The China Syndrome Part III: Wet Markets and BioLabs

Note: This is the third part of a four-part series of essays looking in detail at China’s role in the COVID-19 pandemic. Part One looked at the circumstances surrounding the initial outbreak; Part Two looked at the discovery of human-to-human transmission and the immediate response; this part investigates allegations that the pandemic began in a “wet market” or that the virus escaped from a lab in Wuhan; Part Four examines charges that the Chinese have falsified their pandemic data.

Among the most controversial questions debated in the wake of the SARS-CoV-2 outbreak are how and why the pandemic began in China in the first place. In the previous part of this essay, I argued that, to the extent that China was blameworthy for the pandemic, it was down to a matter of chance. Had the pandemic started in the West instead of China, it would likely have been much worse, so unless you believe in moral luck it doesn’t make sense to blame China. However, if the outbreak began as a result of Chinese negligence or malpractice, then China can still be held responsible even if, once the outbreak had begun, the Chinese authorities handled it more competently than Western government would have. Indeed, the two most popular theories—that the virus arose in a Chinese “wet” market, or that it escaped from a research laboratory—are both explanations that implicate Chinese practices in the outbreak. The problem is that there’s very little evidence to support either one.

The wet market theory

When reports of a mysterious respiratory illness began to emerge from Wuhan, suspicion immediately fell on the Huanan Seafood Market there, an open-air bazaar colloquially known as a “wet market.” Wet markets are simply open-air places where people buy and sell fresh produce such as fruit, vegetables, meat, poultry, and fish (as opposed to dry markets that sell non-perishable goods like grain and household products). What makes these places potentially hazardous is the unregulated trade in wild and exotic animals, which are sometimes caged together or in close proximity and profoundly unsanitary conditions. This enables pathogens to jump between species, and increases the probability that they will undergo the genetic changes needed to infect humans. The 2002–2004 SARS pandemic is still widely thought to have originated in bats and been passed to humans from civets sold in this kind of market in Guangdong.

Asked for his opinion of wet markets during an interview on Fox and Friends in April, Anthony Fauci, Director of the US National Institute of Allergy and Infectious Diseases, was blunt: “I think they should shut down those things right away. It boggles my mind how, when we have so many diseases that emanate out of that unusual human-animal interface, that we don’t just shut it down. I don’t know what else has to happen to get us to appreciate that.” China failed to close its wet markets after the 2002 SARS outbreak, but in response to the SARS-CoV-2 pandemic, it banned wildlife trade and consumption. Although this ban is supposed to be permanent, critics have already identified loopholes that exempt traditional medicine.

The problem is that we don’t actually know that Huanan Seafood Market had anything to do with the outbreak of SARS-CoV-2, and there are good reasons to doubt that it did. As I mentioned in my previous essay, a study published in the New England Journal of Medicine found that 45 percent of the cases who developed symptoms before January 1st had no known link to market. A Lancet study, meanwhile, also noted that the earliest identified case had no known connection to Huanan Seafood Market and that, of the first four known cases, three also had no known links to it. Of the 41 people hospitalized in Wuhan before January 2nd, only 27 could be connected to Huanan Seafood Market. These studies were published by Chinese researchers, but there is no evidence the data are unreliable or that their findings were published at the behest of the Chinese authorities. On the contrary, as Caixin noted, these papers appear to have prompted a statement from the Chinese Ministry of Science and Technology on January 30th, which criticised the researchers for publishing their findings in foreign journals instead of passing them along to the authorities.

Nor does the wet market theory appear to be supported by emerging genetic data. As a virus infects a host, reproduces inside it and then infects another host, it mutates and produces different strains. Those differences accumulate over time and can even give rise to different species. By comparing the genomes of different strains of a virus, we can trace the evolutionary relationships between them. A study used genome-wide and epidemiological data to map the evolution of SARS-CoV-2 and persuasively argued that, while Huanan Seafood Market boosted circulation of the virus and served as a springboard from which it spread to the rest of the city in December, the virus itself almost certainly began circulating elsewhere in Wuhan during the second half of November. (The details of how the authors of that study reached this conclusion are a bit complicated, but if you are interested, I have explained their argument on my blog.) Of course, as we get more data, this picture could change, but this is the story suggested by the data we currently have. Another paper by a different team reached the same conclusion based on a similar argument, and it’s also consistent with the phylogenetic analysis in this paper recently published in Nature.

In this version of events, the market still figures prominently, since it served as a launching pad for SARS-CoV-2, but the virus didn’t originate there and the wild animals sold in the market don’t appear to have played any role in its transmission. This is consistent with what the genetic data say about SARS-CoV-2’s population history. According to the analysis in the May study, the virus went through a first expansion on December 7th, right before patients with a connection to Huanan Seafood Market started showing up in hospitals. No patient with a history of visiting the market developed symptoms until December 10th. Given what we know about its incubation period, this suggests that SARS-CoV-2 didn’t reach Huanan Seafood Market until the beginning of December, where it circulated for a while before spreading to other parts of Hubei province, then to the rest of China and, finally, around the world. It is therefore unsurprising that nobody in Wuhan detected a cluster of pneumonia until late December or that the new disease was initially associated with the market, since back then most (though by no means all) cases were connected to it.

