Screw your freedom and wear mask
by Arnold Schwarzenegger
August 11, 2021
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“When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus,” said David Baltimore, an eminent virologist and former president of CalTech. “These features make a powerful challenge to the idea of a natural origin for SARS2,” he said.
1) The place of origin. Start with geography. The two closest known relatives of the SARS2 virus were collected from bats living in caves in Yunnan, a province of southern China. If the SARS2 virus had first infected people living around the Yunnan caves, that would strongly support the idea that the virus had spilled over to people naturally. But this isn’t what happened. The pandemic broke out 1,500 kilometers away, in Wuhan.
Beta-coronaviruses, the family of bat viruses to which SARS2 belongs, infect the horseshoe bat Rhinolophus affinis, which ranges across southern China. The bats’ range is 50 kilometers, so it’s unlikely that any made it to Wuhan. In any case, the first cases of the COVID-19 pandemic probably occurred in September, when temperatures in Hubei province are already cold enough to send bats into hibernation.
What if the bat viruses infected some intermediate host first? You would need a longstanding population of bats in frequent proximity with an intermediate host, which in turn must often cross paths with people. All these exchanges of virus must take place somewhere outside Wuhan, a busy metropolis which so far as is known is not a natural habitat of Rhinolophus bat colonies. The infected person (or animal) carrying this highly transmissible virus must have traveled to Wuhan without infecting anyone else. No one in his or her family got sick. If the person jumped on a train to Wuhan, no fellow passengers fell ill.
It’s a stretch, in other words, to get the pandemic to break out naturally outside Wuhan and then, without leaving any trace, to make its first appearance there.
For the lab escape scenario, a Wuhan origin for the virus is a no-brainer. Wuhan is home to China’s leading center of coronavirus research where, as noted above, researchers were genetically engineering bat coronaviruses to attack human cells. They were doing so under the minimal safety conditions of a BSL2 lab. If a virus with the unexpected infectiousness of SARS2 had been generated there, its escape would be no surprise.
2) Natural history and evolution. The initial location of the pandemic is a small part of a larger problem, that of its natural history. Viruses don’t just make one time jumps from one species to another. The coronavirus spike protein, adapted to attack bat cells, needs repeated jumps to another species, most of which fail, before it gains a lucky mutation. Mutation — a change in one of its RNA units — causes a different amino acid unit to be incorporated into its spike protein and makes the spike protein better able to attack the cells of some other species.
Through several more such mutation-driven adjustments, the virus adapts to its new host, say some animal with which bats are in frequent contact. The whole process then resumes as the virus moves from this intermediate host to people.
In the case of SARS1, researchers have documented the successive changes in its spike protein as the virus evolved step by step into a dangerous pathogen. After it had gotten from bats into civets, there were six further changes in its spike protein before it became a mild pathogen in people. After a further 14 changes, the virus was much better adapted to humans, and with a further four, the epidemic took off.
But when you look for the fingerprints of a similar transition in SARS2, a strange surprise awaits. The virus has changed hardly at all, at least until recently. From its very first appearance, it was well adapted to human cells. Researchers led by Alina Chan of the Broad Institute compared SARS2 with late stage SARS1, which by then was well adapted to human cells, and found that the two viruses were similarly well adapted. “By the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV,” they wrote.
Even those who think lab origin unlikely agree that SARS2 genomes are remarkably uniform. Baric writes that “early strains identified in Wuhan, China, showed limited genetic diversity, which suggests that the virus may have been introduced from a single source.”
A single source would of course be compatible with lab escape, less so with the massive variation and selection which is evolution’s hallmark way of doing business.
The uniform structure of SARS2 genomes gives no hint of any passage through an intermediate animal host, and no such host has been identified in nature.
Proponents of natural emergence suggest that SARS2 incubated in a yet-to-be found human population before gaining its special properties. Or that it jumped to a host animal outside China.
All these conjectures are possible, but strained. Proponents of a lab leak have a simpler explanation. SARS2 was adapted to human cells from the start because it was grown in humanized mice or in lab cultures of human cells, just as described in Daszak’s grant proposal. Its genome shows little diversity because the hallmark of lab cultures is uniformity.
Proponents of laboratory escape joke that of course the SARS2 virus infected an intermediary host species before spreading to people, and that they have identified it — a humanized mouse from the Wuhan Institute of Virology.
3) The furin cleavage site. The furin cleavage site is a minute part of the virus’s anatomy but one that exerts great influence on its infectivity. It sits in the middle of the SARS2 spike protein. It also lies at the heart of the puzzle of where the virus came from.
The spike protein has two sub-units with different roles. The first, called S1, recognizes the virus’s target, a protein called angiotensin converting enzyme-2 (or ACE2) which studs the surface of cells lining the human airways. The second, S2, helps the virus, once anchored to the cell, to fuse with the cell’s membrane. After the virus’s outer membrane has coalesced with that of the stricken cell, the viral genome is injected into the cell, hijacks its protein-making machinery and forces it to generate new viruses.
But this invasion cannot begin until the S1 and S2 subunits have been cut apart. And there, right at the S1/S2 junction, is the furin cleavage site that ensures the spike protein will be cleaved in exactly the right place.
The virus, a model of economic design, does not carry its own cleaver. It relies on the cell to do the cleaving for it. Human cells have a protein cutting tool on their surface known as furin. Furin will cut any protein chain that carries its signature target cutting site. This is the sequence of amino acid units proline-arginine-arginine-alanine, or PRRA in the code that refers to each amino acid by a letter of the alphabet. PRRA is the amino acid sequence at the core of SARS2’s furin cleavage site.
Viruses have all kinds of clever tricks, so why does the furin cleavage site stand out? Because of all known SARS-related beta-coronaviruses, only SARS2 possesses a furin cleavage site. All the other viruses have their S2 unit cleaved at a different site and by a different mechanism.
How then did SARS2 acquire its furin cleavage site? Either the site evolved naturally, or it was inserted by researchers at the S1/S2 junction in a gain-of-function experiment.
Consider natural origin first. Two ways viruses evolve are by mutation and by recombination. Mutation is the process of random change in DNA (or RNA for coronaviruses) that usually results in one amino acid in a protein chain being switched for another. Many of these changes harm the virus but natural selection retains the few that do something useful. Mutation is the process by which the SARS1 spike protein gradually switched its preferred target cells from those of bats to civets, and then to humans.
Mutation seems a less likely way for SARS2’s furin cleavage site to be generated, even though it can’t completely be ruled out. The site’s four amino acid units are all together, and all at just the right place in the S1/S2 junction. Mutation is a random process triggered by copying errors (when new viral genomes are being generated) or by chemical decay of genomic units. So it typically affects single amino acids at different spots in a protein chain. A string of amino acids like that of the furin cleavage site is much more likely to be acquired all together through a quite different process known as recombination.
Recombination is an inadvertent swapping of genomic material that occurs when two viruses happen to invade the same cell, and their progeny are assembled with bits and pieces of RNA belonging to the other. Beta-coronaviruses will only combine with other beta-coronaviruses but can acquire, by recombination, almost any genetic element present in the collective genomic pool. What they cannot acquire is an element the pool does not possess. And no known SARS-related beta-coronavirus, the class to which SARS2 belongs, possesses a furin cleavage site.
Proponents of natural emergence say SARS2 could have picked up the site from some as yet unknown beta-coronavirus. But bat SARS-related beta-coronaviruses evidently don’t need a furin cleavage site to infect bat cells, so there’s no great likelihood that any in fact possesses one, and indeed none has been found so far.
The proponents’ next argument is that SARS2 acquired its furin cleavage site from people. A predecessor of SARS2 could have been circulating in the human population for months or years until at some point it acquired a furin cleavage site from human cells. It would then have been ready to break out as a pandemic.
If this is what happened, there should be traces in hospital surveillance records of the people infected by the slowly evolving virus. But none has so far come to light. According to the WHO report on the origins of the virus, the sentinel hospitals in Hubei province, home of Wuhan, routinely monitor influenza-like illnesses and “no evidence to suggest substantial SARSCoV-2 transmission in the months preceding the outbreak in December was observed.”
So it’s hard to explain how the SARS2 virus picked up its furin cleavage site naturally, whether by mutation or recombination.
That leaves a gain-of-function experiment. For those who think SARS2 may have escaped from a lab, explaining the furin cleavage site is no problem at all. “Since 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory,” writes Steven Quay, a biotech entrepreneur interested in the origins of SARS2. “At least 11 gain-of-function experiments, adding a furin site to make a virus more infective, are published in the open literature, including [by] Dr. Zhengli Shi, head of coronavirus research at the Wuhan Institute of Virology.”
4) A question of codons. There’s another aspect of the furin cleavage site that narrows the path for a natural emergence origin even further.
As everyone knows (or may at least recall from high school), the genetic code uses three units of DNA to specify each amino acid unit of a protein chain. When read in groups of 3, the 4 different kinds of DNA unit can specify 4 x 4 x 4 or 64 different triplets, or codons as they are called. Since there are only 20 kinds of amino acid, there are more than enough codons to go around, allowing some amino acids to be specified by more than one codon. The amino acid arginine, for instance, can be designated by any of the six codons CGU, CGC, CGA, CGG, AGA or AGG, where A, U, G and C stand for the four different kinds of unit in RNA.
Here’s where it gets interesting. Different organisms have different codon preferences. Human cells like to designate arginine with the codons CGT, CGC or CGG. But CGG is coronavirus’s least popular codon for arginine. Keep that in mind when looking at how the amino acids in the furin cleavage site are encoded in the SARS2 genome.
Now the functional reason why SARS2 has a furin cleavage site, and its cousin viruses don’t, can be seen by lining up (in a computer) the string of nearly 30,000 nucleotides in its genome with those of its cousin coronaviruses, of which the closest so far known is one called RaTG13. Compared with RaTG13, SARS2 has a 12-nucleotide insert right at the S1/S2 junction. The insert is the sequence T-CCT-CGG-CGG-GC. The CCT codes for proline, the two CGG’s for two arginines, and the GC is the beginning of a GCA codon that codes for alanine.
There are several curious features about this insert but the oddest is that of the two side-by-side CGG codons. Only 5 percent of SARS2’s arginine codons are CGG, and the double codon CGG-CGG has not been found in any other beta-coronavirus. So how did SARS2 acquire a pair of arginine codons that are favored by human cells but not by coronaviruses?
Proponents of natural emergence have an up-hill task to explain all the features of SARS2’s furin cleavage site. They have to postulate a recombination event at a site on the virus’s genome where recombinations are rare, and the insertion of a 12-nucleotide sequence with a double arginine codon unknown in the beta-coronavirus repertoire, at the only site in the genome that would significantly expand the virus’s infectivity.
“Yes, but your wording makes this sound unlikely — viruses are specialists at unusual events,” is the riposte of David L. Robertson, a virologist at the University of Glasgow who regards lab escape as a conspiracy theory. “Recombination is naturally very, very frequent in these viruses, there are recombination breakpoints in the spike protein and these codons appear unusual exactly because we’ve not sampled enough.”
Robertson is correct that evolution is always producing results that may seem unlikely but in fact are not. Viruses can generate untold numbers of variants but we see only the one-in-a-billion that natural selection picks for survival. But this argument could be pushed too far. For instance, any result of a gain-of-function experiment could be explained as one that evolution would have arrived at in time. And the numbers game can be played the other way. For the furin cleavage site to arise naturally in SARS2, a chain of events has to happen, each of which is quite unlikely for the reasons given above. A long chain with several improbable steps is unlikely to ever be completed.
For the lab escape scenario, the double CGG codon is no surprise. The human-preferred codon is routinely used in labs. So anyone who wanted to insert a furin cleavage site into the virus’s genome would synthesize the PRRA-making sequence in the lab and would be likely to use CGG codons to do so.
“When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus,” said David Baltimore, an eminent virologist and former president of CalTech. “These features make a powerful challenge to the idea of a natural origin for SARS2,” he said. [1]
1. Chinese virologists. First and foremost, Chinese virologists are to blame for performing gain-of-function experiments in mostly BSL2-level safety conditions which were far too lax to contain a virus of unexpected infectiousness like SARS2. If the virus did indeed escape from their lab, they deserve the world’s censure for a foreseeable accident that has already caused the deaths of three million people. True, Shi was trained by French virologists, worked closely with American virologists and was following international rules for the containment of coronaviruses. But she could and should have made her own assessment of the risks she was running. She and her colleagues bear the responsibility for their actions.
I have been using the Wuhan Institute of Virology as a shorthand for all virological activities in Wuhan. It’s possible that SARS2 was generated in some other Wuhan lab, perhaps in an attempt to make a vaccine that worked against all coronaviruses. But until the role of other Chinese virologists is clarified, Shi is the public face of Chinese work on coronaviruses, and provisionally she and her colleagues will stand first in line for opprobrium.
2. Chinese authorities. China’s central authorities did not generate SARS2, but they sure did their utmost to conceal the nature of the tragedy and China’s responsibility for it. They suppressed all records at the Wuhan Institute of Virology and closed down its virus databases. They released a trickle of information, much of which may have been outright false or designed to misdirect and mislead. They did their best to manipulate the WHO’s inquiry into the virus’s origins, and led the commission’s members on a fruitless run-around. So far they have proved far more interested in deflecting blame than in taking the steps necessary to prevent a second pandemic.
3. The worldwide community of virologists. Virologists around the world are a loose-knit professional community. They write articles in the same journals. They attend the same conferences. They have common interests in seeking funds from governments and in not being overburdened with safety regulations.
Virologists knew better than anyone the dangers of gain-of-function research. But the power to create new viruses, and the research funding obtainable by doing so, was too tempting. They pushed ahead with gain-of-function experiments. They lobbied against the moratorium imposed on Federal funding for gain-of-function research in 2014, and it was raised in 2017.
The benefits of the research in preventing future epidemics have so far been nil, the risks vast. If research on the SARS1 and MERS viruses could only be done at the BSL3 safety level, it was surely illogical to allow any work with novel coronaviruses at the lesser level of BSL2. Whether or not SARS2 escaped from a lab, virologists around the world have been playing with fire.
Their behavior has long alarmed other biologists. In 2014 scientists calling themselves the Cambridge Working Group urged caution on creating new viruses. In prescient words, they specified the risk of creating a SARS2-like virus. “Accident risks with newly created ‘potential pandemic pathogens’ raise grave new concerns,” they wrote. “Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control.”
When molecular biologists discovered a technique for moving genes from one organism to another, they held a public conference at Asilomar in 1975 to discuss the possible risks. Despite much internal opposition, they drew up a list of stringent safety measures that could be relaxed in future — and duly were — when the possible hazards had been better assessed.
When the CRISPR technique for editing genes was invented, biologists convened a joint report by the US, UK and Chinese national academies of science to urge restraint on making heritable changes to the human genome. Biologists who invented gene drives have also been open about the dangers of their work and have sought to involve the public.
You might think the SARS2 pandemic would spur virologists to re-evaluate the benefits of gain-of-function research, even to engage the public in their deliberations. But no. Many virologists deride lab escape as a conspiracy theory, and others say nothing. They have barricaded themselves behind a Chinese wall of silence which so far is working well to allay, or at least postpone, journalists’ curiosity and the public’s wrath. Professions that cannot regulate themselves deserve to get regulated by others, and this would seem to be the future that virologists are choosing for themselves.
4. The US role in funding the Wuhan Institute of Virology.[2] From June 2014 to May 2019, Daszak’s EcoHealth Alliance had a grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to do gain-of-function research with coronaviruses at the Wuhan Institute of Virology. Whether or not SARS2 is the product of that research, it seems a questionable policy to farm out high-risk research to foreign labs using minimal safety precautions. And if the SARS2 virus did indeed escape from the Wuhan institute, then the NIH will find itself in the terrible position of having funded a disastrous experiment that led to the death of more than 3 million worldwide, including more than half a million of its own citizens.
The responsibility of the NIAID and NIH is even more acute because for the first three years of the grant to EcoHealth Alliance there was a moratorium on funding gain-of-function research. When the moratorium expired in 2017, it didn’t just vanish but was replaced by a reporting system, the Potential Pandemic Pathogens Control and Oversight (P3CO) Framework, which required agencies to report for review any dangerous gain-of-function work they wished to fund.
