A debate over whether the U.S. National Institutes of Health (NIH) funded unacceptably risky virus research in China has cast a spotlight on federal funding of what are known as gain-of-function (GOF) virology experiments. But ScienceInsider has learned that the only GOF experiments the United States approved and funded under a 2017 policy—two influenza studies that kicked off controversy over GOF research 10 years ago—have ended.
The previously unreported development emerged quietly over the past few weeks after NIH scrubbed its website of most mentions of the words “gain of function” and the initialism “GOF,” which describe experiments that tweak pathogens to make them more infectious or transmissible. NIH says it undertook the revisions because the terms have been “misused” and are confusing. In part, the terms could lead to confusion because federal rules adopted in 2017 require only a subset of GOF studies—those involving “enhanced potential pandemic pathogens” (ePPPs)—to go through special safety and risk reviews. To meet the ePPP definition, federal officials must conclude a proposed experiment might make more dangerous a pathogen believed to have the potential to cause a pandemic.
Ten years ago, two studies judged to involve a PPP—which modified the H5N1 avian influenza virus so that it spread more easily in ferrets—sparked an uproar from scientists concerned that the modified viruses could escape from the lab or fall into the wrong hands. One of the controversial studies was led by virologist Yoshihiro Kawaoka’s lab at the University of Wisconsin, Madison, the other by virologist Ron Fouchier at Erasmus Medical Center in the Netherlands. The storm led NIH in 2014 to pause funding of those studies and other research that might constitute risky GOF (including some coronavirus studies). In 2017, after lengthy expert deliberations, the Department of Health and Human Services (HHS), NIH’s parent agency, adopted a new “framework” for evaluating such experiments. It dropped the GOF terminology and adopted the ePPP moniker instead.
Then, Kawaoka and Fouchier resubmitted proposals for their paused H5N1 research, which a closed-door federal panel approved and NIH funded in early 2019. The review panel also approved a third project, involving the H7N9 avian influenza virus, but NIH decided to redirect the funding to “alternative approaches,” NIH’s revised site says.
Now, the two H5N1 projects have ended, the site says—Kawaoka’s in August 2020, and Fouchier’s, which was part of a contract to the Icahn School of Medicine at Mount Sinai, in March, according to HHS’s recently updated website on the ePPP framework.
Kawaoka tells ScienceInsider that he didn’t seek to renew the H5N1 project, part of a grant he first won 15 years ago, because he didn’t think the work would be competitive. “With limited resources and pressing societal needs, my research team has shifted to focusing on vaccine development,” he wrote in an email. He now heads a $13.6 million NIH-funded effort to develop pancoronavirus vaccines.
Fouchier says he did not complete his project’s planned experiments. But, he adds, “We did not want to go through the [approval] procedure in the USA a third time.” Instead, he will seek funding from the European Union, which now has regulations covering funding of such work, he wrote in an email.
The end of NIH’s only funded ePPP projects won’t defuse ongoing debate over risky pathogen research. Some critics say the ePPP definition used by the United States is too narrow, and should be broadened so it would have applied to U.S.-funded coronavirus experiments conducted at the Wuhan Institute of Virology in China. (Some observers claim those studies led to the coronavirus pandemic, but an NIH analysis has found the viruses studied are too genetically distant, and many scientists say the COVID-19 virus likely spread to humans from animals.) NIH officials have said they’re open to revisiting the 2017 policy, which could mean a fresh look at the ePPP definition.