Starting back in high school, I had been interested in science and research. Several of us dreamed up an elective course on psychology that we asked one of our senior tutors, Mr. Jones, to teach. We were curious about how scientists designed experiments to study psychological reactions, whether they be of mice in a maze, pigeons in a box, or people in trouble. When someone did something stupid, kids used to say, “A crayfish learns in three lessons.” This individual must be dumber than a crayfish, an allusion to those experiments teaching crayfish how to negotiate a maze.
Then, in college, I did absolutely no research other than figuring out how to get to New York as inexpensively as possible to see Laura. Now in medical school, happily married to Laura, I could broaden my research horizons. As a student I had investigated the decline in placental gonadotropic hormones immediately after delivery, as recounted in Chapter 2. More important than that, I was fascinated to learn at first hand the researches of people like Walter Cannon and A. Baird Hastings. Most of all I admired Fuller Albright. He presided over Ward 4 at the MGH, an area in the Bulfinch Building where there were four or five research beds.
The nurses on Ward 4 were especially trained to measure carefully everything their patients took in and to collect everything they put out. This was necessary so that metabolic changes could be measured
accurately. Ward 4 was one of the first metabolic wards in the country. It was later endowed by the Mallinckrodt Company and was called Mallinckrodt Ward 4. Some years later—and now I am skipping ahead— the National Institutes of Health, inspired by such research units, granted funds to support clinical centers in many teaching hospitals. These were greatly expanded versions of the original Ward 4 at the MGH.
While working at the MGH and attending Fuller Albright’s research seminars, I developed a desire to learn more about metabolic research. In the winter of 1940-1941, 2 years out of medical school, I decided to spend a year in research. My life as a university surgeon, using quantitative biology to study surgical illness, began at that moment.
In many ways my decision to acquire some basic research skills was more crucial in changing my life than was the decision to go into surgery. Coming from a nonmedical, nonacademic background, I did not recognize this choice for what it really was: a branch in the roadway for a young doctor. At the time I did not even realize I was making a big decision. I just wanted to get involved with science.
I set out on this branch in the road when in January 1941, as a junior surgical resident at the MGH, I applied for a fellowship of the National Research Council. Dr. Frederick C. Irving wrote the necessary sponsoring letter. He was the obstetrician who had delivered Nancy and Peter and was soon to deliver Sally, and I felt closer to him than to any other member of the Harvard Medical School faculty. Some time in April, I learned to my delight that I had been awarded this fellowship. I was going to be paid $1,800 for that year—more than I had ever earned before.
When I embarked on that fellowship year in the laboratory, and later spoke of my research, senior members of the faculty began to think of me as a research academic, a potential university surgeon. By contrast, my own plans were to go into clinical practice in Chicago after completing my residency. Dr. Vernon David, a prominent surgeon at the Presbyterian Hospital in Chicago, was a close friend of my father. I had been a patient of his only a few years previously. Before I completed my resi-
dency, Dr. David had offered me a job with him in Chicago. The offer included a small corner of his office in the Loop. As a matter of some note, many of the doctors’ offices in Chicago were situated in the People’s Gas Building. It would have been in this appropriately designated skyscraper that I would have settled.
After I published some research papers, the few members of the surgical community who knew of me at all certainly thought of me as an academic. Ironically, only a few years after Vernon David first talked with me about a job, and after I had published a few papers and made some presentations at national meetings, I was offered a position as the new academic professor of surgery at Presbyterian Hospital. Whether I knew it or not, I was heading on a route toward academia, with signposts clearly visible.
The two paths—clinical practice and academic work—do not have many crossovers. By the time a young surgeon is 3 years out of his residency in private practice (meaning that he is somewhere around 32 to 35 years old), it is almost impossible for him to make the change to academia. He will not be offered an appointment. Such young clinicians, no matter how brilliant or able, will not have the list of publications in basic science journals, the beginning of a reputation in research, the knowledge and know-how, and the concepts and methods of quantitative biology related to their clinical field. They will not have had the experience in laboratory design, administration, and finance required to make the change. They will have gained no funds to support whatever research they might plan. To enter the academic world of American biomedical research, you must start young, by studying and learning the methods of science in a laboratory.
Once in academia, if the call of research fades and young doctors fail to have new ideas, yet wish to continue clinical care of the sick full time, they can always change back to a life in practice. Whatever the connection between these two career pathways, it is a one-way street.
For my fellowship year in biophysics, I joined the research group at the Huntington Memorial Hospital under Joseph Aub. This small hos-
pital was on Huntington Avenue, not too far from Brigham Circle, the Peter Bent Brigham Hospital, and the Harvard Medical School. The Huntington, the only hospital Harvard University ever owned, was devoted entirely to the study and care of cancer. Joseph Aub, as Physician-in-Chief, was working on the definition of abnormal growth. He was also interested in metabolic disease and was a pioneer in the application of isotopes to research, the newest and most rapidly growing hybrid of biology and physics, only then becoming known as “biophysics.”
