COVID-19 lab leak theory

The COVID-19 lab leak hypothesis is an alternative to the natural-spillover-event hypothesis to explain the origin of the COVID-19 epidemic. The hypothesis proposes that SARS-CoV-2, the virus that causes the coronavirus disease 2019, may have originated from an unknown zoonotic disease that was collected by a laboratory in Wuhan, China, where it was held for a number of years and accidentally released, either through an infected laboratory worker or some other form of biosecurity breach, such as improper disposal of biomedical waste, the escape of a laboratory animal or in field work. The hypothesis has often been discredited as a conspiracy theory and conflated with other forms of COVID-19 misinformation, though some scientists including Richard Ebright of Rutgers, David Relman of Stanford University and Marc Lipsitch of Harvard University have said that a lab leak must be investigated as a scenario as part of a credible investigation. The BBC has called it “one of the biggest scientific controversies of our time”.

The lab leak hypothesis draws mainly upon the seeming circumstantial evidence that the Wuhan Institute of Virology is closer in proximity to the early outbreak of the COVID-19 pandemic in Wuhan, Hubei Province, China. A central part of the hypothesis is that scientists from Wuhan Institute of Virology were known to have collected caronaviruses endemic to Yunnan province, which they later subjected to gain of function research, funded with USAID and NIH grants via New York based EcoHealth Alliance, and detailed in scholarly papers sent to Nature. Proponents of the hypothesis have noted that scientists have long debated the risks of causing pandemics through gain of function research and the creation of novel chimeric viruses, due to the accidents and incidents that increasingly occur even in the highest level biosecure laboratories.

Many scientists suggest that the most likely scenario for the origin of SARS-CoV-2 is that of a zoonotic jump from a reservoir host, via an intermediate host, to humans, and some scientists believe that a direct zoonotic jump from a reservoir host to humans is also possible. However, most scientists consider the scenario of a lab leak to be unlikely. Scientists proposing the lab leak hypothesis note that it took from four to ten months to identify the civet cat and camel as the intermediate hosts of the SARS and MERS pandemics, respectively, yet no intermediate host or virus of SARS-CoV-2 has been identified even 14 months after the outbreak of the virus. Other scientists have pointed out that it can take years to determine the exact origins of a zoonotic disease, and in some cases, such as with Ebola and HIV/AIDS, their exact origins still remain unknown.

On 14 January 2021, the World Health Organisation sent an investigation team to Wuhan, China to investigate the origins of the virus. Several members of the team, including Peter Daszak, Marion Koopmans and Dominic Dwyer said they will consider all possible origin scenarios, including a possible lab leak.

Uncertain origins

The exact origins of COVID-19 currently remain unknown. Scientists have agreed that SARS-CoV-2 probably originated in bats, like its closest relatives, RaTG13 and RmYN02; but its exact evolutionary history, the identity and provenance of its most recent ancestors, and the place, time and mechanism of transmission of the first human infection, remain unknown.

Scientists have said that just like with SARS in 2002 and MERS in 2012, the SARS-CoV-2 virus most likely jumped from its primary or "natural reservoir" host into the human population through a secondary or "intermediate" host. Scientists have also suggested that SARS-CoV-2 could have jumped directly from its reservoir host to a small human population, in which it evolved fitness to reproduce, infect and transmit to the wider human population. So far no intermediate host of a precursor virus has been found in humans prior to the outbreak in Wuhan.

While the virus was widely reported in early 2020 to have first jumped from animals to humans at the Huanan Seafood Wholesale Market, possibly via smuggled pangolins, George Gao, the director of Chinese Center for Disease Control and Prevention, told local state media in a visit to Wuhan in mid 2020 that no viruses were detected in animal samples taken from the Wuhan market, and were instead found only in environmental samples and sewage.