I know that a lot of people don’t trust Chinese data, but genetic data are hard to fake, so this should make us more confident that the epidemiological data about the beginning of the outbreak in Wuhan are accurate. Wildlife trade and consumption pose an ongoing risk to public health, which is reason enough to argue that such practices be discontinued. But it doesn’t mean China’s failure to close wildlife markets caused this particular pandemic or that it keeping them open massively increased the risk of a pandemic.

A large proportion of emerging infectious diseases in humans not only come from animals, but specifically from wildlife. According to a 2008 study published in Nature, between 1940 and 2004, 60.3 percent have originated in animals and, of those, 71.8 percent originated in wildlife. In other words, during that period, approximately 43 percent of emerging infectious diseases in humans came from wild animals. But that doesn’t mean they came from wildlife markets and, as far as I can tell, nobody has any idea how much the risk of pandemic would be reduced if China banned wildlife trade and consumption tomorrow. Many factors besides wildlife trade and consumption, such as population growth, urbanisation, deforestation, and so on increase the risk of pandemic. Moreover, people seem to assume that the Chinese government can just press a button and wildlife trade would instantly stop, but it’s not that simple. If only because of widespread corruption among local officials, a lot of wildlife trade would no doubt continue undisturbed. (Of course, if the Chinese government started to enforce a ban with draconian punishments, it might have the desired effect, but presumably that’s not what the people demanding that China do something about wildlife trade have in mind.)

And China is hardly the only country where people trade and eat wild animals—these practices are ubiquitous in South-East Asia, Central Africa, and many other places like Brazil. In fact, a significant proportion of wildlife consumption in China seems to be satisfied by illegal wildlife trade from South East Asia or even Africa. Both Ebola and HIV, which caused one of the worst pandemics in history, have been linked to the consumption of bushmeat in Central Africa. If a disproportionate number of emerging infectious diseases originate in China rather than another country where the trade and consumption of wild animals is also widespread, this is presumably because China is home to almost 20 percent of the world’s population, not because the Chinese authorities are uniquely irresponsible.

The lab escape theories

So, if SARS-CoV-2 did not originate in a wildlife market, then where did it come from? Theories that the virus escaped from a lab or even that it was bioengineered by Chinese researchers and accidentally released, have made their way from blogs, social media, and YouTube channels into the mainstream press and the highest echelons of the US government. During a White House press briefing held on April 30th, President Trump was asked if he had seen evidence that would lead him to conclude with a “high degree of confidence that the Wuhan Institute of Virology was the origin of this virus.” Trump confirmed that he had, adding: “The World Health Organisation should be ashamed of themselves, because they’re like the public relations agency for China… They shouldn’t be making excuses when people make horrible mistakes, especially mistakes that are causing hundreds of thousands of people around the world to die.”

In an interview with ABC’s This Week on May 3rd, US Secretary of State Mike Pompeo was asked if he had also seen this evidence and if he shared Trump’s confidence in it. “There’s enormous evidence,” Pompeo replied, “that that’s where this began.” He pointed to China’s “history of infecting the world” and “history of running substandard laboratories,” and even stated the virus had been bioengineered before immediately walking that statement back. The State Department now appears to be retreating from the lab escape theory entirely, probably because the US intelligence community doesn’t believe it. Nevertheless, a poll conducted in early May found that 49 percent of Americans thought it “definitely true” or “probably true” that SARS-CoV-2 had originated in a Chinese lab.

I won’t waste time on the claim that Chinese researchers deliberately released the virus because it’s absurd on its face. But the theory that SARS-CoV-2 accidentally escaped from a lab deserves scrutiny because it’s not entirely implausible and because it has been promoted not only by US public officials, but also by commentators in mainstream news organisations. However, it’s not easy to discuss this theory, because its adherents employ a kind of “death by a thousand cuts” strategy. They bring up a lot of things which they claim support a version of the lab escape theory, but which, upon closer inspection, are either confused or don’t really support it at all. When this is pointed out, they simply move on to dozens of other alleged incongruities, and continue to insist that the lab escape theory be taken seriously. I can’t realistically hope to address every argument that has been put forward in favour of this theory and, even if I could, I’m not convinced it would be useful or necessary. So instead I’m going to focus on the arguments that have received most mainstream attention and identify some logical flaws in their reasoning.

The misidentification of patient zero

The lab escape theory started to circulate on Chinese social media in February and was soon picked up by Twitter users in the West. A video posted on April 1st by Matthew Tye, a popular American YouTuber who lived in China for 10 years, seems to have played a significant role in popularizing this theory. Tye’s video has accrued more than two million views as of this writing, and Jim Geraghty, whom I mentioned in the second essay in this series, even wrote an article about it for National Review.

