User:Novem Linguae/Essays/There was no lab leak

2021 version

In regards to a possible laboratory accident or "lab leak" of SARS-CoV-2 from the Wuhan Institute of Virology, top quality medical sources describe a lab leak as "highly unlikely", "extremely unlikely", "massive online speculations", "speculations, rumours, and conspiracy theories", "not evidence-based", and "opinion-based narratives".

Top quality, WP:MEDRS sources

Lab leak?

In light of social media speculation about possible laboratory manipulation and deliberate and/or accidental release of SARS-CoV-2, Andersen et al. theorize about the virus' probable origins, emphasizing that the available data argue overwhelmingly against any scientific misconduct or negligence (Andersen et al., 2020)

Immunity, May 19, 2020

In their commentary they wrote "there are speculations, rumours and conspiracy theories that SARS-CoV-2 is of laboratory origin" and that "some people have alleged that the human SARS-CoV-2 was leaked directly from a laboratory in Wuhan where a bat CoV (RaTG13) was recently reported". However, authors have not cited any authenticated source or literature that has claimed the "laboratory engineering".

Le infezioni in medicina (Italian), September 1, 2020

Another unconfirmed hypothesis that has received mixed response is the possibility of the virus originating in Wuhan's Centre of Disease Control and Prevention, located just 300 yards away from Wuhan's animal market or the Wuhan Institute of Virology located eight miles away from the animal market. Conspiracy theories about a possible accidental leak from either of these laboratories known to be experimenting with bats and bat CoVs that has shown some structural similarity to human SARS-CoV-2 has been suggested, but largely dismissed by most authorities.

Postgraduate Medical Journal, February 1, 2021

Our initial findings suggest that the introduction through an intermediary host species is the most likely pathway and one that will require more studies and more specific targeted research.

Similarly and connected to this hypothesis is also the one including the possibility of transmission through the trade of frozen cold-chain products.

There we are making the difference between the introduction of the virus into the human population and the possibility of the circulation of the virus through long-distance and through different settings or the introduction of the virus into a particular setting like a market for example.

Then the hypothesis of a direct spill-over from an original animal source into the human population is also a possible pathway and is also generating recommendation for future studies.

However, the findings suggest that the laboratory incident hypothesis is extremely unlikely to explain introduction of the virus into the human population and therefore is not a hypothesis that will imply to suggest future studies into our work to support our future work into the understanding of the origin of the virus.

World Health Organization, February 9, 2021

Despite these massive online speculations, scientific evidence does not support this accusation of laboratory release theory. Yet, it is difficult and time‐consuming to rule out the laboratories as the original source completely. It is highly unlikely that SARS‐CoV‐2 was accidentally released from a laboratory since no direct ancestral virus is identified in the current database. The complete genome of SARS‐CoV‐2 is deposited in the public database shortly after the outbreaks based on advanced next generation sequencing technologies. There is also no record of laboratory accidents at the WIV, and the former SARS‐CoV accident did not occur at the WIV. Additionally, a recent study further supported the natural origin of SARS‐CoV‐2 from viruses found in Rhinolophus sp. However, an independent forensic investigation is probably the only course of action to prove or disprove this speculation.

Reviews in Medical Virology, February 14, 2021

Another hypothesis is the accidental infection of laboratory staff working on naturally occurring Sarbecoviruses. Accidents happen and have already been reported during the SARS epidemic in Taiwan, Singapore and China (Webster, 2004; WHO, 2004). This is not limited to SARS-CoV (Heymann et al., 2004). When it happened in Beijing in 2004, the information was immediately released and an investigation involving both WHO and Chinese governmental agencies was conducted, patients were identified and treated (WHO, 2004). There is today no evidence that such an accident had happened with SARS-CoV-2. Because of the incubation period of COVID-19, the weak symptoms, the significant rate of asymptomatic patients and the low virulence (with an estimated fatality rate of 3.26%, but more likely around 1% to 2% which is significantly lower than SARS-CoV with 9.6%), an accident could have easily remained unnoticed. But staff members of the Wuhan Institute of Virology have all been tested negative indicating that no accident occurred there (Cohen, 2020). One must remember that SARS-CoV-2 was never found in the wild and that RaTG13 does not exist as real virus but instead only as a sequence in a computer (Zhou et al., 2020a; Ge et al., 2016). It is a virtual virus which thus cannot leak from a laboratory. This hypothesis has been considered as "extremely unlikely" by the official WHO investigation team (Dyer, 2021). Therefore, although a laboratory accident can never be definitively excluded, there is currently no evidence to support it.