Apparent pre-adaptation for human transmission

A number of scientists have observed that COVID-19 has been remarkably well adapted for human transmission from the moment it was first detected, which has been confirmed by the World Health Organisation in its global study on the origins of the virus published in November 2020. A virus crossing from one species to another will usually undergo a process of evolving and adapting for transmission in the new host, as occurred in the early phase of the 2003 epidemic when SARS-CoV developed several advantageous adaptations for human transmission. In a study conducted by scientists, a side-by-side comparison of the evolutionary dynamics between SARS-CoV-2 and SARS-CoV was made with curated genomes from early, to mid, to late epidemic stages, sampled from diverse geographical regions, showing significant disparate genetic diversity. The comparison suggested that SARS-CoV-2 was already well adapted for human transmission by the time it was first detected in late 2019, to an extent more similar to the later stage of the SARS-CoV epidemic.

In comparison to the SARS-CoV epidemic, the SARS-CoV-2 epidemic is missing an early phase during which the virus would have developed adaptive mutations for human transmission. While SARS-CoV progenerated multiple branches of evolution in both humans and animals, SARS-CoV-2 appeared without peer in late 2019, suggesting that there was a single introduction of the human-adapted form of the virus into the human population.

Scientists have presented causative scenarios for this pre-adaptation as being either natural selection in an animal host before zoonotic transfer, natural selection in humans following zoonotic transfer, or the passage of bat SARS-CoV-like coronaviruses in human cell culture or animals in a laboratory.

Mojiang miners pneumonia incident and the origins of RaTG13

In April and May 2012, six miners were admitted to a hospital of the Kunming Medical University with pneumonia-like symptoms, including dyspnoea, aching limbs, sputum/bloody sputum and headaches, after working on clearing bat faeces in a copper mineshaft in Tongguan, Mojiang, Yunnan. Three of the miners died and three survived.

After the Mojiang outbreak, the Wuhan Institute of Virology conducted surveillance of the bat coronaviruses in the Mojiang mine, visiting the site four times between August 2012 and July 2013. The mineshaft was found to have six bat types of which most were horseshoe bats and faecal samples were collected. From these samples, 150 alpha-coronaviruses and two beta-coronaviruses were detected, one of which was a SARS-like beta-coronavirus, named CoV/4991, which was sequenced and submitted to GenBank (accession number KP876546) in 2016.

On 3 February 2020, Zhengli Shi and colleagues from the Wuhan Institute of Virology sent a paper for peer review to Nature titled "Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft"; sharing research carried out in the Mojiang mine shaft, and revealing a coronavirus strain named RaTG13, a beta-coronavirus that infects the horseshoe bat Rhinolophus affinis that was 96.2% identical at the whole-genome level to COVID-19. This paper was widely cited in academic and news media, though it provided very little details about the strain, and had not been reported in Shi's previous studies which highlighted a strain named BtCoV/4991 associated with the same bat species (Rhinolophus affinis).

As COVID-19 began to spread in the US, US Government Agencies and President Donald Trump made statements on the origins of the virus and pointed to the Wuhan Institute of Virology as the possible source. In July 2020, Zhengli Shi granted an interview to Science, to counter Trump's statements and ensuing media reports that her laboratory was responsible. As part of the interview, Shi stated that her laboratory had identified RaTG13 from a bat faecal sample collected from Tongguan, Mojiang county in Yunnan province in 2013, and obtained its partial [[1]](RdRp) sequence, but never isolated or cultured it due to its low similarity to SARS-CoV, until 2018, when her laboratory's NGS sequencing technology and capability were improved. Further sequencing of the virus was done, obtaining its full-length genome sequence, except the 15 nucleotides at the 5’ end. Shi said that her laboratory never isolated or cultured RaTG13 for further studies, and no longer has any of the sample left. She stated it was used many times for the purpose of viral nucleic acid extraction by the time the genome sequencing was finished. Shi noted that in 2020, they compared the sequence of SARS-CoV-2 with their "unpublished bat coronavirus sequences" and found that it shared a "96.2% identity with RaTG13", which lead her to send her paper to Nature.

A few scientists noted similarities between the RaTG13 strain and the BtCoV/4991 strain uploaded to GenBank in 2016, and since BtCoV/4991's full genome sequence was not available, they requested for Shi to provide full-genome samples of BtCoV/4991 to clarify her paper. In April 2020, Rossana Segreto, a molecular biologist at the University of Innsbrucks established that the RdRp of RaTG13 has 100% nucleotide identity with the sequence BtCoV/4991. This finding sparked the interest of scientists studying the origins of the virus, the Mojian miners, and Shi's comments in her interview with Science Magazine referring to unpublished data.