Tye claims to have identified the Wuhan Institute of Virology (WIV) as the source of the SARS-CoV-2 outbreak in Wuhan. The first piece of evidence he presents is a job ad for a postdoc researcher posted to the WIV website on December 24th, before news of the Wuhan outbreak emerged. (Previously, he’d drawn his viewers’ attention to another ad posted on November 18th that sought to recruit someone to work on bat coronaviruses.) Tye speaks fluent Chinese and he tells his viewers that the posting says “we’ve discovered a new and terrible virus and would like to recruit people to come deal with it.” But here’s the text of the job posting in question, which I’ve translated using DeepL/Google with the help of a Chinese speaker (I’ve removed sections irrelevant to the research topic):

Proposed recruitment direction 1: Ecological study of bat migration and virus transmission.

Proposed [recruitment] direction 2: Research on the cross-species infection and pathogenicity of bat viruses.

[…]

Introduction to PI

Shi Zhengli, Ph.D., Researcher, Head of Emerging Viruses Discipline Group, Wuhan Institute of Virus Research, Chinese Academy of Sciences, Director of Emerging Infectious Diseases Research Center, Wuhan Institute of Virus Research, Chinese Academy of Sciences, Director of Key Laboratory of Highly Pathogenic Biology and Biosecurity, Chinese Academy of Sciences, Editor-in-Chief of Virologica Sinica. Long-term research on the pathogen biology of important viruses carried by bats has been carried out to confirm the bat origin of major new infectious diseases in humans and animals such as SARS and SADS, and a large number of new viruses in bats and rodents have been discovered and identified. She has published more than 110 papers in SCI journals such as Nature, Science, Nat Rev Microbiol, Cell Host Microbe, Nat Microbiol, PLoS Pathog, and has been listed in the Elsevier “China Highly Cited Scholars” list (Immunology and Microbiology) for five consecutive years since 2014. Awarded “Advanced Worker” by the Chinese Academy of Sciences and “May Day Labor Medal” by the National Academy.

Main research directions of the subject group

The Emerging Viruses Section focuses on the pathogenesis of emerging viruses and their infection mechanisms, including the discovery of viruses in bats and rodents, the study of early warning and transmission patterns, the study of cross-species infection mechanisms and pathogenicity of important viruses transmitted by bats such as coronavirus, and serology and molecular diagnostic techniques of emerging viruses.

Nothing in this ad, which simply described the ongoing research into infectious zoonotic diseases being carried out at the WIV, justifies Tye’s sinister inference and his summary of it is transparently dishonest. He goes on to repeat a rumour that had been circulating on Chinese social media for a while, according to which the Wuhan outbreak began when a WIV researcher named Huang Yanling became infected in a lab, infected others outside, and subsequently died. (Tye reports additional gossip that her body was secretly cremated and that workers at the funeral home were also infected.) It is true that someone named Huang Yanling used to be a graduate student at the WIV, but nothing else about this story seems to be supported by any evidence.

Tye claims that Huang’s picture and profile were expunged from the webpage of the WIV lab in which she worked, even though information for every other student member of that research group remains available, whether or not they later moved on to another institution. However, there doesn’t seem to be any evidence that Huang’s picture and profile were ever posted on this webpage in the first place. (Tye’s presentation also suggests that Huang is the only student without a picture on that page, but scrolling down reveals two other students with a short biography but no picture and a third with a picture but no biography.) Anyone who has ever browsed lists of graduate students or professors on the websites of research institutions will know that it’s not uncommon to see names without an accompanying picture or information. So this apparent anomaly isn’t evidence of anything.

Still, the story gained enough traction on Chinese social media that, on February 16th, the WIV issued a statement denying it. According to this statement, Huang Yanling worked at the WIV until she graduated in 2015, and has since lived in another province. This account is consistent with her ResearchGate profile, which shows that she hasn’t published anything since 2015. That would be extremely unlikely if she were still working at a research institution. Tye nonetheless contends that, were Huang still alive, the CCP would have produced her for a photo-op. That it has not done so, he says, is compelling evidence that the rumours of her mysterious death are correct. I have no idea why so many people seem to find this argument persuasive. Not only would such a photo-op fail to dispel this rumour, it would probably do precisely the opposite by drawing attention to it. I don’t even think we know what Huang Yanling looks like, because I don’t think we have any pictures of her, so if the Chinese authorities arranged a photo-op with someone they claim to be her, we’d have no way to know that it’s true. Even if there is a picture of her out there, it wouldn’t be difficult for the Chinese authorities to find someone who looks like her for the purposes of a propaganda stunt, something people on the Internet would point out immediately.

In his NRO assessment of the lab escape theory, Jim Geraghty tries to cast suspicion on the WIV’s denial by relating the following anecdote:

On February 17, Zhen Shuji, a Hong Kong correspondent from the French public-radio service Radio France Internationale, reported: “when a reporter from the Beijing News of the Mainland asked the institute for rumours about patient zero, the institute first denied that there was a researcher Huang Yanling, but after learning that the name of the person on the Internet did exist, acknowledged that the person had worked at the firm but has now left the office and is unaccounted for.”