Infection, Genetics and Evolution, March 18, 2021

As for the vast majority of human viruses, the most parsimonious explanation for the origin of SARS-CoV-2 is a zoonotic event. The documented epidemiological history of the virus is comparable to previous animal market-associated outbreaks of coronaviruses with a simple route for human exposure. The contact tracing of SARS-CoV-2 to markets in Wuhan exhibits striking similarities to the early spread of SARS-CoV to markets in Guangdong, where humans infected early in the epidemic lived near or worked in animal markets. Zoonotic spillover by definition selects for viruses able to infect humans. Although strong safeguards should be consistently employed to minimize the likelihood of laboratory accidents in virological research, those laboratory escapes documented to date have almost exclusively involved viruses brought into laboratories specifically because of their known human infectivity.
There is currently no evidence that SARS-CoV-2 has a laboratory origin. There is no evidence that any early cases had any connection to the WIV, in contrast to the clear epidemiological links to animal markets in Wuhan, nor evidence that the WIV possessed or worked on a progenitor of SARS-CoV-2 prior to the pandemic. The suspicion that SARS-CoV-2 might have a laboratory origin stems from the coincidence that it was first detected in a city that houses a major virological laboratory that studies coronaviruses. Wuhan is the largest city in central China with multiple animal markets and is a major hub for travel and commerce, well connected to other areas both within China and internationally. The link to Wuhan therefore more likely reflects the fact that pathogens often require heavily populated areas to become established (Pekar et al., 2021).

Cell, 16 September 2021

"One specific narrative states that the Wuhan Institute of Virology (WIV) team led by Dr. Shi Zheng Li visited the Mojiang mine in 2012 following an accident involving six miners and that they collected SARS-CoV-2 from this mine. Rahalkar and Bahulikar, and followers, make a clear link between the Mojiang mine incident, WIV and SARS-CoV-2. Here, we show, based on the clinical reports, that the Mojiang miners did not developed(sic) COVID-19 or even SARS and were not infected by SARS-CoV-2. We thus dismiss the Mojiang mine as the origin of SARS-CoV-2. Dismissing the Mojiang mine theory leaves the laboratory leak narrative without any scientific support thus making it simply an opinion-based narrative."
"RaTG13 is not a virus but only a sequence generated by metagenomics (Ge et al., 2016; Zhou et al., 2020b). Therefore, there is no evidence that this sequence corresponds to any real and viable virus or even that all reads are coming from the same virus. ... It has no physical existence and thus cannot leak from a laboratory. Furthermore, considering the very high number of mutations separating RaTG13 from SARS-CoV-2 and their phylogenetic distance, RaTG13 can hardly be considered a progenitor of SARS-CoV-2 even if it corresponded to a real virus. The suggested engineering of SARS-CoV-2 for gain of function through in vitro synthesis from the RaTG13 sequence is a narrative making no sense from an operational standpoint. Engineering a complete virus is beyond current technical possibilities."
"... furin activation sites are naturally occurring in different viruses, including coronaviruses, and thus cannot be a proof of genetic engineering (Frutos et al., 2021)." "WIV has conducted gain-of-function experiments but it was in the framework of an official and publicly available NIH grant ... All spike proteins tested were genetically distant from those of SARS-CoV-2 and RaTG13. The swapping of spike proteins only led to slight variations. ... This work showed that the consequences of gain-of-function experiments on SARS-CoV-2-like viruses were extremely limited and certainly not to the magnitude of an epidemic as imagined by tenants of a laboratory accident."
"As a conclusion, there is no evidence to support the Mojiang mine origin of SARS-CoV-2 and any of the laboratory leak theories. ... These narratives are not evidence-based scientific conclusions. ... In a time of geopolitical conflicts characterized by hidden agendas, false information and manipulations, it is essential to rely only on scientific and evidence-based conclusions and to avoid opinion-based narratives."

Environmental Research, 2 October 2021

Zoonotic origin?

