Virologists do regularly fiddle with viral genes to change them, sometimes enhancing virulence or transmissibility, although usually just in animal or cell-culture models. “People do all of these experiments all the time,” says Juliet Morrison, a virologist at the University of California, Riverside. For example, her lab has made mouse viruses that are more harmful to mice than the originals. If only mice are at risk, should it be deemed GOF? And would it be worrying?

The answer is generally no. Morrison’s experiments, and many others like them, pose little threat to humans. GOF research starts to ring alarm bells when it involves dangerous human pathogens, such as those on the US government’s ‘select agents’ list, which includes Ebola virus and the bacteria responsible for anthrax and botulism. Other major concerns are ‘pathogens of pandemic potential’ (PPP) such as influenza viruses and coronaviruses. “For the most part, we’re worried about respiratory viruses because those are the ones that transmit the best,” says Michael Imperiale, a virologist at the University of Michigan Medical School. GOF studies with those viruses are “a really tiny part” of virology, he adds.

But this little slice of the field became the focus when the NSABB talked about regulating or monitoring GOF research (see ‘Evolving terminology’). After the ferret flu studies were eventually published, researchers and regulators struggled to determine what sorts of experiment should receive extra scrutiny as a potential biosecurity risk…

However, as the war of words between Paul and Fauci shows, the terminology is still hotly debated. The chimeric viruses in the Wuhan Institute study were new viruses made in the lab. But the manipulations that made them did not enhance their ability to cause disease in humans. The starting virus, WIV1, could already infect human cells using ACE2. Although some scientists have argued that the work does constitute GOF, at the time the research was approved, it was evaluated by NIAID and considered exempt from the funding pause.