The moratorium, referred to officially as a “pause,” specifically barred funding any gain-of-function research that increased the pathogenicity of the flu, MERS or SARS viruses. It defined gain-of-function very simply and broadly as “research that improves the ability of a pathogen to cause disease.”
But then a footnote on p.2 of the moratorium document states that “[a]n exception from the research pause may be obtained if the head of the USG funding agency determines that the research is urgently necessary to protect the public health or national security.”
This seemed to mean that either the director of the NIAID, Anthony Fauci, or the director of the NIH, Francis Collins, or maybe both, would have invoked the exemption in order to keep the money flowing to Shi’s gain-of-function research, and later to avoid notifying the federal reporting system of her research.
“Unfortunately, the NIAID Director and the NIH Director exploited this loophole to issue exemptions to projects subject to the Pause –preposterously asserting the exempted research was ‘urgently necessary to protect public health or national security’—thereby nullifying the Pause,” Dr. Richard Ebright said in an interview with Independent Science News.
But it’s not so clear that the NIH thought it necessary to invoke any loopholes. Fauci told a Senate hearing on May 11 that “the NIH and NIAID categorically has not funded gain-of-function research to be conducted in the Wuhan Institute of Virology.”
This was a surprising statement in view of all the evidence about Shi’s experiments with enhancing coronaviruses and the language of the moratorium statute defining gain-of-function as “any research that improves the ability of a pathogen to cause disease.”
The explanation may be one of definition. Daszak’s EcoHealth Alliance, for one, believes that the term gain-of-function applies only to enhancements of viruses that infect humans, not to animal viruses. “So gain-of-function research refers specifically to the manipulation of human viruses so as to be either more easily transmissible or to cause worse infection or be easier to spread,” an Alliance official told The Dispatch Fact Check.
If the NIH shares the EcoHealth Alliance view that “gain of function” applies only to human viruses, that would explain why Fauci could assure the Senate it had never funded such research at the Wuhan Institute of Virology. But the legal basis of such a definition is unclear, and it differs from that of the moratorium language which was presumably applicable.
Definitions aside, the bottom line is that the National Institutes of Health was supporting research of a kind that could have generated the SARS2 virus, in an unsupervised foreign lab that was doing work in BSL2 biosafety conditions.
State Department investigators say they were repeatedly advised not to open a “Pandora’s box.”
Only two other labs in the world, in Texas and North Carolina, were doing similar research. “It’s not a dozen cities,” Dr. Richard Ebright said. “It’s three places.”
Memo
MRN: 18 BEIJING 138
Date/DTG: Jan 19, 2018 / 190739Z Jan 18
From: AMEMBASSY BEIJING
Action: WASHDC, SECSTATE ROUTINE
E.O.: 13526
TAGS: SHLH, ETRD, ECON, PGOV, CN
Captions: SENSITIVE
Reference: 17 WUHAN 48
Subject: China Opens First Bio Safety Level 4 Laboratory
1. (SBU) Summary and Comment: The Chinese Academy of Sciences (CAS) has recently established what is reportedly China's first Biosafety Level 4 (BSL-4) laboratory in Wuhan. This state-of-the-art facility is designed for prevention and control research on diseases that require the highest level of biosafety and biosecurity containment. Ultimately, scientists hope the lab will contribute to the development of new antiviral drugs and vaccines, but its current productivity is limited by a shortage of the highly trained technicians and investigators required to safely operate a BSL-4 laboratory and a lack of clarity in related Chinese government policies and guidelines. (b)(5) [DELETE] (b)(5) (b)(5) End Summary and Comment.
China Investing in Infectious Disease Control
2. (U) Between November 2002 and July 2003, China faced an outbreak of Severe Acute Respiratory Syndrome (SARS), which, according to the World Health Organization, resulting in 8,098 cases and leading to 774 deaths reported in 37 countries. A majority of cases occurred in China, where the fatality rate was 9.6%. This incident convinced China to prioritize international cooperation for infectious disease control. An aspect of this prioritization was China's work with the Jean Merieux BSL-4 Laboratory in Lyon, France, to build China's first high containment laboratory at Wuhan's Institute of Virology (WIV), an institute under the auspices of the Chinese Academy of Sciences (CAS). Construction took 11 years and $44 million USD. and construction on the facility was completed on January 31, 2015. Following two years of effort, which is not unusual for such facilities, the WIV lab was accredited in February 2017 by the China National Accreditation Service for Conformity Assessment. It occupies four floors and consists of over 32,000 square feet. WIV leadership now considers the lab operational and ready for research on class-four pathogens (P4), among which are the most virulent viruses that pose a high risk of aerosolized person-to-person transmission.
Unclear Guidelines on Virus Access and a Lack of Trained Talent Impede Research
3. (SBU) In addition to accreditation, the lab must also receive permission from the National Health and Family Planning Commission (NHFPC) to initiate research on specific highly contagious pathogens. According to some WIV scientists, it is unclear how NHFPC determines what viruses can or cannot be studied in the new laboratory. To date, WIV has obtained permission for research on three viruses: Ebola virus, Nipah virus, and Xinjiang hemorrhagic fever virus (a strain of Crimean Congo hemorrhagic fever found in China's Xinjiang Province). Despite this permission, however, the Chinese government has not allowed the WIV to import Ebola viruses for study in the BSL-4 lab. Therefore, WIV scientists are frustrated and have pointed out that they won't be able to conduct research project with Ebola viruses at the new BSL-4 lab despite of the permission.
(b)(6) [DELETE]
(b)(6) Thus, while the BSL-4 lab is ostensibly fully accredited, its utilization is limited by lack of access to specific organisms and by opaque government review and approval processes. As long as this situation continues, Beijing's commitment to prioritizing infectious disease control -- on the regional and international level, especially in relation to highly pathogenic viruses, remains in doubt.
(b)(6) [DELETE] noted that the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory. University of Texas Medical Branch in Galveston (UTMB), which has one of several well-established BSL-4 labs in the United States (supported by the National Institute of Allergy and Infectious Diseases (NIAID of NIH)), has scientific collaborations with WIV, which may help alleviate this talent gap over time. Reportedly, researchers from TMB are helping train technicians who work in the WIV BSL-4 lab. Despite this (b)(6) [DELETE] they would welcome more help from U.S. and international organizations as they establish "gold standard" operating procedures and training courses for the first time in China. As China is building more BSL-4 labs, including one in Harbin Veterinary Research Institute subordinated to the Chinese Academy of Agricultural Sciences (CAAS) for veterinary research use (b)(6) [DELETE] the training for technicians and investigators working on dangerous pathogens will certainly be in demand.
Despite Limitations. WIV Researchers Produce SARS Discoveries
6. (SBU) The ability of WIV scientists to undertake productive research despite limitations on the use of the new BSL-4 facility is demonstrated by a recent publication on the origins of SARS. Over a five-year study, (b)(6) [DELETE] (and their research team) widely sampled bats in Yunnan province with funding support from NIAID/NIH, USAID, and several Chinese funding agencies. The study results were published in PLoS Pathogens online on Nov. 30, 2017 (1), and it demonstrated that a SARS-like corona viruses isolated from horseshoe bats in a single cave contain all the building blocks of the pandemic SARS-coronavirus genome that caused the human outbreak. These results strongly suggest that the highly pathogenic SARS-coronavirus originated in this bat population. Most importantly, the researchers also showed that various SARS-like coronaviruses can interact with ACE2, the human receptor identified for SARS-coronavirus. This finding strongly suggests that SARS-like coronaviruses from bats can be transmitted to humans to cause SARS-like disease. From a public health perspective, this makes the continued surveillance of SARS-like coronaviruses in bats and study of the animal-human interface critical to future emerging corona virus outbreak prediction and prevention (b)(5) [DELETE] (b)(5) WIV scientists are allowed to study the SARS-like coronaviruses isolated from bats while they are precluded from studying human-disease causing SARS coronavirus in their new BSL-4 lab until permission for such work is granted by the NHFCP.
1. Hu B, Zeng L-P, Yang X-L, Ge X-Y, Zhang W, Li B, et a1. (2017) Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 13(11): e1006698. https://doi.org/10.1371/journal.ppat.1006698
Signature: BRANSTAD
Drafted By: (b)(6) [DELETE]
Cleared By: (b)(6) [DELETE]
Approved By: (b)(6) [DELETE]
Released By: (b)(6) [DELETE]
Info: CHINA POSTS COLLECTIVE ROUTINE
Dissemination Rule: Archive Copy
UNCLASSIFIED
SBU
Blocking pro-democracy activist from attending event
Pro-democracy activist and secretary-general of Demosisto Joshua Wong was allegedly disallowed by Asia Society Hong Kong from speaking at a book launch originally scheduled to take place at its Hong Kong venue on June 28, 2017. It was understood that Asia Society Hong Kong was approached by PEN Hong Kong to co-curate the book launch, but negotiations stalled upon the former's request for a more diverse panel of speakers. PEN Hong Kong, a non-profit organization supporting literature and freedom of expression, eventually decided to relocate the launch of Hong Kong 20/20: Reflections on a Borrowed Place – of which Wong was one of the authors – to the Foreign Correspondents Club. Joshua Wong says that Asia Society Hong Kong needs to give a “reasonable explanation” for the incident.
“The mission of PEN Hong Kong is to promote literature and defend the freedom of expression. To bar one of the contributors to our anthology, whether it is Joshua Wong or somebody else, from speaking at our launch event would undermine and in fact contravene that mission,” said PEN Hong Kong President Jason Y. Ng.
Back to November 2016, Asia Society Hong Kong also canceled a scheduled screening of Raise The Umbrellas, a documentary on the 2014 Occupy protests with appearance of Joshua Wong. Asia Society Hong Kong has similarly cited the lack of balanced speaker representation at the pre-screening talk as the reason for not screening the film.
US Congressman Chris Smith, co-chairperson of the Congressional-Executive Commission on China, expressed that “The Asia Society has some explaining to do after two events that featured Joshua Wong prominently were canceled over the past nine months,” said the New Jersey representative. “I commend PEN Hong Kong for not appeasing the Asia Society’s demands.”....
On July 10, 2017, Forbes magazine ran an article revealing Hong Kong real estate magnate and Asia Society Co-chair Ronnie Chan (a US citizen) to be the political force behind the Joshua Wong incident. It alleged that wealthy Asians have been behind US think tanks and NGOs and effectively turning them into foreign policy tools of the People's Republic of China (Beijing).
-- Asia Society, by Wikipedia
“If the pandemic started as part of a lab leak, it had the potential to do to virology what Three Mile Island and Chernobyl did to nuclear science.”
The 2019 Military World Games and Sick Athletes
The 7th International Military Sports Council Military World Games (MWGs) opened in Wuhan on October 18, 2019. The games are similar to the Olympic games but consist of military athletes with some added military disciplines. The MWGs in Wuhan drew 9,308 athletes, representing 109 countries, to compete in 329 events across 27 sports. Twenty-five countries sent delegations of more than 100 athletes, including Russia, Brazil, France, Germany, and Poland. [65] ["Military Games to Open Friday in China.” China Daily, 17 Oct. 2019, http://www.china.org.cn/sports/2019- 10/17/content_75311946.htm.]
The PRC government recruited 236,000 volunteers for the games, which required 90 hotels, three railroad stations, and more than 2,000 drivers. [66] [“2019 Military World Games Kicks off in Central China's Wuhan.” CISION, 17 Oct. 2019, http://www.prnewswire.com/news-releases ... orldgames- kicks-off-in-central-chinas-wuhan-300940464.html.] An archived version of the competition’s website from October 20, 2019, lists the more than thirty venues that hosted events for the MWGs across Wuhan and the broader Hubei province. [67] [“Competition Venues.” Wuhan 2019 Military World Games, https://web.archive.org/web/20191020154 ... on_venues/.] The live website is no longer accessible – it is unclear why it was removed.
During the games, many of the international athletes became sick with what now appear to be symptoms of COVID-19. In one interview, an athlete from Luxembourg described Wuhan as a “ghost town,”[68] [Houston, Michael. “More athletes claim they contracted COVID-19 at Military World Games in Wuhan.” Inside the Games, 17 May 2020, https://www.insidethegames.biz/articles ... s-covid-19] and recalls having his temperature taken upon arriving at the city’s airport. In an interview with The Financial Post, a Canadian newspaper, one member of the Canadian Armed Forces who participated in the games said (emphasis added):This was a city of 15 million people that was in lockdown. It was strange, but we were told this was to make it easy for the Games’ participants to get around. [I got] very sick 12 days after we arrived, with fever, chills, vomiting, insomnia.… On our flight to come home, 60 Canadian athletes on the flight were put in isolation [at the back of the plane] for the 12-hour flight. We were sick with symptoms ranging from coughs to diarrhea and in between. [69] [Francis, Diane. “Diane Francis: Canadian Forces Have Right to Know If They Got COVID at the 2019 Military World Games in Wuhan.” Financial Post, 25 June 2021, https://financialpost.com/diane-francis ... taryworld- games-in-wuhan.]
The service member also revealed his family members became ill as his symptoms increased, [70] [Ibid.] a development that is consistent with both human-to-human transmission of a viral infection and COVID-19. Similar claims about COVID-19 like symptoms have been made by athletes from Germany, France, Italy, [71] [Houston.] and Sweden. [72] [Liao, George. “Coronavirus May Have Been Spreading since Wuhan Military Games Last October.” Taiwan News, 13 May 2020, http://www.taiwannews.com.tw/en/news/3932712.]
By cross referencing the listed MWG venues with publicly available mapping data, it is possible to visualize the venues (in black) in relation to the WIV Headquarters (in red) and the abovementioned hospitals (in blue). The green figures represent athletes who have publicly expressed their belief they contracted COVID-19 while in Wuhan and are mapped at the venues which hosted the events in which they competed. Some of these athletes resided in the military athletes’ village.
Map 2: WIV Headquarters, Hospitals, MWG Venues, and Sick Athletes
At least four countries who sent delegations to the MWGs have now confirmed the presence of SARS-CoV-2 or COVID-19 cases within their borders in November and December 2019, before the news of an outbreak first became public....
As stated above, athletes from France, Italy, and Sweden also complained of illnesses with symptoms similar to COVID-19 while at the MWGs in Wuhan. The presence of SARS-CoV-2 in four countries, on two separate continents, suggests a common source. If, as presumed, SARS-CoV-2 first infected humans in Wuhan before spreading to the rest of the world, the 2019 Military World Games in Wuhan appears to be a key vector in the global spread – in other words, potentially one of the first “super spreader” events.
-- The Origins of COVID-19: An Investigation of the Wuhan Institute of Virology, by House Foreign Affairs Committee
The significance of the Master’s thesis
These findings of the thesis are significant in several ways.
First, in the light of the current coronavirus pandemic it is evident the miners’ symptoms very closely resemble those of COVID-19 (Huang et al, 2020; Tay et al., 2020; M. Zhou et al., 2020). Anyone presenting with them today would immediately be assumed to have COVID-19. Likewise, many of the treatments given to the miners have become standard for COVID-19 (Tay et al., 2020).
Second, the remote meeting with Zhong Nanshan is significant. It implies that the illnesses of the six miners were of high concern and, second, that a SARS-like coronavirus was considered a likely cause.
Third, the abstract, the conclusions, and the general inferences to be made from the Master’s thesis contradict Zheng-li Shi’s assertion that the miners died from a fungal infection. Fungal infection as a potential primary cause was raised but largely discarded.
Fourth, if a SARS-like coronavirus was the source of their illness the implication is that it could directly infect human cells. This would be unusual for a bat coronavirus (Ge et al., 2013). People do sometimes get ill from bat faeces but the standard explanation is histoplasmosis, a fungal infection and not a virus (McKinsey and McKinsey, 2011; Pan et al., 2013).
