Science's COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
The coronavirus pandemic has thrust virologist Shi Zhengli into a fierce spotlight. Shi, nicknamed "Bat Woman," heads a group that studies bat coronaviruses at the Wuhan Institute of Virology (WIV), in the Chinese city where the pandemic began. Many have speculated that SARS-CoV-2, the pathogen that causes COVID-19, accidentally escaped from her lab—a theory promoted by U.S. President Donald Trump. Some have even suggested it could have been engineered there.
China has forcefully rejected such claims, but Shi herself has said very little publicly—until now. On 15 July, Shi emailed Science answers to a series of questions about the virus' origin and her research. In them, she hit back at speculation that the virus leaked from WIV. She and her colleagues discovered the virus in late 2019, she says, in samples from patients who had a pneumonia of unknown origin. "Before that, we had never been in contact with or studied this virus, nor did we know of its existence," Shi wrote.
"U.S. President Trump's claim that SARS-CoV-2 was leaked from our institute totally contradicts the facts," she added. "It jeopardizes and affects our academic work and personal life. He owes us an apology."
Shi stressed that over the past 15 years, her lab has isolated and grown in culture only three bat coronaviruses related to one that infected humans: the agent that causes severe acute respiratory syndrome (SARS), which erupted in 2003. The more than 2000 other bat coronaviruses the lab has detected, including one that is 96.2% identical to SARS-CoV-2, are simply genetic sequences that her team has extracted from fecal samples and oral and anal swabs of the animals. She also noted that all staff and students in her lab recently tested negative for SARS-CoV-2, challenging the notion that one of them triggered the pandemic.
Shi was particularly chagrined about the 24 April decision by the U.S. National Institutes of Health (NIH), made at the White House's behest, to ax a grant to the EcoHealth Alliance in New York City that included bat virus research at WIV. "We don't understand [it] and feel it is absolutely absurd," she said.
Shi's responses—available in full at scim.ag/ShiZhengli—are "a big contribution," says Daniel Lucey of Georgetown University, an outbreak specialist who blogs about SARS-CoV-2 origin issues. "There are a lot of new facts that I wasn't aware of. It's very exciting to hear this directly from her." The answers were coordinated with public information staffers at the Chinese Academy of Sciences, of which WIV is part, and evolutionary biologist Kristian Andersen of Scripps Research suspects they were "carefully vetted" by the Chinese government. "But they're all logical, genuine, and stick to the science," he says.
Richard Ebright, a molecular biologist at Rutgers University, New Brunswick, who has long urged for an investigation into the possibility that a lab accident spawned the pandemic, is unimpressed, however. "Most of these answers are formulaic, almost robotic, reiterations of statements previously made by Chinese authorities and state media," Ebright says.
Shi's responses come at a time when questions about how the pandemic originated are increasingly causing international tensions. Trump frequently calls SARS-CoV-2 "the China virus" and has said China could have stopped the pandemic in its tracks. China, for its part, has added an extra layer of review for researchers who want to publish on the pandemic's origins and has asserted that SARS-CoV-2 may have originated in the United States. Calls for an independent, international probe into the origin are mounting, and two researchers from the World Health Organization are now in China to discuss the scope and scale of a possible mission. Lucey says Shi's answers to Science's questions could help guide the investigation team.
PETER DASZAK of the EcoHealth Alliance, who has long worked with Shi, describes her as social, open, and something of a goodwill ambassador for China at meetings, where she converses in both French and English. (She's also a renowned singer of Mandarin folk songs.) "What I really like about Zhengli is that she is frank and honest, and that just makes it easier to solve problems," he says.
Shi studied at Wuhan University and WIV, then earned a Ph.D. at the University of Montpellier II in France. She returned to WIV in 2000, initially focusing on viruses in shrimp and crabs. A turning point in her career came in 2005, when she published a study in Science with Daszak and other researchers from China, Australia, and the United States. The paper reported the first evidence that bats harbored coronaviruses closely related to the lethal virus that jumped from civets to humans and caused the worldwide outbreak of SARS in 2003.
Daszak has continued to work with Shi and her WIV team to sample wild animals and hunt for more coronaviruses. They have published 18 more papers together. Shi "is extremely driven to produce high-quality work," Daszak says. "She will go out in the field, and gets involved in the work, but her real skills are in the lab, and she's one of the best I've worked with in China, probably globally."
