several teams independent of the Wuhan institute have uncovered more than a dozen close relatives of SARS-CoV-2 in China, Japan, Laos, Thailand, and Cambodia. In a preprint paper posted in September 2021, a team of Laotian and French scientists reported the discovery of viruses in Laos that, according to Robertson, shared a common ancestor with SARS-CoV-2 as recently as a decade ago. These new discoveries are evidence that SARS-CoV-2 most likely evolved in the wild, says Robertson, who was not involved in the study. “We are closing in on the SARS-CoV-2 progenitor,” he says.
But even if none of the bat coronavirus samples from Shi’s team are to blame for the pandemic, they aren’t the only viruses the scientists work with. Part of their research involves studying how the machinery of viruses works; and that has involved genetic mixing and matching of different pathogens to probe the function of viral genes. Could one of those chimeric viruses have been the source of the pandemic? To find out, I needed to talk to Shi.
Genetic tinkering
Bat woman takes her nickname seriously. A bat key ring lay on the desk in her office when I visited. A picture of her releasing a bat during a virus-hunting expedition hung near the window. Above the door was a green and yellow ceramic plate depicting a flying bat, which Shi bought on a field trip in Sichuan province.
“Bats are a symbol of blessing in traditional Chinese culture,” she told me. They are called bian fu, meaning “flat” and “blessing,” respectively. “We often see bat motifs in jewelry, ceramics, and buildings in remote villages,” she said.
As the researchers’ collection of bat coronavirus sequences grew—especially after 2012, when they first managed to culture live viruses—they wanted to pinpoint the genetic ingredients that allow those viruses to infect humans, so scientists could develop drugs and vaccines to counter them.
Shi was particularly interested in whether the spike protein was the sole factor that affected a coronavirus’s ability to infect cells, or whether other parts of the pathogen’s genome also had a role. One of her bat coronavirus sequences, SHC014, seemed ideal for such an inquiry. It was 95% identical to SARS-CoV-1 across the genome, but its spike was very different, and pseudovirus studies showed it was unable to facilitate entry into cells from several species, including humans. Did this mean that it was unable to infect humans?
Scientists could not test this question directly because they hadn’t managed to isolate a live virus from the bat sample. But two genetic approaches could help shed light. One was to synthesize the virus from its genomic sequence; the other was to see whether SARS-CoV-1 could still cause disease if its spike was replaced with that of SHC014.
Shi didn’t have the necessary tools to do this type of genetic work, so in July 2013 she emailed Ralph Baric—a towering figure in viral genetics at the University of North Carolina at Chapel Hill—about joining forces along those lines of inquiry.
The collaboration with Baric was not a close one, Shi told me: there was no exchange of laboratory staff, and Shi’s main contribution was to provide SHC014’s genomic sequence, which was yet to be published at the time. The findings, published in Nature Medicine in 2015, were surprising. It turned out that both the synthesized SHC014 and the SARS-CoV-1-SHC014 chimera were able to infect human cells and make mice sick. Both were less lethal than SARS-CoV-1, but—worryingly—existing drugs and vaccines that worked against SARS were unable to counter their effects.
Meanwhile, Shi’s team was attempting similar tinkering in her own lab in a project funded by the US National Institutes of Health, which aimed to probe the genetic ingredients that could allow bat viruses to cause SARS-like diseases in humans. But while Baric focused on the human pathogen SARS-CoV-1 in the Nature Medicine paper, Shi used only its bat relatives—mostly WIV1, the first bat coronavirus the team had isolated. Their real-world risk to humans was unknown. By the time the pandemic broke out, her team had created a total of a dozen or so chimeric viruses by swapping WIV1’s spike with its counterpart from newly identified sequences of bat coronaviruses, only a handful of which could infect human cells in a petri dish.
There were more surprises in store. In an unpublished experiment, released by the NIH in response to a Freedom of Information Act lawsuit brought by The Intercept, the researchers tested the ability of three such chimeras to infect mice expressing human ACE2. Compared with their parental strain, WIV1, the three chimeric viruses grew a lot more quickly in the mouse lungs in the early stage of the infection, but WIV1 caught up by the end of the experiment.
