A few years ago—we don't know how many, but before 2019—bats infected with a still-unknown coronavirus lived in caves in Yunnan, a southern Chinese region bordering Vietnam, Laos, and Myanmar. Later, as early as December 2019, Wuhan hospitals received the first 174 cases of severe Covid-19, a disease caused by a new coronavirus descended from that of bats.
Between the Yunnan caves at an undetermined time and Wuhan in 2019, the virus traveled 1,500 km, a distance that only human intervention can explain. But were these humans wildlife traffickers who turned out to be infected, or scientists collecting samples to study or even modify them in the laboratory? Experts are still divided on the subject, although the laboratory hypothesis is gaining momentum, while the Chinese government, for its part, proposes a completely different scenario.
Emergence through zoonosis, the first reflex
- The place : the Huanan market in Wuhan, a 50,000 m² enclosed space where live animals are sold.
- The source : a still unidentified wild animal that was allegedly offered for sale there and infected the surrounding humans, serving as an intermediary with the bat.
Credits: MARTIN BERTRAND / Hans Lucas / Hans Lucas via AFP
Several scientific arguments support this hypothesis. First, the history of previous epidemics. The hypothesis of emergence by zoonosis (contamination by animals, editor's note), this is the first reflex, which refers to the natural history of similar emerging diseases such as SARS in 2003, probably transmitted by the civet, and MERS in 2011 transmitted by the camel", explains Marc Eloit, virologist and former director of the "Discovery of Pathogens" laboratory at the Pasteur Institute. Then, the geographic convergence of cases around the market area seems to point to it as the epicenter of the epidemic, which is what researchers expect to observe if this is where the virus emerged. The market area in fact emerges from the analysis of the location of homes and workplaces of 155 cases of Covid-19 among the first 174 cases, according to a 2022 publication in the journal Science. In this same work, the positive samples for Covid-19 also point to a corner of the western zone of the Huanan Market where wild animals were sold.
But the zoonosis hypothesis also has its flaws. For starters, while MERS, for example, regularly re-emerges on a small scale in its natural reservoir (camels), Covid-19 has never appeared in any animal. Moreover, “ SARS-CoV-2 has never been found in animals other than through human contamination. And that really speaks against the hypothesis of emergence through zoonosis," specifies the epidemiologist Renaud Piarroux, head of department at the Pitié Salpêtrière hospital (AP-HP) and author of Sapiens and Microbes – Epidemics of the Past (CNRS Editions). As for the convergence of cases around the market, it is also compatible with contamination by an infected human – and not just an animal. The data points to a very significant contamination event at the Huanan market, but it is extremely difficult to determine how the virus arrived at this market.", points out Belgian epidemiologist Marius Gilbert, who sat on the country's scientific council during the Covid-19 crisis. Especially since the corner of the market pointed by the positive Covid-19 samples certainly includes probable locations of potentially infected wild animals, but also an unventilated Mahjong room and toilets, two places of potential contamination between humans.
The appearance in the viral genome of the furin cleavage site, which gave the virus its pandemic potential and which no other virus in the same sarbecovirus family possesses, also remains unexplained, while experiments conducted to mimic its re-emergence have yielded nothing. And if this sequence did not emerge through successive mutations, it must have been acquired in one go by chance, during an infection at the same time as another virus: this rare phenomenon is called recombination. But here too, no potential donor organism has been identified. Nature has many attempts and starting points. Thousands of animals (and sometimes humans) involved in the wildlife trade are infected with viruses, creating thousands of opportunities for a virus to acquire the mutations necessary to become a pandemic virus.", objects pro-zoonosis researcher Alex Crits-Christophe. This is indeed what usually happens, but there is no trace of these many infected animals nor of these multiple attempts at viral emergence have not been highlighted so far.
Finally, one element in particular sows doubt: after five years and despite the significant Chinese scientific and financial resources, no animal or precursor virus (close ancestor) has been found, where the civet of the first SARS and the camel of MERS had been identified within a few months.
The laboratory accident, from irrefutable manipulation to the DEFUSE project
- The place : one of the laboratories of the Wuhan Institute of Virology (WIV), located in an urban area
- The source : an infected employee, improperly disposed waste, poorly controlled cell culture, insufficient safety standards, etc.
Wuhan Institute of Virology. Credits: YOMIURI SHIMBUN / Yomiuri / The Yomiuri Shimbun via AFP
Be careful, in science, an "irrefutable" theory or argument is not a good thing: it means it cannot be proven wrong, and therefore must be based on solid evidence to gain consensus. Some versions of the theories that the Covid-19 virus accidentally emerged from the Wuhan Institute of Virology (WIV) laboratory are of this kind. The laboratory accident theory covers several possible scenarios, all of which result in the virus emerging from Wuhan and then being transported to the Huanan market by an infected human.
The virus could have been genetically modified to give SARS-CoV-2 according to the plans of the DEFUSE research project, issued in 2018 but never funded. In this case the mysterious furin cleavage site sequence would have been artificially inserted.