Bringing that National Research Council fellowship stipend with me meant that Aub would not have to pay me even though he paid for my equipment. Waldo Cohn and Austin Brues were the two scientists who introduced me to isotope research. I was assigned a Geiger counter and the job of calibrating it each morning. For a whole year I saw no patients and did not scrub on any operations. I took a course in nuclear physics. I learned by direct observation that the amount of a radioactive substance present is proportional to the number of nuclear disintegrations per second, some of which made a click on the Geiger counter. A curie of any radioactive substance yields radiation at the rate of 3.7 x 1010 nuclear disintegrations per second. I had entered the world of applied physics and isotope research.
We had learned in medical school that certain dyes concentrate in abscesses. It was my plan to make one of these dyes radioactive so that when it was injected it would collect near the abscess, and its location could be detected from outside the body with a Geiger counter. Much as I would like to claim originality for this concept, the idea came from Valy Menkin, one of our teachers in pathology. In his writings Menkin stated that if this dye could somehow be made detectable, it might be useful as a way to diagnose and localize abscesses. That was 8 or 10 years before radioactive isotopes became available.
An isotope of an element is its twin sister, having identical chemical properties but a different atomic weight. The number after the name of the element indicates its weight relative to hydrogen. Some isotopes are radioactive, some not; most are natural, some manmade. The nonradioac-
tive isotopes of some common elements (deuterium for hydrogen, heavy nitrogen) differ by weight only. They can be measured by mass spectrometry.
Tracers are spies, informers. If radioactive, they announce by their radiation where they are and therefore where their compatriots are, like a bellwether that tells where the flock is. Radioactive isotopes have the additional feature that they can be detected from a distance by their radiation, such as from outside the body with a Geiger counter, or with a gamma camera, which takes a picture showing the “hot spots.” Radioactive isotopes make ideal tracers. I was to learn how to make use of this wonderful new scientific method, first used only a few years earlier, after Lawrence of Berkeley, California, invented the atom smasher (as the newspapers called it), or cyclotron.
To accomplish our mission of finding abscesses by means of radioactivity, we needed to make a radioactive dye. For this synthetic challenge I was fortunate in enlisting the aid of a young organic chemist, Lester Tobin. He had been studying under Louis Fieser, our teacher of organic chemistry, an expert in organic synthesis (making new compounds such as drugs). Tobin synthesized the radioactive derivative of a dye called trypan blue by linking two radioactive bromine atoms to its phenyl groups. We obtained the radioactive bromine by bombardment at the cyclotron either at Harvard or at MIT. In his book Why Smash Atoms?, Arthur Solomon explained how cyclotrons worked and how this all came about and thus helped our generation grasp the physics involved.
To make bromine radioactive, we placed an organic fluid, bromoform (the bromine analogue of chloroform), in glass bottles for neutron bombardment. Two physicists, Leo Szilard and T.A. Chalmers, had described this nuclear reaction. When a bromine atom in this fluid was hit by a neutron, it would be knocked off the bond attaching it to the bromoform molecule and be rendered radioactive. These radioactive bromine atoms would then become soluble in water. The radioactive bromine could therefore be separated from the bromoform by using an ordinary separatory funnel (high-school chemistry). This yielded highly active radiobromine. Szilard later became famous as a pioneer in the development of the atomic bomb.
As junior-grade researchers working closely with the group at
MIT under Professor Robley D. Evans (Chairman of the Department of Nuclear Physics), we occasionally attended biophysics seminars. I had taken some physics courses. One toe was immersed in nuclear physics. Later that year, MIT held a meeting on practical applications of nuclear physics. To my delight, I was invited.
The last speaker was a man I had never heard of before. His name was Enrico Fermi and the title of his talk was “Uranium Fission.” He made it clear that the atoms of certain heavy elements (that were unstable and spontaneously radioactive) would be split apart when hit by neutrons, causing them to release an immense burst of energy. Uranium was one such element. I listened with some interest because I had been using a uranium salt (uranyl zinc acetate) in my job with the Geiger counter. In his lecture Fermi was describing the basic nuclear reaction of the first atomic bomb. The term “uranium fission” was not mentioned again in public nor published in any form until after the war. About 2 years earlier, in 1939, Albert Einstein, in collaboration with Szilard, had written his famous letter to President Roosevelt about the military potential of Fermi’s discovery of uranium fission. Get enough of the right isotope of uranium in one clump—a critical mass—and it would touch itself off with its own neutrons, causing one hell of an explosion. At that time no one knew of the letter; few even in that audience grasped the implications of Fermi’s talk. Certainly not I. But after that moment the whole concept became highly classified, and those of us who worked with radioactive isotopes and nuclear physics were required to have security clearance, even including this young surgeon who was learning biophysical techniques to locate abscesses.
Lester Tobin and I went ahead with our work, but we were very careless with the everyday hazards of handling radioactive materials. We did not even wear exposure badges when working around the cyclotron. The only precaution we took was to remove our wristwatches, since the extremely powerful magnets of a cyclotron would ruin a watch forever. We even carried those big bottles of radioactive bromine under our arms and out to the car! Fortunately, neither of us has (as yet) suffered any consequences. And I fathered three more children. Maybe we were lucky as well as careless.