"The suspected animal-to-human jumping of 4 betacoronaviruses including the human coronaviruses OC43(1890), SARS-CoV-1(2003), MERS-CoV(2012), and SARS-CoV-2(2019) indicates their significant pandemic potential. The presence of a large reservoir of coronaviruses in bats and other wild mammals, culture of mixing and selling them in urban markets with suboptimal hygiene, habit of eating exotic mammals in highly populated areas, and the rapid and frequent air travels from these areas are perfect ingredients for brewing rapidly exploding epidemics." (abstract)
"The origin of SARS-CoV-2 is still unknown. Recombination is a frequent event for the viral subgenus Sarbecovirus, which contains SARS-CoV, bat SARS related CoV, and SARS-CoV-2. Some studies suggested that the bat SARS-CoV-2-like coronaviruses are recombinants of lineages related to SARS-CoV and SARS-CoV-2, and SARS-CoV-2 may result from recombinations between these bat SARS related coronavirus and the pangolin SARS related coronavirus [55, 56]. However, another study suggested that recombination may not be involved in the generation of SARS-CoV-2, but the RBD of SARS-CoV-2 shares the same ancestral trait as bat viruses. The divergence date between SARS-CoV-2 and bat sarbecovirus has been estimated to be 1948." (later in the article – no mention of labs or leaks or anything)

Emerging Microbes & Infections, March 2021.

Since SARS-CoV-2 very likely has a zoonotic origin, it is important to identify the original animal reservoir to prevent future similar outbreaks. Therefore, during the last months, a significant number of different animal species were either sampled in the field or experimentally infected with SARS-CoV-2, in order to evaluate their susceptibility to infection and to assess their potential as animal reservoirs.

Advances in Virus Research, April 2021.

"The emergence of SARS-CoV-2 has resulted in a health crisis not witnessed since the 1918–19 Spanish influenza pandemic. The most plausible origin of SARS-CoV-2 is natural selection of the virus in an animal host followed by zoonotic transfer."

The Lancet. Respiratory Medicine, May 2021.

"There is a strong evidence that SARS‐CoV‐2 virus originated in bats; however, the intermediate animal host is still unknown. Several studies showed that pangolins, snakes, turtles, and mink are all possible intermediate hosts, however, further investigations are needed. It is worth mentioning that recent findings that analyse the probable animal reservoir to Covid‐19 suggest the snake as a reservoir, based on relative synonymous codon usage bias. 67 However, the missing link or intermediate link for animal to human transmission of SARS‐CoV‐2 from a recent study suggests the DNA and protein sequence of Malayan pangolins. 69"
"SARS‐CoV‐2 was first identified in Wuhan city in China in hospitalized patients who previously visited the Huanan wet seafood market where various animals including chickens, pigs, pangolins, bats, snakes, frogs, rabbits, and marmots are sold for human consumption, proposing a suitable environment for zoonotic infection spill‐over to humans. Scientists believe that these traditional Chinese practices might be responsible for the SARS‐CoV‐2 pandemic in humans and that the recurrent interactions between humans and animals without proper biosafety measures present a substantial risk for the occurrence of zoonotic diseases. Zoonotic CoVs have crossed the species barrier twice in the past 2 decades (SARS‐CoV; 2002 and MERS‐CoV; 2012). Thus, scientists have speculated that SARS‐CoV‐2 resulted from a zoonotic spillover event as well. Zoonotic CoVs need to propagate in their zoonotic reservoirs, and then, seek the chances to spillover via intermediate hosts into susceptible human targets, where they can maintain human‐to‐human transmission. Bats have been revealed as the natural hosts for several human CoVs, including HCoV‐NL63, HCoV‐229E, SARS‐CoV, and MERS‐CoV. Genome sequence analysis confirmed that SARS‐CoV‐2 is 96% identical to the bat CoV RaTG13 at the whole‐genomic level, and hence bats are believed to be the primary source of origin for the novel SARS‐CoV‐2. However, the intermediate host that is yet to be elucidated. Researchers proposed two hypotheses for the emergence of SARS‐CoV‐2: (1) Natural selection may have occurred in an animal host before transmission to mankind; and (2) natural selection of viruses may have occurred in humans after zoonotic transmission. In this regard, studies involving the use of animal models or cell culture are in need to help clarify these two scenarios."

Reviews in Medical Virology, November 2020.

SARS-CoV-2 has a zoonotic origin, similar to the causative viruses of these previous outbreaks. The repetitive introduction of animal viruses into human populations resulting in disease outbreaks suggests that similar future epidemics are inevitable.