The differences surprised Shi, but what puzzled her the most was that the chimera causing the most weight loss in infected mice—an indicator of its pathogenicity—was WIV1-SHC014, whose spike was most dissimilar to that of SARS-CoV-1. The one whose spike was most similar had no effect on the animals’ weight.
The results from genetic studies in both Baric’s and Shi’s labs—both collaborating with the New York–based EcoHealth Alliance—have provided compelling evidence that the spike protein is not the only factor in whether a virus can make an animal sick, researchers say. “We can’t assess the emergence potential of viruses using only pseudovirus assays or predictions based on genomic sequences and molecular modeling,” Shi told me.
None of the chimeras created in Shi’s labs was closely related to SARS-CoV-2, and therefore, none could have been the cause of the pandemic. But it does seem that the team created at least one chimeric virus, WIV1-SHC014, with a functional gain—that is, increased pathogenicity—relative to the parental strain, WIV. Critics like Richard Ebright, a molecular biologist at Rutgers University, regard this as the type of gain-of-function research that ought to be subject to strict regulatory oversight. But Shi says that in none of those studies—including her collaborations with Baric and with EcoHealth—did the teams intend to create more dangerous viruses. None of the chimeras had been reasonably anticipated at the time of proposal to have increased transmissibility or pathogenicity in mammals.
According to an NIH spokesperson, the grant Shi jointly applied for with the EcoHealth Alliance—the only one with a sub-award to the Wuhan institute—“was reviewed and determined by experts to fall outside the scope” of its regulatory framework for gain-of-function research.
Virologists such as the University of Utah’s Goldstein argue that such genetic studies could help protect us from future pandemics. In the past year, research teams including Baric’s have demonstrated the possibility of developing so-called pan-coronavirus vaccines that could simultaneously block a group of coronaviruses—including SARS-CoV-1, SARS-CoV-2, their bat relatives that Shi has discovered, and potentially other relatives that are yet to be identified. Last September, NIH announced an award of $36.3 million to further such work. Discovering novel viruses in the wild and using genetic techniques to probe their function in the lab, researchers say, could point toward ways of mitigating and treating future disease outbreaks similar to SARS and covid-19.
Biosafety challenges
Even though none of those chimeric viruses was the source of covid-19, there are still concerns that the biosafety standards in the Wuhan lab might not have been rigorous enough to prevent research activities from causing the pandemic.
Studies involving live viruses and genetic tinkering are inherently risky. Accidents can happen even with the most stringent biosafety precautions in place. Scientists might get inadvertently infected in the lab; genetic mixing and matching might unexpectedly create a superbug whose ability to escape overmatches the biosafety designation of its parental strains.
I asked Shi how China regulates coronavirus research to minimize the risks.
“China doesn’t have a blanket biosafety regulation on all coronavirus research,” she said. “Everything is assessed on a case-by-case basis.” Studies of SARS-CoV-1 and SARS-CoV-2, for instance, have to be done in BSL-3 labs, whereas the human coronaviruses that cause the common cold are handled under BSL-2 conditions. What about bat viruses?
The Wuhan institute’s biosafety committees ruled a decade ago that while work with animals must be carried out in BSL-3, molecular and cell-culture work involving bat coronaviruses can be done in BSL-2, albeit in biosafety cabinets with air filtration and under negative pressure to keep viruses inside.
Some scientists, like Ebright, regard this as unsafe. Bat coronaviruses are, as he puts it, “uncharacterized agents” with unknown virulence and transmissibility. “The only acceptable approach is to start with a high biosafety-level assignment … and to lower the biosafety-level assignment only if and when it is determined it is prudent to do so,” he told me in an email.
Others, however, don’t think Shi’s work indicates lax biosafety standards in China. The dominant view among scientists worldwide was—and to some extent still is—that bat coronaviruses would most likely have to evolve in an intermediate animal first before they could infect humans. “Every institute’s biosafety committee has to balance the real risks with the potential risks,” says the University of Saskatchewan’s Rasmussen, adding that the Wuhan institute’s biosafety designation was reasonable at the time.
