Sir Alan Hodgkin (1914-1998).

Abstract

E very now and then giants come along, raise the bar, and lift us all; Alan Hodgkin was one of them. He never worked for a Ph.D.; didn't have a research supervisor; and built, borrowed, or begged equipment to ask and answer his own questions. Yet despite—or because of—what might be viewed today as these initial “handicaps,” as a second-year undergraduate, Hodgkin began an active research career that spanned more than 50 years. His studies resulted in landmark discoveries that rewrote textbooks, established the keystones of modern physiology, and set new standards for experimental neuroscience. He is most recognized for his work on nerves. As a 20-year-old undergraduate at Trinity College, Cambridge, Hodgkin established that the action potential is propagated electrically by currents spreading passively in a local circuit. Later, with Andrew Huxley, he made the first intracellular recordings from squid axon and discovered unexpectedly that the action potential overshot zero by many tens of millivolts. This demonstrated that the action potential was generated by selective changes in the electrical properties of the surface membrane and did not involve proteins in the axoplasm as many thought. Their excitement was cut short 3 weeks later when Hitler's army marched into Poland and England was plunged into war. Hodgkin was assigned to research on radar and spent the next 5 years working as a physicist, an unusual assignment for a biologist who was self-taught in mathematics and physics, but he was an excellent choice. Hodgkin was a quick study, creative, with penetrating intelligence and common honesty. “Alan, what was the most important thing you learned at school?” “To read widely and work on my own.” “Yes, but what did you like the best about school?” “The holidays.” [A. L. Hodgkin, Chance and Design , 1992]. Boyhood holidays were spent exploring the outdoors, which was the original source of Hodgkin's enthusiasm for natural history. It was through a keen interest in bird watching that he first recognized the essential relationship between observation (research) and learning. The war ended, and Hodgkin and Huxley returned to their work on the giant axon. Using a feedback circuit to clamp membrane voltage at fixed levels they dissected the ionic basis of the action potential, and discovered voltage-gated sodium and potassium conductance changes, showing how their properties could account for the excitation and propagation of the nerve impulse. The Nobel Prize in Physiology or Medicine recognized their work in 1963. Hodgkin became president of the Royal Society in 1970 and switched to research on vision, the focus of his experimental work for the rest of his career. He began working with M. G. F. Fuortes at Woods Hole on the photoreceptors of the horseshoe crab, Limulus . They investigated the long delay that preceded the electrical response evoked by a light flash and attributed it to the time taken for a signal to pass through a cascade of chemical reactions. They recognized that stages of chemical amplification may underlie the generation of the photoresponse and that feedback mechanisms were likely to be responsible for the reciprocal changes in response sensitivity and time resolution that occur when the receptor is light- or dark-adapted. Rarely working with more than one person at a time, Hodgkin undertook research on retinal cones and rods that lasted 17 years and through elegant experimentation and imaginative quantitative analysis established many tenets of retinal photoreceptor physiology. As with his work on the electrical properties of nerve, Hodgkin's research on vision redefined the landscape, expanded the vocabulary, and focused attention on the next set of crucial questions. Alan Hodgkin was a tall man, with a quiet disposition, a good sense of humor, and lively eyes that could express a full range of emotions. He was modest despite his achievements. He did not put his name on any work that he did not fully participate in. He had no interest in having a large research group and felt that one collaborator at a time was best, two were awkward, and more than that impossible. He was fun to work with. Experiments were rarely planned ahead of time, as there was the unexpressed sense that this would somehow ruin the chase by quenching the feeling of exploration and discovery that was, after all, the point of the process—the chance in Chance and Design .