On 19 May 2020, two Indian molecular biologists, Monali Rahalkar and Rahul Bahulikar, published a preprint on the origins of RaTG13, and the next day received a message from an anonymous Twitter user named "TheSeeker268" pointing to two academic works in Chinese on cnki.net, the official website for Masters and Ph.D. theses in China. The Masters and PHD Theses by Li Xu and Canping Huang, focussed on the Mojiang miners. It indicated that, based on antibody tests processed by the Wuhan Institute of Virology, the miners' illness appeared to be primarily viral and probably related to SARS-like coronaviruses originating from horseshoe bats.. Monali Rahalkar from Agharkar Research Institute, Pune and Rahul Bahulikar from BAIF, Pune, published their findings in in Frontiers in Public Health journal, 'Lethal Pneumonia Cases in Mojiang Miners (2012) and the Mineshaft Could Provide Important Clues to the Origin of SARS-CoV-2' , Rahalkar and Bahulikar 2020, https://www.frontiersin.org/articles/10.3389/fpubh.2020.581569/full. Various questions were raised in their paper for WIV, the institute which analyzed the miners samples, collected samples from the same mine, and why this incident was not reported to health agencies. They concluded that 'the coincidence between the 2012 illness in Mojiang miners, the subsequent samplings, and finding the nearest SARS-CoV-2 relative from this single mine warrants further inquiry, and the data along with the full history of this incident would be invaluable in the context of the current pandemic'.The striking similarities between the Mojiang pneumonia cases and COVID-19 are noteworthy, as is the fact that RaTG13/CoV4991, the next genomic relative of SARS-CoV-2 was found in the same mineshaft.

In an interview with Scientific American on 1 June 2020, Dr Shi Zhengli of the Wuhan Institute of Virology was asked about her investigation into the deaths of miners in Mojiang from SARS-like viruses. Shi attributed the deaths to a fungus, saying "it would have been only a matter of time before they caught the coronaviruses if the mine had not been promptly shut". This statement contradicted the findings of The Masters and PHD Theses by Li Xu and Canping Huang, sourced from cnki.net.

On 17 November 2020, Shi Zhengli of the Wuhan Institute of Virology made an addendum to a study on the bat-origins of SARS-CoV-2 in Nature, clarifying that CoV/4991 was indeed RaTG13, and that it was found in 2012-2013 "in an abandoned mineshaft in Mojiang County in Yunnan Province", confirming that the virus closest to the SARS-CoV-2 was linked to the mine-shaft in Mòjiāng, and that the Wuhan Institue of Virology had stored it since 2013 and worked on in undisclosed ways. The addendum also revealed eight more SARS viruses sampled from bats in the mine, which had not been previously disclosed.

Wuhan Institute of Virology

The Wuhan Institute of Virology is one of two medical research facilities in Wuhan known to have collected coronaviruses from Yunan.

Professor Shi Zhengli, a Director at the Wuhan Institute of Virology had a longstanding partnership with Professor Ralph Baric of the University of North Carolina, with whom she collaborated through funds granted by NIH and USAID’s PREDICT programme, via EcoHealth Alliance. Shi and Baric co-wrote a paper on a gain of function research project carried out in UNC’s facilities, in which they created a chimeric SARS virus by combining one from bats with a strain that had been adapted to mice.

Scientists have questioned what gain of function research may have been carried out in the Wuhan Institute of Virology and with which viruses.

Entanglement with conspiracy theories

Several notable political commentators and conspiracy theorists, including Steve Bannon and Guo Wengui have proposed that SARS-CoV-2 could have been released from a bioweapons research laboratory.

Richard Ebright commented for a Washington Post "fact check" to distinguish between the possibility that the virus was engineered as a bioweapon, and the possibility that the virus entered the human population via a lab leak.

David Relman said that a deliberate engineering scenario is unlikely because "one would not have had the insight a priori to design the current pandemic virus".

Chinese government response

The Chinese government is alleged to be clamping down on research into the origins of COVID-19. According to Associated Press, a research team that recently visited the Mojian mine to take samples had them confiscated, and coronavirus specialists have been ordered not to speak to journalists, while fringe theories that the virus originated from outside China are promoted in state media.

