Steven C. Hebert: a personal dedication

Gerhard H. Giebisch1 1Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA. Correspondence: Gerhard H. Giebisch, Yale University School of Medicine, Department of Cellular and Molecular Physiology, 333 Cedar Street, Box B-106, New Haven, Connecticut 06520-8026, USA. E-mail: gerhard.giebisch@yale.edu Iremember vividly the phone call I received at 7:30 in the morning on April 15, 2008, from a friend of Steve Hebert, who told me, “Steve is dead.” When I rushed to Steve’s house, about 10 minutes from ours, I was told by Pat, Steve’s wife, that Steve had mentioned mild stomach discomfort the night before but had gone to bed without complaint. She found him dead next to her the next morning. Steve had died in his sleep, apparently from cardiovascular disease. As we waited for the arrival of the funeral service and I recovered from the initial shock, the severity of the personal loss became clear to me. Steve was the paradigm of the gifted self-made man. He was born in Rockford, Illinois. His family moved to Inagua, a small Bahamian island, where his father, an electrical contractor, was in charge of developing salt recovery facilities. He was effectively home-schooled for several years before the family returned to Fort Lauderdale, Florida. Although his parents had not attended college, they had, as Steve told it, a deep interest in higher education and thus encouraged Steve’s educational efforts. He entered Florida State University at age 15, majored in math and physics, but discovered an early interest in medicine and finished college in three years before entering the University of Florida Medical School. Two of his teachers stimulated his early interest in fluid metabolism and research: the nephrologist Robert Cade, who later developed Gatorade, and Tom Maren, a pharmacologist who studied carbonic anhydrase, a critical enzyme for acid–base transport. Another interest became the focus of Steve’s attention when he met a lovely nurse, Patricia Robertson, and they married in 1970. The couple then moved in Pat’s trailer to Birmingham, where Steve joined the residency program in internal medicine at the University of Alabama–Birmingham (UAB). During medical rounds he attracted the attention of Thomas Andreoli, the newly appointed chief of nephrology at the UAB Hospital. I believe that this event played a major role in the subsequent fateful transition in Steve’s life from an undefined interest in medicine to the pursuit of research. After his residency, Steve stayed at UAB as a research fellow with Tom Andreoli, whom he credited with kindling a lasting fascination with renal electrolyte metabolism. Their personal friendship lasted until Steve’s untimely death. However, Steve never lost interest in patient care or in kidney disease. After his fellowship ended in 1975, he was drafted and spent two years in the Navy, stationed at Eastern Virginia Medical School in Norfolk, where he was assigned to a clinical nephrology unit, which stimulated his interest in understanding the mechanisms underlying abnormalities in fluid and electrolyte metabolism. After his military service, Steve returned to Alabama, where he was appointed assistant professor in Tom Andreoli’s nephrology section. Steve studied the mechanism of salt and water transport in the cortical collecting tubule and the thick ascending limb of Henle’s loop. He used the technically demanding method of isolated perfused tubules, which he learned from Jim Schafer, with whom he also started a lasting friendship. He first identified the individual ion transporters of the apical and basolateral membranes, thereby providing a cell model that accounted for normal transport characteristics. During this period he maintained a cordial relationship with his main competitor, Rainer Greger in Freiburg. When Tom Andreoli moved to Houston in 1979 to become the chair of medicine, Steve accompanied him there. During his five-year stay he worked with Peter Friedman to identify the mechanism of the effect of antidiuretic hormone and diuretics on transport in the thick ascending limb. They also traveled to the Mount Desert Island Biological Laboratory in Salisbury Cove in Maine, where they studied water and urea movement in the kidneys of cartilaginous fish. In 1984 Steve accepted a faculty position at Harvard in Barry Brenner’s renal section. There, Steve made an audacious decision to clone the main distal salt transporters of the nephron, which changed his career. Steve recalled from his Mount Desert Island days that the sodium-chloride cotransporter is expressed in high concentrations in the flounder bladder, and he succeeded in cloning it from that epithelium. A few years later, Steve and his colleagues also succeeded in cloning and defining the molecular structure of the furosemide-sensitive mammalian sodiumpotassium-chloride cotransporter. These triumphant studies established Steve as a world leader in renal physiology. Steve’s discovery and cloning, Steven C. Hebert: a personal dedication