Fifth, the sampling by the Shi lab found that bat coronaviruses were unusually abundant in the mine (Ge at al., 2016). Among their findings were two betacoronaviruses, one of which was RaTG13 (then known as BtCoV/4991). In the coronavirus world betacoronaviruses are special in that both SARS and MERS, the most deadly of all coronaviruses, are both betacoronaviruses. Thus they are considered to have special pandemic potential, as the concluding sentence of the Shi lab publication which found RaTG13 implied: “special attention should particularly be paid to these lineages of coronaviruses” (Ge at al., 2016). In fact, the Shi and other labs have for years been predicting that bat betacoronaviruses like RaTG13 would go pandemic; so to find RaTG13 where the miners fell ill was a scenario in perfect alignment with their expectations.
The Mojiang miners passaging proposal
How does the Master’s thesis inform the search for a plausible origin of the pandemic?
In our previous article we briefly discussed how the pandemic might have been caused either by a virus collection accident, or through viral passaging, or through genetic engineering and a subsequent lab escape. The genetic engineering possibility deserves attention and is extensively assessed in an important preprint (Segreto and Deigin, 2020).
We do not definitively rule out these possibilities. Indeed it now seems that the Shi lab at the WIV did not forget about RaTG13 but were sequencing its genome in 2017 and 2018. However, we believe that the Master’s thesis indicates a much simpler explanation.
We suggest, first, that inside the miners RaTG13 (or a very similar virus) evolved into SARS-CoV-2, an unusually pathogenic coronavirus highly adapted to humans. Second, that the Shi lab used medical samples taken from the miners and sent to them by Kunming University Hospital for their research. It was this human-adapted virus, now known as SARS-CoV-2, that escaped from the WIV in 2019.
We refer to this COVID-19 origin hypothesis as the Mojiang Miners Passage (MMP) hypothesis.
Passaging is a standard virological technique for adapting viruses to new species, tissues, or cell types. It is normally done by deliberately infecting a new host species or a new host cell type with a high dose of virus. This initial viral infection would ordinarily die out because the host’s immune system vanquishes the ill-adapted virus. But, in passaging, before it does die out a sample is extracted and transferred to a new identical tissue, where viral infection restarts. Done iteratively, this technique (called “serial passaging” or just “passaging”) intensively selects for viruses adapted to the new host or cell type (Herfst et al., 2012).
At first glance RaTG13 is unlikely to have evolved into SARS-CoV-2 since RaTG13 is approximately 1,200 nucleotides (3.8%) different from SARS-CoV-2. Although RaTG13 is the most closely related virus to SARS-CoV-2, this sequence difference still represents a considerable gap. In a media statement evolutionary virologist Edward Holmes has suggested this gap represents 20-50 years of evolution and others have suggested similar figures.
We agree that ordinary rates of evolution would not allow RaTG13 to evolve into SARS-CoV-2 but we also believe that conditions inside the lungs of the miners were far from ordinary. Five major factors specific to the hospitalised miners favoured a very high rate of evolution inside them.
i) When viruses infect new species they typically undergo a period of very rapid evolution because the selection pressure on the invading pathogen is high. The phenomenon of rapid evolution in new hosts is well attested among corona- and other viruses (Makino et al., 1986; Baric et al., 1997; Dudas and Rambaut 2016; Forni et al., 2017).
ii) Judging by their clinical symptoms such as the CT scans, all the miner’s infections were primarily of the lungs. This localisation likely occurred initially because the miners were exerting themselves and therefore inhaling the disturbed bat guano deeply. As miners, they may already have had damaged lung tissues (patient 3 had suspected pneumoconiosis) and/or particulate matter was present that irritated the tissues and may have facilitated initial viral entry.
In contrast, standard coronavirus infections are confined to the throat and upper respiratory tract. They do not normally reach the lungs (Perlman and Netland, 2009). Lungs are far larger tissues by weight (kilos vs grammes) than the upper respiratory tract. There was therefore likely a much larger quantity of virus inside the miners than would be the case in an ordinary coronavirus infection.
Comparing a typical coronavirus respiratory tract infection with the extent of infected lungs in the miners from a purely mathematical point of view indicates the potential scale of this quantitative difference. The human aerodigestive tract is approximately 20cm in length and 5cm in circumference, i.e. approximately 100 cm2 in surface area. The surface area of a human lung ranges from 260,000-680,000 cm2(Hasleton, 1972). The amount of potentially infected tissue in an average lung is therefore approximately 4500-fold greater than that available to a normal coronavirus infection. The amount of virus present in the infected miners, sufficient to hospitalise all of them and kill half of them, was thus proportionately very large.
Evolutionary change is in large part a function of the population size. The lungs of the miners, we suggest, supported a very high viral load leading to proportionately rapid viral evolution.
Furthermore, according to the Master’s thesis, the immune systems of the miners were compromised and remained so even for those discharged. This weakness on the part of the miners may also have encouraged evolution of the virus.
iii) The length of infection experienced by the miners (especially patients 2, 3 and 4) far exceeded that of an ordinary coronavirus infection. From first becoming too sick to work in the mine, patient 2 survived 57 days until he died. Patient 3 survived 120 days after stopping work. Patient 4 survived 117 days and then was discharged as cured. Each had been exposed in the mine for 14 days prior to the onset of severe symptoms; thus each presumably had nascent infections for some time before calling in sick (See Table 2 of the thesis).
In contrast, in ordinary coronavirus infections the viral infection is cleared within about ten to fourteen days after being acquired (Tay et al., 2020). Thus, unlike most sufferers from coronavirus infection, the hospitalised miners had very long-term bouts of disease characterised by a continuous high load of virus. In the cases of patients 3 and 4 their illnesses lasted over 4 months.
iv) Coronaviruses are well known to recombine at very high rates: 10% of all progeny in a cell can be recombinants (Makino et al., 1986; Banner and Lai, 1991; Dudas and Rambaut, 2016). In normal virus evolution the mutation rate and the selection pressure are the main foci of attention. But in the case of a coronavirus adapting to a new host where many mutations distributed all over the genome are required to fully adapt to the new host, the recombination rate is likely to be highly influential in determining the overall speed of adaptation by the virus population (Baric et al., 1997).
Inside the miners a large tissue was simultaneously infected by a population of poorly-adapted viruses, with each therefore under pressure to adapt. Even if the starting population of virus lacked any diversity, many individual viruses would have acquired mutations independently but only recombination would have allowed these mutations to unite in the same genome. To recombine, viruses must be present in the same cell. In such a situation the particularities of lung tissues become potentially important because the existence of airways (bronchial tubes, etc.) allows partially-adapted viruses from independent viral populations to travel to distal parts of the lung (or even the other lung) and encounter other such partially-adapted viruses and populations. This movement around the lungs would likely have resulted in what amounted to a passaging effect without the need for a researcher to infect new tissues. Indeed, in the Master’s thesis the observation is several times made that areas of the lungs of a specific patient would appear to heal even while other parts of the lungs would become infected.
v) There were also a number of unusual things about the bat coronaviruses in the mine. They were abnormally abundant but also there were many different kinds, often causing co-infections of the bats (Ge et al., 2016). Viral co-infections are often more infectious or more pathogenic (Latham and Wilson, 2007).
As the WIV researchers remarked about the bats in the mine:“we observed a high rate of co-infection with two coronavirus species and interspecies infection with the same coronavirus species within or across bat families. These phenomena may be owing to the diversity and high density of bat populations in the same cave, facilitating coronavirus intra- and interspecies transmissions, which may result in recombination and acceleration of coronavirus evolution.” (Ge et al., 2016).
The diversity of coronaviruses in the mine suggests that the miners were similarly exposed and that their illness may potentially have begun as co-infections.
Combining these observations, we propose that the miners’ lungs offered an unprecedented opportunity for accelerated evolution of a highly bat-adapted coronavirus into a highly human-adapted coronavirus and that decades of ordinary coronavirus evolution could easily have been condensed into months. However, we acknowledge that these conditions were unique. They and their scale have no exact scientific precedent we can refer to and they would be hard to replicate in a lab; thus it is important to emphasize that our proposal is fully consistent with the underlying principles of viral evolution as understood today.
In support of the MMP theory we also know something about the samples taken from the miners. According to the Master’s thesis, samples were taken from patients for “scientific research” and blood samples (at least) were sent to the WIV.
“In the later stage we worked with Dr. Zhong Nan Shan and did some sampling. The patient* tested positive for serum IgM by the WuHan Institute of Virology. It suggested the existence of virus infection” (p62 in the section “Comprehensive Analysis”.)
(*The original does not specify the number of patients tested.)
The Master’s thesis also states its regret that no samples for research were taken from patients 1 and 2, implying that samples were taken from all the others.
We further know that, on June 27th, 2012, the doctors performed an unexplained thymectomy on patient 4. The thymus is an immune organ that can potentially be removed without greatly harming the patient and it could have contained large quantities of virus. Beyond this the Master’s thesis is unfortunately unclear on the specifics of what sampling was done, for what purpose, and where each particular sample went.
Given the interests of the Shi lab in zoonotic origins of human disease, once such a sample was sent to them, it would have been obvious and straightforward for them to investigate how a virus from bats had managed to infect these miners. Any viruses recoverable from the miners would likely have been viewed by them as a unique natural experiment in human passaging offering unprecedented and otherwise-impossible-to-obtain insights into how bat coronaviruses can adapt to humans.
The logical course of such research would be to sequence viral RNA extracted directly from unfrozen tissue or blood samples and/or to generate live infectious clones for which it would be useful (if not imperative) to amplify the virus by placing it in human cell culture. Either technique could have led to accidental infection of a lab researcher.
Our supposition as to why there was a time lag between sample collection (in 2012/2013) and the COVID-19 outbreak is that the researchers were awaiting BSL-4 lab construction and certification, which was underway in 2013 but delayed until 2018.
We propose that, when frozen samples derived from the miners were eventually opened in the Wuhan lab they were already highly adapted to humans to an extent possibly not anticipated by the researchers. One small mistake or mechanical breakdown could have led directly to the first human infection in late 2019.
Thus, one of the miners, most likely patient 3, or patient 4 (whose thymus was removed), was effectively patient zero of the COVID-19 epidemic. In this scenario, COVID-19 is not an engineered virus; but, equally, if it had not been taken to Wuhan and no further molecular research had been performed or planned for it then the virus would have died out from natural causes, rather than escaped to initiate the COVID-19 pandemic....
Further questions
The hypothesis that SARS-CoV-2 evolved in the Mojiang miner’s lungs potentially resolves many scientific questions about the origin of the pandemic. But it raises others having to do with why this information has not come to light hitherto. The most obvious of these concern the actions of the Shi lab at the WIV.
Why did the Shi lab not acknowledge the miners’ deaths in any paper describing samples taken from the mine (Ge et al., 2016 and P. Zhou et al., 2020)? Why in the title of the Ge at al. 2016 paper did the Shi lab call it an “abandoned” mine? When they published the sequence of RaTG13 in Feb. 2020, why did the Shi lab provide a new name (RaTG13) for BtCoV/4991 when they had by then cited BtCoV/4991 twice in publications and once in a genome sequence database and when their sequences were from the same sample and 100% identical (P. Zhou et al., 2020)? If it was just a name change, why no acknowledgement of this in their 2020 paper describing RaTG13 (Bengston, 2020)? These strange and unscientific actions have obscured the origins of the closest viral relatives of SARS-CoV-2, viruses that are suspected to have caused a COVID-like illness in 2012 and which may be key to understanding not just the origin of the COVID-19 pandemic but the future behaviour of SARS-CoV-2.
These are not the only questionable actions associated with the provenance of samples from the mine. There were five scientific publications that very early in the pandemic reported whole genome sequences for SARS-CoV-2 (Chan et al., 2020; Chen et al., 2020; Wu et al., 2020; P. Zhou et al., 2020; Zhu et al., 2020). Despite three of them having experienced viral evolutionary biologists as authors (George Gao, Zheng-li Shi and Edward Holmes) only one of these (Chen et al., 2020) succeeded in identifying the most closely related viral sequence by far: BtCoV/4991 a viral sequence in the possession of the Shi lab at the WIV that differed from SARS-CoV-2 by just 5 nucleotides.
-- A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic [W/Comments], by Jonathan Latham, PhD and Allison Wilson, PhD
Barack Obama's tenure as the 44th president of the United States began with his first inauguration on January 20, 2009, and ended on January 20, 2017.
-- Presidency of Barack Obama, by Wikipedia
77 US Nobel Laureates in Science
May 21, 2020
Dear Secretary Azar and Director Collins:
The 77 signatories of this letter, American Nobel Laureates in Physiology or Medicine, Chemistry, and Physics, are gravely concerned about the recent cancellation of a grant from the National Institutes of Health (NIH) to Dr. Peter Daszak at the EcoHealth Alliance in New York. We believe that this action sets a dangerous precedent by interfering in the conduct of science and jeopardizes public trust in the process of awarding federal funds for research.
For many years, Dr. Daszak and his colleagues have been conducting highly regarded, NIH-supported research on coronaviruses and other infectious agents, focusing on the transmission of these viruses from animal hosts to human beings. Their work depends on productive collaborations with scientists in other countries, including scientists in Wuhan, China, where the current pandemic caused by a novel coronavirus arose. Now is precisely the time when we need to support this kind of research if we aim to control the pandemic and prevent subsequent ones.
As has now been widely reported, the grant to the EcoHealth Alliance was abruptly terminated by NIH on April 24, 2020, just a few days after President Trump responded to a question from a reporter who erroneously claimed that the grant awarded millions of dollars to investigators in Wuhan. Despite the misrepresentation of Dr. Daszak’s grant, despite the high relevance of the studies to the current pandemic, and despite the very high priority score that his application for renewal had received during peer review, the NIH informed Dr. Daszak and his colleagues that the grant was being terminated because “NIH does not believe that the current project outcomes align with the program goals and agency priorities.” Such explanations are preposterous under the circumstances.
We are scientists who have devoted our careers to research, both in medical and related scientific disciplines that bear on the overall health and well-being of society, as well as fundamental scientific research, much of it supported by NIH and other federal agencies. We take pride in our nation’s widely admired system for allocating funds based on expert review and public health needs. The abrupt revoking of the award to Dr. Daszak contravenes these basic tenets and deprives the nation and the world of highly regarded science that could help control one of the greatest health crises in modern history and those that may arise in the future.
We ask that you act urgently to conduct and release a thorough review of the actions that led to the decision to terminate the grant, and that, following this review, you take appropriate steps to rectify the injustices that may have been committed in revoking it.
Peter Agre Chemistry 2003 James P. Allison Medicine 2018
Sidney Altman Chemistry 1989 Frances H. Arnold Chemistry 2018
David Baltimore Medicine 1975 Barry Clark Barish Physics 2017
Paul Berg Chemistry 1980 J. Michael Bishop Medicine 1989
Elizabeth H. Blackburn Medicine 2009 Michael S. Brown Medicine 1985
William C. Campbell Medicine 2015 Mario R. Capecchi Medicine 2007
Thomas R. Cech Chemistry 1989 Martin Chalfie Chemistry 2008
Steven Chu Physics 1997 Elias James Corey Chemistry 1990
Robert F. Curl Jr. Chemistry 1996 Johann Deisenhofer Chemistry 1988
Andrew Z. Fire Medicine 2006 Edmond H. Fischer Medicine 1992
Joachim Frank Chemistry 2017 Jerome I. Friedman Physics 1990
Walter Gilbert Chemistry 1980 Sheldon Glashow Physics 1979
Joseph L. Goldstein Medicine 1985 Carol W. Greider Medicine 2009
David J. Gross Physics 2004 Roger Guillemin Medicine 1977
Leland H. Hartwell Medicine 2001 Dudley R. Herschbach Chemistry 1986
Roald Hoffmann Chemistry 1981 H. Robert Horvitz Medicine 2002
Louis J. Ignarro Medicine 1998 William G. Kaelin Jr. Medicine 2019
Eric R. Kandel Medicine 2000 Wolfgang Ketterle Physics 2001
Brian K. Kobilka Chemistry 2012 Roger D. Kornberg Chemistry 2006
Robert J. Lefkowitz Chemistry 2012 Anthony J. Leggett Physics 2003
Michael Levitt Chemistry 2013 Roderick MacKinnon Chemistry 2003
John C. Mather Physics 2006 Craig C. Mello Medicine 2006
William E. Moerner Chemistry 2014 Mario J. Molina Chemistry 1995
Ferid Murad Medicine 1998 Douglas D. Osheroff Physics 1996
James Peebles Physics 2019 Saul Perlmutter Physics 2011
William D. Phillips Physics 1997 H. David Politzer Physics 2004
Sir Richard J. Roberts Medicine 1993 Michael Rosbash Medicine 2017
James E. Rothman Medicine 2013 Randy W. Schekman Medicine 2013
Richard R. Schrock Chemistry 2005 Gregg L. Semenza Medicine 2019
Phillip A. Sharp Medicine 1993 Hamilton O. Smith Medicine 1978
George P. Smith Chemistry 2018 Horst L. Stormer Physics 1998
Thomas C. Sudhof Medicine 2013 Jack W. Szostak Medicine 2009
Joseph H. Taylor Jr. Physics 1993 Kip Stephen Thorne Physics 2017
Susumu Tonegawa Medicine 1987 Daniel C. Tsui Physics 1998
Harold E. Varmus Medicine 1989 Steve Weinberg Physics 1979
Rainer Weiss Physics 2017 Carl E. Wieman Physics 2001
Eric F. Wieschaus Medicine 1995 Torsten N. Wiesel Medicine 1981
Frank Wilczek Physics 2004 Robert Woodrow Wilson Physics 1978
Michael W. Young Medicine 2017
Department of Health & Human Services
National Institutes of Health
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland 20892
8 July 2020
Drs. Aleksei Chmura and Peter Daszak
EcoHealth Alliance, Inc.
