Health

SARS-CoV-2: WHO-China report dismisses lab-origin hypothesis as being ‘extremely unlikely’

This article has been updated. Latest update: 9/4/2021.

The report of the ‘Joint WHO-China Study’ of the possible origins of SARS-CoV-2 holds no surprises. Its main messages – that a lab origin is “extremely unlikely” and that the virus most likely spread naturally, either directly from an animal to humans or via an intermediate host – had already been pushed out in press conferences given by the WHO team.

The study was conducted in Wuhan from January 14 to February 10 this year. The joint international team comprised 17 Chinese members and 17 international experts from other countries, the World Health Organisation (WHO), the Global Outbreak Alert and Response Network (GOARN), and the World Organisation for Animal Health (OIE). The Food and Agriculture Organisation of the United Nations participated as an observer.

The authors of the 123-page report (plus annexes), which was released yesterday (Tuesday) after several delays, state: “Direct zoonotic spillover 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; introduction through a laboratory incident was considered to be an extremely unlikely pathway.”

While giving no credence to the lab origin hypothesis, the report’s authors do state: “Although rare, laboratory accidents do happen, and different laboratories around the world are working with bat CoVs.”

They also suggest that there should be “regular administrative and internal review of high-level biosafety laboratories worldwide” and say that any new evidence supplied about possible leaks should be followed up.

The WHO director-general, Tedros Adhanom Ghebreyesus, noted yesterday that the team had visited several laboratories in Wuhan and considered the possibility that the virus entered the human population as a result of a laboratory incident.

“I do not believe that this assessment was extensive enough, he said. “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.”

The authors of the new report admit that no intermediate hosts have so far been implicated in the origin of Covid-19, but add that “a range of species can be infected by SARS-CoV-2 experimentally (for example, raccoon dogs, ferrets, rabbits, cats, golden Syrian hamsters, bats, macaques, marmosets and white-tailed deer) or by presumed or demonstrated exposure to humans with Covid-19 (for example, mink, gorillas, captive large felids, domesticated cats and dogs)”.

They recommend surveys for SARSr-CoVs in farmed wildlife or livestock “that have potential to be infected, including species bred for food such as ferret-badgers and civets, and those bred for fur such as mink and raccoon dogs in farms in China, in Southeast Asia, and in other regions”. 

The report’s authors say it remains possible that the virus entered Wuhan via frozen food imported from another area of China or even from overseas, but add: “There is no conclusive evidence for foodborne transmission of SARS-CoV-2 and the probability of a cold-chain contamination with the virus from a reservoir is very low.

“While there is some evidence for possible reintroduction of SARS-CoV-2 through handling of imported contaminated frozen products in China since the initial pandemic wave, this would be extraordinary in 2019 where the virus was not widely circulating.”

There have been serious concerns about the makeup of the WHO team, and not least the presence of the president of the US-based EcoHealth Alliance, Peter Daszak, who has had a long-standing involvement in gain-of-function research projects in China.

Daszak told Nick Schifrin of PBS (The Public Broadcasting Service) on March 29: “There’s no evidence that the viruses that that lab was working with or even the genetic sequences were the progenitor, the ancestor of SARS-CoV-2.”

Daszak added: “When you visit the lab, when you talk to the management, it is an efficiently run lab. They do audits, safety checks.”

It was Daszak who drafted a letter from 27 health scientists that was published in The Lancet on February 19 and condemned as “conspiracy theories” suggestions that Covid-19 does not have a natural origin.

The WHO-China report is widely considered to be heavily biased to suit the wishes of the Chinese government.

Jamie Metzl, who is a member of a WHO advisory committee on human genome editing, tweeted the following on March 29: 

 

Metzl added: “By bending over backwards to validate the zoonotic jump hypothesis despite the clear absence of evidence and glibly discounting the lab leak hypothesis without meaningful consideration, the report shows why having the Beijing government co-investigate a possible lab leak and deadly cover up is like asking the Kremlin to co-investigate Chernobyl.”

In an interview with Lesley Stahl for ‘60 Minutes’ on CBS News Metzl said: “The WHO inquiry was far from comprehensive, because, as it has done since the beginning of the outbreak, the Chinese government withheld information.

“I wouldn’t really call what’s happened now an investigation. It’s essentially a highly chaperoned, highly curated study tour … Everybody around the world is imagining this is some kind of full investigation. It’s not. This group of experts only saw what the Chinese government wanted them to see.”

 

Metzl (pictured left) says that while the WHO team were at the Wuhan Institute of Virology (WIV) they didn’t demand access to the records and samples and key personnel.

“It was agreed first that China would have veto power over who even got to be on the mission,” Metzl said. “On top of that, the WHO agreed that, in most instances, China would do the primary investigation and then just share its findings with these international experts, so these international experts weren’t allowed to do their own primary investigation.”

Metzl tweeted on March 29:

He tweeted on March 31 that the international team saw its task as finding a zoonotic source of animal transition in the wild, not seeking the actual source of the pandemic. “There’s a big difference,” Metzl said. “They set out to prove one hypothesis, not fairly examine all of them.”

Metzl says that one path to a full investigation would be to revise the current terms of reference to allow for an unrestricted forensic investigation. “We could also try for a new World Health Assembly resolution or UN mandate,” Metzl said. “China will try to block these, but our starting point must be what’s required.”

David Relman, who is a medicine and microbiology professor at Stanford University, told Schifrin that the WHO-China report relies too much on summary judgments by Chinese scientists. “We can’t simply dismiss one idea as very unlikely and hold another as very likely when, in both cases, we have no direct evidence, Relman said.

Relman said he would call the report “somewhat superficial, skewed, and incomplete”.

He added: “As a scientist, the thing we value the most and the thing upon which we most rely are data. And when I look at this report, I’m struck by the fact that there are very few primary data, original data, on which we can judge the kinds of assessments that are made, in some cases quite enthusiastically in this report.”

Writing in the Wall Street Journal on March 29, Drew Hinshaw, Jeremy Page, and Betsy McKay said: “Most of the research for the report was conducted by Chinese scientists, almost all of whom work for the state. Under the terms of that study, China conducted the bulk of the research, which was presented to the team of international scientists recruited by the WHO, during their visit in January and February.”

In an opinion piece in The Washington Post, Josh Rogin writes: “Determining the origin of the SARS-CoV-2 virus should have nothing to do with politics. It is a forensic question, one that requires thorough investigation of all possible theories, and one that should encompass both the scenario that the virus jumped from animals to humans in nature as well as one related to human error in a Wuhan lab.

“But a fatally flawed investigation by the World Health Organisation and Chinese officials and experts only muddies the waters, and it places the WHO further at odds with the US government and the Biden administration.”

The US Secretary of State Antony Blinken said on CNN. “We’ve got real concerns about the methodology and the process that went into that report, including the fact that the government in Beijing apparently helped to write it.”

Rogin points to declassified US intelligence alleging that the WIV was conducting undisclosed research on bat coronaviruses and had secret research projects with the Chinese military.

“The Biden administration is not claiming the lab-accident theory is correct, but it is calling for China to disclose more information about the labs,” Rogin writes.

The US State Department said in a fact sheet about activity at the Wuhan Institute of Virology (WIV), published on January 15, 2021, that it had obtained evidence showing that researchers at the institute became sick with flu-like symptoms in autumn 2019.

The new WHO-China report states, however: “The three laboratories in Wuhan working with either CoVs diagnostics and/or CoVs isolation and vaccine development all had high quality biosafety level (BSL3 or 4) facilities that were well-managed, with a staff health monitoring programme with no reporting of Covid-19 compatible respiratory illness during the weeks/months prior to December 2019, and no serological evidence of infection in workers through SARS-CoV-2-specific serology-screening.”

A member of the DRASTIC team of independent investigators, Gilles Demaneuf, says that every word of the new report had to be validated by China. It is a joint report, Demaneuf says, and “nothing can be printed without joint agreement”.

Demaneuf, who is an engineer and data scientists based in New Zealand, points out that, in Chinese, the report is called the China–WHO joint team report, with the emphasis on China, whereas in English it is the WHO–China report. “China would not tolerate calling it the WHO-China report in Chinese,” Demaneuf said.

He says the report is based on studies conducted exclusively by local scientists, “who too often flatly refused to provide the underlying granular data or to consider possible improvements”.

