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The Rise and Fall of the Raccoon Dog Theory of Covid-19

A new paper by a prominent American virologist has called into question a string of high-profile news reports about the role that raccoon dogs may have played in the emergence of the Covid-19 pandemic.

Late last month, Jesse Bloom, a computational virologist at the Fred Hutchinson Cancer Center in Seattle released a paper in which he analyzed raw genomic data from hundreds of environmental swabs that Chinese scientists collected from cages, carts, and other surfaces at the Huanan Seafood Wholesale Market in Wuhan, China. The swabs were collected beginning on January 1, 2020, after Chinese authorities abruptly shut down the market amid the worsening Covid-19 outbreak in the city.

The Huanan seafood market’s role in the emergence of the Covid-19 pandemic is at the center of a hot debate. Many of the early Covid cases in Wuhan (though not all) have been linked to the market, which was known to sell live animals, including species like common raccoon dogs that are susceptible to infection with SARS-CoV-2. Some have argued that these and other findings make the market the likely site of one or more natural spillover events in which SARS-CoV-2 first entered the human population from a raccoon dog or another intermediate animal host. But no infected animal was found at the market, and others have argued that the bustling facility was more likely the site of a super-spreader event, in which a virus that had already entered the human population in late 2019 was amplified. Which was it: the site of the original spillover or only a super-spreader venue? This question has been a key battleground in the tumultuous debate about Covid-19’s origin.

Given this context, the raw data from the environmental swabs have long been seen as a possible clue to what happened at the Huanan Seafood Wholesale Market. But the data only became available to the global research community in 2023, after years in which Chinese Center for Disease Control and Prevention and its researchers kept it out of the public domain. The data has since sparked a firestorm of discussion, including numerous stories in mainstream news outlets that have relied on the data to report a link between raccoon dogs and Covid’s origin. Bloom’s new paper helps clarify what has become something of a confused, and confusing, media spectacle.

Bloom’s paper, which was published as a preprint on bioRxiv on April 26, found that the data from the swabs provide no evidence one way or another about whether raccoon dogs or other animals at the market were infected with SARS-CoV-2. It also highlights what is perhaps the most significant limitation of the data from the environmental swabs collected by Chinese scientists. The swabs were collected, Bloom writes, “at least a month after the first human infections in Wuhan.”

“It is just very hard to take data collected that far downstream of initial entry into humans and to convincingly support any precise scenario for how the virus got into humans,” he said in an interview.

“Even if you had animal-to-human transmission in the market in December, by the time you collected samples in January, it could have been easily spreading back from humans to animals,” added Sergei Pond, a computational virologist at Temple University who was not involved in Bloom’s research. “Any self-respecting defense attorney would have a field day with this.”

Members of staff of the Wuhan Hygiene Emergency Response Team drive their vehicle as they leave the closed Huanan Seafood Wholesale Market in the city of Wuhan, in Hubei, Province on January 11, 2020, where the Wuhan health commission said that the man who died from a respiratory illness had purchased goods. - China said on January 11, 2020 that a 61-year-old man had become the first person to die from a respiratory illness believed to be caused by a new virus from the same family as SARS (Sudden Acute Respiratory Syndrome), which claimed hundreds of lives more than a decade ago. Forty-one people with pneumonia-like symptoms have so far been diagnosed with the new virus in Wuhan, with one of the victims dying on January 8, 2020, the central Chinese city's health commission said on its website. (Photo by NOEL CELIS / AFP) (Photo by NOEL CELIS/AFP via Getty Images)

Members of staff of the Wuhan Hygiene Emergency Response Team drive their vehicle as they leave the closed Huanan Seafood Wholesale Market in the city of Wuhan, in Hubei province, China, on Jan. 11, 2020.

Photo: Noel Celis/AFP via Getty Images

Bold, Exaggerated Headlines

Bloom’s analysis contains other significant insights (more on that below), but he was not the first nor the only scientist independent of Chinese institutions to obtain and analyze some of the raw data from the Huanan market environmental swabs. In March, an international team of virologists, evolutionary biologists, and other scientists — many of whom have been starring players in the heated scientific and social media debates about Covid’s origins — discovered that a portion of the raw data had been uploaded by Chinese researchers to a global online database. The international group put together their own independent report on the available data and first informed the World Health Organization of their preliminary findings on March 11. Before the report was ready to be released publicly, the press got wind of the team’s work. What followed was a bumper crop of bold headlines.

“The Strongest Evidence Yet That an Animal Started the Pandemic,” declared The Atlantic in a March 16 headline. “New Data Links Pandemic’s Origins to Raccoon Dogs at Wuhan Market,” announced the New York Times that same day. “New Evidence Supports Animal Origin of Covid Virus through Raccoon Dogs,” wrote the Scientific American a day later. The news of a link between raccoon dogs and Covid’s origins spread like a conflagration.

What was this strong evidence? The Atlantic’s March 16 story described the international team’s work like this:

“A new analysis of genetic sequences collected from the market shows that raccoon dogs being illegally sold at the venue could have been carrying and possibly shedding the virus at the end of 2019,” wrote The Atlantic’s Katherine Wu. “It’s some of the strongest support yet, experts told me, that the pandemic began when SARS-CoV-2 hopped from animals into humans, rather than in an accident among scientists experimenting with viruses.”