460 W. 34th St.
Suite 1701
New York, NY 100001
Re: NIH Grant R01 A11 10964
Dear Drs. Chmura and Daszak:
In follow-up to my previous letter of April 24, 2020, I am writing to notify you that the National Institute of Allergy and Infectious Diseases (NIAID), an Institute within the National Institutes of Health (NIH), under the Department of Health and Human Services (HHS), has withdrawn its termination of grant R01AI110964, which supports the project Understanding the Risk of Bat Coronavirus Emergence. Accordingly, the grant is reinstated.
However, as you are aware, the NIH has received reports that the Wuhan Institute of Virology (WIV), a subrecipient of EcoHealth Alliance under R01AI110964, has been conducting research at its facilities in China that pose serious bio-safety concerns and, as a result, create health and welfare threats to the public in China and other countries, including the United States. Grant award R01AI110964 is subject to biosafety requirements set forth in the NIH Grants Policy Statement (e.g., NIH GPS, Section 4.1.24 “Public Health Security”) and the Notice of Award (e.g., requiring that “Research funded under this grant must adhere to the [CDC/NIH Biosafety in Microbiological and Biomedical Laboratories (BMBL)].”). Moreover, NIH grant recipients are expected to provide safe working conditions for their employees and foster work environments conducive to high-quality research. NIH GPS, Section 4. The terms and conditions of the grant award flow down to subawards to subrecipients. 45 C.F.R. § 75.101.
As the grantee, EcoHealth Alliance was required to “monitor the activities of the subrecipient as necessary to ensure that the subaward is used for authorized purposes, in compliance with Federal statutes, regulations, and the terms and conditions of the subaward . . .” 45 C.F.R. § 75.352(d). We have concerns that WIV has not satisfied safety requirements under the award, and that EcoHealth Alliance has not satisfied its obligations to monitor the activities of its subrecipient to ensure compliance.
Moreover, as we have informed you through prior Notices of Award, this award is subject to the Transparency Act subaward and executive compensation reporting requirement of 2 C.F.R. Part 170. To date you have not reported any subawards in the Federal Subaward Reporting System.
Therefore, effective the date of this letter, July 8, 2020, NIH is suspending all activities related to R01AI110964, until such time as these concerns have been addressed to NIH’s satisfaction. This suspension is taken in accordance with 45 C.F.R. § 75.371, Remedies for Noncompliance, which permits suspension of award activities in cases of non-compliance, and the NIH GPS, Section 8.5.2, which permits NIH to take immediate action to suspend a grant when necessary to protect the public health and welfare. This action is not appealable in accordance with 42 C.F.R. § 50.404 and the NIH GPS Section 8.7, Grant Appeals Procedures. However, EcoHealth Alliance has the opportunity to provide information and documentation demonstrating that WIV and EcoHealth Alliance have satisfied the above-mentioned requirements.
Specifically, to address the NIH’s concerns, EcoHealth must provide the NIH with the following information and materials, which must be complete and accurate:
1. Provide an aliquot of the actual SARS-CoV-2 virus that WIV used to determine the viral sequence.
2. Explain the apparent disappearance of Huang Yanling, a scientist / technician who worked in the WIV lab but whose lab web presence has been deleted.
3. Provide the NIH with WIV’s responses to the 2018 U.S. Department of State cables regarding safety concerns.
4. Disclose and explain out-of-ordinary restrictions on laboratory facilities, as suggested, for example, by diminished cell-phone traffic in October 2019, and the evidence that there may have been roadblocks surrounding the facility from October 14-19, 2019.
5. Explain why WIV failed to note that the RaTG13 virus, the bat-derived coronavirus in its collection with the greatest similarity to SARS-CoV-2, was actually isolated from an abandoned mine where three men died in 2012 with an illness remarkably similar to COVID-19, and explain why this was not followed up.
6. Additionally, EcoHealth Alliance must arrange for WIV to submit to an outside inspection team charged to review the lab facilities and lab records, with specific attention to addressing the question of whether WIV staff had SARS-CoV-2 in their possession prior to December 2019. The inspection team should be granted full access to review the processes and safety of procedures of all of the WIV field work (including but not limited to collection of animals and biospecimens in caves, abandoned man-made underground cavities, or outdoor sites). The inspection team could be organized by NIAID, or, if preferred, by the U.S. National Academy of Sciences.
7. Lastly, EcoHealth Alliance must ensure that all of its subawards are fully reported in the Federal Subaward Reporting System
During this period of suspension, NIH will continue to review the activities under this award, taking into consideration information provided by EcoHealth Alliance, to further assess compliance by EcoHealth Alliance and WIV, including compliance with other terms and conditions of award that may be implicated. Additionally, during the period of suspension, EcoHealth Alliance may not allow research under this project to be conducted. Further, no funds from grant R01AI110964 may be provided to or expended by EcoHealth Alliance or any subrecipients; all such charges are unallowable. It is EcoHealth Alliance’s responsibility as the recipient of this grant award to ensure that the terms of this suspension are communicated to and understood by all subrecipients. EcoHealth Alliance must provide adequate oversight to ensure compliance with the terms of the suspension. Any noncompliance of the terms of this suspension must be immediately reported to NIH. Once the original award is reinstated, NIH will take additional steps to restrict all funding in the HHS Payment Management System in the amount of $369,819. EcoHealth Alliance will receive a revised Notice of Award from NIAID indicating the suspension of these research activities and funding restrictions as a specific condition of award.
Please note that this action does not preclude NIH from taking additional corrective or enforcement actions pursuant to 45 CFR Part 75, including, but not limited to, terminating the grant award. NIH may also take other remedies that may be legally available if NIH discovers other violations of terms and conditions of award on the part of EcoHealth Alliance or WIV.
Sincerely,
Michael S Lauer, MD
NIH Deputy Director for Extramural Research
Email: Michael.Lauer@nih.gov
cc: Dr. Erik Stemmy
Ms. Emily Linde
[W]e now believe it’s time to completely dismiss the wet market as the source of the outbreak. We also believe the preponderance of the evidence proves the virus did leak from the WIV and that it did so sometime before September 12, 2019.
This is based upon multiple pieces of evidence laid out in the report, including:
• The sudden removal of the WIV’s virus and sample database in the middle of the night on September 12, 2019 and without explanation;
• Safety concerns expressed by top PRC scientists in 2019 and unusually scheduled maintenance at the WIV;
• Athletes at the Military World Games held in Wuhan in October 2019 who became sick with symptoms similar to COVID-19 both while in Wuhan and also shortly after returning to their home countries;
• Satellite imagery of Wuhan in September and October 2019 that showed a significant uptick in the number of people at local hospitals surrounding the WIV’s headquarters, coupled with an unusually high number of patients with symptoms similar to COVID-19;
• The installation of a People’s Liberation Army’s bioweapons expert as the head of the WIV’s Biosafety Level 4 lab (BSL-4), possibly as early as late 2019; and
• Actions by the Chinese Communist Party and scientists working at or affiliated with the WIV to hide or coverup the type of research being conducted at there.
-- The Origins of COVID-19: An Investigation of the Wuhan Institute of Virology, by House Foreign Affairs Committee
A classified study of the origin of SARS-CoV-2 conducted a year ago by scientists at the Lawrence Livermore National Laboratory, the Department of Energy’s premier biodefense research institution, concluded the novel coronavirus at the heart of the current pandemic may have originated in a laboratory in China, Sinclair has learned.
Researchers at Livermore’s “Z Division,” the lab’s intelligence unit, issued the report May 27, 2020, classified “Top Secret.” Its existence is previously undisclosed. The Z Division report assessed that both the lab-origin theory and the zoonotic theory were plausible and warranted further investigation. Sinclair has not reviewed the report but confirmed its contents through interviews with multiple sources who read it or were briefed on its contents.
In an email to Sinclair, a Livermore spokesperson confirmed the existence of the report but declined to provide additional information. “Because the report you are referring to is classified,” wrote Lynda Seaver, director of public affairs, “it would be inappropriate for our lab to discuss this.”
-- Classified study found COVID-19 could have originated in Chinese lab, by James Rosen, ABC7 News, 5/3/21
Christopher Ashley Ford (born 1967) is an American lawyer and government official who served from January 2018 until January 2021 as Assistant Secretary of State for International Security and Non-Proliferation. He was nominated to that position by President Donald Trump, and confirmed unanimously by the U.S. Senate on December 21, 2017. After October 21, 2019, Ford also, by delegation from Secretary of State Michael Pompeo, performed the duties of the Under Secretary of State for Arms Control and International Security until his resignation from the Department of State on January 8, 2021.
Before his appointment as Assistant Secretary of State, Ford served in the Trump Administration as Special Assistant to the President and Senior Director for Weapons of Mass Destruction and Counterproliferation on the United States National Security Council staff, and a senior U.S. State Department official in the George W. Bush Administration working on issues of nuclear proliferation and arms control verification and compliance policy. He has also worked as a Senate staffer, as well as for the Hudson Institute.
-- Christopher Ashley Ford, by Wikipedia
Memo
From: Ford, Christopher A <FordCA@state.gov>
Sent: Friday, January 8, 2021 4:15:55 PM
To: Biegun, Stephen E <BiegunSE@state.gov>; StilwellDR@state.gov>; Berkowitz, Peter <BerkowitzP@state.gov> [DELETE] Krach, Keith J <KrachKJ@state.gov>
Cc: [DELETE] DiNanno, Thomas G <DiNannoTG@state.gov>; [DELETE]; Yu, Miles <YuMM@state.gov>; [DELETE]; Feith, David <FeithD@state.gov> [DELETE]
Subject: Summary of January 7, 2021, scientific panel discussion organized by AVC on the origins of SARS-CoV-2
Good afternoon, all:
We had a really valuable discussion yesterday evening with a fascinating panel of scientific experts organized by AVC on the question of the origins of the SARS-CoV-2 virus. It was something of a marathon session that lasted nearly three hours, and produced important insight on a number of fronts. I wrote up a summary of the event last night, and want to share it with all of you. I've attached in-line text below, as well as a PDF of the same information. (I didn't know what form will be more useful to you, so I adopted a "belt and suspenders" approach.) It's a long document, but hopefully interesting, and the issues are important.
Best.
- Chris
The Hon. Christopher A. Ford
Assistant Secretary for International Security and Nonproliferation
Performing the Duties of the Under Secretary for Arms Control and International Security ("T")
U.S. Department of State
Washington, D.C.
United States of America
Tel. (202) 647-1522
fordca@state.gov
TEXT FOLLOWS:
SUMMARY OF JANUARY 7, 2021, AVC PANEL DISCUSSION ORIGINS OF SARS-CoV-2 AND THE PANDEMIC
Yesterday evening, at my insistence, AVC convened a panel of scientists to discuss arguments made by a contractor on AVC's payroll that the Wuhan Institute of Virology (WIV) was most likely the origin of the SARS-CoV-2, the virus that causes the disease COVID-19. AVC has apparently been briefing this argument inside the Department and some interagency partners for some weeks, apparently on instructions from a staffer at S/P who told them they should not inform me or others of this work, nor involve the Intelligence Community. (I learned of this project only in mid-December, when AVC came to brief me on their contractor's findings, and immediately asked AVC to set up an opportunity for these scientific claims to be discussed and evaluated by scientific experts.) If well-founded, AVC's findings would be extremely significant, and have huge policy and political consequences, so I asked the Bureau to set up a scientific panel in order to help assess the validity of AVC's assessments. Several outside scientists picked by AVC served on the panel, and representatives from my office, AVC, ISN, OES, EAP, and INR, as well as NSC staff, also attended and took part in the nearly three-hour meeting. (I myself also attended.) It was a very valuable discussion.
AVC's argument is heavily based upon what it claims is the statistical improbability of SARS-CoV-2 occurring naturally, through zoonotic transmission outside of a laboratory. Under examination at the expert panel, however, these claims largely fell apart.
The panel did seem to agree on the importance of pressing China to show more transparency and asking tough questions about the origins of SARS-CoV-2. In particular, it was generally agreed that it's important to collect more data, including through widespread sampling of coronaviruses in the wild. There was also agreement that China's so far unexplained failure to report details of a cluster of six cases of pneumonia in 2013, three of which proved lethal, connected to a mine shaft in Yunnan where scientists later found the closest known relative to SARS-CoV-2 (a virus known as "RaTG13") was a grave public health failure that needs to be investigated. Beijing should have reported these prior illnesses to the international health community, and the viruses potentially associated with them, in order to inform coronavirus researchers and public health officials about the potential threat. All participants seemed also to agree that China should be pressed for answers about such things as the nature of any work done at WIV on novel coronaviruses, whether any safety incidents occurred, what data is in WIV's virus sequencing database (which was mysteriously taken offline early in the pandemic), and when exactly the PRC realized (despite its early representations) that SARS-CoV-2 was only in its "wet market" environmental samples -- and not its live animal samples -- leading them to conclude that the market was not the source of the outbreak.
These sorts of questions should indeed provide us with lots of grist for pressing China for answers and highlighting its non-transparency and history of failing to report (or even covering up) critical information. I am asking AVC and ISN to collaborate on drawing up a list of questions and points that could be useful in this regard.
When it comes to the statistical analysis AVC has used to show that SARS-CoV-2 was most probably the product of a laboratory release, to include genetic engineering of the virus, however, AVC's case rests primarily on a non-published Bayesian statistical analysis prepared for AVC by one scientist -- a pathologist, rather than a virologist, epidemiologist, or infectious disease modeler, who admitted to us that he had "never done a Bayesian analysis before" this -- who participated in the panel. AVC did not provide us with the actual paper before yesterday's discussion, so most other participants had not had the chance to study it in detail. (INR's resident epidemiologist, who has used Bayesian analysis frequently, has concerns about the validity of applying this underlying model and data to this hypothesis, and is presently reviewing the document.)
On the basis even of what was discussed in the meeting yesterday, however, AVC's statistical case seems notably weak. Their analysis revolves around drawing conclusions about how statistically likely it is that SARS-CoV-2 appeared naturally (zoonotically) compared to being engineered in or released from a laboratory, largely based upon differences between SARS-CoV-2 and other bat coronaviruses.
Over the course of a nearly three-hour discussion, however, it appeared that this statistical analysis is crippled by the fact that we have essentially no data to support key model inputs. Critically, we have no data on the vast majority of bat coronaviruses that exist in the wild -- which is to say, we have very little of baseline information against which AVC's analysis compares SARS-CoV-2. (At present, only perhaps 0.02 percent of such bat viruses, and perhaps 20 percent of bats though to carry coronaviruses have apparently been sampled, and there is enormous diversity in the bat virus population.) This is certainly a good argument for doing much more sample collection, and for pressing the PRC to do things like restore public access to WIV's virus sequencing database (and presumably excoriating and embarrassing the CCP if it refuses). But our general lack of knowledge about the diversity of bat coronaviruses that exist that is, the comprehensiveness of the comparison set -- undermines AVC's arguments about laboratory origin being likely because of the improbability of SARS-CoV-2 developing from any known coronavirus. (By loose analogy, in politics, it 's hard to learn much from comparing poll results if you have only a very small sample size and have no idea whether your samples are actually representative of the population at large.)