He added: “Secondly, it was painfully negotiated with the local half of the team, which was never in a position to assert its scientific independence being subjected to a very strict State Council gag-order.”

The team’s evaluation of a possible lab-related accident was limited to a short, guided tour of a few labs and to a few complaisant conversations held there, Demaneuf says. “As a result, a true investigation into the possible SARS-CoV-2 origins is now needed more than ever,” he added.

DRASTIC (Decentralised Radical Autonomous Search Team Investigating Covid-19) is made up of scientists, journalists, and other independent researchers who investigate anomalies in the narratives about SARS-CoV-2, collect and present evidence, and put forward questions and hypotheses.

The members launched a petition in the form of an open letter to the WHO team in which they beseeched the scientists on the team “to conduct the investigations with transparency, impartiality, and bravery without bowing to any pressure or national interest”.

Critics of the mission, and the resulting report, would say that the team has bowed to Chinese pressure and has been neither brave nor impartial, and has not acted transparently.

A bizarre situation arose after the WHO team completed its visit to China. What was announced by the team in a press conference on February 9 was completely at odds with what was later stated by Tedros.

At the February 9 press conference the head of the WHO team, Peter Ben Embarek (pictured left), said the team’s findings suggested that the possibility that SARS-CoV-2 originated from a laboratory in Wuhan was “extremely unlikely”. A possible lab origin was not in the hypotheses that the team would suggest for future studies, Ben Embarek said.

He said he had spoken extensively with lab personnel in Wuhan about the lab-related hypotheses and they were the best ones “to dismiss any of these claims”.

On February 12, Tedros took a different line altogether and said that all hypotheses about the origin of SARS-CoV-2 remained on the table and required further study.

In his remarks to WHO member states yesterday, he thanked the team for their work. “As far as WHO is concerned, all hypotheses remain on the table,” he said.

“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 as we do.

“Finding the origin of a virus takes time and we owe it to the world to find the source so we can collectively take steps to reduce the risk of this happening again. No single research trip can provide all the answers.”

Tedros noted that the WHO-China report presented a comprehensive review of available data, suggesting that there was unrecognised transmission of SARS-CoV-2 in December 2019, and possibly earlier.

“The team reports that the first detected case had symptom onset on the 8th of December 2019. But to understand the earliest cases, scientists would benefit from full access to data including biological samples from at least September 2019,” he said.

“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.”

Tedros (pictured left) said he welcomed the recommendations for further studies to understand the earliest human cases and clusters, to trace the animals sold at markets in and around Wuhan, and to better understand the range of potential animal hosts and intermediaries.

“The role of animal markets is still unclear,” he said. “The team has confirmed that there was widespread contamination with SARS-CoV-2 in the Huanan market in Wuhan, but could not determine the source of this contamination.

“I welcome the recommendations for further research, including a full analysis of the trade in animals and products in markets across Wuhan, particularly those linked to early human cases.”

Tedros said he concurred with the team’s conclusion that farmers, suppliers, and their contacts will need to be interviewed.

“The team also addressed the possibility that the virus was introduced to humans through the food chain. Further study will be important to identify what role farmed wild animals may have played in introducing the virus to markets in Wuhan and beyond,” he added.

In an interview with Science magazine, published on February 14, Ben Embarek said the team was not closing the door on the lab-source hypothesis, but that it would not be investigating it in the coming weeks and months.

He said the team had difficulties designing future studies to look into the laboratory claims within its joint group. “ … if you want to explore such a hypothesis further, you need a different mechanism,” Ben Embarek said.

“You need to do a formal audit, and that’s far beyond what our team is mandated to do or has the tools and capabilities to do.”

The fact that the lab-origin hypothesis was listed or assessed as extremely unlikely was not the same as if it had been listed or assessed as impossible, Ben Embarek said.

“We’re not closing the door … It’s not something we’re going to pursue in the coming weeks and months. But our assessment is out there, and the topic is on the table.”

When the team was in China, the politics was always in the room “on the other side of the table”, Ben Embarek told Science.

Members of the DRASTIC team have pointed out the flaws in the arguments put forward by Ben Embarek.

António Duarte (@AntGDuarte) tweeted to him: “If ‘the mission could not carry out the formal audit needed to explore the [lab origin] possibility further’ how could it be deemed ‘extremely unlikely’?”

The Seeker tweeted to Ben Embarek that he should be saying “we weren’t able to eliminate the possibility of a lab origin because they won’t let us investigate” rather than “it was assessed as a not likely scenario”. The act of suppressing should have raised the level of inquiry even more, The Seeker says.

Ben Embarek said yesterday that the investigation into the origin of SARS-CoV-2 was a “work in progress”. He said that the latest mission only “scratched the surface” of a very complex set of studies that needed to be conducted.

He said that, in examining the arguments for and against the various hypotheses and pathways, the team tried to stay focused on hard facts and to stay away from “suspicions, ideas, theories, and so on”.

Former CDC director Robert Redfield (pictured below), speaking in a clip released by CNN on March 26, caused shock waves when he said he thought that SARS-CoV-2 most likely escaped from a laboratory in Wuhan.

“I have spent my life in virology. I do not believe this somehow came from a bat to a human and, at that moment in time, the virus that came to the human became one of the most infectious viruses that we know in humanity for human-to-human transmission,” Redfield told CNN’s Sanjay Gupta.

“Normally, when a pathogen goes from a zoonote to a human, it takes a while for it to figure out how to become more and more efficient in human-to-human transmission. I just don’t think this makes biological sense.”

Redfield emphasised that he was not implying any intentionality and was simply giving his opinion.

He added: “If I was to guess, this virus started transmitting somewhere in September, October in Wuhan. That’s my own view; it’s only opinion.

“I am of the point of view that I still think the most likely aetiology of this pathogen in Wuhan was from a laboratory; you know, escaped.”

It’s not unusual for respiratory pathogens that are being worked on in a laboratory to infect a laboratory worker, Redfield said.

“ … I have coronavirus that I’m working on. Most of us in a lab are trying to grow virus; we try to help make it grow better and better and better and better and better and better so we can do experiments and figure out about it.”

In its fact sheet about activity at the WIV, the US State Department said: “The US government has reason to believe that several researchers inside the WIV became sick in autumn 2019, before the first identified case of the outbreak, with symptoms consistent with both Covid-19 and common seasonal illnesses.

“This raises questions about the credibility of WIV senior researcher Shi Zhengli’s public claim that there was ‘zero infection’ among the WIV’s staff and students of SARS-CoV-2 or SARS-related viruses.

“Accidental infections in labs have caused several previous virus outbreaks in China and elsewhere, including a 2004 SARS outbreak in Beijing that infected nine people, killing one.”

The State Department added: “Despite the WIV presenting itself as a civilian institution, the United States has determined that the WIV has collaborated on publications and secret projects with China’s military. The WIV has engaged in classified research, including laboratory animal experiments, on behalf of the Chinese military since at least 2017.”

WHO-China recommendations

The WHO-China report authors say that, “in order to further study the potential for (frozen) food as a source of infection or the cold chain as an introduction pathway of SARS-CoV-2”, case-control studies of outbreaks in which the cold chain product and food supply is positive would be useful to provide support for cold chain products and food as a transmission route”.

They say that if there are credible links to products from other countries or regions with evidence for circulation of SARS-CoV-2 before the end of 2019, such pathways would also need to be followed up.

“Screening of leftover frozen cold chain products sold in Huanan market from December 2019 if still available is needed, particularly frozen animal products from farmed wildlife or linked to areas with evidence for early circulation of SARS-CoV-2 from molecular data or other analyses.”

The report’s authors also say that “consideration should be given to further joint review of the data on respiratory illness from the on-site clinics at the military games in October 2019”.

Chinese officials have reportedly suggested that a US delegation to the military games might have introduced the virus to Wuhan.

The authors of the WHO-China report say there is a need for more data from China’s blood banks. “Given the outstanding questions and the potential for limited clusters that would not be detected through the studies done so far, access to systematically collected historic samples including routinely stored blood bank samples would be of great added value for the origins studies,” they write.

DRASTIC team digs for answers 

One of the issues raised by the DRASTIC team is the fact that a database containing unpublished information about the sequencing of samples collected by researchers from the WIV on trips to an abandoned copper mine in Yunnan has been taken offline.

Six of the men who were working in the Yunnan mine, removing bat faeces from a cave, suffered a severe pneumonia-like illness in 2012. Three of them died.

