There Is No Evidence Strong Enough to End the Pandemic-Origins Debate
The recent fight over wet-market raccoon dogs underscores just how much prior beliefs can affect interpretation.
Updated at 8:59 p.m. on May 24, 2023
Three and a half years since the start of a pandemic that has killed millions of people and debilitated countless more, the world is still stuck at the start of the COVID-19 crisis in one maddening way: No one can say with any certainty how, exactly, the outbreak began. Many scientists think the new virus spilled over directly from a wild animal, perhaps at a Chinese wet market; some posit that the pathogen leaked accidentally from a local laboratory in Wuhan, China, the pandemic’s likely epicenter. All of them lack the slam-dunk evidence to prove one hypothesis and rule out the rest.
That’s not to say nothing has changed. Those embroiled in the origins fracas now have much more data to scrutinize, debate, and re-debate. In March, I reported that the case for a zoonotic origin had acquired a consequential new piece of support: An international team of scientists had uncovered genetic data, collected from a wet market in Wuhan in the weeks after the venue was closed on January 1, 2020, that linked the coronavirus to wild animals. This evidence, they said, indicated that one of those creatures could have been shedding SARS-CoV-2, the virus that causes COVID-19; one of the most intriguing bits of data pointed to raccoon dogs, a foxlike creature that was already known to be vulnerable to the virus. The finding wasn’t direct evidence of an animal infection, but, stacked alongside other clues, “this really strengthens the case for a natural origin,” Seema Lakdawala, a virologist at Emory University who wasn’t involved in the research, told me at the time.
Not everyone agreed that the finding counted as a substantial new insight. When the researchers who originally collected the samples, many of them from the Chinese Center for Disease Control and Prevention, published their own analysis of the data in April—a revision of an earlier report—they emphasized that there was no clear evidence that the virus had been introduced to the market by a wild animal. Then, this month, Jesse Bloom, a computational biologist at Fred Hutchinson Cancer Center, in Seattle, posted a third analysis of the market data, inspired in part, he told me, by his concern that the public discussion of the initial findings, and their connection to raccoon dogs, had overinflated their worth. The international team’s report, he argued, hardly moved the needle on the origins debate at all—certainly not “much beyond where it was before,” he told me.
Bloom’s analysis, too, set off a wave of fervor—including a fresh spate of claims that he told me were “exaggerated,” or even outright wrong; some even asserted, for instance, that his preprint proves that raccoon dogs “weren’t infected, which is not an accurate summary,” he said. All the while, researchers have been squabbling on social media over the minutiae of statistical methodology, and what constitutes a meaningful amount of viral RNA; some have even come to loggerheads publicly at conferences.
At the crux of this particular fight is a difference of interpretation, with one camp of researchers contending that the recent data matter a lot, and another asserting that they matter much less, or perhaps not even a little bit at all. Under most other circumstances, a scientific scuffle this deep in the weeds might hold the attention of a few dozen people for a few months at best. Here, though, the central topic is one of the most consequential in recent memory—a virus that’s left its mark on the world’s entire population, and will continue to do so. Which has made it easy for pitched battles over differences in scientific opinion to become a public spectacle—and difficult, maybe even impossible, for the debate to ever end, no matter what evidence might emerge next.
The genetic sequences analyzed in the March report contained evidence of a zoonotic origin that is more circumstantial than direct. Researchers extracted them from swabs taken from surfaces in and around Wuhan’s Huanan Seafood Wholesale Market from January to March of 2020, weeks after the first known COVID cases were documented in Wuhan. That makes these environmental samples “a useful part of the story,” Alice Hughes, a conservation biologist at the University of Hong Kong, told me. Though, by themselves, “they are limited in what they are able to tell us.”
By the time the swabs were collected by China CDC researchers, Chinese officials had hastily closed Huanan; many vendors had likely disappeared with their animals, or culled them en masse. The swabs could show only where the virus had once been, or which animals the venue had sold—more akin to dusting a crime scene for fingerprints than catching a vagrant in the act. And although they could show where animal and viral genetic material had mixed, they couldn’t guarantee that those two types of genetic material had been deposited at the same time. Nor could they distinguish between, say, a sick creature sneezing on the bars of its cage and an infected human coughing on an enclosure housing healthy wildlife. Those answers could have come from swabs taken directly from the noses or mouths of live animals for sale at Huanan in late November or early December of 2019. But as far as researchers know, those swabs don’t exist—or at least, the public has no record of them.
