Don C. Wiley (1944–2001)

htm). For Don was not a person to consider, even for a Don Wiley changed how we picture molecular organizamoment, a “bread-and butter” project to back up his tion at the cell surface. Indeed, he helped to create how more ambitious strivings. His determination never to we picture it. His two monumental contributions, the waste time on something ordinary was probably reinstructures of influenza virus hemagglutinin in its various forced by the influence of Jim Watson, an intense scienstates and the structures of class I and class II MHC tific presence in the Harvard of the 60s and 70s. In molecules in combination with peptides, superantigens, any case, by 1974, he had found a direction that would and T cell receptors, redefined molecular virology and dominate the rest of his career, by seizing upon viral immunology. He was one of the pioneers who transsurface glycoproteins—the influenza virus hemagglutiformed the specialty then known as “protein crystallognin (HA) in particular—as a route toward unraveling the raphy” into the discipline we now call “structural molecular mechanisms of cell-cell recognition. Of Don’s biology.” success in turning this part of cell biology into crystallogDon burst upon the scene of protein crystallography raphy, Max Perutz once wrote that Don had now “done in 1971, at the landmark Cold Spring Harbor Symposium the impossible—twice.” The first time was, of course, on Protein Structure. Fresh from the triumph of a 5.5 Å his graduate-student success with ATCase. structure of aspartate transcarbamoylase (ATCase) and Skeptics tried to dissuade Don from studying viral a recently completed PhD thesis, he arrived from Camglycoproteins. These were known to have somewhat bridge in a newly acquired sports car. He continued to variable glycosylation, and there were even doubts cut a dashing figure throughout the meeting. He had about the rigidity of their protein components. Don figbeen recruited (from Tufts) to the Biophysics graduate ured that he would worry about such issues when the program at Harvard by Donald Caspar, who remained time came: you can always talk yourself out of a chalan important intellectual influence, but he was ultimately lenge, and the real trick is to avoid crippling inhibitions. lured by the ATCase project to pursue thesis research Don was enormously fortunate in finding John Skehel in William Lipscomb’s laboratory in the Department of as a collaborator on the HA project, as was John in Chemistry. In 1967, the structural basis of allosteric regfinding Don. Skehel published an account of the prepaulation was a major (and contentious) problem. It repreration and apparent crystallization of soluble HA in 1972. sented the “next level” of structural complexity, beyond Don contacted him when he first read the paper, almost the three or four simple enzymes for which atomic resotwo years later. They built up a striking scientific and lution models were then at hand. By 1971, Don had personal friendship. Don spent six months in Skehel’s changed all that, not yet by fully solving the problem laboratory in Mill Hill, pushing the project forward, and of course—that took another two decades of work in they spoke on the telephone at least weekly, and someLipscomb’s laboratory—but by defining the route to an times more often, during the ensuing decades. Don and answer. I were also jointly fortunate that Harvard had allowed I first met Don shortly after he arrived at Harvard. I us to establish a shared laboratory. Each of us was able was a student in Caspar’s laboratory in the so-called to contribute to the other’s progress and to provide “Jimmy Fund” Building of the Children’s Cancer Reencouragement in the inevitable intervals of perceived search Foundation, and Don did an extended rotation despair. By 1977, Don had also succeeded in recruiting there. He carried out diffraction experiments on lipid a superb postdoctoral fellow, Ian Wilson (now at the phases, perhaps nucleating his career-long interest in Scripps Research Institute), who was instrumental in membranes. We collaborated while he was a graduate pushing the HA effort to completion. student, working out how to use the newly introduced The HA structure was completed in 1980, and back-torotating-drum film scanners to index and integrate preback papers describing the molecule and its antigenic cession and, later, oscillation photographs. We were properties were published in Nature in 1981. It redefined recruited by the Department of Biochemistry and Molecin molecular language the three central properties of ular Biology in the same year, and when Don accepted the protein—receptor binding, antigenic variation, and his appointment, a few months after I accepted mine, membrane fusion. Almost overnight, vast areas of virolhe came to propose that we set up our laboratories ogy had become chemistry. Don later said that he betogether. Sitting in my tutor’s room in Lowell House, lieved that “the discovery” was actually not the strucwe fantasized how would we build up what we called ture, but an experiment, motivated by the structure, “structural molecular biology” (a phrase we had learned carried out by John Skehel in the following year (see from Caspar and Carolyn Cohen) amidst the “informaSchlesinger interview). Skehel showed that HA under-