Bat out of hell? COVID is global but questions over Wuhan lab leak won’t go away

“In the wake of any disaster — a train derailment, a plane crash, a rocket explosion, a reactor meltdown, a terror attack or a war — the causes of the disaster are investigated and the findings are used to inform policy changes to reduce the risks and the impacts of future disasters.

“In the wake of the Covid-19 disaster — the greatest disaster the world has faced since World War II — an investigation of the causes of the disaster and policy changes to reduce the risks and impacts of similar future disasters are urgently needed. However, no such investigation has occurred. The World Health Organisation (WHO) mission was not set up to be an investigation, did not operate as an investigation, provided absolutely no new information, and as such cannot, even in principle, help reduce the risks and the impacts of similar future disasters,”Richard H Ebright, an American molecular biologist and member of the Board of Governors, Professor of Chemistry and Chemical Biology at Rutgers University, exclusively told India Today.

True. The world is yet to strongly question the origin of the SARS-CoV-2 virus. Unless that is done, there is no way countries can protect themselves and their people in the future. Numerous scientists and experts have slowly started voicing their opinions on the origin of the virus. Most recently, a group of 18 scientists led by Jesse Bloom, who pursues the evolution of viruses at the Fred Hutchinson Cancer Research Center in the US, has written a letter wanting an inquiry into whether the virus was an accidental leak due to human errors or if it originated naturally.

“We must take hypotheses about both natural and laboratory spillovers 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 minimise the impact of conflicts of interest,” the letter added.

At India Today, we decided to get in touch with these groups of scientists and researchers to understand more on the possibilities of the SARS-CoV-2 virus being a result of an accidental lab leak. Some of the sources in our communications cannot be revealed, owing to privacy and risks attached to their standing in the scientific community and those who may not agree with their questioning.

Politics behind the origin of SARS-CoV-2
In the immediate aftermath of the breaking out of this pandemic in December 2019, the Chinese government was quick to point fingers at the Wuhan wet market as the source. This in turn made experts to draw parallels to SARS (2002) and MERS (2012) as these had its origins in animals.

Given the genome of the SARS-CoV-2 also belonged to the family of beta-coronaviruses like that of SARS and MERS, initially, it was believed that SARS-CoV-2 was also completely natural like its predecessors. However, the wet market theory soon proved insufficient as epidemiologists found cases that had no link to the wet markets, even during the initial phase of the spread.

Given the fact that Wuhan, the place where the first-ever Covid-19 case was detected also housed the Wuhan Institute of Virology (one of the world’s leading centres for coronavirus research), many experts had opined their concerns on a possible lab leak theory. But these were quick to be dismissed by the Chinese government and specific scientific communities that later were found to have stakes in the Wuhan Institute of Virology (WIV).

Peter Daszak, the president of the EcoHealth Alliance of New York, had organised and drafted a letter via the Lancet and got a group of 27 scientists to condemn “conspiracy theories suggesting that Covid-19 does not have a natural origin”.

Specific email leaks show that a few scientists raised concerns and objections to the generalised statement even before scientific evidence was available. The timing of this publishing was especially critical as it was released as early as February 18, 2020, when the scientific community barely had enough evidence to identify the origins of the virus. This truly raised a lot of eyebrows. Only later was Peter Daszak’s involvement known.

It is not surprising to learn that Peter Daszak’s organisation has been funding the coronavirus research at the Wuhan Institute of Virology for years before the pandemic. This strong conflict of interest was not declared to the readers of the Lancet letter.

Centres like the Wuhan Institute of Virology have for years been creating highly dangerous viruses. Their primary reasons to create these viruses are to learn more about future pandemics and prevent natural spillovers like SARS and MERS. If the SARS-CoV-2 pandemic was indeed owing to a lab leak, no one had a bigger stake in dismissing discussions around the same than people like Daszak.

There was another group of scientists, led by Kristian G. Andersen of the Scripps Research Institute, who also tried to support the natural origins theory of the SARS-CoV-2 virus. But experts warn that this theory falls flat on numerous lines.

Andersen’s assertion was that the virus strain did not look like it was manipulated. But given this assertion was arrived at as early as March 17, 2020, and that today’s science had ample ways and methods using which strains could be modified without leaving trails or marks.

Another argument of Andersen supporting the natural origin theory was that the spike protein of SARS-CoV-2 virus binds well to the ACE2 receptor in humans but in a different way as compared to the best fit calculations. Hence, he asserts that it is of a natural occurrence. But this theory has been rejected by many other experts, calling it a too simplistic form of argument.

