Superflu: reply to Vox

Vox recently ran a piece by Susannah Locke on a new study in Cell, in which scientists showed only five mutations are needed to make H5N1 avian influenza transmissible in ferrets. (I’ve talked a bit about this here.) The research is controversial because it is dual-use: it could be used to advance our understanding of viruses, but it could also be used to create a deadly pandemic. You might remember a similar controversy about H5N1 back in 2011; some of the same players in that saga are involved here. In particular, the group is headed up by Ron Fouchier of Erasmus University.

Dual-use doesn’t get a lot of play in the news, so it is always nice to see some coverage. The article in Vox, however, doesn’t give the full story. In particular, the article doesn’t pay attention to some of the nuances of the 2011-2012 debate that inform—or should inform—thinking on this new research. Vox isn’t taking responses or op-eds from outsiders right now, so instead I’ve made a few notes below.

Stupid, or Simple?

A lot of the trouble back in 2011 was unavoidable: the National Science Advisory Board for Biosecurity (NSABB), for the first time in its history, recommended the partial censorship two scientific papers based on their ability to enable acts of bioterrorism. This move was always going to sit poorly with the life sciences community, where openness is the norm. And, though the NSABB later reversed their recommendation in response to revised copies of the papers, the episode prompted a year-long moratorium on H5N1 research that would lead to similar types of result, as well as new regulations at the NIH over the funding and pursuit of this so-called “gain-of-function” research.

Part of that furor, however, was caused by Ron Fouchier. Fouchier, who claimed at the 2011 European Scientific Working group on Influenza meeting in Malta that his group had created “probably one of the most dangerous viruses you can make” also referred to his work as a “really stupid experiment.” These and other bold claims circulated widely during the debate, and were assuredly a source of stress as researchers, government officials, and journalists sought to work through the issues.

Fouchier’s claims were hardly what caused the NSABB’s recommendation. But it certainly stirred up a storm, and bought about a lot more scrutiny of dual-use than normally occurs. Unsurprisingly, Fouchier stopped using such bold rhetoric. But in doing so he further muddied the waters of the public debate, by excessively playing down the risks of his research.

A great example can be found in Fouchier seeking to qualify his “really stupid” statement:

In his Malta talk, Fouchier called this a “really stupid” approach, a phrase widely interpreted to mean he regretted it. In fact, he says, he just meant that the technique, called passaging, is a simple one compared to the sophistication of creating targeted mutations. The confusion may have stemmed in part from the fact that the Dutch word for “stupid” can also mean “simple.”

So something was possibly lost in translation. Yet Fouchier’s about-face doesn’t mesh well with other claims he’s made about the risks of his research: for example, that “bioterrorists can’t make this virus [that my team created], it’s too complex, you need a lot of expertise.”

He wants to say that the experiment is simple, but also that it’s too complex for bioterrorists. Yet we already know that bioterror, whether it be committed in Oregon or Japan, is not necessarily the purview of the academy. We also know, from history, that having a high technical competence is far from a guarantee moral probity.

Fouchier’s also doesn’t address the risks that come from widespread attempts to reproduce these results. A recent article in Slate illustrated how SARS, foot and mouth, and H1N1 flu have all escaped their labs. We shouldn’t just be concerned about a bioterrorist brewing a batch of superflu, but just the significance of run-of-the-mill laboratory accidents.

How dangerous?

In trying to understand the risks of the H5N1 studies, few things are more contested than the case-fatality rate (CFR) of H5N1: how many people with the disease die, divided by the number of people who get the disease. The WHO lists 650 reported cases of H5N1, with 386 deaths, giving rise a CFR of 60%. That’s a really big number—most influenza pandemics have a CFR of less than 0.1%.

Supporters of the research have insisted that 60% can’t be the true CFR. The reason they give is that there must be more cases we don’t know about; cases that either aren’t reported, or cases where infected individuals don’t display symptoms severe enough to trigger detection. For each case we don’t know about that isn’t fatal, the CFR drops. And if the CFR drops, then gain-of-function research is less of a problem.

Appealing to the CFR, however, runs into two problems. For a start, there simply aren’t—at least as far as we can tell—that many people walking around with H5N1 who aren’t being picked up. A study in 2008 suggested that there may be subclinical infections in Thailand; research in China, however, found that there was little evidence for subclinical infections. An investigation into two villages in Cambodia found that only a small number of individuals tested positive for H5N1: 1% of the sample.

But a bigger problem is that 60% is a huge CFR. “Spanish Flu,” which killed 50–100 million people in 1918, only had a CFR of around 2.5%. Standing a potential human-transmissible H5N1 against Spanish Flu should give people nightmares. But what it means for Fouchier and company is that even if it turned out that for every 1 case of H5N1 we found, we missed 24 more, we’d still cause to be worried.

Power in the platform

This all matters, quite simply, because there is power in the platform. Public debates rise and fall on the data supplied, and who is given the authority to depict a particular debate. Fouchier is an expert; of that there is no doubt. But he is an expert in influenza. Not bioterrorism, not public health, and not dual-use. He’s also been demonstrably confusing when it comes to the ways he presents his research.

It’s troubling, then, that the Vox piece is almost entirely based on Fouchier’s account of what happened—an account which is, as above, sketchy. It’s really good to see dual-use in the news, but on this issue more than one perspective is necessary. The history of dual-use should be written by more than one group.

The Center for Biological Futures over at The Fred Hutchison Cancer Research Center maintains a good repository of documents relating to the H5N1 dual-use case in 2011-2012.

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One thought on “Superflu: reply to Vox

  1. Pingback: What Am I Reading? 8 June 2014 | The Broken Spoke

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