Once we had figured out how to produce sterile abscesses in the
bellies of anesthetized rabbits, Lester and I injected some of the radioactive dye and mounted a Geiger counter over the animal. To our delight (but surely no surprise) we could tell where the abscess was by the counts per minute. It took us about 7 months of hectic work to arrive at this point.
Later that spring (at the urging of Dr. Aub) we submitted an abstract of our work to the Society for Clinical Investigation. This was the leading organization of young medical scientists (known as the Young Turks) who were turning over new ground. We were thrilled to be given a place on the program of the society’s meeting at Atlantic City in April 1942. I was given 12 minutes to describe our research and demonstrate the localization of abscesses with a Geiger counter. In addition we showed that this dye tended to concentrate in tumors and theorized that a technique like this might be used to diagnose abscesses and treat tumors. We submitted three articles (on the radioactive dye synthesis, the abscess work, and tumor localization) to the Journal of Clinical Investigation and were pleased (and this time we were surprised) when our manuscripts were accepted and then published.
What we were doing, without having a word for it, was to stir around at its very beginnings in the field later called “nuclear medicine.” Nowadays, radiologists use radioactive isotopes for diagnosis and treatment daily in all major hospitals. I am proud of these early ideas, of Tobin’s organic synthesis, and of our early successful application of nuclear physics in the laboratory.
Our radioactive dye had other applications as well. In his lab at the MGH, Oliver Cope was examining changes in the permeability of capillaries in burned animals. By injecting the radioactive dye into these experimental animals, we could discern minute changes in permeability produced by even a tiny burn because we could detect a few molecules of the dye leaking out of the bloodstream into the lymph. This led to a better understanding of the fluid leak in burn injury, which requires plasma and fluid replacement. By then (1942) we were working under the wartime Office of Scientific Research and Development.
About that time I conceived the principle of diluting isotopes in the body to measure the body’s chemical components. By injecting minuscule amounts of isotopes into the body and measuring the extent of
their dilution, we could determine how much there was of the substance in which they were diluted. We first applied this principle to burns, and it became the basis of our treatment of burn injury, providing a way of measuring the fluid requirement of burned patients and representing the beginning of a study known as “Body Composition,” a term we later used to describe this rapidly growing area of knowledge.
Upon finishing the residency in November 1943, I could return to serious research along with the clinical tasks of assisting Leland McKittrick. I was very busy, but it was wartime and so was everyone else: some at home, others abroad fighting the war.
After a couple of years of riding the two horses of clinical practice and academic work, it became obvious that my heart was in academia and, as Oliver Cope had warned, there was not time for both. By now my career ambivalence was vanishing. After the war, and with the return of many staff colleagues, I concentrated entirely on my academic and surgical work at the MGH. A couple of years later, the Barnes Hospital and Washington University in St. Louis offered me a professorship. They had read my papers and knew of the direction my work was taking. Surely this was yet another clear sign that the surgical establishment had made a choice of which way I would go. I thanked Bob Moore, the Dean at Washington University, who had come to visit and tried to recruit me, but told him I wanted to stay in Boston.
Those wonderful years at the MGH following my residency, from 1943 to 1948, were vital not only to my clinical development but also to my long-range plans in biological science and surgery. I am grateful to Edward Churchill and Oliver Cope for giving me so much help in those crucial years—crucial for all young doctors starting out either in practice or in academia—and to Leland McKittrick for giving me such a joyous introduction to the private practice of surgery. My debt to the MGH is boundless.
In 1947 I sent a review article to Surgery, Gynecology & Obstetrics, a major surgical journal with an international circulation. Entitled “The Use of Isotopes in Surgical Research,” it was given the leadoff position in the
January 1948 issue. To me it was old stuff going back 8 years. But for many of the surgical readers, it contained new ideas and attracted a lot of attention. In it I described in understandable terms, without physics or formulas, the principle of isotope dilution, the meaning of body composition, and their potential for improving surgical care.
Some of the most pressing problems of surgery in the 1930s and 1940s were the dangerous inaccuracy, inadequacy, and often disastrous ineffectiveness of supportive care for patients who had sustained severe injuries, burns, or major operations. These problems of midcentury surgery came into focus as anesthesia, asepsis, the increased range of surgery, and two world wars had brought surgery to greater prominence in the treatment of a remarkable range of illnesses. This change in the scope of surgery was to be expected in historical terms about the time our generation entered the field. We did not invent it. Maybe our generation was acutely aware of the need for greater accuracy and depth of knowledge as we saw the methods of surgery spread to patients in every specialty of medicine.
Supportive care might include intravenous infusions of water, salt, or sugar; transfusions of blood and plasma to replace lost fluids or blood; and nutritional (dietary) support by mouth or vein. The amount of fluid given often missed the mark by a wide margin. While flying blind can be a problem in internal medicine, it is in surgery that such inadequacies are especially dangerous. This is because of the responsibility of surgeons for the care of massive injuries, wounds, burns, and major operations, all of which produce abrupt and potentially lethal changes in the bodily economy.
