WAS COVID VIRUS CREATED IN A WUHAN LAB?

Manoj Pandey*

Caution: This is a rather long article. Partly because there is so much to discuss on this topic and partly because many passages from research documents and quotes from knowledgeable persons had to be reproduced verbatim to avoid the chance of misinterpretation in paraphrasing the exact statements/ claims. If in a hurry, you may like to go straight to a particular section by clicking its link in the index below.

Disclosures: 

1. I have given more arguments and cited more documents that suggest the lab-origin of SARS-CoV-2 virus than those supporting natural-origin: that is because the latter is the mainstream theory and the counter-point needs to be taken note of. 

2. Some of the research papers cited are preprints or not peer-reviewed, and web-references are prone to be withdrawn/ removed/ blocked/ modified over time.

3. In quoting resources, care has been taken not to quote them out of context. Selective it is because quotes have been used for supporting the point under discussion.

INDEX * Why the fuss now? * What does the WHO investigation report say? * How has the investigation report been received? * The mainstream view: SARS-CoV-2 originated naturally * The counter-narrative: lab origin * Where are we?

Explaining technical terms

The article will use some technical terms, so let us recall what they mean before we discuss the topic:

• SARS-CoV-2: The viral strain that causes COVID-19 infection. It is one of the thousands of coronaviruses that cause viral flu in humans and many animals.

• Gain of function research: Research in which pathogens (mostly viruses) are subjected to specific stress while they are replicated in the lab, to create new variants that can be exploited for fighting viruses that can evolve naturally. This leads to the creation of mutants or recombinants that have gained a new function such as being more transmissible, virulent, or resistant to existing vaccines. It is argued that such research can put humans ahead of possible natural mutations, thus allowing for a better response to future pandemics. 

• WIV: Wuhan Institute of Virology, China. This is one of the many Chinese organizations engaged in virology. They run research labs of different safety levels including labs in Wuhan and nearby areas in which research on coronaviruses is being carried out for over a decade.

• Serial passage: A simple but effective method of creating new viruses in the lab, in which some genetic manipulation is done and the virus is made to infect lab animals or cultures. The viruses that come out with potentially useful traits are then passed on to another set of cultures or animals. This is repeated in a series to achieve a virus strain with ‘desirable’ qualities.

• Chimera: A mythical monster with body parts taken from different animals. A virus whose genome is made from gene sequences taken from different strains is called chimera virus. Such a virus can arise in nature and can be created in the lab by recombination (=mixing DNA/RNA sequences) of genes of different viruses.

• Zoonotic infection: Infection that has jumped from an animal species to humans.

Why the fuss now, after nearly one and a half years?

When the novel coronavirus (later named SARS-Cov-2) first made headlines in December 2019, scientists discussed the possible ways the virus could have originated. One of the possibilities was that the virus might have originated in the Wuhan virology lab. It was no secret that very risky biological experiments were being conducted in the lab and it was required to maintain a very high level of biosafety standards so that any virus being studied/ created in the lab did not go out of the lab. 

However, China bunked lab origin hypothesis as a conspiracy theory. A prominent group of scientists, without proof this way or that, came out with a joint statement in a reputed research journal Lancet, strongly endorsing the view that the virus had a natural origin.

The then US President Donald Trump kept repeating his accusations that China was hiding some sensitive information about the origin of the virus. But Trump was known to make sweeping anti-China statements, and thus his views were seldom taken seriously. When Australia and some other countries raised their voice against the suppression of data by China, the Chinese authorities reacted sharply, even threatening them. As the US intelligence agencies could not find a link between the COVID-19 virus and the Wuhan lab, the lab origin hypothesis lost its appeal but it kept on simmering beneath the surface.

Some of the scientists that raised the lab origin theory were also linked with establishments not favourable to China, their papers had not been published in topmost research journals, and they did not have ‘proven facts’ in hand. On the other hand, the pro-natural origin lobby was very aggressive and even WHO leadership seemed to be attuned to the Chinese version. These factors led to the lab origin views getting sidelined even in the scientific community.

In January 2021, after long negotiations with China on the terms of reference and constitution of the team, WHO sent a team of international scientists to China for studying the outbreak of the pandemic in Wuhan. The team was not well-received (had to undergo quarantine on reaching Wuhan, etc.) but it did produce a report in March 2021 after studying the origin and spread of the virus jointly with Chinese counterparts. We shall discuss the joint team’s report in the next section; in short, it gave a green chit to China as far as the possibility of lab origin of COVID-19 virus is concerned. 

It is the perfunctory nature of the conclusions drawn in the report indicate that China has hidden data from the team and  seemingly it dictated the report to the visiting team. The way the investigations were carried out and the report was prepared shatter the confidence of the world community on the substance of the report. This has led to a call for an impartial investigation on the origin and early spread of SARS-CoV-2.

What does the WHO investigation report say on the origin of COVID-19 virus?

The joint team examined four possible pathways the virus could have moved from animals to humans. Please note that the report has skirted a clear indication and, instead, given the possibility of each of the four pathways in this scale: very likely> likely> possible> unlikely> extremely unlikely.

• direct zoonotic spill over is considered to be a possible to likely pathway;  

• introduction through an intermediate host is considered to be a likely to very likely pathway;

• introduction through cold/ food chain products is considered a possible pathway; and

• introduction through a laboratory incident was considered to be an extremely unlikely pathway. 

