Sunday, August 31, 2014

The debate over influenza research is still on

H5N1 virion. Photo Cynthia Goldsmith/Jackie Katz

Two years ago, a controversy emerged about the research on influenza virus H5N1, and the potential risk associated with it. This controversy followed the publication of two research articles in Science and Nature, and I wrote about it in January 2012 in this blog post. Briefly, scientists have used so-called “gain-of-functions” experiments, in which strains of influenza viruses are selected for new traits such as higher transmissibility between ferrets (the preferred animal model in these studies). The objections that were raised by some critics of this research were of two kinds: first, the information available in these papers could be used by terrorists in order to produce bioweapons; second, modified influenza viruses could escape the lab by accident and create a pandemic. The first objection led to a very rare decision in scientific publishing, namely the redaction of the articles to remove potentially sensitive data. The important public concern also led the authors of these studies to promulgate a moratorium on this type of work. After this temporary stop, the experiments started again with additional biosafety measures. 

The debate, however, is far from over. The reason for this? Well, the recent publications of several studies dealing with influenza virus, most notably a paper by Y. Kawaoka (the author of the 2012 Nature publication) on avian influenza viruses related to the 1918 “Spanish flu” virus. This research triggered a heated response from several scientists, which was loudly echoed in the mainstream press (see for instance in the Guardian and in the Independent). In that particular case, it seems that the scientific community is truly divided on the matter. An example of this dissent was the publication of a statement of concern by a group of scientists known as the Cambridge Working Group, which in essence asked for a better assessment of the risks of virus research via the organization of a conference that would deal with all present issues. Such a meeting could resemble the famous Asilomar conference of 1975, where the risks associated with recombinant DNA were debated. Other virologists, however, have fought back these reactions of distrust and have created another group, Scientists for Science, which aims at promoting the benefits of this research, and highlight the fact that serious safety regulations are already in place for virus research. 

The situation, it seems to me, is now polarized between a pro and an anti camp. In the 'anti' camp, we find for instance Marc Lipsitch, an epidemiologist from Harvard who published a paper criticizing this research, and Roberto Kolter, microbiologist and former president of the American Society for Microbiology, also from Harvard, who was quoted in the Independent saying that  the scientists doing this work are so immersed in their own self-aggrandisement, they have become completely blind to the irresponsibility of their acts". Defending the validity of the research on influenza virus we find, of course, Kawaoka himself, who insists that the knowledge we gain on viruses can help save lives. Other open and vocal supporters of the research include Vincent Racaniello, virologist at Columbia University and host of the excellent TWiM and TWiV podcasts, who defends the value of these experiments. Racaniello denounces the misrepresentation of the nature of these modified viruses, and the exaggerated claim that they could be deadlier than previous pandemic viruses. His “Ferrets are not humans!” has become almost a leitmotiv: he means by this that transmissibility between ferrets does not entail transmissibility between humans

Fortunately, the divide between the two camps is not at all irreconcilable. Both camps are in favor of the convening of an Asilomar-type conference, and this could be the opportunity to assess the situation with an open mind and the best of our current science. This, at least, is advocated by Arturo Casadevall and Michael Imperiale in a very recent paper in mBio. (This excellent paper was an inspiration for this blog post, and many of my summary elements come from it; it is a must-read for anyone who wants to get the full picture of the debate at play.) Casadevall and Imperiale rightly point out that the value of gain-of-functions experiments is not contested, but they “believe that the crux of the debate surrounding GOF experiments is not their value but their potential risk” (p.2). 

Indeed, one thing that muddles the debate is the difficulty to estimate the risk-benefit of such experiments. Recent biosafety failures in prestigious institutions such as the Center for Disease Control in Atlanta have shown that accidents can happen. In that respect, I believe it is disingenuous to affirm that lab-modified viruses could not escape. The key thing, here, is the dangerosity of these lab strains. It seems clear that the media and some scientists were guilty of using an exaggerated rhetoric, talking about 'doomsday' and the 'deadliest' virus (read Racaniello's take on this rhetoric). On the other hand, the unintentional release of a lab virus, and the consequences of it, could be disastrous for the population and for science as a whole. I cannot help feeling worried at the thought of recombined viruses escaping the lab. 

Hopefully, this global conference will be organized soon, and decisions will be taken that advance both research and public safety. That would be much needed.


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