Shi told Science her lab was thrust into the pandemic on 30 December 2019, the day her team first received patient samples. "Subsequently, we rapidly conducted research in parallel with other domestic institutions, and quickly identified the pathogen," she wrote.
It didn't long take for suspicions and rumors to arise, first on China's social media sites and then in Western media. On 2 February, Shi posted a note on her own social media site saying SARS-CoV-2 was "nature punishing the uncivilized habits and customs of humans," and that she would "bet my life that [the outbreak] has nothing to do with the lab." Partly as a show of support for Shi, Daszak and 26 other scientists from eight countries published a statement of solidarity with Chinese scientists and health professionals in The Lancet in February. In a March Nature paper that analyzed SARS-CoV-2's genetic makeup, Andersen and other evolutionary biologists argued against it being engineered in a lab.
In her written answers to Science, Shi explained in great detail why she thinks her lab is blameless. WIV has identified hundreds of bat viruses over the years, but never anything close to SARS-CoV-2, she says. Although much speculation has centered on RaTG13, the bat virus that most closely resembles SARS-CoV-2, differences in the sequences of the two viruses suggest they diverged from a common ancestor somewhere between 20 and 70 years ago. Shi notes that her lab never cultured the bat virus, making an accident far less likely.
Some suspicions have focused on a naming inconsistency. In 2016, Shi described a partial sequence of a bat coronavirus that she dubbed 4991. That small part of the genome exactly matches RaTG13, leading some to speculate that Shi never revealed the full sequence of 4991 because it actually is SARS-CoV-2. But Shi explained that 4991 and RaTG13 are one and the same. The original name, she says, was for the bat itself, but her team switched to RaTG13 when they sequenced the entire virus. TG stands for Tongguan, the town in Yunnan province where they trapped that bat, she said, and 13 for the year 2013.
That's "a very logical explanation," says Edward Holmes, an evolutionary biologist at the University of Sydney. Shi's reply also clarified to him why 4991 held such little interest to her team that they didn't even bother to sequence it fully until recently: That short genetic sequence was very different from SARS-CoV, the virus that caused the 2003 outbreak. "In reading this the penny dropped: Of course, they would have been mainly interested in bat viruses closely related to SARS-CoV … not some random bat virus that is more distant," Holmes says.
Shi mentioned other factors that she says exonerate her lab. Their research meets strict biosafety rules, she said, and the lab is subject to periodic inspections "by a third-party institution authorized by the government." Antibody tests have shown there is "zero infection" among institute staff or students with SARS-CoV-2 or SARS-related viruses. Shi said WIV has never been ordered to destroy any samples after the pandemic erupted.
Labs that presumably had strict biosafety rules have had accidents: The SARS virus escaped from several labs after the global outbreak was contained in 2003. And even if everyone in the institute tested negative for the virus today, an infected person could have left WIV months ago. Still, Holmes says, the answers are "a clear, comprehensive, and believable account" of what occurred at WIV.
BUT THEN where did the virus come from? Shi concurs with the scientific consensus that it originated in bats and jumped to humans either directly or, more likely, via an intermediate host. Her lab tested samples from Huanan Seafood Wholesale Market, which Wuhan officials initially fingered as a possible origin because some early patients had links to it, and found RNA fragments from the virus in "door handles, the ground and sewage," she wrote—but not in "frozen animal samples." But the market's role was called into question when two papers revealed that up to 45% of the first confirmed patients—including four of the five earliest cases—did not have any links to it. "The Huanan seafood market may just be a crowded location where a cluster of early novel coronavirus patients were found," Shi says.
Researchers from WIV and Huazhong Agricultural University didn't find the virus in farmed animals and livestock around Wuhan and in other places in Hubei province, she wrote. Years of surveillance in Hubei have never turned up bat coronaviruses close to SARS-CoV-2, she said, leading her to believe the jump to humans happened elsewhere.
Shi provided few details on China's efforts to pin down the origin. "Many groups in China are carrying out such studies," she wrote, using multiple approaches. "We are publishing papers and data, including those about the virus's origins."
Daszak supports the push for an international research effort—which he cautions could take years—and says Shi's group should play a prominent role in it. "I hope and believe that she will be able to help WIV and China show the world that there is nothing to these lab escape theories, and help us all to find the true origins of this viral strain," he says. Shi ended her answers on a similar note. "Here, I would like to make an appeal to the international community to strengthen international cooperation on research into the origins of emerging viruses," she said. "I hope scientists around the world can stand together and work together."
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