Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited”

Lipsitch, Marc; Inglesby, Thomas V.

Considering a particular sequence change may help to further illuminate this issue. The CDC team's description of the public health benefits of GOF experiments refers to the lysine mutation at PB2 position 627 as an important factor in raising the level of concern for animal or zoonotic human virus isolates (28) . The H1N1 strain of 2009 created a pandemic that caused over 100,000 to 200,000 respiratory deaths globally (38, 39) despite lacking this mutation. Had there been surveillance in place for the viruses giving rise to that pandemic, the lack of this mutation might have misled experts into thinking the virus carried a lower risk and focusing attention on other viruses-a false negative. Indeed, Fouchier's lab was the first to demonstrate that in that genetic background, there was no detectable effect of the mutation (40) . This is just one anecdote-though arguably the most pertinent, as it is the only modern pandemic-supporting the general fact that interpreting surveillance through the lens of particular mutations remains an unproven and error-prone technique (37) .