While the report discussed at length the first three possibilities, it rejected the fourth possibility, almost summarily. More intriguingly, the report mentions that frozen food could be the carrier of the virus from some other countries, also that such symptoms were observed in countries with which China was trading frozen food, and that there is a great similarity between the genomes of a virus found in pangolins being smuggled into China and SARS-CoV-2. Continuing in the same streak, the report recommends that follow-up studies should be conducted on suspected cases around the world reported before the end of January 2020.

Those associated with writing committee recommendations on sensitive issues and making joint statements when two nations do not agree to a point, would know how the reports are written. Much of the joint report contains the briefs presented by the party in question (Chinese authorities), draws safe inferences, talks of limitations, and equates them with limitations elsewhere, and profusely recommends future actions.

How has the investigation report been received by scientists, others?

The international team that visited China had no independent authority to examine people, visit places, and collect data and they fully depended on the host country. China’s overall conduct (of tight control on data and extreme secrecy) does not inspire confidence that it would share any data that would incriminate it, even raises doubts about its scientific or medical capabilities. In fact, in February 2020, Chinese health authorities had ordered its scientists not to share any data, documents or specimens related to the pandemic. They must ‘prioritize the interests of the country’… anyone violating this request would be ‘dealt with severely in accordance with discipline, laws, and regulations’, it said.

Fourteen countries including the US, Canada, Japan, Australia and the UK have issued a joint statement on the joint report. It says: “We voice our shared concerns that the international expert study on the source of the SARS-CoV-2 virus was significantly delayed and lacked access to complete, original data and samples. Scientific missions like these should be able to do their work under conditions that produce independent and objective recommendations and findings. We share these concerns not only for the benefit of learning all we can about the origins of this pandemic, but also to lay a pathway to a timely, transparent, evidence-based process for the next phase of this study as well as for the next health crises.”

The Chinese reaction (even pre-action, as Chinese officials started running stories before the report came out) is on these lines: The report was made in the spirit of cooperation and understanding by the international and Chinese teams, in a time-bound schedule. The WHO team had scientists from as many as ten countries. The report was made on scientific principles. The team was allowed unhindered field and lab visits and interactions with all concerned. To help the team, China started compiling data much earlier than the actual visit of WHO team and provided all data required for the study. China also says, tracing the origin of the virus is a long-term task. About 30 scientists working for 30 days could not have completed it to the full extent.  

In the initial stages of the pandemic, the WHO was seen as being accommodative towards China’s viewpoint. However, the way China delayed the visit of the WHO-led international investigation team, manipulated the terms and constitution of the team and supervised the ‘investigation’, WHO itself has said that a more meaningful investigation needs to be done. Within the very narrow limits in which he could criticise China, WHO Director-General, Tedros Adhanom Ghebreyesus, has made these critical statements after receiving the report :

“…I do not believe that this assessment was extensive enough. Further data and studies will be needed to reach more robust conclusions… Although the team has concluded that a laboratory leak is the least likely hypothesis, this requires further investigation, potentially with additional missions involving specialist experts, which I am ready to deploy… In my discussions with the team, they expressed the difficulties they encountered in accessing raw data. I expect future collaborative studies to include more timely and comprehensive data sharing… As far as WHO is concerned, all hypotheses remain on the table. This report is a very important beginning, but it is not the end. We have not yet found the source of the virus, and we must continue to follow the science and leave no stone unturned…”

In May 2021, 18 scientists from the US, the UK, Canada and Switzerland wrote an article in Science , a reputed research magazine, asking for an independent investigation into the origin of the virus: “We must take hypotheses about both natural and laboratory spill overs seriously until we have sufficient data. A proper investigation should be transparent, objective, data-driven, inclusive of broad expertise, subject to independent oversight, and responsibly managed to minimize the impact of conflicts of interest. Public health agencies and research laboratories alike need to open their records to the public. Investigators should document the veracity and provenance of data from which analyses are conducted and conclusions drawn, so that analyses are reproducible by independent experts.” 

Anthony Fauci, the most visible face and a reasoned voice on COVID-19 in the US government – as the director of the National Institute of Allergies and Infectious Diseases (NIAID) – had been a votary of natural origin of SARS-CoV-2. One of his earlier statements is: “…very, very strongly leaning toward this… could not have been artificially or deliberately manipulated… Everything about the stepwise evolution over time strongly indicates that evolved in nature and then jumped species.” However, in a major shift from his earlier stance, in a public discussion on the subject earlier this month, he showed doubt about the natural origin: “I am not convinced about that, I think we should continue to investigate what went on in China until we continue to find out to the best of our ability what happened… Certainly, the people who investigated it say it likely was the emergence from an animal reservoir that then infected individuals, but it could have been something else, and we need to find that out.”

At the time of writing this article, the World Health Assembly (the plenary of WHO, in which all member nations are represented) is having its 9-day meeting. Many nations have called for an in-depth expert-driven investigation into the origin of SARS-CoV-2. “We underscore the importance of a robust, comprehensive and expert-led inquiry into the origins of Covid-19,” the US representative said. The US President Joe Biden has also issued a public statement that US intelligence agencies are divided on the issue and he has asked the agencies to come out with a conclusive report within 90 days. It says: “…shortly after I became President… I had my National Security Advisor task the Intelligence Community to prepare a report… the U.S. Intelligence Community has “coalesced around two likely scenarios” but has not reached a definitive conclusion on this question. Here is their current position: “while two elements in the IC leans toward the former scenario and one leans more toward the latter – each with low or moderate confidence… I have now asked the Intelligence Community to redouble their efforts to collect and analyse information that could bring us closer to a definitive conclusion, and to report back to me in 90 days.”

