Why did a US advisory board reverse its stance on publishing mutant flu papers?

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Late last year, two teams of scientists announced that they had mutated the H5N1 ‘bird flu’ virus so that it can spread easily between mammals, an ability that their wild cousins lack. The research aimed to understand how natural viruses could evolve into more dangerous forms. But it also raised concerns that the mutant strains could cause a pandemic if they were accidentally released or used in a terrorist attack. (For the background to this controversy, here’s my explainer.)

Last year, the US National Science Advisory Board for Biosecurity (NSABB) – an independent advisory board to the government – recommended that both papers should be published with significant redactions. The full information would only be released to selected scientists. But on 30 March, after a two-day meeting, the NSABB announced that it had changed its mind.

The scientists who led the research – Ron Fouchier from Erasmus Medical Center in Rotterdam, and Yoshihiro Kawaoka from University of Wisconsin-Madison – have since revised their papers. The NSABB voted unanimously to publish Kawaoka’s altered manuscript. Fouchier’s was more contentious, but the board voted 12 to 6 in favour of publishing it.

These recommendations are not the final word. Both manuscripts still have to go through the usual process of peer review, and the US government hasn’t weighed in yet. But should the process now go smoothly, nothing will be redacted from either paper. Fouchier has confirmed that his manuscript will include the full genetic sequence of his mutant strain.

What prompted this U-turn? Fouchier and Paul Keim, acting chair of the NSABB, spoke about the decision at a press conference this morning, held ahead of a Royal Society meeting on Tuesday and Wednesday.

First, the NSABB received new information about the benefits and the risks of the mutant strains. This mysterious evidence remains confidential. Fouchier spoke of “new epidemiological information” that illustrates the benefits of the research, which will partially emerge in his paper, and partially in a third one. No one would comment on who is behind this extra research, what it shows, or when it will be released.

Even with this added evidence, Keim suspects that if the NSABB would have voted against publishing the papers if they had returned in their original form. As it is, they had been revised. They do not contain any new data, but they have been rephrased to clarify some ambiguities. Fouchier said that he was granted more space by Science to explain the public health benefits of the research.

Critically, while the original paper focused on the virus’s transmissibility, the new version clarifies the fact that the airborne mutants do not kill the ferrets they infect. “There was a misconception within the NSABB about the lethality of our virus,” says Fouchier. “The information was in the original but it was not as clear or explicit as it could have been.” Keim joked, “I suspect Ron will write papers differently for the rest of his life.”

But that information also took its time to emerge into the public sphere. For months, the media and the public were labouring under the impression that the airborne mutants were just as deadly as their wild counterparts. This mistaken belief was only corrected in March.

Other details may also be incorrect. It was widely reported that Fouchier’s virus is five mutations away from its wild cousins, but at the end of the press conference, he noted that he never said that. He only described a “handful” of mutations. Presumably, the actual details will emerge when the paper does.

This raises an obvious question: why didn’t Fouchier, or anyone else in the know, correct the misconceptions as they were spreading? Fouchier says that he did not feel able to comment on the details while it was under review by Science, and then later by the NSABB. “We have to be really careful about how we communicate the details of the studies,” he says. “Only when I had permission to talk about this, and was encouraged to do so by the journal and the NIH, did we do so.”

But despite this wary attitude, both Keim and Fouchier provided quotes that arguably magnified the significance of the virus in the press. Fouchier described it as “probably one of the most dangerous viruses that you can make”, and Keim said, “I don’t think anthax is scary at all compared to this.” Both of them stand by their words. “I’ll stick by that comment without any problems,” says Fouchier. “Maybe I’d put it slightly differently next time but it is the truth. Flu viruses are scary and if they acquire the ability to go airborne in humans, they cause pandemics.”

Keim notes that there is still uncertainty about the viruses. Ferrets are widely recognised as the best model animals for human flu infections, but they do not provide an exact replica. The fact that the airborne mutants were not lethal in ferrets does not completely rule a danger.

So what now? The papers will be published and the research will continue, slowed only by a few months. Fouchier says that the delay was necessary to investigate the issue and communicate it to the public. “We needed to take this time,” he says. Keim agrees, noting that the debate has alerted people to the problem of “dual-use research”, which could be used for either good or ill, and how such research should be managed. “It’s not settled,” he says.

“There are experiments that should not be done,” Keim says. He mentioned that as recently as the 1970s, US researchers were studying the progression of syphilis in black people, who were neither told about their condition not treated. “Now we think of these as the most abhorrent experiments that we could imagine. What’s changed is our culture and the way we perceive them. But what’s changing now is not our culture but our technology. The ability to re-engineer organisms is a rapid, cheap and effective fashion… will make possible experiments that we may not think should be done. There was little policy in this area and little engagement.”

That has already changed. A day ahead of the NSABB’s volte face, the government released a new policy to govern dual-use research. Effectively immediately, any research proposals involving a list of dangerous pathogens, including H5N1 flu, Ebola and anthrax, will have to be assessed by US federal research agencies. At Nature, Declan Butler and Heidi Ledford explain:

“Under the new guidelines, research judged to be of risk would then be subject to mitigation measures such as modifications to the proposed research, tougher biosecurity or biosafety precautions, and determinations of how the research should be communicated, and to whom. If federal department and agencies consider that mitigation measures do not rule out serious risks of the research, they would have the authority to request voluntary redaction of results, classify the research and withhold or withdraw research funding.”

Keim says that this policy affected his personal view of the risk and benefits of the two mutant flu papers. “For me, whether or not these particular papers were dangerous was always predicated on the thought of what comes next. What’s the next experiment? We’re going to be watching that.” He, and the NSABB more broadly, is in favour of maintaining academic freedom via local control rather than stifling regulations, and he thinks the new policy will achieve that. “If we could identify high-potential dangerous experiments early on, and manage them effectively, we could release the rest of science from that burden.”