Chinese President Xi Jinping has said his country will support a "comprehensive" World Health Organization-led review "conducted in an objective and impartial way" after the pandemic has subsided.

On 20 January 2021, Chinese government spokesperson Hua Chunying countered the claims from the US State Department that the virus may have leaked from the Wuhan Institute of Virology.

Statements on COVID-19 origin as a lab leak

By politicians and agencies

A research dossier compiled by the Five Eyes intelligence alliance states that China intentionally hid or destroyed evidence of the coronavirus outbreak and indicated that some of the five intelligence agencies believe that the virus may have been leaked from the Wuhan Institute of Virology, a claim initially dismissed as a conspiracy theory because Chinese officials insisted the virus came from the local wet markets, according to the Australian Daily Telegraph. A senior US intelligence source told Fox News that while most intelligence agencies believe COVID-19 originated in the Wuhan lab, “it was thought to have been released accidentally.”

On 30 April 2020 at the White House, US President Donald Trump was asked by a reporter: "Have you seen anything at this point that gives you a high degree of confidence that the Wuhan Institute of Virology was the origin of this virus?". "Yes, I have. Yes, I have," said the president, without specifying what. "And I think the World Health Organization [WHO] should be ashamed of themselves because they're like the public relations agency for China." Asked later to clarify his comment, he said: "I can't tell you that. I'm not allowed to tell you that." 

On 30 April 2020, the US Defense Intelligence Agency issued a press release, stating that the virus was not "man-made" or "genetically modified" and that the Intelligence Community "will continue to rigorously examine emerging information and intelligence to determine whether the outbreak began through contact with infected animals or if it was the result of an accident at a laboratory in Wuhan."

On 3 May 2020 US Secretary of State Mike Pompeo said on ABC's "This Week" that there was "enormous evidence" that the coronavirus pandemic originated in a laboratory in Wuhan, China, saying "I can tell you that there is a significant amount of evidence that this came from that laboratory in Wuhan." Pompeo added "These are not the first times that we've had a world exposed to viruses as a result of failures in a Chinese lab," pointing at China's "history of running substandard laboratories." Pompeo later clarified in a radio interview: "We don’t know if it came from the Wuhan Institute of Virology. We don’t know if it emanated from the wet market or yet some other place. We don’t know those answers."

On 22 October 2020, former Czech Minister of Health Roman Prymula, an epidemiologist, said "It is almost certain that the virus came from a laboratory in China. Not that it was artificially made there, but it escaped because various research was commonly carried out there, based on natural reservoirs, that is, on various bats and the like. On a model animal (intermediate hosts of the virus) the virus apparently got out, got on the market and a global catastrophe began." Prymula further stated "It’s not an artificial virus. There’s a lot of evidence for that. The virus is very complicated." Prymula said, adding, "If someone created the virus, it would be a genius I’d take my hat off."

On 2 January 2021, multiple newspapers reported on a call between U.S. national security adviser Matthew Pottinger and members of the parliament of foreign nations on China and the WHO investigation into the origins of COVID-19. During the call, Pottinger claimed that a lab origin is a "credible possibility" of the virus and called on MPs to decry the investigation by the WHO as a "Potemkin exercise". Iain Duncan Smith, a British MP and former Tory leader who attended, was quoted by the Daily Mail as saying that Pottinger's remarks were "a 'stiffening' of the U.S. position" on the laboratory theory amid reports that Americans were in contact with a whistleblower from the Wuhan Institute of Virology.

On 15 January 2021, the U.S. State Department published a "fact sheet", stating that the U.S. government was not sure if the outbreak of the virus began "through contact with infected animals", or as a result of "an accident at a laboratory" in Wuhan. The document stated; "The U.S. government has reason to believe that several researchers inside the WIV became sick in autumn 2019, before the first identified case of the outbreak, with symptoms consistent with both COVID-19 and common seasonal illnesses." It further stated that the institute has "engaged in classified research, including laboratory animal experiments, on behalf of the Chinese military since at least 2017".