The assertion that WIV kept "thousands of coronaviruses" was also questioned in our discussion, since while it is true that WIV sequenced great numbers of viruses, such sequencing most commonly involves the possession of viral genomic material rather than live viruses. (This may have bearing on the risk of accidental release from a laboratory, since only live viruses entail a risk of infection, and genetic material is not infectious.) One of the panelists also noted the incredible difficulty of isolating live virus from bat samples, which are usually fecal samples, and that this is extremely unreliable and usually not successful. We don't seem to know anything about how many, and which, live viruses were actually kept at WIV -- which is, again, a powerful reason to ask more tough questions of the PRC, but not at this point reason to conclude laboratory escape.
Similarly, AVC has argued that based on the degree of difference between SARS-CoV-2 and its closest known relatives -- the above mentioned "Ra TG 13" coronavirus from the mine in Yunnan -- it is highly unlikely that SARS-CoV-2 occurred through natural genetic evolution, and thus more likely to have been engineered. This analysis is also gravely flawed, however, since it assumes that RaTG13 is the immediate precursor of SARS-CoV-2. But the panelists seemed to agree that RaTG13 was probably not the immediate precursor of SARS-CoV-2: it is merely the closest known relative -- which is a big difference -- and they all freely admitted we still have an exceedingly poor grasp of what's really "out there" in the bat virus world. As one panelist put it, we'd do better to collect more data than to "mess around with" trying to do statistical probabilities on the basis of such an incomplete data set; the resulting uncertainties are just too huge to make that approach useful.
(Note: The panelists agreed that AVC's supposedly statistical claims about WIV as a point of origin might be much more compelling if we discovered that WIV had actually done work with a precursor virus that really was much closer to SARS-CoV-2 than any yet known. End Note.)
Another problem related to assertions made about the likelihood that SARS-CoV-2 came from WIV that were based on WIV's proximity to "patient zero" for the COVID-19 pandemic, and the claim that there's no known evidence of human exposure to SARS-like coronaviruses in the Wuhan area compared to looking at exposure rates in human populations near a cave in Yunnan known to have SARS-like bat coronaviruses. There was disagreement, however, about the degree to which these geographic matters tell us anything useful. One panelist pointed out that although a point of origin in Wuhan seems more likely than transit from Yunnan, we actually don't know when or where "patient zero" actually was in the first place. Moreover, it was also pointed out that SARS-CoV-2 symptoms vary hugely from asymptomatic to very symptomatic (raising the possibility that cases will be missed, especially early in an outbreak before everyone knows to be looking for the disease), contagion can occur days before symptoms manifest, large numbers of people go back and forth between Yunnan and Wuhan all the time, and large parts of China, particularly rural areas where exposure to animals in higher, have poor health care systems and disease surveillance. Accordingly, conclusions on such bases, multiple participants noted, are not likely to be strongly compelling. While there did seem to be agreement that while there are likely more potential virus precursors in the Yunnan area than in Wuhan, it is still hard to draw too many conclusions at this point because relatively little was known about the total universe of bat coronavirus anywhere. (This lack of data was perhaps the strongest recurring theme of the scientific discussion.)
I hope this summary of the discussion was useful, for those of us involved found it very much so. In concluding this account, let me add two notes that were not discussed in yesterday's marathon scientific discussion, but that I believe to be important:
First, I would strongly caution against arguing that the PRC was "required" by the Biological Weapons Convention (BWC) to report all of its work at WIV, for that is not the case. In fact, the confidence-building mechanisms (CBMs) of the BWC expressly require only reporting on Biosafety Level Four (BS L-4) facilities, which China has done. (Work with most coronaviruses is not, in fact, normally conducted under BSL-4 conditions, whether in China or the United States.) The BWC's CBMs merely "suggest" reporting on BSL- 3 facilities if they are the highest-level ones that a given country possesses, and despite AVC's suggestions, it is not suspicious that the PRC stopped reporting on BSL-3s when their first BSL-4 facility opened (at WIV): doing exactly that is permissible under the BWC CBMs, and in fact this is what one would expect if they actually followed the instructions set forth in the BWC's CBM guide. (As I pointed out to David Stilwell last weekend, that guide is available online at https://unoda-web.s3-accelerate.amazona ... e-2015.pdf.)
I would also caution you against suggesting that there is anything inherently suspicious -- and suggestive of biological warfare activity -- about People's Liberation Army (PLA) involvement at WIV on classified projects. It's certainly possible that the PLA did secret BW work at WIV, but we have no information to suggest this. And it would be difficult to say that military involvement in classified virus research is intrinsically problematic, since the U.S. Army has been deeply involved in virus research in the United States for many years.
In any event, thanks for your patience with a long message. I thought the scientific discussion yesterday evening was extraordinarily valuable, and it should be very helpful in allowing us to fine-tune our messaging to and about the PRC. In the event that the Chinese suddenly respond to such questioning with an uncharacteristic degree of transparency and honesty, the global health community will be able to acquire more and better data, which may help clear up these critical questions, and increase the world's preparedness for the next pandemic. If, on the other hand, the PRC stonewalls and dissimulates, its refusal to entertain or respond to such pointed and important questions will help us expose the CCP even further as being disingenuously irresponsible in an area critical to global health security. In either event, therefore, yesterday evening's discussion will have been very helpful. My thanks to Tom DiNanno, Janey Wright, Thomas Cherry, and David Asher for setting up the meeting.
Response to Former Assistant Secretary Ford's "SUMMARY OF JANUARY 7, 2021, AVC PANEL DISCUSSION ORIGINS OF SARS-CoV-2 AND THE PANDEMIC"
12/9/2021 [actually 1/9/2021]
AVC is providing the following response in light of the fact that Former Assistant Secretary Ford’s memo was an inaccurate and misleading rendition of the event that mischaracterized the panel's exchanges and used references out of context.
• This event was not convened at the former assistant secretary’s “insistence”
It was conceived, organized, and hosted by AVC following weeks of emails and discussions between AVC personnel and several eminent scientists. The ground work that led to this concept was part of AVC’s preparation for the drafting of the annual compliance report and was further advanced by the knowledge, provided by S/P staff, that Department leadership desired to have the issue examined by a panel of outside experts. Former Assistant Secretary Ford’s only “insistence” in this matter was to insist on attending at the last minute, and to insist on disrupting the discussions between the experts by posing long-winded and ill-informed questions the purpose of which appeared to be to disrupt the proceedings and discredit the entire effort. That violated the ground rules established for what was to be an exchange of views between the scientific panel members with time reserved at the end of the panel discussion for questions or comments by the State attendees.
• The panel was NOT convened to “discuss arguments made by a contractor on AVC’s payroll”
The panel was convened to conduct a peer level review of draft studies by two scientists. The comments of the participants were not for attribution and the panel was understood to be only a starting point in a continuing dialogue. The panelists were never briefed on any AVC assessment or working hypothesis nor were they made aware of internal USG deliberations. AVC’s draft findings were never the topic of discussion – though the discussions went a long way toward validating some of AVC’s current findings. AVC is at a loss to understand Former Assistant Secretary Ford’s apparent confusion or previous lack of interest in this topic, one of the most important matters of the past twelve months.
• Former Assistant Secretary Ford was briefed on AVC’s initial classified and unclassified findings back on December 2nd.
AVC took the initiative to brief the former assistant secretary and ISN technical experts on AVC’s initial findings. AVC received no comments from, nor any followup by, the former assistant secretary nor his staff after the brief. During that brief, however, T staff made clear their apprehension and contempt for AVC engagement on SARS-COV-2 origins as part of our compliance analysis.
• Since AVC’s engagement with the interagency on this issue, the NIC has amended its previous assessment and is now much closer to AVC’s initial findings which did not accept the proposition of a natural occurrence of the virus to the exclusion of a lab escape possibility (despite the NIC’s apparent refusal to consider a number of important technical and open source evidence). A chronology of AVC interagency engagement is attached.
• When Former Assistant Secretary Ford implied agreement among panelists on various points, his summary mischaracterized the nature and content of the exchange of views.
This was not a policy deliberation within the department. As the moderator clearly explained in the introduction, the focus of the exchange was NOT to find agreement, it was to discover where there were questions or uncertainty such that the hypotheses and associated data sets before the panel could be refined and improved. The panel did not take a poll, and silence never implied consent. The panel was not there to validate the former assistant secretary’s notions of what policy should be pursued, but to critique and refine the draft analyses of Dr. Quay and Dr. Chan.
• AVC’s findings to date have never included “a non-published Bayesian statistical analysis”.
AVC requested the NIC to conduct a Bayesian analysis of COVID-19’s origin based on scientific and intelligence evidence in December. Despite the importance of this question and the resources at the NIC’s disposal, the NIC, to our knowledge, has not conducted the requested analysis. Having not received the requested analysis from the NIC, AVC requested that Dr. Steven Quay extend his current investigation into the origins of COVID-19 to include a Bayesian analysis of two important competing hypotheses in his findings. AVC knows of no similar substantive scientific analysis prior to AVC’s request to Dr. Quay. It was this work which was the focus of the scientific panel – NOT AVC’s findings.
• The Bayesian statistical analysis that was the subject of the evening’s discussion was NOT prepared by a pathologist.
Dr. Quay is a renowned biochemist Phd, MD, and biotech entrepreneur with 78 patents to his name (bio attached). Moreover, Former Assistant Secretary Ford failed to acknowledge the contributions of Dr. Chan, whose work was also the subject of this panel’s discussion. Her deep expertise of Chinese duplicity and lack of transparency was very insightful and helpful as AVC looks at compliance issues. The fact that AVC was able to attract such eminent scientists, across multiple biological disciplines, all focused on the question of COVID-19’s origin, for more than two and a half hours, to review Dr. Quay’s and Dr. Chan’s work, speaks very highly of their competence to make original contributions on this important matter. Despite the cynical attempt to impugn Dr. Quay’s qualifications in this matter Dr. Ford praised the panel diversity and qualifications the same day he penned his memo. Most who attended this review of Dr. Quay’s work do not know that he has also collaborated with a very highly qualified bio statistician regarding this and previous work. This individual was not available and thus his contributions were not included in the discussion. The CVs of the panelists are attached, which demonstrate the extraordinarily high and diversified level of scientific expertise present on this panel.
• AVC and Dr. Quay welcomed any inputs from INR’s epidemiologist.
• The former assistant secretary misunderstood a key point of the scientific discussion when he states, “this statistical analysis is crippled by the fact that we have essentially no data to support key model inputs. Critically, we have no data on the vast majority of bat coronaviruses that exist in the wild”.
On the contrary, we don’t need to know every bat coronavirus genome to understand the likelihood of a zoonotic vs. lab origin. We merely need to reliably estimate the number of bat coronaviruses there are, and factor this into our weighting of our present knowledge about bat coronaviruses. This is how Bayesian analysis works. Fortunately for the world, and unbeknownst to some of the panelists, this calculation had already been done, conservatively so, by Dr. Daszak who is one of the world’s greatest proponents of the zoonotic origin hypothesis.
• The former assistant secretary’s identification of what is NOT known about the parthenogenic contents of the Chinese labs, while true, is totally irrelevant to the Bayesian approach which focuses on what we DO know, specifically what current evidence can be quantified and weighed.
This approach allows us to consider all relevant quantifiable evidence in order to calculate the likelihood of a given hypothesis. Bayesian analysis was designed to help determine the probability of an event when there is uncertainty and data is incomplete, which as Dr. Muller, the moderator, pointed out, is the circumstance in almost all scientific inquiry. Dr. Ford’s injection of personal viewpoints was entirely inappropriate and disruptive of the flow of the panel members’ discussion.
• The former assistant secretary’s RaTG13 strawman completely misrepresented AVC’s findings.
AVC has never assumed that RaTG13 is the immediate precursor of SARS-CoV-2. RaTG13 is significant for other reasons having to do with its potential as a backbone for the creation of a parthenogenic chimeric viruses. It is also significant given the suspect behavior of PRC scientists regarding disclosure of information about this virus and the clouded and questionable nature of previous disclosures about its origin, genomic structure, and laboratory experimentation.
• The former assistant secretary is mistaken if he is implying that AVC, or any of the scientists, would “conclude laboratory escape” based on Dr. Quay’s paper or any of the discussions.
Again, this was not a policy discussion aimed at reaching a consensus conclusion. The purpose of the panel was to assist Dr. Quay in refining his Bayesian analysis of two different hypotheses, laboratory origin being one and zoonotic origin being the other. This entire effort was intended to be a discussion among scientific experts on the two presentations, deliberately avoiding the introduction of any policy issues or attempts to force a conclusion or consensus – as was made clear by the ground rules, the opening comments by Dr. Muller as moderator, and AVC SBO DiNanno as host. It should be noted that no panelist questioned the Bayesian approach. The moderator of the panel, Dr. Muller, and the majority of the panel, without objection from any member, believed that a Bayesian analysis was an appropriate tool for an investigation of this question and that the appropriate next step was to identify elements of that analysis that were in question and attempt to refine the model. The only significant questions raised dealt with the weighting, or ability to assign weights, to individual elements of the Dr. Quay’s 19-element assessment. That being said, inputs were solicited by the panel and are welcome.
• Either through misunderstanding of the moderator’s instructions, or on purpose, the former assistant secretary managed on multiple occasions to sidetrack the panel discussion away from its scientific mission by interjecting comments and questions in violation of the ground rules under which the panel members agreed to participate in this event.
• Over the past months, members of Former Assistant Secretary Ford’s staff, and some AVC staff members, warned AVC leadership not to pursue an investigation into the origin of COVID-19. Both AVC and ISN staff members stated that AVC would “open a can of worms” if it continued.
When asked, none of these staff members could or would elaborate, but their reluctance to pursue this effort was evidenced by failure to provide information when requested and a complete lack of responses to briefings and presentations that were undertaken by AVC. AVC will continue to pursue its statutory mandate to investigate all matters dealing with BWC compliance including aspects of this pandemic that may indicate a failure by the PRC to honor its treaty obligations and commitments.
• The actions of Dr. Ford regarding this entire effort, including his interruption of the panel discussion and the parting shot of his memorandum to the Secretary, appears to be part of a continuing effort to impose his pre-conceived conclusion about the origin of the virus uninformed by the mass of open source material presented by AVC or the substance of the exchanges that took place during the panel discussion. His attitude and that of his staff was also demonstrated by a hostility to even posing questions to the PRC related to the Biological Weapons Convention or the WHO International Health Regulations, the latter of which are legally-binding, clearly violated, and related to the origin of the virus and the activities that took place at the Wuhan Institute of Virology.
On January 7th AVC was honored to host a scientific discussion involving several of the world’s most accomplished experts in the fields of biochemistry, molecular biology, zoonotic diseases, immunology, biological warfare, aerosol physics, and synthetic biology, regarding the first substantive scientific Bayesian analysis of two COVID-19 origin hypotheses. They graciously devoted almost three hours of their time without compensation to help refine Dr. Quay’s outstanding work, agreed to consider further refinement of his analysis, and are to be commended for those selfless contributions to get to the root causes of the global pandemic.
United States Government Expert Analysis on the WHO-Convened Global Study of the Origins of SARS-CoV-2 Joint China-WHO Report
April 5, 2021
TOPLINE POINTS
• While the report includes some new relevant information potentially related to the origins of COVID-19, the report has not significantly improved our understanding of how the virus might have started circulating in Wuhan, which was called for in the study’s Terms of Reference (TOR) for the investigation.
• Conclusions made by the joint expert team lack raw data and/or supporting information in the final report and annexes. In fact, some sections of the report appear to contradict or undermine conclusions in other parts of the report.
• The information and analyses presented in the report did not provide clear scientific support for any one hypothesis, and additional work is needed to identify the origins and circumstances leading to the emergence of SAR-CoV-2 in the hopes of reducing the probability of a similar event.