The miners had a high fever, dry cough, sore limbs and, in some cases, headaches – all symptoms that are now associated with Covid-19.

“The WIV’s wild animal virus database and its password-protected section containing unpublished virus sequences are no longer available publicly, and even the pages describing it have now been taken offline,” the DRASTIC team said.

“Can WIV clarify what happened to the samples collected from the Mojiang miners between 2012 and 2019 and whether they are still available for independent analysis? the team ask in their petition.

“Did WIV culture any virus from the Tongguan mineshaft pneumonia cases in animals or cell lines? If so, were the sequences used as ‘backbones’ for creating other viruses?”

There has been much discussion – and speculation – about a bat coronavirus that was reportedly discovered in a faecal sample collected in the abandoned mine in Yunnan in 2013.

The virus was initially referred to as RaBtCoV/4991, but later, when its whole genome was sequenced, it was renamed RaTG13. The genomic sequence of RaTG13 is reported to be 96% identical to that of SARS-CoV-2.

The director of the Centre for Infectious Diseases at the WIV, Shi Zhengli, says that RaTG13 is the same sample as the one referred to as RaBtCoV/4991 in a scientific paper published by researchers from the WIV in 2016.

Zhengli says RaTG13 was never cultured in her laboratory and insists that SARS-CoV-2 did not originate there.

Scientists call for a full, unrestricted investigation

An international group of 26 scientists published an open letter on March 4 calling for a “full and unrestricted international forensic investigation into the origins of Covid-19”.

They wrote: “As scientists, social scientists, and science communicators who have been independently and collectively looking into the origins of the Covid-19 pandemic, we believe it essential that all hypotheses about the origins of the pandemic be thoroughly examined and full access to all necessary resources be provided without regard to political or other sensitivities.”

The scientists, who include Jamie Metzl, say the WHO investigation in China was “opaque and restrictive” and its scientific validity was greatly compromised.

The WHO team, they say, did not have the mandate, the independence, or the necessary accesses to carry out a full and unrestricted investigation into all the relevant SARS-CoV-2 origin hypotheses.

Signatories of the open letter have commented about the new report.

Colin Butler, who is an honorary professor of public health at the Australian National University in Canberra, said: “This report is based on outdated scientific knowledge. It could have been written in 2003, when SARS occurred. Since then, techniques to manipulate the genetics of both laboratory animals (e.g. “humanised mice”) and viruses have evolved enormously.

“The rate of this technological evolution has far outpaced accompanying developments in ethics and transparency, meaning that an accidental leak from a laboratory of a novel pathogen with genuine global pandemic potential has never been as high.

“The failure of the report’s authors to understand these twin issues is of deep concern, analogous to the innocence of researchers into nuclear fission from a more innocent age.”

Günter Theißen, who is a professor of genetics at the Friedrich Schiller University in Jena, Germany, said the report provided a shocking example of how empirical science should not be done.  “The authors take one scenario, the natural zoonose hypothesis, for granted – the working group was asked ‘to identify the zoonotic source of the virus’, as if this were the only possible scenario – and they do everything to corroborate their view.

“Alternative hypotheses, such as a lab accident, are dismissed as conspiracy theories, or considered being extremely unlikely.”

The report’s authors maintain that all available data support a zoonose, “which ignores numerous published evidence saying otherwise”, Theißen says. “This is not only arrogant, it is against everything we have learned from 17th century Francis Bacon, 20th century Karl Popper to contemporary epistemologists and science theorists as to how empirical research should be done.”

As long as the hypothesis that humans have helped to generate SARS-CoV-2, or to straddle the barrier from animals to humans at the onset of Covid-19, is not falsified, it should stand as one reasonable scientific hypothesis beside others, Theißen says.

“Considering only ‘politically correct‘ theories about the origin of SARS-CoV-2, especially a natural zoonose, as reasonable, but all others as conspiracy theories, is not only bad science. It is easily a recipe for the next disaster.”

Rossana Segreto, who works in the department of microbiology at the University of Innsbruck in Austria said: “If the molecular sequence data suggests that SARS-CoV-2’s supposed zoonotic jump most likely happened between mid-November and early December 2019, as the report asserts, this time frame would be too short to explain the perfect human adaptation of SARS-CoV-2, detected from its first appearance.

“The combination of low rate of evolution in the early phase of transmission, high adaptation for human infection and transmission from the earliest strains, as well as the human and mouse peptide mimicry, is more consistent with a laboratory origin – possibly connected to the use of humanised mice as animal model – than a natural one.”

Indian researcher Monali C. Rahalkar, who is a member of DRASTIC, said: “The report supports the possibilities of direct zoonosis or through intermediate hosts though there is no support, as all the tested animals tested negative.”

There has been no genetic or serological evidence for SARS-CoV-2 in a wide range of domestic and wild animals tested to date, Rahalkar says.

The report fails to include details of the RaTG13 sample, she adds. “This was collected from a mine in Mojiang, and there is no reference to this mine in the report.”

It would have been crucial for the WHO team to visit and resample from the Mojiang mine, Rahalkar says.

In November 2020, WIV declared that they had eight more SARS-like coronavirus samples from the same site, collected between 2012 to 2015, Rahalkar points out, but, to date, neither the sequences of these samples nor their IDs, with the location, are available in public databases or papers.

The authors of the WHO-China report talk about BSL3 and BSL4 facilities for coronavirus research, whereas Shi Zhengli told Science magazine that the scientists used BSL2 and BSL3 facilities for coronavirus research, Rahalkar also points out.

Nikolai Petrovsky from Flinders University in Australia said: “It remains vitally important that we understand how SARS-CoV-2 virus from the very first known human infections was so exquisitely well adapted to not only infect but also to transmit between humans, a feature not typical of other zoonotic virus spillovers to humans at their origin.

“This report does nothing to address this key and unique feature of SARS-CoV-2 and how this came about.”

There remains a need for further intensive scientific investigation into all potential sources of the virus, “to provide answers to critical questions that this team does not appear for political reasons comfortable to tackle”, Petrovsky says.

One of the letter’s signatories, Richard Ebright, who is a microbiologist working at Rutgers University in the US, told Rowan Jacobsen, writing for Boston Magazine in September last year: “For the substantial subset of virologists who perform gain-of-function research avoiding restrictions on research funding, avoiding implementation of appropriate biosafety standards, and avoiding implementation of appropriate research oversight are powerful motivators.”

Jacobsen wrote: “Antonio Regalado, biomedicine editor of MIT Technology Review, put it more bluntly. If it turned out Covid-19 came from a lab, he tweeted, ‘it would shatter the scientific edifice top to bottom’.”

In their original open letter, the scientists say that, while the “collaborative” process of discovery mandated by the WHO in May 2020 was meant to enable a full examination of the origins of the pandemic, structural limitations built into the mission to Wuhan made it “all but impossible” for the mission to realise this aspiration.

Half of the joint team was made up of Chinese citizens whose scientific independence might be limited, the scientists point out.

International members of the joint team had to rely on information the Chinese authorities chose to share with them, and any joint team report had to be approved by both the Chinese and international members of the team, they add.

They note, for example, that international members of the joint team, “by their own admission”, often relied on verbal assurances given to them by their Chinese counterparts rather than independent investigation, particularly regarding the possibility of a laboratory- or research-related accident.

They also note that the selection process of international experts on the team did not adequately screen for conflicts of interest and that the skills represented in the team were purely focused on public health and zoonosis to the detriment of forensic skills suitable for investigating a laboratory- or research-related accident.

Also, the investigation’s terms of reference were significantly limited, the 26 scientists say. They stipulated, for instance, that most of the field work had to be conducted by the Chinese side with the results simply communicated to the international members of the joint team for review and discussion, in a format chosen by the Chinese side.

The 26 scientists say in their letter that, based on their analysis, “and as confirmed by the global study convened by the WHO and Chinese authorities”, there is as yet no evidence demonstrating a fully natural origin of SARS-CoV-2.

“The zoonosis hypothesis, largely based on patterns of previous zoonosis events, is only one of a number of possible SARS-CoV-2 origins, alongside the research-related accident hypothesis,” the scientists wrote.

The scientists say it must be made clear that any findings of the joint committee, while potentially useful to a limited extent, represent neither the official position of the WHO nor the result of an unrestricted, independent investigation.

They lay out in detail the core problems that they say undermined the investigation along with the way they consider a full and unrestricted investigation should be organised.

