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Living History of Physiology
Karlman Wasserman
 Karlman Wasserman was born in Brooklyn, New York in 1927 and graduated
from high School in Passaic, New Jersey in June 1944. World War II was
still quite active, allied troops just having landed in Normandy in
their European campaign. Not having yet reached the age of 18, he
joined the U.S. Army in the Army Specialized Training Reserve program to
start college education in basic engineering at Princeton University.
After finishing three quarters of college training at Princeton, he was
called to active duty in April, 1945, having already reached the age of
18 years. He trained in the infantry at Fort McClellan, Alabama. In
September of 1945, he was sent overseas to Japan as a member of the post
World War II Army of Occupation.
After completion of his service
in December, 1946, he was able to continue his education, using the GI
bill, at Upsala College in East Orange, New Jersey, near his home. He
majored in chemistry and minored in biology, both of which he enjoyed.
After graduating with a Bachelor’s degree in September, 1948, with one
year left on his GI bill, he applied to Tulane University Graduate
School, in New Orleans, for training in Physiology. This turned out to
be a good fit, since he enjoyed the study of Physiology very much,
particularly the experimental component.
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.
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