• The report does not provide substantive guidance for future investigations, such as prevention of new outbreaks/spillover events, design of studies of novel outbreaks of unknown origin, or lessons on treatments/risk factors for patients.
Methodology
• When reviewed by the international experts, Phase 1 studies appear to have needed additional data and analyses, and some of those analyses may still be underway. The need to refine the design of the studies and interpretation of the analyses suggests problems in the initial parts of the investigation.
• The report does not appear to have fulfilled the TOR, which lays out more extensive studies, such as comprehensive epidemiological analyses and mapping of supply chains of animals and products.
• Summary data were presented to the external panel, but raw data did not seem to be available for analyses, other than viral genome sequence data.
• The report revealed several types of tests and studies that were not yet completed, despite the long time elapsed and potential relevance to the origins of the virus, for example retrospective testing of all available clinical and surveillance samples from Wuhan.
• Some referenced articles have not been peer-reviewed and others appear to have been withdrawn. References claimed to support infectivity actually appear to describe stability.4
Key Findings
• The report lists four possible pathways of emergence, but it does not include a description of how these hypotheses were generated, would be tested, or how a decision would be made between them to decide that one is more likely than another. Therefore, it is difficult to understand how each of these could have a probability assigned to it.
• The qualitative risk assessment does not discuss the level of uncertainty associated with different classifications.
• The analysis of the possible pathways of emergence (p.115-123) does not link up well to the three sections presenting the analyses by the working groups. They are a blanket statement of likely versus unlikely, with no link to why the data presented in the report makes one more or less likely.
• The report only provides a cursory look at the laboratory incident hypothesis, and the evidence presented seems insufficient to deem the hypothesis “extremely unlikely.”
• The joint team’s assessment is that “introduction through cold/ food chain products is considered a possible pathway.” Although such a pathway is theoretically possible, there is no evidence presented in the report to indicate that it is, in reality, an actual pathway. The report notes the probability of a cold-chain contamination with the virus from a reservoir is very low, it is not emphatically stated in the up-front summary.
• Lack of key data and information on fomite transmission, such as infectious dose, undermines the conclusions about transmission via cold-chain products.
• Alternate explanations for contamination of containers or packaging, such by handling through a COVID-19 infected person, are not adequately explored.
• The three sections presenting working group analyses read more like generalized literature reviews without linkages to the possible pathways of emergence. The report does not bring the three analyses together or discuss how the data from across the analyses informed their conclusions. For example, data from the Huanan Seafood Market is examined by all three working groups, but at no point is that information all clearly brought together to make an overall statement about the role of the Huanan Seafood Market in the early spread of SARS-Cov_2.
Report Recommendations
• The report does not appear to prioritize among the various recommendations, and recommendations may have feasibility challenges at this stage of the pandemic. For example, results of farm surveys could be confounded by human to animal transmission over the past year.
• Phase 2 studies are not well laid-out, with specific, targeted questions to ask to resolve origins questions.
USG EXPERT ANALYSIS
Main Findings of Working Groups
• Epidemiology
• The report concluded that none of the data analyzed showed evidence of widespread circulation of SARS-CoV-2 in Wuhan before December 2019, although could not exclude the possibility of undetected low-level circulation, and suggested additional research to investigate this issue.
• Contrary to the TOR’s mandate for the mission to analyze “in-depth reviews of hospital records for cases compatible with COVID-19 before December (page 6), most data analysis and interpretation has been performed on previously compiled assessments from limited sources (a few hospitals and centers). Data are primarily presented as already processed, summary data. It is not evident that raw data was made available to be examined or re-analyzed by the team, or that the team had access to ask for more information beyond what was presented. The data presented do not show the extensive mild/asymptomatic cases that should have been likely before the severe cases were detected. The selection of only two hospitals in Wuhan which show extremely low cases of influenza (e.g., Annex: Figure 3 shows only 20-60 adult confirmed influenza cases in peak influenza season) warrants further discussion.
• The epidemiologic data provided was difficult to follow and the different pieces didn’t seem to be consistent with each other. For example, the trends in Influenza-like illness (ILI) data seemed relatively flat year-round in previous years and early in 2019, which was surprising given the seasonal nature of influenza (page 19, figure 1). The 2017-2018 influenza season was a severe epidemic in the Northern hemisphere (as documented by China in the peer-reviewed literature: e.g. https://bmcinfectdis.biomedcentral.com/ articles/10.1186/s12879-019-4181-2 ) and thus Wuhan data showing a flat baseline was inconsistent with previously published data, with the graphic presented in Annex: Figure 1 (page 137), and not expected. Furthermore, Figures 4 and 5 do not correlate to the data presented in Figures 1-3 reporting ILI cases and percent influenza in adults and pediatrics from one hospital each.
• Several types of disease surveillance and mortality data presented from Fall 2019 indicate no evidence of the early circulation of SARS-CoV-2, however the possibility was not excluded and follow-on studies were recommended to further explore this issue. It is unclear why some of the follow-on work is recommended. For example, it is suggested that next steps include further review of data on respiratory illnesses from on-site clinics at the Military Games in October 2019. However, in the discussion of the Military Games and other international events -- it is noted that there are no clusters of fever or respiratory illness.
• Additionally, an increase in ILI and laboratory confirmed influenza cases was noted in December 2019, particularly in children. Details were not provided on which subtype(s) were present in these children or if samples were also tested for COVID-19. These results were also not consistent and did not correlate with data on deaths during the same time period, or in next month, as those were found to be in older adults. Without access to the raw data it is difficult to understand the trends in respiratory cases before and during December 2019, and into January 2020.
• Although early reported cases were linked to the Huanan market (or other markets), there were as many cases not linked to markets and also sporadic cases in the community earlier than the first markets cases. This suggests that the virus was circulating unnoticed in the community prior to the first clusters detected associated with the Huanan market.
• The report is not clear about which team considered the 92 cases to be compatible with SAR-CoV-2 infection, the team from 233 health institutions or the international team.
• Investigation into possible earlier cases should have occurred and is still needed. This is another example of a missed opportunity to further evaluate the initial cases.
• It is not clear how many “other cases” were reviewed and how they were excluded as incompatible. This appears to be a missed opportunity to thoroughly review the epidemiological studies to identify other possible exposures.
• USG Position
• The report’s conclusions are based on limited data sets which likely should be expanded. The recommendations to look further into details and an expanded data set derived from more hospitals and local, regional and national registers are reasonable and justified. However, it seems rather unlikely that new conclusions will be drawn from surveillance data. Thus, new approaches should be considered such as intensified testing of archived material and blood bank specimens (mentioned by the team) to find answers for the emergence of SARS-CoV-2.
• Molecular Epidemiology
• Combining worldwide and early molecular epidemiology was well done. Overall, this section has the format of a manuscript/review article rather than an investigation report. Conclusions, such as linking genomic with epidemiological data, sequence quality control and studying closely related bat sequences, are supported and justified. Other conclusions, such as spreading event at the Huanan Market and unrecognized circulations/introductions, are rather hypothetical. Environmental sample sequences from other countries need to be further verified and supported by additional investigations. This seems very vague and lacks strategy/concept.
• Some new genetic analyses were generated as part of this study, which is useful to the origin questions. One of the conclusions is that genetic sequences diversity indicates additional sources or unrecognized circulation, but that is not correlated with the epidemiologic data section.
• Viral genome sequences from the earliest human cases in December 2019 were not included for analysis and comparison, only sequences available after January 2020. Based on sequences available to date, molecular analyses suggest the virus most likely emerged between September and November 2019.
• The sequences available for analysis from January 2020 already showed different sequences clusters present in the infected people.
• Access to viral genomes from the first cases in December, if they exist, would be more informative to better characterize the earliest sequences and cases, and perhaps better inform on timeline and source of emergence.
• USG Position:
• There is a need for more early sequences if material is still available/ accessible. This would include specimens from human cases (e.g., blood draws), animals (wildlife and domestic) and environment. A worldwide accessible database needs to be implemented with quality control at entering level. Data analysis needs to be performed by a team of international experts rather than local/national entities. A global effort seems possible on this topic if all countries and researchers agree to a joint concept/strategy.
• Animal and Environmental Studies
• The report concludes that coronaviruses that are phylogenetically related to SARS-CoV-2 have been identified in multiple animals, but did not identify a specific host. This section of the report includes material on possible cold chain transmission.
• A significant amount of work has been summarized in this section, unfortunately, with little outcome in identifying the source/reservoir/intermediate host. Some of the presentations, such as the presentation on SARS-CoV-2 in mink in the Netherlands, is odd and appears peripheral to information requested in the TOR. The link to bats has some evidence based on coronavirus diversity in bats (based on the literature, not findings from the investigation) but this report does not present sufficient data to make conclusions.
• Environmental sampling seems insufficient as it is largely related to the Huanan Market. The same holds true for frozen food and cold-chain products, as the portion of the report looking at cold-chain transmission is 2 pages long (p.110-111) and includes minimal data to analyze the possibility of infection as a result of frozen foods, nor citations to support the assertions. All laboratory evidence so far speaks against frozen food as a source, but current investigations seem insufficient for final conclusions.
• Samples (sample types not clear besides feces) were collected and tested from a number of different wild and domestic animal species, including rabbits, cats, dogs, rodents, porcupines, poultry, swine etc., from different locations and times (total numbers, timing and locations are a bit hard to follow and summarize). All samples tested as a part of this effort were negative for SARS Cov-2 and for antibodies to SARS CoV-2.
• Previous and other published data were also presented and summarize the SARS CoV-2 related viruses sequences detected in bats and pangolins to date. These data support the potential for bats and/or pangolins to be a potential part of the transmission chain of spillover of the virus from animals to people.
• USG Position:
• An area with little attention so far seems to be wildlife farms/traders and breeding farms of wildlife species (nearby or far-away) including illegal farming .If a potential animal source cannot be identified on the nearby consumer market, one should go up the trading and production line. This could be geographically far away as wildlife products are often brought in from long distances. Environmental sampling on different markets within and outside the province may be helpful. The identification of the origin is less likely to be determined through environmental sampling, but data could be supportive. While frozen food and cold-chain products have not been excluded by the current investigations, it is noteworthy that no evidence has been presented is occurring. Further investigations are warranted because viruses are rather stable in cold environments and while contaminated food products could theoretically be a source of infection, there remains no direct evidence of transmission of COVID-19 via cold chain products to date nor does the report present any such evidence. However, highest priority would be investigations into wildlife farms and breeding facilities around Wuhan and greater China, and discussion of frozen or cold-chain food products should differentiate between frozen wildlife products and commercial products. In addition, studies examining wildlife for potential reservoir/amplifying species in China should be expanded. Finally, a global effort should be initiated to look into reservoir/intermediate host species.
Possible Pathways of Emergence
• Direct zoonotic transmission
• Data from this report did not shed any additional light on this hypothesis.
• While the global scientific community agrees that this is a likely source, the studies documented in the report did not uncover much new information on the original virus reservoir—no analysis of new data, or visits to possible locations in Wuhan or elsewhere.
• The published data to date show that the most closely related viruses, but not any sequences identical to SARS CoV-2, have been found in a number of Rhinolophid bats species in China, Japan Cambodia and Thailand. This is also the group of bats that has been shown to carry SARS CoV-1 related viruses. This is still the strongest evidence to date based on the published literature that bats may be linked in some way to the emergence of SAR CoV-2.
• USG Position:
• The evidence provided in the report does not support this hypothesis over others; however, the published data fit best with the hypotheses of either a direct zoonotic transmission or transmission via an intermediate animal host.
• Introduction through intermediate host followed by zoonotic transmission
• Data from this report did not shed much additional light on this hypothesis. There is some evidence to support an intermediate animal host or hosts may be linked to transmission to people.
• Published data to date show that pangolins also carry viruses related to SARS CoV-2 (90% similarity). Additionally, also from the literature and/or experimental studies, other species have been shown to be susceptible to COVID-19 infection.
• Introduction via an intermediate host is not well separated from “direct zoonotic transmission,” and it is not clear what evidence would distinguish these two hypotheses.
• USG Position:
• The evidence provided in the report does not support this hypothesis over others; however, the published data fit best with the hypotheses of either a direct zoonotic transmission or transmission via an intermediate animal host.
• Introduction through the cold/food chain
• The joint team’s assessment is that “introduction through cold/ food chain products is considered a possible pathway.” Although such a pathway is theoretically possible, the evidence presented in the report does not suggest that it is, in reality, an actual pathway.
• Currently, there are no data to support the hypothesis that the introduction came through foodborne transmission; therefore, it is not likely that the introduction came through foodborne transmission. However, this route of transmission cannot be excluded either at the moment.
• Not only is infection via frozen food items considered low likelihood, for this to be the source of the original Wuhan infections, there would need to be a high level of SARSCoV- 2 infection in another community for food products to carry enough virus to provide an infectious dose. It seems unlikely that such a high rate of infection in any other city or country would have been missed.
• This section included discussion of environmental sampling and description of vendors at the Huanan market, a description of the supply chain for and sampling of animals at the market (in Jan – March, 2020), domestic animal testing, and further testing of livestock and captive wildlife for SARS-CoV-2. It also includes discussion of what is termed the “study on cold-chain products”. However, it does not appear to be a well-designed study, but rather some opportunistic surveillance; the sampling design and any rationale for it is not discussed.
• They present data from China that indicate that some imported cold-chain samples have tested positive and that some workers at import facilities had Covid-19 which demonstrates an association, but not causality.
• Furthermore, they do not provide any details about the analytical methods or provide any details of the handling of the product before it was sampled to control for potential contamination within China. Note that from our understanding the imported products are sampled at a special warehouse that the products are moved to after they clear Chinese customs and many of the positives were from samples collected on the outside packaging, leaving opportunity for contamination from workers to have occurred.
• Lastly, they do not discuss the false positive rate of the tests used (or provide data on the performance of positive and negative controls). Note that we heard at one point, only about 40 samples of imported cold-chain product out of about 1.5 million samples tested positive (or < 0.003%).
• The report does not discuss the temporal relationship between tests and cases or any potential confounding factors (e.g., person-to-person spread, or transfer of RNA from already infected, asymptomatic cases to the packaging), which are key considerations for drawing conclusions about causality rather than associations.
• Documented evidence or peer-reviewed scientific publications are needed to support these statements.
• This paragraph points to the potential for other exposures besides cold-chain seafood.
• The report focuses a great deal on the exterior packaging of frozen products. More information is needed about the potential for the shipping container itself to serve as the point of contamination. More information is needed to document the traceability of particular shipping containers. Consideration needs to be given to the point at which the shipping container may have become contaminated, such as when it was in a shipping yard in China.
• This is noteworthy, as there is a recommendation to conduct further testing of stored product. It is also interesting that no domestic products were sampled and tested.
• There is no further information about these “index cases” and how they were evaluated for other exposures.
• This supports the argument against this theory and is the same conclusion many other countries, including the United States has reached.
• USG Position:
• Although it might be theoretically possible that the cold-chain could be involved in transmission of CoV-2, there is no credible evidence presented in the report to support that it actually occurred. If contaminated food entered markets such as the Huanan Market, one would likely have to assume that clusters/outbreaks would have occurred in another location, which has not yet been detected.
• Introduction through a laboratory incident
• The main report does not describe sufficient investigation into a potential laboratory incident, and there are no data presented in the report on this scenario. In the Annex, there are short visits described to Hubei CDC, Wuhan CDC and Wuhan Institute of Virology (WIV), though there is limited discussion of potential laboratory accidents or examination of records to dismiss the possibility. Possibilities for a lab-associated origin could include: direct infection of a laboratory worker; infection of a field worker collecting animal specimens; or improper disposal of an infected animal from a laboratory resulting in a human being infected.
• The report reveals that WIV leadership said none of the staff tested positive for the virus or antibodies to the virus, however there were few details provided on employee health monitoring, dates of antibody and PCR screening, and numbers of lab members tested on those dates.
• Data presented regarding laboratory visits by the team to investigate possible sources of the outbreak also does not include adequate data to examine possible exposure by laboratory workers in the field while sampling bats or other animals, which could have led to the first case.
• USG Position:
• There was minimal investigation into this possibility. The assessment of this hypothesis being extremely unlikely is justified based on the narratives provided by the labs, however one should not give the impression that this is based on data derived from a forensic investigation of the laboratory.