Experimental and Molecular Medicine, April 2021.

The emergence of a zoonotic pathogen in humans, such as SARS-CoV-2, was not unpredicted. Of the novel or re-emerging infectious diseases affecting humans in the 21st century, most (75%) have been zoonotic in origin, with their natural reservoirs being other vertebrates. The majority (over 70%) of these diseases with zoonotic origin have originated from wildlife, such as HIV/AIDS, the Ebola virus, and severe acute respiratory syndrome (SARS). Globally, known events of zoonotic disease emerging from wildlife have significantly increased over the past 80 years, raising public health, economic, societal and environmental concerns, as exemplified by the COVID-19 pandemic. The current weight of evidence suggests that SARS-CoV-2, or its progenitor, probably emerged in humans from a zoonotic source in Wuhan, China, where it was first identified in 2019. Although evidence on the origins of SARS-CoV-2 are inconclusive, bats have been suggested to be the most probable evolutionary source for the virus.

The Lancet. Planetary Health, November 2021.

2025 version

It's been 4 years since I wrote the above. Is there a chance that scientific opinion has shifted in the past few years? Let's check some newer scientific literature.

To survey MEDRS-quality sources, a good technique is to use PubMed with certain strict filters applied (meta-analysis, review, systematic review, exclude preprints, MEDLINE). I believe that doing a PubMed search of a term such as "covid laboratory leak", and then perusing the top 10 results, should be a good technique for surveying top quality sources regarding the lab leak.

Here's a link to the search. I performed this search on 2025-01-28. Of the first 10 results, 5 of them were relevant to the lab leak theory. I will quote some of each of them here. I am not going to cherry pick here. This is a summary of every relevant search result, regardless of its conclusion.

Search result 1 - The origins of COVID‐19 pandemic: A brief overview

• https://pmc.ncbi.nlm.nih.gov/articles/PMC9874793/
• 2022-10-20
• Transboundary and Emerging Diseases

Despite the fact that animal host of SARS‐CoV2 has not yet been identified, zoonotic origin is supported by a substantial body of research. Even though laboratory accidents cannot entirely be ruled out, it can be deduced from the current research that the emergence of SARS‐CoV‐2 likely stemmed from natural adaptation.

Search result 2 - SARS-CoV-2 origins: zoonotic Rhinolophus vs contemporary models

• https://www.tandfonline.com/doi/10.1080/02648725.2022.2115682
• 2022-06-22
• Biotechnology and Genetic Engineering Reviews

we strongly support the zoonotic origin of the infamous SARS-CoV-2 in bats and its transfer to human beings through the most probable evolutionary hosts, pangolins and minks. We also support the contemporary ‘Circulation Model’ that simply mirrors the concept of evolution to explain the origin of the virus which, the authors believe, is the most rational school of thought.

Search result 3 - What do we know about the origin of COVID-19 three years later?

• https://pmc.ncbi.nlm.nih.gov/articles/PMC9995320/
• 2023-03-09
• Revista Clínica Española
• Translated from Spanish using Google Translate:

Do these findings close the discussion regarding the origin of SARS-CoV-2?

No, as we can see, there are two theories that could coexist or be resolved by choosing one of them. It is a fundamental aspect in public health to be able to define the transmission chains and find their origin. So, on the one hand, it seems clear that the origin of the transmission took place in the Huanan market. But on the other hand, there are still three fundamental questions without a definitive answer. The first, where did the virus come from? The second, what was the intermediary animal? And the third, why has the virus genome not reproduced 100% in any of the CoVs found in bats?

To provide a definitive answer to these questions, we need further virological and genomic studies, as well as the collaboration of the Chinese government.

Search result 4 - An updated review of the scientific literature on the origin of SARS-CoV-2

• https://pmc.ncbi.nlm.nih.gov/articles/PMC9420317/
• 2022-08-28
• Environmental Research

Based on the information here reviewed, the only true facts are that, nowadays, there is not a definitive and well demonstrated conclusion on the origin of SARS-CoV-2. Although most data certainly point to a natural origin, the intermediate host has not been found, and the hypothesis of a laboratory-leak has not been yet scientifically discarded.

