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5 years later, smoking gun points to China’s Wuhan lab in search of Covid-19 origin
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  • 5 years later, smoking gun points to China’s Wuhan lab in search of Covid-19 origin

5 years later, smoking gun points to China’s Wuhan lab in search of Covid-19 origin

Madhur Sharma • December 28, 2024, 07:17:19 IST
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Five years after SARS-CoV-2, the virus that causes Covid-19 disease, first emerged in China’s Wuhan, the evidence so far makes a convincing case for a laboratory-origin of the virus, indicting Chinese researchers and their collaborators abroad for a pandemic unseen in living memory that sickened over 770 million people and killed over 7 million

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5 years later, smoking gun points to China’s Wuhan lab in search of Covid-19 origin
Security personnel stand guard outside the Wuhan Institute of Virology (WIV) during the Feb. 3 visit of the World Health Organization (WHO) team investigating the origins of the SARS-CoV-2, the virus that triggered the Covid-19 pandemic. (Photo: AFP)

In early December 2019, the first clinically diagnosed case of Covid-19 was identified in Hubei province’s Wuhan city, according to Chinese authorities.

By the last week of December, the genome of the virus had been sequenced and a Chinese doctor figured out that human-to-human transmission was ongoing.

The logical next step would have been to make the genome public and tell the world everything about novel coronavirus, which had not yet been formally named. It would later be called SARS-CoV-2 — standing for Severe Acute Respiratory Syndrome Coronavirus 2, named after a similar outbreak a few years earlier.

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Instead, the Chinese authorities imposed a gag order on doctors and scientists and started destroying patients’ samples or transferring them to designated institutions.

It was only on January 5, 2020, that a Chinese scientist, Zhang Yongzhen, uploaded the genome to a US-based database but inexplicably embargoed access till July. Two days later, Zhang submitted a paper to the journal Nature detailing the genome which he co-authored with Edward Holmes, a virologist at the University of Sydney, Australia.

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By January 10, Nature sent out the manuscript for peer review. Around the same time, criticism surfaced by prominent scientists like Jeremy Farrar —who would go on to be the Chief Scientist of the World Health Organization (WHO)— about papers being submitted to journals even though the WHO was being kept in the dark. Two days later, under pressure, Zhang shared the genome with Holmes, who in turn uploaded it to a website run by a British biologist.

This is how the world learnt about the genome of SARS-CoV-2 nearly two weeks after it was sequenced and that too from a Sydney-based virologist and not Chinese authorities.

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On January 14, the WHO told the world that there was no evidence of human-to-human transmission — a lie China is alleged to have deliberately fed to the WHO.

In the first weeks when transparency and cooperation were critical to contain the outbreak and prepare for the fallout, Chinese authorities apparently did everything to mislead the world.

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From all the evidence gathered by epidemiologists over the past five years, experts seem to conclude that Covid-19 was not an inevitable pandemic.

In any other open country, the authorities would have taken the logical steps of alerting the world and sharing the genome at once and the novel coronavirus outbreak would have been little more than a kitchen fire, says Jamie Metzl, a Senior Fellow at Atlantic Council who has previously served at the US Department of State and National Security Council.

With its actions, China turned a kitchen fire into a global inferno, says Metzl.

“The Chinese government turned the equivalent of a stove fire into a kitchen fire, the kitchen fire into a city fire, and the city fire into ultimately a global inferno. In the critical first days and weeks, the Chinese government did everything wrong and everything possible for political purposes to prevent the kind of response that was so urgently needed. If not for the unique pathologies of the Chinese state, there almost certainly would not have been a pandemic,” says Metzl.

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Strange features of virus raised eyebrows from the onset

From the onset, two features of SARS-CoV-2 stood out.

One, the virus was pre-adapted to infect humans from day one.

Usually, when pathogens emerge, they take time to master the human-to-human transmission, which means that the ‘original’ strain is imperfect compared to later strains.

In a study in May 2020, three researchers at the Broad Institute of MIT and Harvard noted that SARS-CoV-2 “was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV” — the SARS-CoV being the coronavirus that caused the SARS epidemic of 2002-03.

Around 40 bodies being buried in a trench in New York during the Covid-19 pandemic. (Photo: Reuters)

Two, SARS-CoV-2 carried something called ‘furin cleavage sites’ (FCS). The FCS on the spike protein of the virus allows it to enter human cells. In simple words, it is the FCS that allows SARS-CoV-2 to infect humans.

What made the presence of FCS in SARS-CoV-2 strange was its rarity in the family of coronaviruses to which SARS-CoV-2 belongs. Richard H Ebright, a molecular biologist at Rutgers University, says that SARS-CoV-2 is the only one of more than 800 known SARS-related coronaviruses that has FCS.

