Monday, February 7, 2022

Made in China: On the Lab-Leak Origin of Covid

By Jim Geraghty

Thursday, February 03, 2022

 

When Covid-19 first darkened our lives in the opening months of 2020, it was not only reasonable but logical to suspect that the virus had originated from some animal sold, slaughtered, or served in a Wuhan wet market.

 

In November 2017, Smithsonian magazine published an eerily prescient feature piece by Melinda Liu titled “Is China Ground Zero for a Future Pandemic?” It offered a vivid portrait of China’s urban wet markets as the perfect petri dish for viruses jumping species: “Stalls overflowed with graphic evidence of the morning’s brisk trade: boiled bird carcasses, bloodied cleavers, clumps of feathers, poultry organs. Open vats bubbled with a dark oleaginous resin used to remove feathers. Poultry cages were draped with the pelts of freshly skinned rabbits. . . . These areas — often poorly ventilated, with multiple species jammed together — create ideal conditions for spreading disease through shared water utensils or airborne droplets of blood and other secretions.”

 

A wet market appeared to be the origin of the first SARS outbreak. Researchers Wenhui Li et al., as they wrote in the Journal of Virology in December 2020, were able to determine, fairly quickly, that “exotic animals from a Guangdong marketplace are likely to have been the immediate origin of the SARS-CoV that infected humans in the winters of both 2002–2003 and 2003–2004. Marketplace Himalayan palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides) harbored viruses highly similar to SARS-CoV.” Americans saw and heard relatively little coverage of that outbreak at the time, as it peaked right around when the U.S. was invading Iraq in 2003. But the first SARS pandemic infected more than 8,000 people and killed more than 700.

 

Just about every virologist in the world is certain that SARS-CoV-2 — the coronavirus that causes Covid — is most like those found in bats; they differ on whether it is likely to have jumped directly from bats to human beings, or whether it passed through an intermediate species such as a pangolin — the scaly-skinned mammals that are among the most widely illegally trafficked species in the world.

 

As luck would have it, a Chinese health inspector, Xiao Xiao, conducted routine monthly surveys of all 17 wet-market shops selling live wild animals for food and pets across Wuhan, in an effort to identify the source of a separate disease, the tick-borne severe fever with thrombocytopenia syndrome. His detailed report revealed that Wuhan’s wet markets sold all kinds of animals — “38 species, including 31 protected species sold between May 2017 and November 2019 in Wuhan’s markets.” But his report also noted that “no pangolins (or bats) were traded, supporting reformed opinion that pangolins were not likely the spillover host at the source of the current coronavirus (COVID-19) pandemic.”

 

Thus, the first problem with the wet-market theory is that apparently Wuhan wet markets didn’t sell or trade bats or pangolins. Could it be another mammal species? Sure. Do we know for certain that SARS-CoV-2 passed through another mammal before jumping into humans? No.

 

Another major complication with the natural spillover theory is that no one in China has been able to find SARS-CoV-2 naturally occurring in animals in China — or at least, that is what Chinese health authorities are telling the world. A detailed analysis by Antonio Regalado in MIT Technology Review in March 2021 noted that “no food animal has been identified as a reservoir for the pandemic virus. That’s despite efforts by China to test tens of thousands of animals, including pigs, goats, and geese, according to Liang Wannian, who leads the Chinese side of the research team. No one has found a ‘direct progenitor’ of the virus, he says, and therefore the pandemic ‘remains an unsolved mystery.’”

 

As we know, SARS-CoV-2 is quite contagious among human beings. So why is this super-contagious virus so difficult to find in a bat?

 

In addition to the inability to find bats or pangolins in the wet markets in the pre-pandemic surveys, a few other facts don’t fit easily with the narrative of the wet-market origin.

 

A significant portion, although not all, of the first Covid cases could be traced back to the Huanan Seafood Market — 27 of 41 patients, according to a key early assessment published in the medical journal the Lancet. But a later, larger study of the first 99 people diagnosed with COVID found that only 49 could be traced back to the Huanan Seafood Market.

 

It is likely that the seafood market was a key location in the early spread of the virus, but not necessarily the origin point. After examining the Lancet’s data, Georgetown University professor and pandemic specialist Daniel Lucey contended, as quoted by Jon Cohen in Science (January 26, 2020), that “the virus came into that marketplace before it came out of that marketplace.”