The sequences from these environmental samples, then, are “what we have,” says Katherine Xue, a computational virologist at Stanford who previously worked with Jesse Bloom, the author of the May preprint, but was not involved in any of the new reports. And “we want to do what we can with what we have.” When the international team behind the March analysis found that several market samples contained genetic material from both the virus and a wild animal known to be susceptible to it—including the common raccoon dog—they said that the best explanation for this commingling was an infection.
As I reported at the time, the data don’t constitute direct evidence of an infected raccoon dog at the market. “But this is exactly what we would observe if infected raccoon dogs were in fact present in this location,” says Kristian Andersen, a computational biologist and virologist at the Scripps Research Institute and one of the authors of the March analysis. Which, they wrote in their analysis, “identifies these species, particularly the common raccoon dog, as the most likely conduits for the emergence of SARS-CoV-2 in late 2019.”
Other researchers, though, think that calling the evidence even supportive of an animal origin for the outbreak is a stretch. The samples were taken too long after the outbreak’s start to be meaningful, some said; the data were too shaky to even hint at the idea of an infected raccoon dog, others insisted, much less one that might have passed the virus to us.
Bloom, too, was unswayed. The swabs contained genetic material from many creatures at the market—some of them alive, some dead; some that we now know can host the virus, others that almost certainly do not. In Bloom’s analysis, he explains that the species repeatedly highlighted as potential hosts weren’t the animals that were most frequently and notably commingled with the virus in the market swabs. “If you’re trying to figure out if there is a meaningful association between raccoon dog and viral genetic material,” he told me, there should be a lot of raccoon-dog genetic material in the places where the virus was found, and far less where the virus was not.
But that wasn’t the case for raccoon dogs—or “any of the animals that could conceivably have been infected,” Bloom told me. Instead, in his analysis he saw the virus most closely linked to several kinds of fish, which aren’t known to be viable hosts for it. People, Bloom told me, were the probable source of SARS-CoV-2 in those spots. All of that “probably just suggests that it had been spread around the market by humans by the time” the swabs were taken, diminishing the samples’ usefulness.
Several other scientists not involved in Bloom’s preprint were quick to point out the limits and flaws in his approach. To draw meaningful conclusions from this type of analysis, researchers would need samples amassed at about the same time, with the same collection goals in mind. That wasn’t the case for these samples, Zach Hensel, a biophysicist who has been publicly critical of Bloom’s report, told me. Researchers took them over the course of many weeks after Huanan’s closure, altering their tactics as more intel came to light. A first foray into the market, for instance, targeted the parts of the venue where COVID cases had been identified, a strategy that would, by design, turn up more virus-positive samples; another, conducted days later, focused on stalls that had been discovered to have housed wildlife, regardless of their proximity to sick people. Many samples in the latter set, then, would be expected to be virus-negative—and were. Sloshing them together with the first set of swabs and trying to pull patterns out could end up masking actual associations between the virus and any wild animal hosts.
Bloom also points out that many of the swabs that turned up mammalian DNA, including one containing raccoon-dog genetic sequences that some members of the international team initially emphasized, had relatively little material from the virus on them. But genetic material, especially RNA—the basis of SARS-CoV-2’s genome—degrades fast; a difference of even a few days could artificially deflate how important a particular swab looked. Alice Hughes also pointed out that certain market locales highlighted in Bloom’s preprint, including surfaces around duck or fish tanks, might have better preserved viral RNA simply because they were cold or damp. When I brought up these concerns with Bloom, he admitted that “there are certainly a lot of confounders” that could have skewed his results. His main goal, he said, was just to show that “the samples are not sufficient to answer whether or not there were infected animals.”
Bloom’s re-analysis doesn’t mark a major shift in thinking for Hughes, who told me she thinks “there is reasonable support for a zoonotic origin.” Felicia Goodrum, a virologist and an immunologist at the University of Arizona who has written repeatedly on the origins debate but was not involved in the team’s analysis, agrees. The Huanan market is “most likely where the spillover occurred,” she told me. “I really, truly believe that, based on the accumulation of the evidence.”
Data never sit alone in a vacuum: They’re amassed, interpreted, and reinterpreted alongside the totality of evidence that precedes them. By themselves, the sequences from the Huanan market couldn’t say much. But they fit a broader, more detailed scenario that researchers on the team behind the March analysis had been exploring for years.