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As for the odds of FCS being found naturally in SARS-CoV-2, Ebright says the FCS of SARS-CoV-2 has codon usage that is highly unusual for a bat SARS-related coronavirus — the codon refers to a sequence of three nucleotides which together form a unit of genetic code in a DNA or RNA molecule.

Ebright tells Firstpost, “The FCS of SARS-CoV-2 contains two consecutive CGG codons, where CGG is one of six synonymous codons for the amino acid arginine and is used rarely —less than 1 in 30 codons for arginine— in bat SARS-related coronaviruses but is used frequently in humans.

“Mathematically, the probability of encountering a natural SARS-related coronavirus having two consecutive CGG codons would be less than 1/30 assuming non-independent codon selection for the two codon positions. The probability would be less than 1/9,000 assuming independent codon selection for the two codon positions.”

Overall, the combined probabilities of encountering a natural SARS-related coronavirus possessing FCS and having two consecutive CGG codons is less than 1 in 24,000 to less than 1 in 720,000, says Ebright, the Board of Governors Professor of Chemistry and Chemical Biology at Rutgers and Laboratory Director at the Waksman Institute of Microbiology.

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Against this backdrop, Broad Institute scientists Shing Hei Zhan, Benjamin E Deverman, and Alina Chan cautiously floated the possibility of SARS-CoV-2 originating in a laboratory since the probability of these features in nature was extremely rare. They noted that the “possibility that a non-genetically-engineered precursor could have adapted to humans while being studied in a laboratory should be considered, regardless of how likely or unlikely”.

There was one more feature of the SARS-CoV-2 outbreak that could not be missed. Of all the places in China, the outbreak happened in Wuhan and essentially next door to Wuhan Institute of Virology (WIV), the laboratory with a vast collection of coronaviruses that had long been a hub for gain of function (GoF) research — the GoF research refers to the process that gives capabilities to a pathogen that it does not naturally have, such as increased virality and transmissibility or the ability to infect organisms it would not naturally infect.

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Wuhan, far from the jungles where bats live, was the unlikeliest place for a natural spillover but the likeliest place for the virus to leak from a lab.

From Mojiang to Wuhan lab

In 2012, six sick men were admitted in Kunming, the capital of China’s Yunnan province. They had respiratory issues, fever, muscle ache, and fatigue — familiar symptoms. They had worked in a human-made mine in the province’s Mojiang county.

Four of them suffered respiratory failure and three died.

The immediate suspicion was that they had been infected by an unknown virus. The doctor treating them was so alarmed that they noted that if such cases of severe pneumonia arose again, precautions would need to be taken to prevent transmission in hospital.

If these symptoms, the unknown nature of the pathogen, and doctor’s concern about transmission sound familiar, then that’s because these persons were indeed infected by a SARS-like virus.

None of this information was shared by Chinese authorities. This information is known to us because Prasenjit Ray, who goes by the name ‘The Seeker’ on X, spent days scouring the databases on the internet to find two theses written by Chinese medical professionals about the Mojiang incident in May 2020.

Since outbreak in Wuhan, China in 2019, Covid-19 has formally infected at least 770 million people and killed over 7 million. The photograph shows isolated intensive care unit in Wuhan in February 2020. (Photo: AP)

Several Chinese researchers visited the mine in the coming years. They included a team led by Shi Zhengli of Wuhan Institute of Virology (WIV), who is known as ‘Bat Woman’ for her work on bat coronaviruses. The team had seven expeditions during 2011-15.

In 2016, Shi and her team published a paper in which they disclosed that they had found a new SARS-like coronavirus in the mine in 2013. They named it BtCoV-4991 and published its partial genome.

Four years later, in January 2020, scientists at Wuhan University were analysing the genome of SARS-CoV-2. As they ran it through databases, the genome showed 98.7 per cent match with BtCoV/4991. The finding was published in a paper on February 5.

In a normal course, the finding could have caused an earthquake as the virus behind a spiralling outbreak threw up a nearly 99 per cent match with a sample that had been in WIV for seven years — next door to where the outbreak happened. However, that was not the case as the finding was overshadowed by another paper two days ago.

On February 3, Nature published a paper by Shi on the genome of SARS-CoV-2. Nonchalantly, she mentioned that SARS-CoV-2 had matched 96.2 per cent with another virus, RaTG13, collected in Yunnan — the same province with the Mojiang mine. Inquisitive scientists and observers quickly noted that the internet had no mention of RaTG13 at all.

