Where did the pandemic start? Anywhere but here, argue papers by Chinese scientists echoing party line

When Alice Hughes downloaded a preprint from the server Research Square in September 2021, she could hardly believe her eyes. The study described a massive effort to survey bat viruses in China, in search of clues to the origins of the COVID-19 pandemic. A team of 21 researchers from the country’s leading academic institutions had trapped more than 17,000 bats, from the subtropical south to the frigid northeast, and tested them for relatives of SARS-CoV-2.

The number they found: zero.

The authors acknowledged this was a surprising result. But they concluded relatives of SARS-CoV-2 are “extremely rare” in China and suggested that to pinpoint the pandemic’s roots, “extensive” bat surveys should take place abroad, in the Indochina Peninsula.

“I don’t believe it for a second,” says Hughes, a conservation biologist who’s now at Hong Kong University. Between May 2019 and November 2020, she had done her own survey of 342 bats in the Xishuangbanna Tropical Botanical Garden, a branch of the Chinese Academy of Sciences (CAS) in Yunnan province where she worked at the time. As her team reported in Cell in June 2021, it found four viruses related to SARS-CoV-2 in the garden, which is about three times the size of New York City’s Central Park.

The new study had sampled bats near that same location, at an abandoned mine that had yielded another close SARS-CoV-2 relative in 2013, and at other sites in nearly half of China’s 31 provinces. And yet the only thing researchers found were viruses close to SARS-CoV-1, which caused the outbreak of severe acute respiratory syndrome 2 decades ago.

Edward Holmes, an evolutionary biologist at the University of Sydney who coauthored the Cell paper with Hughes, dismisses the preprint with a single word: “Bullshit.” Although Holmes has no evidence the team behind the study did anything underhanded, “There is a big contradiction between this study and others that needs to be explained,” he says.

But the paper meshed with a growing political reality in China. From the start of the pandemic, the Chinese government—like many foreign researchers—has vigorously rejected the idea that SARS-CoV-2 somehow originated in the Wuhan Institute of Virology (WIV) and escaped. But over the past 2 years, it has also started to push back against what many regard as the only plausible alternative scenario: The pandemic started in China with a virus that naturally jumped from bats to an “intermediate” species and then to humans—most likely at the Huanan Seafood Market in Wuhan.

Beijing was open to the idea at first. But today it points to myriad ways SARS-CoV-2 could have arrived in Wuhan from abroad, borne by contaminated frozen food or infected foreigners—perhaps at the Military World Games in Wuhan, in October 2019—or released accidentally by a U.S. military lab located more than 12,000 kilometers from Wuhan. Its goal is to avoid being blamed for the pandemic in any way, says Filippa Lentzos, a sociologist at King’s College London who studies biological threats and health security. “China just doesn’t want to look bad,” she says. “They need to maintain an image of control and competence. And that is what goes through everything they do.”

The idea of a pandemic origin outside China is preposterous to many scientists, regardless of their position on whether the virus started with a lab leak or a natural jump from animals. There’s simply no way SARS-CoV-2 could have come from some foreign place to Wuhan and triggered an explosive outbreak there without first racing through humans at the site of its origin. “The idea that the pandemic didn’t originate in China is inconsistent with so many other things,” says Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Center who has argued for more intensive studies of the WIV lab accident scenario. “When you eliminate the absurd, it’s Wuhan,” says virologist Gregory Towers of University College London, who leans toward a natural origin.

Yet Chinese researchers have published a flurry of papers supporting their government’s “anywhere-but-here” position. Multiple studies report finding no signs of SARS-CoV-2–related viruses or antibodies in bats and other wild and captive animals in China. Others offer clues that the virus hitched a ride to China on imported food or its packaging. On the flip side, Chinese researchers are not pursuing—or at least not publishing—obvious efforts to trace the sources of the mammals sold at the Huanan market, which could yield clues to the virus’ origins.

Wu Zhiqiang, a virologist at Peking Union Medical College who is the lead author of the Research Square preprint, wouldn’t say whether the government vetted his study, which is still under review at a journal. But he denies that his results were influenced by Beijing, let alone cooked up to please it. “We do not represent the government or anyone else,” writes Wu, who says his team is not arguing that the pandemic originated outside China. “We just stand by our data, and all our data are open access.”