Geraghty invites us to wonder why the WIV might deny that Huang Yanling had ever worked there, only admitting it when it was pointed out that her name was listed on the institute’s website. Does this not indicate that this elusive individual was indeed SARS-CoV-2 patient zero? It does not, because Geraghty’s reporting is (again) highly misleading.

Here is a translation of what the Radio France Internationale article says a few paragraphs after the passage Geraghty quoted:

Beijing News tried to verify the information with researcher Shi Zhengli, who specializes in bat coronavirus research, and Chen Quanjiao, who works on influenza; neither could confirm if there was a staffer named Huang Yanling in the institute. They further commented there were more than 1000 staffers in the institute, not a single one was infected during the pandemic. Netizens subsequently pointed out Huang’s name was on the official page of the institute, but the content related to her had been deleted.

By quoting the first paragraph of the Radio France Internationale and omitting the second, Geraghty makes it sound like the WIV had been caught in a lie, evidence of which remained on its own website. In fact, the report simply shows that neither Shi nor Chen were able to recall the name of a particular researcher in a team of over 1,000 who had most likely left the facility five years earlier. This interpretation is corroborated by the original Beijing News article.

So there is no real evidence that Huang Yanling had anything to do with the outbreak in Wuhan and, in fact, we have every reason to believe she stopped working at the WIV several years ago. But there are many additional reasons to think Tye’s story is implausible. First, it’s worth keeping in mind that, according to the South China Morning Post (which claims to have seen confidential government data), the first person believed to have been infected by SARS-CoV-2 is a 55-year-old man. Without more details, it’s hard to know what to make of this report, but it’s another piece of evidence that makes Tye’s story unlikely. If Huang Yanling was still a graduate student in 2015, she would have been in her late 20s or early 30s in 2019, and a woman of that age is overwhelmingly unlikely to die even if she has been infected by SARS-CoV-2.

Indeed, according to a recent French study, the infection fatality rate for a woman between 30 and 39 is only 0.01 percent. So even if Huang Yanling had still been working at the WIV and had been infected by SARS-CoV-2 there, it’s very unlikely that she would have died. Moreover, as I explained in the first part of this essay, everything indicates that nobody, including the local health authorities, had noticed the cluster of pneumonia in Wuhan until late December. If Huang Yanling were patient zero, she would presumably have been infected sometime in November. Had she subsequently died she would almost certainly have already been dead or at least been hospitalized in a very serious condition by late December. It is implausible that, if a woman in her late 20s or early 30s who worked with viruses in a research lab had been hospitalized with pneumonia shortly before cases of pneumonia of unknown etiology had started to show up in hospitals, people wouldn’t have connected the dots.

The theory that Huang Yanling was patient zero is entirely without merit. It’s just an unsubstantiated rumour dreamed up and circulated by random people on the Internet. But unlike most of these theories, otherwise intelligent people have allowed themselves to be persuaded that it deserves to be taken seriously. Similarly unsubstantiated theories circulate on Facebook and Twitter all the time in the West, and Chinese social media is no different. Notwithstanding the many awful characteristics of the Chinese regime and the police state it runs, it’s important to maintain the same epistemic standards when assessing accusations of Chinese malfeasance that we would ordinarily employ when scrutinising any other hypothesis.

Yuri Deigin and “Project Evidence”

But not everybody who believes that SARS-CoV-2 escaped from a lab thinks that Huang Yanling was patient zero. There are many people who think it’s likely that SARS-CoV-2 originated from a lab in Wuhan, yet don’t claim to know which researcher was infected first, so I want to discuss the lab escape theory more generally. We should distinguish between at least two versions of this theory. According to the first version, SARS-CoV-2 emerged in the wild and infected animals from which samples were taken by researchers in Wuhan, which somehow led to someone being infected and ultimately to the outbreak. According to the second version, SARS-CoV-2 was artificially created in a lab, accidentally infected someone and started the outbreak.

Defenders of the lab escape theory usually cite two sources. The first is a document entitled “Evidence SARS-CoV-2 Emerged From a Biological Laboratory in Wuhan, China” published on a website called “Project Evidence” by an anonymous group who describe themselves as researchers. The group forwards evidence that SARS-CoV-2 escaped from a lab and, while they don’t conclude that this is definitely what happened, it is clearly the impression they are trying to convey. While they reject the theory that SARS-CoV-2 was an artificially created bioweapon released intentionally, they don’t rule out the possibility that it was bioengineered. However, they seem to think that a naturally evolved virus escaped from a lab after someone accidentally became infected. The other source proponents of the lab escape theory often cite is a blog post entitled “Lab-Made? SARS-CoV-2 Genealogy Through the Lens of Gain-of-Function Research,” written by a biotech entrepreneur named Yuri Deigin. As the question mark in the title indicates, Deigin doesn’t claim that SARS-CoV-2 definitely originated from a lab either and, in his conclusion, he even maintains that a natural origin is more likely. However, throughout his post, he points out “strange coincidences,” which he evidently thinks point to a lab escape.