By academics

On 5 February 2020, Richard Ebright, a biology professor at Rutgers University in New Jersey, told the BBC that genomic sequencing of the coronavirus showed no proof that it had been artificially modified, yet he could not rule out the possibility that the unfolding pandemic could be the result of a "lab incident." Ebright said the coronavirus was a cousin of one found in bats captured by the institute in caves in the southwestern province of Yunnan in 2003, and that samples had been kept in the Wuhan lab since 2013.

On 6 February 2020 two Chinese Scientists Botao Xiao and Lei Xiao, both from Wuhan universities, posted a paper to ResearchGate titled "The possible origins of the 2019-nCoV coronavirus", positing that the virus did not come from horseshoe bats that were being sold in the Wuhan market, as there were no known colonies of this species of the bat within 90 kilometres of Wuhan, also pointing out that out of 59 people being interviewed, it was found that there were no horseshoe bats being sold in the area. The researchers theorised that the coronavirus originated from bats being used for research at either one of two research laboratories in Wuhan, namely the Wuhan Center for Disease Control and Prevention (WHDC), 280 metres away from the Wuham market, or the Wuhan Institute of Virology (WIV), Chinese Academy of Sciences, which is 12 kilometres away. The short paper summarised "somebody was entangled with the evolution of 2019-nCoV coronavirus". The paper was later withdrawn under unknown circumstances.

Filippa Lentzos, a senior research fellow at King's College London writing in the Bulletin of the Atomic Scientists, called for a forensic investigation to include all origin theories, saying "While there is, as of yet, little concrete evidence for them, there are several indications that collectively suggest this is a serious possibility that needs following up by the international community." In a follow-on piece Lentzos wrote more on what an investigation would entail, explaining "investigating the range of possible spillover sites - from the wet market, to an accidental lab or fieldwork infection, or an unnoticed lab leak - requires a forensic investigation. Obtaining case histories, epidemiological data, and viral samples from different times and places, including the earliest possible samples from infected individuals and samples from wildlife, is paramount". Lentzos said that in order to uncover the origins of the virus, investigation would need to begin rapidly before "relevant data diminishes or disappears entirely as time passes." Lentzos later said in an interview that she felt compelled to right the second piece in order to distinguish more between false allegations of bioweapons and the more legitimate line of inquiry into a lab leak.

On 24 Nov 2020, David A. Relman, a US microbiologist at the Stanford University School of Medicine, published an opinion piece in Proceedings of the National Academy of Sciences of the United States of America in which he called for a complete, international, and transparent investigation into the possibility that SARS-CoV-2, the virus which causes COVID-19, leaked out of a lab in China. Relman points out that the "origin story" of the coronavirus is still missing key details and that an objective analysis necessitates "addressing some uncomfortable possibilities," including a release from a lab. Relman stressed that if the infection was a result of bats transmitting the virus to humans, it must be known in order to prevent such infections in the future. Likewise, if the virus had escaped from a high Biosafety Level 4 lab, such as the Wuhan Institute of Virology, then it is essential to delve into "the chain of events and prevent this from happening again."

On 22 December 2020 in an interview with the BBC, Dr Daniel Lucey, a senior scholar and adjunct professor of infectious diseases at the Georgetown University School of Medicine in Washington DC said he believes that the virus is most likely of a natural origin, but that he would not want alternative origin theories to be ruled out, given that 12 to 13 months have passed since the virus first emerged and no animal has been found as the intermediate host. Lucey said: "So, to me, it's all the more reason to investigate alternative explanations. Might a Chinese laboratory have had a virus they were working on that was genetically closer to Sars-Cov-2, and would they tell us now if they did?" Lucey concluded: "Not everything that's done is published."

On 16 January 2021 in an interview with the Spectator, Professor Francois Balloux of University College London said that the virus looks "very natural" and when asked about the lab leak theory, he answered "I think we cannot rule this out at this stage and I hope there will be a proper investigation to clarify that, but even if it happened, to be absolutely brutally honest, similar things have happened before, and there is always a small risk that something can escape from a lab".

In an interview with Science Magazine, Marc Lipsitch Professor in the Department of Epidemiology at the Harvard T.H. Chan School of Public Health said the WHO investigation team will need to consider the lab leak hypothesis.