The governments of the US, Australia, Canada, Czechia, Denmark, Estonia, Israel, Japan, Latvia, Lithuania, Norway, the Republic of Korea, Slovenia, and the United Kingdom issued a statement yesterday saying they were voicing shared concerns that the WHO-China report was significantly delayed and the team 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,” the governments said.

“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.

“It is critical for independent experts to have full access to all pertinent human, animal, and environmental data, research, and personnel involved in the early stages of the outbreak relevant to determining how this pandemic emerged.”

The governments urged momentum for “expert-driven phase 2 studies”.  Going forward, they said, “there must now be a renewed commitment by WHO and all member states to access, transparency, and timeliness”.

The European Union also issued a statement, saying that it regretted “the late start of the study, the delayed deployment of the experts and the limited availability of early samples and related data”, but considered the work carried out to date and the WHO-China report as a helpful first step.

“We are looking forward to further engagement with the secretariat and the experts on the content of the report as well as on the implementation of its recommendations,” the EU said.

As outlined in the report, further work would have to be pursued to understand the origin of SARS-CoV-2 and its introduction into the human population, the EU added.

“This will require further and timely access to all relevant locations and to all relevant human, animal and environmental data available, including data from the first identified Covid-19 cases and cases picked up by surveillance systems, as well as further serologic testing of blood samples,” it said.

“We request the WHO to continue the studies and present a clear timeline for the follow-up work, and we wish to be regularly briefed on plans for, and progress of, its next phases. We also request that the DG allocate the resources necessary to complete this work.

“The identification of the source of the SARS-CoV-2 virus will require full and transparent cooperation by all WHO member states and a collaborative effort by scientists from various disciplines.”

At a press briefing on April 7 spokesman for the US Department of State Ned Price said the WHO-China report lacked crucial data, information, and access. “It represents a picture that is partial and, in our view, incomplete,” Price said.

The Department of State called on the WHO to re-evaluate the criteria and the terms of the study process, Price said.

Price said the Department of State urged the WHO to ensure that the second phase of the study commenced without further delay, including in China, “in a way that respects and adheres to principles of transparency and openness, is driven by experts, and is free from interference, including political interference”.

WHO team member Marion Koopmans, who dismisses the lab leak hypothesis, is seen admitting on camera in February 2020, in an interview, brought to public attention by the White Coat Waste Project. that researchers in labs in China were manipulating coronaviruses before the pandemic.

As a member of the scientific advisory board of the Centres for Disease control of Guangdong, China, Koopmans has advised on the building of the laboratory capacity for emerging infectious disease detection in the Guangdong region.

Koopmans has authored scientific research papers and journal articles backed by Chinese Communist Party grants.

In a biography provided by the WHO it’s stated that she has “ongoing research collaborations trying to unravel emergence and spread of viruses through the animal production chain in this region”.

New call for a full investigation

[UPDATE] A group of 24 scientists, social scientists, and science communicators, who include the signatories of the open letter published on March 4, published a second open letter on April 7 calling for a new inquiry into the origins of SARS-CoV-2 that would include biosafety and biosecurity experts, biodata analysts, and experienced forensic investigators.

“Calling for a full investigation into the origins of the pandemic by the best available means is not intended to point fingers at any one country,” the letter’s signatories said.

“Its purpose is to leave no stone unturned in seeking to understand how this catastrophe began so we can prioritise efforts to address our greatest shortcomings for the benefit of all people and all nations.”

The joint study team saw its priority as seeking a zoonotic origin, not as fully examining all possible sources of the pandemic, the letter’s authors state.

“Well over a year after the initial outbreak, critical records and biological samples that could provide essential insights into pandemic origins remain inaccessible,” they add. “This withholding of key resources that could and should have been made available undermined the credibility of the joint study team work.”

The letter’s signatories say they fully support the statement made by Tedros Adhanom Ghebreyesus on March 30 “that all origin hypotheses must still be examined, including the possibility of a lab-related incident, that China must be more forthright in sharing essential data and biological samples, and that the WHO is prepared to send additional missions and experts to China in order to thoroughly examine all origin hypotheses”.

They say the principles articulated by the WHO director-general and the statements made by 14 countries and the EU will require a renewed commitment by the WHO and all member states “to a full and unrestricted forensic and scientific investigation based on access, transparency, and timeliness”.

The letter’s authors – who hail from from France, Spain, the UK, Germany, the US, Australia, New Zealand, Belgium, India, and Japan – say this “essential goal” must be realised in at least one of three possible concrete steps.

They are calling for a revision of the existing terms of reference agreed by the WHO and China.

The revised terms should replace the veto power by any government over the composition of the team of international experts and there should be a provision requiring final decisions regarding the make-up of the international expert group to be made by the WHO executive board, the group says.

The international team should incorporate a wider skill set, including biosafety and biosecurity experts, biodata analysts, and experienced forensic investigators, they add.

The transparent selection of the team of experts must be guaranteed and there must be a more robust process for dealing with possible conflicts of interest, the group says.

“Such a process should prevent any conflict of interest involving prior professional association with laboratories and institutions relevant to the investigation,” the letter’s signatories write.

There should be an official mandate allowing international experts to request full or significant access to all sites, records, and samples of interest, and to interview relevant people without the presence of government authorities and with the assistance of translators provided by the WHO, the group adds.

“If these revisions cannot be agreed upon and implemented in the very near term, a second option would be for interested governments to propose a new resolution at the May 2021 World Health Assembly,” the letter’s signatories write.

They say a new resolution should call for the following:

  • an unrestricted international forensic and scientific investigation into the origins of the pandemic, fully examining all Covid-19 origin hypotheses, with full access to all records, samples, and personnel relevant to the investigation irrespective of location;
  • the timely and comprehensive sharing of raw data relevant to the emergence of Covid-19 within the framework of Open Science and the FAIR principles; and
  • improved national and international regulatory oversight of laboratories doing high-risk virology research, with specific emphasis on “gain-of -function research of concern”.

If it proves impossible for the terms of reference to be quickly revised or for a new and sufficient World Health Assembly resolution to be passed in the coming session, the best remaining alternative would be for governments seeking a full and credible examination into the origins of the pandemic to come together to develop a new and independent process, with China’s cooperation if possible, but without it if not, the group says.

The group says this process should outline what a full and unrestricted investigation of all origin hypotheses would entail, draw on the combined knowledge of government agencies and global experts to examine all the hypotheses to the fullest possible extent, and pool the knowledge and intelligence of cooperating governments in a collaborative effort to probe essential questions.

A secure whistleblower system should be established that allows scientists and others in China and other countries to share relevant information without fear of retribution, the group adds.

Also, transparent public hearings should be held that are designed to examine all hypotheses “in the most data-driven and responsible manner possible”, the letter’s signatories say.

The letter’s signatories point to numerous incorrect or contradictory statements made in Annex D7 of the WHO-China report.

They say that the deleted WIV database is wrongly described as an “Excel spreadsheet that had been on the website for 10 years” when it is “a 61.5MB MySQL database that had been released only a few years ago”. This database represents only one of multiple WIV databases that have been taken offline, the letter’s signatories say.

“Annex D7 states that the database was taken offline after being attacked by hackers,” the group writes. “On another occasion Prof. Shi Zhengli explicitly stated that the database was attacked by hackers during the pandemic and then taken offline.

“This is in contradiction with the fact that the database was taken offline on September 12, 2019, before the official start of the pandemic.”

The letter’s authors also point to the statement in Annex D7 that “none of [the viruses from the mine] has higher similarity to SARS-CoV-2 than the RaTG13 has”.

They write: “It is actually not possible to make such an assertion when the 7896 clade viruses are also very similar to SARS-CoV-2 based on their RdRp, but have still not been fully published more than a year after the start of the pandemic (only the short RdRp sections have been published).”

They add that, in Annex D7, the WIV director Yuan Zhiming categorically refutes any possibility of a laboratory leak of SARS-CoV-2. “Dr Yuan Zhiming had nevertheless repeatedly denounced structural issues with many labs in China before the pandemic,” they write.

The letter’s authors point out that the few visits detailed in the report’s annexes only cover some of the institutions in Wuhan with P2 and P3 labs that were known to be involved in BatCoV research.

“A proper investigation should first clearly identify and then cover all the labs in Wuhan that were actively working on BatCoVs in 2019 without exception, and also the Wuhan Institute of Biological Products (next door to the WIV), which may have been involved in a BatCoV vaccine development programme,” they write.