And it’s not uncommon for labs around the world to culture uncharacterized animal viruses in BSL-2 facilities. Ebright told me in an email that current US guidelines place only three coronaviruses—SARS-CoV-1, SARS-CoV-2, and MERS-CoV—under BSL-3 rules. Some contagious animal coronaviruses that can infect human cells in a petri dish, including deadly pig viruses that originated in bats, are—like Shi’s viruses—designated BSL-2 agents. (In the US, culturing rabies virus, another deadly pathogen that often lives in bats, is also designated as a BSL-2 task even though the virus has a fatality rate of nearly 100% in humans.)
Rasmussen told me that the emergence of covid-19 means we should reevaluate those biosafety standards for viruses with unknown risks. “I think the pandemic has changed that risk-benefit equation,” she said.
China’s high-level laboratories face other challenges besides the difficulty of making biosafety judgment calls. Money is one major issue. While there’s often ample funding to purchase cutting-edge equipment and build state-of-the-art laboratories such as the Wuhan institute’s BSL-4 facility, scientists often struggle for funding to train workers or to cover the cost of running those labs.
“I think the pandemic has changed that risk-benefit equation.”
Angela Rasmussen, University of Saskatchewan
Such obstacles are hardly a secret. When the US embassy in Beijing sent a delegation to visit the Wuhan Institute of Virology in early 2018, managers of the institute lamented about them to embassy staff. And Yuan Zhiming, director of the BSL-4 facility, detailed the challenges of high-level biosafety laboratories in China in a paper in September 2019.
Some have painted such challenges as a clear sign of lax standards. In an article published in April 2020, Washington Post columnist Josh Rogin wrote that after the US officials’ visit of the Wuhan institute in 2018 they “sent two official warnings back to Washington about inadequate safety at the lab.” According to Rogin, unnamed sources familiar with the unclassified cables “said that they were meant to sound an alarm about the grave safety concerns,” and one anonymous Trump administration official told him 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 newspaper column marked a turning point in the debate over covid-19’s origins, catapulting the lab leak theory into the mainstream. Several mainstream media outlets have used its assertions as evidence that the Wuhan institute has a record of “spotty” or “shoddy” biosafety practice.
The cables themselves, which were publicly released several months later (with some parts redacted), cautioned about inadequate staffing but didn’t identify any specific dangerous biosafety practices. One cable, sent on January 19, 2018, mentioned the shortage of trained staff “needed to safely operate this high-containment laboratory” in a section that discussed how a lack of trained workers could “impede research.” According to the second cable sent three months later, this “opens up even more opportunities for expert exchange.” The January cable also noted the Wuhan institute’s ability “to undertake productive research despite limitations” and said that the work “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.”
Some scientists are appalled by what they perceive as misrepresentation of the embassy cables. “The concerns raised in the cable did not appear to focus on any specific safety concerns or egregious activities within the laboratory by current staff,” Jason Kindrachuk, an infectious-disease expert at the University of Manitoba in Winnipeg, Canada, told me in an email. It highlighted, he adds, how “these current limitations may be remedied through” additional help from the international community, including the US. In any case, Bill Hanage, an infectious-disease expert at Harvard, told me in an email that he doesn’t think the existence of the cables shed any light on the covid-19 origins debate.
Rogin told MIT Technology Review in an email that he stands by his reporting in his 2020 article.
Shi says that the lack of trained staff means that China cannot make the most out of the facility, but it doesn’t mean that it was using untrained personnel to work in BSL-3 or BSL-4 labs. The Wuhan institute, she adds, abides by the international norms of biosafety governance and that her research before the pandemic was geared toward bat viruses closely related to the original SARS virus. “RaTG13 was the closest SARS-CoV-2 relative we had ever had,” she said. “We could not have leaked what we did not have.”
Shi also denied suggestions that the first human infection could have involved someone from her team—who caught the virus either in the lab or in the field. Between the beginning of the outbreak in Wuhan and the first vaccine shots, she told me, every member of her team was tested multiple times for viral nucleic acids to detect ongoing infections and for antibodies that would indicate past exposure. “Nobody was tested positive,” she said. “None of us has been infected by coronaviruses under any circumstances, including while sampling bats in the field.”