 

Another complication is that bat viruses don’t seem to jump easily into humans, and when they have done so in the past, they did not set off massive life-threatening pandemics. Research published by the Wuhan Institute of Virology in 2018 examined the villagers who lived closest to the coronavirus-carrying bats in Yunnan Province and concluded that natural “spillover” from bats directly to humans is “relatively rare” — just 2.7 percent of the villagers had antibodies indicating ex­posure to a bat virus.

 

* * *

 

There are two naturally occurring viruses that are par­ticularly similar to SARS-CoV-2. The first is RaTG13, which shares 96.2 percent of its genome with SARS-CoV-2, according to a paper released by the Wuhan Institute of Virology’s Shi Zhengli. This virus was collected from bat feces in a copper-mine shaft in Tongguan, Mojiang, Yunnan Province, China, that was the site of a small-scale deadly viral infection with some curious similarities to Covid.

 

In April 2012, six miners were assigned to clean bat guano from the mine shaft. Four miners had been working at the site for two weeks, and two had been working there for four days when they all grew ill with a cough and fever and experienced difficulty breathing, aching limbs, heavy and bloody mucus and saliva, and headaches — symptoms of a viral respiratory infection that are similar to the effects of Covid. All six miners were admitted to a Kunming hospital in late April and early May, and three died — one after two weeks, one after a month and a half, and one after three months. The other three survived.

 

Dr. Zhong Nanshan, a prominent Chinese pulmonolo­gist whose high-profile role has been compared to that of Dr. Anthony Fauci in the United States, consulted on the cases of the miners. Recognizing that the virus afflicting the miners could be comparable to SARS, researchers sent blood samples to the Wuhan Institute of Virology for antibody testing.

 

In 2012 and 2013, teams of researchers from the Wuhan Institute of Virology conducted a study of coronaviruses in bats in that abandoned mine shaft — and one of the samples they collected was RaTG13.

 

The second virus that is particularly similar to SARS-CoV-2 is really a cluster of three similar viruses discovered in Laos in autumn 2021. A team led by Marc Eliot, a virologist at the Pasteur Institute in Paris, collected saliva, feces, and urine samples from 645 bats in caves in northern Laos and found three new viruses that were each more than 95 percent identical to SARS-CoV-2, which they named BANAL-52, BANAL-103, and BANAL-236.

 

Some skeptics of the lab-leak theory contend that the BANAL viruses proved that SARS-CoV-2 is likely a naturally occurring virus, and because Laos was roughly 1,000 miles from Wuhan, this pointed away from the notion that the Covid pandemic could be traced back to a leak from Wuhan Institute of Virology or any other labs in the city. But there is ample reason to believe that viruses from Laos — perhaps not the BANAL trio, but similar ones — were also shipped from Laos to the Wuhan Institute of Virology.

 

In 2010, Wildlife Trust, a nonprofit international conservation organization dedicated to protecting wildlife, announced it was rebranding itself under the name EcoHealth Alliance. The organization’s president, Peter Daszak, declared that his group had become “the central organization defining the intersection of local conservation and global health” and touted itself as being “on the forefront of informing the public, businesses, and the scientific community about emerging diseases, including potential pandemics.” It is safe to say that EcoHealth Alliance is one of the largest, best funded, and best connected nonprofits, focusing upon “field research and develop[ing] tools to save ecosystems and predict and prevent pandemics.”

 

For decades, EcoHealth Alliance staff and scientists went out into the wild collecting viruses and conducting research on how those viruses worked. The watchdog organization White Coat Waste filed a Freedom of Information Act request for communications between the U.S. National Institute of Allergy and Infectious Diseases and EcoHealth Alliance. In June 2018, EcoHealth Alliance’s chief of staff, Aleksei Chmura, emailed Adam Graham, a grant-management specialist at the U.S. NIAID, and discussed collecting viruses from bats in countries that neighbor China, including Burma, Vietnam, Cambodia, and Laos. The email detailed plans to “arrange for shipment of bats and other high-risk host species to Wuhan Institute of Virology Laboratory in China” and “all samples collected would still be tested at the Wuhan Institute of Virology in China.”

 

So it is quite plausible that a sample of a bat virus from Laos could end up behind the walls of the Wuhan Institute of Virology. The institute housed one of the largest collections of coronaviruses found in bats in the world — if not the largest.