Prompted by a discussion on an online forum on February 20, Rosanna Segreto, a microbiologist at the University of Innsbruck in Austria, figured out there was a 100 per cent match between BtCoV/4991 and RaTG13. It was clear the two were the same.

It was only in July that Shi of WIV admitted that BtCoV/4991 and RaTG13 were the same — the BtCoV/4991 being a partial sequence of the full genome of RaTG13.

In short, the WIV and its top coronavirus researcher Shi were aware that SARS-CoV-2 had a 96.2 per cent match with a virus they had found in 2013 and they did not share it with the world. The WIV did not just hide it from the world, but it also renamed BtCoV/4991 as RaTG13 — to confuse the world, whether on purpose or not.

Even though WIV’s duplicity had been detected, the significance of RaTG13 was not learnt until May when Ray, known better as The Seeker, would find the theses mentioned above.

Connecting the dots

Once Ray figured out the significance of RaTG13 and the theses he had found, he shared them with Monali Rahalkar, a scientist at the Agharkar Research Institute (ARI), Pune, and Rahul Bahulikar, a Senior Scientist at the BAIF Development Research Foundation, Pune.

Rahalkar and Bahulikar were among the first to connect the dots between the infection at Mojiang, the ongoing Covid-19 pandemic, and how RaTG13 fit into the picture.

In a paper in Frontiers in Public Health in October 2020, Rahalkar and Bahulikar indicated that a virus similar to SARS-CoV-2 had infected six workers in the Mojiang mine. They noted that workers and the Covid-19 patients showed the same symptoms and progression of the disease:

  • CT scans of Covid-19 patients and miners were very similar, both showing ground-glass opacities, peripheral consolidation, and clear indications of bilateral pneumonia characteristic in Covid-19;

  • both miners and Covid-19 patients showed elevated D-dimer values and pulmonary thromboembolism;

  • similar treatment in both cases including antivirals, steroids, mechanical ventilation, antibiotics for secondary bacterial infections, and antifungals for secondary fungal infections;

  • and elevated Serum Amyloid A protein, an inflammatory marker that shows characteristic high values in viral infection.

At the time, the only visible difference between the disease in Mojiang and Covid-19 appeared to be that while SARS-CoV-2 causing Covid-19 was highly transmissible, the Mojiang virus did not appear to be that transmissible as only six cases were reported.

In their book ‘Viral: The Search for the Origin of Covid-19’, the Broad Institute’s Alina and science writer Matt Ridley note that it suggests that “the virus or viruses responsible for their illness very likely had not evolved to be as transmissible among humans as SARS-CoV-2 is” and the mine workers only fell sick “perhaps because they had been exposed to massive doses of the virus via the disturbed dust of bat guano within the confines of a poorly ventilated mineshaft for extended periods of time”.

In their paper, Rahalkar and Bahulikar concluded: “Although we cannot say that RaTG13 or SARS-CoV-2 infected the miners, there is a high chance that it could be a virus quite similar in genetic composition to these two.”

Separately, Rahalkar tells Firstpost that even though RaTG13 was a 96.2 per cent match to SARS-CoV-2 on RNA level, the two viruses are much more similar.

“The interesting part is that at the amino acid-level, similarities between most of the proteins of the two viruses are 98-99 per cent. The two viruses are more similar than we think,” says Rahalkar, a Scientist-E at the Nanobioscience Group at ARI Pune.

A blueprint of virus emerges

In 2021, a 75-page proposal dating to 2018 emerged that detailed how US and Chinese scientists wanted to insert furin cleavage sites (FCS) into SARS-like coronaviruses.

The proposal, called ‘Project DEFUSE: Defusing the Threat of Bat-borne Coronaviruses’, was submitted to the US Defense Advanced Research Projects Agency (DARPA), which rejected it. It was written by EcoHealth Alliance, the New York-based non-governmental organisation that had collaborated for years with the Wuhan Institute of Virology (WIV).

In the proposal first reported by The Intercept, the scientists had proposed to create SARS coronaviruses with furin cleavage sites in their spike proteins. This meant that more than a year before the outbreak at Wuhan, scientists had outlined exactly how they were going to insert FCS into a SARS-like coronavirus. Essentially, the DEFUSE proposal was a blueprint for creating SARS-CoV-2 in a lab — the FCS is what gave SARS-CoV-2 the potential to cause a pandemic.

Since the beginning, the improbability of FCS occuring in SARS-CoV-2 in nature had irked scientists, prompting many to say it was a sign of the virus originating in a lab. The DEFUSE proposal confirmed their suspicions.

