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Francis Collins and Anthony Fauci emailed about whether NIH funded Wuhan lab before secret call

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Posted on by Emily Kopp

Leaders in infectious diseases research funding may have unduly shaped the public’s understanding of where COVID-19 began, emails suggest. (Photo credit: NIH images)

In the earliest days of the pandemic, Anthony Fauci and Francis Collins emailed about coronaviruses under study at the Wuhan Institute of Virology and about whether they had steered money to the lab, an email obtained by U.S. Right to Know shows.

Collins, then leader of the National Institutes of Health, and Fauci, leader of its infectious diseases institute, exchanged emails on February 1, 2020, about a preprint authored by Zhengli Shi, director of the Wuhan Institute of Virology’s Center for Emerging Infectious Diseases. The preprint described bat coronaviruses under study at the lab, including a coronavirus 96 percent genetically similar to the coronavirus that causes COVID-19. 

The emails show that Collins and Fauci were concerned about links between the Wuhan Institute of Virology and NIH.

“In case you haven’t seen this preprint from one week ago,” Collins said in a February 1, 2020, email to Fauci. “No evidence this work was supported by NIH.” 

“I did see it, but did not check the similarities. Obviously we need more details,” Fauci replied, a little before noon.

Some details of the short exchange are redacted. 

The email shows that these concerns were top of mind at a critical time. 

About two hours after the email exchange, Collins and Fauci would join a secret teleconference with a group of virologists who were closely examining the novel coronavirus. The teleconference touched off a high profile push to discredit the lab leak hypothesis. 

The revelation that Collins and Fauci were discussing whether NIH had funded work on coronaviruses similar to SARS-CoV-2 at the Wuhan lab in the hours before suggests that politics may have been at play.

Those virologists’ claims that the virus could not have been engineered may have been influenced by Collins and Fauci. The NIH leaders may have sought to obscure links between federal funding and coronavirus research at the advancing pandemic’s epicenter. The emails raise questions about these virologists’ assurances that their deliberations were apolitical.

An analysis that framed the teleconference was called “Coronavirus sequence comparison[1].pdf.” This document has apparently not been released to the public, so it’s not clear which coronavirus they were comparing to COVID-19. 

But it’s clear from notes exchanged after the call that an analysis comparing the spike proteins of SARS-CoV-2 and RaTG13, the Wuhan Institute of Virology coronavirus with a 96 percent identical genome, had been performed. 

The February 1 teleconference kicked off the drafting of an influential correspondence arguing against the idea that SARS-CoV-2 had been engineered. 

“The proximal origin of SARS-CoV-2” in Nature Medicine claimed “strong evidence that SARS-CoV-2 is not the product of purposeful manipulation.” 

It has been cited in 752 media outlets.

Collins and Fauci were repeatedly updated on its drafting and provided “advice and leadership.” 

While not disclosed, the participation of NIH’s leaders in drafting the correspondence presented a conflict of interest.

Because while Collins had concluded that NIH did not support that particular study, the agency had indeed funded the Wuhan Institute of Virology for coronavirus work, including the engineering of chimeric viruses that combine components of multiple viruses to make them more infectious to human cells.

Fauci had been alerted days before that his institute, the National Institute of Allergy and Infectious Diseases, supported a “virus hunting” nonprofit called EcoHealth Alliance with a grant called “Understanding the Risk of Bat Coronavirus Emergence” and that the Wuhan Institute of Virology was a collaborator, according to an email shared with U.S. Right to Know by the House Committee on Oversight and Reform. 

Their concerns might have been aggravated further when lead authors of “The proximal origin of SARS-CoV-2” shared concerns that the genome of SARS-CoV-2 appeared “inconsistent with expectations from evolutionary theory.”

The virologists’ concerns about features of the virus that appeared engineered were shared with Collins and Fauci on January 31, 2020, and again on February 2. 

RaTG13

The preprint authored by Shi about viruses related to SARS-CoV-2 – including RaTG13 – would eventually be published in Nature and continued to trouble the NIH leaders.

An addendum was added months later clarifying that miners had become sick and died after visiting a cave in Yunnan Province in 2012 where RaTG13 was found after independent researchers uncovered this information, despite RaTG13 being named something else in the earlier literature, stoking suspicions of obfuscation. 

In August 2020, Collins emailed his predecessor Harold Varmus, former director of the NIH, about an article describing NIH’s pressure on EcoHealth Alliance to provide records about the Wuhan Institute of Virology, and another link to an article calling attention to the fact that RaTG13 was identical to the coronavirus that had sickened the miners and postulating a lab origin of SARS-CoV-2.