 

EcoHealth Alliance has earned its scrutiny and suspicion in the two years since the Covid pandemic started. Science writer David Quammen joined Chmura on a trip to China in 2009. In Quammen’s 2013 book, Spillover: Animal Infections and the Next Human Pandemic, he describes his conversation with Chmura about the lack of safety gear:

 

At this moment I became conscious of a dreary human concern: Though we were searching for SARS-like coronavirus in these animals, and sharing their air in a closely confined space, none of us was wearing a mask. Not even a surgical mask, let alone an N95. Um, why is that? I asked Aleksei. “I guess it’s like not wearing a seat belt,” he said. What he meant was that our exposure represented a calculated, acceptable risk. You fly to a strange country, you jump into a cab at the airport, you’re in a hurry, you don’t speak the language — and usually there’s no seat belt, right? Do you jump out and look for another cab? No, you proceed. You’ve got things to do. You might be killed on the way into town, true, but probably you won’t. Accepting that increment of risk is part of functioning within exigent circumstances. Likewise in a Chinese bat cave. If you were absolutely concerned to shield yourself against the virus, you’d need not just a mask but a full Tyvek coverall, and gloves, and goggles — or maybe even a bubble hood and visor, your whole suit positive-pressurized with filtered air drawn in by a battery-powered fan. “That’s not very practical,” Aleksei said.

 

Oh, I said, and continued handling the bagged bats. I couldn’t disagree. But what I thought was, Catching SARS — that’s practical?

 

We also know that another research institution in the same city, the Wuhan Center for Disease Control, was also doing research on coronaviruses found in bats — and it is probably worth noting that the Wuhan CDC building is less than a mile from the Huanan Seafood Market.

 

Bat coronaviruses are the specialty of virologist Tian Junhua. In 2017, the Chinese state-owned Shanghai Media Group made a seven-minute documentary about him, entitled “Youth in the Wild: Invisible Defender.” Videographers followed Tian Junhua as he traveled deep into caves to collect bats. “Among all known creatures, the bats are rich with various viruses inside,” he says in Chinese. “You can find most viruses responsible for human diseases, like rabies virus, SARS, and Ebola. Accordingly, the caves frequented by bats became our main battlefields.”

 

Ominously, Tian Junhua described being infected with viruses during his excursions, getting sick, and self-isolating for two weeks. As stated in a May 2017 report by Xinhua News Agency, repeated by the Chinese news site JQKNews.com:

 

In the process of operation, Tian Junhua forgot to take protective measures. Bat urine dripped on him like raindrops from the top. If he was infected, he could not find any medicine. It was written in the report. The wings of bats carry sharp claws. When the big bats are caught by bat tools, they can easily spray blood. Several times bat blood was sprayed directly on Tian’s skin, but he didn’t flinch at all. After returning home, Tian Junhua took the initiative to isolate for half a month. As long as [infection during] the incubation period of 14 days does not occur, he will be lucky to escape.

 

We know for a fact that the people collecting samples do not always follow the necessary safety procedures. And the risk of accidental infection does not disappear once the viruses and bats are brought back to the laboratories.

 

* * *

 

Lab accidents happen. The first argument against the lab-leak theory that can be safely dismissed is the notion that Chinese scientists were simply too careful or too diligent to ever let a virus escape their lab. Accidents occur even in the most well-trained and highly regarded research facilities in the world. In June 2014, the U.S. Centers for Disease Control and Prevention determined that they had unintentionally exposed personnel to potentially viable anthrax. A month later, the U.S. Food and Drug Administration found samples of smallpox, dengue, and spotted fever just sitting in a storage room. A decade earlier, the Chinese CDC’s National Institute of Virology in southern Beijing had accidentally released SARS. Twice.

 

In February 2019, Lynn Klotz, a senior science fellow at the Center for Arms Control and Non-Proliferation, laid out a report in Bulletin of the Atomic Scientists detailing that from 2009 to 2015, a federal program “received a total of 749 incident reports from select-agent research facilities,” including “1) needle sticks and other through the skin exposures from sharp objects, 2) dropped containers or spills/splashes of liquids containing pathogens, and 3) bites or scratches from infected animals.”

 

Some virologists contend that if the world wants to know how to counter and defeat particularly dangerous and contagious viruses, they need to work with and study particularly dan­gerous and contagious viruses. Because those particularly dangerous viruses aren’t always readily available for research and experimentation, they contend they must create them through “gain-of-function research” — taking existing viruses and, through various means, making them more infectious, contagious, or virulent. Other virologists see this research as an accident waiting to happen.

 

In October 2014 — not too long after the embarrassing but nonfatal incidents at the CDC and FDA — Dr. Francis Collins, director of the U.S. National Institutes of Health, announced a pause in federal funding of gain-of-function research experiments with influenza, SARS, and MERS viruses, as NIH wanted to evaluate whether the research was worth the potential risks. But NIH allowed one ongoing international research effort to continue, an effort that included Ralph Baric, an infectious-disease researcher at the University of North Carolina, and the Wuhan Institute of Virology’s Shi Zhengli.