China has strongly reacted to it, saying that the US is stigmatizing China. It has questioned the US’s leaning on intelligence rather than scientists. It also says, it supports “a comprehensive study of all early cases of COVID-19 found worldwide and a thorough investigation into some secretive bases and biological laboratories all over the world”.

In short, the issue of the origin of SARS-CoV-2was never purely scientific but now it is mired in serious geo-political and economic rivalry. I will, still, try to limit the discussion to the scientific domain.

The mainstream view: SARS-CoV-2 originated naturally 

The votaries of this hypothesis have these main facts and arguments to offer:

• The lab origin theories have been propounded and spread by anti-China scientists, politicians and countries.
• Wuhan labs were not doing gain of function research (as explained above, research that creates pathogens so as to get ahead of natural evolution). The documents provided by Chinese authorities clearly show that.
• SARS-COV-2 is a chimera virus, and such viruses routinely originate in nature.
• There is 4% difference between the genome of SARS-CoV-2 and that of RaTG13 virus (the closest relative of SARS-CoV-2, found in Yunnan bats), which is too high for using RaTG13 for creating SARS-CoV-2 in a lab. Other viruses have more distantly related genomes.
• Perhaps the population had been infected by SARS-CoV-2 much earlier, and it developed into a highly infectious disease when it crossed a threshold. Though the infection was reported in late December 2019, it has been found using molecular inference and epidemiological simulation techniques that the strain had infected humans in mid-October 2019.
• There were reports of similar symptoms appearing in people in different parts of the globe in 2019. It is reported that this or a very similar virus was already spreading in Italy and Brazil before the infection broke out in Wuhan. 
• It could be a case of bat virus jumping to an intermediate host (most probably pangolin) and then to humans. Pangolins smuggled into China were found to have a genome similar in some respects. In earlier SARS infections, this type of jumping was proved.
• Frozen food consignments into China are a likely source of SARS-CoV-2. Even now, China keeps on rejecting foreign shipments of frozen food as they have traces of COVID-19 virus.
• No traces of lab manipulation have been found in SARS-CoV-2 genome.

Many mainstream scientists hold the view that lab origin of SARS-CoV-2 is not plausible. Very early in the progression of the pandemic, this group, steered by Andersen and Daszak, had tried to tilt the bar in favour of natural origin hypothesis. In an article in research journal Nature in March 2020 , Andersen and his team concluded irrefutably that the virus was not man-made: “the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone… we do not believe that any type of laboratory-based scenario is plausible.” The only thing that needed to be found out, they reckoned, was how exactly the bat virus changed and infected humans and what was the intermediate animal if any.

In a highly damaging article published in January 2021 in the reputed scientific journal Nature, a well-known strong votary of natural origin hypothesis,  Angel Rasmussen, has not only called lab origin a bunch of conspiracy theories , she has even claimed that she was getting serious threats for countering this viewpoint : “…there is no credible evidence that SARS-CoV-2 was ever known to virologists before it emerged in December 2019, and all indications suggest that, like SARS-CoV and MERS-CoV, this virus probably evolved in a bat host until an unknown spill over event into humans occurred… often contradictory and sometimes outright ridiculous conspiracy theories that spread faster than the virus itself: SARS-CoV-2 was the result of a laboratory accident or was intentionally engineered, and this was concealed to hide either spectacular incompetence or a complex international conspiracy involving Bill Gates, the Chinese Communist Party and 5G wireless network infrastructure with an end goal of ushering in a new world order. The proof presented to corroborate these theories relied heavily on cherry-picked evidence ranging from withdrawn preprints to secret diplomatic cables about vague lab safety information to grossly overinterpreted satellite and mobile phone data, all of which prove exactly nothing about SARS-CoV-2 origins… The lead author of those preprints, Yan Li-Meng, has personally attacked scientists engaged in combating this misinformation with evidence, including me. As a result, I’ve been threatened with violence and sexual assault, an occupational hazard of misinformation debunking that I’ve unfortunately come to expect. Although this is deeply unpleasant, I am more concerned about the long-term effects of this type of misinformation for scientists around the world and our ability to conduct impactful scientific research on emerging viruses with pandemic potential.”

As we shall see later, scientists who are not convinced about the natural origin hypothesis have dug out facts that refute the majority of their claims and found loopholes in their reasoning.

The counter-narrative is not all anti-natural origin; it has many nuances

If on one hand, there is the view that ‘SARS-CoV-2 originated naturally. Full stop.’, there are different shades of the views not agreeable to this absolute view. Before going further, let us be clear that everybody who is not agreeing with the natural-origin theory is not saying that China has released this virus as part of bio-warfare. What the majority is saying is that there is a need for a thorough scientific investigation so that the truth comes out. It is more so, because there are many circumstantial evidences and logical inferences that indicate its lab origin. Within the lab origin hypothesis, there are different shades: the virus was natural but escaped during collection and transportation, it was created with the purpose of gain of function research but with no malevolent intent, the escape occurred as researchers got infected, as the and so on.

There is a good amount of circumstantial evidence and logic in favour of lab origin of SARS-CoV-2. However, there is no proof in the form of fingerprints of a lab. The records that could prove the involvement of labs are not shared publicly. Even the mandatory technical records of experiments are not available for any scrutiny. It is interesting to note that one has to come out with convoluted conjectures about how a bat virus in a distant cave jumped to humans and became highly virulent but the lab origin hypothesis is simple and numerous indicators point towards that.

Let us now come to the broad indicators of lab origin of SARS-CoV-2.