If someone decided to alter a virus without leaving a trail, they would do exactly this. To give an easy analogy, a student copying an assignment from another top ranker classmate will do so in a precarious way so as to not leave behind a trail of having copied the assignment wherein which the copying student may make small mistakes intentionally in order for him or her to not be found out.

It is also a common practice of virologists to get spike proteins to bind to targets not by calculation, but by splicing in spike protein genes from other viruses.

Another argument in the Andersen camp is that it is difficult to manipulate RNA, which is what the SARS-CoV-2 virus is made of. But, again, today’s science has ample methods to convert the RNA genome to DNA, manipulate the DNA and then convert it back to the RNA form. There are DNA backbones that enable such manipulations. The fact that these assertions from specific pockets of the scientific community were made within months of the pandemic breakout casts strong aspersions on their intent and needs.

The gain-of-function experiments
The SARS and MERS had ample evidence suggesting natural origins. The intermediaries when it comes to host species for SARS were identified within four months of its outbreak. Similarly, the host species of MERS was identified within nine months of its outbreak. But a similar identification has not been achieved for SARS-CoV-2 virus, 16 months since its outbreak.

The February 2021 visit by WHO officials to China did not result in any significant answers to this question. In fact, the WHO report did not even allocate 5 per cent of its resources and time to probe the lab-leak angle and instead focused all its efforts on pointing towards a natural origin theory. The natural emergence has remained a conjecture which, however plausible to begin with, has not gained a shred of supporting evidence in over a year now.

Jamie Metzl, a member of a WHO advisory committee on human genome editing, expressed his strong opinions against the methodology of the WHO fact-finding committee that visited China. He felt that the committee did not even bother to look into the most basic questions before dismissing the possibility of a lab leak.

Speaking exclusively to India Today, Alina Chan of the Broad Institute (MIT) and Harvard added that “scientists have found very strong evidence pointing to the natural origins of SARS and MERS. If that kind of evidence existed for SARS2, I would happily say so, but such evidence does not yet exist or has not been made public.”

It has been a common practice of scientists to manipulate a virus’s genes and see how the same makes a jump from an animal to human beings to predict future pandemics. This has resulted in scientists around the world enhancing animal viruses that can seriously infect people and study the effects of the same. For example, the 1918 flu virus was recreated in labs to study how it affected the people back then. These kinds of enhancement of viral capabilities are called as the gain-of-function experiments.

The Wuhan Institute of Virology too was involved in many of such experiments in the past. Most recently in 2015, led by China’s leading expert on bat viruses, Shi Zheng-li or “Bat Lady”, mounted frequent expeditions to the bat-infested caves of Yunnan in southern China and collected around a hundred different bat coronaviruses. Her work is especially important given the context of this article.

She along with Ralph S. Baric, an eminent researcher at the University of California, worked on enhancing the potency of bat viruses to attack humans so as to examine their potential to affect humans. They created a novel virus by taking the backbone of the SARS1 virus and replacing its spike protein with one from a bat virus. This manufactured virus was able to infect the cells of the human airway when tested against a lab culture of such cells.

After this event, Shi was part of numerous other experiments involving bats and inter-species transmission of coronavirus. Most of these involved using the S-protein sequence data and analysis of ACE receptor binding. In non-technical terms, it meant creating a novel coronavirus having a really high possible infectivity for human cells. These approaches could have potentially generated SARS2-like viruses.

“It is clear that the Wuhan Institute of Virology was systematically constructing novel chimeric coronaviruses and was assessing their ability to infect human cells and human-ACE2-expressing mice,” opined Richard H. Ebright. He further added: “It is also clear that, depending on the constant genomic contexts chosen for analysis, this work could have produced SARS-CoV-2 or a proximal progenitor of SARS-CoV-2.”

Fast forward to 2021, we can confirm that the value of such gain-of-function studies in preventing the SARS2 epidemic was zero. On the flip side, if indeed the SARS2 virus was generated in a gain-of-function experiment, the risk was catastrophic.

There is more on this from the horse’s mouth himself. In an interview given just before the outbreak of the Covid pandemic (December 9, 2019), Peter Daszakconceded that the WIV was part of experiments that created over 100 new SARS like coronaviruses and that these viruses do not have anti-vials or vaccines.

He said, “Some of them get into human cells in the lab, some of them can cause SARS disease in humanised mice models and are untreatable with therapeutic monoclonals and you can’t vaccinate against them with a vaccine.”

It is noteworthy and critical to remember that within months of the Covidoutbreak, Peter Daszak led a team of scientists to declare that the SARS-CoV-2 virus was not a result of a lab leak, very well knowing the experiments that the Wuhan Institute of Virology was running.