I saw many burned patients go into shock or die in the first 24 hours because of inadequate fluid treatment. Sometimes I was guilty of the same errors because there were no reliable guides. If the surgeon could have estimated a patient’s blood volume from simple age-sex-weight tables (not available at that time) and could assess the degree of plasma loss based on the blood cell count, he could have done a more accurate job of estimating how much replacement fluid was needed. I recall a patient having an adrenal tumor removed—a dangerous operation at that time because of sodium loss from the body—who was literally drowned by saline infusions that greatly exceeded any rational need. Such deaths were often termed postoperative pneumonia because the extra fluid in the lungs was audible by stethoscope, as in pneumonia. But it was not pneumonia in any sense of that term. Nor was it infection. It was simply too much fluid. Pulmonary edema.
These treatment errors came about because no one knew how much fluid there was in the body to begin with, in its various fluid compartments, or pools. No one could appreciate the meaning of the extent of water or sodium losses without knowing the normal baseline values. Some of these losses could actually be due to relocation within the body: from the blood plasma to the lymph in burns, for example. Using isotopes, we solved the mystery of the whereabouts of the lost plasma of burns. It was in the body but in the wrong place. This loss of plasma could be lethal without a drop of plasma escaping from the body.
Until several years after World War II, even such matters as avoiding dehydration in intestinal obstruction or vomiting, or managing an imbalance of chemicals in the blood, were dangerously mishandled. Today, these are simple, even routine problems, easily corrected. Disasters could have been avoided had the surgeon known normal body composition and the meaning of fractional gains and losses of tissue and fluid. Our studies of body composition led to a definition of the biochemistry of surgical illness as well as a sounder estimate of the most urgent needs of sick or injured patients. They also led directly to research in the biology of surgical convalescence, the chemistry of getting well.
Chemical methods for measuring blood volume had already been developed and exploited by Magnus Gregerson, the physiologist at Columbia, and had been extended to other aspects of the bodily economy by
John Stewart, an MGH surgeon a few years ahead of me in the residency. My special opportunity arose from the ability—gained in that glorious year as a National Research Council fellow at the Huntington Hospital— to use isotopes (both stable and radioactive) for this work. Through isotope dilution we could get a better handle on body composition, on the needs of sick surgical patients, and how to treat them more accurately.
We measured total body water, extracellular water, blood volume, the total mass or weight of body cells, total sodium, and total potassium. From these we could accurately estimate total body nitrogen and hydrogen, body fat, and the weight of the skeleton. The stuff of which the body is composed could be measured accurately and without pain or inconvenience in the living by using new biophysical tools: isotope tracers. In this work we were lucky in being able to do the whole job with tiny doses of radioactivity.
The principle of isotope dilution is disarmingly simple. To measure an unknown volume of water, put a known bit of salt in it and find out how much it is diluted. This is a familiar chemical principle. If you have a bucket of fresh water and you don’t know how much is in it, put in a gram (1.0 gram) of salt. Stir the salt around and let it equilibrate, that is, come to rest fully diluted and distributed. Then take a small sample. If there is 0.001 gram of salt (1/1,000th of a gram, or 1 milligram) in each milliliter of the water, then the salt must have been diluted in 1,000 milliliters (i.e., 1 liter) of solution. You have measured the unknown volume of water in the bucket by adding a known amount of tracer to it and measuring the extent of the tracer’s dilution.
We adapted this principle, using radioactive isotopes, to measure several key elements of which the body is composed: water (using heavy hydrogen, or deuterium, and later hydrogen of weight 3, or tritium), potassium (using 42K), sodium (using 24Na), and chloride (using radiobromide, 36Br, which behaves like chloride). Later we used heavy nitrogen (15N) to measure the rates of protein synthesis. We used radioactive chromium, as developed by Seymour Gray in the Department of Medicine, for measuring the red cell volume and Evans blue dye (Gregerson) for the plasma volume. A small sample of blood was all that was required to measure the extent of dilution and the total body composition.
In explaining the measurement of volume by dilution, the drink-of-whiskey model is a good one. A jigger of whiskey in a small glass of water is harsh stuff. Put it in a quart of water, well... lots weaker. The taste (i.e., concentration) of the whiskey reflects the volume of water you have added. You are measuring a volume by dilution of a tracer. By the same token, the density of dye color is inversely proportional to the volume of water added to soften the color.
We live on a planet constantly bombarded by radiation from outer space (cosmic rays and solar flare emissions). We have a naturally occurring radioactive isotope of potassium (40K) in every cell of our bodies, mixed intimately with the chromosomes and genes that guide our growth and behavior. We are also hit by radiation from the Earth itself (uranium, radium) and from medical tests (x-rays, nuclear medicine). When radiation doses are increased far above this natural background level, cancer and other diseases can result. Genetic changes are sometimes produced. Therefore, in our studies of body composition we were careful to see to it that the total dose of radiation did not exceed that from a one-shot diagnostic x-ray. In pregnancy, even very small doses of radiation are dangerous to the unborn child, so we did not use radioactive isotopes in studying the body composition in pregnant women or in young children.
It is said that Archimedes first conceived of the physical principles by which some things float and others sink while he was floating in a bathtub. I can claim a certain kinship with the great floater, because it was while taking a bath that I first conceived of the idea of measuring the amount of water in the body by diluting an isotopic tracer for water. An isotope of either hydrogen or oxygen would be required to measure the total amount of water, which is a compound of these two elements (H2O). Isotopes of each element differ in atomic weight but not in chemical properties. Hydrogen (H) has an atomic weight of 1. Deuterium (D), as one might guess from its name, is an isotope of hydrogen of weight 2. It is also called heavy hydrogen. Deuterium is not radioactive; it is a stable isotope. When combined with oxygen, deuterium makes heavy water.