Indicators in favour of lab origin

There are many indicators, some of them evident, suggesting why lab origin is more plausible than natural origin. Some of these have been discussed in detail later on.

• The disease appeared suddenly and from a single variant. Scientists say, in the case of natural origin, there are so many stages the bat virus would have to cross before being able to attack humans and with such ferocity. However, no intermediary strains have been discovered so far either in human or animal populations in Wuhan. In fact, there was hardly any diversity in the initial samples of COVID-infected people, which gives rise to the suspicion that unlike what would happen in a natural origin case, a uniform SARS-CoV-2 variant started infecting people at once and from a single source.

In a detailed paper, Latham and Wilson have argued that direct zoonotic (from animals to humans) origin of SARS-CoV-2 in Wuhan is highly improbable owing to the lack of big bat population and other factors, and indeed the head of WIV’s coronavirus research had initially said she never expected such an outbreak in Wuhan. Was it also a coincidence, the paper argues, that the team led by Zhengli Shi in WIV had been doing research on a very similar virus (SARS-CoV) for years. There are other ‘curious’ coincidences that can happen in nature but their probability is extremely low, especially all the coincidences working together, it argues.

The earlier coronavirus attacks from the same region of China (SARS1 and MERS) had left traces of their origin. If SARS-CoV-2 were nature’s baby, there should have been tell-tale evidence of that, especially with the highest level of research capabilities available in WIV. If that was the case, Chinese scientists would have used these as the strongest evidence of a natural origin.

• It is also noteworthy that pangolins were not sold in Wuhan markets, and bats usually hibernate during winter months period and in any case are not found in Wuhan. So, the epidemic suddenly exploding in Wuhan does not favour the natural origin hypothesis.

• A number of high-security labs do exist in Wuhan. It could be a rare coincidence that WIV has labs in the area, in which research on coronaviruses is going on, and SARS infections have been starting from Wuhan. But this raises doubt, isn’t it? In addition, it is worth noting that a lab of high safety level was shifted to the Wuhan campus in late-2019. The  WHO-China joint report also notes that “The Wuhan CDC laboratory moved on 2nd December 2019 to a new location near the Huanan market. Such moves can be disruptive for the operations of any laboratory.” Scientists say that such movements increase the risk of leakage of viral samples manifold.

• Research in the lab on coronaviruses was going on in the WIV labs for a long time. It is documented that very sophisticated genetic research on bat coronaviruses, including a type similar to SARS-CoV-2, was going on in WIV.

• ‘Gain of function’ is the raison d’être for such research. Even if the WIV researchers had no intention of creating a biological weapon but to be ahead of natural viruses so as to control pandemics in the future, they were undoubtedly creating new viruses with higher infectivity, etc. Such research is inherently too risky. There are examples of such research being paused in the past due to apprehensions of unknown and uncontrollable infections.

• There is a long history of leaks from labs worldwide, including WIV labs. Leaks do happen from viral labs, and rather too often. WIV cannot be given a clean chit on that count, especially when there are reports that in 2018, US inspectors had raised doubt at the biosafety standards being maintained by them.

• Researchers of the lab have been collecting bat samples from places where a very near-relative of SARS-CoV-2 is available. It is reported that no near-cousin of SARS-CoV-2 has ever been found in bats in Wuhan or even the province in which Wuhan is located (Hubei), but WIV researchers had been collecting virus samples from bats and were maintaining a huge repository of coronavirus strains.

• Researchers working on coronaviruses are reported to have become sick with a disease with symptoms similar to COVID-19. This new revelation points to possible infection by a lab strain.

• Researchers have been telling about research that could create new viruses, just before the epidemic started. The head of WIV coronavirus research (Zhengli Shi) and that of EcoHealth Alliance (Peter Daszak) – a funding body with a vested interest in this research – had talked of the creation of chimera viruses, the significance of such research and the likely huge risks.

• China’s authorities have clamped down on data sharing and publication of research papers. When you are seen hiding or suppressing facts, you become a suspect. Moreover, any health authority or national government will not like to take the blame for starting a pandemic either with an ulterior motive or due to the failure of the system. So, it is natural to suspect that China was trying to suppress facts unfavourable to it.

It is reported that China’s National Health Commission in May 2020 sent a document (not available online) asking virology labs to destroy COVID-19 samples or send them to the depository institutions designated by the state. Later in the same month, after international outcry, the Chinese government admitted to the destruction, but said it was for public safety.

• Immediately as the pandemic spread, China’s almost categorical inference that the seafood market was the source of the pandemic, also raised doubt that it was doing so to divert attention from the lab.

• China even officially stated through a simultaneous release by many diplomatic missions that the US might have introduced COVID virus into Wuhan. This seems to be a counter-narrative to put the US in the defensive. Fine, if it was only a political response to incessant accusations by Trump and his supporters. Yet, some see it as a tactic to divert attention from the lab origin hypothesis.

• Chinese authorities had delayed the visit by the international team and then created hurdles in their independent working. They closely monitored its activities, including visits, deliberations and note-taking. These acts of Chinese authorities raise further suspicion that they had something sensitive to hide.

• Inclusion of Peter Daszak in the international investigation team, though he had a clear-cut conflict of interest – and accepting his self-certificate that he did not have a conflict with the investigation – has also raised eyebrows. It is no surprise that it was he who was in the forefront of orchestrating the huge campaign in favour of the natural origin hypothesis. Recall that Peter Daszak, President of EcoHealth Alliance, was the only American scientist in the WHO team. His organization has funded SARS-related projects in WIV.