Both these documents, especially the first, are confused, but they make so many points that I’m not going to be able to debunk every one. (The first also favourably reviews the theory that Huang Yanling was patient zero, which I’ve just discussed.) They bury the reader under a mass of information, the sheer weight of which seems convincing, but most of it is confused and/or doesn’t really support the lab escape theory. Unfortunately, most casual readers won’t realise this and, notwithstanding the authors’ caveats, will come away with the impression that SARS-CoV-2 probably did originate in a lab. I have no doubt that Deigin and the people behind “Project Evidence” believe what they have written, but on some crucial points their reasoning is flawed and their conclusions, consequently, are highly misleading. Here, I’ll address the central arguments offered in support of the theory that SARS-CoV-2 is a bioengineered virus and will avoid technical details. (For those interested, I discuss this more at length on my blog.)

Different coronaviruses have different spike proteins on their surfaces. These bind to different types of receptors and allow them to infect different types of cells in different species. SARS-CoV-2 has a spike protein that allows it to bind to a receptor known as ACE2 found on certain human cells. The receptor-binding domain (RBD) in these spike proteins plays a key role in this binding process. The closest known relative of SARS-CoV-2 is a bat coronavirus called RaTG13-CoV. Even though SARS-CoV-2 is genetically very similar to RaTG13-CoV overall, they are very different in the part of the genome that codes for the RBD. The RBD of SARS-CoV-2’s spike protein differs from that of RaTG13-CoV because it can infect humans easily, whereas RaTG13-CoV probably can’t, or at least not very efficiently. In the part of the genome that codes for the RBD, SARS-CoV-2 is much closer to coronaviruses found in pangolins, which is why researchers believe that, although it ultimately originated in bats, the ancestor of SARS-CoV-2 may have passed through pangolins. This is where they think it acquired the ability to infect humans by recombination with a pangolin coronavirus.

In other words, a pangolin already infected with a coronavirus was somehow infected by a bat coronavirus, and replication produced a new virus that could infect humans even though neither of the original viruses could do so efficiently. This sequence of events is not as unlikely as it sounds, because pangolins and bats have recently been observed sharing burrows in Gabon, so it is not unreasonable to assume that it could also have happened in China. Of course, this is just one possibility, and the actual story could turn out to be more complicated. It is also possible that the virus went from a bat to a pangolin, then back to a bat or some other animal, before infecting humans. Alternatively, there may be undiscovered bat coronaviruses that are very similar to SARS-CoV-2 in the RBD, not because they acquired this part of their genome through recombination with a pangolin coronavirus, but because they independently evolved in this way. In fact, it’s possible that pangolin coronaviruses acquired this RBD from bats, not vice-versa. The truth is that we don’t know. However, since overall SARS-CoV-2 is genetically closer to RaTG13-CoV than to any other virus we know about, but is much closer to pangolin coronaviruses in the RBD, our best theory for the moment is that it was the result of a recombination event during which a relative of RaTG13-CoV acquired the RBD of a relative of those pangolin coronaviruses.

Such recombinations occur naturally all the time, but they can also be produced artificially. Scientists often create such chimeras because it allows them to examine the role played by different parts of a virus. If, for instance, you want to know whether the RBD is what makes one virus more infectious to humans than another, you could replace the RBD of the former with that of the latter and see if the resulting chimera can more easily infect human cells in culture. More generally, if you want to bioengineer a virus to perform a particular task, you can mix and match components of different viruses or simulate natural selection in an existing virus until you get an organism that can perform as desired. Of course, those strategies are not mutually exclusive, you can use a combination of both. So, it’s certainly possible that SARS-CoV-2 was artificially created in this way. But lots of things are possible that never happen. At issue when attempting to determine the origin of SARS-CoV-2, is what is likely, not what is possible.

Deigin and the anonymous group behind “Project Evidence” point out that researchers at the WIV have long been involved in the kind of research I just described with bat coronaviruses. That is true, but it is not, by itself, evidence that SARS-CoV-2 was bioengineered there except in a very weak sense. But Deigin and the people behind “Project Evidence” add that RaTG13-CoV was discovered in samples collected from bats in Yunnan, more than 1,000 kilometres from Wuhan. So, even allowing for the intermediary recombinations and mutations needed to produce SARS-CoV-2, that’s a lot of distance to cover. But bat coronaviruses are massively under-sampled. We know about a handful of them, but there are thousands more we haven’t even discovered yet. It is perfectly possible that there are bats in Hubei province or somewhere else closer to Wuhan than Yunnan that carry an even closer relative of SARS-CoV-2, it’s just that scientists have not stumbled upon them yet. This is entirely unsurprising, since the probability they would chance upon those particular coronaviruses is infinitesimal. There are plenty of bats in Hubei and, as this study shows, they also carry coronaviruses.