“Tony and I would like the chance to speak to you about this,” he wrote.

Collins announced his retirement in October 2021 after 12 years as director of NIH. Fauci announced his retirement in August 2022 after 38 years as the director of NIAID.

Collins currently serves as science advisor to President Joe Biden, while Fauci serves as his chief medical advisor. 

Despite stepping back from their roles at NIH, both Collins and Fauci could be called to testify about the origins of COVID-19 if Republicans win a majority in either chamber of Congress this fall, according Republicans poised to wield the gavel in key committees. 

The new emails in this report were obtained from a Freedom of Information Act request to the National Institutes of Health. 

Correction 9/7 4:25 p.m.: This article has been corrected to reflect the relationship between RaTG13 and the sickness experienced by the miners is uncertain.

FOIA reveals another secret call on COVID’s origin. The details are redacted.

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Posted on by Emily Kopp

Wellcome Trust Director Jeremy Farrar, pictured here in 2019, hosted a series of teleconferences with top virologists discussing whether the pandemic was the result of a lab accident in early 2020. Notes from a Feb. 7 meeting were obtained by USRTK, but are fully redacted. (Photo credit: World Economic Forum)

Top virologists may have continued privately discussing “all theories” of the pandemic’s origin in the days after they began outlining an influential article that dismissed the lab leak theory in February 2020, an email obtained by U.S. Right to Know suggests.

The group — led by Wellcome Trust Director Jeremy Farrar and University of Sydney virologist Edward Holmes — apparently continued dissecting the data on Feb. 7, three days after the article was first drafted.  

“Eddie Holmes and a small group have been looking extensively at the origins and evolution of n-CoV including all theories,” Farrar wrote in an email on the morning of Feb. 8, 2020, to National Academy of Medicine President Victor Dzau, referring to an early abbreviation for the new novel coronavirus.

“This is the latest summary, written as part of a series of [teleconference] discussions we set up and included [National Institute of Allergy and Infectious Diseases Director Anthony Fauci] and [National Institutes of Health Director Francis Collins] as well as a small group from USA, UK, Europe and Australia,” Farrar wrote. 

It’s not clear whether the group had concluded the virus arose naturally by that date, or whether the lab origin hypothesis was still in play. 

Six pages of notes from the Feb. 7 discussion are fully redacted.

Dzau forwarded Farrar’s message to National Academy of Sciences President Marcia McNutt and President Trump’s Office of Science and Technology Policy Director Kelvin Droegemeier. 

McNutt later forwarded the email with an attachment called “Summary.Feb7.pdf.” 

The redacted documents surface as questions swirl about whether virologists consulting with NIH leadership may have prepared a public relations blitz to marginalize the “lab leak theory” at the same time they privately wrestled with it. 

Three days earlier, on Feb. 4, Farrar had shared with Fauci a first draft of a correspondence co-authored by Holmes titled “​​The proximal origin of SARS-CoV-2” that ultimately dismissed the possibility of a lab accident, according to emails transcribed by congressional staff. 

Farrar held a series of teleconferences with about 11 scientists around the world in early February. Fauci attended at least two of these teleconferences, according to a separate email released under FOIA by BuzzFeed News. 

While a Feb. 1 meeting of the Farrar group had been disclosed through that earlier FOIA request and a subsequent congressional investigation, the Feb. 7 meeting has not been previously reported. 

In a tweet after this story’s publication, Scripps Research virologist Kristian Andersen, a coauthor of the “proximal origin” article, said that the emails reported by U.S. Right to Know do not refer to one of these teleconferences, but did not provide further detail.

“There was no ‘teleconference’ on Feb 7,” he wrote. “Time for a new conspiracy theory.”

Andersen did not directly reply to a request for comment.

These teleconferences have come under scrutiny in recent months, as journalists and congressional committees have uncovered that three of the five authors of the “proximal origin” article had concluded on Jan. 31 that the genome of SARS-CoV-2 was “inconsistent with expectations from evolutionary theory.”

On Feb. 4, Farrar emailed Fauci and Collins that he was split “50-50” between a lab origin and natural origin and that Holmes was split “60-40,” leaning toward a lab origin. 

The participation of Fauci and Collins on the calls and their possible involvement in the shaping of the “proximal origin” article have raised concerns about a conflict of interest. NIH funded coronavirus research at the Wuhan Institute of Virology, a connection Fauci may have been aware of by Feb. 1.

