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Paradigm Shift Intervention Monitoring
Transmission Bioterrorism 101
The above comments re-iterate the NSABB position, and raise serious concerns about the competency of the board, which should resign in mass and be replaced with board members who have some familiarity with influenza evolution and associated scientific literature.
Recent reports have indicated that the two receptor binding domain (RBD) changes added to the Fouchier Indonesia clade 2.1 isolate were among the three changes used by the CDC in their recently published study. The two changes, which have always been discussed as a pair, are Q226L and G228S, which have been the subject of discussion and research since H5N1 was reported in humans in the 1997 outbreak in Hong Kong. These are the two changes cited by WHO when they offer assurances that H5N1 has not acquired a “mammalian” RBD.
Similarly, the change in the second gene is almost certainly PB2 E627K, which also has been under discussion and experimentation since the 1997 outbreak. It was present in a sub-set of human cases in 1997, and was also present in the only fatality in the 2003 H7N7 outbreak in the Netherlands, and has been actively researched by the Kawaoka lab. It is also in both H5N1 isolates used in the CDC study.
Thus, the “secret” changes used by Fouchier are the three most well known H5N1 changes. The “news” in the embargoed Science paper is the fact that these three changes, when augmented by two additional changes selected by passage 10 times in ferrets, lead to efficient transmission which maintains lethality in ferrets.
Passage of influenza in animals to select for a more virulent influenza has been cited in publications from the 1930’s and 1940’s. The first human influenza virus was named WS/33 because it was identified in the Wilson Smith lab in 1933. Influenza was ciculating in London, and experimental ferrets (used in distemper studies) developed flu symptoms. One ferret sneezed in the face of a lab technician, Christopher Mathewes, who then developed symptoms. A filtrate from Mathewes was used to infect healthy ferrets, who then developed the flu. WS/33 was subsequently passaged in mouse brain, to create a neurotropic and more virulent influenza, which was name WSN/33 and is currently in use in influenza labs worldwide.
Thus, the “recipe” for a transmitting H5N1 is to start with clade 2.1 from Indonesia, add the three most widely described changes in H5N1 research, and passage the virus 10 X in ferrets.
However, as noted in the CDC paper, as well as the embargoed Nature paper, similar transmissions can be generated by clade 2.2 H5 from Egypt, or clade 188.8.131.52 H5 from Vietnam, when supplemented by clade 1 internal genes and a human N2 or 7 H1N1pdm09 genes, respectively.
The recipes are considered a “state secret” by the US NSABB, and the request for redacted publications should be rejected out of hand.
The current NSABB board is hazardous to the world’s health, and should be replaced.