Bear in mind that, although RaTG13-CoV is the closest relative of SARS-CoV-2 that we know about, it’s still pretty distantly related and only about 96 percent similar genetically. Their most recent common ancestor probably goes back decades and there is no reason to think much closer relatives don’t circulate in Hubei province. If scientists in Wuhan had accidentally been infected by RaTG13-CoV (assuming such an infection were even possible), the result would not have been SARS-CoV-2 but something much closer genetically to RaTG13-CoV. Similarly, if scientists at the WIV had artificially created a virus by replacing the RBD of RaTG13-CoV with that of a pangolin coronavirus, the result would have been very different from SARS-CoV-2 unless they had simulated natural selection to create a very different virus. This process, however, would have left signs in the genome of the virus that it had recently been under strong selection, but this is not the case. In short, if scientists artificially created SARS-CoV-2, they almost certainly didn’t use RaTG13-CoV but another bat coronavirus that nobody knows about. I suppose this is possible, but there is no evidence it happened.

If researchers at the WIV had been conducting experiments like these, it’s surprising that no scientists elsewhere had heard about them. Nor is there any evidence that anyone has discovered a bat coronavirus more closely related to SARS-CoV-2 than RaTG13-CoV. Furthermore, structural analyses would apparently have predicted that the RBD of the pangolin coronavirus was not especially well suited to binding human ACE2, so it is highly unlikely researchers would have used it to create a chimera for this purpose. This is not necessarily dispositive; researchers may have wished to create this chimera for some other reason, but we’re now adrift in a world of ad hoc hypotheses and idle speculation. Besides which, as far as we know, nobody at the WIV even knew about these pangolin coronaviruses until February of this year, when a team of researchers at other institutions realised that they were very similar to SARS-CoV-2 in the RBD and uploaded the genomes to public databases.

Until very recently, we had every reason to believe that even RaTG13-CoV had not been fully sequenced by researchers at the WIV until January. According to a paper about SARS-CoV-2 published in Nature at the beginning of February by Shi Zhengli and colleagues, they had previously detected the presence of RaTG13-CoV, along with various other coronaviruses, in samples collected from bats, but initially had only sequenced a short region of the genome called the RdRp. (As this paper explains, this particular region is highly conserved among coronaviruses, making it a good target when testing for coronaviruses in samples.) Although the language in the paper is ambiguous, it suggests that, after SARS-CoV-2 emerged and was sequenced, they looked at the data they already had and noticed similarities, so they sequenced the full RaTG13-CoV genome. This scenario was plausible since, until the similarity with SARS-CoV-2 was noticed, it seems they had no reason to sequence the whole genome, which is expensive and time-consuming.

Deigin thinks Shi Zhengli and her team had probably already sequenced the full genome of RaTG13-CoV before the outbreak of SARS-CoV-2, but his argument is confused. He points out that RaTG13-CoV is probably the same as BtCoV/4991, another bat coronavirus, the discovery of which was reported by Shi and her team in a 2016 paper. A partial sequence was posted on NCBI at the same time. Deigin argues that BtCoV/4991’s RdRp sequence is identical to that of RaTG13-CoV and Shi Zhengli has recently confirmed that BtCoV/4991 and RaTG13-CoV were indeed the same virus. But this doesn’t mean they had already sequenced the whole genome of RaTG13-CoV by 2016. Most of the papers that cite the article on the coronavirus detection method only sequenced the RdRp region needed for detection, so there is nothing remotely unusual about this. (In another paper they published in 2015, Shi Zhengli and her team obtained 64 partial sequences, but only selected 11 of the samples for whole genome sequencing.) Deigin thinks they had probably sequenced the whole genome back then because, in another paper they published in 2019, BtCoV/4991 is included in a phylogenetic tree, and Deigin doesn’t think “RaBtCoV/4991’s place in that tree was determined based solely on” a short RdRp sequence, even though this is exactly what the paper says they did. Furthermore, papers that use the detection method based on the RdRp commonly include phylogenetic trees of coronaviruses using only RdRp sequences, so Deigin’s whole objection is unconvincing.

Shi Zhengli explained in a recent interview in Science magazine that her team had sequenced RaTG13-CoV’s full-genome in 2018. Strictly speaking, this is not inconsistent with what they said in the paper published in February, but it contradicts the most natural reading of it. In any case, it doesn’t really matter, because the fact that RaTG13-CoV had already been sequenced before 2020 gives us no reason to think that SARS-CoV-2 was artificially created by replacing the RBD of a bat coronavirus with that of a pangolin coronavirus. Indeed, as I’ve already explained, even if SARS-CoV-2 was created in that way, RaTG13-CoV was almost certainly not used as a backbone.