Ordinary water is H2O. Heavy water is D2O. Tritium (the hydrogen isotope of weight 3) is radioactive.
For isotope dilution of a water tracer, heavy water certainly seemed the way to go. It can be detected because of the tiny difference in its weight or specific gravity. Needless to say, like all young scientists, I thought my idea of measuring total body water by deuterium dilution was original. I therefore wrote to Professor Harold Urey (who had discovered deuterium), told him of my idea for body water measurement, and asked if I could obtain some of this isotope. He replied helpfully, sending me a little test tube of deuterium (as heavy water) from an atomic reactor. I still treasure this gift in my personal museum.
More important, in his reply Professor Urey told me that the idea would certainly work and that a Hungarian scientist living in Sweden, Georg von Hevesy, had considered this possibility a few years before. There is nothing new under the sun. I then wrote to von Hevesy, who told me this story. While having tea in the Rutherford Physics Laboratory in Cambridge, England, in 1934, he and his partner (H.J.G. Moseley, the physicist) mused over the fact that, “If there were a little heavy water in this tea, we could measure how much water was in our own bodies.” They had not done the experiment. It remained for us to accomplish this in our laboratories in the next few years and to define the normal total body water content in human beings of both sexes and all ages as a basis for studying changes in body water content in disease. Georg von Hevesy became a friend and to him we later dedicated our book on body composition (The Body Cell Mass).
But first we had to prove that the method really worked. Start simple. So we began by measuring the total body water of rabbits by deuterium dilution, injecting heavy water as normal saline solution. After we had finished the measurement (which required two or three blood samples over the course of an hour), we killed the rabbits by injection of an anesthetic. After weighing each carcass carefully, we took each to absolute dryness in a vacuum desiccator and weighed it again. This may sound complicated, even bulky, but it was a simple principle. Kitchen chemistry. A bit smelly. I had as assistants two young women, Margaret Ball and Caryl Magnus, who did the hard part, the analytic steps. If you weigh something while it is wet (a sponge, let us say), then take it to
absolute dryness so that it won’t lose any more weight with further drying, the difference between the wet weight and the dry weight will equal the weight of water that was in the sponge at the start. Same with the rabbit.
You can imagine our elation when we found that the amount of water in the rabbit’s body, as measured by drying, correlated perfectly with the total body water, as measured by heavy water (deuterium) dilution in the living animal. Our new and elegant isotopic method, based on nuclear physics and chemistry, really worked.
From this beginning, we developed methods for measuring some of the other substances in the body using radiobromide for the volume of extracellular fluid, a principle based on studies done a few years before by our chemistry mentor at Harvard Medical School, A. Baird Hastings. We also measured the total weights of sodium and potassium in the body by dilution of their radioactive isotopes, an entirely original idea. And it worked, as proven again by analysis of the whole rabbit. We were on our way. The dream was to analyze the human body while the patient lay quietly in bed, reading the morning paper.
Once assured that the low doses of radioactivity were safe and that the method was accurate in laboratory animals, we studied people. To begin with, we studied ourselves, our wives, and our families. In the women and children we used only nonradioactive deuterium and the blue dye, so as to avoid even tiny doses of radiation. Because we were interested in changes throughout the age groups, we measured the total body water in our children and enlisted willing patients who were compositionally normal or awaiting study or operation. With an able team and laboratory staff we could get the job done. We perfected the method to the point of a single injection of several tracers and simultaneous measurements of equilibrium concentrations, all in 2 to 3 hours: “one-shot” body composition. James D. McMurrey, later a surgeon of Houston, Texas, was a leader in the development of the multiple simultaneous compositional methods.
We had shown that all the potassium in the body exchanges with
the radioactive tracer (unlike sodium, about a third of which is trapped in bone). About 98% of body potassium is within cells, at a chemically constant concentration in normal health. In disease, this concentration fluctuates with the osmotic strength of the plasma and can be estimated accurately. Thus, in measuring total body potassium we were, quite directly, measuring the total mass (weight) of all the cells of the body. The total body cell mass is the engine of the body that needs fuel and oxygen to keep going, since it does all the work of exercise, secretion, and thinking (the brain is a very active tissue metabolically). It is the central core. All else (skin, bone, tendons, fascia, cartilage, joints) is chassis and is, interestingly, sodium-rich, while the cells are potassium-rich with (normally) only tiny concentrations of sodium.
The concept of the body cell mass was a major fruit of our findings and our thinking and became the title of the book we published in 1963 describing the findings of almost 20 years of research.