• The avowed Chinese strategic policy to use bioengineering as an important tool for military and economic dominance makes the country suspect in the eyes of defence experts. Giving the charge of the WIV lab in Wuhan to a serving military general who is an expert on SARS viruses, they say, points to this.

An article in India Defence Review finds a strong possibility of China’s strategic design in coronavirus research. It reveals that besides the Shi team, Chinese army’s research labs have viral strains with genome very similar to that of SARS-CoV-2. It concludes: “The above observations when read in conjunction ring a warning bell. The Chinese ambition of weaponizing biotech, the civil military fusion policy in the domain of biological sciences, the role of the PLA affiliated institutes in conducting gain of function research on viruses, the close similarity of the Covid virus to the ones researched by its army, the quick entry of its army and Major General Chen Wei in Wuhan and taking over of the Wuhan institute of Virology, the quick control over the virus and development of a vaccine in China while the world still struggles with it, point towards an act of an “opportunistic bioterrorism”.”

• The February 2020 letter by scientists strongly favouring natural origin is being seen by some as a deliberate attempt to scotch any attempt to involve WIV with the pandemic. Even an accidental leak – not a deliberate one – was strongly scoffed at and termed a ‘conspiracy theory’.  Such hurry in issuing a letter and lobbying for support is unusual for the scientific community, critics say.

A number of research articles came out during the middle of 2020, pointing towards the possibility of lab origin of SARS-CoV-2, but the mainstream scientists had created such pressure that the opposite voices were lost in the din. Some prominent research journals (most particularly Lancet) became purveyors of coloured opinions on the matter.

A plausible explanation for the mainstream scientific community aggressively coming out in support of the natural origin hypothesis is that if Wuhan lab’s culpability or lapse is exposed, that would put a lid on the gain of function research. With this vested interest, Peter Daszak and others depending on this high-potential research lobbied and created conditions in which any opposition to their viewpoint would invite their wrath. It may be noted that scientists with career and funding in their minds cannot afford to go against the tide.

• There are many research papers that show in minute details why the insertions and modifications in the RNA strand of SARS-CoV-2 look more likely to be lab-induced than occurring in nature. We shall come to that later.

• Now even many of the earlier votaries of the natural origin hypothesis are asking for an independent investigation and saying that all possibilities are open. This change of heart seems to have occurred because they have realized that the earlier stand in favour of natural origin was premature and one-sided and that more indicators, including genetic evidence, credibly challenge the natural origin hypothesis.

Wuhan lab’s history of virus research

It is a fact that WIV and other Chinese virology labs were collecting hundreds of wild coronaviruses from different parts of China. WIV has been in the forefront of this exploration and maintains a store of over 1500 virus strains, which are used for studies, including genetic manipulation. It is also a fact that in 2013 itself, a coronavirus that has the capability of spreading like the SARS-CoV-2 had been isolated in the Wuhan lab.

The WIV lab under Zhengli Shi had tools and trained scientists for doing the most advanced research including gene splicing and joining.

Scientists point to the fact that not all genetic manipulations in virology labs involve gene splicing and joining. In fact, much research is done through simpler ‘serial passage’ of viruses in lab animals to create new variants or chimera viruses. Such research was definitely ongoing in WIV as shown by research papers released just before the pandemic outbreak, some of which were withdrawn after a clampdown by Chinese authorities. 

It has been reported that the team led by Zhengli Shi had been creating chimera viruses for at least 4-5 years prior to the COVID-19 outbreak. Humanized mice (mice in which functioning human genes or tissues have been incorporated) taken from the University of Carolina were being infected with coronaviruses for the gain of function research in 2019 in WIV labs. The intention was not biowarfare but creating vaccines that could take care of a wide range of SARS-related infections.

In a video interview released a few weeks before the onset of COVID-19, Peter Daszak divulged that gain of function research that was going on in WIV could result in chimera viruses that had a risk of spilling over to humans.

A research paper of mid-2020 gives circumstantial evidence to prove that SARS-CoV-2 leaked from a WIV lab, not necessarily as part of some biowarfare project or even genetic engineering. It talks of two viral strains very similar to SARS-CoV-2, which had been collected by the labs in 2012-13 from a mine in Yunnan province, and its association with a disease contacted by miners working in the mine. The symptoms were quite similar to those of COVID-19. So, the infection might have spread from bats to humans (miners) and to others through infected tissue samples preserved in WIV labs. The paper says, “…First, inside the miners RaTG13 (or a very similar virus) evolved into SARS-CoV-2, an unusually pathogenic coronavirus highly adapted to humans. Second, that the Shi lab used medical samples taken from the miners and sent to them by Kunming University Hospital for their research. It was this human-adapted virus, now known as SARS-CoV-2­, that escaped from the WIV in 2019.”

The paper also gives strong reasons such as the prevalence of many strains of viruses in the same bat population, the working conditions in the mine and the pathology of miners to hypothesize how fast evolution of the virus occurred in miners’ lungs – which could not happen in normal human population so fast in a natural progression. It comes out with alternative scenarios, all purportedly more plausible than the mainstream hypothesis of a natural jump of bat virus to humans through an intermediate host. 

It is to be noted that RaTG13 is the virus most closely related to SARS-CoV-2, and WIV lab – and perhaps other labs including military virology labs – were actively working on it. However, till her paper of January 23, 2020, there was not much literature indicating that the genome of a virus strain (RaTG13) in their possession since 2013 was 96% identical to that of SARS-CoV-2.

A recent Wall Street Journal investigative report says, three researchers from WIV became sick in November 2019 accordingly to a previously undisclosed U.S. intelligence report ‘with symptoms consistent with both COVID-19 and common seasonal illnesses’. Chinese authorities have called this expose as one more instance of anti-China hype created by the US.