Yet Holmes, who has close and long-standing ties with Chinese scientists, worries they have become entangled in the government’s political messaging. “There’s clearly an official narrative that’s come down from on high that appears to be: ‘The investigations have been completed now, and they couldn’t find where it came from,’” Holmes says. “It’s no longer China’s problem—this is about a problem from elsewhere.” He says his collaborators in China have become increasingly guarded, wary of contradicting that narrative with their own findings and opinions.

Hughes left Xishuangbanna in December 2021 after 9 years in China because it had become too difficult to continue her bat research there. Most origin-related research required government review, she says, and she also needed a green light from CAS. “The dialogue is just: ‘We don’t want it to have come from here in any form,’” she says. “And that’s not a sensible way of doing science.”

Science attempted to discuss these issues with George Gao, who until last month headed the Chinese Center for Disease Control and Prevention (CCDC) and is a lead author on several key papers about the pandemic’s origins. “What can I say?” Gao texted back. “Best wishes.”

The notion that it all began at the sprawling Huanan market in downtown Wuhan was not controversial at first. A 31 December 2019 report from the Wuhan Municipal Health Commission announced a cluster of 27 unexplained pneumonia cases linked to the market, which was immediately closed. Three weeks later, after a novel coronavirus had been identified as the cause, government researchers concluded in the China CDC Weekly that “all current evidence points to wild animals sold illegally in the Huanan Seafood Wholesale Market.” On 27 January, the official Chinese news agency Xinhua reported that 33 “environmental samples” from the market had tested positive for the virus and all but two came from areas selling wildlife. Again, the results suggested “the virus stems from wild animals on sale at the market,” the article stated.

That spring and summer, origin research continued apace in China, Hughes says. Her group dug into bat samples it had collected in 2019 at the Xishuangbanna gardens and discovered one of the closest relatives of SARS-CoV-2 yet found, which shared 93.3% of its genetic sequence, a finding it published in June 2020 in Current Biology. “Throughout 2020, we were encouraged to do more work,” Hughes says.

But the Chinese government’s counternarrative had started to take shape. By the end of January, published reports about the earliest cases suggested almost half had no connection to Huanan, raising doubts about its role as the outbreak’s origin. The lab-leak theory had also started to circulate internationally, and before long, then–U.S. President Donald Trump began blaming WIV, which had studied bat coronaviruses for 15 years, for sparking the “kung flu” pandemic with the “China virus.” In March 2020, Zhao Lijian, a spokesperson for China’s foreign ministry, flipped the tables, asking whether the virus came from a U.S. Army lab at Fort Detrick in Maryland.

The Chinese government also began to clamp down on interactions between origin researchers and the media. Suddenly, giving an interview required permission from the Ministry of Science and Technology. “Part of that was for a good reason,” Hughes says. “There was some very bad science going on, and they didn’t want that to come out.”

The country’s new mindset colored a March 2021 report from an international team sent to China earlier in the year to study the origin of the pandemic under the auspices of the World Health Organization (WHO). The report deemed a laboratory accident “extremely unlikely” but ranked the frozen food scenario as “possible.” A direct zoonotic spillover ranked higher, as “possible-to-likely,” yet the report questioned whether the jump could have happened at the Huanan market, claiming animals that might have carried the virus weren’t there. “No verified reports of live mammals being sold around 2019 were found,” the report flatly stated.

Dutch virologist Marion Koopmans, a prominent member of the WHO team, acknowledges politics played a role in both statements. Koopmans says she never put much stock in the frozen food route. As to the notion that mammals weren’t sold at the Huanan market, she says the international scientists on the mission were “highly skeptical” of the claim. They even showed their Chinese counterparts a photo Holmes had taken a few years earlier at that very market that showed a caged raccoon dog—a species known to be highly susceptible to SARS-CoV-2 and able to transmit it.

But in the end, hard evidence that the market sold mammals in 2019 was lacking, and the international scientists went along with the “no verified reports” phrasing, Koopmans says, to avoid “the political situation.”

To Chris Newman, an ecologist at the University of Oxford who has long studied the illegal sale of wildlife at Chinese markets, the report marked a significant shift in the Chinese government’s strategy. “They tried to start to change the narrative, and they’ve been sort of trapped in that ever since,” Newman says. “They’re trying to look for any alternative explanation, however implausible that might be. It’s almost like being caught in a childish lie.”