Scientific arguments supporting the possibility of a lab-leak
Nicholas Wade, a British author and science writer, shared his work with India Today. He lists a set of arguments in his research that look at the possibility of SARS-CoV-2 not being a result of a natural origin.

PLACE OF ORIGIN: Virus samples that are similar to the SARS-CoV-2 virus have been found in bat caves in Yunnan which is 1,500 km away from Wuhan. If this was a natural spillover, then the people in Yunnan would have been the first to have been infected. There are many details suggesting that the pandemic broke out in Wuhan as early as in September 2019, which was basically a cold month during which bats hibernate. There is also no proof of the bats infecting an intermediate host before the virus jumped onto a human. All we do know is that the Wuhan Institute of Virology performed research and experiments on genetically engineered bat coronaviruses to attach human cells.

Dr Alina Chan opined: “The most important consideration for me is how a virus, whose closest relatives all reside in South China, made its way up into Wuhan in Central China, a thousand miles, without leaving any trace of its first spillover into humans and transmission among humans before hitting Wuhan.”

The Wuhan Institute of Virology had sampled more than a thousand bats in Hubei province where Wuhan is located. They never found any virus closely related to SARS-CoV-2. They had also sampled hundreds of people in Wuhan and checked for SARS antibodies – zero had signs of exposure to SARS viruses.

“In contrast, you have a lab that possibly has the largest collection of SARS and SARS2-like viruses. They’ve only very slowly and grudgingly revealed that they have at least nine SARS2-like viruses in their collection and had been studying these in the years leading up to 2019. They’ve also taken down a database with more than 22,000 entries of viruses collected from wild animals, and we heard that they have several dozen new SARS viruses in their possession. Why have these sequences not been shared with the public even in the context of the worst pandemic of our lifetime (hopefully)?”

EVOLUTION OF THE VIRUS: Unlike SARS1, which was documented in having successive changes in its spike protein during its step-by-step evolution into a dangerous pathogen, the SARS-CoV-2 virus hardly changed until the recent mutations.

From its very first appearance, it was well adapted to human cells. Researchers led by Alina Chan of the Broad Institute compared SARS2 with late-stage SARS1, which by then was well adapted to human cells, and found that the two viruses were similarly well adapted.

Alina Chan further added: “By the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV-2.” Experts have also opined that the early strains identified in Wuhan showed limited genetic diversity, which suggests that the virus may have been introduced from a single source.

THE FURIN CLEAVAGE SITE: The Furin cleavage site sits at the heart of the puzzle of where this virus came from. The spike protein has two sub-units with different roles: S1 and S2. After the virus’s outer membrane has coalesced with that of the stricken cell, the viral genome is injected into the cell, hijacks its protein-making machinery, and forces it to generate new viruses. But this invasion cannot begin until the S1 and S2 subunits have been cut apart. And there, right at the S1/S2 junction, is the Furin cleavage site that ensures the spike protein will be cleaved in exactly the right place.

Of all known SARS-related beta-coronaviruses, only SARS2 possesses a Furin cleavage site. All the other viruses have their S2 unit cleaved at a different site and by a different mechanism. How then did SARS2 acquire its Furin cleavage site? Either the site evolved naturally, or it was inserted by researchers at the S1/S2 junction in a gain-of-function experiment. Considering the virus did not change a lot before it started infecting humans, the natural origin theory falls flat here.

Did China cover up? Did they already plan to protect them but failed to inform the world? Were they hiding a lab leak?
This may read or sound like a Hollywood science thriller. Because, to understand the evolution of bat-based coronaviruses and the role of the Wuhan Institute of Virology, we may have to go back to April 2012 in Mojiang county. Six miners were given a job of clearing bat waste and bat feces from a copper mineshaft in Tongguan, Mojiang, Yunnan. After working for 14 days in the case of four miners, and 45 days in the case of the last two miners, they started facing breathing problems, cough, and fever which required immediate admission to the Kunming hospital in late April and early May. Three of the miners died in the course of 100 days and three survived.

It is believed that they probably were asked to clean up the shaft for a USAID-sponsored bat sampling project led by Shi Zheng-li. A few months after this outbreak, there was a six-month disease control enforcement in Mojiang county. It also led to multiple visits to the county by China’s Center for Disease Control and Prevention (CDC) officers. Probably, there was a bigger outbreak than it was made to believe. The reason this article alludes to this since none of the deaths of the miners made it to the official Chinese CDC statistics for that year (2012).

