In memoriam: Warren M. Zapol, MD
David Polaner, MD, FAAP
It is perhaps ironic that two of the most groundbreaking and innovative therapies for the care of our sickest pediatric patients were developed by a man who was not a pediatric anesthesiologist. Warren M. Zapol, the Reginald Jenny Distinguished Professor of Anesthesia at Harvard, and Chair Emeritus of the Department of Anaesthesia at Massachusetts General Hospital, who was a principal contributor to the invention of ECMO and originated the idea of inhaled nitric oxide, passed away last week at the age of 79. Up to literally the week before his death he was still actively running his lab at MGH and advancing the frontiers of medicine in ways that will continue to impact patients with pulmonary hypertension, cardiorespiratory failure, sickle cell disease, Leigh disease and even COVID-19. I had the tremendous fortune to have trained and worked in Warren’s lab, and the even greater honor to have called him my friend and mentor.
Warren lived an extraordinary life, filled with adventure and exploration, discovery and innovation, and deep and meaningful relationships with colleagues from around the world. He received his undergraduate degree from MIT and attended medical school at the University of Rochester. Following his internship at Boston City Hospital he went to the NIH, where he worked with Ted Kolobow to perfect the membrane lung and develop ECMO (yes, he did his fellowship before his residency!). His next step was anesthesia residency at the MGH, the institution where he spent his entire professional career, eventually rising to the chair of the department. Warren worked in the thoracic ORs and the Respiratory ICU and ran an exceptionally active laboratory where animal physiology was the proving ground for innovative therapies and discoveries that he then brought to the bedside. His creativity, however, could not be contained by the walls of the Wellman Building; he spent nine summers at McMurdo Station and on the Ross Ice Shelf in Antarctica studying how Weddell seals, the deepest and longest duration diving mammals, were able to tolerate severe levels of hypoxia, studied the Ama diving women of Korea, and was frequently asked to travel around the world doing research and providing care to critically ill patients.
In 1988 nitric oxide was identified as the endothelial relaxing factor that regulated vascular tone. Warren had the tremendous insight to speculate that because it was a gas it could be therapeutically given by inhalation, and because it was inactivated nearly instantly in the circulation, its effect would be limited to the microcirculation immediately adjacent to its diffusion across the alveolar-capillary interface. Furthermore, because it would only reach ventilated regions of the lung, it would enhance ventilation-perfusion matching. I remember very vividly the day Claes Frostell (now Professor of the anesthesia department at the Karolinska Institute in Stockholm) first administered it to a highly instrumented but awake lamb in the lab- no matter what model of pulmonary hypertension we used, NO reversed it within seconds. Warren immediately recognized the implications for persistent pulmonary hypertension of the newborn, and tasked Jesse (Jay) Roberts and me to develop a delivery system for newborns and submit an IRB application as fast as possible. The first infant we treated was being prepared for ECMO cannulation. While the ECMO team skeptically stepped aside, Warren, Jay, and I hooked up the circuit and within one minute the infant’s oxygen saturations reached 100%. As everyone looked on in awe, selective pulmonary vasodilation, one of Warren’s dreams, had been achieved.
Warren’s greatest legacy, beyond the pioneering therapies and discoveries that have saved thousands of lives, is the close personal relationship he had with his many fellows and colleagues. He was relentlessly optimistic, unwaveringly supportive, and unsurprisingly always expected excellence. We were all always in awe of his amazing productivity and brilliance, but loved him equally as a person, and are honored to have known and worked with him.
David Polaner, MD, FAAP