In order to believe that SARS-CoV-2 was bioengineered, we would need to assume that researchers at the WIV had previously discovered a bat coronavirus closely related to SARS-CoV-2 (though almost certainly not RaTG13-CoV), and also pangolin coronaviruses almost identical in the RBD to those discovered by researchers at other institutions (who didn’t report this discovery until February of this year). They then replaced the RBD of the former with that of the latter to create a chimera (not just a pseudovirus that can’t replicate after infecting a cell, as most of the studies mentioned by Deigin and the people behind “Project Evidence” did, but a fully infectious virus), without any researcher anywhere else in the world having ever heard anything about any of this.

In other words, this requires all sorts of purely ad hoc hypotheses, most of which are rather unlikely. Sure, it’s possible, but why introduce all these hypotheses unless it has already been decided that SARS-CoV-2 was artificially created at the WIV? Again, a lot of things are possible, but we don’t usually believe them unless we have a good reason to do so—and nor should we.

The State Department cable

The theory that SARS-CoV-2 evolved naturally, but then accidentally escaped from a Wuhan lab is scarcely more plausible. Of course, as the people behind “Project Evidence” correctly point out, viruses have escaped from labs before, but there’s no reason to think it happened on this occasion. We’d need to assume that scientists at the WIV discovered SARS-CoV-2 before the outbreak in Wuhan. Alternatively, they discovered a closely related virus that infected someone at the lab, circulated in humans (or possibly another species) for a while and gave rise to SARS-CoV-2 by accumulating enough mutations to make it well-adapted for humans. Shi Zhengli has said that after word reached her that a new coronavirus had appeared in Wuhan, she and her team immediately went through their records but were unable to find anything that matched the sequences found in samples taken from patients. Obviously, she could be lying, but there is no evidence that she is. As Dennis Carroll, the former director of USAID’s emerging threats division, told Vox, scientists like to talk to one another about their work and it would be surprising if researchers at the WIV had discovered a virus as unusual as SARS-CoV-2 without anyone else hearing about it. Again, this is hardly dispositive, but it makes an unsupported theory unlikely to begin with.

Nevertheless, versions of this theory have been defended by the Washington Post columnist David Ignatius and his colleague Josh Rogin. The latter’s articles, in particular, have received a good deal of attention so I want to take a moment to examine their claims here. Back in April, Rogin reported on the contents of some State Department cables, excerpts of which appeared to have been leaked to him by an anonymous source. The cables had originally been transmitted by US officials following a 2018 visit to the WIV (where the first laboratory in China to achieve the highest level of international bioresearch safety, BSL-4, had recently opened). Rogin reported that the authors of these cables noted a “shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory.” He then added that “sources familiar with the cables said they were meant to sound an alarm about the grave safety concerns at the WIV lab, especially regarding its work with bat coronaviruses.” But that inference is not at all clear from the short passages quoted in Rogin’s article, and without the context provided by the rest of the cable, it was not possible to determine whether or not the US officials who wrote it were actually worried that a lab accident might result in an outbreak.

The same could be said about the only other part of the cable that Rogin quoted verbatim:

“Most importantly,” the cable states, “the researchers also showed that various SARS-like coronaviruses can interact with ACE2, the human receptor identified for SARS-coronavirus. This finding strongly suggests that SARS-like coronaviruses from bats can be transmitted to humans to cause SARS-like diseases. From a public health perspective, this 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.”

Rogin then suggested that this was intended to warn that Shi Zhengli’s work on bat coronaviruses in particular represented a threat to public health. However, absent more context, this passage is more naturally understood to mean the opposite—that Shi’s work was important to prevent the emergence of another coronavirus that can transmit to humans.

If the full cable had vindicated Rogin’s interpretation—or the interpretation his source conveyed to him and that he had uncritically reported—why had the entire text not been leaked? The answer to this question was eventually provided in July, when the State Department did finally release them—with a few redactions—after the Washington Post filed a Freedom of Information Act lawsuit. It’s now clear that the spin from Rogin’s sources was extremely misleading. The authors of the cable didn’t express any “grave safety concerns,” they simply pointed out that a lack of adequately trained personnel limited productivity and that the WIV would welcome help from the US to train more people. In the passage describing the work that Shi’s team was doing on bat coronaviruses, there is no indication that this research was alarming or that it could result in a public health disaster. On the contrary, the cable’s authors write that, despite the lack of appropriately trained personnel limiting productivity, WIV researchers had already completed important work that helped to understand the origins of SARS-CoV-1, and re-emphasised the importance of continuing to monitor SARS-like coronaviruses in bats. In short, Rogin’s original reporting of the cable’s content and meaning was false.

Rogin may not have had access to the full unredacted texts of the cables back in April, and been misled about their content by his sources. Nevertheless, that hardly excuses his sloppiness—since the passages he quoted did not support the interpretation of the cable his sources provided, he should have asked for more context before publishing them or else been a lot more cautious in his reporting. A journalist of Rogin’s experience knows full well that government officials leak misleading information to further their agendas and his failure to include the necessary health warnings borders on professional malpractice. When the redacted cables released by the State Department failed to support his narrative, Rogin published the redacted sections on Twitter. In what looked like an attempt by a journalist to rescue a discredited story, he insisted that these passages upheld his original reporting. They do not.