The scientists, including Fauci, have countered that the about-face —  from believing a lab origin was probable on Feb. 1 to a consensus that it was improbable in the article first circulated on Feb. 4 — simply reflected the scientific method at work. 

Notes from the Feb. 7 meeting may help clarify whether this shift indeed reflected rigorous scientific inquiry or amounted to a coverup. 

Requests to Farrar, Dzau, McNutt, each of the five “proximal origin” authors, and NIH to see notes from the Feb. 7 meeting were not returned. 

While Farrar’s memoir Spike describes his sleepless nights following these teleconferences on the pandemic’s source, it does not mention the Feb. 7 meeting. Farrar’s book describes the Feb. 1 meeting, then jumps to the March 17 publication of the “proximal origin” paper. 

Farrar directed questions to a media officer for the Wellcome Trust, who cited a January statement about COVID’s origins.  

“The scientific evidence continues to point to SARS-CoV-2 crossing from animals to humans as the most likely scenario,” the statement reads. “However, as the efforts to gather evidence continue, it is important to stay open-minded and work together internationally to understand the emergence of Covid and variant strains.”

Holmes did not respond to a request for comment. 

The National Academies 

Farrar’s email to the leader of the National Academy of Medicine coincided with a call by the White House Office of Science and Technology Policy for the prestigious professional society to investigate the pandemic’s origin. 

“I sent a memo from OSTP to [the National Academies of Sciences, Engineering, and Medicine] about data needs … and a meeting was held that same day, though I didn’t attend (one of my staff did),” Droegemeier told U.S. Right to Know in an email. “NASEM responded in writing on February 6 saying that additional genomic sequence data were needed to determine the origin of the virus.”

The NASEM held a call with experts on Feb. 3, including two U.S.-based collaborators of the Wuhan Institute of Virology. 

Andersen was also on the call. 

Andersen described the possibility that the virus was manipulated as “crackpot” in an email to the other NASEM participants. He urged the Academies to push back on it more forcefully in its public response to OSTP. 

Just four days after voicing concerns that the viral genome appeared “inconsistent with expectations from evolutionary theory,” he recommended the Academies use the language “consistent with [natural evolution]” in its reply.

Droegemeier said he did not recall the email from Farrar and does not have access to emails since he left public service. 

U.S. Right to Know obtained the email through a Freedom of Information Act request to OSTP as part of an investigation into risky virology research funded with taxpayer dollars. 

Updated June 3, 1:13 p.m. to reflect public comments by Kristian Andersen

Virologists push back on more regulation of viruses made more lethal in the lab

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Posted on by Emily Kopp

An electron microscope image shows SARS-CoV-2. (Photo credit: NIH)

Virologists pushed back on the possibility of tighter regulation of viruses tweaked in the lab to be more lethal at a public meeting Wednesday.

An enhanced pandemic potential pathogen is a virus or microbe that has gained increased transmissibility —  capacity to spread from person to person and reverberate throughout a population —  or virulence — capacity to cause serious disease.

Experiments that are reasonably anticipated to generate deadlier pathogens are supposed to receive heightened oversight from the Department of Health and Human Services under what is nicknamed the HHS “P3CO,” short for the pandemic potential pathogen committee.

Though established just a few years ago, critics say the committee’s work is hidden from public view, suffers from glaring loopholes and needs a reboot. Work that contributes to vaccine development or results from viral surveillance efforts in nature is exempted from this extra layer of review, for example. 

Speculation by some in the U.S. intelligence community that SARS-CoV-2 may have seeped out of a lab at the pandemic’s epicenter may have prompted a public meeting to consider whether current policies are adequate. Reporting irregularities by a nonprofit partner of the lab involved in gain-of-function research on coronaviruses and funded by the National Institutes of Health called EcoHealth Alliance has also led many to conclude the P3CO needs to apply to more research projects and be more accountable to the public.

One million Americans have died of COVID-19. A review by the U.S. intelligence community last summer about whether the novel coronavirus spilled over from an animal or spilled out of a lab was inconclusive.

The Office of Science and Technology Policy and NIH cohosted the meeting Wednesday.

White House COVID-19 testing czar Tom Inglesby was harshly critical of the existing framework. His top recommendation: Scientists should be required to explain in detail the goals of undertaking such research in the first place, and why less perilous methods could not reach the same goal. 

“There must be an extraordinary and public justification,” he said. “I do think there are experiments we shouldn’t do.”

But lobbying groups representing virologists and other life scientists pushed back.

“The systems of review should not be a solution looking for a problem,” said Felicia Goodrum, president of the American Society for Virology. 

Goodrum said regulation risks “tying two hands behind our backs” when it comes to modeling pandemic risks. 

