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Tracing the Virus’s Origins

Experts from China and the World Health Organization wear face masks during a visit to the Wuhan Tongji Hospital in Wuhan, Hubei Province, China, February 23, 2020. (China Daily via Reuters)

On the menu today: One scientific research paper makes the case that SARS-CoV-2 — the type of coronavirus that causes COVID-19 — must have spent time percolating in a pangolin, the anteater-like species that is one of the world’s most heavily trafficked animals. But how does that square with other studies suggesting the Huanan Seafood Market wasn’t the origin point for the virus, and other scientists contending that a jump straight from bats to humans was more likely?

Does COVID-19 All Trace Back to Pangolins?

Yesterday someone sent me this article in Nature Medicine, arguing that the scenario of an accidental laboratory infection of SARS-CoV-2 — the type of coronavirus that causes COVID-19 — is unlikely, because the virus has certain features that indicate it evolved through a considerable period of natural selection, and those traits are just too similar to coronaviruses from pangolins for the virus to have jumped straight from bats to humans.

Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world27, and there are documented instances of laboratory escapes of SARS-CoV28. We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2.

In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. 1a) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV11. The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation.

The authors of this study are cautious; they note that we don’t know what we don’t know: “Although no animal coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled.” It’s conceivable that somewhere out there is a bat with a strain of the coronavirus that is nearly identical to SARS-CoV-2 found in humans, but that bat hasn’t been found yet.

While it is possible that one of the two major laboratories in Wuhan, China, researching coronaviruses also had pangolins in their labs, at this point we have no evidence indicating that those labs used those animals. (We do have strong evidence that they both used bats.)

If the genomes of the SARS-CoV-2 virus point to this virus percolating in pangolins for a while before jumping to humans, they point to a pangolin, and make the lab accident or improperly disposed viral material scenarios less likely. There certainly is enough evidence to suggest that illegal consumption of pangolins was occurring, probably throughout China and almost certainly within Wuhan.

But this piece of the puzzle is a challenging fit with other research that was pointing away from the origin of COVID-19 being the Huanan Seafood Market.

First, as that February article in The Lancet noted, “27 (66%) of 41 patients had been exposed to Huanan seafood market.” This meant that a third couldn’t be traced back to the market. A separate study in the New England Journal of Medicine could only tie 30 of the first 47 cases back to the market. 

As noted yesterday, two microbiologists in Australia, John S. Mackenzie and David W. Smith, are more skeptical that COVID-19 jumped to humans through pangolins:

The closest known wildlife sequence to SARS-CoV-2 remains the sequence from the virus isolated from an Intermediate horseshoe bat, but there were significant differences in the receptor-binding domain between the two viruses. Malayan pangolins (Manis javanica) have been suggested as potential intermediate hosts, and SARS-like viruses have been identified in pangolins seized in anti-smuggling operations in southern China, but they only shared about 85–92% homology with SARS-CoV-2.

But probably the most glaring not-fitting puzzle piece is the study of the genomic data that suggesting the strain of the virus found in the market evolved from other strains found elsewhere, not the other way around:

By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 (whose descendants included all samples from the Huanan Seafood Wholesale Market) was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Phyloepidemiologic analyses suggested that the SARS-CoV-2 source at the Huanan Seafood Wholesale Market was potentially imported from elsewhere. The crowded market then boosted SARS-CoV-2 circulation and spread it to the whole city in early December 2019.

Did someone encounter or eat a pangolin elsewhere in Wuhan away from the Huanan Seafood Market, contract SARS-CoV-2, travel around the city infecting others, then go to the market and set off the bigger outbreak? And from that, they ended up contracting a strain of the coronavirus that originated in bats was unrelated to the research on coronaviruses in bats going on in two major laboratories in the city? It is possible, but it is a remarkable sequence.

I feel like the “laboratory accident” scenario is being dismissed out of hand by some people who do not realize that this sort of sequence of events already happened in China 16 years ago:

SARS has sent the head of another top official in China rolling. Yesterday, director Li Liming of the Center for Disease Control and Prevention (CDC) resigned, along with several lower-ranking officials, after a report by a panel of experts blamed China’s most recent outbreak of severe acute respiratory syndrome on a series of flaws at the CDC’s National Institute of Virology in southern Beijing.

