a research career by Macfarlane Burnet. Laver was such an adventurous soul that, when he finished his doctoral work in London, he and his wife drove home to Australia rather than fly. Several years later he and Webster took their historic stroll, found the beach littered with carcasses of wedge-tailed shearwaters (another seabird, of the species Puffinus pacificus), and wondered—with the South African terns in mind—whether these birds too might have been killed by influenza. Laver suggested, almost as a lark, that it would be good to go up to the Great Barrier Reef and sample some birds there for influenza. The Great Barrier Reef is not generally perceived as a hardship venue. They might get a bit of fishing, bake in the sun, enjoy the clear blue-green waters, and do the science. Laver asked his boss at the Australian National University, in Canberra, to fund Webster and him for such a study. You must be hallucinating, said the boss. Not on my dollar, you’re not. So they appealed to the World Health Organization, in Geneva, where a trusting officer gave them $500, a substantial bit of money at the time. Laver and Webster went to a place called Tryon Island, fifty miles off the coast of Queensland, and found influenza virus in wedge-tailed shearwaters.
“So we have flu, related to human flu, in the wild migratory birds of the world,” Robert Webster told me, forty years later. In the scientific literature he had been rather unassuming about this work but in conversation he laid it out: Sure, Graeme Laver made the discovery that waterfowl are the reservoirs of influenza, with my help. Laver by now was dead, but fondly remembered by Dr. Webster.
Robert Webster today is arguably the most eminent influenza scientist in the world. He grew up on a New Zealand farm, studied microbiology, did his doctorate at Canberra, worked and cavorted with Laver, then moved to the United States in 1969, taking a post at St. Jude Children’s Research Hospital in Memphis, and has been there (apart from his frequent travels) ever since. He was almost eighty when I met him but still on the job, still robust, and still at the forefront of influenza research as it responds daily to viral news from all over the world. We spoke in his office, upstairs in a sleek building at St. Jude’s, after he had bought me a cup of strong coffee in the hospital cafeteria. On the office wall hung two mounted fish—a large green grouper and a handsome red snapper—as though in tribute to Graeme Laver. One of the things that makes influenza so problematic, Webster said, is its propensity to change.
He explained. First of all there’s the high rate of mutation, as in any RNA virus. No quality control as it replicates, he said, echoing what I’d heard from Eddie Holmes. Continual copying errors at the level of individual letters of code. But that’s not the half of it. Even more important is the reassortment. (“Reassortment” means the accidental swapping of entire genomic segments between virions of two different subtypes. It’s similar to recombination, as occurs sometimes between crossed chromosomes in dividing cells, except that reassortment is somewhat more facile and orderly. It happens often among influenza viruses because the segmentation allows their RNA to snap apart neatly at the points of demarcation between genes: those eight railroad cars in a switching yard.) Sixteen available kinds of hemagglutinin, Webster reminded me. Nine kinds of neuraminidase. “You can do the arithmetic,” he said. (I did: 144 possible pairings.) The changes are random and most yield bad combinations, making the virus less viable. But random changes do constitute variation, and variation is the exploration of possibilities. It’s the raw material of natural selection, adaptation, evolution. That’s why influenza is such a protean sort of bug, always full of surprises, full of newness, full of menace: so much mutation and reassortment.
The steady incidence of mutations yields incremental change in how the virus looks and behaves. Ergo you need another flu shot every autumn: This year’s version of flu is different enough from last year’s. Reassortment yields big changes. Such major innovations by reassortment, introducing new subtypes, which may be infectious but unfamiliar to the human population, are what generally lead to pandemics.
But it’s not all about human disease. Different subtypes, Webster noted, have their affinities for different species of host. H7N7 does well among horses. The dead terns in South Africa, back in 1961, had been infected with H5N3.