Dr. Wasserman's Ph.D. research was on capillary permeability to macromolecules, under the tutelage of Hymen S. Mayerson, Chairman of the Department. Dr. Wasserman studied transport of radioactively labeled albumin and globulins, and later, dextrans, from the capillary circulation into the thoracic lymphatic duct and lymphatic circulation of specific organs, including the lung. It was a productive period leading to the award of a Ph.D. in Physiology in June 1951, less than three years after receiving his Bachelor's degree. He was encouraged to stay on in the Department at Tulane and was made an instructor in Physiology, lecturing on aspects of Respiratory Physiology. The Korean War had started and the U.S. Army was looking for a fluid that could be used to treat hypovolemic shock secondary to acute blood loss. The questions being addressed by Dr. Wasserman's research were relatively ideal for answering this question. The U.S. Army was interested in dextran molecules because of their low incidence of allergic reactions in man. The question was what would be the best molecular size of dextran to minimize renal loss and maximize the oncotic force needed to expand the plasma volume. Under an Army contract awarded to Professor Mayerson, Dr. Wasserman ascertained and documented the optimal molecular size of dextran to support the blood volume as a replacement fluid to treat hemorrhagic shock.
During the summers of 1951 to 1953, Dr. Wasserman, also performed research in comparative physiology in the Marine Biological Laboratory in Salisbury Cove, Maine, giving him the opportunity to meet investigators from other parts of the Country. From these exposures, he decided that he should broaden his education to include Medicine. He applied to and was admitted to Tulane Medical School in 1954. With support from his Department, he was retained on the faculty in Physiology until he graduated with his MD degree in 1958. Thus during this period, Dr. Wasserman was both teacher of Physiology and a student of Medicine.
For Internship, Dr. Wasserman applied and was selected to train on the Osler Service in Internal Medicine at Johns Hopkins. During the year, he received a call from the National Institutes of Health, offering him a special fellowship for further training with Dr. Julius H. Comroe, Jr. who just started the Cardiovascular Research Institute at the University of California in San Francisco. He heard Dr. Comroe speak at APS meetings several times in the past and was impressed with his clarity of speech and ideas. He accepted this offer and in the following summer moved, with his growing family, from Baltimore to San Francisco, for a new experience in which research and teaching skills were stressed. This would later serve as a model of how to effectively incorporate a patient care service with research when he would become head of his own Division.
When arriving at the Cardiovascular Research Institute, Dr. Wasserman was asked by Dr. Comroe about his major area of research interest. His response was the pulmonary circulation. That was the last organ system on which he worked in his studies on capillary permeability. Dr. Comroe responded very quickly, describing a controversy in which two sets of highly skilled investigators, from different institutions, obtained different results with respect to the pattern of pulmonary capillary blood flow during the cardiac cycle. A new ingenious non-invasive method had been reported to measure pulmonary capillary blood flow during the cardiac cycle, in humans, while breath-holding with a gas mixture of N2O and O2 in a body plethysmograph from the analysis of the instantaneous pressure changes during the cardiac cycle. The reporting investigative group obtained results that showed that pulmonary capillary blood flow through the pulmonary capillary bed during the cardiac cycle was pulsatile with a peak to mean ratio of approximately 2.5:1. The other group, using the same technique, maintained that the finding of pulsatile pulmonary capillary blood flow was an artifact. Dr. Comroe asked Dr. Wasserman to investigate the problem to see who was right, using a different technique to solve the problem. Dr. Wasserman did so, using a very sensitive and rapidly responding Krogh spirometer mounted with an electronic recording transducer. Later, he modified the body plethysmograph to record N2O flow into the pulmonary circulation, directly. Using this technique, he was able to show that pulmonary capillary blood flow was pulsatile during the cardiac cycle in normal subjects, but became less pulsatile with increased pulmonary vascular resistance. This flow-modified body plethysmograph gave much cleaner signals and provided peak to mean flow ratios under resting and exercise conditions, with vasoactive drugs, and in cardiac patients, without requiring breath-holding.