Wu reported, among other things, that the international team of researchers had “discovered that several market samples that tested positive for SARS-CoV-2 were also coming back chock-full of animal genetic material — much of which was a match for the common raccoon dog, a small animal related to foxes that has a raccoon-like face.”

At the time The Atlantic published its article on March 16, the international team’s report was not yet publicly available; it wouldn’t be released until the following week. In the days before and after the report’s release, several of its authors gave interviews to top news outlets about their findings. One of the scientists involved in the international team’s analysis was quoted in The Atlantic saying: “This is a really strong indication that animals at the market were infected. There’s really no other explanation that makes any sense.” Another author told the New York Times: “This isn’t an infected animal. But this is the closest you can get without having the animal in front of you.”

The actual text of the international team’s report, though, offered more limited conclusions than the press statements of some of its authors.

“Declarations in the media are what people as individuals think and their interpretation and different people in the group had different certainty on what you can deduce,” said Florence Débarre, a French evolutionary biologist and one of the authors of the international team’s report, who did not speak to The Atlantic for its story.

The international team’s report appeared on Zenodo on March 20. Contrary to the quoted assertions of a few days before, the published report did not claim that its findings could only sensibly be explained by infected animals at the market, or that its work was the closest you could get without having an infected animal in front of you. What it did convincingly show was that raccoon dogs and other mammals susceptible to SARS-CoV-2 were being sold at the market in the run-up to its closure on January 1, 2020. “It was a significant finding given that the Chinese CDC had not mentioned them before in the context of these data,” Débarre said.

The international team’s report also said that the genetic material from susceptible nonhuman animals were at their “highest frequency” in stalls in the southwest corner of the market, where live wildlife was known to have been sold and where most SARS-CoV-2 genetic material was collected. And the team’s report engaged in a metagenomic analysis of the data they had from the environmental swabs: Among other things, the team parsed the mix and quantity of animal genetic material found in environmental swabs that had been designated as positive for SARS-CoV-2 by the China CDC.

The team found that there were several SARS-CoV-2 positive swabs from the market that also contained some quantity of genetic material from raccoon dogs and other susceptible mammals. As the New York Times reported in its March 16 story, one swab, in particular, caught the researchers’ eyes: a swab labeled Q61. This swab was collected from a cart in the southwest corner of Huanan market on January 12, 2020; it was designated as positive for SARS-CoV-2 in the China CDC’s data set; and when the international team analyzed the contents of the swab, it contained a large quantity of raccoon dog genetic material and very little human genetic material.

As one of the team’s scientists told the New York Times: “We were able to figure out relatively quickly that at least in one of these samples, there was a lot of raccoon dog nucleic acid, along with virus nucleic acid.”

In the end, based on these and other findings, the international team stated the following in their report: “Although we cannot identify the intermediate animal host species from these data, a plausible explanation for the co-occurrence of the genetic material of SARS-CoV-2 and susceptible animals is that a subset of these animals were infected. Combined with the previously published observation of the strong association of the earliest reported Covid-19 cases with the west side of the market, and the clustering of SARS-CoV-2-containing environmental samples near the wildlife stalls, this provides further support for the hypothesis that wildlife were the source of the first human SARS-CoV-2 infections.” Elsewhere in the report, the author’s write that their findings identify “these species, particularly the common raccoon dog, as the most likely conduits for the emergence of SARS-CoV-2 in late 2019.”

View of a raccoon dog or Tanuki (Nyctereutes procyonoides) at the Chapultpec Zoo in Mexico City on August 06, 2015. A month ago nine raccoon dog pups were born. This species is native from Japan and China, and the parents of the cubs were donated by Japan. AFP PHOTO / ALFREDO ESTRELLA        (Photo credit should read ALFREDO ESTRELLA/AFP via Getty Images)

View of a raccoon dog at the Chapultepec Zoo in Mexico City on Aug. 6, 2015.

Photo: Alfredo Estrella /AFP via Getty Images

Statistically Insignificant

This is where Jesse Bloom entered the picture. After the international team’s work made major headlines across the news media, the Chinese researchers posted their own analysis of the Huanan seafood market swab data online, in a revision to an earlier preprint from February 2022. A peer-reviewed version was then published in the scientific journal Nature. That paper confirmed the presence of raccoon dogs and other susceptible animals at the market but noted that the environmental samples “cannot prove that the animals were infected.” At this point, Bloom decided to jump in too and take his own look at the raw data.

Bloom’s analysis took a slightly different approach than the international team that preceded him. Among other things, he was working from a more complete data set, which had been released by the Chinese researchers after they posted their paper. And Bloom not only looked at the quantity and type of animal genetic material in the environmental swab data, but he also analyzed and published the quantity of SARS-CoV-2 genetic material found in the swabs. When Bloom looked under the hood, he made some surprising findings.

