Roderick MacKinnon was born in Melrose, Massachusetts, a suburb of Boston, and grew up in Burlington, an outer suburb of Boston. He is the fourth of seven children. His father had not gone to college, but he picked up computer programming on his own and became a professional programmer. His mother was a substitute teacher as well as homemaker for the seven kids and her husband. MacKinnon was always interested in science, collecting snakes, birds, and other things. Though his parents were observant Roman Catholics, the children attended public schools. After fifth grade MacKinnon went to summer school because they offered a science enrichment program that included giving him a microscope. He loved to look at all kinds of things through that microscope. He remembers his fourth-grade teacher as being good and a high-school science teacher being "inspirational." MacKinnon's first sport was hockey, but after several years he dropped that and turned to gymnastics. He excelled at gymnastics, competing at the state level, being recruited by colleges, and actually considering becoming an Olympic gymnast. Late in his senior year of high school he suddenly realized that he did not want to do gymnastics all his life; luckily he had been in honors classes and his grades were good. He decided to go to the University of Massachusetts in Boston and transfer the next year. He very much enjoyed studying and found that science came easily to him, so he continued his undergraduate work in biochemistry at Brandeis University. He loved the stimulating intellectual climate there. Unsure what he wanted to do after college, MacKinnon entered Tufts University medical school. He felt all along that he really did not want to practice medicine, that it was not science in the sense he wanted. After finishing his residency he quit medicine and took a postdoc in the lab of Christopher Miller, a professor who had known him at Brandeis. He developed an interest in ion channels, and he learned to play the violin. Here he explains how his childhood interest in understanding natural systems, his interest in problem-solving activities, and his ongoing appreciation for mathematics led to his decision to leave medicine. MacKinnon's willingness to teach himself new techniques and the practice of letting an experiment "speak" to him helped him learn from Miller the artificial bilayer system for studying ion channels. Observation is important in MacKinnon's experimental method, he says. He began work on charybdotoxin, an ion channel inhibitor, in the Miller lab. Next he describes the Miller lab's efforts to expression-clone a calcium-activated potassium channel and the mutagenesis work required to identify the Shaker potassium channel pore. He found that the active site of a potassium channel is made up of a linear sequence, and he explains the significance of his discoveries. From there he accepted a position at Harvard Medical School. Deciding to apply a structural biology approach to the study of ion channels, he identified the tetrameric structure of the Shaker potassium channel. Here he talks more about the decision to apply a structural biology approach. He turned down a Howard Hughes Medical Institute position at University of California, San Diego, which he regrets every time he needs to write a new grant proposal. Then his department at Harvard was reorganized. Although things were going well for him at Harvard, he spoke with Torsten Wiesel at a Pew Scholars Program in the Biomedical Sciences meeting and was invited to Rockefeller University to give a talk. He loved Rockefeller and accepted a position there. Then he suffered the difficulties involved in moving a lab. His lab members did not want to leave Harvard, so he was forced to decrease the size of his lab. Miller warned him about the professional risks involved in focusing on ion channel structure, but MacKinnon likes to "jump in feet first." MacKinnon talks about his teaching and research responsibilities at Rockefeller; about recent molecular genetics work that poses new questions about channel structure; the current state of ion channel structure research; his collaborative work with Gary Yellen on potassium channels; and possible collaborations with other scientists. He tells how he began the biochemistry involved in ion channel research with Pew Scholars Program in the Biomedical Sciences funding, and he goes on to discuss his National Institutes of Health (NIH) and McKnight Endowment Fund for Neuroscience grants specifically and NIH support of basic research in general. He explains how one must write grants to meet the different criteria of the individual funding agencies, but he remains committed to his area of interest, despite funding pressures. He extols his wife's, Alice Lee MacKinnon's, ability as a crystallographer. He concludes by discussing the importance of being able to learn new material; the differences in individual styles of learning; the dedication required of MacKinnon's lab personnel; and teaching lab personnel how to do science.
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