Politics of mistrust
Many scientists are dismayed by the way Shi and the Wuhan Institute of Virology are often portrayed in Western media. Even those with no connection to Shi or the Wuhan institute—such as the University of Glasgow’s Robertson and the University of Saskatchewan’s Rasmussen—call it shockingly biased and say it is driven partly by geopolitical motives and deep-rooted prejudice.
To China experts like Joy Zhang, a sociologist at the University of Kent in Canterbury, UK, who specializes in science governance in China, it’s hard to separate the specific allegations against Shi from the general suspicions of China. “Shi is a victim of the Western mistrust of China and Chinese science,” she says.
Such mistrust of Chinese scientific practices is obvious among some. Filippa Lentzos, a biosecurity expert at King’s College London, told me in February last year that “it’s simply too late” to find out what happened because “everything, for instance, in the Wuhan Institute of Virology freezers would have been cleared out. The data records would have been scrubbed or cleaned up.” She says it’s still her view now.
Shi finds Lentzos’s allegations that her lab would destroy critical records “baseless and appalling.”
“If that’s what they think, then there is nothing we can do to convince them otherwise,” she told me. “Even if we gave them all the records, they would still say we have hidden something or we have destroyed the evidence.”
Some in the West agree. “I’m quite distressed by people throwing this kind of extremely serious allegation around,” Nancy Connell, a microbiologist and member of NIH’s National Science Advisory Board for Biosecurity, told me in February last year, when she was with the Johns Hopkins Center for Health Security. “It’s highly irresponsible.”
But even if the lab leak theory is partly fueled by a deeply rooted mistrust of China, the country’s questionable credibility record and a sequence of curious missteps have not helped.
During the SARS outbreak in 2002-’03, Chinese officials downplayed its extent for months until a prominent military surgeon blew the whistle. At the onset of covid-19, China also obscured information about the early cases and clamped down on domestic debate. This was exacerbated when, in March 2020, a number of Chinese ministries ruled that scientists had to seek approval to publish any work related to covid-19 research.
Meanwhile, several Chinese institutions, including the Wuhan Institute of Virology, instructed their scientists—with rare exceptions—not to speak to the press. For some, this was something of a relief. Conducting interviews on politically sensitive subjects in English is prohibitively daunting to many Chinese speakers, as any language errors, especially regarding tenses and auxiliary verbs, can easily be misconstrued—with grave consequences. At the same time, many Chinese scientists had become reluctant to talk to Western journalists for more straightforward reasons: the majority of reporters who had contacted them, they said, didn’t seem to understand the intricacies of the science and showed strong preconceived ideas.
“I just wanted to put my head down and concentrate on my work,” Shi told me. “I thought the storm would just blow over after some time.”
Some of the Wuhan institute’s behavior has certainly raised red flags. In February 2020, for example, it took its virus databases offline, and they remain unavailable to outsiders—prompting some to suggest that they might contain information critical to covid-19’s origins. Shi told me that the part of the databases that had been publicly available before the pandemic contained only published information; the Wuhan institute, like research organizations in other parts of the world, had unpublished data that could be shared upon request via portals for academic collaborations. The institute, she says, took the databases offline because of security concerns; there had been thousands of hacking attempts since the beginning of the pandemic. “The IT managers were really worried somebody might sabotage the databases or, worse, implant virus sequences for malicious intent,” she said.
Instead of tackling the publicity crisis directly, China has exacerbated mistrust by running obfuscation and disinformation campaigns of its own.
Still, the University of Kent’s Zhang says, China’s behavior has to be understood in the country’s larger political, media, and cultural context. China, with its totally different media tradition, “has neither the vocabulary nor the grammar of the Western press to deal with a publicity crisis,” she told me. “The first instinct of Chinese officials is always to shut down communication channels.” To them, she said, this often seems safer than dealing with the situation proactively. Several top Chinese scientists, who asked not to be named for fear of political repercussions, told me that this also reflects a lack of confidence among China’s top leaders. “While eager to assert itself as a global power, China is still terribly insecure,” one of them said.