Goodrum added that the inherently unpredictable nature of manipulating viruses means that it’s unwieldy to determine whether or not an experiment will make a virus more dangerous, so the regulations should be lax.

“We must be careful about dichotomizing research as simply either ‘risky’ or not because it is not possible to absolutely predict the biology of a virus with the committee,” she said.  

But Gregory Koblentz, director of the biodefense graduate program at George Mason University, said that an EcoHealth Alliance grant that funded research that made coronaviruses more deadly by swapping their spike proteins is emblematic of lapses in oversight at NIH. 

The research was not regulated as gain-of-function work, but NIH did add language to the grant requiring extra reporting if the viral engineering led to viruses that were 10 times more pathogenic. (The chimeric viruses proved to be much more pathogenic than even that threshold, but EcoHealth Alliance did not report it.) That language amounts to a “tacit admission” that NIH reasonably anticipated the work was gain of function, Koblentz said.

Stefano Bertuzzi, CEO of the American Society for Microbiology, conceded that labs should report more often to Congress and that scientists could do a better job allaying public concerns, but stated that the framework is otherwise sufficient. 

Bertuzzi signaled he is concerned that Congress could step in.

Labs taking steps toward greater transparency “helps guard against well intended but sometimes overly prescriptive legislative approaches that could undermine the important work that needs to take place.” 

Gigi Gronvall, senior scholar at the Johns Hopkins Center for Health Security, said that the “breathless hyping of risks” overshadows strong existing biosafety measures, such as U.S. efforts to train maximum containment labs abroad.

Asked which risks have been misunderstood, Gronvall said that “there is a lot of gray” and that the proper expertise is needed to interpret gain-of-function experiments, but did not go into further detail. 

Indeed, some experts called for decreased transparency for controversial research. Colorado State University Biosafety Rebecca Moritz called for limiting the scope of public records requests. U.S. Right to Know has submitted a public information request for records about the university’s research on bat coronaviruses in collaboration with EcoHealth Alliance, the U.S. Department of Defense (DoD) and the Defense Advanced Research Projects Agency.

The documents raise questions about the contagion risks, for example, of shipping of bats and rats infected with dangerous pathogens.

Kanta Subbarao, director of the World Health Organization’s Collaborating Centre for Reference and Research on Influenza, disputed the idea that research that contributes to vaccine development or results from surveillance should be included in the framework. 

Many representatives of the life science and biodefense fields emphasized weighing any regulation against lost opportunities for science. But members of the public who participated in the meeting were much more skeptical of the value of certain gain-of-function work.  

Alina Chan, a molecular biologist at the Broad Institute, said that the public should not be surprised by controversial gain-of-function experiments for the first time in scientific papers, long after the research has been approved and completed. 

Chan called for controversial experiments to be published on preprint servers and the genomes of novel viruses to be deposited into publicly available databases within a year of discovery.

She also called for greater transparency from private “virus hunting” organizations and middlemen between the NIH and labs, an apparent allusion to the EcoHealth Alliance and the Global Virome Project. 

Kevin Esvelt, a biologist at the Massachusetts Institute of Technology, said creating novel viruses in the lab, combined with the ease of synthesizing viruses from a genome sequence, poses a national security threat.

“More Americans have died of COVID than would perish if a Russian Topol SS-25 thermonuclear warhead were to be detonated in the center of Washington, DC,” said Esvelt. “Pandemic viruses can be more lethal than thermonuclear weapons. That makes them a proliferation concern.”

Public Comments on the WHO Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) Members

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Posted on by Shannon Murray

The World Health Organization has proposed 26 scientists for a new group to investigate the origins of the Covid-19 pandemic, as well as future outbreaks. WHO plans to appoint members to the new Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) after a two week review to gather public opinion on the proposed choices, which ends this week.

WHO’s terms of reference to strengthen public trust and transparency require that SAGO individuals “must be free of any real, potential, or apparent conflicts of interest. However several proposed panel members have clear conflicts of interest. For more this topic, see reporting in the BMJ, Covid-19: New WHO group to look into pandemic origins is dogged by alleged conflicts of interest

U.S. Right to Know has submitted comments describing conflict of interest concerns involving several proposed SAGO members. Below is the text of our public comments and you can find the PDF at this link.

From: U.S. Right to Know
Date: October 26, 2021
To: WHO Headquarters
RE: Public comments on SAGO members

Dear WHO staff:

Thank you for the opportunity to comment on the proposed Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) committee members.

We represent U.S. Right to Know, a nonprofit investigative public health group based in the United States.

