In Memoriam: Steven C. Hebert, M.D., Renowned Yale Nephrologist

Steven C. Hebert, M.D., the chair and C.N.H. Long Professor of Cellular and Molecular Physiology and professor of medicine, died suddenly on April 15 from apparent cardiovascular disease.

Hebert was a board-certified nephrologist who devoted his career to the science of renal fluid and electrolyte regulation, through which the kidney keeps the heart, brain and muscles functioning normally. He made major contributions to medicine, notably in the cloning of genes that mediate or regulate the transport of sodium, potassium and calcium across cell membranes. His work won him election to the National Academy of Sciences (NAS) in 2005, and his research was the basis for a new class of drugs which are used to treat hyperparathyroidism, a hormonal disorder that affects many of the more than 1 million patients worldwide with end-stage kidney disease.

“Steve Hebert was a dynamic leader of his department and a major force in nephrology,” said Dean Robert J. Alpern, M.D., the Ensign Professor of Medicine. “He was thoroughly honest, critical and resourceful in the pursuit and resolution of major problems in transport physiology. These qualities earned him worldwide respect, and he will be deeply missed by the scientific community.”

Hebert was born in 1946 in Rockford, Ill., and lived for part of his childhood on the island of Great Inagua in the Bahamas, where his father was a contractor for the Morton Salt Co. In a profile published in 2006 in the Proceedings of the National Academies of Sciences, he recalled watching bulldozers pile dried sea salt into mountains 150 feet high and speculated that his interest in metabolic salts may have had its genesis there. Surging ahead of his classmates, he entered Florida State University at age 15 and graduated after three years.

Hebert received his medical degree from the University of Florida in 1970, and then completed his residency in internal medicine and a nephrology fellowship at the University of Alabama at Birmingham (UAB). He was a faculty member at UAB, Eastern Virginia Medical School, the University of Texas Medical School in Houston, Harvard Medical School and Brigham and Women’s Hospital (where he ran the Laboratory of Molecular Physiology and Biophysics, Renal Division). In 1997, he was recruited to Vanderbilt University as director of the Division of Nephrology and the Ann and Roscoe R. Robinson Professor of Medicine. In 2000 he was offered the chairmanship at Yale. This gave him the opportunity to lead a world-class department and to continue his close collaboration with fellow NAS member Gerhard Giebisch, M.D., a longtime friend and mentor and now professor emeritus in the department.

With colleagues he launched two biotech companies based in Portland, Maine—MariCal, a collaboration with scientists in the aquaculture industry, and Pearl Development Group.
Hebert spent the early part of his career exploring the kidney’s basic processes, using the tools of traditional physiology—radioactive tracers to track ions as they cross cell membranes, and light microscopy to measure the volume of cells in single tubules of the nephron, the kidney’s basic unit.

In the late 1980s, he faced a choice: continue with the tried-and-true laboratory methods at his disposal or risk a leap headlong into the world of molecular genetics. Using a technique called expression cloning, in which genes are isolated according to their function, Hebert and his colleagues saw the chance to identify the molecules that transport salts across membranes and regulate calcium levels in the blood.

In the early 1990s, Hebert’s laboratory made three fundamental discoveries about how the kidney handles potassium, sodium and calcium. His group identified a channel that regulates potassium excretion and is involved in Bartter’s syndrome type II, an inherited disorder that causes sodium and potassium to be lost in the urine. He and his colleagues also identified two sodium chloride transporters that are the target sites for important diuretic drugs. His subsequent discovery of a calcium-sensing receptor known as CaSR led to the development of a new class of drugs that modulate calcium-receptor activity.

Most recently, with John Geibel, M.D., D.Sc., Hebert worked on a research project he considered one of the most important of his career. It dealt with the role of the CaSR receptor in the prevention and treatment of acute diarrheal disease. The two colleagues demonstrated in an animal model that diarrhea could be reversed almost immediately by activating the CaSR receptor. In patients, such treatment would have a major impact on health problems in developing countries, where diarrheal disease kills some 3 million infants and children each year. “It was Steve’s hope that bringing this project to fruition would be the crowning achievement of his lifelong career efforts,” said Geibel, his close collaborator.

Hebert was a recipient of the Homer W. Smith Award, the top research prize given by the American Society of Nephrology, the A.N. Richards Award from the International Society of Nephrology, and the Carl W. Gottschalk Distinguished Lectureship from the American Society of Physiology. He was inducted into the American Society for Clinical Investigation in 1988 and the Association of American Physicians in 1993. Last year, Hebert was named the American coordinator for the Transatlantic Network on Hypertension-Renal Salt Handling in the Control of Blood Pressure, an international, $6 million research project on hypertension funded by the Paris-based Leducq Foundation. This project involved close collaboration with Yale colleague Richard P. Lifton, M.D., Ph.D., Sterling Professor of Genetics, and scientists in Switzerland, Mexico and France.

As an accomplished physician-scientist who understood the profound connection between basic science and clinical medicine, Hebert was devoted to the teaching and training of medical students, graduate students and postdoctoral fellows. He was known as a generous and attentive mentor who dedicated his life to the highest academic ideals and an exceptional teacher and lecturer, as illustrated by his numerous awards and invited lectures. He served on the editorial boards of all the major journals in nephrology and was invited to write numerous reviews on the different topics of his work.

“Although highly successful in all of these different venues, Dr. Hebert was unique in never forgetting his roots,” his departmental colleagues wrote in an obituary they prepared. “He was at his happiest reviewing research findings with the next generation of scientists and imparting his wealth of knowledge. In addition to his landmark scientific achievements, his lasting legacy will include the many students and trainees whom he inspired to pursue academic and research careers.”

Hebert is survived by his wife, Patricia (Robertson) Hebert; his son, Steven C. Hebert Jr. of Fort Lauderdale, Fla.; and two grandchildren, Kyle and Cameron Hebert, also of Fort Lauderdale. A family service will take place Sunday in Florida. A memorial service at Yale is being planned for the near future.