Recommendations for Next Steps
The lack of definitive conclusions in the report is not surprising given the mandate of the team and the circumstances in interacting with the Chinese colleagues and the difficulty tracing the origins of emerging infectious diseases.
On a positive note, the report summarizes a tremendous amount of data (published or unpublished) and provides reasonable and justified recommendations for second-phase investigations. It also lays out many deficiencies as well as needs for future investigations. Finally, it provides two likely (not surprising) scenarios for the emergence of SARS-CoV-2 in the human population. Future investigations should be more timely and better prepared with direct involvement of the team leading the investigation and countries/laboratories performing it. On a negative note, the report does not exclude any of the four scenarios or provide support for any scenario beyond what was known previously. There was no direct investigation into the scenario of a laboratory incident – something that the investigation was not set up to allow. One could view the report as a decent start into a second-phase investigation. Future studies need to focus on broader searching for virus hosts (e.g., expanding animals sampled), more coherent hypothesis testing, and specific targeted questions that refine details about the origins of the virus/outbreak. Every recommendation for Phase 2 work should specify joint review to ensure the WHO team has access to data it needs to conduct thorough analyses.
Identifying the source of an epidemic/pandemic is not an easy task and success is not a given. The biggest lesson learned from the investigation/report is that transparency and real-time information/data sharing is key in the fight against infectious disease events of global dimension. It is also important to acknowledge that trying to do these "origin" studies after outbreaks/ epidemics/ pandemics start is never going to be easy. For many outbreaks, the source and spillover mechanism were not conclusively identified during or after the outbreaks, or the understanding of the origins came many years later. We must understand that expanded efforts to understand new pathogens and where they come from before there are widespread outbreaks is needed. Otherwise, we will continue to do the same thing over and over again—that is, wait until after outbreaks start while hoping for better results on sources of the pathogens.
Origins Review USG Expert Group
Mara Burr, JD, LLM
Director, Multilateral Relations
Office of Global Affairs
US Department of Health and Human Services
Mara.Burr@hhs.gov
Ray Arthur, PhD
We—our work, our research is open, and we have a lot of international collaboration. And from my knowledge, all our research work is open, is transparency. So, at the beginning of COVID-19, we heard the rumors that it’s claimed in our laboratory we have some project, blah blah, with army, blah blah, these kinds of rumors. But this is not correct because I am the lab’s director and responsible for research activity. I don’t know any kind of research work performed in this lab. This is incorrect information.
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BEIJING: Chinese military scientists allegedly investigated weaponising coronaviruses five years before the COVID-19 pandemic and may have predicted a World War III fought with biological weapons, according to media reports referring to documents obtained by the US State Department.
According to 'The Sun' newspaper in the UK, quoting reports first released by 'The Australian', the "bombshell" documents obtained by the US State Department reportedly show the Chinese People's Liberation Army (PLA) commanders making the sinister prediction.
US officials allegedly obtained the papers which were written by military scientists and senior Chinese public health officials in 2015 as part of their own investigation into the origins of COVID-19.
Chinese scientists described SARS coronaviruses, of which COVID is one example, as presenting a "new era of genetic weapons".
Coronaviruses are a large family of viruses, several of which cause respiratory diseases in humans – ranging from a common cold to Severe Acute Respiratory Syndrome (SARS).
The PLA papers referenced seem to fantasise that a bioweapon attack could cause the "enemy's medical system to collapse".
It references work by US Air Force colonel Michael J. Ainscough, who predicted World War III may be fought with bioweapons.
The paper also includes musing that SARS "which hit China in 2003" could have been a man-made bioweapon deliberately unleashed by "terrorists".
They reportedly boasted the viruses could be "artificially manipulated into an emerging human disease virus, then weaponised and unleashed in a way never seen before".
The document lists some of China's top public health figures among the authors and has been revealed in an upcoming book on the origins of COVID, titled 'What Really Happened In Wuhan'.
China reported the first COVID-19 case in the central Chinese city of Wuhan in late 2019 and since then the deadly disease has become a pandemic, affecting more than 157,789,300 people and causing over 3,285,200 deaths worldwide.
Tom Tugendhat MP and Australian politician James Paterson said the document raises major concerns about China's transparency on the origins of COVID-19.
Tugendhat, chairman of the House of Commons Foreign Affairs Select Committee, was quoted in ‘The Sun' as saying: "China's evident interest in bioweapons is extremely concerning.
Even under the tightest controls these weapons are dangerous.
"This document raises major concerns about the ambitions of some of those who advise the top party leadership."
Peter Jennings, the executive director of the Australian Strategic Policy Institute (ASPI), told news. com. au that the document is as close to a "smoking gun" as we've got.
"I think this is significant because it clearly shows that Chinese scientists were thinking about military application for different strains of the coronavirus and thinking about how it could be deployed," said Jennings.
"It begins to firm up the possibility that what we have here is the accidental release of a pathogen for military use," added Jennings.
He also said that the document may explain why China has been so reluctant for outside investigations into the origins of COVID-19.
"If this was a case of transmission from a wet market it would be in China's interest to co-operate, we've had the opposite of that."
Among the 18 listed authors of the document are People's Liberation Army scientists and weapons experts.
Robert Potter, a cyber security specialist who analyses leaked Chinese government documents was asked by The Australian to verify the paper.
He says the document definitely is not fake.
"We reached a high confidence conclusion that it was genuine. It's not fake but it's up to someone else to interpret how serious it is," Potter told news. com.au.
"It emerged in the last few years, they (China) will almost certainly try to remove it now it's been covered."
Questions remain over the origins of the deadly virus after a much derided World Health Organisation (WHO) probe earlier this year, with the organisation ordering a further investigation which factors in the possibly of a lab leak.
Most scientists have said there is no evidence that COVID-19 is manmade, but questions remain whether it may have escaped from a secretive biolab in Wuhan, from where the pandemic originated.
China is known to have been carrying out high risk "gain of function" research at the Wuhan Institute of Virology (WIV), which is near the outbreak's ground zero at the Huanan Seafood Market.
There is no evidence so far to suggest it was intentionally released by China.
Meanwhile, in Beijing, the state-run Global Times newspaper slammed The Australian for publishing the article to smear China.
An academic book that explores bioterrorism and possibilities of viruses being used in warfare was interpreted as a conspiracy theory by The Australian, which deliberately and malignantly intends to invent pretexts to smear China, Chen Hong, a professor and director of the Australian Studies Center at East China Normal University, told the newspaper.
"It is a shame for anti-China forces in Australia to back their own ideology against China at the expense of basic professional journalistic ethics, conspiring to twist the real meaning of the book," Chen said.
-- Chinese scientists discussed weaponising coronavirus in 2015: A paper titled The Unnatural Origin of SARS and New Species of Man-Made Viruses as Genetic Bioweapons suggested that World War Three would be fought with biological weapons, by The New Indian Express, 5/10/21
“When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus,” said David Baltimore, an eminent virologist and former president of CalTech. “These features make a powerful challenge to the idea of a natural origin for SARS2,” he said.
-- The origin of COVID: Did people or nature open Pandora’s box at Wuhan?, by Nicholas Wade
The National Institutes of Health (NIH) today [December 19, 2017] lifted a 3-year moratorium on funding gain-of-function (GOF) research on potential pandemic viruses such as avian flu, SARS, and MERS, opening the door for certain types of research to resume.Donald Trump's tenure as the 45th president of the United States began with his inauguration on January 20, 2017 and ended on January 20, 2021.
-- Presidency of Donald Trump, by Wikipedia“The Godfather of [gain-of-function virology research], the head of the pyramid, is a guy you may have heard of called Anthony Fauci,” Rogin said. “So, Anthony Fauci, the hero of the pandemic, is the most important person in the world of gain-of-function research there is . . . Basically, he is the one disbursing all the grants for this, he is the one who pushed to turn it back on after Obama turned it off, that’s another crazy story, he turned it back on without really consulting the White House.”
“He consulted the Office of Science and Technology Policy, which is part of the White House, but the White House put a pause on it and he undid the pause,” Rogin continued. “The details are a little sketchy. I’m not saying he did anything necessarily wrong or illegal, but I’m saying that a lot of people that I know inside the Trump administration had no idea that he had turned this back on. He found a way to turn it back on in the mess of the Trump administration because the Trump administration is full of a bunch of clowns, so you could get things done if you knew how to work the system.”
As Rogin himself admits, “the details are a little sketchy,” and we’ll have to take a look at the sourcing included in whatever article this piece of news appears in before alleging any wrongdoing.
-- Fauci Reportedly Relaunched NIH Gain-of-Function Research without Consulting White House, by Jack Crowe, National Review, April 27, 2021
The action coincides with today's release of a US Department of Health and Human Services (HHS) framework for guiding funding decisions about proposed research involving pathogens that have enhanced potential for creating pandemics.
Experts involved in the discussions welcomed the development, but some said the new framework still leaves key unanswered questions, such as how to responsibly report findings from the funded lab work in medical journals. Meanwhile, in research labs, some scientists plan to resume experiments and are relieved the pause has ended. Both groups are eager to see how the new review process works in real life.
In a statement today, NIH Director Francis Collins, MD, PhD, said "We have a responsibility to ensure that research with infectious agents is conducted responsibly, and that we consider the potential biosafety and biosecurity risks associated with such research." He added that he is confident that the review process spelled out in the new framework "will help to facilitate the safe, secure, and responsible conduct of this type of research in a manner that maximizes the benefits to public health."...
In light of controversial research on H5N1 viruses in 2012, the Obama administration in 2014 announced a pause of federally funded GOF research and asked a government advisory group to reevaluate federal GOF funding policies and put together recommendations to help officials make their decisions.
The expert group, called the National Science Advisory Board for Biosecurity (NSABB), commissioned a 1,000-page risk-benefit assessment to help them make their final guidance, which they finalized in June 2016, along with an ethics white paper. As part of the process, the NSABB held two National Academies symposia on GOF issues....
The framework, condensed into a 6-page document, spells out a multidisciplinary review process that involved the funding agency and a department-level review group that considers the merits and possible research benefits and the potential to create, transfer, or use an enhanced potential pandemic pathogen (PPP). In January in the final days of the Obama administration, the White House Office of Science and Technology Policy (OSTP) released guidance the departments can use to follow through with the reviews.
There are eight criteria in the framework for guiding HHS funding decisions, which stipulate, for example, that the research has been evaluated by an independent expert review as scientifically sound, that the potential risks and benefits are justified, that there are no other equally effective but less risky options for answering the research question, and that the research team and facility have the capacity to do the work safety and securely and to respond rapidly if there are any accidents, protocol lapses, or security breaches.
Regarding issues surrounding publication, the criterion says that the research results are expected to be responsibly communicated, based on applicable laws, regulations, and policies, along with terms and conditions of funding.
Also, the framework stipulates that the work will be done with the support of funding mechanisms that allow appropriate risk management and ongoing institution and federal oversight of the research. And finally, the criteria state that the research must be ethically justifiable...
Marc Lipsitch, PhD, professor of epidemiology and director of the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health, has been deeply involved in the GOF discussions and has argued for a much more rigorous approach for evaluating the experiments. He has pushed for experts to consider safer ways to assess potential pandemic virus threats and for an international approach to tackling the issues.
"My overall take is that this is a small step forward," he said, adding that it includes a department-level review of the most concerning types of research, which have been defined appropriately after extensive time and debate. "The question is how such reviews will play out in practice."
However, Lipsitch said one problem is that the guidance specifies that research groups that propose work with enhanced pathogens will need to convince reviewers that there is no feasible, equally effective alternative way of addressing the scientific question with a less risky approach.
"If this means no alternative to answer with certainty the question of whether a specific strain that occurs in nature can very easily evolve to acquire a ferret-transmissible phenotype, then this criterion will always be satisfied," he said. "This is a scientific question that can uniquely be answered with dangerous experiments, and cannot be answered safely. But it is not a very useful one, because every strain in nature is different."
Michael Osterholm, PhD, MPH, who was a member of the NSABB during the controversy over the H5N1 papers, said he believes the GOF work can be done safely, but he doesn't agree that scientists doing the federally funded work should be unfettered.
Osterholm said his main concern regards the public health implications of the publicly available details about how the work is communicated, which the new framework doesn't spell out. "How we detail that information needs to be considered," such as more finely specifying when findings are open to the general public, when they're disseminated on a "need to know" basis, and when the information is classified.
"Until we have that part solved, I'm concerned about the work being done," he said.
Osterholm, director of the University of Minnesota's Center for Infectious Disease Research and Policy, which publishes CIDRAP News, added that some research is needed to answer key questions, such as what it would take for Ebola to become a respiratory virus, findings that would have implications for preparedness. "If it were the case, I don't want the public to have a blueprint on how to do it," he said.
Tom Inglesby, MD, director and chief executive officer at the Center for Health Security at Johns Hopkins Bloomberg School of Public Health, has also been deeply involved in discussions about issues related to the research pause. He said the requirements for the multidisciplinary, department-level pre-funding review and the involvement of the White House OSTP are excellent.
He added that the emphasis on enhanced potential pandemic pathogens is correct and focuses the framework on where it should be, such as on harmful consequences, immunity disruption, conferred resistance, and reconstructed extinct pathogens. "Though for the policy to be successful it needs to, at a minimum, be able to oversee the creation of novel strains that may be highly transmissible and highly virulent and should probably focus on that most intently to start."
A potentially serious weakness of the new framework is that surveillance activities involving potential pandemic pathogens (PPPs), including sampling and sequencing, aren't considered to be enhanced PPPs and would be exempt from reviews, Inglesby said, adding that surveillance as a rationale doesn't change potential risks of novel PPP strains. "There are serious debates about whether specific enhanced PPP projects are materially useful to on-the-ground surveillance programs," he said.
Inglesby's other concerns revolve around the lack of hard details of how the experiment reviews will work, such as the process for weighing the risks and benefits and the criteria for judging if researchers and institutions have the capacity to do the work safely. "I would have liked to see if this framework was working as intended before the moratorium was ended," he said, suggesting that agencies funding the work publish their experiences using the new framework to show how it functions.
-- Feds lift gain-of-function research pause, offer guidance, by Lisa Schnirring, December 19, 2017
Table 1: WIV Researchers on CCP Propaganda Committees
WIV Researcher / Lab Affiliation / Propaganda Committee [12] [“Party Branch.” Wuhan Institute of Virology, http://www.whiov.cas.cn/djkxwh/dqzz/dzb/]
Liu Qiaojiue / Key Laboratory of Special [13] [Wang Q, et. al. “Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase.” Cell, 23 July 2020, 182(2):417-428.e13, https://pubmed.ncbi.nlm.nih.gov/32526208/] Pathogens and Biosafety / Party Branch of Research Center for Emerging Infectious Diseases
Zhang Xiaowei / Key Laboratory of Special [14] [Zhang, Xiaowei et al. “Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.” Journal of Neuroinflammation, 30 Aug. 2016, 13(1):209. https://pubmed.ncbi.nlm.nih.gov/27576490/] Pathogens and Biosafety and Key Laboratory of Virology / Party Branch of the Research Center for Microbiology and Nanobiology
Shen Xurui / Key Laboratory of Special Pathogens and Biosafety [15] [Zhou, Peng et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin.” Nature March 2020, 579(7798): 270- 273. https://pubmed.ncbi.nlm.nih.gov/32015507/] / Graduate Party Branch of the Research Center for Emerging Infectious Diseases
Tang Shuang / State Key Laboratory of Virology [16] [Abudurexiti, Abulikemu, et al. “Taxonomy of the order Bunyavirales: update 2019.” Archives of Virology, July 2019, 164(7): 1949-1965. https://pubmed.ncbi.nlm.nih.gov/31065850/] / Party Branch of the Research Center for Microbial Resources and Bioinformatics
Wu Yan / State Key Laboratory of Virology [17] [Su, Hai-Xia et al. “Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients.” Acta Pharmacologica Sinica, September 2020, 41(9): 1167-1177. https://pubmed.ncbi.nlm.nih.gov/32737471/] Party Branch of Molecular Virus and Pathology Research Center
He Lihong / State Key Laboratory of Virology [18] [Shao, Wei et al. “Functional Characterization of the Group I Alphabaculovirus Specific Gene ac73.” Virologica Sinica, Dec. 2019, 34(6): 701-711. https://pubmed.ncbi.nlm.nih.gov/31317397/] / Party Branch of the Research Center for Microbial Resources and Bioinformatics
Wang Qingxing / State Key Laboratory of Virology [19] [Su, Haixia et al. “Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease.” Nature Communications, 15 June 2021, (2(1): 3623. https://pubmed.ncbi.nlm.nih.gov/34131140/] / Graduate Party Branch of the Research Center for Molecular Viruses and Pathology
Yang Mengsi / State Key Laboratory of Virology [20] [Zhang, Juan, et. al. “Passive cancer targeting with a viral nanoparticle depends on the stage of tumorigenesis.” Nanoscale, 8 July 2021, 13(26):11334-11342, https://pubmed.ncbi.nlm.nih.gov/34165123/] / Graduate Party Branch of the Research Center of Microbiology and Nanobiology
(b)(6) [DELETE] Thus, while the BSL-4 lab is ostensibly fully accredited, its utilization is limited by lack of access to specific organisms and by opaque government review and approval processes. As long as this situation continues, Beijing's commitment to prioritizing infectious disease control -- on the regional and international level, especially in relation to highly pathogenic viruses, remains in doubt.