In 1960, Dr. Comroe returned from the American Heart Association meeting and called Dr. Wasserman into his office. He explained that it had been reported that heart disease was reaching epidemic proportions in the United States. He asked Dr. Wasserman how heart failure could be detected in its earliest stages, non-invasively, in populations. Dr. Wasserman had the view that the major role of the circulation was to support cellular respiration. Thus, he responded that the earliest detection of heart failure would be under the physiological stress of exercise, when cellular (muscle) respiration was increased. The O2 uptake at which the circulation failed to track the O2 requirement of exercise would result in anaerobiosis and lactic acidosis (the anaerobic threshold). Dr. Wasserman explained that the lactic acid must be buffered mole for mole, by the volatile buffer, bicarbonate, producing an equal number of CO2 molecules added to the CO2 produced by aerobic metabolism. Dr. Wasserman further suggested that the technology was available in the Institute to make this measurement breath-by-breath. Dr. Comroe then told Dr. Wasserman to do it.
While starting his work on exercise at the Cardiovascular Research Institute in San Francisco, Dr. Wasserman was committed to a new position at Stanford. He obtained a grant from NIH to set up his laboratory at Stanford, where he continued to develop the technique to measure the anaerobic threshold during exercise. While convinced that the concept was sound, he found that it wasn't as easy to measure as he theorized. He needed to change the techniques of measurement twice from his original plan, before he felt that he could reliably measure the lactic acidosis threshold in all types of patients and normal subjects. Key to this achievement was his collaboration with Dr. William L. Beaver, a physicist working at Central Research at Varian Associates in Palo Alto, who was assigned by Varian to work with Dr. Wasserman. This was again a good fit, enabling the use of digital computers for breath-by-breath exercise gas exchange. A number of papers were published from this collaboration, considerably advancing exercise testing as a clinical tool.
In 1967, Dr. Wasserman was invited by UCLA to become Division Chief at Harbor General Hospital, now Harbor-UCLA Medical Center. Dr. Brian J. Whipp, then a pre-doctoral Fellow with Dr. Wasserman at Stanford, moved with him, helping to set up the research exercise physiology laboratory and collaborating in exercise physiology research. The collaboration with Dr. Beaver continued. In the course of their research, unanticipated physiological events in exercise gas exchange were discovered, which increased the team's interest in respiratory control. The move to Los Angeles further heightened the interest in respiratory control by the discovery of patients without carotid bodies, these patients having had their carotid bodies resected, presumably for relief of their symptom of dyspnea. Thus research was directed in this area, with studies being done, using arterial catheters to monitor changes in blood gases and hydrogen ion concentration during exercise in humans with and without carotid bodies. The Fellowship program was set up by Dr. Wasserman to encourage all Fellows to engage in research, and most did.
About 1977, the U.S. Department of Labor approached Dr. Wasserman, asking if he could evaluate shipyard workers for lung disease and exercise impairment, in order to evaluate their disability, if any. Presumably, these subjects were exposed to asbestos in the environment of their work. Did these workers have evidence of exercise limitation and could the exercise limitation be due to asbestos? Dr. Wasserman agreed to engage in the study. This incorporated the post-doctoral M.D. fellows in the exercise lab and a number of clinical and physiological research studies were reported. The then new computerized breath-by-breath system developed by Dr. Beaver, with modifications by Dr. Darryl Sue, was the methodology being used.
The research involving exercise testing on large numbers of subjects brought physicians and physiologists from other parts of the country and other countries to the laboratory to see how the research was being done. To concentrate the timing of these visits, the Division started to give courses in exercise physiology and pathophysiology (Practicums). By 2009, 53 courses were completed in Torrance, California, 13 courses had been completed in Japan and 13 courses had been completed in Europe. A book, currently in its fourth edition, entitled "Principles of Exercise Testing and Interpretation: Pathophysiology and clinical applications" is used as the course syllabus.. The book was translated from English into Japanese, Chinese and Portuguese. Dr. Wasserman is now Professor Emeritus on Recall at UCLA David Geffen School of Medicine. He is currently active in addressing physiological problems and collaborating with investigators in the United States and other countries.