They add: “Annex D7 provides neither the nature nor the details of research involving bat coronaviruses in Wuhan laboratories in 2019 – including but not limited to possible BatCoV vaccine development programmes, pathogenicity studies involving animal experiments, usage of passaging, gain-of-function and genetic manipulation techniques –  which should be one of the very first steps towards rationally identifying some of the main risk factors in a lab-related accident scenario.”

The WHO-China report does not specify the number of people tested for antibodies (IgG) within the Wuhan Institute of Virology and other laboratories in Wuhan where research on bat coronaviruses was being carried out.

“From the results (all negative) we can only infer that a small fraction of the 590 WIV staff and students were actually tested,” the open letter signatories say.

“Indeed with the reported prevailing background antibodies (IgG) positive rate of around 4% in urban Wuhan around April 2020, the probability of no positive antibodies test (IgG+) amongst any reasonable number of potentially directly exposed staff and students becomes quickly extremely small, and is effectively null for the full population of 590,” they add.

“A proper review of tests should instead encompass all staff (including maintenance staff), all students, and all construction and temporary workers on site at the WIV, the WIPB, and at the other Wuhan P3 labs of interest, plus all sample collection staff (some of whom may not work at labs).”

In the arguments against the hypothesis that SARS-CoV-2 originated in a laboratory made in Annex D7 of the WHO-China report, it is stated that there is “no serological evidence of infection in workers through SARS-CoV-2-specific serology-screening”.

It is also stated that WIV staff had to report any symptoms every day after the outbreak of Covid-19 began.

“Serum samples were preserved annually for laboratory staff,” the report states.  There was extra testing during the Covid-19 outbreak, according to the laboratory director Yuang Zhiming, the report adds.

“There had been no reports of unusual diseases, none diagnosed, and all staff tested negative for SARS-CoV-2 antibodies,” it states.

Ben Embarek told Science magazine on February 14 this year that he was told that the serum from the staff of the WIV was retrospectively tested. “They tested samples from early 2019 and from 2020,” Ben Embarek said.

On July 15, 2020, Shi Zhengli told Science magazine in an emailed answer to the question “Is it possible that someone associated with the institute became infected in some other way, for instance while collecting, sampling, or handling bats?” that such a possibility did not exist.

Zhengli said: “Recently we tested the sera from all staff and students in the lab and nobody is infected by either bat SARSr-CoV or SARS-CoV-2. To date, there is ‘zero infection’ of all staff and students in our institute.”

Gilles Demaneuf says it would be extremely unlikely that there were no positives when WIV staff were tested in March 2020.

“Hence, the statement that nobody at the WIV tested positive for SARS-CoV-2 is very likely untrue and the WIV should provide case histories of the employees/students that did test positive,” he said.

“With near absolute certainty some employees or students of the WIV had been infected with SARS-CoV-2 by March 2020.”

Demaneuf says the situation is worse when one considers the four labs mentioned by Ben Embarek.

“The total staff and student population around these labs must be larger, by a few hundreds of individuals, than the WIV population,” Demaneuf said. “Any claim that nobody tested positive nor was infected in these four labs is mathematically strictly impossible, not to say absurd.”

Demaneuf suggests that either a very small number of people at the VIW were tested, which would make the testing totally irrelevant, or a larger number of people were tested and lies are being told about the results. “Necessarily quite a few of those tested would have been positive; it’s a mathematical certitude,” he said.

“It was stated in a Chinese research paper that the background antibody seropositivity level (IgG+) was about 4.4% for urban Wuhan in April 2020 and this is in line with other seropositivity estimates for Wuhan.”

The joint study team used different evidentiary standards for the four origin theories it considered, the open letter’s authors say.

“At this stage there is still no direct evidence for either pathway nor any verified data or evidence sufficient to rule any one out, while historical evidence amply supports both,” they write.

“In particular, a primary conclusion of the report, that SARS-CoV-2 was most probably introduced into the human population through an intermediate host, is not supported by the negative results of all the 80,000 tested samples of wildlife, livestock (35 species), and poultry. That pathway remains entirely theoretical, which at the very least shows the necessity to remain open to other pathways.”

The group says that the final process used by the joint study team for assessing the likelihood of the lab pathway – “essentially a show of hands by the joint study team members based on an extremely superficial review” – failed to reach some most basic standards of credible analysis and assessment.

At his press conference on April 8, the Chinese foreign ministry spokesman, Zhao Lijian, said the purpose of the two “so-called open letters” was “obviously to mount pressure on the WHO and the joint mission”.

Zhao Lijian said: “These signatories can deceive no one as to whether their letters are meant to make a true proposal for scientific and professional origin-tracing or target a specific country with presumption of guilt.”

He said the Chinese side had provided “an abundance of manpower and material support” to the joint mission.

“We fully respect and have made every effort to meet the requests independently put forward by the mission as to the places they would like to see,” he added. “China’s openness and transparency is well commended by the mission.”

Zhao Lijian said the origin-tracing study was indeed affected by political factors, but that did not come from China, but from the United States and some other countries, “who are bent on politicising the origin-tracing issue in an attempt to disrupt China’s cooperation with WHO and discredit China”.

Jamie Metzl, who is one of the letters’ signatories, tweeted the following:

[ENDS UPDATE]

Possible gain-of-function origin

On March 25, DRASTIC team members published a new paper about the possible lab origin of SARS-CoV-2.

In the paper published in Environmental Chemistry Letters, Rossana Segreto et al. say that, while a natural origin is still possible and the search for a potential host in nature should continue, “the amount of peculiar genetic features identified in SARS-CoV-2′s genome does not rule out a possible gain-of-function origin, which should be therefore discussed in an open scientific debate”.

Segreto et al. say that several characteristics of SARS-CoV-2 taken together are not easily explained by a natural zoonotic origin hypothesis. These include a low rate of evolution in the early phase of transmission; the lack of evidence for recombination events; a high pre-existing binding to human angiotensin-converting enzyme 2 (ACE2); a novel furin cleavage site (FCS) insert; a flat ganglioside-binding domain (GBD) of the spike protein that conflicts with host evasion survival patterns exhibited by other coronaviruses; and high human and mouse peptide mimicry.

Also, the researchers say, initial assumptions against a laboratory origin by contrast have remained unsubstantiated.

“Furthermore, over a year after the initial outbreak in Wuhan, there is still no clear evidence of zoonotic transfer from a bat or intermediate species,” Segreto et al. write. “Given the immense social and economic impact of this pandemic, identifying the true origin of SARS-CoV-2 is fundamental to preventing future outbreaks.

“The search for SARS-CoV-2′s origin should include an open and unbiased inquiry into a possible laboratory origin.”

The researchers say that the low binding affinity of SARS-CoV-2 to bat ACE2 studied to date does not support Chiroptera as a direct zoonotic agent.

“Furthermore, the reliance on pangolin coronavirus receptor binding domain (RBD) similarity to SARS-CoV-2 as evidence for natural zoonotic spillover is flawed, as pangolins are unlikely to play a role in SARS-CoV-2′s origin and recombination is not supported by recent analysis,” Segreto et al. write.

“At the same time, genomic analyses pointed out that SARS-CoV-2 exhibits multiple peculiar characteristics not found in other Sarbecoviruses.”

Segreto et al say that, although two pangolin coronaviruses exhibited strong binding to human ACE2,, binding to pangolin ACE2 was approximately tenfold weaker and binding to bat Rhinolophus ferremequinum ACE2 was very weak, with similar relative binding relationships exhibited by SARS-CoV-2.

“This indicates that neither pangolin coronavirus had adapted well to pangolins and that more research is required to validate the viability of coronaviruses to spread naturally between pangolins,” Segreto et al. write.

“Because of a 10–15% divergence throughout the entire spike protein with the exclusion of the N-terminal domain, Boni et al. (2020) concluded that SARS-CoV-2 is unlikely to be a recombinant of an ancestor of pangolin coronavirus and the closest SARS-CoV-2 relative, RaTG13.”

Segreto et al say that a novel multibasic furin cleavage site (FCS) confers numerous pathogenetically advantageous capabilities, the existence of which is difficult to explain though natural evolution.

SARS-CoV-2 to human ACE2 binding is far stronger than SARS-CoV, yet there is no indication of an amount of evolutionary adaptation that SARS-CoV or MERS-CoV underwent, they add.