From such data we could define normal values for human body composition as well as growth and aging in those terms. We found sudden changes at puberty for both sexes. When a girl reaches puberty she gains fat that helps form her breasts and the curves of her feminine figure. This is fatty or adipose tissue deposited in characteristic locations. At puberty the relative amounts of water and potassium (muscle) therefore fall. Meanwhile, her figure changes from that of a young girl to that of a mature woman. Her male counterpart at puberty does just the opposite, losing notable amounts of fat, gaining water and potassium (muscle), looking less chubby and more angular, lean, and muscular, as he matures into an adult man. The male has a larger body cell mass than the female—a larger total metabolism—but is often less resistant to hardship and starvation.
From time to time we published our findings in both the clinical and the scientific literature. This had a remarkable effect. Doctors began to think more clearly about the body composition of their patients and how it was affected by disease and treatment. Many young scientists were attracted to our laboratories from several different disciplines and from foreign countries. Within a few years similar work was undertaken in other labs, often by our pupils. The exact composition of the human body and the effects of disease on body composition are of interest and impor
tance to cardiologists, internists, pediatricians, nutritionists, dietitians, and even veterinarians.
To finish this job, measurements in hundreds of sick patients before and after treatment now became our task—one that was to occupy our laboratory staff and successive groups of young physicians, surgeons, and scientists for many years. We started this task at the MGH but then moved to the Brigham. These results, too, were published in the scientific journals as well as in clinical papers and chapters in textbooks. This work was to lead to my recognition as a scientist not only among surgeons but also by scientists from other fields. Many other laboratories here and abroad took up the work, and it remains a lively field of study 50 years after our first start. The findings have made surgery safer and have assisted in the care of medical and pediatric patients everywhere.
Within a year or two of starting these studies of human body composition in health and disease, we broadened our focus to investigate the forces that drive convalescence (described in the next chapter). Changes in the human body after severe injury involve characteristic alterations not only in body composition, but also in metabolism and in the hormone secretions of the endocrine glands.
To discern the sequence of changes that occur within the human body after injury became our most important ongoing quest. I suppose this quest was born in reasonably full-fledged form somewhere around 1945, when we began to measure total body water with deuterium and to measure the loss of nitrogen and potassium after injury. Later, this work became dignified as a field of study known as “metabolism in convalescence,” or the biology of getting well. Since nearly all of surgery involves the care of patients after injury or operation, this chemistry and physiology, the biology of convalescence, is central to the understanding and care of surgical patients.
You do not need to be a researcher, chemist, or biologist to be thrilled by the strong natural forces and inner drive that lead to recovery after severe injury. We all sense this when we witness the recovery of someone we know who has had a bad infection, a major operation, or a broken bone.
At first the body is struck down. The patient is in pain and is listless, wants to stay in bed, and can’t do much else. No appetite; weight and fat are lost rapidly. Precious water and salt are rigorously conserved.
Nitrogen (and therefore protein) is lost, muscles shrink, the patient feels weak and has no interest in much of anything.
Then comes a turning point. In ordinary major abdominal operations this usually comes at 2 or 3 days. After a severe burn it may take a week or longer; in multiple fractures, as seen in automobile accidents or war wounds, this turnabout may be postponed as much as 10 days. This spectacular turn of events, readily visible to all, is that suddenly the patient takes a much greater interest in surroundings, food, and people. There is a desire to get up, get eating, and get going. Patients ask for the newspaper or turn on the TV. They are once again interested in the world outside the hospital and eager to join it. In women, the first sign of recovery may be a bit of lipstick, the “positive lipstick sign.” Visitors are welcomed. But the patient is still quickly exhausted because the muscles are just not there to match ambition; they take longer to rebuild. Weight loss seems to increase sharply for a day or two. If you examine this seeming enigma, you find that it is because the patient is now making more urine. A diuresis. The swelling around the burn or fracture (as an example) goes away. During this time the area of the injury itself becomes not only less swollen but also much less painful and tender. Toward the end of this phase, the stitches are removed (or reabsorbed) because the skin has gained enough tensile strength to hold itself together without the help of stitches.
Then the patient moves into the third phase of convalescence. The recovering economy of the body starts to rebuild muscles. The rehabilitation phase. The teenage football player with the broken leg doesn’t need to be told what is going on. He begins to feel stronger. The body cell mass, the muscles, and strength increase with eating and intake of protein. Bones heal much more slowly than skin, and fractured bones cannot take the full load of body weight for several more weeks. Muscles rebuild at an intermediate rate. In burns, the skin covering is also slow to heal, sometimes taking weeks or months. Rehabilitation exercises and physiotherapy as well as an appetizing protein diet help muscle regrowth. Libido returns. Women usually have no monthly periods after severe injury, but a few months later the menses return. The patient who felt ready to leave the hospital some time after the turning-point phase now may feel strong enough to consider a return to work. Nowadays, doctors often permit patients to return to work too soon (at least in my opinion).
Metabolic studies show that for several weeks muscle protein is still being resynthesized. The doctor should be saying, “Don’t go back to work until you feel strong enough.”
Finally, starting about 5 or 6 weeks after major surgery or injury (several months after a severe burn), muscle mass has returned to near normal but body fat is yet to be regained. In the fourth phase this fat is restored, and the patient finally gets back up to normal weight. It requires calories to rebuild protein in muscle; when the muscle is rebuilt to the size needed for daily demands, those calories (now extra calories) are stored as fat.
