Plan included work on humanized and 'batified' mice, adding furin cleavage sites, and 'vaccinating' wild bats
By Keoni Everington, Taiwan News, Staff Writer
2021/09/27 13:26
Top of cover page of grant proposal EHA submitted to DARPA. (EcoHealth Alliance DEFUSE screenshot)
TAIPEI (Taiwan News) — Leaked documents from a scuttled research grant proposal calling for collaboration between labs in Wuhan and the U.S. military are raising concerns about the dangerous nature of the experiments on coronaviruses possibly conducted prior to the start of the pandemic
On Sept. 21, Drastic Research, an international network of scientists investigating the origins of the pandemic, exposed a grant proposal presented to the Defense Advanced Research Projects Agency (DARPA) by U.S.-based research organization EcoHealth Alliance (EHA) and headed by British zoologist Peter Daszak. The documents, which were leaked by an anonymous whistleblower, detail a US$14 million proposal dubbed “Project DEFUSE" that sought to identify the spillover risk of coronaviruses to "US warfighters" but was ultimately rejected due to potential gain of function (GoF) and DURC (dual use research of concern) research elements.
The proposal for the US$14 million grant, titled DEFUS (Defusing the Threat of Bat-Borne Coronaviruses), was submitted in 2018 and would have run from that year until 2022. EHA was requesting US$14,209,245 in funding and would have allocated US$1,182,877 to the Wuhan Institute of Virology (WIV), with much of the rest subcontracted to the University of North Carolina, National University Singapore, United States Geological Survey Wildlife Health Center, and Palo Alto Research Center.
Among the more controversial proposed experiments presented in the application were the creation of bat coronavirus chimeras that would contain human-specific furin cleavage sites (FCS), the introduction of these viruses into humanized and "batified" mice, and a grandiose plan to "vaccinate" wild bats in caves against coronaviruses.
The mention of inserting FCS is significant because scientists consider the presence of these on the spike protein of SARS-CoV-2 to be one of the reasons why the virus is able to easily infect humans. Within the betacoronaviruses of sarbecovirus lineage B, the polybasic furin cleavage site is unique to SARS-CoV-2, according to News Medical Life Sciences.
Scientists who favor the lab-leak hypothesis point to the unusual presence of the FCS as an indication of manipulation in a laboratory. Advocates of the natural origin hypothesis argue that although the FCS is not documented in other sarbecoviruses, it does appear in other distant relatives such as MERS.
"Humanized mice" describes mice that have been genetically modified to express the human ACE2 protein, and in this proposal, WIV lead researcher Shi Zhengli (石正麗) — also known as "Bat Woman," would oversee work on these rodents. "Batified mice" refers to mice that have been irradiated and injected with the bone marrow of bats to simulate the response of bats to viruses and treatments.
The most ambitious phase of the project was to vaccinate wild bats using aerosolized viruses. This was to include both broadscale immune boosting with "immune modulators" and targeted immune boosting with "novel chimeric polyvalent recombinant spike proteins."
In one of the most controversial segments, the authors of the project proposed synthesizing spike glycoproteins, which bind to human cell receptors, and inserting them into SARSr-CoV backbones to assess whether they could cause SARS-like disease while declaring that it would not constitute GoF or DURC." However, in his summary sheet of the grant proposal, James Gimlett, program manager of DARPA's Biotechnical Technolgies Office, wrote that the team had failed to "mention or assess the potential risks" of GoF or DURC.
Gimlett then stated that the team's approach of synthesizing spike proteins and inserting them into the backbones of SARS-related coronaviruses "does potentially involve GoF/DURC research" and that if the project was approved, an "appropriate DURC risk mitigation plan should be incorporated" into the documentation. His conclusion was to deny funding for the proposal due to lack of "data, statistical analyses, model development," doubts about the efficacy of the bat inoculation program, and concerns over GoF/DURC.
As for similar projects that successfully secured funding, The Intercept on Sept. 6 released 900 pages of documents detailing work that EHA engaged with the WIV with funding from the U.S. National Institute of Health (NIH). One of the grants was a 5-year project slated to run from 2014 to 2019 titled “Understanding the Risk of Bat Coronavirus Emergence," which provided EHA with a total of US$3.1 million, including US$599,000 allocated to the WIV.
In the grant notice, EHA stated that it had generated a chimeric virus with a spike protein with a 10% divergence from SARS-CoV. The notice added that the chimera had "replicated in primary human airway epithelium, using the human ACE2 receptor to enter into cells" in the transgenic mice.
In 2019, just before the known start of the pandemic, WIV assistant researcher Hu Ben (胡犇) began his work on a project titled "Pathogenicity of 2 new bat SARS-related covs to transgenic mice expressing human ACE2." No information about this research has been released to the public since the start of the pandemic, including data on the eight chimeric viruses the WIV had been infecting the mice with.
Stuart Neil, a professor of virology at King's College London, conceded on Twitter that the DARPA documents reveal "GoF however you want to cut it." Neil said that he was "troubled" that the information is only being released at this late date and that there are "aspects of this proposal that are concerning from a DURC and GoF point of view."
Jamie Metzl, a WHO committee member, said on Twitter that given the revelation of Daszak's "undisclosed conflicts of interest & material nondisclosure" of the DARPA grant application, the time has come for the WHO to begin an official investigation into his participation in the study of COVID's origins and to "retract its deeply flawed report." Rutgers University microbiologist Richard Ebright wrote that the EHA application "outlines several risky research projects" that included the introduction of human-specific cleavage sties into SARS-like viruses.
Alina Chan, a molecular biologist at the Broad Institute of MIT and Harvard, reacted on Twitter to the leaked DARPA documents by remarking that such information would have been invaluable at the start of the pandemic: "Imagine if the public had this info in Jan 2020."
Chan noted that while scientists such as Neil have pointed out that the proposal was not successful, it does not mean such work was not already underway at the time of the proposal. "When you see this level of detail, there's a good chance some preliminary work has been done."
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