According to the WHO terms of reference, SAGO members “must be free of any real, potential, or apparent conflicts of interest,” and “must respect the impartiality…required of WHO.”1 The following proposed SAGO members do not meet these standards for SAGO membership:

(1) Dr. Supaporn Wacharapluesadee is a subcontractor on a 2020 multi-million-dollar NIH grant2 to EcoHealth Alliance. Her lab at Chulalongkorn University is slated to receive a $1.07 million subcontract. According to the EcoHealth Alliance, Dr. Wacharapluesadee is a longstanding collaborator for “more than 10 years.”3 Between 2014 and 2019, she was funded by a UC Davis USAID PREDICT 2 grant, in which the EcoHealth Alliance was deeply involved.4 Since 2013, Dr. Wacharapluesadee has been a co-author on multiple publications5,6,7,8 with the EcoHealth Alliance, including four with its president, Dr. Daszak.9,10,11,12

The EcoHealth Alliance has conducted research on SARS related-CoVs with the Wuhan Institute of Virology. Anyone with personal, financial or academic ties to the EcoHealth Alliance (including grant funding, co-authorship or other research collaboration) or the Wuhan Institute of Virology, cannot be a SAGO member, because such ties could impair their judgment in an investigation of zoonotic and/or lab origins of SARS-CoV-2. Any such ties constitute an impermissible conflict of interest.

Dr. Wacharapluesadee’s association and subcontractor role with the EcoHealth Alliance plainly constitutes a conflict of interest and is disqualifying under the WHO terms of reference.

(2) Dr. Christian Drosten. Dr. Drosten signed a letter in the Lancet, orchestrated by Dr. Daszak,13 arguing that the SARS-CoV-2 lab origin hypothesis is a conspiracy theory.14 Such prejudgement is disqualifying; it is incompatible with the standard of “impartiality” in the WHO SAGO terms of reference.

Moreover, Dr. Drosten served on a bat conference advisory committee with the Ecohealth Alliance and Dr. Zhengli Shi of the Wuhan Institute of Virology.15 Dr. Drosten’s funding and continued research collaborations rest on the zoonotic potential of bat coronaviruses. For these reasons, Dr. Drosten has a personal stake in SAGO’s outcome, because it is to his personal and professional advantage to declare a zoonotic origin for SARS-CoV-2. This, too, disqualifies him from being a SAGO member.

(3) Dr. Katherin Summermatter. Dr. Summermatter has claimed that a lab leak origin of SARS-CoV-2 is a “typical conspiracy theory.”16 Such prejudgment is disqualifying.

(4) Dr. Marion Koopmans. At a scientific conference,17 Dr. Koopmans claimed that a lab origin hypothesis of SARS-CoV-2 has been debunked, along with “meteorites” and “snake origins” of SARS-CoV-2.18 She has asserted that “we found not a grain of evidence for a lab escape theory” of SARS-CoV-2.19 Such prejudgment is inconsistent with the impartiality required of SAGO members, and is disqualifying.

Erasmus University’s Viroscience department, led by Dr. Koopmans, puts the EcoHealth Alliance as first on its list of collaborators.20 The disclosure also states that the viroscience department is “closely involved” in the EcoHealth Alliance. This conflict of interest, too, is disqualifying. Dr. Koopman’s membership in the conflicted, discredited and failed Global Study of Origins of SARS-CoV-2 is also disqualifying.

The first WHO-convened Global Study of Origins of SARS-CoV-2 failed for several reasons. It was tarnished by conflicts of interest. It failed to seriously investigate the possibility of a lab origin, while advancing the dubious cold chain, frozen food hypothesis. It seemed to act as a public relations instrument of the EcoHealth Alliance and the Chinese government. Participation in this botched WHO panel must be disqualifying for SAGO membership, including for these proposed SAGO members:

(5) Dr. Vladimir Dedkov
(6) Dr. Elmoubasher Farag
(7) Dr. Thea Fischer
(8) Dr. Hung Nguyen-Viet
(9) Dr. John Watson
(10) Dr. Yungui Yang

Of the disciplines listed in the SAGO terms of reference, only Drs. Blackwell and Summermater come from the disciplines of “biosafety, biosecurity, occupational health and safety, or laboratory safety and security, ethics and social sciences.” This is unbalanced. The proposed SAGO members do not include enough experts from these fields in the terms of reference. Scientists from diverse fields of study, not merely infectious disease, should be included in SAGO for many reasons, including to offset any conflicts of interest from zoonotic origins infectious disease researchers. We urge WHO to add at least three additional members from these disciplines to SAGO.

