Learning from the 1918 virus

The word that scientists at the Armed Forces Institute of Pathology and colleagues at Mt. Sinai School of Medicine and elsewhere have succeeded in sequencing the 1918 pandemic flu virus is major news. The virus contains eight segments, of which five had already been sequenced. The newly published work in the journal Nature completes the process.

The most important lesson is that 1918 was an entirely avian (bird) virus. The 1957 and 1968 pandemics were caused by reassortments that mixed bird and human virus genes, but the 1918 virus seems to have jumped from birds to humans in one step. Thus what happened n 1997 when H5N1 did the same thing is not unprecedented as was thought at the time. This also means that WHO's repeated statements that the feared "mutation" of H5N1 has not yet occurred because the virus is still all bird is not valid.

We don't as yet know what changes in the viral genome are needed to make it "go pandemic" (achieve efficient human-to-human transmission) or what genetic changes confer the unusual virulence seen in current cases and the 1918 virus. The 1918 virus, as revealed in the recent work, seems to have less than a dozen amino acid differences (in the three genes just sequenced) compared to the "normal" avian virus, and some (but not all) of those changes are also in evidence in the current H5N1. The researchers interpret this to mean the H5N1 is still early in the process of human adaptation. The additional (unspoken) inference is that the process of human adaptation is underway.