History has always supported a zoonotic scenario: A wet-market spillover is what researchers are fairly certain started the SARS outbreak in China in 2002, potentially via infected masked palm civets. In this latest outbreak, the Huanan market was one of only four wet markets in all of Wuhan that has consistently been documented selling an array of live, coronavirus-susceptible wildlife; the earliest known COVID cases were detected near the venue, centering “on it like a bull’s-eye,” says Michael Worobey, an evolutionary biologist at the University of Arizona and one of the authors of the March report. Scientists analyzing genetic sequences collected from the venue have also detected two distinct coronavirus lineages from the outbreak’s earliest days—a likely indication, some researchers have argued, that the pathogen spilled over from animals into humans twice.
The missing clincher for them is which creature might have initially carried the virus into the market. The raccoon-dog swab was particularly compelling to the team not only because it contained gobs of animal genetic sequences, and very few human ones—but also because it had been plucked from a stall where Eddie Holmes, one of the report’s authors, had snapped a photo of a raccoon dog in a cage years before. The clues to a possible animal host, Worobey told me, were “right in the very stall we said they would be.”
But data are also amassed, interpreted, and reinterpreted by humans, who have their own biases. The experts now quarreling over the importance of the recent data approached the new evidence having already drawn tentative conclusions and made their opinions known. Kristian Andersen was an early proponent of a zoonotic origin, and has repeatedly denounced the notion of a lab leak; Worobey was later to voice his support for the zoonotic hypothesis, but is now no less enthusiastic. And long before they and their colleagues stumbled across the data that yielded their March analysis, which didn’t become publicly available until recently, the researchers had been hoping that such sequences would appear—noting in a 2022 paper that this sort of intel could constitute an essential and still-missing puzzle piece. Now that the evidence has emerged, and fits with their established thinking, it feels validating, Worobey told me. “After two years or more of us sometimes even being mocked for saying that plausible intermediate hosts, including raccoon dogs, which we knew could transmit the virus, were there,” he said, “there’s the genetic evidence, putting that to rest, finally.”
Bloom, by contrast, has long positioned himself as an agnostic moderate, and isn’t yet budging from his neutral territory. Others who have come out vocally in favor of a lab-leak scenario have cast their own doubts on the international team’s analysis. In a landscape so sparsely populated by data, it gets all too easy for people to fill in the gaps with speculation; “what starts off as a weak preference,” Hughes told me, “becomes almost like a religion.” I’ve been reporting now for three years on many controversial COVID stories, along the way interviewing hundreds of opinionated scientists about dozens of thorny questions. Through it all, this debate has stood out for being so ignitable. Individual data points have become catalysts; single statements have been endlessly scrutinized. And experts have staked out territory and stuck to it almost dogmatically—many of them to the point of avoiding admitting past mistakes. COVID’s origins are now shrouded in combustible gas, with matches scattered everywhere: Lighting up a single point, normally harmless enough, inevitably sets off a conflagration.
All of this leaves the world trying to peer through the smoke. “All hypotheses are on the table,” Maria Van Kerkhove, the World Health Organization’s technical lead on COVID-19, told me. “We can’t take any off.” To her mind, though, “there’s much more evidence to support a zoonotic origin.”
More evidence could still emerge. The international team isn’t yet done analyzing the Chinese researchers’ original data set, which was recently released in fuller form. They’re eager to mine the sequences to tease out the subspecies of some of the market’s potential SARS-CoV-2 hosts, which could inform searches for the virus out in nature or on animal farms; other experiments, analyzing how degraded certain genetic samples are, could hint at how much time passed between the moment the biological material was dropped and the moment it was picked up. Van Kerkhove has also separately been pressing the Chinese researchers for more information on how these and other samples might have been collected, and any intel on where the market’s animals might have been sourced from—which could guide searches for evidence of the virus or its relatives on farms or in the wild. These bits of data, too, would all be incremental, with no single shred of evidence acting as total proof or disproof. But each could constitute a clue, Van Kerkhove told me, to continue nudging the conversation along.
In the grand scheme of things, though, the world probably won’t ever get data that will conclusively end the debate. Even if scientists were to turn up virus-positive samples from a live creature from the market—direct evidence of an infected animal—it would remain technically possible that a human caught the virus first, then passed it on to the venue’s wildlife. But data that aren’t debate-ending can still be notable. And the recent sequences from the market swabs could easily, and frustratingly, end up being one of the best clues to the pandemic’s roots that the world is likely to get.