As it happened, Newman knew the statement about the Huanan market was dead wrong. “Somebody was misleading the World Health Organization here,” he says. Newman had helped conceptualize and write a study led by Zhou Zhao-Min of China West Normal University that surveyed mammals sold in Wuhan markets for 2 years prior to the pandemic, looking for the source of a tick-borne infection. It documented nearly 50,000 mammals for sale at Wuhan’s animal markets, including Huanan. Among the species were raccoon dogs and civets, also highly vulnerable to SARS-CoV-2.

The team could have published the study as a preprint, but it wanted the “credibility” of a peer-reviewed paper, Newman says. That took a long time. The paper finally appeared in Scientific Reports in June 2021—revealing the glaring misdirection in the WHO report published 3 months earlier. Zhou and Newman had sent a draft of their paper to WHO in October 2020, realizing its potential significance for the origins debate, but the agency had not done anything with it. “That was a big glitch,” Koopmans says. “I find that annoying—I’m putting it mildly.”

Zhou and the other Chinese co-author, Xiao Xiao, did not respond to repeated requests from Science for interviews about the study. “When the paper did finally come out, they were both taken aside by their institutions and told off,” Newman says. “They were told to cease all work on wildlife trade. And they were quite worried.”

The paper left out a key detail that might help clarify the pandemic’s origin: It did not say whether the researchers collected ticks—which suck mammalian blood—or took biological samples directly from the animals. Either could be tested for antibodies to SARS-CoV-2 or genetic remnants of the virus itself to find out which animal species harbored it. Newman wasn’t involved with the sample collection, so he asked Zhou, but to no avail. “Zhou is not at liberty to say, and he doesn’t reply,” Newman says. “It’s so self-evident that surely somebody in the Chinese CDC has done exactly that. Surely somebody knows the answer.”

Everyone from lab-leak proponents to WHO Director-General Tedros Adhanom Ghebreyesus and U.S. President Joe Biden criticized the WHO report, and in its wake, China’s willingness to probe the origins of the pandemic took another nosedive. The government scuttled ambitious follow-up plans proposed by the group: studies of viral genomes of the earliest cases, to trace the initial spread; retrospective analyses of Chinese hospital records prior to the outbreak and of illnesses in high-risk groups such as farmers and veterinarians; and mapping supply chains of farms that sold to the Huanan market. “The derailment of this whole process is horrible,” Koopmans says.

The finger-pointing at other countries also ramped up. On 17 September 2021, The Lancet published a four-page correspondence by Wu and authors at CCDC and several of the country’s top academic institutions claiming the WHO committee had carried out “an extensive investigation in Wuhan in the past year.” The letter argued it was now “reasonable” to start a “worldwide” hunt for the origin and laid out a plan for doing so. Invoking the lofty rhetoric common in global health circles—“humankind must work together”—the article stressed that the massive global investigation it proposed “should be carried out by scientists on the basis of science alone, without interference or coercion from political forces.”

By now more than two dozen reports from Chinese scientists have suggested the virus came from elsewhere. Many, including Wu’s Lancet letter, explored the imported frozen food hypothesis. After China had all but stopped COVID-19 transmission by March 2020, researchers linked small outbreaks to imported salmon at a Beijing market, frozen cod offloaded at shipping docks in Qingdao, and imported pollock packaged by a company in Dalian. Other scientists tested more than 50 million swabs of frozen food packages from across China and found that nearly 1500 had genetic remnants of the virus. In the China CDC Weekly they asserted it “cannot be ruled out” that just such contamination triggered the initial Huanan market outbreak.

Yet researchers rarely detected infectious virus on the food—only viral RNA—and food regulators in the United States, Europe, Australia, and New Zealand have dismissed this route of transmission. There’s also nothing that connects imported frozen food at the Huanan market to the outbreak there.

Besides, if the virus arrived in Wuhan on frozen food, “it means the virus had to be already circulating somewhere else, and there’s no evidence of that,” Koopmans says. Studies from Spain, Italy, France, Brazil, and the United States have reported finding genetic pieces of the virus—or antibodies to it—in stored tissue from patients or wastewater samples that predate the Wuhan outbreak. Chinese scientific papers and media have made much of such findings, but skeptics say the viral traces may be contaminants and the antibodies could be responses to other pathogens that “cross-react” with SARS-CoV-2.

As for the frozen food route, Holmes says it’s not even worth discussing. “You might as well just say it came from cosmic dust.”

China has not allowed foreign researchers into the country to conduct independent origin studies, but that hasn’t stymied all investigations. On 26 February, a large international team that included Holmes and Michael Worobey, an evolutionary biologist at the University of Arizona, published two preprints that offered a new analysis of the outbreak’s early days—and pointed directly at the Huanan market. (Science published peer-reviewed versions—here and here—online on 26 July.)