The WIV-University of North Carolina experiment

In his April op-ed, Rogin had also mentioned the controversy that erupted in 2015 around the kind of research Shi Zhengli’s team has been conducting, when a study involving the creation of chimera viruses was published in Nature and some researchers questioned whether this kind of work was really worth the risk. The people behind “Project Evidence” also cite this paper as evidence that people at the WIV were experimenting on bat coronaviruses. The only problem is that, although researchers at the WIV were involved in that paper (specifically, they provided the spike sequence used to create the chimeric virus), the controversial experiment was performed at the University of North Carolina, not the WIV. So it’s misleading to use this study to support a claim that “other scientists questioned whether Shi’s team was taking unnecessary risks,” when in fact it was a US-based team of researchers that was at the centre of this controversy. In any case, research on SARS-like coronaviruses at the WIV might not even have been conducted at the BSL-4 lab, since this level of biosafety is not required for this kind of work, so even if we could be sure that there were serious safety issues with the BSL-4 lab at the WIV, it would be largely irrelevant. And even if there weren’t enough properly trained personnel at the WIV to safely operate a BSL-4 lab, it would not show that research that doesn’t require that safety level could not be conducted safely over there.

In short, no matter which version of the lab escape theory you prefer, it requires several hypotheses that are purely ad hoc. In particular, it requires the assumption that, unbeknownst to anyone else, researchers at the WIV had discovered and experimented on SARS-CoV-2 or a coronavirus more closely related to SARS-CoV-2 than RaTG13-CoV. But there simply isn’t any evidence for this or any evidence to support the theory that SARS-CoV-2 escaped from a lab at all. Sophisticated proponents of the lab escape theory admit there is no direct evidence that it did, but they think the fact that the outbreak started in Wuhan, precisely where one of the few labs where people study bat coronaviruses happen to be, constitutes indirect evidence. Their argument is a bit technical, so I won’t discuss it here, but if you’re interested you can find a refutation on my blog.

A naturally occurring spillover event

It is far more likely that the pandemic began with a naturally occurring zoonotic spillover event. In 2018, Shi Zhengli and her team published a paper that reported the results of a serological study conducted of 218 residents in four villages in Yunnan. These villages were located near caves where Shi and her colleagues had sampled bat coronaviruses closely related to SARS-CoV-1 and, therefore, to SARS-CoV-2. They discovered that six people, or about 2.7 percent of the sample, had antibodies for these coronaviruses, which suggests they had previously been infected. In another study published in 2019, Shi and her team reported the results of a similar serological survey performed on 1,497 residents of rural areas in three provinces of Southern China (Yunnan, Guangxi, and Guangdong), which found that nine people, or about 0.6 percent of the sample, tested positive for antibodies to bat coronaviruses. This may not seem like very many, but antibodies to coronaviruses apparently wane pretty quickly, so the seroprevalence found by those surveys probably underestimates the proportion of people who have been infected by bat coronaviruses at one point or other in those areas.

Hundreds of millions of people live in rural China, so every year millions of people are probably infected by bat coronaviruses. The overwhelming majority of those infections never result in a pandemic because those viruses are not very good at infecting humans and/or the people who are infected never transmit them to someone else because they live in low-density areas. (Even with SARS-CoV-2, which is quite good at infecting humans and for which most cases are located in densely populated areas, the vast majority of infections are a dead-end.) However, if a person contracts a bat coronavirus that has mutated to become particularly efficient at infecting humans, and if that person then travels to a densely populated area while contagious, then you have a pandemic. Of course, such a chain of events is evidently very unlikely or we’d be dealing with pandemics all the time. But if millions of people are infected by bat coronaviruses every year in China, then outbreaks will inevitably occur from time to time. This has been made significantly more likely by economic development and urbanisation, both of which have led to human encroachment on the habitat of bats and increased circulation between rural and urban areas.

Somewhere in rural China, someone probably became infected by SARS-CoV-2 or its ancestor and then travelled to Wuhan or infected someone who did. Perhaps he came to sell produce or to visit his family. In any case, the virus eventually reached Huanan Seafood Market, which served as a springboard from which the virus spread to the rest of Wuhan, and eventually across the entire world. The original spillover event may not even have occurred in Hubei, since Wuhan is a major transportation hub in the middle of China, and a very large number of people from all over China pass through it every day. We’ll probably never know for sure how the outbreak started, but given how many people are likely infected by bat coronaviruses in China every year, this is the most plausible scenario. By contrast, only a very small number of people work in labs that study bat coronaviruses in Wuhan and, unlike regular people who come in contact with bats, they are trained in extremely strict safety protocols. So I don’t see why we should regard the lab escape theory as anything other than a theoretical possibility that is not particularly likely.

Part Four of this series can be found here.