For instance, he took a close looked at swab Q61: the swab featured in the New York Times article that contained a great deal of raccoon dog genetic material and was also purportedly positive for SARS-CoV-2. What Bloom found was that the swab indeed contained a significant quantity of raccoon dog genetic material but very low amounts of SARS-CoV-2 genetic material.

As Bloom reports in his paper, “This sample tested negative by RT-qPCR and appears to have been called positive on the basis of containing 1 of ~200,000,000 reads that mapped to SARS-CoV-2.”

In other words, as Sergei Pond explained, the swab Q61 that got all that media attention was not all it was reported to be.

“One read out of 200,000,000 is completely statistically insignificant,” said Pond. “It really had no SARS-CoV-2. There is no evidence based on genetic analysis there was SARS-CoV-2 in that sample. One read out of 200,000,000 — it could have been a low level of trace contamination.”

What’s more, as Bloom’s preprint reports, Q61 was the only swab above a certain threshold for raccoon dog genetic material that contained any SARS-CoV-2 RNA at all: “13 of the 14 samples with at least 20% of their chordate mitochondrial material from raccoon dogs contain no SARS-CoV-2 reads, and the other sample [swab Q61] contains just 1 of ~200,000,000 million reads mapping to SARS-CoV-2.” When Bloom plotted the quantity of animal genetic material found in the swabs with their SARS-CoV-2 RNA content, he determined that there was in fact a negative correlation between the abundance of SARS-CoV-2 and genetic material from raccoon dogs in the swabs.

“I wouldn’t read too much into these correlations, but to the extent SARS-CoV-2 genetic material is associated with any of the material from these species, it is not with species that we think could have been infected with SARS-CoV-2,” he said. “It just sort of suggests that by the time these samples were collected, SARS-CoV-2 was all over the place, probably unrelated to the distribution of the animals and animal products [at the market].”

Photo taken on Dec. 29, 2022, shows Wuhan's Huanan seafood wholesale market, which has been closed for about three years since the initial outbreak of the novel coronavirus there. The Chinese government eased its strict antivirus measures earlier in the month. (Kyodo via AP Images) ==Kyodo

Wuhan’s Huanan Seafood Wholesale Market, which has been closed for about three years since the initial outbreak of the novel coronavirus, on Dec. 29, 2022.

Photo: Kyodo via AP

Media Hype vs. Scientific Method

Bloom notes that his preprint confirms many of the international team’s findings, including the presence of raccoon dogs and other susceptible mammals at Huanan market in the run-up to January 1, 2020. But the bottom line, Bloom said, is that “when looked at carefully these data are not sufficient to conclude anything either way about whether there were infected animals.”

He also had pointed words (at least in the context of a staid scientific paper) for the media coverage of this matter. The findings from his preprint, Bloom writes, “are somewhat inconsistent with related media articles that emphasized co-mingling of raccoon dog and viral material (Wu 2023; Mueller 2023) — in fact, raccoon dogs are one of the species with the least co-mingling of their genetic material and SARS-CoV-2.” Instead, Bloom found that the greatest co-mingling of viral and animal material involved species that were “almost certainly not infected with SARS-CoV-2,” such as fish and livestock.

James Alwine, a virologist and emeritus professor at the University of Pennsylvania, who has written on the Covid origin debate and favors the natural spillover hypothesis, said he worries about the negative impact that sensational headlines and overhyped press statements have on the credibility of scientists.

“I must say I am always worried about the sensationalism that comes out with every one of these discoveries, because it just goes against my idea of how science should be talked about to the public,” he said. “And you know,” he added, “scientists are humans just like all of us, they get carried away and don’t always say the right things. But it has a deleterious effect.”

Apart from the media coverage, Alwine was keen to point out that the papers from Bloom and the international team actually show the iterative scientific process at work. Indeed, Bloom and some of the key scientists from the international team have had a professional and fruitful debate since their respective publications appeared. Several authors on the international team, including Débarre, have offered feedback on Bloom’s preprint. Bloom, in turn, slightly revised the piece to incorporate some of their comments.

Débarre, for her part, noted that despite Bloom’s findings regarding the Q61 swab, the international team still showed that raccoon dog genetic material was located in the same area of the market, indeed in the same stall, where other separate swabs found SARS-CoV-2 material.

“Overall we pretty much agree with what Jesse Bloom concludes,” she told me. “It is more a matter of interpretation in how you weigh other data and other pieces of evidence to form an interpretation.”

In terms of the broader picture — the overall debate about the origin of Covid-19 and whether it spilled over from nature or emerged out of a lab — Bloom told me he remains agnostic.

“I mean it is obviously hard when you are interpreting what is all circumstantial evidence. All publicly available evidence right now about how SARS-CoV-2 entered humans, it is all circumstantial,” he said.

“I think it is very unclear how SARS-CoV-2 first entered humans,” he added.

Since incorporating the comments he received, Bloom has submitted his preprint for peer review at a scientific journal. According to Débarre, the international team is working on new analyses that it hopes to submit for peer review at a future date.

The post The Rise and Fall of the Raccoon Dog Theory of Covid-19 appeared first on The Intercept.