While funding for gain-of-function research was paused, the EcoHealth Alliance project that was carried out with the Wuhan Institute of Virology was reviewed by the NIH, according to a statement by the NIH to the Washington Post from 19 May 2021. It was determined that this work did not involve gain-of-function research. In this statement, the NIH also said that:
"NIH has never approved any grant to support 'gain-of-function' research on coronaviruses that would have increased their transmissibility or lethality for humans."
The NIH told the Wall Street Journal what work the specific studies carried out by EcoHealth Alliance and the Wuhan Institute of Virology involved.
"The research by EcoHealth Alliance, Inc. that NIH funded was for a project that aimed to characterize at the molecular level the function of newly discovered bat spike proteins and naturally occurring pathogens. Molecular characterization examines functions of an organism at the molecular level, in this case a virus and a spike protein, without affecting the environment or development or physiological state of the organism. At no time did NIAID fund gain-of-function research to be conducted at WIV."
As Alina Chan, a molecular biologist at the Broad Institute of MIT and Harvard, explained, the EcoHealth Alliance/Wuhan Institute of Virology research did not fall under the moratorium because it was using natural viruses and it could be reasonably argued that these were not likely to be highly transmissible and highly virulent in humans.
Stanley Perlman, a microbiologist at the University of Iowa, told FactCheck.org that EcoHealth's research was about "trying to see if these viruses can infect human cells and what about the spike protein on the virus determines that." According to FactCheck.org, Perlman did not think there was anything in the EcoHealth grant description that would be gain-of-function research.
As shown above, the definition of gain-of-function research is difficult to pin down. But in relation to the NIH's definition of gain-of-function research, the research described in EcoHealth's grant application didn't fall under the NIH's definition from 2014.
No evidence that coronaviruses were engineered to be more dangerous for humans
A 2017 study published by researchers at the Wuhan Institute of Virology, listing the NIH as a funding body, appears related to this grant[4]. The researchers wanted to test whether the spike protein of new wild coronaviruses, which they isolated in bats, would allow the coronaviruses to enter human cells.
The problem with studying coronaviruses is that they are hard to culture in the lab[5]. To carry out their study, the researchers used the genetic sequence of a coronavirus (WIV1) that does replicate in vitro (in the lab) and inserted the spike proteins of the newly isolated viruses. In this way, they could test whether the newly isolated viruses could replicate in human cells in a lab dish.
Data included in the publication[4] showed that these experiments did not enhance the viruses' infectivity. The experiments therefore did not make viruses more dangerous to humans or more transmissible.
All parties involved in the NIH grant to EcoHealth Alliance and the Wuhan Institute of Virology stated that this work did not involve gain-of-function research, according to a fact check by PolitiFact. The NIH told PolitiFact that:
"The research supported under the grant to EcoHealth Alliance Inc. characterized the function of newly discovered bat spike proteins and naturally occurring pathogens and did not involve the enhancement of the pathogenicity or transmissibility of the viruses studied."
However, Richard Ebright, professor of chemistry and chemical biology at Rutgers University and a critic of gain-of-function research, told the Washington Post that "the research was—unequivocally—gain-of-function research. The research met the definition for gain-of-function research of concern under the 2014 Pause."
And Kevin Esvelt, a biologist at the MIT Media Lab, stated in a fact-check by PolitiFact that "certain techniques that the researchers used seemed to meet the definition of gain-of-function research".
On the other hand, Joel Wertheim, an evolutionary biologist at the University of California San Diego, told PolitiFact that the experiments carried out in the 2017 study, despite using recombinant RNA technology, don't meet the criteria for gain-of-function research in virology.
This is because the researchers didn't allow the created viruses to keep on replicating in human cells, which would enable them to adapt and enhance the viruses' transmissibility or pathogenicity. According to Wertheimer, similar approaches as employed in the 2017 study – inserting virus surface proteins into the backbone of other viruses – are also used in other instances, such as making vaccines, which do not qualify as gain-of-function research.
"The work ultimately was not aimed at creating viruses that were more infectious. It was taking parts of natural viruses and studying them in well-characterized virus genome backbones," Chan wrote about the EcoHealth/Wuhan Institute of Virology research.
Esvelt also emphasized that the research involved in this 2017 study couldn't have led to the emergence of SARS-CoV-2. According to Esvelt's statement to PolitiFact, the work reported in the Wuhan Institute of Virology's 2017 study[4] didn't lead to the creation of SARS-CoV-2, because the genetic sequences of the virus studied in the paper and SARS-CoV-2 differ too much.
The closest known relative to SARS-CoV-2 is yet another bat coronavirus, called RaTG13, which was discovered after miners in the Yunnan Province of China developed pneumonia[6]. The group of researchers at the Wuhan Institute of Virology collected and sequenced RaTG13. The genetic sequence of SARS-CoV-2 is 96% similar to that of RaTG13[6]. As a Health Feedback review from March 2021 pointed out, this genetic gap between RaTG13 and SARS-CoV-2 is too wide to be bridged by engineering.
In the same review, Robert Garry, a professor of microbiology at the University of Tulane, concurred: "While 96% sounds close, in evolutionary terms, it is quite distant, and it would take decades of evolution for the genome of RaTG13 to resemble that of SARS-CoV-2. The difference is about 1,200 bases or 400 amino acids. Gain-of-function research cannot close that gap." He added, "This would require a virus much closer than RaTG13, at least 99% similar or more likely 99.9% similar."
Conclusion
The NIH indirectly funded research at the Wuhan Institute of Virology, a sub-contractor to a grant awarded to EcoHealth Alliance. This grant was reviewed during the NIH's funding pause on gain-of-function research, and was determined to not fall under the definition of gain-of-function research used by the NIH for the funding pause.
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