Without FCS, it’s “unlikely” SARS-CoV-2 would have caused a worldwide pandemic, says Ebright, the molecular biologist at Rutgers.

In research published in Nature in August 2020, scientists led by Bryan A Johnson of the University of Texas Medical Branch (UTMB) showed that the loss of FCS attenuated SARS-CoV-2. They found that SARS-CoV-2 without FCS “replicated less efficiently” in human cells and caused only mild damage to lungs. In short, the FCS is what makes SARS-CoV-2 lethal.

Johnson et al noted that SARS-CoV-2 without FCS had about 10-fold reduction in viral load at 48 and 72 hours after infection, “which indicates that the loss of the furin cleavage site impairs viral replication”. They also noted that SARS-CoV-2 without FCS was attenuated in a human respiratory cell line and had reduced viral pathogenesis in both hamsters and humanised mice.

Rahalkar, the scientist at ARI Pune, tells Firstpost that RaTG13, which was discovered by WIV’s Shi in 2013, ties in with DEFUSE perfectly.

“Though RaTG13 was not a direct ancestor of SARS-CoV-2, it was the nearest sequence to the virus with the WIV — having an overall match of 96.2 per cent and up to 98-99 per cent match at amino acid-level. Dr Shi at WIV and EcoHealth President Dr Daszak proposed that consensus sequences would be created from natural ones and these quasi-species would be used for the synthesis of new backbones. The RaTG13 sequence could have been a guideline for preparing a new backbone and a virus under DEFUSE,” says Rahalkar.

The smoking gun points to Wuhan lab

Even after the DEFUSE proposal surfaced in 2021, several supporters of SARS-CoV-2’s natural-origin said the proposal had called for the insertion of “human-specific proteolytic cleavage sites” into SARS-like coronavirus — and not furin cleavage sites. They wanted to give EcoHealth Alliance and their partners at WIV a benefit of doubt.

The benefit of doubt was shoved off the table in early 2024 when US Right to Know published more than 1,400 pages of communication between scientists who drafted the DEFUSE proposal. The US RTK secured the documents under the US Freedom of Information Act (FOIA).

While the language of the formal DEFUSE proposal published in 2021 called for the insertion of “human-specific proteolytic cleavage sites” in a portion of the spike protein called the S2, earlier drafts of DEFUSE published by US RTK were more explicit, according to Emily Kopp, who reported these documents for US RTK.

Kopp reported that even though the final DEFUSE proposal used a relatively generic term, proteolytic cleavage sites, which allowed scientists to claim a benefit of doubt, the communications showed they were referring to FCS and insertion of FCS at S1/S2 junction in the SARS-CoV-2 — exactly where it came to be in the virus that emerged a year later in Wuhan.

Shi Zhengli inside a laboratory at the Wuhan Institute of Virology in 2017. (Photo: AP)

Ray, better known as The Seeker, who has been central to the debate of Covid-origin since 2020, tells Firstpost that DEFUSE serves as the Rosetta Stone for the understanding of the origin of SARS-CoV-2 — the Rosetta Stone being the ancient inscription that allowed the world to decipher ancient Egypt’s hieroglyphics after being in dark for nearly 1,500 years.

Ray says, “It sheds a great deal of light about their research intentions leading up to the pandemic and it goes beyond just the furin cleavage site (FCS). The entire genome of SARS-CoV-2 aligns with what was outlined in DEFUSE. Almost every feature of the virus, from the spike protein to the FCS and the insertion of restriction sites, matches with what was outlined in the DEFUSE proposal.”

Ray says that even the timeline of the outbreak in Wuhan and the filing of the DEFUSE proposal align perfectly. He says that “any viruses developed under DEFUSE protocols would have been ready by the time Covid-19 emerged in Wuhan, which also helps explain the timing of the outbreak”.

In conclusion, Ray says DEFUSE is “about as close to a smoking gun as we’re likely to get”.

Ebright, the Board of Governors Professor of Chemistry and Chemical Biology at Rutgers, says that the DEFUSE proposal seals the case for the lab-origin of SARS-CoV-2.

While making his case for the lab-origin of SARS-CoV-2, Ebright refers to another proposal involving the WIV that was funded by the US National Institutes of Health (NIH) and involved GoF research.

Ebright makes his case: “In 2018, just one year before the pandemic, the Wuhan Institute of Virology and its collaborators proposed in a grant proposal to NIH to construct additional genetically modified SARS coronaviruses, proposing to construct viruses with spikes having higher binding affinities for human SARS receptors, hypothesising that such viruses would have enhanced pandemic potential.