 

In 2015, that team of scientists, Vineet Menachery and colleagues, announced in Nature Medicine that they had “generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone.” This was a new kind of virus that was resistant to existing treatments: “Both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein.”

 

The announcement inflamed the concerns of certain re­searchers that gain-of-function research was too risky — that it generated too little useful knowledge and created the potential for disaster. In a 2015 article by Declan Butler in Nature, Simon Wain-Hobson, a virologist at the Pasteur Institute, warned that “if the virus escaped, nobody could predict the trajectory.” In the same article, Richard Ebright, a molecular biologist and biodefense expert at Rutgers University, concurred: “The only impact of this work is the creation, in a lab, of a new, non-natural risk.”

 

Collins and the NIH restored funding for gain-of-function research in 2017, after concluding that very few government-funded gain-of-function experiments posed a significant threat to public health and pledging greater scrutiny of grant requests.

 

Baric dismisses the notion that his work ever contributed to the creation of a supervirus. But over the course of 2021, Baric did grow more concerned about the safety standards in Chinese laboratories. In September 2021, Baric told CNN: “Their papers indicate that they did much of their work with these bat viruses under Biological Safety 2 conditions. There are many more laboratory accidents or laboratory-acquired infections in BSL-2 as compared to BSL-3. We do all the research in our lab on bat-related coronaviruses under Biological Safety 3 enhanced conditions. We wear portable air-breathing apparatuses with tied-back suits so the workers are protected from anything that might be in the laboratory.”

 

In 2015, the Wuhan Institute of Virology become China’s first laboratory to achieve the highest level of international bio­research safety, Biosafety Level 4. Up until then, the institute was doing its research in Biosafety Level 2 labs.

 

In early January 2018, the proud Chinese scientists invited U.S. scientists to tour the Wuhan institute, the crown jewel of the Chinese Academy of Science’s viral research. But U.S. consul general Jamie Fouss and Rick Switzer, the embassy’s counselor of environment, science, technology, and health, were more unnerved than impressed by what they saw, and they sent two sensitive but unclassified memos back to Washington.

 

The first memo, dated January 19, 2018, states that the in­stitute’s “current productivity is limited by a shortage of the highly trained technicians and investigators required to safely operate a [Biosafety Level] 4 laboratory and lack of clarity in related Chinese government policies and guidelines.” The second memo, dated April 19, 2018, noted that the Wuhan Institute of Virology’s “English brochure highlighted a national security role, saying that it ‘is an effective measure to improve China’s availability in safeguarding national bio-safety if [a] possible biological warfare or terrorist attack happens.’”

 

EcoHealth Alliance was clearly interested in gain-of-function research in its work with the Wuhan Institute of Virology. A March 2018 grant proposal from EcoHealth to the Defense Advanced Research Projects Agency (DARPA) proposed “introduc[ing] appropriate human-specific cleavage sites” into SARS-like viruses; in other words, to take existing bat viruses and make them more likely to infect human beings. The proposal declared, “Dr. Shi, Wuhan Institute of Virology, will conduct viral testing on all collected samples, binding assays and some humanized mouse work.”

 

(Before the pandemic, Chinese research scientists had engineered a supply of mice with “humanized” lungs, to give a better sense of how these viruses would affect human beings. Some U.S. officials have wondered if the Chinese scientists’ supply of mice with “humanized” lungs had a more sinister purpose, as part of an effort to develop viruses more likely to kill human beings. But at this point, there is no concrete evidence that the virus research in the Wuhan labs was connected to a desire to develop biological weapons.)

 

The NIH revealed last year that EcoHealth Alliance had un­intentionally made viruses more virulent during their research work with the Wuhan Institute of Virology in 2019. “The limited experiment described in the final progress report provided by EcoHealth Alliance was testing if spike proteins from naturally occurring bat coronaviruses circulating in China were capable of binding to the human ACE2 receptor on a mouse model,” NIH’s Lawrence Tabak wrote.

 

“All other aspects of the mice, including the immune system, were unchanged,” the letter continued. “In this limited ex­periment, laboratory mice infected with the SHC014 WIV1 bat corona­virus became sicker than those infected with the WIV1 bat coronavirus.” NIH emphasized that “as sometimes occurs in science, this was an unexpected result of the research, as opposed to something that the researchers set out to do.”