We urge you to replace the ten above persons with the list below, who would be exemplary SAGO members. Their presence and participation would inspire public trust in the SAGO.

Dr. Filippa Lentzos
Dr. Richard Ebright
Dr. Jesse Bloom
Dr. Alina Chan
Dr. David Relman
Alison Young
Edward Hammond
Milton Leitenberg
Dr. Stuart Newman
Dr. Michael Antoniou

Thank you for considering our comments.

Sincerely,

Shannon Murray, PhD, Staff Scientist
Gary Ruskin, Executive Director

1https://cdn.who.int/media/docs/default-source/scientific-advisory-group-on-the-origins-of-novel-pathogens/sago-tors-final-20-aug-21_-(002).pdf
2https://documentcloud.org/documents/21055988-risk-zoonotic-virus-hotspots-grant-notice
3https://documentcloud.org/documents/21055988-risk-zoonotic-virus-hotspots-grant-notice, pg. 358.
4https://documentcloud.org/documents/21055988-risk-zoonotic-virus-hotspots-grant-notice, pg. 78.
5https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739538/
6https://pubmed.ncbi.nlm.nih.gov/34218820/
7https://journals.sagepub.com/doi/10.1177/2050312121989631
8https://journals.asm.org/doi/10.1128/MRA.01457-18
9https://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0289-1
10https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33990224/
11https://www.pnas.org/content/118/15/e2002324118.long
12https://bmcpublichealth.biomedcentral.com/articles/10.1186/1471-2458-14-684
13https://usrtk.org/biohazards-blog/ecohealth-alliance-orchestrated-key-scientists-statement-on-natural-origin-of-sars-cov-2/
14https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30418-9/fulltext
15https://usrtk.org/wp-content/uploads/2021/01/CSU_records.pdf, pg. 1572.
16https://www-1815-ch.translate.goog/news/wallis/aktuell/es-werden-sachen-behauptet-die-weder-hand-noch-fuss-haben-153159/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=en-GB&_x_tr_pto=nui
1721 Feb 2020, KNAW-symposium, Marion Koopmans, ‘From spillover to global threat: science in action’.
18https://www.youtube.com/watch?v=J24IfCS7HEs&t=832s
19https://www.youtube.com/watch?t=112&v=8KbUPh43304&feature=youtu.be
20https://www.erasmusmc.nl/en/research/departments/viroscience, see “Collaboration.”
21https://cdn.who.int/media/docs/default-source/scientific-advisory-group-on-the-origins-of-novel-pathogens/sago-tors-final-20-aug-21_-(002).pdf

Written by Shannon Murray

How NIH-funded research in China could have led to the COVID-19 pandemic

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Posted on by Shannon Murray

A multimillion-dollar bat coronavirus research grant, funded by the National Institutes of Health (NIH), was made public last week, revealing that researchers based in Wuhan, China had manipulated coronaviruses in ways that led to increased severity of infection, employing platforms that tested the ability of bat coronaviruses to use human receptors.

The grant documents underscore the perils of the collection of and experimentation on potentially pathogenic viruses, and shed new light on U.S.-funded coronavirus experiments in Wuhan, China for five years prior to the COVID-19 pandemic.

The new information disclosed in the grant proposal and its interim reports do not establish that the research led to the pandemic. But they do suggest that it was possible.

The NIH-funded, five-year grant was awarded in 2014 to the U.S.-based EcoHealth Alliance, with EcoHealth President Peter Daszak as “principal investigator” in collaboration with several researchers in China, including two working at China’s Wuhan Institute of Virology (WIV).  A key collaborator on the grant was Ralph Baric, of the University of North Carolina, providing expertise in mouse models for coronavirus infections. The grant was renewed in 2019 but then cancelled in 2020 as the pandemic set off panic around the globe.

A copy of the research plan and interim reports, titled “Understanding the Risk of Bat Coronavirus Emergence,” was obtained through litigation against the NIH and publicly released by The Intercept. The documents show that the NIH grant was for $3.1 million, of which $599,000 went to the WIV and to researcher Zhengli Shi, who specialized in the study of severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and similar viruses, called SARS related (SARSr)-CoVs.

Many scientists have posited a possible lab origin of SARS-CoV-2, and suggested the WIV as a possible source for the origin of the novel coronavirus SARS-CoV-2, which causes COVID-19.