Further to this, in 2013, a Thai tourist in Yunnan died as a result of a multiple organ failure caused by an “unexplained pneumonia”. The symptoms were very similar to the 2012 miner’s incident and eerily similar to the SARS-CoV-2 symptoms (which we will delve deep into later). The interesting thing here is that this tourist was admitted to the same hospital as that of the miners. Again, this too was not part of the CDC statistics for 2013.

Around the same time, China’s Ministry of Science & Technology initiated a project (2013FY113500) to identify and investigate viral pathogens and its relationship with major infectious diseases. This was just months before Shi Zheng-li went on a bat sampling expedition.

A multi-year bat surveillance project was carried out in that exact mine by multiple labs across China (including WIV & China CDC). In the same year, a report released by a Kunming medical university doctor (who also treated the miners in 2012) revealed that the miners succumbed to a pneumonia that was caused by SARS-like coronavirus from Rhinolophussinicus which are uncannily identical to Covid-19.

A peer-reviewed article by doctors-cum-scientists Monali C. Rahalkar and Rahul A.Bahulikar delves deep into the clues that point towards the origin of SARS-CoV-2. The study mentions that retrospective analysis of the pneumonia cases shows striking similarities with Covid-19. Bilateral pneumonia, vascular complications like pulmonary thromboembolism, and secondary infections are the main similarities. The treatment regimens were similar to the current treatments for Covid-19. A thesis featuring medical reports, radiological images such as CT scans, and detailed information regarding the diagnosis and treatment of the miners are in this link.

On a closer look at the six cases (miners), Monali and Rahul could observe that the main clinical symptoms in the six patients from the Mojiang mine were cough and fever, and the main accompanying symptoms were dyspnea, aching limbs, sputum/bloody sputum, and headache.

Radiography results showed interstitial pneumonia, ground-glass opacities, and severe acute respiratory distress syndrome (ARDS) in the first four patients who also required a mechanical ventilator (patients 2-4). Some patients (1, 2, and 4) showed clotting complications such as pulmonary thromboembolism or thrombosis and elevated D-dimer values. The conclusion is that the pneumonia cases were due to viral pneumonia, primarily from SARS-like coronaviruses originating from horseshoe bats.

Speaking exclusively to India Today, Dr Monali Rahalkar said, “The nearest relative of SARS-CoV-2 was found in horseshoe bats, RaTG13. The natural reservoir of SAR-CoV-2 is also believed to be horseshoe bats which are present in Yunnan mainly. RaTG13 was collected from a bat-infested cave in Mojiang, Yunnan. This place is about 1,500km away from Wuhan. It is practically impossible that the horseshoe bats flew such a distance. These are small bats and can maximum fly distances of 20km. RaTG13 was collected by WIV in 2013, though they did not mention this name till the outbreak. The fact that the same place where RaTG13 was collected also had an incidence of lethal pneumonia case in mine workers (3/6 died), and the retrospective analysis done by us telling that this was very much like Covid-19. Therefore, it is highly probable that Wuhan laboratories were working on these types of bat coronaviruses.”

Now, the obvious questions are what did CDC and the WIV do with all this information and the subsequent sampling of the bats from these regions? Why were these cases not recorded and their facts not released to the outside world? Given the eerily close proximities between the April 2012 miner’s incident and the SARS-CoV-2 outbreak, did China already know how to handle the pandemic and did not share the same with the rest of the world? Or did one of their experiments result in a lab accident leading to the release of the virus from WIV? Why was the pathogen database associated with the project 2013FY113500 of Dr. Shi not accessible anymore?

Probable signs of a lab leak?
It is very critical to note that the project 2013FY113500 was under review by China’s ministry of science and technology, with September 30, 2019, being the deadline. During this time, the MoST did a few other things.

Firstly, it released a tender to identify five major novel viral pathogens from wild animals and carry out a biosecurity risk assessment by testing them on small animals.

Secondly, MoSTblocked access to the WIV pathogen database.

At the same time, the Wuhan city center for disease control and prevention released an emergency tender to purchase virus detection kits that included 40,500 PCR testing kits. The Wuhan CDC also released tenders to dispose of 2.5 tons of hazardous biochemical waste from their labs.

There are now some OSINT-based data obtained that shows mysterious blips in Google search and Wikipedia trends for the terms “Coronavirus” and “SARS”, in Hubei province in September 2019.

Eric Haseltine, Ph.D., is a former intelligence officer who started looking at the possibilities of search trends showing up on Google and Wikipedia based on theories that the outbreak first started between September and early October.

Both Google and Wikipedia keep meticulous records of terms and phrases searched on their respective sites, showing what search terms in the past were of interest, and in some cases, where these search terms were of interest. If people in a position to know had started to see evidence of a new disease outbreak, it is possible, even likely, they would have searched Google and Wikipedia for relevant information.

