Gain of Function

"You take an animal virus and you increase its transmissibility to humans, you're saying that's not gain-of-function?" he asked.

But George Mason University's Gregory Koblentz, an expert in biodefense and dual use research, pointed out that WIV1 wasn't an animal virus enhanced to infect humans through gain-of-function research, because it was already shown to pose a danger to humans.  

"Sen. Paul is wrong when he says that the coronaviruses that were the subject of this research only infect animals and not humans and that this research was 'gain-of-function' because it enabled an animal virus to infect humans," Koblentz said. "The WIV1 strain was already known to be able to infect humans."

Even before the virus was edited in the lab, researchers found WIV1 was "poised for human emergence," writing it could infect human airway cells "with no significant adaptation required."

Fauci said the grant proposal "was judged by qualified people up and down the chain" in the federal government not to comprise gain-of-function research.

Experiments in synthetic biology that create engineered, or "chimeric," viruses that are "reasonably anticipated" to gain properties that make them more dangerous are supposed to get extra scrutiny by the government. At the time of the 2017 study, the government had implemented a pause on these experiments altogether.  

Changing the virus

The researchers in Wuhan spliced the WIV1 virus with other novel coronaviruses expressing spike proteins and grew them in the lab. The scientists tested whether the new engineered viruses could infect human-like cells with the ACE2 receptors that spike proteins bind to. They could.

Among the coauthors credited are Shi Zhengli, a Wuhan Institute virologist, and Peter Daszak, the president of EcoHealth, a nonprofit that served as a private intermediary between Wuhan and the NIH. The research received funding from NIH and USAID.

A key question is whether adding different spike proteins to a virus already known to infect human cells made that virus even more infectious or virulent.

Richard Ebright, a Rutgers microbiologist and biosecurity expert whom Paul cited at the hearing, says yes.

"The research was, unequivocally, gain-of-function research," he said. "There can be no serious doubt that Fauci knows this."

Others dispute whether it was, or say it's hard to know, but that the experiment was potentially dangerous. Not a lot is known about the novel coronaviruses that the Wuhan researchers edited into WIV1.

"A certain set of experiments that have been published by the Wuhan Institute … I view as particularly risky," said Relman of Stanford, calling attention to the WIV1 research.

"I'm not saying they led to this outbreak or pandemic by any means," he said, referring to COVID-19.

University of North Carolina researcher and Wuhan Institute of Virology collaborator Ralph Baric had already studied the WIV1 bat coronavirus and found it "to be a virus 'poised for human emergence,'" Relman said.

Relman described the experiment: The spike proteins of other novel coronaviruses found in samples taken from bats, whose virulence and transmissibility were unknown, were added to the WIV1 virus. Then those new viruses were grown in the lab.

Virologists argue this sort of research is important to learn about how viruses evolve in nature and where new outbreaks could emerge, while critics like Relman are not convinced.

"Their approach for studying novel sequences that they found in other samples was to take a piece of the genome, a piece of that sequence, and swap it into this WIV1 virus. They then resurrected this virus and grew them in the laboratory," Relman continued. "Now we're talking about a chimeric virus with properties we don't know and can't predict well."

Defense of the research

Virologists are less concerned about the WIV1 study.

Stephen Goldstein, a researcher of dangerous pathogens at a high-security lab in Utah and skeptic of the so-called "lab leak" theory, noted the paper showed some of the edited viruses were less infectious than the original WIV1.  

Georgetown University virologist Angela Rasmussen, another critic of the lab leak theory, acknowledged that the viruses were infectious to human-like cells, but said studying a cell line in a lab, as the Wuhan researchers did, isn't a good predictor of the virus' ability to infect real people.

"The definition [of gain-of-function research] refers to increased transmissibility and pathogenicity in humans, and you can't determine either of those things in a cell line," she said in an email. "That can test infectivity in an artificial system but is not remotely analogous to showing the virus is 'transmissible,' because there's a lot more to transmission in the real world than just receptor binding and entry."

Rasmussen said attempts by Paul to link WIV1 to the coronavirus that causes COVID-19 are a "politically motivated smear," echoing Fauci's argument that it's "molecularly impossible" they are related. Fauci was "right to call Sen. Paul a liar," she said.

The assurances of virologists have not alleviated the concerns of other researchers.

"What I would apply here is a little common sense. And if what you are doing is creating recombinants of a dangerous human virus that you know to have potential to be more infectious or more lethal, then I think that by any reasonable understanding of the term, you are engaged in gain-of-function," said Edward Hammond, a biosafety researcher and activist.

The rationale behind the NIH's approval of the grant is mysterious, because its reviews of gain-of-function research are confidential and there is relatively little public information about NIH's process.

Rasmussen acknowledged more discussion is needed about how the government reviews this sort of work.

Koblentz said the disagreement between Fauci and Paul shows how little is known about what the government views as gain-of-function research and what it doesn't.

"How 'enhanced' would a virus have to be to count as an enhanced potential pandemic pathogen?" said Koblentz. "It would be really useful for NIH to document these reviews and explain their reasoning and assessment."

Best wishes,

John Coffey


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