May 9, 2012

H5N1 Influenza Research Finally Published After Public Debate

The long-awaited publication of the first H5N1 influenza paper resulting from months of debate over research justification and publication risk has occurred (more background here). Nature has published the article from the laboratory of Yoshihiro Kawaoka at the University of Wisconsin, who has succeeded in creating an H5N1 virus with an altered surface protein (HA) that allows for ready transmissibility in the ferret animal model of influenza (long used as an approximate model of human influenza behavior). The actual virus is a hybrid of H5N1 and H1N1 (responsible for the 2009 pandemic) and thus exhibits features of both. What the scientists were asking was whether an influenza virus can pick up the transmission characteristics of the seasonal flu with the mortality characteristics of more deadly influenza strains. The answer is yes, in that the new influenza could be spread in droplets between animals (like seasonal spread). The lab identified the precise mutations in the HA surface protein which account for its new properties. Of note is the commentary in the article that advocates for this kind of research in order for science to anticipate the composition of new pandemic strains that could arise in the wild. Interestingly, the novel virus showed susceptibility to an existing antiviral – Tamiflu – as well as reactivity with some existing vaccine compositions.  Now that the data has been released, we can expect more policy responses on several fronts: 1) How should influenza research be managed – for example, as a select agent subject to certain controls and oversight (an example is the reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments; 2) Continued refinement of the NIH-originated dual-use research policy to focus on the experiments that are most likely to create pathogens with elevated risk profiles 3) More attention to biosafety (laboratory) management, as debate ensues over when high-risk influenza research should require the highest level BL-4 containment facilities, rather than the current BL-3; 4) Journal-level publication strategies that recognize the risk of data dissemination but seek critical risk review in addition to standard peer review, and 5) Further refinement of NSABB procedures and deliberative processes (as suggested by a a critical assessment of the recent H5N1 deliberations and the NIH response to the criticism; and 6) Increased attention to public health surveillance efforts to determine whether they fully exploit new knowledge that has been generated (such as the H5N1 mutations now identified in the article which alter transmissibility) so as to further justify the risks incurred with dual-use research. From the Kawaoka et al. article: "Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures."

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