The researchers also point to the flat topography of the GBD in the N-terminal domain (NTD) of SARS-CoV-2, which they say does not conform with typical host evasion evolutionary measures exhibited by other human coronaviruses.

“The combination of binding strength, human and mouse peptide mimicry, as well as high adaptation for human infection and transmission from the earliest strains might suggest the use of humanised mice for the development of SARS-CoV-2 in a laboratory environment,” Segreto et al. add.

Segreto et al. also say that imported frozen food contaminated with SARS-CoV-2 is an “exceedingly unlikely source of the initial outbreak in Wuhan”.

The Mojiang mine

Monali Rahalkar says that the fact that researchers from the Wuhan Institute of Virology collected the RaTG13 sample supports the lab origin hypothesis.

In a preliminary abstract published on September 17 in Frontiers in Public Health, Rahalkar (pictured left) and Rahul A. Bahulikar say that RaTG13 (RaBtCoV/4991) was collected from the Tongguan mineshaft in Mojiang, Yunnan, in 2013.

“Surprisingly, the same mineshaft was also associated with a severe pneumonia-like illness in miners in 2012 killing three of the six miners,” Rahalkar and Bahulikar write.

“A master’s thesis (in the Chinese language) was found on the cnki.net website which described in detail the severe illness in miners. The thesis concluded that a SARS-like CoV originating from Chinese horseshoe bats (Rhinolophus) was the predicted causative agent.”

The thesis was written by the Chinese doctor, Li Xu, who treated the miners and sent their tissue samples to the WIV for testing, and was published in May 2013.

Rahalkar and Bahulikar explain that the cases were remotely monitored by a prominent pulmonologist in China.

“The 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,” Rahalkar and Bahulikar write.

‘The treatment regimes were similar to the currently given treatment for Covid-19. We propose that the Mojiang mineshaft and the miners’ illness cases could provide important clues to the investigation of the origin of SARS-CoV-2.”

In their full, peer-reviewed article, published in Frontiers in Public Health on October 20, Rahalkar and Bahulikar write that the striking similarities between the Mojiang pneumonia cases and Covid-19 are noteworthy, “as is the fact that RaTG13/CoV4991, the next genomic relative of SARS-CoV-2 was found in the same mineshaft”.

The two researchers write: “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.

“The coincidence between the 2012 illness in Mojiang miners, the subsequent samplings, and finding the nearest SARS-CoV-2 relative from this single mine warrants further inquiry, and the data along with the full history of this incident would be invaluable in the context of the current pandemic.”

Rahalkar and Bahulikar go into detail about Li Xu’s master’s thesis, in which he concluded that “the pneumonia cases were due to viral pneumonia, primarily from SARS-like coronaviruses originating from horseshoe bats”.

“Three of the miners died in the course of ~100 days and three survived. The thesis featured medical reports, radiological images such as CT scans, and detailed information regarding the diagnosis and treatment of the miners.”

Radiography showed interstitial pneumonia, ground-glass opacities, and severe acute respiratory distress syndrome (ARDS) in some of the patients and some showed clotting complications such as pulmonary thromboembolism or thrombosis and elevated D-dimer values.

Dr Zhong Nanshan, an expert in respiratory diseases and a national advisor about the SARS and Covid-19 epidemics, provided remote consultation for the two patients who had the most serious illness.

Nanshan’s conclusion that the Mojiang miners’ pneumonia appeared to be primarily viral and that it was most probably due to bat-related coronaviruses, is noteworthy, Rahalkar and Bahulikar say.

Rahalkar and Bahulikar add that, according to a translation of a PhD thesis by Canping Huang, supervised by George Gao, the “blood test results of four cases showed that: four people carried SARS virus IgG antibodies, of which two were discharged with higher antibody levels … and two which were hospitalised had lower antibody levels …”.

Rahalkar and Bahulikar ask: “Why were the severe pneumonia cases in 2012 not mentioned in any of the WIV publications before 2020?’ and ‘Were any SARS-like CoV isolated from the bat faecal samples collected in 2012–13?’.

They also ask why the Mojiang miners pneumonia cases in 2012 were not reported to any public health agency such as the WHO and why programmes like PREDICT didn’t mention the lethal pneumonia cases as a mini-outbreak.

Rahalkar has issued a detailed critique of an addendum that has been added to the article published by Zhou Peng, Shi Zhengli et al. in Nature on February 3, 2020, entitled A pneumonia outbreak associated with a new coronavirus of probable bat origin’.

The addendum was published in Nature on November 17 and provides further information about RaTG13.

In the original paper, the researchers said they obtained full-length genome sequences from five patients at an early stage of the outbreak in Wuhan.

“The sequences are almost identical and share 79.6% sequence identity to SARS-CoV,” Zhengli et al. said.

The researchers said that a short region of RdRp from BatCoV RaTG13 showed high sequence identity to 2019-nCoV.

“Simplot analysis showed that 2019-nCoV was highly similar throughout the genome to RaTG13, with an overall genome sequence identity of 96.2 percent,” they said. The SARS-CoV-2 genome and its spike glycoprotein show 96.11% and 92.86% identities to the Rhinolophus affinis bat coronavirus, respectively.

In her critique of the addendum, Rahalkar states: “For the first time the WIV authors admit that the Mojiang mineshaft miners had severe respiratory disease. Further they also tell us that they collected the sample which they renamed RaTG13 from the same mineshaft.

“This is the first written evidence that WIV agrees that they collected a virus or a sample, which is until now the closest neighbour of SARS-CoV-2, from a mineshaft. And that the same mineshaft was the reason why the miners, or people working cleaning the mine, got ill.”

Rahalkar asks why the information presented in the addendum is coming nine and a half months after the original article was published.

Rahalkar challenges the statement in the addendum about patient samples testing negative for SARS antibodies. Referring to the PhD thesis by Canping Huang, she says he clearly wrote that the four miners tested positive for SARS IgG antibodies.

She also points out that there is no reference in the addendum to the fact that six miners fell ill and three of them died. “The addendum fails to give any account of the death of the other two miners,” Rahalkar writes.

“There are CT scans in the master’s thesis identical to those of Covid-19 patients,” she said.

WIV researchers state in the paper by Ge Xing-Yi in 2016 that they only discovered one SARS-like CoV, when they had in fact found eight more, Rahalkar adds. No details about these eight SARS-like CoVs are given in the addendum, she says. No IDs or sequences are provided.

Segreto asks in a tweet: “Why it is not disclosed in the Addendum of the Zhou paper that the other 8 betaCoVs identified with RaTG13 belong to the 7896 group but #DRASTIC had to discover it? Why they do not release their spike’s sequence? Why the access to that cave is blocked?”

In Annex D7 (Wuhan Institute of Virology) the WHO-China report’s authors refer to the “matter of morbidity and mortality in miners in a mine in Mojiang, Yunnan Province”. They place their remarks under the title ‘Conspiracy theories’.

The authors write that doctors sent Shi Zhengli the samples for testing after the miners had been ill for about three months. Miners had been to the cave two or three times and the cave was one metre thick with bat faeces, they add.

“Professor Shi’s team went there in 2012–15 about seven times to look for novel viruses. They found no viruses close to SARS-CoV but there was a rat henipa-like virus (Mojiang paramyxovirus), as reported by another group in China,” they write.

“Samples taken during subsequent visits to the cave were found to contain no viral sequence related to SARS-CoV-2 (like RaTG13),” the authors said. “None of them has higher similarity to SARS-CoV-2 than the RaTG13 has.”

The authors conclude that none of these viruses are the progenitor virus of SARS-CoV-2. This would usually entail more than 99% genome similarity, they say.

“None could be isolated,” the WHO-China authors write. “The reported illnesses associated with the miners, according to the WIV experts, were more likely explained by fungal infections acquired when removing a thick layer of guano.”

In an article about the controversies in Annex D7, Rahalkar points out that the authors of the WHO-China report “assume” that all the coronavirus research was done in P3 and P4 laboratories. On the contrary, she says, Shi Zhengli said that all the coronavirus research conducted in Wuhan was done in P2 and P3 labs (Q and A in Science magazine, July 2020).

Rahalkar points to the article in Frontiers in Public Health that she co-wrote, which goes into comprehensive detail about the six Mojiang miners, and to the PhD thesis by Canping Huang in which it is stated that four of them carried SARS virus IgG antibodies.

