Point of View
Leaked Grant Proposal Details High-Risk Coronavirus Research
The proposal, rejected by U.S. military research agency DARPA, describes the insertion of human-specific cleavage sites into SARS-related bat coronaviruses.
September 24 2021, 3:16 a.m.
A grant proposal written by <https://www.documentcloud.org/documents/21066966-defuse-proposal> the U.S.-based nonprofit the EcoHealth Alliance and submitted in 2018 to the Defense Advanced Research Projects Agency, or DARPA, provides evidence that the group was working — or at least planning to work — on several risky areas of research. Among the scientific tasks the group described in its proposal, which was rejected by DARPA, was the creation of full-length infectious clones of bat SARS-related coronaviruses and the insertion of a tiny part of the virus known as a “proteolytic cleavage site” into bat coronaviruses. Of particular interest was a type of cleavage site able to interact with furin, an enzyme expressed in human cells.
The EcoHealth Alliance did not respond to inquiries about the document, despite having answered previous queries from The Intercept about the group’s government-funded coronavirus research. The group’s president, Peter Daszak, acknowledged the public discussion of an unfunded EcoHealth proposal in a tweet <https://twitter.com/PeterDaszak/status/1439256807160090627> on Saturday. He did not dispute its authenticity.
Since the genetic code of the coronavirus that caused the pandemic was first sequenced, scientists have puzzled over the “furin cleavage site.” This strange feature on the spike protein of the virus had never been seen in SARS-related betacoronaviruses, the class to which SARS-CoV-2, the coronavirus that causes the respiratory illness Covid-19, belongs.
The furin cleavage site enables the virus to more efficiently bind to and release its genetic material into a human cell and is one of the reasons that the virus is so easily transmissible and harmful. But scientists are divided over how this particular site wound up in the virus, and the cleavage site became a major focus of the heated debate over the origins of the pandemic.
Many who believe that the virus that caused the pandemic emerged from a laboratory have pointed out that it is unlikely that the particular sequence of amino acids that make up the furin cleavage site would have occurred naturally.
Adherents of the idea that SARS-CoV-2 emerged from a natural spillover from animal hosts have argued that it could have evolved naturally from an as-yet undiscovered virus. Further, they argued, scientists were unlikely to have engineered the feature.
“There is no logical reason why an engineered virus would utilize such a suboptimal furin cleavage site, which would entail such an unusual and needlessly complex feat of genetic engineering,” 23 scientists wrote earlier this month in an article <https://www.sciencedirect.com/science/article/pii/S0092867421009910> in the journal Cell. “There is no evidence of prior research at the [Wuhan Institute of Virology] involving the artificial insertion of complete furin cleavage sites into coronaviruses.”
But the proposal describes the process of looking for novel furin cleavage sites in bat coronaviruses the scientists had sampled and inserting them into the spikes of SARS-related viruses in the laboratory.
“We will introduce appropriate human-specific cleavage sites and evaluate growth potential in [a type of mammalian cell commonly used in microbiology] and HAE cultures,” referring to cells found in the lining of the human airway, the proposal states.
The new proposal, which also described a plan to mass vaccinate bats in caves, does not provide conclusive evidence that the virus that caused the pandemic emerged from a lab. And virus experts remain sharply divided over its origins. But several scientists who work with coronaviruses told The Intercept that they felt that the proposal shifted the terrain of the debate.
Tipping the Scales
“Some kind of threshold has been crossed,” said Alina Chan, a Boston-based scientist and co-author of the upcoming book “Viral: The Search for the Origin of Covid-19.” Chan has been vocal about the need to thoroughly investigate the possibility that SARS-CoV-2 emerged from a lab while remaining open to both possible theories of its development. For Chan, the revelation from the proposal was the description of the insertion of a novel furin cleavage site into bat coronaviruses — something people previously speculated, but had no evidence, may have happened.
“Let’s look at the big picture: A novel SARS coronavirus emerges in Wuhan with a novel cleavage site in it. We now have evidence that, in early 2018, they had pitched inserting novel cleavage sites into novel SARS-related viruses in their lab,” said Chan. “This definitely tips the scales for me. And I think it should do that for many other scientists too.”
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