Google Trends, which displays “normalised” search traffic for specific queries, localized to specific geographic regions, showed two “blips” in search interest in China for the terms “Coronavirus” and “SARS’, one in Hubei province ( where Wuhan is the capitol) in September 2019 and one in Beijing in October 2019. Because the data are normalised (given as ratios of search to the maximum number of searches for that term), only Google knows the actual raw numbers of searches for any given term, but the normalised data do give an indication of changes in the relative volume of search.

Wikipedia, which does reveal the raw numbers of searches for particular terms, showed a jump in baseline search interest in “Coronavirus” from under 100 per day to 1,124 searches on October 12, 2019. On the same day, Wikipedia searches for Severe Acute Respiratory Syndrome (SARS-novel coronavirus is now also called SARS-CoV-2) jumped from a baseline of 200-300 searches per day to 1,334 per day.

Taken together, the “blips” in Google and Wikipedia search records suggest a heightened curiosity about SARS/Coronavirus much earlier than December 2019. All of the above actions by WCDC and MoST also suggests that there could have been a possible bio-containment failure at one of their labs, possible in WIV during the September -October 2019 timeframe.

September 2019 also saw a few more events that are noteworthy. On September 6, the Zhifang Sewage treatment plant in Wuhan was officially shut down and the sewage from the plant was directly transferred to the Jiangxia STP for advanced treatment. The Jiangxia STP is in very close proximity to the WIV lab complex.

Soon after, there were multiple on-site lab safety inspections at Wuhan. A month later (October 2019), Hubei Health Commission gave license approval to numerous companies in Wuhan for making/procuring disinfectants, Sodium Hypochlorite, Pipelines, and Pipe fittings.

Not to forget, scientifically, many phylogenetic studies also point towards the Covid-19 outbreak starting around September-October2019.

To sum up, Alina Chan felt: “We know that the WIV was sampling tens of thousands of animals and even thousands of people living near these SARS virus hotspots in Southern China. It is entirely plausible that SARS-CoV-2 may have made its way to Wuhan because of these research activities. If that is what happened, we need to convene an international forum that also includes non-scientist stakeholders to review the types of pathogen research occurring worldwide and decide how to move forward globally to prevent another pandemic occurring.”

There is no visible proof of a lab spillover, but a hypothesis of a lab leak is supported by robust circumstantial evidence and a long pattern of scientific misconduct by China-based researchers. Scientific, media and forensic community needs to verify the possibility of a laboratory spillover.

Dr Monali opined that there is a slightly higher possibility of the SARS-CoV-2 virus being a result of a lab modified virus. “The main features, the receptor-binding domain and the Furin cleavage site are the two features which could give indications of lab modifications. The virus when detected and caused infection was adapted to human beings and hence the possibility that the virus is lab-made or genetically modified using a backbone is possible.”

“Wuhan hosted one of the two most premium laboratories working on SARS and SARS-like coronaviruses, WIV. Wuhan was the place where the outbreak started. There were two other institutes, Wuhan CDC and Wuhan University, with research going on coronaviruses. Apart from that, there are other laboratories in China situated in Guangdong and other places doing research on coronaviruses with collaborations to the Wuhan laboratories,” she added.

Professor Richard H. Ebright added that “the genome sequence of SARS-CoV2 indicates that its progenitor was either the bat coronavirus RaTG13 (collected by Wuhan Institute of Virology in 2013 from a bat colony in a mine in Yunnan province in which miners had died from a SARS-like pneumonias in 2012; partly sequenced by Wuhan Institute of Virology in 2013-2016; fully sequenced by Wuhan Institute of Virology in 2018-2019; published by Wuhan Institute of Virology in 2020) or a closely related bat coronavirus.”

Dr Alina Chan has a similar view on the need for a thorough investigation. “We have all the technology we need to answer this question. In my opinion, the difficulty is actually launching an investigation into the origins and the obstacles were largely due to human factors rather than any technical challenges. For instance, China has not granted open access to the raw data in the early days of the outbreak, and international investigators cannot talk freely to the first patients, or examine banked patient samples for signs of the virus circulating before the detected outbreak. But there are still ways to investigate even without cooperation from China.”

We have a virus extremely adapted to humans without any close intermediate version, neither in humans, nor in the animals. Today, we have no plausible hypothesis to explain how the virus could have appeared in Wuhan in a natural way. But the fact that the epicentre was Wuhan, in close proximity to several virology labs specialising in CoVs, it is conceivable that the virus spilled from a laboratory. India Today