This normal sequence of convalescence has deep roots in evolution. It is driven in part by hormones and is reflected by changes in body composition (some of them hormone-induced) and by the net balance of important nutrients such as nitrogen, salts, vitamins, and total calories.
When we first became interested in pulling this fascinating picture together and doing the research to understand it better, it was only 8 years after I had been a pupil in the physiology classes of Walter B. Cannon, who contributed the first hormonal (endocrine) data to this field. He was the first pioneer in studying bodily changes after injury. David Cuthbertson was the first to show the protein loss after injury. I was fortunate to have known both men, one as my professor of physiology, the other as a friend whom I had met in Scotland when I was visiting professor in Edinburgh with Sir James Learmonth in 1952.
Walter Cannon spent most of his life studying the autonomic nervous system. In his book Bodily Changes in Pain, Hunger, Fear and Rage; An Account of Recent Researches into the Function of Emotional Excitement, he showed that certain types of stress or excitement elicited an outpouring of the adrenal medullary hormones epinephrine and norepinephrine, sometimes called the fight-or-flight hormones. Now we know that these hormones produce profound changes in the metabolism of sugar and fat, with changes in heart rate and other adaptations to a reduced circulating volume of blood. In many cases of stress or injury—and most certainly in big operations, severe accidents, or burns—this line of defense is the first
evidence of the body’s response to injury. It is not so much “fight or flight” as it is “hard times ahead.” These same adrenal medullary hormones, acting via the pituitary (as shown by George Thorn), then activate increased secretion of their next-door neighbors, the adrenal cortical hormones, to engage the body as a whole not only in emergency damage control, but also in initiating the long process of getting well.
David Cuthbertson was a veterinary researcher in Scotland. In experiments on rats he showed that after fracture of the femur there was a marked outpouring of nitrogen, a proxy for body protein. All protein contains nitrogen, and most of the nitrogen of the body is in protein. If you are losing more protein than you are taking in, you are said to be in negative nitrogen balance. Protein is disappearing. Building directly on Cuthbertson’s first studies in rats, we showed that the same thing is true in humans and that in certain types of very severe injury or infection the loss of body protein can be massive. During the nitrogen buildup phase it reloads again. Cuthbertson used the term “ebb” for the early nitrogen loss and “flow” for the resumption of synthesis. To this background we added data on many surgical patients, along with studies of water and salt balance, body composition, and the activity of the endocrine glands; it was clear that Cannon and Cuthbertson were the pioneers who had provided the basis for our emerging understanding of convalescence as an innate biological sequence after injury. In Darwinian terms its survival value is obvious: this is how the fittest survive after injury.
In those years (1946 to 1952) we were setting out to fill in this intricate picture of human survival. In 1952 I was invited to Edinburgh as visiting professor of surgery. Through the kindness of my host Sir James Learmonth, I had an opportunity to meet David Cuthbertson. We became friends, and 32 years later, in 1984, David (later Sir David) was present when I had the pleasure of giving the first Cuthbertson Lecture of the European Society of Nutrition, in Milan. Five years later Sir David died at the age of 88.
When I asserted that the whole of convalescent biology is an adaptation to injury that is important to survival, an innate chemical and physiologic process of the human body, people sometimes had trouble understanding what I was saying. Even if I stated that it is a survival mechanism, the product of millions of years of evolution, many still did
not grasp my meaning. For the species to survive, individuals must survive the severe adversity of injury, fractures, and burns.
To understand the body’s program for convalescence it helps to recognize two other familiar processes or programs analogous to convalescence: pregnancy and growth. Like convalescence, each involves a stimulus, certain nerve mediators, hormone activation, massive changes in body composition, a target date for completion, and an event signalling that completion. Each is deeply programmed in our genetic makeup. Each of these basic bodily programs might be restated, in rather stilted terms, as a “sequence of changes in composition and chemistry with accompanying hormone stimuli, a targeted outcome, and a set length of time to get there,” a biological process essential to survival of the species.
To gather data on this matter in the human being after injury, we studied a great many patients. To our patients, this research did not seem very remarkable or upsetting because their care was unchanged thereby. Mostly we measured their diet and their output, their gains and losses. In many instances we admitted them to a small metabolic ward, a sort of surgical version of Ward 4 at the MGH (Chapter 2). We had established this research unit in 1954 with an endowment in honor of Laura’s father, Edmund B. Bartlett, given in his memory by Laura’s mother and called the Bartlett Unit. In this metabolic unit we were able to measure everything we needed without running around all over the hospital. While this arrangement might have seemed at first glance to be inconvenient to the patients, actually it was not. Each patient was given a single room and had special nurses attending to them around the clock without having to pay extra. Most important were their overall surgical care, their urine collections, dietary analyses, and their one-shot multiple-isotope injection to determine body composition. The tracer dose of radioactivity was tiny and within the established safety guidelines.
We studied lesser kinds of surgical injury as well as severe, life-endangering trauma. Patients were selected who had all sorts of difficulties, including major operations, minor operations, and some severe injuries, compound fractures, total body crush (a term used by residents to
denote severe injury from an automobile accident), and major burns. My son Peter came down with acute appendicitis at this time. With his informed consent (about which I was the butt of a certain amount of ribbing in later years), he was admitted for the study of the metabolic responses to a very simple operation: appendectomy.
