So he

enrolled for a Ph.D. at Harvard University, under the supervision of the famous insect endocrinologist, Carroll Williams, graduating in 1957. The lab pioneered studies of metamorphosis and its control by ecdysone and juvenile hormone, particularly in Lepidoptera. His first paper in 1953, on the cyanide sensitivity of the heartbeat in the Cecropia silkmoth (Harvey and Williams, 1953), introduced two themes for the Romidepsin molecular weight rest of his career – energetics and caterpillars. Bill would continue publishing in the area of energetics and diapause until the early sixties, when he took a fellowship to Copenhagen. In Karl Zerahn’s lab, he worked closely with Signe Nedergaard, and discovered the extraordinary Cabozantinib ic50 physiology of one of the most remarkable tissues in biology. The caterpillar midgut transports potassium ions from blood to lumen so fast that it can generate transepithelial potentials in excess of 150 mV, and short circuit currents in excess of 1 mA/cm2 (Harvey and Nedergaard, 1964). Of course,

this was absolutely the best place in the world to make such a discovery, since Zerahn was a colleague of Nobel laureate George de Hevesy as he introduced radioisotopes as tracers. Later Zerahn was a co-inventor with Ussing of the eponymous Ussing chamber for the measurement of epithelial transport. (Incidentally, the pedigree is even more distinguished, because Ussing was in turn a student of August Krogh, the Nobel-winning father of comparative physiology.) As a result, a flurry of papers followed, characterising the tissue, its structure and its remarkable transport properties. Bill returned to a Faculty post at the University of Massachusetts, where he served as Assistant, then Associate and Professor from 1961 to 1969. He also visited John Treherne and Arthur Ramsay in Zoology at Cambridge – another world centre of insect physiology – as a Guggenheim Fellow, in 1967–8. On his return, opportunity beckoned once again, and Bill took up a position as Professor Pyruvate dehydrogenase lipoamide kinase isozyme 1 of Biology at Temple

University in Philadelphia, where he remained till his ‘retirement’ in 1996. In extended collaborations with Zerahn, Nedergaard, Wood, Haskell and others, he used microelectrodes, the short circuit technique and radioisotope fluxes to show that the midgut current was carried entirely by potassium ions, confirming the existence of Ramsay’s so-called “potassium pump”. He linked this pump to the protein decorations that were first described by Gupta and Berridge in 1966. In an ultrastructural paper with Anderson that same year he had reported similar decorations on the cytoplasmic surface of apical membranes of midgut goblet cells (Anderson and Harvey, 1966). Harvey reviewed the presence of these decorations across a wide range of transporting epithelial cells and introduced the term ‘portasomes’.