Gain-of-function: redux

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The gain-of-function crowd are at it again. A new study, released in Cell, has described how H5N1 highly pathogenic avian influenza can be engineered to become transmissible between mammals, using five mutations. The new research builds off the 2011-2012 work of Ron Fouchier and Yoshihiro Kawaoka; work that caused a ruckus for its potential for misuse, and led to the National Science Advisory Board for Biosecurity (NSABB) initially recommending the censorship of the papers.

The NSABB hasn’t commented on the Cell study; according to Michael Osterholm, the group hasn’t met in 18 months. Near as I can tell, they didn’t meet or we’re consulted about a similar study in H7N1. In both cases, the informal risk assessments pointed to the benefits of the studies outweighing the risks. And that, apparently, was that.

The lack of consultation with the NSABB is concerning. It raises questions about what exactly that board is doing about the concerns that define its existence. It also stomps all over a staple of good ethics and regulation: treat like cases alike. Rather than assuming that the likeness of these publications warrants immediate publication, however, we should remember the history. The NSABB’s decision was controversial, and followed serious deliberation. This should have, at the least, led to these new studies being flagged for review by the NSABB. That the NSABB wasn’t involved is, to me, more problematic than the new publications.

Make no mistake, there will be more research like this: the flu lobby has informed us that this is the case. In the wake of the Tamiflu revelations—that the antiviral stockpiled by governments the world over doesn’t work, and actually causes serious adverse events in children—pressure for gain-of-function research is also likely to increase. As governments scramble to appear to be doing something, I suspect more of these publications will be funded.

But to what end? The arguments haven’t changed since 2011. Predicting viral mutation with an eye to vaccines or surveillance isn’t a good strategy at all, because what we can create in the lab isn’t necessarily what nature will brew up. It is like playing blind darts: you aren’t likely to succeed, and could put someone’s eye out in the process. This isn’t an argument that can be sustained, and requires a misinterpretation of how viruses work to seem convincing.

Moreover, knowing the specific evolutionary pathway of a virus is hardly the most burdensome part of vaccine production. Vaccines need to be created, tested, stored, distributed, and used. These latter stages are incredibly time-consuming and costly. Gain of function research doesn’t add to these steps in a meaningful way.

Put another way, if the flu lobby were some of my former undergraduate chemistry students, I’d be failing them for not being able to identify the limiting reagent in this reaction, much less give me a valid rate equation.

It also detracts from the fact that the politics and logistics of vaccines don’t make them great tools in the event of a pandemic. And without Tamiflu, our best options are the social and political—and ethically fraught—solutions that rely on people and public health. Isolation; quarantine; surveillance. These raise important rights and privacy issues that haven’t been adequately discussed. I don’t think many people are ready for what quarantine means in the event of a serious outbreak.

The malevolent uses of dual-use research of concern, however, become more acute the less prepared we are. Gain-of-function research needs an institution to benefit us; it needs us to be unprepared or complacent to harm us. We’re definitely unprepared right now.

I’m not saying we should censor the new H5N1 or H7N1 research. I’ve made it clear elsewhere that we are not be wrong to do so, but in this case that ship has long since sailed. What we need to do now is have a bigger, better conversation about pandemic preparedness, public health, and dual-use.

NB: Written in transit. I’ll endeavour to have more comprehensive links up when I’m back at my computer.