Geneticist Gerald Fink at the Massachusetts Institute of Technology in Cambridge was chosen to chair the panel. The recommendations in the resulting 'Fink report', published in 2004, set out seven 'deadly sins': types of research that should warrant close scrutiny, such as experiments to render a vaccine ineffective or to make a pathogen more virulent. The report also called for the creation of a national advisory board to further explore the issues on a national and international stage. This would become the NSABB, an independent panel that is managed and supported by the National Institutes of Health (NIH). In June 2005, NIH director Elias Zerhouni swore in 23 NSABB members in Bethesda. Paul Keim, a microbiologist at Northern Arizona University in Flagstaff and acting chair of the NSABB, says that the ceremony involved the raising of hands. “We all kept from giggling,” he says.
Right away, the board started to flesh out guidelines for a US policy on dual-use research. Its flagship document, released in 2007 and building on the Fink report, emphasized local self-governance, suggesting, for example, that investigators monitor their own and colleagues' projects, possibly with the help of existing institutional biosafety committees.
Although not officially part of the board's remit, the NIH also called on the NSABB to review the occasional paper that raised biosecurity concerns. The first two to land in the board's lap, in 2005, dealt with efforts to resurrect the Spanish flu virus that was responsible for millions of deaths immediately after the First World War. The board recommended that the papers be published in full. Keim says he now wishes that the group had had more time to deliberate over the Spanish flu work, which raised many of the same issues as the current debate. “I guess I have some regrets about that decision because of the impact it would have had on policy,” he says.
Nevertheless, the papers the board received last October were different from those it had handled before. Their roots go back to 1997, when H5N1 started devastating bird populations worldwide and health officials voiced alarm about the catastrophe that could ensue if the disease gained the ability to jump between humans. In 2006, the NIH convened a blue-ribbon panel to identify priority research on avian influenza. Among other projects, it highlighted the need for experiments to see how bird flu might evolve the ability to spread from person to person. Soon after, the NIH commissioned and funded several such projects, including one from Ron Fouchier at the Erasmus Medical Center in Rotterdam, the Netherlands, and one from Yoshihiro Kawaoka at the University of Wisconsin-Madison and the University of Tokyo. Robert Webster, a virologist at St Jude Children's Research Hospital in Memphis, Tennessee, and a member of the blue-ribbon panel, says that it paid close attention to the stringent biosafety requirements of such work, but that dual-use concerns “didn't really surface”.
They should have, says Keim. The experiments committed at least two of the Fink report's deadly sins: they deliberately changed the host range of a pathogen and they increased its transmissibility. “You think about adapting H5N1 to mammals,” Keim says, and you quickly “realize that there is the potential to do something very dangerous”.
Concerns surfaced in September 2011, when Fouchier presented his results at a high-profile meeting in Malta. He described, in ominous terms, how he had mutated wild H5N1 virus to make it more likely to infect human cells. He had then let the virus evolve in ferrets, a good model for human transmission, until it was able to spread through the air by a cough or a sneeze. Kawaoka took a different approach, mutating a single gene from H5N1 and plugging it into a less pathogenic viral genome. What resulted — two influenza viruses that could spread in mammals, that most humans had never been exposed to and that stemmed from a virus with the potential to kill — was worrying.