In Search of Covid's Origins, Scientists Reignite Polarizing Debate on Wuhan 'Lab Leak'

This�KHN�story first published on�California Healthline, a service of the�California Health Care Foundation.

Once dismissed as a conspiracy theory, the idea that the covid virus escaped from a Chinese lab is gaining high-profile attention. As it does, reputations of renowned scientists are at risk – and so is their personal safety.

At the center of the storm is Peter Daszak, whose EcoHealth Alliance has worked directly with Chinese coronavirus scientists for years. The scientist has been pilloried by Republicans and lost National Institutes of Health funding for his work. He gets floods of threats, including hate mail with suspicious powders. In a rare interview, he conceded that he can't disprove that the deadly covid-19 virus resulted from a lab leak at the Wuhan Institute of Virology – though he doesn't believe it.

"It's a good conspiracy theory," Daszak told KHN. "Foreigners designing a virus in a mysterious lab, a nefarious activity, and then the cloak of secrecy around China."

But to attack scientists "is not only shooting the messenger," he said. "It's shooting the people with the conduit to where the next pandemic could happen."

Yet what if the messengers were not only bearing bad news but also accidentally unleashed a virus that went on to kill more than 3 million people?

The generally accepted scientific hypothesis holds that the covid virus arose through natural mutations as it spread from bats to humans, possibly at one of China's numerous "wet markets," where caged animals are sold and slaughtered. An alternative explanation is that the virus somehow leaked from the Wuhan Institute, one of Daszak's scientific partners, possibly by way of an infected lab worker.

The lab leak hypothesis has picked up more adherents as time passes and scientists fail to detect a bat or other animal infected with a virus that has covid's signature genetics. By contrast, within a few months of the start of the 2003 SARS pandemic,�scientists found the culprit coronavirus in animals sold in Chinese markets. But samples from 80,000 animals to date have failed to turn up a virus pointing to the origins of SARS-CoV-2 – the virus that causes covid. The virus's ancestors originated in bats in southern China, 600 miles from Wuhan. But covid contains unusual mutations or sequences that made it ideal for infecting people, an issue explored in depth by journalist Nicholas Wade.

Scientists from the Wuhan Institute have collected thousands of coronavirus specimens from bats and registered them in databases closed to inspection. Could one of those viruses have escaped, perhaps after a "gain of function" experiment that rendered it more dangerous?

Daszak, who finds such theories specious, was the only American on a 10-member team that the World Health Organization sent to China this winter to investigate the origins of the virus. The group concluded its work without gaining access to databases at the Wuhan Institute, but dismissed the lab leak hypothesis as unlikely. WHO Director-General Tedros Adhanom Ghebreyesus, however, said the hypothesis "requires further investigation."

On Friday, 18 virus and immunology experts published a letter in the journal Science demanding a deeper dive. "Theories of accidental release from a lab and zoonotic spillover both remain viable," they said, adding that the Wuhan Institute should open its records. One of the signatories was a North Carolina virologist who has worked directly with the Wuhan Institute's top scientists.

That demand is "definitely not acceptable," responded Shi Zhengli, who directs the Center for Emerging Infectious Diseases at the Wuhan Institute. "Who can provide evidence that does not exist?" she told MIT Technology Review. Shi has said that thousands of attempts to hack its computer systems forced the institute to close its database.

Many leading virologists continue to believe that "zoonotic transmission" – from a bat or some other animal to a human – remains the most likely origin story. Yet the lack of evidence for that is troubling, 17 months after the emergence of covid, said Stanley Perlman, a University of Iowa virologist who was not among the Science letter signatories.

The fact that no bat or other animal has been found infected with anything resembling the covid virus, which suddenly swept through Wuhan at the end of 2019, "has put the lab leak hypothesis back on the table," although there is no evidence supporting that theory either, he said.

Alina Chan, a Broad Institute postdoctoral researcher who signed the Science letter, agrees that there is no "dispositive" evidence either way for covid's emergence. But a network of amateur sleuths have put together evidence, she said, that the Wuhan Institute has covid-like viruses in its collection that it has not deposited in global databases, as would be customary during a global pandemic. Chan and others are particularly curious about a bunch of SARS-like viruses that the institute collected from a cave in Yunnan province where guano miners suffered a deadly outbreak of respiratory disease in 2012.

"We don't have access to that data," Chan said. She and other scientists wonder why the covid virus was so ideally suited to human-to-human transmission from the onset without signs of an intermediate host or circulation in the human population before the Wuhan outbreak.

In a paper posted to a virology forum last week, Robert Garry of Tulane University, who doubts the lab leak hypothesis, brought forth a new fragment of "spillover" evidence: The WHO report shows that some of the first 168 cases of covid were linked to two or more animal markets in Wuhan, he said, with strains from different markets showing slight differences in their genetic sequence. "Maybe one animal was in a truck with a bunch of cages and then it spread it to another species and that's where the shift took place," Garry said.

Garry and other international scientists have worked with Shi and her lab for years. The evidence for Garry's supposition isn't airtight, he admitted, but it's more convincing than "contriving something where some of the world's leading virologists are covering up at the behest of the Chinese Communist Party," he said.

Shi has no greater defender in the United States than Daszak, whose EcoHealth Alliance was a wildlife protection organization when he joined it two decades ago. The group has since expanded its goals from protecting endangered animals to protecting humans endangered by the pathogens trafficked with those animals. The more than $50 million EcoHealth Alliance had received in U.S. funding since 2007 includes contracts and grants from two NIH institutes, the National Science Foundation and the U.S. Agency for International Development, as well as Pentagon funds to look for organisms that could be fashioned into bioterror weapons.

