An acrimonious debate about covid’s origins will rumble on
WHERE DID covid-19 come from? You might imagine that the question would be a matter for science. Instead it has become embroiled in acrimony, politics and, at times, conspiracy theory. New diseases in people almost always come from close contact between human populations and animals. A spillover happens when viruses from an animal species jump into humans and then go on to wreak havoc. But the idea that SARS-CoV-2, the virus that causes covid-19, instead leaked from a Chinese research laboratory has persisted since the earliest days of the pandemic. Though this theory has rested largely on rumours and circumstantial evidence, it has nevertheless set the stage for a bitter three-and-a-half year row. It had been hoped that information from Americas intelligence services could resolve the row in favour of one theory or another. Those hopes were scotched late on June 23rd, when a report was delivered by the Office of the Director of National Intelligence (ODNI)as directed by Congresson the potential links between the Wuhan Institute of Virology (WIV) and the origin of the pandemic. It contained no evidence of a laboratory leak. However, anyone hoping the report would burnish instead the hypothesis that covid-19 emerged in a food market in Wuhan would also have been disappointed. The report concluded that both a natural and laboratory-associated origin remain plausible. Most new infectious diseases originate in animals. Those include Ebola, Zika, HIV, and the original SARS (whose emergence in 2003 was thought to be tied to animal sales). Such events are often tied to the sale of live animals or the consumption of bushmeat. China also has extensive wildlife and livestock farming, wildlife trafficking, many live animal markets and lax regulations. Soon after a mysterious new pneumonia appeared in China, the source of the disease was quickly pinned to the animals sold in the Huanan Seafood Market in Wuhan. Many (although not all) of the people who had become sick had worked at or visited this site. Yet a natural spillover is not the only route by which a new virus might enter humans. Researchers at the Wuhan Institute of Virology (WIV) had also been carrying out high-risk research on coronaviruses in inadequate biosafety conditions. Scientists in the city also conducted field trips to sample bats and collect viruses from remote regions of China. These activities could have provided a route for a new virus to be accidentally picked up by humans in the laboratory, who could then have gone on to start an outbreak in Wuhan. Since the start of the pandemic, two tribes have battled it out in online discussions of the origins of covid: the zoonati and the lab leakers. Michael Worobey, professor of ecology and evolutionary biology at the University of Arizona, didnt start out as a zoonati, a term that was once pejorative on social media and thrown at those who didnt support a laboratory leak. (Dr Worobey says the word has been happily co-opted.) He says there are three main lines of evidence that support the market hypothesis: geographic, zoonotic and evolutionary. The strongest evidence is probably the first: the spatial pattern of the earliest cases which centred on a small animal market in a city of 11m people. Although there was some bias towards collecting cases from the market (given its early implication in the outbreak), Dr Worobey says the very earliest onset cases, ones that just turned up in hospitals, lived in a bullseye right around the market. It is also clear that animals that could be infected with SARS-CoV-2 were being sold in the Huanan Seafood Market. By June 2021 this zoonotic line of evidence was firmed up in a paper published in Scientific Reports. More recently it was realised that swabs of the surfaces and corners of the market collected in January 2020 indicated that various species such as raccoon dogs, badgers, mink and civet cats were present before the pandemic. None of these animals were disclosed by the Chinese authorities; they were found thanks to market surveillance under way before the outbreak. The animals were sold alive, in cages stacked on top of one another, and in poor conditions. Many shops offered butchering services. And the route to the market would also have brought stressed animals into close contact, allowing for the intermingling and amplification of coronaviruses. One note of caution here is that, although the animals found at the market were capable of hosting the human variant of SARS-CoV-2, whether the pandemic virus emerged here is not provable with the information available. The viruses picked up by the swabs taken at the market in January 2020 could also have come from infected humans in the market, rather than from animals. The third line of evidence for the market hypothesis comes from studying how different specimens of the virus are related to each other, from an evolutionary point of view. As coronaviruses replicate, random mutations occur in its genome and are passed on to successive generations. Over time these changes will accrue. If viruses are sampled from many different people over time, it is possible to work out which viruses begat other viruses, and the amount and rate of the changes can tell scientists roughly what the viruss evolutionary history looks like. In 2022 Jonathan Pekar of the University of California, San Diego, and colleagues found that two major lineages of SARS-CoV-2 appeared at the start of the outbreak in Wuhan, known as A and B. These were likely, said the researchers, to be the result of at least two separate spillover events in humans. The combination of the geographic pattern of cases around the market, a short timeline for the emergence of the virus, and two independent lineages, paint a picture of a market-related event tied to a group of infected animals carrying similar (but not identical) versions of the SARS-CoV-2 virus that jumped. Again, not everyone agrees. Other scientists have challenged the idea that the two lineages of SARS-CoV-2 represented separate introductions. As they differ by only two mutations, one lineage could have evolved into another within humans, they argue, rather than coming from separate spillover events. The question is whether quibbles like these create enough wriggle room to leave open the possibility that the pandemic started elsewhere, leaving the market to be simply a place where the number of infections in humans was amplified. The hope was that the ODNI would resolve this issue one way or another, particularly in relation to persistent rumours that scientists at the WIV were infected with the first cases of covid-19. On this matter the report was clearalthough some researchers at WIV did fall ill in the autumn of 2019, the symptoms reported were not diagnostic of covid-19. In other words, they could have been sick with any disease. Another remaining area of uncertainty concerns missing data from the early days of the outbreak in Wuhan. Maria Van Kerkhove, an infectious disease epidemiologist at the World Health Organisation says her group has repeatedly asked for an independent re-analysis of surveillance cases in 2019 that had been ruled out as being covid-19. And also she has asked for more information about the 174 early cases of covid-19 that China has disclosed. What this obfuscation and opacity from China amounts to is unclear. However, Dr Worobey points out that there were probably only a handful of cases of covid in late November 2019, and that six retrospective studies, including on throat swabs, blood donors and plasma samples, do not find a signal of a larger outbreak in Novemberalthough they did find that influenza was relatively common at the time. Prior to the release of the ODNIs report, two-thirds of Americans believed a laboratory leak was the cause of the pandemic, according to a poll by The Economist and YouGov. This impression came despite the growth of scientific papers pointing to the market. Last weeks release of intelligence will not persuade people on either side that they might be wrong. Instead it will fuel a new cycle of claims and counterclaims. Yet with further new information not expected, the marginal gains of continuing the row are rapidly diminishing. The hunt for the heroes and villains of covid is drawing energy and attention from the more obviously urgent need to improve global biosecurity in the animal trade and lab safety. The mysterious origins of covid may, for now, need to take a back seat. Correction (June 28th): Most infectious diseases come from animals. However, the article originally cited a specific proportion coming from wildlife in error. Also, editing conflated two studies showing the presence of animals in the Wuhan market. This has also been corrected. Sorry.