Advances in biomedical technologies, such as genome editing and synthetic biotechnology, have the potential to provide new avenues for biological intervention in human diseases. These advances may also have a positive impact by allowing us to address risks in new approaches. However, the proliferation of such technologies means they will also be available to the ambitious, careless, inept, and outright malcontents, who may misuse them in ways that endanger our safety. For example, while CRISPR-related techniques provide revolutionary solutions for targeted cellular genome editing, it can also lead to unexpected off-target mutations within genomes or the possibility of gene drive initiation in humans, animals, insects, and plants. Similarly, genetic modification of pathogens, which may expand host range as well as increase transmission and virulence, may result in new risks for epidemics. For example, in 2013, several groups showed that influenza H5N1 viruses with a few nucleotide mutations and H7N9 isolates reasserted with 2009 pandemic H1N1 virus could have the ability for airborne transmission between ferrets. Likewise, synthetic bat-origin SARS-like coronaviruses acquired an increased capability to infect human cells. Thus, modifying the genomes of animals (including humans), plants, and microbes (including pathogens) must be highly regulated. [32] [Gao, George F. “For a better world: Biosafety strategies to protect global health.” Biosafety and Health, June 2019, 1(1): 1-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147920/]
The maintenance cost is generally neglected; several high-level BSLs have insufficient operational funds for routine yet vital processes. Due to the limited resources, some BSL-3 laboratories run on extremely minimal operational costs or in some cases none at all. [35] [Ibid.]
Table 2: WIV Procurement Projects in 2019
Project Name / Location / Date / Budget (USD)
Maintenance Project of P3 Laboratory and Laboratory Animal Center in Zhengdian Park [37] [“Announcement of Competitive Consultation on Maintenance Project of P3 Laboratory and Laboratory Animal Center in Zhengdian Park, Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 1 March 2019, https://archive.is/7eCPU#selection-229.0-229.185] / WNBL / March 1, 2019 / $401,284.10
Procurement of Positive Pressure Protective Clothing [38] [“Announcement of a single source for the purchase of positive pressure protective clothing project by Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 21 March 2019, https://archive.is/VUcNA#selection-229.0- 229.157] / WNBL / March 21, 2019 / $177,161.40
Hazardous Waste Treatment System Renovation Project [39] [ “Announcement on the transaction of the hazardous waste treatment system renovation project in Zhengdian Park, Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 31 July 2019, https://archive.is/3CW03#selection- 229.0-229.166] / WNBL / July 31, 2019 / $1,521,279.28
Procurement Project of The Environmental Air Disinfection System and The Scalable Automated Sample Storage Management System [40] [“Announcement of winning the bid for the procurement project of the environmental air disinfection system and the scalable automated sample storage management system of the Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 14 Aug. 2019, https://archive.is/1nXLD#selection-229.0-229.228] / Unclear / August 14, 2019 / $132,200,025.47
Security Service Procurement Project [41] [“Competitive consultation on the procurement project of security services in Zhengdian Science Park, Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 12 Sept. 2019,https://archive.is/tUi75#selection-229.0- 229.156] / WNBL / September 12, 2019 / $1,281,022.33
Central Air Conditioning Renovation Project [42] [“Competitive Consultation on Central Air Conditioning Renovation Project of Wuhan Institute of Virology, Chinese Academy of Sciences.” China Government Procurement Network, 16 Sept. 2019, https://archive.is/bfoTD#selection-229.0-229.131] / Unclear / September 16, 2019 / $606,382,986.11
Procurement of Air Incinerator and Testing Service [43] [“The Wuhan Institute of Virology of the Chinese Academy of Sciences plans to use a single-source procurement method to publicize the procurement of air incineration devices and test service projects.” China Government Procurement Network, 3 Dec. 2019, https://archive.is/Jifqr#selection-229.0-229.197] / Unclear / December 3, 2019 / $49,388.81
Table 1: Virus data display of bat samples
Data element name / Example
Sample ID / 162387A
Sample tissue type / Anal
Animal type / bat
Source species / Rousettus leschenaultil
Species molecular identificatno / Rousettus sp.
Collection date / 2016-08-21
country / China
province / Yunnan
city / Miaoxin village, Mengna county, Sipsongpanna
GPS information: 101.51944.21.78127
Whether high-throughput sequencing / No
Whether the virus is isolated / No
publishing / Luo Y, Yi B. Jiang RD, et al. Virol. Sin. 2018;33(1):87-95. doi:10.1007/s12250-018-0017-2
Remarks / --
Detection Method / PCR-based
Virus name / Coronaviridae
Test results / Positive
blast result / btcov HKU9
Virus classification / HKU9
Virus sequence / See references for details
Similarity / 9436
Sequence length / 398bp
Sequence-encoded gene / Partial RdRp
…all our work regarding the different type of bat coronavirus (partial sequences or full-length genome sequences) have been published and the sequence and sample information have been submitted to GenBank. [49] [Ibid.]
We—our work, our research is open, and we have a lot of international collaboration. And from my knowledge, all our research work is open, is transparency. So, at the beginning of COVID-19, we heard the rumors that it’s claimed in our laboratory we have some project, blah blah, with army, blah blah, these kinds of rumors. But this is not correct because I am the lab’s director and responsible for research activity. I don’t know any kind of research work performed in this lab. This is incorrect information. [58] [Eban, Katherine. “The Lab-Leak Theory: Inside the Fight to Uncover COVID-19's Origins.” Vanity Fair, 3 June 2021, http://www.vanityfair.com/news/2021/06/ ... 9s-origins.]
Academic Committee of State key laboratory of virology, WIV, CAS
Director:
Zihe RAO, Tsinghua University, China.
Deputy Directors:
Hongyang WANG, The Second Military Medical University, China.
Hongbin SHU, Wuhan University, China.
Members
Jianfang GUI, Institute of Hydrobiology, Chinese Academy of Sciences, China.
Fusheng WANG, 302 Military Hospital of China, China.
Hualan CHEN, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China.
Zhenghong YUAN, Fudan University, China.
Ningshao XIA, Xiamen University, China.
Linqi ZHANG, Tsinghua University, China.
Musheng ZENG, Sun Yat-sen University, China.
Jianguo WU, Wuhan University, China.
Xinwen CHEN, Wuhan Institute of Virology, Chinese Academy of Sciences, China.
Ke LAN, Wuhan University, China.
This was a city of 15 million people that was in lockdown. It was strange, but we were told this was to make it easy for the Games’ participants to get around. [I got] very sick 12 days after we arrived, with fever, chills, vomiting, insomnia.… On our flight to come home, 60 Canadian athletes on the flight were put in isolation [at the back of the plane] for the 12-hour flight. We were sick with symptoms ranging from coughs to diarrhea and in between. [69] [Francis, Diane. “Diane Francis: Canadian Forces Have Right to Know If They Got COVID at the 2019 Military World Games in Wuhan.” Financial Post, 25 June 2021, https://financialpost.com/diane-francis ... taryworld- games-in-wuhan.]
[I got] very sick 12 days after we arrived, with fever, chills, vomiting, insomnia.… On our flight to come home, 60 Canadian athletes on the flight were put in isolation [at the back of the plane] for the 12-hour flight. We were sick with symptoms ranging from coughs to diarrhea and in between.
-- Canadian Athlete
“You can engineer a virus without leaving any trace. The answers you are looking for, however, can only be found in the archives of the Wuhan laboratory.”
– Dr. Ralph Baric
Article and Publication: “Bats Are Natural Reservoirs of SARS-Like Coronaviruses,” in Science (2005).
Participants: Li Wendog, primary author; Shi, second author and one of three corresponding authors; Peter Daszag; additional scientists from Australia and China.
Funding: The paper was supported in part by funding from the PRC government, who provided a special grant for Animal Reservoirs of SARS-CoV from the State Key Program for Basic Research (grant no. 2005CB523004) and the State High Technology Development Program (grant no. 2005AA219070) from the Ministry of Science and Technology.
It was also funded by the U.S. government, through the NIH and NSF, who provided funding in the form of an ‘Ecology of Infectious Diseases’’ award (no. R01-TW05869) from the John E. Fogarty International Center and the V. Kann Rasmussen Foundation.
Purpose: The scientists hoped to identify the origins of SARS by identifying species of bats which are a natural host for SARS-like coronaviruses.
Conclusion: “These findings on coronaviruses, together with data on henipaviruses (23–25, 28), suggest that genetic diversity exists among zoonotic viruses in bats, increasing the possibility of variants crossing the species barrier and causing outbreaks of disease in human populations. It is therefore essential that we enhance our knowledge and understanding of reservoir host distribution, animal-animal and human-animal interaction (particularly within the wet-market system), and the genetic diversity of bat-borne viruses to prevent future outbreaks.” [81] [Ibid.]
Relevance: This conclusion would drive the next fifteen years of collaboration between the WIV and Peter Daszak, with Shi directing the laboratory work.
Article and Publication: “Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin” in Journal of Virology.
Participants: WIV researchers and Linfa Wang. Shi is listed as the corresponding author.
Funding: This work was funded by the PRC government and grants from Australia and the European Commission.
Purpose: This study focused on the receptors used by the spike protein of SARS-like coronaviruses, which are the major surface structures that enable coronaviruses to bind to receptors on cells. To test this, researchers created multiple chimeric viruses by inserting different sequences of the SARS-CoV spike protein into the spike protein of the SARS-like virus being examined, and tested them against bat, civet, and human ACE2 expressing cells.
Conclusion:
One of these chimeric viruses was able to enter cells through the human ACE2 receptor. ACE2 is an abbreviation for angiotensin converting enzyme-2, which is a protein found on the surface of cells and tissues throughout the human body, including the nose, mouth, and lungs. “In the lungs, ACE2 is highly abundant on type 2 pneumocytes, an important cell type present in chambers within the lung called alveoli, where oxygen is absorbed and waste carbon dioxide is released.” [84] [Sriram, Krishna, et al. “What Is the ACE2 Receptor, How Is It Connected to Coronavirus and Why Might It Be Key to Treating COVID-19? The Experts Explain.” The Conversation, 25 May 2021, https://theconversation.com/what-is-the ... ing-covid- 19-the-experts-explain-136928.] ACE2 is also the location where SARS-CoV-2’s spike protein binds to human cells. Researchers concluded that “a minimal insert region” is “sufficient to convert the SL-COV S [SARS-like coronavirus spike protein] from non- ACE2 binding to human ACE2 binding.” [85] [Ren.]
Relevance: In other words, WIV researchers were able to take a SARS-like coronavirus that does not infect humans and modify it so it was able to do so. Also importantly, this work was done under BSL-2 conditions.
Article and Publication: “Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor” in Nature. [86] [Ge, Xing-Yi et al. “Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor.” Nature, 30 Oct. 2013, 503(7477): 535-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389864/]
Participants: WIV and EcoHealth researchers, including Hu,. Shi, Daszak, and Wang who are credited for designing the experiments. Shi and Daszak listed as corresponding authors.
Funding: The study was funded by grants from the PRC government (including grant no. 2013FY113500), as well as the National Institute of Allergy and Infectious Diseases (NIAID) (no. R01AI079231), a NIH/NSF “Ecology and Evolution of Infectious Diseases” award (no. R01TW005869), an award from the NIH Fogarty International Center supported by International Influenza Funds from the Office of the Secretary of the Department of Health and Human Services (no. R56TW009502), and USAID’s Emerging Pandemic Threats PREDICT program. [87] [Ibid.]
Purpose: This work marked “the first recorded isolation of a live SL-CoV” [88] [Ibid.] [SARS-live coronavirus], which researchers isolated from bat fecal samples and named WIV1. Additionally, they identified two novel bat coronaviruses (SCH014 and Rs3367) and reported “the first identification of a wild-type bat SL-CoV capable of using ACE2 as an entry receptor.” [89] [Ibid.]
Conclusion: “Finally, this study demonstrates the public health importance of pathogen discovery programs targeting wildlife that aim to identify the ‘known unknowns’—previously unknown viral strains closely related to known pathogens. These programs, focused on specific high-risk wildlife groups and hotspots of disease emergence, may be a critical part of future global strategies to predict, prepare for, and prevent pandemic emergence.” [90] [Ibid.]
Relevance: By isolating a wild-type (common strain in nature) SARS-like coronavirus that binds to ACE2, and testing it in human lung tissue, the authors proved that bat coronaviruses are capable of infecting humans directly, without having to pass through an intermediate host.
For important emerging emergencies and virulent viruses (influenza virus, Ebola virus, coronavirus, Marburg virus, arenavirus, etc.), by studying their ability to invade different host cells and their ability to replicate in different host cells, analyze the key molecules affecting their cross-species infections and their pathogenic mechanisms. Including: virus invasion, virus replication and assembly, and infection model. [112] [“Guidelines for the application of the ‘Pathogen Host Adaptation and Immune Intervention’ project of the Chinese Academy of Sciences Strategic Leading Technology.” Chinese Academy of Sciences, 6 Sept. 2018, https://archive.is/spmNg#selection-3389.0-3389.160]
Coronaviruses are pretty good – I mean you’re a virologist, you know all this stuff – but the… you can... um manipulate them in the lab pretty easily. The spike protein drives a lot of what happens with the coronavirus – zoonotic risk. So, you can get the sequence, you can build the protein, and we work with Ralph Baric at UNC to do this, insert it into a backbone of another virus, and do some work in the lab. So, you can get more predictive when you find a sequence – you’ve got this diversity. Now, the logical progression for vaccines is, if you’re going to develop a vaccine for SARS, people are going to use pandemic SARS, but let’s try to insert some of these other related [viruses] and get a better vaccine. [119] [Racaniello, Vincent. “TWiV 615: Peter Daszak of EcoHealth Alliance.” YouTube, interview by Vincent Racaniello,19 May 2020, https://www.youtube.com/watch?v=IdYDL_RK--w]
This finding was surprising as a zoonotic virus typically exhibits the highest affinity initially for its original host species, with lower initial affinity to receptors of new host species until it adapts. As the virus adapts to its new host, mutations are acquired that increase the binding affinity for the new host receptor. Since our binding calculations were based on SARS-CoV-2 samples isolated in China from December 2019, at the very onset of the outbreak, the extremely high affinity of S protein for human ACE2 was unexpected. [122] [Piplani, S., et. al. “In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin.” Scientific Reports, 24 June 2021, 11(13063) https://www.nature.com/articles/s41598-021-92388-5]
Molecularly cloned viruses were indistinguishable from wild type.
– Dr. Ralph Baric
We established a reverse genetics system for coronaviruses, and based on the genomic backbone of WIV1, we established a scheme to replace the S gene without traces, constructed infectious BAC clones of 12 S-gene chimeric recombinant viruses, and successfully rescued. Four of these recombinant viral strains (including Rs4231, Rs4874, Rs7327, and SHC014) were tested for ACE2 utilization by these strains in humans, civets, and bats.
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