The outbreak earlier this year, which sickened eight people in Beijing and Anhui Province and killed one (ScienceNOW, 27 April), started when two workers at the CDC lab, independently from each other, developed SARS. The most likely source of their infection, the report concludes, is a batch of supposedly inactivated SARS virus that was brought from a high-containment facility into a low-safety diarrhea research lab where the two were working. Apparently, the inactivation process–adding a mix of detergents to the virus–did not work properly, according to the study, of which only a five-paragraph summary has been released. In a breach of standard safety procedures, the researcher who carried out the inactivation–identified only by a family name, “Ren”–had not tested whether the virus was truly inactive, according to the panel.

Some scientists hailed the report and Li’s resignation. “This is a clear sign to Chinese scientists and the rest of the world that the Chinese government is taking [biosafety] seriously,” says Guan Yi, a virologist at the University of Hong Kong. But others are disappointed that many details about the incident and the lab’s operating procedures remain hidden. “I was hoping for a full, more open account of what happened,” says Tony Della-Porta, an Australian biosafety consultant who helped investigate earlier SARS escapes in Singapore and Taiwan.

(If you’ve ever thought your job was difficult, just think of the words “low-safety diarrhea research lab.”)

For what it’s worth, the “accidental release from a lab” scenario is apparently being contemplated by senior officials in the British government, and David Ignatius’ column in the Washington Post Friday suggested that either U.S. intelligence officials or unspecified “scientists” can’t rule out that scenario.

CNN recently spoke to some of the country’s top virologists and found there isn’t a clear consensus yet:

Rutgers University bioweapons expert Dr. Richard Ebright told CNN, “the possibility that the virus entered humans through a laboratory accident cannot and should not be dismissed… It is absolutely clear the market had no connection with the origin of the outbreak virus, and, instead, only was involved in amplification of an outbreak that had started elsewhere in Wuhan almost a full month earlier.”

“I think people went into the fish market who were already infected,” Vincent Racaniello, a microbiology professor at Columbia University, told CNN. “In bats, these viruses are intestinal viruses, and they are shedding the bat feces, which we call guano,” he said. “And if you go into a bat cave, it is littered with guano. And farmers in many countries harvest the guano to fertilize their fields.”

Dr. Simon Anthony, a professor at the public health grad school of Columbia University, told CNN, “Early in the outbreak … everyone was talking about the thing having emerged from the wet market. And now I think the data calls into question whether or not that’s really true.”

Some might ask why we should bother looking into this if clear answers are likely to never be found; the Chinese government certainly isn’t going to welcome outside investigators to go poking around the city of Wuhan and its own labs, trying to determine the source of the virus. But the origin of the coronavirus is the biggest and most consequential mystery in the world right now. Until we know how this virus got into humans, we live with the risk of it happening again with another strain — perhaps an even more virulent or contagious one.

As noted earlier, from the first cases of COVID-19, the Chinese government has lied and lied and lied.

There are two other dogs that aren’t barking, so to speak. First, the Chinese government has reopened the wet markets. (Some folks are arguing the reopening is a good thing.) Even a regime as callous as the one in Beijing wouldn’t want to roll the dice on another pandemic. Why are Chinese authorities not worried about a second outbreak at those markets, or some new virus emerging from their crowded, unsanitary conditions? Maybe Chinese authorities are just insanely reckless. Or maybe they have some reason to believe that the market wasn’t really the origin point for SARS-CoV-2.

The other non-barking dog stems from the fact that a regime like the one in Beijing would be likely to be able to either A) find the vendor or vendors who originally sold either bats or pangolins or B) find any old vendor to use as a scapegoat. In fact, you might have figured the regime would have already held a show trial and/or execution by now. The regime says the origin of this virus is still a mystery . . . and authoritarian regimes that like their populaces to see them as all-knowing and all-powerful are not usually big fans of unsolved mysteries. What’s going on with this?

ADDENDA: Boy, if you’re not reading NR these days, you’re missing a ton. Dan McLaughlin tries to make sense of the hash of legal decisions about Wisconsin’s election today — who in their right mind holds a primary during a stay-at-home order? — while Avik Roy brings the reassuring news that there are 104 different COVID-19 treatments currently in preclinical or clinical studies. Michael Brendan Dougherty surprises us all by looking at the governance of China’s neighbors and concluding, “suddenly something like the Trans-Pacific Partnership makes a great deal more geopolitical sense.” Kathryn Jean Lopez talks with Fr. John Maria Devaney, a Dominican priest who ministers as a hospital chaplain in New York City, talking about what he’s living in an epicenter of this crisis. John Fund warns about the unintended consequences of the federal government’s effort to protect the airline industry.

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