 

EcoHealth was supposed to notify NIH if it enhanced a virus’s ability to grow by a factor of ten. Instead, the work with the Wuhan Institute of Virology created novel coronaviruses that enhanced viral growth by 1,000-fold to 10,000-fold — and the heavier viral loads made the mice sicker.

 

Shortly after the Wuhan Institute of Virology was achieving these breakthroughs in gain-of-function research, making bat coronaviruses much more contagious, another potentially ominous event developed: According to the Wall Street Journal, U.S. intelligence determined that three researchers from China’s Wuhan Institute of Virology became sick enough in November 2019 that they sought hospital care “with symptoms consistent with both Covid and common seasonal illness.” They may have just had the seasonal flu. Or they may have brought their work home with them, so to speak.

 

* * *

 

Finally, there is the undeniably suspicious behavior of the Chinese government since the first cases were reported in Wuhan in December 2019. Until January 21, 2020, the Wuhan Regional Health Commission insisted that “no clear evidence of human-to-human transmission has been found.” On January 4, 2020, former CDC director Dr. Robert Redfield was incredulous during a phone call with his Chinese counterpart, George Gao. Redfield described asking his old friend Gao, “George, you don’t really believe that mother and father and daughter all got it from an animal at the same time, do ya?” Gao insisted there was no evidence of human-to-human transmission. But Redfield recounted that two days later, Gao broke down during a call, “audibly and tearfully distraught after finding ‘a lot of cases’ in the community who had never visited the wet market.”

 

In late January and early February, the Chinese government ordered all labs processing samples of the strange new virus to destroy them. On January 3, China’s National Health Commission ordered institutions not to publish any information related to the unknown disease and ordered labs to transfer any samples they had to designated testing institutions, or to destroy them. The justification for this order was public safety, although it is hard to see the public-safety benefit in suppressing information about the disease.

 

It took a year to get a World Health Organization investigative team into Wuhan, and when that team arrived, it encountered angry refusals to turn over raw data about the earliest cases. According to the New York Times, “disagreements over patient records and other issues were so tense that they sometimes erupted into shouts among the typically mild-mannered scientists on both sides.” The Chinese government has refused to allow another team of investigators to enter Wuhan or the labs in the city. The Chinese government does not care if it looks guilty.

 

A much-hyped U.S. intelligence-community investigation completed in August offered almost nothing useful, declaring, “All agencies assess that two hypotheses are plausible: natural exposure to an infected animal and a laboratory-associated incident.” Ninety days of effort, with all the resources of the U.S. government, generated nothing new.

 

To paraphrase Ebright, in the autumn of 2019, there were three institutions in the entire world that were doing gain-of-function research on novel coronaviruses found in bats. One was in Galveston, Texas, one was in Chapel Hill, N.C., and the third was in Wuhan, China.

 

In theory, the pandemic could have started with some random Chinese person who didn’t have any connection to the bat coronavirus research conducted at the Wuhan Institute of Virology or the Wuhan CDC. This person would have a spectacularly unlucky run-in with a bat or other animal, and that random Chinese person caught the exceptionally rare naturally occurring animal virus that infects, sickens, and spreads among human beings like wildfire. This same hyper-contagious bat virus would have the exceptionally unusual trait of being ex­tremely difficult to find in bats.

 

This extraordinarily unlucky person would then travel to the metaphorical doorstep of one of the three labs in the world doing gain-of-function research on novel coronaviruses found in bats and start infecting other people in the city of Wuhan. Under the natural-origin theory, the Wuhan laboratories just happen to be mind-bogglingly unlucky that events played out in a way that so closely mimics the consequences of a lab accident.

 

That would be a remarkable series of coincidences.

 

Or, within the walls of an institution that we know was doing gain-of-function research on coronaviruses found in bats, aiming to make them more contagious and virulent, at an institution that we know was insufficiently staffed to operate safely, a single employee may have not worn his personal protective equipment correctly one day in late 2019. A single employee may have been scratched or bitten by a bat, or inhaled a virus shed by a bat undergoing the stress of an anal swab, or just carelessly wiped his eyes or nose or mouth. After that employee left the lab and returned home for the evening, he would have been shedding viruses once the infection took hold — in his home, through the public-transportation system and streets and sidewalks, and perhaps he or a family member visited a seafood market.

 

As of this writing, more than 5.6 million people around the world have perished from Covid, and 354 million have been infected.

 

The first great mystery of this pandemic is how it got started — a question that must be answered to adequately prepare us for another pandemic in the future.

 

The second great mystery of this pandemic is why so many powerful people don’t seem to feel any sense of urgency about solving the first great mystery.

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