Search result 5 - Tracing the origin of Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2): A systematic review and narrative synthesis

• https://pmc.ncbi.nlm.nih.gov/articles/PMC9538017/
• 2022-09-07
• Journal of Medical Virology

Debunking misinformation and enhancing awareness about the necessity of research to determine the origin of pathogens are of utmost importance. The fact that the COVID‐19 pandemic occurred in the same region where the WIV is located, a state‐of‐the‐art virology laboratory that performs research on bat coronaviruses, fueled speculation that SARS‐CoV‐2 was developed in a laboratory. Notwithstanding the rhetoric, there seems to be no compelling proof that SARS‐CoV‐2 was ever reported to virologists before it emerged in December 2019, and all indicators imply that, like SARS and MERS, this virus most likely evolved in a bat host unless an unknown human spillover event occurred.

Nevertheless, this accomplished hardly anything to halt the proliferation of often paradoxical and, at times, completely absurd conspiracy theories that propagated more rapidly than the disease outbreak itself. For example, it has been claimed that SARS‐CoV‐2 was either the consequence of a laboratory error or was purposefully manufactured or it was produced for GoF investigations, which were previously undertaken with bat SARS‐like coronaviruses to investigate the cross‐species transmission risk. However, performing such research under global prying eyes seems unlikely. Furthermore, disease emergence due to a natural cause has a long history: most new viruses that have caused epidemics or pandemics in humans have originated organically from wildlife reservoirs. As a result, the overwhelming opinion is that this virus entered into a susceptible human host through contact with an infected animal, alternatively through contact with infectious animal tissues.

Summary of these 5 search results

Interestingly, most of these papers are from 2022, with only one paper from 2023, and zero papers from 2024. This suggests to me that progress on researching the origin of SARS-CoV-2 has stalled, probably due to the Chinese government not cooperating.

I would summarize the above conclusion of each paper as the following:

1. zoonotic origin "likely", lab leak "cannot be ruled out"
2. zoonotic origin "strongly support"
3. zoonotic origin possible, lab leak possible, need more studies and China's cooperation to make a conclusion
4. zoonotic origin "most data certainly point to it", lab leak "hypothesis not yet scientifically discarded"
5. zoonotic origin is the "overwhelming opinion", lab leak "no compelling proof"

Three of these bullet points use superlatives such as "strongly", "most", and "overwhelming" to support the zoonotic origin theory. One bullet point uses no superlative, but still supports zoonotic origin, calling it "likely". One bullet point states there is not enough data to make a conclusion due to the Chinese government not cooperating.

Overall, it is my opinion that most of these papers favor zoonotic origin, and none of them favor the the lab leak theory. Most of these papers say that a lab leak was theoretically possible, but that no compelling evidence has been found for it so far.

Does the COVID-19 lab leak theory Wikipedia article need a rewrite?

Now the million dollar question. Does our Wikipedia article COVID-19 lab leak theory present the information in a way that matches the conclusions of the papers above? Does it have the correct tone? Does it get any facts wrong? Does it get the WP:WEIGHT right? Here's the lead of that article as it's currently written on 2025-01-28:

The COVID-19 lab leak theory, or lab leak hypothesis, is the idea that SARS-CoV-2, the virus that caused the COVID-19 pandemic, came from a laboratory. This claim is highly controversial; most scientists believe the virus spilled into human populations through natural zoonosis (transfer directly from an infected non-human animal), similar to the SARS-CoV-1 and MERS-CoV outbreaks, and consistent with other pandemics in human history.[1] Available evidence suggests that the SARS-CoV-2 virus was originally harbored by bats, and spread to humans from infected wild animals, functioning as an intermediate host, at the Huanan Seafood Market in Wuhan, Hubei, China, in December 2019.[5][6] Several candidate animal species have been identified as potential intermediate hosts.[13] There is no evidence SARS-CoV-2 existed in any laboratory prior to the pandemic,[14][15][16] or that any suspicious biosecurity incidents happened in any laboratory.[17]

My conclusion: This looks good to me. It correctly states that most scientists favor zoonotic origin. It correctly states that the transmission chain is likely bats -> possible intermediate animal -> humans. It correctly states that lab leak has zero hard evidence. I do not think we need to change anything in the first paragraph of the article COVID-19 lab leak theory.

What would it take to get me to change my mind? I think a top quality scientific paper showing up in my PubMed search above that states that the lab leak theory is more likely than zoonotic origin, or that hard evidence (not circumstantial evidence) has been found that supports the lab leak theory, would be a good start. But such a paper does not appear to exist as of 2025-01-28.