Before the clampdown on publication of research papers, Shi – as a scientist perhaps oblivious to the political fallout – had been revealing how her research was closely related to SARS-CoV-2 – her expansive explorations of caves for bat viruses, a virus strain very close to SARS-CoV-2, her work on anti-SARS viruses and so on. It is also reported that in her public appearances, Zhengli Shi had earlier expressed apprehension of a pandemic happening due to this type of viruses.

One of the aims of the research project in WIV given to NIH of the USA for seeking grant was, “We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding…” Clearly, the project was engaged in genetic manipulation of coronaviruses for gain of function research.

This excerpt from a 2019 paper by Shi and his team also shows the direction of research in Wuhan labs: “…anti-SARS-CoV strategies in development, such as anti-RBD antibodies or RBD-based vaccines, should be tested against bat SARSr-CoVs. Recent studies demonstrated that anti-SARS-CoV strategies worked against only WIV1 and not SHC014… Thus, future work should be focused on the biological properties of these viruses using virus isolation, reverse genetics and in vitro and in vivo infection assays. The resulting data would help the prevention and control of emerging SARS-like or MERS-like diseases in the future.”

Lab leaks cannot be ruled out

Even if the intention of a lab or country is noble in doing research in which unnatural creatures are created, there is a huge risk of creating monsters. Once these are created, these can leak in many ways in addition to being misused for creating biological weapons, by terrorists or rogue governments.

The second scary aspect of such research is that leaks happen more often than you would believe; a report says, since the 1960’s at least one leak has been reported every year, and the number of unreported cases could be even more. It is also now known that the US was on the verge of creating risky mutants around 2014 and then the US National Institute of Health (NIH) put a moratorium on the dual-use gain of function research (The moratorium was lifted in 2017). It is also widely believed that the swine flu epidemic was caused by a virus that leaked from a lab.

The Center for Arms Control and Non-Proliferation says, the odds that any given potential pandemic pathogen might leak from a lab could be greater than one in four. A conservative analysis circulated in 2017 meeting of the Biological Weapons Convention hinted at thousands of possible leaks of pathogenic material from research labs across the globe.

So, leaks from labs are not uncommon – and the Wuhan lab of WIV cannot be given a clean chit unless it proves itself above board on the strength of data and records. There is a public record of four cases of lab leaks from Chinese virology labs.

Leaks can occur in many ways: lax safety can result in researchers being infected, leaks can occur during transportation from lab to lab or from field to lab, leaks can also occur when lab animals are not properly disposed of. In fact, there are reports that animals discarded in these labs were sold by employees in the wet market for making a few bucks on the side.

It is reported that in a message sent in 2018 by US inspectors to Washington, they had said that the WIV’s lab did not meet the safety standards. It said, “The new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory.” The cable said further: “Most importantly, the researchers also showed that various SARS-like coronaviruses can interact with ACE2, the human receptor identified for SARS-coronavirus. This finding strongly suggests that SARS-like coronaviruses from bats can be transmitted to humans to cause SARS-like diseases. From a public health perspective, this makes the continued surveillance of SARS-like coronaviruses in bats and study of the animal-human interface critical to future emerging coronavirus outbreak prediction and prevention.”

One line of arguments suggesting a big probability of lab leak is that the standards of labs with lower biosafety levels must have been poorer. It is likely that the top lab (of biosafety level 4 or BSL 4) was reserved for very specialized gene-splicing work, serial passage experiments were carried in labs within the same complex with much lower safety levels (=BSL2). If so, there was a more-than-normal risk of a leak from Wuhan labs.

After a new set of guidelines on lab safety was issued by Chinese authorities in February 2020, Global Times, a Chinese state media outlet, reported about chronically inadequate safety standards and complicity of lab employees in Chinese viral research labs, quoting reliable officials (of course, emphasizing that now things were fully in control, especially in Wuhan labs). Look at these quotes from the report: “…Laboratories in China have paid insufficient attention to biological disposal… Some researchers discharge laboratory materials into the sewer after experiments without a specific biological disposal mechanism… A minor SARS virus infection in Beijing and Anhui in 2004 was resulted from insufficient management and improper inactivation process at a lab… Li Ning, a leading expert at transgenic technologies at China Agricultural University, was sentenced to 12 years in prison on January 2 for grafting 37.56 million yuan…”

A research paper by Chinese academics, published in February 2020, which strongly indicated lab origin of SARS-CoV-2 was blocked repeatedly by Chinese authorities (but is still available as web archive: ref 20). It said: “Somebody was entangled with the evolution of 2019-nCoV coronavirus. In addition to origins of natural recombination and intermediate host, the killer coronavirus probably originated from a laboratory in Wuhan. Safety level may need to be reinforced in high risk biohazardous laboratories.  Regulations may be taken to relocate these laboratories far away from city center and other densely populated places.”

How apprehensive of a lab leak, Shi herself was when the pandemic took place can be seen from her interview to Scientific American, a research journal. The article based on her interview says, “…she frantically went through her own lab’s records from the past few years to check for any mishandling of experimental materials, especially during disposal. Shi breathed a sigh of relief when the results came back: none of the sequences matched those of the viruses her team had sampled from bat caves.”