Instead of tackling the publicity crisis directly, China has exacerbated mistrust by running obfuscation and disinformation campaigns of its own. Its foreign ministry, for instance, has insinuated that biomedical labs at a military base in Maryland may have created SARS-CoV-2 and leaked it to the public. Then there are the apparent falsehoods. The Chinese members of the WHO mission insisted in their report that “no verified reports of live mammals being sold [at the Huanan market] around 2019 were found.” In June, however, a paper published in Scientific Reports showed that many vendors sold live mammals illegally at several markets in Wuhan, including the Huanan market, just before the pandemic.
Many scientists in the West are dismayed by such obfuscation. Even those who consider the lab leak theory highly unlikely are adamant that this behavior is unacceptable. “If China is lying about this, what else is it lying about?” says one virologist who strongly supports the natural origins theory.
Wu Zhiqiang—a virologist with the Beijing-based Institute of Pathogen Biology at the Chinese Academy of Medical Sciences and a member of the WHO mission—denies that his team lied. He told me that tracking down illegal wildlife trade was beyond the scope of the scientific mission. “We had to work with the information provided by the various ministries and were unable to verify the sale of live mammals at the Huanan market,” he says. Studies of disease origins, he adds, are always based on incomplete data, but Chinese scientists are following up clues to probe the market link: “It takes time and patience to learn the scientific truth.”
Adding fuel to the mistrust, though, is the role of the EcoHealth Alliance’s Daszak. His close ties with Shi’s lab and his role as a member of the WHO mission’s international team are potentially in conflict. Critics say he can also be less than forthcoming. In February, for instance, he told several media outlets that he was impressed with China’s openness—at a time when the team was under tremendous pressure to conform to the Chinese narrative. While giving the impression that he knows very well what’s going on at the Wuhan institute, Daszak and his organization have also provided incorrect statements about its research activities.
Such incidents, critics say, have raised questions about whether Daszak had a disproportionate—or even misleading—role in the WHO mission. But scientists like the University of Utah’s Goldstein, who do not collaborate with Daszak, told me that there is no evidence that Daszak “wielded disproportionate influence” in the 11-member team.
Daszak told me in an email that his potential conflicts of interest had been declared to the WHO before he joined the mission team. He says that there is lots of misreporting about him and his work in the media and that he is often not given the chance to respond to accusations. EcoHealth Alliance, he adds, has acted “with scientific integrity and honesty.”
“It’s now over two years since the first efforts to willfully politicize the pandemic origins, and to undermine science and the work that scientists do in often difficult circumstances,” says Daszak. “All of us have lost due to this politicization. When you mix politics with science, you get politics.”
“Clear and immediate threat”
On a hot July afternoon last year, I joined Shi and her team on a virus-hunting trip to a bat cave in Hubei province. (The team does not want the exact location of the cave disclosed, to avoid unwelcome media attention.) Dusk was falling fast, and the air smelled acrid and musty. Thousands of horseshoe bats clung to the cave ceiling—quiet, motionless, and evenly spaced out, like fighter jets on an airfield waiting for orders to take off.
To capture bats, researchers used a gigantic net made of fine nylon mesh suspended between two poles. Shi and Yang pushed the poles against the entrance of the cave, adjusting their position to cover the gaps between the net and the rocks. We switched off our headlamps and waited in the dark. Moments later, a fluttering sound ricocheted above us. A shadow swirled around and shot into the net, like insects flying into a spider web. The bat immediately got tangled. “Here we go,” shouted Shi. “Our first catch!”
The cave, at the bottom of a lush hill in a small village, is Shi’s home base. She uses it for sampling viruses, training students, and developing technologies that trace the movements of bats and the pathogens they carry. So far, it has yielded only distant relatives of known coronaviruses; their significance is unclear. (Bats in another cave in Hubei, however, have yielded SARS-like viruses.) “We are just collecting pieces of the jigsaw puzzle,” Shi told me. “We never know what will cause the next pandemic.”
And the team keeps doing that work. The pandemic has lent extra urgency to one aspect of its research: determining the exposure risks that rural people face. In previous studies, Shi and her colleagues found that up to 4% of people living close to bats and working closely with wildlife in southern China were infected with dangerous animal-borne viruses, including coronaviruses; the infection rate was 9% among butchers. The Laotian and French team that discovered close relatives of SARS-CoV-2 found that one in five people who’d had direct contact with bats and other wildlife had coronavirus antibodies.