Coronaviruses (CoVs) emerging from wildlife are a “significant threat to global health,” the grant claims, with bats considered a “natural reservoir of these viruses.” With that in mind, the authors said that the purpose of their research was to “examine the risk of future coronavirus…emergence from wildlife” using a range of research techniques and to understand “what factors increase the risk of the next CoV emerging in people…” The work involved screening more than 30 species of bats for CoVs and then developing strategies for assessing the potential spillover of coronaviruses from bats to humans, according to the grant documents.

But it is possible that, in seeking to learn how to avoid spillover events, the work actually caused one.

How it could have happened

How might the EcoHealth Alliance grant have caused, or contributed to, the pandemic? Here are some possible scenarios based on a close reading of the grant.

  • During fieldwork, collection, and containment of bat SARSr-CoV samples, people could have been accidentally infected. The research involved collecting samples from bats in four Chinese provinces: Yunnan, Guangdong, Guangxi and Fujian. The researchers explained their prolific sampling of Chinese bats and identification of new coronaviruses: “We have identified sequences from 268 novel bat-CoVs (140 from China alone),” they wrote in the grant. “We have an additional 5000+ clinical samples from free-ranging bats and rodents from Guangdong province.”

The grantees acknowledged that their work had serious implications, writing in the grant documents that “some SARSr-CoVs currently circulating in bats in southern China are likely able to infect and replicate within people.” [Emphasis in original].

In fact, the most closely related virus to SARS-CoV-2 identified to date was found by WIV scientists in a mineshaft in Mojiang (Yunnan Province). In 2012-2013, six miners experienced acute respiratory distress syndrome after exposure to bat feces in this mineshaft, and three died.

  • There is evidence of lax bat-handling practices and minimal use of personal protective equipment (PPE) at WIV and Wuhan University, where parts of the research were conducted. By their own admission, the researchers noted, this work could be dangerous. “Fieldwork involves the highest risk of exposure to SARSr-related or other bat CoVs, while working in caves with high bat density overhead and the potential for fecal dust to be inhaled,” according to the grant documents.

The grant documents state that “Tyvek suits and HEPA-filtered Powered Air Purifying and Supplied Air Respirator Systems (PAPRs) will additionally be worn in cave systems where there is a higher risk of contact with aerosolized bat feces.”

If any of those bat samples contained a close relative of SARS-CoV-2 infectious to humans, an accidental infection during the course of fieldwork, subsequent lab procedures, or containment could have led to a transmissible SARSr-CoV with greater similarity to SARS-CoV-2 than the currently reported strains. In fact, analysis of some early strains of SARS-CoV-2 shows that they may be more similar to bat coronaviruses than previously thought, based on evidence recovered from viral sequences deleted from NIH sequence archives.

  • During lab experimentation with the bat coronaviruses, it is possible that a novel virus was produced with greater similarity to SARS-CoV-2 than those reported in the NIH grant. The researchers stated in the grant that they developed an in vivo model, that is, mice genetically engineered to carry human angiotensin-converting enzyme 2 (hACE-2), the receptor for SARS-CoV-1 and SARS-CoV-2. The research group also reported that they were successful in generating new SARS-like coronaviruses. They did this by splicing the RNA sequences of the novel spike proteins they discovered into the viral ‘backbone’ of known lab strains.  This kind of novel virus is called a chimera because it consists of genetic elements from different viruses.

In this way, the researchers created three chimeric viruses, each with a different spike protein, from bats.

  • Though the grant does not mention a virus similar enough to SARS-CoV-2 to be a direct progenitor, it is possible that other chimeric viruses were tested in this model, but were not reported in the grant. The researchers had access to troves of novel coronaviruses collected during fieldwork, including unreported bat viruses. It is common for researchers to present some but not all data in interim grant reports. The research described in the grant established a platform that could have easily been used to study other chimeric viruses more closely related to SARS-CoV-2 than those mentioned in the grant.

There are indications of this within the grant documents. While results from infection of hACE-2 mice with three chimeric viruses were presented, the researchers wrote in the grant, “[w]e cannot anticipate exactly how many viruses we will find that are candidates for experimental models…and that we will identify approximately 20 viruses that will be used for mouse infection experiments.”  It is possible that the researchers generated a novel chimeric virus with more similarity to SARS-CoV-2 than those reported.

Experiments on human ACE-2 mice

The NIH grant describes important research on mice with human ACE-2 receptors.

The researchers infected the hACE-2 mice with the chimeric SARS-like bat coronaviruses to see how sick they would get, and whether they would shed infectious virus compared to the original viral strain. They found that hACE-2 mice infected with some of the chimeric viruses lost more body weight and shed more virus in the lungs than those infected by the original viral strain at certain time points. This research resulted in chimeric viruses that gained infectious and pathogenic properties.