Risks associated with gain of function research

There seems to be a big, legitimate, reason why scientists in Wuhan and other similar labs worldwide should be doing research on coronaviruses. There is always an urge to be ahead of pathogens. This gain of function research has been in practice for long, including in the USA. In as early as 2006, coronaviruses had been found to have the potential to be a carrier/ vector for HIV vaccines. Similarly, scientists have been on the job to create in the lab a vaccine that can neutralise all types of coronaviruses – and the best way to achieve that is genetic manipulation. 

In fact, labs such as those in WIV are created with this intention. Success in the gain of function research not only gives scientists an edge over nature in dealing with infectious diseases, it gives a huge scientific edge to the lab. For the country, it can result in enormous strategic and economic benefits.

With an eye on such huge likely gains, scientists and national authorities ignore the red alert raised by scientists themselves. Look at what was highlighted at a symposium on the concerns about the gain of function research way back in 2014 : “…the GoFR strains themselves were a threat to public health in two ways: First, because the knowledge of how to tweak an influenza virus into a potential pandemic pathogen could be used by bioterrorists or for biological warfare purposes. Second, because the tweaked viruses could escape (or could be stolen) from the laboratory and could cause a pandemic.” Yet, such research is going on in many countries, without adequate safeguards.

It is known that NIH of the US has been giving grants to EcoHealth Alliance, which in turn was funding research projects in WIV. NIH insists that the grant was not for the gain of function research but to investigate bat viruses that could infect humans in the future. Many scientists feel that the type of research being carried out in WIV was GoF research, couched in technicalities so as to avoid closer scrutiny. Interestingly, Shi and her colleagues were closely collaborating with US universities on this type of research. A high level of completion, a sort of race, could also be seen between her team and that led by Ralph Baric for achieving a high level of precision in creating chimera viruses.

Genetic logic suggests the possibility of lab origin

Now comes the highly technical but most definitive aspect of the origin of SARS-CoV-2. Without going into all dissections made by scientists to prove lab origin of SARS-CoV-2, let us talk of some clear-cut indicators.

The genetic sequence of SARS-CoV-2 is without doubt chimeric (=made from parts of different strains). Its main genetic thread is very similar to a bat virus but bat viruses do not have the ability to cross to humans and to bind the spike protein the way SARS-CoV-2 does. This small part seems to have come from another strain. In nature, such ‘recombinations’ do happen but rarely; in a lab, these can be done in different ways and with techniques that leave no trace of manipulation.

A scientific article in BioEssays , after analysing many possibilities of jump of SARS-CoV-2 from bats to an intermediary and then to humans infers: “… the available evidence does not point definitively toward a natural origin for SARS-CoV-2, rather, much of it is more consistent with what would be found if the novel coronavirus had arisen from the serial passage of a “precursor” progenitor virus in a lab, or from bats infecting a commercial mink farm somewhere in China, which would also provide the conditions for serial passage. However, more evidence is required before a conclusive judgement can be made one way or the other.”

Another scientific paper in the same journal says, “On the basis of our analysis, an artificial origin of SARS-CoV-2 is not a baseless conspiracy theory that is to be condemned and researchers have the responsibility to consider all possible causes for SARS-CoV-2 emergence. … could arise from site-directed mutagenesis experiments, in a context of evolutionary studies or development of pan-CoV vaccines or drugs. A recent article in Nature affirms that a laboratory origin for SARS-CoV-2 cannot be ruled out, as researchers could have been infected accidentally, and that gain-of-function experiments resulting in SARS-CoV-2 could have been performed at WIV…”

In September 2020, a group of scientists led by Li-Meng Yan came out with a paper in which they have given detailed technical reasons why the SARS-CoV-2 virus is a genetically-manipulated strain. It will serve the purpose of this article to note what they concluded: “…evidence …together, strongly contradicts the natural origin theory. The evidence shows that SARS-CoV-2 should be a laboratory product created by using bat coronaviruses ZC45 and/or ZXC21 as a template and/or backbone. Building upon the evidence, we further postulate a synthetic route for SARS-CoV-2, demonstrating that the laboratory creation of this coronavirus is convenient and can be accomplished in approximately six months.” 

In one of their papers, this group of scientists has categorically stated that “SARS-CoV-2 is an Unrestricted Bioweapon created by the CCP regime.” Let us leave aside the biological weapon theory in the present discussion, though that cannot be ruled out. 

It is difficult, scientists say, that a special feature in the RNA of bat viruses, the furin cleavage site, which is essential for a SARS virus to attack humans, evolved by sudden mutation or recombination by multiple viral attacks. On the other hand, at least 11 gain of function experiments, adding a furin site to make a virus more infective, have been published including those by Zhengli Shi.

One line of logic runs like this: The genome of SARS-CoV-2 has great similarity with a Yunnan bat virus while its key portions (that make it infectious to humans) are similar to the virus found in a set of pangolins being smuggled into China in 2019. The pangolins died with COVID-like symptoms and their samples were shared with viral labs in China and Hongkong. It is inconceivable that a highly active and technologically capable team did not try recombination of these viral sequences in the lab.

Scientists say, insertion of the furin cleavage and another typical RNA sequence that helps AEC2 binding with human cells needs a series of mutations and ‘crossings’ between different strains. This can happen in nature but has a very low probability. If it had happened in nature, researchers should have found intermediary viruses. On the other hand, there is no doubt that Zhengli Shi had been creating chimera viruses since 2007, and had indeed been working on furin cleavage and ACE2 receptor sites in coronavirus RNA. The natural origin hypothesis is not able to explain this.

Gene splicing is in practice for decades. Chimeric coronaviruses were being created even in 1999 for the gain of function research. In 2002, a breakthrough was achieved in viral gene manipulation when scientists first translated the RNA into DNA, then made all manipulations on it and finally transcribed the DNA back into viral RNA.