“The same year, they detail in the DEFUSE proposal that they plan to construct genetically modified SARS coronaviruses having a ‘furin cleavage site’ inserted at the spike ‘S1-S2’ border and to construct these viruses by synthesising six nucleic-acid building blocks and assembling the six nucleic-acid building blocks using the reagent ‘BsmBI’.

“Then, a year later in 2019, a novel SARS-related coronavirus having a spike with extremely high binding affinity for human SARS receptors, a furin cleavage site at the spike S1-S2 border, and a genome sequence with features enabling assembly from six synthetic nucleic-acid building blocks using BsmBI as a reagent for assembly —a virus having the exact features proposed in the 2018 NIH and DARPA proposals— emerged at the doorstep of the WIV.

“Taken together, the presence of a spike having an extremely high affinity for human SARS receptors, the presence of a furin cleavage site at the spike S1-S2 border, the unusual codon usage of the furin cleavage site, the sequence features enabling assembly from six synthetic nucleic-acid building blocks with BsmBI as reagent for assembly, and the one-for-one match between these features and the features proposed in the 2018 proposals by WIV and collaborators make an extremely strong case —a ‘smoking gun’— for a research-related origin of SARS-CoV-2.”

Metzl, the biotech futurist at the Atlantic Council, tells Firstpost that the overwhelming weight of the available circumstantial and logical evidence points to a research-related origin of SARS-CoV-2.

Metzl highlights that Wuhan is a highly unlikely place for a natural spillover of the virus as it does not have any bat-eating culture. Moreover, he says that no animal source of the virus has been found in five years. On the other hand, he says Wuhan is the likeliest place for the lab-origin.

Metzl tells Firstpost, “Out of all the places in the world and even in China, the SARS-CoV-2 emerged in Wuhan where you have people who work on such viruses — the people who had just the previous year outlined how to make exactly the same virus. In Wuhan, people don’t have the same dietary habits as in southern China or Southeast Asia where eating wild animals such as bats is far more common. Wuhan is also outside of the migratory path of the type of horseshoe bats that are ancestral carriers of this virus.

“For SARS-CoV-2 to emerge at such a place where hardly any wild animals are sold and where no animals infected with the original strain of the virus were found, you would not just need to win the lottery but win it five times in a row for a spillover. It really strains incredulity to think that any hypothesis other than lab-origin could be determined. The logical analysis based on available evidence points heavily in favour of a research incident-related origin of SARS-CoV-2.”

As for those who ask if it can be 100 per cent proven, then Metzl says no, but adds that few things in the world come with 100 per cent certainty.

Metzl says that one needs to look at how one development after another aligned over the years for the outbreak to happen at Wuhan in 2019.

“What are the chances that all of these things would align in just this one place that has China’s first and largest BSL-4 virology institute that was doing exactly this chimeric genome editing of viruses and has the world’s largest collective of SARS coronaviruses?” asks Metzl.

“As for the 100 per cent certainty, if our standard for anything was 100 per cent absolute, irrefutable proof, there are a whole lot of things we wouldn’t be able to prove. Can I prove 100 per cent irrefutably that my parents are actually my parents? We can live with 99.9 per cent certainty and I am 99.99 per cent sure of the research incident-related origin of the virus,” says Metzl.

A lawyer by training, Metzl frames his final argument like a prosecutor: “The evidence in favour of a lab-origin of SARS-CoV-2 is such that any reasonable jury in any reasonable court of law would convict China for sparking the Covid-19 pandemic. Consider these two points. Firstly, if there was a trial of a mafia boss or a gang leader and potential witnesses started dying one by one, we wouldn’t say, ‘Oh, there’s no smoking gun, this guy must be innocent.’ We would say that the murder of these witnesses one by one is at least an indirect indication of guilt.

“Secondly, if I applied for a grant to paint New York’s Central Park purple, just like the WIV and their collaborators applied for the grant for the DEFUSE proposal, and even after the rejection of my application, if we would wake up one morning to find the Central Park painted purple, I would be on the top of the list of suspects. So even though the DEFUSE proposal was wisely rejected, the virus outlined in the proposal still emerged a year later next door to the applicant WIV. These are enough grounds for a conviction in any jury trial.”

As Metzl rests his case, it is time the world knew the truth — and that can tumble out only from the closet of China if complete access is given to international investigators.

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Written by Madhur Sharma
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Madhur Sharma is a senior sub-editor at Firstpost. He primarily covers international affairs and India's foreign policy. He is a habitual reader, occasional book reviewer, and an aspiring tea connoisseur. You can follow him at @madhur_mrt on X (formerly Twitter) and you can reach out to him at madhur.sharma@nw18.com for tips, feedback, or Netflix recommendations see more

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