Early reports suggesting some cases were not connected to the market mistakenly identified people as having the disease who did not, the authors contended. They combined spatial analyses of where infected people lived and worked, genetic sequencing of early viral samples, and the location of positive environmental samples and the stalls that sold mammals highly susceptible to SARS-CoV-2 to conclude the market was the “epicenter” of the pandemic.

But a preprint from China published a day earlier by Gao and many co-authors from CCDC reached a starkly different conclusion. The study analyzed more than 1000 environmental samples from the Huanan market and found SARS-CoV-2 in 73 of them, indicating the virus was in the sewer, on the ground, and in “containers,” some of which Worobey suspects may have been cages that held mammals, based on their location.

In a so-called metagenomic analysis, the researchers also found several samples had a blend of viral and human RNA, “which highly suggests the SARS-CoV-2 might have derived from Homo sapiens” in the market, the authors wrote. In other words, humans didn’t catch SARS-CoV-2 from animals at the market. Instead, people might have brought it to the market from elsewhere.

Again, the researchers mentioned viral traces on imported frozen food and the retrospective studies from other countries as clues to a foreign origin. “Definitely, more work involving international coordination is needed to investigate the real origins of SARS-CoV-2,” they concluded.

Worobey and Holmes were gobsmacked by what the study didn’t say. In a graphic that illustrates the metagenomic analysis, dots show the virus mixed with RNA from several species other than humans, but the preprint does not specify which species. “They ignore all the other animals in there,” Holmes says.

A researcher who claims to have reviewed the manuscript for Nature says it’s not clear whether the omission was intentional or due to sloppy science, but either way, “I said you cannot publish this unless they release the raw data.” The reviewer, who asked not to be named, noted that the paper also includes an analysis of a sample from a defeathering machine at the market that found only human DNA. “Either only humans were defeathered or the analysis was wrong—pick your favorite,” the reviewer says. Gao did not reply to Science’s specific request to discuss the metagenomic data.

In an attempt to reboot the origin probe, WHO last year created the Scientific Advisory Group for the Origins of Novel Pathogens (SAGO), a new international team of 26 people. SAGO’s preliminary report, issued on 15 May, offers recommendations echoing those of the earlier team, with two major differences: It calls for more studies of a potential “laboratory incident”—although members from China, Russia, and Brazil dissented—and it recognizes that the Huanan market did sell mammals susceptible to the virus.

But by then, “anywhere but here” had become the Chinese government’s party line. “More and more clues from the international science community are pointing the origins of SARS-CoV-2 to sources around the world,” Zhao, the foreign press ministry spokesperson, asserted at a 10 June press conference in response to the SAGO report. He again brought up the controversial reports of very early cases outside China and called for investigations at the “highly suspicious” Fort Detrick laboratory.

Wu says many Chinese researchers remain open to the idea that the virus originated in China. “We have never ruled out Wuhan or China in the next phase of the investigation, and Chinese researchers are still working on it and continuously getting data,” he says. He stresses that, in response to peer reviewers, his team has “toned down” some of its bold assertions in the Research Square preprint about the bat survey in China. For example, instead of calling viruses related to SARS-CoV-2 in Chinese bats “extremely rare,” the manuscript now says they “might be rare.”

But the clampdown on bat research that Hughes experienced has continued, especially at the local level, says Aaron Irving, a bat researcher at Zhejiang University. “People are now often scared to help out bat researchers in case they also get in trouble,” he says. Irving stresses that his institution still supports his work, but what he calls “nonscientific interference” has taken a toll. “Everyone in the bat field got a little secretive and protective too because they don’t want to be targeted.”

Some researchers think too much time has passed to solve the origin mystery. But others who favor a natural origin say they only need a few more jigsaw pieces to complete the puzzle. Newman suspects Chinese officials and researchers may already hold some of those pieces. “They should be in a position to know an awful lot more than we are currently told,” he says.

There is no shame in admitting that the virus came from wild animals illegally sold at a market, Newman adds. “To leave it as an open question, it’s just going to breed intrigue about why the Chinese have not given us a clear explanation,” Newman says. “Why the smoke and mirrors? Whereas if they come up with something that we could all just accept, well, then it will be case closed. Can’t we persuade them that this is the right thing for everybody to do?”

Source: Science Mag