William Graeme Laver PhD, FRS (1929–2008)

After the Burnet School at the Walter and Eliza Hall Institute in Melbourne changed its focus from influenza to immunology, the influenza research program moved with Frank Fenner's group to ANU, where it was anchored by Stephan Fazekas de St. Groth. There the pioneering influenza work of Sir MacFarlane Burnet continued, with Graeme Laver as biochemist and Stephan Fazekas as the mathematical modeler of virus neutralization. I (Rob Webster) joined the group in 1959 to carry on the virus neutralization studies. To elucidate the subunit structure of influenza viruses, Graeme gently dissociated the lipid bilayer of the virus with the mild detergent sodium deoxycholate and established the basis for the first Australian subunit influenza vaccine. Before that accomplishment, only intact inactivated influenza vaccines had been used in Australia and they were considered undesirably reactogenic. Studies first in rabbits and then in children established the proof of principle for the vaccine. The ANU paid Laver and myself 10 shillings each for the patent rights. Australian subunit influenza vaccines have been further improved, but the fundamental principle established by Laver remains the same: that the proteins must be kept in their native conformation for the vaccine to be effective. Further studies with Robin Valentine of the National Institute of Medical Research at Mill Hill, London, established the morphology of the hemagglu-tinin (HA) and neuraminidase (NA) subunits by electron microscopy, and later work with Nick Wrigley produced the first electron microscopy images of antigen-antibody complexes. After the emergence of the Asian influenza pandemic in 1957 the influenza community, led by Martin Kaplan of the World Health Organization (WHO), began searching for the origins of influenza pandemics. During a fishing trip to the Southeast coast of Australia, near Bateman's Bay, New South Wales, Laver and I found the beaches littered with dead mutton birds (Puffinus pacificus). Knowing that A ⁄ Tern ⁄ South Africa ⁄ 61 (H5N3) influenza virus had been isolated from seabirds, we speculated that the mutton birds might have been killed by an influenza virus. In 1970, serological studies of mutton birds on the Great Barrier Reef of Australia found the first evidence of human N2 neuraminidase–inhibiting antibodies, and in 1973 influenza viruses were isolated for the first time from wild migratory seabirds. These findings provided the first links in the chain of evidence that subsequently showed that the migratory aquatic birds of the world are the natural reservoirs of all …