There is evidence in the PhD thesis and elsewhere, she says, that is completely at odds with claims in the WHO-China report for which “no further support (medical or other documents)” is provided. that the miners most likely had fungal infections.

“They disregard what Dr Zhong Nanshan said: that the miners had primary viral infection most likely due to the bat coronaviruses and the fungal infections were secondary,” Rahalkar said.

“The WIV skilfully does not mention either the master’s thesis by Li Xu or the PhD thesis by Canping Huang.

“If fungus was the primary cause, it has to be proven by aspiration of the fluid and cultivation of the causative fungus, and its identification. No such work, supporting its statements, has been demonstrated by the WIV.”

The authors of the WHO-China report have completely overlooked the fact that SARS-CoV-2’s  nearest neighbour, RaTG13, was collected from a cave where miners got a Covid-19-like illness, Rahalkar says.

In addition, she says, it’s stated in Annex D7 that the miners had been to the cave two or three times, but, according to Li Xu’s master thesis, four of them worked 12 hours a day for 14 days and the others worked there for four to five days.

Rahalkar is curious to know what kind of samples the WIV received from the Mojiang miners, whether the samples are still stored in the WIV, and whether they are available for study by other researchers.

“It would also be of particular value to know whether any viruses were isolated and if there is any DNA/RNA available from these samples,” she said. “It would also be useful to know if PCR was performed on the miners’ samples.” When was the mineshaft in Mojiang closed down? she asks.

The list of questions continues: “Why was the Mojiang mine being visited by researchers until October 2014? Was the mine open for researchers and were any samples brought after 2014? Did any of the researchers who visited the Mojiang mineshaft get infected by any coronavirus between 2012 and 2019? Are there any whole genome sequences available for SARS-like CoV originating from this mine?”

Recently, more than eight news reporters were blocked from visiting the Tongguan mine, Rahalkar points out. “Why didn’t the WHO team visit the mine and recommend resampling?” she asks.

In May 2013, China’s Ministry of Science and Technology initiated a project (2013FY113500) to identify and investigate viral pathogens and their relation with major infectious diseases. “Why is the pathogen database associated with this project not accessible anymore?” Rahalkar asks.

Rahalkar also takes issue with the statement in the WHO-China report that “all fieldwork is done with full PPE”. Numerous photos of WIV researchers show that this was not the case, she says.

Conflict of interest

DRASTIC members point out that the WHO’s terms of reference do not even mention a possible laboratory origin. They also highlight Peter Daszak’s serious conflict of interest.

Referring to an early draft of the letter published in The Lancet, Daszak (pictured left) said in an email sent on February 6, 2020: “I’ve not seen the final version yet, but the draft version that we (and expert group that met last week) edited has the following sentence: ‘The initial views of the experts is [sic] that the available genomic data are consistent with natural evolution and that there is currently no evidence that the virus was engineered to spread more quickly among humans.’

“I think this is a bit too specific, because there are other conspiracy theories out there. Our current statment [sic] neatly refutes most of them by saying that ‘We stand together to strongly condemn conspiracy theories suggesting that 2019-nCoV does not have a natural origin.

“Scientific evidence overwhelmingly suggests that this virus originated in wildlife, as have so many other emerging diseases’.”

Daszak added: “Please note that this statement will not have EcoHealth Alliance logo on it and will not be identifiable as coming from any one organization or person, the idea is to have this as a community supporting our colleagues.”

The email from Daszak was obtained by the investigative research group U.S. Right to Know.

In another email obtained by ‘U.S. Right to Know’ Daszak tells University of North Carolina researcher Ralph Baric that they should not sign the statement condemning the lab-origin theory.

“I spoke with Linfa last night about the statement we sent round. He thinks, and I agree with him, that you, me and him should not sign this statement, so it has some distance from us and therefore doesn’t work in a counterproductive way,” Daszak wrote.

Daszak continued: ” I’ll send it round some other key people tonight. We’ll then put it out in a way that doesn’t link it back to our collaboration so we maximize an independent voice.”

Baric agreed with Daszak’s suggestion not to sign the statement, writing back: “Otherwise it looks self-serving and we lose impact.” Daszak did ultimately sign the statement, but he was not identified as its lead author or coordinator.

In an interview with virologist Vincent Racaniello on December 9, 2019, Daszak talks openly about manipulating coronaviruses in the lab: “Coronaviruses are pretty good … you can manipulate them in the lab pretty easily.

“Spike protein drives a lot of what happens with a coronavirus; zoonotic risk. So you can get the sequence; you can build the protein; and we work with Ralph Baric at UNC [The University of North Carolina] to do this. Insert into the backbone of another virus and do some work in the lab.”

Alina Chan and Matt Ridley wrote in an article published in the Wall Street Journal on January 15 that a spokesman for Daszak told them: “The Lancet letter was written during a time in which Chinese scientists were receiving death threats and the letter was intended as a showing of support for them as they were caught between important work trying to stop an outbreak and the crush of online harassment.”

However, Ridley, who is a journalist, businessman, author, and member of the UK’s House of Lords, and Chan, who is a postdoctoral fellow at the Broad Institute of MIT and Harvard in the US and is one of the signatories of the open letter published on March 4, point out that Daszak wrote an opinion piece in June for The Guardian headlined “Ignore the conspiracy theories: scientists know Covid-19 wasn’t created in a lab”.

Daszak is also leading The Lancet Covid-19 commission’s task force, which was set up to investigate the origins of SARS-CoV-2.

Ridley and Chan tweeted the following on March 29:

Ridley said in a radio interview: “We were expecting a whitewash and a whitewash is what we’ve got.

“We’ve got a report that, in 300 pages, dismisses, in one paragraph, as very unlikely the idea that the virus leaked out of a laboratory, but then spends twenty or thirty pages going into great detail about how 45,000 animals … poultry and wildlife and things have been tested in China, all found negative, yet nonetheless concludes that it’s very likely that one of them carried the virus to Wuhan.”

The main research that is cited in defence of the natural-origin hypothesis is that conducted by Kristian G. Andersen et al. who say it is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related coronavirus. Andersen et al’s findings have been challenged, however.

Senate Bill calls for report on SARS-CoV-2 origin

A bipartisan Bill has been introduced in the US Senate that calls for a report on the origins of the Covid-19 pandemic that includes “a detailed account of information known to the United States government regarding the WIV and associated facilities, including research activities on coronaviruses and gain-of-function research, any reported illnesses of persons associated with the laboratory with symptoms consistent with Covid-19 and the ultimate diagnosis, and a timeline of research relevant to coronaviruses”.

The Bill was introduced by Senator Robert Menendez, who chairs the Senate Foreign Relations Committee, and Senator Jim Risch.

The Bill says the report, which would be submitted to the appropriate Congress committees, should also include an overview of US engagement with the People’s Republic of China (PRC) with respect to coronaviruses that includes a “detailed accounting of United States engagement with the WIV and similar labs in the PRC specific to coronaviruses”, including a detailed accounting of research and funding sponsored by the US government.

There should also be an assessment of “any additional scrutiny of United States government funding to support gain-of-function research in the PRC after the moratorium on such funding was lifted in 2017” and whether US government funding was used to support gain-of-function research in China during the moratorium on gain-of-function research from 2014 to 2017, the Bill states.

The Bill says there should be an assessment of the most likely origin of SARS-CoV-2, including a detailed review of all information the US possesses that it has identified as potentially relevant to the source or origin of SARS-CoV-2, “including zoonotic transmission and spillover, the Wuhan Institute of Virology (WIV), or other sources of origin, transmission, or spillover, based on the information the United States government has to date”.

The Bill says the US government should identify the leading credible theories about the aetiology of SARS-CoV-2 and indicate the steps it has taken to validate those theories.

The government should also indicate any variance in assessment or dissent among or between US intelligence agencies, executive agencies, and executive offices about the most likely source or origin of SARS-CoV-2, and the basis for such variance or dissent, the Bill states.

The Bill also says the US government should describe all steps it has taken to identify and investigate the source of SARS-CoV-2, including a timeline of such efforts and a detailed description of the data that the US and the WHO have requested and have access to in order to determine the origin of SARS-CoV-2.

There should also be an account of efforts by the PRC “to cooperate with, impede, or obstruct” any inquiry or investigation to determine the source and transmission of SARS-CoV-2, including into a possible lab leak, or, by the PRC or the Chinese Communist Party, including by national and local governmental and health entities, “to create or spread misinformation or disinformation” regarding the source and transmission of SARS-CoV-2.

