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Media Myth on H5N1 Transmission Cookbook Recipe
Recombinomics Commentary 17:30
May 16, 2012

In December, the National Scientific Advisory Board for Biosecurity warned against publishing Fouchier's study and a similar study from Wisconsin.

In March, that same advisory board looked at revised versions and said the Wisconsin study was safe to publish. But some on the panel broke ranks on publishing Fouchier's work. Twelve said yes; six said no.

Michael Osterholm, an infectious diseases expert at the University of Minnesota, was one of the six "no" votes on the board. In a letter to NIH after the vote, Osterholm described the studies as "nearly a complete cookbook" for those who would do harm.

The above comments are from recent widely viewed reports from CNN and ABC news on the upcoming Science paper by Ron Fouchier.  However, the report perpetuates the media myth that the information in the report would act as a “cookbook” for those who would do harm.
The use of H5N1 as a bioweapon is far from clear since a transmitting H5N1 would not be controlled.

However, beyond that consideration is the fact that the “cookbook” recipe for a transmitting H5N1 had already been published in Virology in early November, 2011, a month prior to the NSABB warning on the papers submitted to Nature (Kawaoka) and Science (Fouchier).  The Virology paper (by Rubin Donis and associates at the CDC) was remarkably similar to the Nature and Science papers.  The publication in Virology was not redacted and described in detail the creation of H5N1 that passed by contact or aerosol from ferret to ferret.  The paper used the two most cite receptor binding domain changes, Q226L and G228S to identify a third change, Q196R, which limited binding to mammalian (gal 2.6) receptors.  Those three H5 changes were generated on one of the first sequences from Egypt (and egret isolate from early 2006, A/egret/Egypt/1162/2006) which was placed on a clade 1 background (one of the first H5n1 cases in Vietnam) with a seasonal N2.  This fully detailed “cookbook” recipe was published in early November, 2011.  The attack rate for contact ferrets was 100%, while those exposed via aerosol was 50%.

The Fouchier recipe was almost identical.  His lab used the first human H5N1 from Indonesia, A/Indonesia/5/2005.  The H5 changes were the same as the first two selected by the CDC (Q226L and G228S) along with PB2 E627K (which was also in the PB2 used by the CDC).  This construct was then passed in ferrets, which led to the selection of two more changes which increased aerosol passage to 100%.  This result was presented at a scientific meeting prior to the NSABB censorship request, and the success of formula using three changes supplemented by two changes identified via ferret passage were widely cited in media reports in 2011.  More recent reports noted that all three of the initial change (2 in H5 and 1 in PB2) matched those used by the CDC.

Thus, the claim that publication of the Fouchier recipe would benefit “those who would do hard” was false. Since the CDC paper was published, and media reports described the relationship between the Fouchier and CDC papers.

Moreover, the NSABB committee unanimously voted for publication of the Kawaoka (Nature) paper, which also started with two receptor binding changes (Q226L and N224K) placed on an H1N1pdm09 background.  As was seen in the Fouchier paper, the two H5 changes were subsequently supplemented by two additional changes which were selected by passage in ferrets.  One change, N158D abolished the glycosylation site, which was already abolished in the egret wild bird sequence used by the CDC.  Recent comments by Fouchier strongly suggest that this change was one of the two changes selected by ferret passage of his construct.  The second Kawaoka change, T318I, stabilized the H5 and increased transmission frequencies to 100%.

Thus, like the CDC publication, the Kawaoka paper fully detailed the methodology and changes that led to 100% transmission, so the vote of the 6 members to block the publication of the Fouchier paper, and the leaked e-mail were just two more examples of media stunts, that had nothing to do with cookbook recipes that would enable those who would do harm.

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