Daszak has co-authored at least 21 research papers on bat coronaviruses since 2005, finding hundreds of viruses capable of infecting people. He estimated that about 1 million people a year are infected with bat viruses – a number that's grown as humans encroach on bat habitats.

He recalled a 2019 visit to a cave filled with millions of bats. "Tourists were going in there in shorts, and we were in there in full PPE. They asked us, 'What are you doing?' and we told them, 'We're looking for viruses like SARS.'''

In April 2020, citing what he said was evidence of the virus's link to the Wuhan lab, President Donald Trump ordered the NIH to cancel a five-year, $3.7 million grant for EcoHealth Alliance's bat virus research. But about 70% of the group's annual $12 million budget continues to come from the U.S. government, Daszak said.

When the NIH grant was frozen, Daszak called the lab leak hypothesis "pure baloney," saying he was confident his Chinese scientific partners were not hiding anything. But he admits it is impossible to disprove.

"There are plenty of reasons to question China's openness and transparency on a whole range of issues including early reporting of the pandemic," he told KHN. "You can never definitively say that what China is telling us is correct."

Daszak said he thinks it more likely that China is covering up the role of the country's wildlife markets in covid's origin. Farming of these animals employs 14 million people, and the government has closed and reopened the markets since SARS. Following the covid outbreak, the Chinese authorities' investigation of Wuhan's animal markets, where the virus could have mutated after passage through different species, was incomplete, Daszak said.

"People don't realize how sensitive China is about this," he said. "It's plausible that they recognized there were cases coming out of a market and they shut it down."

A Controversy With Roots

The scientific conflict over the lab hypothesis is partly rooted in a debate over gain-of-function experiments, work that in theory could lead to the creation and release of more infectious or deadly organisms. In such experiments, scientists in a lab can, for example, test a virus's ability to mutate by exposing it to different cell types or to mice genetically engineered with human immune system traits.

At least six of the 18 signatories of the Science letter are part of the Cambridge Working Group, whose members worry about the release of pathogens from the growing number of virus labs around the world.

In 2012, Dr. Anthony Fauci, who leads NIH's National Institute of Allergy and Infectious Diseases, came out in support of a moratorium on such research, posing a hypothetical scenario involving a poorly trained scientist in a poorly regulated lab: "In an unlikely but conceivable turn of events, what if that scientist becomes infected with the virus, which leads to an outbreak and ultimately triggers a pandemic?" Fauci wrote.

In 2017, the federal government lifted its pause on such experiments but has since required some be approved by a federal board.

In his questioning of Fauci in the Senate last week, Sen. Rand Paul (R-Ky.) cited a 2015 paper written by Shi, Ralph Baric of the University of North Carolina and others in which they fused a SARS-like virus with a novel bat virus spike protein and found that it sickened research mice. The experiment provided evidence of the perils that lurked in Chinese bat caves, but the authors also raised the question of whether such studies were "too risky to pursue."

Critics have jumped on this paper as evidence that Shi was conducting "gain of function" experiments that could have created a superbug, but Shi denies it. The research cited in the paper was conducted in North Carolina.

Using a similar technique, in 2017, Baric's lab showed that remdesivir – currently the only licensed drug for treating covid – could be useful in fighting coronavirus infections. Baric also helped test the Moderna covid vaccine and a leading new drug candidate against covid.

Research into covid-like viruses is vital, Baric said. "A terrible truth," he said, "is that millions of coronaviruses exist in animal reservoirs, like bats, and unfortunately many appear poised for rapid transmission between species."

Baric told KHN he does not believe covid resulted from gain-of-function research. But he signed the Science letter calling for a more thorough investigation of his Chinese colleagues' laboratory, he said in an email, because while he "personally believe[s] in the natural origin hypothesis," WHO should arrange for a rigorous, open investigation. It should review the biosafety level under which bat coronavirus research was conducted at the Wuhan Institute, obtaining detailed information on the training and safety procedures and efforts to monitor possible infections among lab personnel.

Fauci also told KHN, in an email, that "we at the NIH are very much in favor of a thorough investigation as to the origins of SARS-CoV-2."

Scaling the Wall of Secrecy

U.S.-China tensions will make it very difficult to conclude any such study, scientists on both sides of the issue suggest. With their anti-China rhetoric, Trump and his aides "could not have made it more difficult to get cooperation," said Dr. Gerald Keusch, associate director of the National Emerging Infectious Diseases Laboratory Institute at Boston University. If a disease had emerged from the U.S. and the Chinese blamed the Pentagon and demanded access to the data, "what would we say?" Keusch asked. "Would we throw out the red carpet, 'Come on over to Fort Detrick and the Rocky Mountain Lab?' We'd have done exactly what the Chinese did, which is say, 'Screw you!'"

Still, while China has shut off its laboratories to outside inquiry, that doesn't mean all investigative avenues are closed, Chan said. Many Chinese scientists were in contact with colleagues and journals outside the country as the pandemic emerged. Those communications may contain clues, Chan said, and someone should methodically interview the contacted individuals.

It's worth recalling that the only U.S. bioterror attack so far in the 21st century consisted of a U.S. bioterrorism researcher mailing anthrax spores to politicians and journalists. Hundreds of millions of dollars go into researching organisms around the world and there are risks of leaks, accidental or intentional, no matter how sophisticated the lab, Chan said.

But it would be unwise to limit support for global virus research, said Jonna Mazet, a University of California-Davis professor who led a USAID-funded program that trained scientists around the world to collect and research animal viruses. For her pains, she has received death threats and hacking attacks on her computers and home alarm system.

"If we don't do the work," she said, "we're just sitting ducks for the next one."

KHN correspondent Rachana Pradhan contributed to this report.