There is extensive literature on gain of function research being carried out in top labs for years,  but let me pick up one because it has the signatures of the top researchers in the area , talks of creation of a chimera virus from distinct strains, involves ACE2 receptors and  human pathogenicity, and has been funded by EcoHealth Alliance. It clearly says: “…we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis… we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo…”

Shi is a top researcher who has created a number of chimera viruses using the new technology and tested them for human pathogenicity. The latest technology makes genetic manipulation of viruses much easier and the DNA route does not leave a trace of manipulation in viral RNA.

A science writer who has dissected both the hypotheses in great detail concludes this about the possibility of lab origin: “It’s documented that researchers at the Wuhan Institute of Virology were doing gain-of-function experiments designed to make coronaviruses infect human cells and humanized mice. This is exactly the kind of experiment from which a SARS2-like virus could have emerged. The researchers were not vaccinated against the viruses under study, and they were working in the minimal safety conditions of a BSL2 laboratory. So, the escape of a virus would not be at all surprising.

In all of China, the pandemic broke out on the doorstep of the Wuhan institute. The virus was already well adapted to humans, as expected for a virus grown in humanized mice. It possessed an unusual enhancement, a furin cleavage site, which is not possessed by any other known SARS-related beta-coronavirus, and this site included a double arginine codon also unknown among beta-coronaviruses. What more evidence could you want, aside from the presently unobtainable lab records documenting SARS2’s creation?”

The opposing groups of scientists find holes in their opponents’ genetic theories and feel that they are being selective in their logic. Mainstream scientists have sought to discredit the other view and have come out with many articles and research papers on the subject. On the other hand, scientists supporting lab origin have come up with equally strong arguments. In the latest paper published in March 2021 , Yan and her associates have sought to rebut each point of criticism of their earlier papers.

So, where are we?

Depending on which side you are on, you can question the other scientists’ qualifications, affiliations and intent. At the political level and in the media, you can call the others as indulging in misinformation: either at the behest of China, WIV and scientists with a vested interest in the gain of function research or from the side of scientists bent upon proving their conspiracy theories and those inimical to China.

In absence of clear proof for or against natural origin of SARS-CoV-2, the two sides will keep fighting and humanity will remain at a loss.

Many indicators suggest an unnatural origin, and each of them needs to be examined dispassionately. There is smoke in the air, and it must be cleared.

The idea should be not to demonize scientists in Chinese labs, nor to claim that SARS-CoV-2 has definitely originated in a lab, nor to conclude that Chinese authorities were working on a sinister design (unless there is solid proof of that). What is needed is an open mind to find out how SARS-CoV-2 originated. Perhaps an independent investigation comes out with proof of natural origin that is not presently available.

However, the lack of trust between China and some other nations at political and geo-strategic levels is so high that expecting an independent investigation will be naïve. The truth behind the origin of SARS-CoV-2 may give many lessons for the future. The ignorance, as it is today, might cost humanity in terms of another epidemic of similar proportions.

References

1. A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic
2. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence
3. Biosafety guideline issued to fix chronic management loopholes at virus labs
4. Covid 19: The Chinese Military and Maj Gen Chen Wei
5. Did the SARS-CoV-2 virus arise from a bat coronavirus research program in a Chinese laboratory? Very possibly.
6. Dual Use Research on Microbes: Biosafety, Biosecurity, Responsibility
7. How China’s ‘Bat Woman’ Hunted Down Viruses from SARS to the New Coronavirus
8. Investigate the origins of COVID-19
9. Joint Statement on the WHO-Convened COVID-19 Origins Study                 
10. Lab-Made? SARS-CoV-2 Genealogy Through the Lens of Gain-of-Function Research
11. Might SARS-CoV-2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?
12. On the origins of SARS-CoV-2
13. Origin of Covid — Following the Clues
14. Origin of SARS-CoV-2, the virus behind COVID-19 or coronavirus pandemic: facts, assumptions and myths
15. Peter Daszak of EcoHealth Alliance
16. Statement by President Joe Biden on the Investigation into the Origins of COVID-19
17. Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19
18. The Case Is Building That COVID-19 Had a Lab Origin
19. The genetic structure of SARS-CoV-2 does not rule out a laboratory origin
20. The possible origins of 2019-nCoV coronavirus
21. The proximal origin of SARS-CoV-2
22. The Wuhan Laboratory Origin of SARS-CoV-2 and the Validity of the Yan Reports Are Further Proved by the Failure of Two Uninvited “Peer Reviews” Opening Statement
23. Timing the SARS-CoV-2 index case in Hubei province
24. Unusual Features of the SARS-CoV-2 Genome Suggesting Sophisticated Laboratory Modification Rather Than Natural Evolution and Delineation of Its Probable Synthetic Route
25. WHO Director-General’s remarks at the Member State Briefing on the report of the international team studying the origins of SARS-CoV-2
26. WHO-convened global study of origins of SARS-CoV-2: China Part
27. Why China and the WHO Will Never Find a Zoonotic Origin For the COVID-19 Pandemic Virus
28. Wuhan lab infected ‘humanized mice’ with bat coronaviruses in 2019

*Manoj Pandey is a former civil servant. He does not like to call himself a rationalist but insists on scrutiny of apparent myths as well as what are supposed to be immutable scientific facts. He maintains a personal blog, Th_ink

Disclaimer: The views expressed in this article are the personal opinion of the author and do not reflect the views of raagdelhi.com which does not assume any responsibility for the same.