By the media

On 16 April 2020, CNN quoted unnamed US intelligence and national security officials who said that the US government is looking into the possibility that virus spread from a Chinese laboratory rather than a wet market. One intelligence official said the virus may have accidentally been released from a laboratory in Wuhan. The source said sensitive intelligence was being collected to pursue the theory.

On 1 May 2020, the BBC published an editorial "Coronavirus: Is there any evidence for lab release theory?" Excerpt: "Pathogens can be made to mutate in a laboratory without the directed manipulation of their genes. In so-called "passage experiments", viruses or bacteria are passed from one lab animal to another in order to study how the agents adapt to their hosts. Past experiments have succeeded in making viruses more transmissible between animals using this low-tech method. But, again, there is no evidence that this played any role in the origin of the novel coronavirus."

On 1 May 2020, CBS News reported that two scenarios were being examined by the intelligence community about the origins of the novel coronavirus, quoting a senior U.S. intelligence official as saying that “evidence of both scenarios exists,” but the official didn’t say which of the two scenarios is deemed to be more likely.

On 9 September 2020, Boston magazine published a piece titled "Could COVID-19 Have Escaped from a Lab?" detailing investigations by Alina Chan of the Broad Institute into several anomalous aspects of the virus and its possible origins. Chan focused her research on the seeming preadaptation of the virus to humans, given that the genomes found on surfaces in the Wuhan seafood market earlier in the year were the same in circulation in human-to-human transmission elsewhere around the world later in the year. Chan uploaded a preprint to bioRxiv, which was cited in a Newsweek report titled "Scientists Shouldn’t Rule Out Lab as Source of Coronavirus, New Study Says.", and elicited criticism from a number of scientists, including Peter Daszak of EcoHealth Alliance and Jonathan Eisen of UC Davis, challenging the notion that the virus was preadapted to humans. Chan was able to test her hypothesis as news broke that the coronavirus had jumped from humans to minks at European fur farms, and the mink version was shown to rapidly mutate.

On 14 November 2020, the Washington Post published an article titled "The coronavirus’s origins are still a mystery. We need a full investigation." noting that "troubling questions in China that must be examined, including whether the coronavirus was inadvertently spread in an accident or spill from the Wuhan Institute of Virology, which had previously carried out research on bat coronaviruses."Template:Unreliable source

On 22 December 2020, BBC investigative journalist John Sudworth published a report titled "Covid: Wuhan scientist would 'welcome' visit probing lab leak theory". Sudworth attempted to access the copper mine in Tongguan where the Mojiang Miners Pneumonia Incident occurred but was tailed by plain clothed police and blocked by checkpoints and obstacles. In an interview with Shi Zhengli of the Wuhan Institute of Virology, Sudworth asked if the WHO would be able to access the Institute's data and records to which Shi answered "I would personally welcome any form of visit based on an open, transparent, trusting, reliable and reasonable dialogue. But the specific plan is not decided by me." The BBC subsequently received a call from the Institute's press office, saying that Shi was speaking in a "personal capacity and her answers had not been approved."

On 22 December 2020, Le Monde published a piece titled "At the origin of the Covid-19 pandemic, a SARS-CoV-2 virus with still enigmatic sources" questioning the origin of the virus as an accidental lab leak.

On 31 December 2020, the The Times published an article titled "How did Covid-19 start? Hunt for patient zero has become caught in a clash of great powers" noting the differing opinions of scientists on the origins of the virus, as a zoonotic jump or accidental lab leak. The article quotes Peter Daszak as saying "If you had no politics, no conspiracy theories, no geopolitical pressure, no previous US State Department heads who said, 'China's to blame for this outbreak and there need to be reparations' it would be straightforward to find a lot more out." The article quotes a contrary opinion from Dr Alina Chan "No country wants to admit they have covert human pathogen research, ongoing that is causing mass death around the world." The article concludes "Publicly, many senior scientists have opposed this idea. We ... strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin, one group wrote in The Lancet in February. Privately, some scientists say it was not so absurd."

On 4 January 2021, The New Yorker published a cover story titled "The Lab-Leak Hypothesis For decades, scientists have been hot-wiring viruses in hopes of preventing a pandemic, not causing one. But what if …?" by Nicholson Baker.

See also

• Investigations into the origin of COVID-19
• SARS conspiracy theory