Such findings suggest that viruses closely related to SARS-CoV-2 might be spreading over a massive geographic range, stretching at least 3,000 miles from Japan to Cambodia. A combination of population growth, wildlife trade, rampant deforestation, and improved transportation in those places has made it increasingly easily for animal pathogens to cross over to humans.
Robertson, the University of Glasgow virologist, says this is a clear and immediate threat: “It’s quite terrifying, really, to think how we can fuck this up by not finding out where [those viruses] are and risk more spillover.”
To watch out for viruses jumping between species, many scientists say, China should build on the WHO mission findings and set up long-term surveillance. Perhaps farms in southern China that supplied animals to the Huanan market should be a focus, or species known to be susceptible to SARS-CoV-2, such as civets, minks, badgers, raccoon dogs, and people who live close to wildlife or work in the animal trade. This wouldn’t just help pin down the origins of covid-19, says Fabian Leendertz, an expert on zoonotic diseases and the founding director of the Helmholtz Institute for One Health in Greifswald, Germany, who was a member of the WHO mission. “It’s also about reducing the risk of the next pandemic,” he says . “It can help strengthen capacity building in neglected rural areas. It should be a concerted global effort.”
But such international collaborations with China are getting increasingly unlikely because of the allegations leveled at the Wuhan institute.
Meanwhile, according to a WHO spokesperson, all hypotheses are still on the table and the lab leak theory would require further investigation, potentially with additional missions involving biosafety and biosecurity experts. Last November, the WHO put together an advisory group to probe the origins of covid-19 and future epidemics and to guide studies of emerging pathogens. The group, says the spokesperson, will release its first set of recommendations in the coming weeks.
Shi now realizes the controversial nature of her work and agrees that there’s an urgent need to step up regulation and oversight of risky research. She welcomes a broader societal debate about searching for new viruses in the wild and tampering with their genomes in the lab—which some biosafety experts ardently oppose. But “they don’t have to crucify me for that end,” she told me.
After talking to dozens of scientists involved over the past year, it has become clear to me that people’s opinions about the lab leak theory, to a large extent, depend on whether or not they believe Shi. Some support her, partly because they know her as a person or understand her work, or because they are willing to put up with the messy reality of science and China’s lack of transparency. Others, possibly driven by a deep mistrust of China, grave biosafety concerns, or an intense desire for greater transparency, simply reject every piece of evidence that she offers to define her work, and regard any inconsistencies as deliberate attempts to cover up a crime.
Not surprisingly, the allegations have taken a personal toll. “I’m a human being as well, you know,” Shi told me. “Have they considered what it feels like to be wrongly accused of unleashing a pandemic that has killed millions?”
Since the outbreaks, Shi has received numerous abusive emails and phone calls, even death threats. She has been called a liar, a mass murderer, and an accomplice of the Chinese Communist Party (even though she’s not a member). In May 2020, it was falsely rumored that she had defected to France with nearly 1,000 classified documents.
At Shi’s bat-themed office, I asked her how the past two years have marked her. Her girlish face suddenly dimmed.
“I can’t bear looking back,” she said, and turned her head away.
A long silence ensued.
“I used to admire the West. I used to think it was a just and meritocratic society. I used to think it must be wonderful to live in a country where anybody could criticize the government.”
“What do you think now?” I pressed.
“Now I think if you are Chinese then it doesn’t matter how good you are at your job—because you are tried by nationality,” she said. “I’ve now realized that the Western democracy is hypocritical, and that much of its media is driven by lies, prejudices, and politics.”
Shi paused and drew a sharp breath. Her body tensed, blood flushing her cheeks. The air swelled and seemed to grow hotter.
“They’ve lost the moral high ground as far as I’m concerned,” she said. And if politics overpowers science, “then there will be no basis for any cooperation.”
The reporting was supported by a grant from the Pulitzer Center.
Jane Qiu is an award-winning independent science writer based in Beijing and a former Knight Science Journalism Fellow at MIT.