The fact remains that for the theory of voluntary genetic modification to hold, whether or not it follows the DEFUSE project, it would be necessary to explain why the insertion of the cleavage site by furin contains the unusual amino acid sequence PRRAR, instead of the more classic RRAR or the PRRVR variant which increased the lethality of a MERS virus in experiments carried out in 2017. The DEFUSE project proposed to introduce sub-optimal cleavage sites, which can lead to a non-canonical sequence." suggests Etienne Decroly. Furthermore, to obtain SARS-CoV-2 through such manipulations, a basic carrier is required, that is, a known virus to be genetically modified. This virus would be precisely the one—or one of its descendants—that was infecting bats in the Yunnan caves at the beginning of this story. While no candidate has yet been identified, the WIV's viral databases likely contained many as-yet unpublished sequences.
If this is not directed genetic manipulation, other experiments aimed at accelerating the evolution of the virus could also have been carried out in the laboratory. This could be an accident during sampling, viral culture, or even during serial passage experiments on humanized transgenic mice.", that is to say modified to express human genes or possessing human tissues, suggests CNRS research director Etienne Decroly, author of Virology Experiments – Benefits and Risks (Quæ Editions).
These are possible hypotheses, but difficult to demonstrate in the absence of an investigation. Only documents from the Wuhan laboratory revealing their activities and the health status of their employees in 2019 could shed light on the matter. The very existence of the DEFUSE project should be sufficient to justify a serious investigation by the World Health Organization (WHO) within the laboratories concerned, in order to assess the possibility of manipulation of a progenitor virus of the epidemic", Etienne Decroly decides. For him, as for many researchers, no hypothesis between zoonosis and laboratory release can be formally ruled out.
US Responsibility, the Chinese Scenario
- The place : outside Wuhan, potentially in the United States
- The source : an American laboratory accident and frozen food
Frozen food. Credits: ZHOU YI / XINHUA / Xinhua via AFP
In China, the few elements that are a consensus among scientists are formally refuted. In its White Paper published in April 2025, the Chinese government refutes any possibility that Wuhan was the natural starting point of the virus, which would rather have been brought there via frozen products. They rely on several large-scale scientific analyses, from which no trace of SARS-CoV-2 emerged before December 2019 in Wuhan. First, no trace of the virus in 80,000 samples taken from wild and farm animals throughout the country. Second, no abnormal grouping of severe cases (clusters) was observed in 76,000 medical records between October and December 2019, that is to say before the diagnosis of the first official cases of Covid-19. There was also no trace of antibodies against the Covid-19 virus in nearly 44,000 blood donations from more than 32,000 donors made in Wuhan between 1er September 2019 and early December – about half of the total donations over this period. This is a surprising result given that the vast majority of Covid-19 cases are asymptomatic or moderate, and that Wuhan hospitals began receiving severe cases in early December 2019. When you are in the hospital, it is because you were infected 15 days earlier and as we know that there are only 1 in 2% people who end up with severe pneumonia, that means that there were already more than 100 infected patients in mid-December.", reasons Etienne Decroly. Two studies also suggest the start of an epidemic between mid-October and mid-November 2019, in the journals PLoS One And Science.
The Chinese government, however, claims to have identified cases of Covid-19 as early as September 24, 2020, in Qingdao (Shandong Province), more than 1,000 km northeast of Wuhan, a few days after handling infected packages of frozen food. "(This) demonstrates that transport in the cold chain is a route of transmission of SARS-CoV-2," concludes the White Paper. In another paragraph, the Chinese government notes at length cases of unidentified flu reported in several American states as early as spring 2019 and concludes not only that the virus was circulating in the United States as early as December 2019, but that it could have originated from a laboratory accident. Laboratory incidents have occurred repeatedly in the United States and laboratory management is a source of concern.", it is written in the White Paper.
Scientifically, no expert gives credence to the Chinese government's scenarios, as studies have shown very low transmission of Covid-19 via surfaces and frozen food.
Human responsibility
“ If we base ourselves on scientific facts, we have no proof of anything.", summarizes Marc Eloit. More than five years after the emergence of Covid-19, the scientific debate is far from over. Much data is missing", regrets virologist Christine Rouzioux, member of the Academy of Medicine and co-signatory of a report draws lessons to avoid future zoonoses or laboratory accidents. She deplores in particular, like the WHO SAGO expert group which investigated the origins of Covid-19, a lack of transparency from China.
“ We could have made progress if we had known exactly which animals they tested, whether in the Wuhan market or in the breeding farms, and their exact results, with the places and dates of samples, all of this remains very vague.", confirms Virginie Courtier, research director at the CNRS and head of the "Evolution and Genetics" team at the Jacques-Monod Institute. Whether new decisive data are revealed or not, the state of the current investigation is sufficient to raise the responsibility of human activities in the emergence of epidemics. " Transporting animals over such a distance is no more a natural process in the animal trade than it is in laboratory activities.", points out Marius Gilbert.
Discover the other episodes of our great eScientific investigation into the origins of Covid-19 :
– Episode 1
: anatomy of the virus, these strange elements which sow doubt
– Episode 2: How the DEFUSE project fueled the theory of a virus released from a laboratory
– Episode 3 : Wild animals or Mahjong room, where could the virus have emerged at the Huanan market in Wuhan?
– Episode 4 : Is it too late to identify an animal responsible for the emergence of the virus?
– Episode 5 : How "Proximal Origins," one of the most influential publications of all time, influenced the scientific debate
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