“We’ll infect them [hACE-2 mice] with cultured bat coronaviruses and determine which organs become infected and whether these mice are capable of shedding infectious virus”, the grant proposed. The grant aimed to study tissues of the chimeric virus-infected hACE-2 mice for virus replication.

The grant proposed testing different transmission routes in which the mice could be infected, comparing nasal infection versus other routes. The grant outlines, “[W]e will perform in vivo infection experiments in humanized mice modified to carry human ACE2…gene in the Wuhan Institute of Virology BSL-3 animal facility…[t]his work will provide information about viral pathogenicity, tissue tropism, transmission route, and infection symptom.”

An outstanding question is whether the chimeric viruses can be transmitted between the hACE-2 mice. Whether the scientists explicitly reported on this is not the question, but rather, was a novel chimeric bat virus engineered that was also transmissible between hACE-2 mice?  While the grant does not discuss repeated passage of viruses in hACE-2 mice, the platform also sets up biosafety concerns about this possibility.

A weakness in the prominent “proximal origin” paper?

Some scientists who have argued against a lab origin for SARS-CoV-2 contend that the virus has a signature of it being adapted in an animal host with an intact immune system, for which no such appropriate laboratory model has been described.

One of these arguments against a lab origin of SARS-CoV-2, advanced by scientist Kristian Andersen and colleagues, and published as an influential correspondence in Nature Medicine, was “[s]ubsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described.” [Emphasis ours.]

However, the grant shows this is not correct; the experimentation on the hACE-2 mice establish such a model.

Infection of hACE-2 mice with the novel chimeric bat coronaviruses could have supported new viruses with sequence changes that make them better able to infect human cells. These could be more similar in sequence to SARS-CoV-2 than the original chimeric virus infecting strains.  The hACE-2 expressing mice could have enabled some human adaptation of the chimeric SARS-like bat coronaviruses in vivo, generating viruses with more similarity to SARS-CoV-2 than those reported to date.  This is another possible explanation for how NIH-funded research in China could have led to the COVID-19 pandemic.

The bottom line

In addition to searching for spillover events, the research outlined in the grant had the potential to generate a spillover event. This could have occurred as an accidental infection during fieldwork and laboratory handling of bat SARSr-CoVs; during containment or storage of them; or during the laboratory engineering of novel chimeric bat coronaviruses; or, after these novel viruses were used to infect hACE-2 mice, leading to a more infectious, transmissible, and/or pathogenic virus that was a precursor to SARS-CoV-2. The possibility of a lab leak or lab-acquired infection with any of these novel coronaviruses during lab experimentation raises serious biosafety concerns.

Though the bat coronavirus grant project has concluded, it is entirely possible that other studies using this platform were performed or are now being performed, including those related to viral transmission. It is noteworthy that it took civil litigation to bring these grant documents to light, even though the research itself was paid for by U.S. taxpayers. It is also noteworthy that EcoHealth Alliance has received nearly $40 million in multiple grants from the Department of Defense, and DOD grant data is often considered classified and withheld from the public.

And though the 5-year bat coronavirus research grant was only renewed for one additional year, a $7.5 million NIH grant, titled “Understanding Risk of Zoonotic Virus Emergence in EID Hotspots of Southeast Asia,” was awarded to EHA in 2020 to expand on the platforms established in the 2014 grant.

This newer grant, with Daszak again as principal investigator, was also made public last week by the Intercept. The new grant is a consortium grant that adds more collaborators and lab sites where the research will be performed, including a BSL-4 facility in Boston.  Funding is approved for the budget cycle of June 17, 2020 through May 31, 2025.

The bottom line is this: It is unclear whether the work performed under the 2014 bat coronavirus NIH grant played a role in the COVID-19 pandemic. But the EcoHealth Alliance and WIV collection and storage of SARS-related bat coronaviruses, and the creation and use of chimeric novel bat coronaviruses with human ACE-2 expressing mouse platforms, could have sparked the pandemic.

Congress should launch an investigation into U.S. government funding of this type of risky research as part of a full and thorough investigation of the origins of the pandemic.

U.S. Right to Know believes transparency in science is essential to protection of public health, including preventing future pandemics.

Dr. Shannon Murray is a staff scientist at U.S. Right to Know. She received her Ph.D. in the Molecular and Cellular Biology Program at the Fred Hutchinson Cancer Research Center from the University of Washington. She was a postdoctoral fellow at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Written by Shannon Murray. Editing by Carey Gillam