The Bill states that “it is critical to understand the origins of the Covid–19 pandemic so the United States can better prepare, prevent, and respond to pandemic health threats in the future”.

It adds: “Congress shares the concerns expressed by the United States government and 13 other foreign governments that the international team of experts dispatched to the People’s Republic of China by the World Health Organisation … to study the origins of the SARS-CoV-2 virus was ‘significantly delayed and lacked access to complete, original data and samples’.”

The WHO-China report lays out the following four scenarios, giving the evidence for and against each hypothesis:

Direct zoonotic transmission 

Some of the arguments cited in support of this hypothesis 

  • Most emerging diseases originate from animal reservoirs and there is strong evidence that most of the current human coronaviruses have originated from animals.
  • Surveys of the bat virome conducted following the SARS epidemic in 2003 have found SARSr-CoV in various bats, particularly Rhinolophus bats, and viruses with the high genetic similarity to SARS-CoV-2 have been found in Rhinolophus bats sampled in China in 2013, Japan in 2013, Thailand in 2020, and Cambodia in 2010.
  • Recently, two distinct types of SARSr-CoV were detected in Malayan pangolins. The RaTG13 and pangolin coronaviruses do bind to human ACE2, although the fit is not optimal.
  • Seeding of SARS-CoV-2 in mink populations has shown that mink are highly susceptible and, given the available evidence, the possibility that minks are the primary source of SARS-CoV-2 cannot be ruled out.

 Arguments against 

  • Although many betacoronavirus sequences have been found in a range of bats, isolation of viruses from them is rare, and only a few of the identified full genomes have human ACE2 binding properties.
  • Because several contact residues between the bat and pangolin viruses and the human ACE2 receptor are distinct from those in SARS-CoV-2, the affinity is low, and the viruses are genetically still quite distinct from SARS-CoV-2.
  • The link with, and focus on, bats may be spurious as far less sampling has been done of other animal species.
  • Contacts between humans and bats or pangolins are not likely to be as common as contact between humans and livestock or farmed wildlife, and virus presence in host animals is likely variable and seasonal, further decreasing the likelihood of an infectious contact.
  • Despite the consumption of bat and other wild animal meat in some countries, there is no evidence for the transmission of coronaviruses from such encounters, and the trace-back investigation found no evidence for the presence of bats or pangolins (or their products) in the Huanan market.

Introduction via an intermediate host followed by zoonotic transmission

Some of the arguments cited in support of this hypothesis 

  • Although the closest related viruses have been found in bats, the evolutionary distance between these bat viruses and SARS-CoV-2 is estimated to be several decades, suggesting a missing link (either a missing progenitor virus, or evolution of a progenitor virus in an intermediate host).
  • An intermediary step involving an amplifying host has been observed for several other emerging viruses (henipaviruses, influenza viruses, SARS-CoV, and MERS-CoV).
  • The increasing number of animals shown to be susceptible to SARS-CoV-2 includes animals that are farmed in sufficient densities to allow potential for enzootic circulation.

 Arguments against 

  • SARS-CoV-2 has been identified in an increasing number of animal species, but genetic and epidemiological studies have suggested that these were infections introduced from humans rather than enzootic virus circulation.
  • Based on epidemiological analysis and genetic sequencing of viruses from new cases throughout 2020, there is no evidence of repeated introduction of early SARS-CoV-2 strains of potential animal origins into humans in China.
  • There was no genetic or serological evidence for SARS-CoV-2 in a wide range of domestic and wild animals tested to date.
  • The screening of the major livestock species was done across the country and provided no evidence for circulation of a related virus.

 Introduction through the cold/food chain

Some of the arguments cited in support of this hypothesis 

  • Since the near-elimination of SARS-CoV-2 in China, the country experienced some outbreaks related to imported frozen products in 2020.
  • Screening programmes found some limited evidence for the presence of SARS-CoV-2 in different batches of unopened packages and containers.
  • Foodborne outbreaks with enteric viruses are common and – when entering the food supply – may lead to geographically dispersed outbreaks that can be difficult to detect.
  • Although typical foodborne infections are thought to be restricted to enteric pathogens (pathogens in the intestines), there is some evidence that the oral route could lead to SARS-CoV-2 infection.

 Arguments against 

  • There is no conclusive evidence for foodborne transmission of SARS-CoV-2 and the probability of cold chain contamination with the virus from a reservoir is very low.
  • Industrial food production has high levels of hygiene criteria and is regularly audited.
  • In 2020, most viruses were found in low concentrations and are not amplified on cold chain products
  • There is no evidence of infection in any of the animals tested after the Wuhan outbreak.

 Introduction through a laboratory incident

Some of the arguments cited in support of this hypothesis 

  • Although rare, laboratory accidents do happen, and different laboratories around the world are working with bat CoVs.
  • When working in particular with virus cultures, but also with animal inoculations or clinical samples, humans could become infected in laboratories with limited biosafety or poor laboratory management practice, or if there is negligence.
  • RaTG13, detected in bat anal swabs, has been sequenced at the Wuhan Institute of Virology.
  • The Wuhan CDC laboratory moved on December 2, 2019, to a new location near the Huanan market. Such moves can be disruptive for the operations of any laboratory.

 Arguments against

  • Human ACE2 receptor binding and a furin cleavage site in SARS-CoV-2 have been found in animal viruses and elements of the furin cleavage site are present in RmYN02 and the new Thailand bat SARSr-CoV.
  • The WHO team says the laboratories in Wuhan in which researchers were working with either CoVs diagnostics and/or CoVs isolation and vaccine development all had high-quality biosafety level facilities that were well managed.
  • No disruptions or incidents were reported in relation to the Wuhan CDC laboratory’s move.

 

Report annexes can be accessed here.

Members of the WHO investigating team

Peter Daszak

Daszak is a zoologist and president of the EcoHealth Alliance. He is also leading The Lancet Covid-19 commission’s task force investigating the origins of SARS-CoV-2.

Marion Koopmans

Koopmans is a Dutch virologist who heads the Erasmus Medical Centre’s Department of Viroscience in Rotterdam. She is a member of the WHO’s scientific advisory group and has been involved in tracing outbreaks of Sars-CoV-2 among farmed minks in the Netherlands.

Vladimir Dedkov 

Dedkov is an epidemiologist. He is the deputy director for research at the Pasteur Institute in Saint Petersburg in Russia.

Dominic Dwyer 

Dwyer is a medical virologist and director of the Centre for Infectious Diseases and Microbiology Laboratory Services at Westmead Hospital in Sydney, Australia. He has advised the Australian government on pandemic preparedness and worked with the WHO during the SARS outbreak in Beijing. He’s a member of the WHO’s Global Outbreak Alert and Response Network (GOARN).

John Watson

Watson is an epidemiologist and doctor who is an honorary professor at the London School of Hygiene and Tropical Medicine and a visiting lecturer at University College London.  He headed the UK’s infectious disease surveillance and control programme for 24 years and was formerly England’s deputy chief medical officer

Thea Kølsen Fischer 

Fischeris a professor in viral epidemics and infections at the University of Copenhagen and head of research at the Nordsjællands Hospital in Denmark.

Farag El Moubasher

El Moubasher is an epidemiologist who heads the infectious diseases control programme in Qatar’s Ministry of Public Health.

Hung Nguyen-Viet 

Nguyen-Viet is an ecologist who is co-leader of the animal and human health programme at the International Livestock Research Institute in Vietnam.

Ken Maeda 

Maeda is a veterinary microbiologist at Japan’s National Institute of Infectious Diseases. He has published research on such topics as the Japanese encephalitis virus and novel viruses found in bats.

Fabian Leendertz

Leendertz is a vet by training. At Germany’s Robert Koch Institute, he has led research into highly pathogenic microorganisms in tropical Africa since 2007. A particular focus of his work is how diseases jump from wild, non-human primates to humans.

The international team also included five WHO experts led by Peter Ben Embarek; two Food and Agriculture Organization (FAO) representatives and two World Organisation for Animal Health (OIE) representatives.

My original article, ‘SARS-CoV-2: lab-origin hypothesis gains traction’, which includes comprehensive information about previsous laboratory leaks, can be found here and there is a French translation (before updates) @ France Soir.  


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