Our studies showed clearly that in patients of all ages, of both sexes, and with a variety of injuries or operations, the process of injury and healing followed essentially the same sequence. In all instances there was the stimulus of injury, such as accidental trauma, elective surgery, or even an acute infection. This was accompanied by psychological and emotional changes, including fear and apprehension, as well as neurological responses, especially those of pain. Endocrine changes (alterations in the blood level of hormones) showed (just as Cannon had shown) that the adrenal medulla was one of the first glands to respond, followed by the outer layers of the adrenal (the cortex) with cortisone-like hormones. The pituitary gland is activated at the outset to stimulate these adrenal cortical changes and, in addition, to secrete antidiuretic hormone, which conserves body water. Since salt and water are retained, it is important not to give too much at this stage, especially in older people. The body shifts its energy source from burning carbohydrate (sugar) in food to oxidizing its own stored fat for calories. As one patient put it, “My operation was the world’s most effective and expensive form of weight loss.” Muscle protein is also hydrolyzed (chewed up) in this catabolic (destructive) process, the amino acids (building blocks) thus being made available by the metabolic mill from which new proteins can be synthesized and wounds can be healed. Then comes the long rebuilding phase, or anabolic (constructive) period of rebuilding body protein and finally body fat.
We began to publish some papers (occasionally a chapter in a book) about the metabolism of convalescence. Younger physicians, surgeons, and medical students who read about this work were evidently fascinated and wanted to know more about it. Many came to work with us. They understood the basics immediately. The analogy between convalescence and the bodily sequences of pregnancy and normal growth helped to explain convalescence to doubting practitioners.
In pregnancy the stimulus to metabolic change is the fertilization of the egg by the sperm. The bodily changes occur first in the uterus, then
in the mother’s metabolism of food as she passes nourishment along to the growing fetus. She gains water and salt, and her blood pressure rises. Her mammary glands enlarge and as she nears term her pelvic ligaments relax before labor begins. After the baby is born, her breasts continue to make milk proteins at a spectacular rate. When these protein factories are no longer needed because of weaning, the metabolic sequence is complete and her body returns to normal, though it will never be quite the same. Something has been accomplished by all these complex interlocking changes in hormones and body composition: the product is a well-nourished baby. The whole sequence is targeted for completion in about a year, including both pregnancy and the suckling phase.
The same sort of sequence occurs in the normal growth and later development of the child. After its birth and that intense protein synthesis in mother’s milk, the baby picks up the synthesis of protein at a rapid rate as well as the multiplication of all the body cells and elongation of the skeleton. All these events proceed in a precisely programmed way. The sex hormones kick in with a boot at puberty and produce the fat deposition that we call curves in the adolescent girl as well as breast growth and readiness for pregnancy; ovulation and menstrual periods begin. The young man grows muscle and loses fat, the sex organs get larger, and he has a more urgent libido. These sequences finally peak out with the emergence of the finished product: an adult human being. The duration of this particular metabolic-endocrine sequence is about 14 to 16 years for girls and 16 to 18 for boys.
Convalescence from injury is a closely similar sequence. Now, the stimulus is injury itself, the sequence consisting initially of loss of body protein with retention of water and salt, followed by gradual healing and rebuilding, as mentioned above. The duration here seems to be determined by the severity and nature of the injury. When it is all over (maybe 2 to 4 weeks after an ordinary abdominal operation, 2 or 3 months after a compound fracture of the thigh), we have the final product: a convalescent person who is ready to return to society, work, and procreation. With a healed wound.
Obstetricians need to know the bodily changes in pregnancy to care effectively for their pregnant patients. Pediatricians need to know the normal sequence during growth to care effectively for their young pa-
tients. By the same token, surgeons need to know the normal changes in the body during convalescence to care effectively for their patients after an operation or injury.
We think of convalescence as a normal sequence, that is, a predictable sequence in normal people. Sometimes the injury is too severe for the body to accommodate with a normal recovery. Shock and starvation are two special aspects of severe injury that interrupt the normal sequence of getting well and threaten survival.
The term “shock” refers to prolonged deficiency of blood flow usually due to loss of blood or extracellular fluid volume. With transfusion and intravenous fluids we can usually prevent or abate shock if we can get there soon enough. But in civilian accidents far from civilization and in combat settings, the flow deficiency is sometimes just too prolonged. Evolution has provided strategies for survival after expectable injuries in an animal’s daily struggle for existence. If the injury is so severe that prolonged shock results, then the bodily response alone is not enough. Without the surgeon’s help, death ususally results.
As for starvation, a person can feed his body from within by oxidizing fat for calories and mobilizing muscle protein for its building blocks (amino acids). But only for a while. Meeting daily or even extraordinary expenses by drawing on your bank balance can go on for only so long before new funds and new metabolic riches are needed to replenish deposits. This means taking in fuel in the form of carbohydrate, fat, and protein, plus vitamins and minerals, somehow, by some route but preferably by mouth. The best route for food intake is that planned by nature: eating and chewing and swallowing. But when that fails, there are other ways.
During the war Fuller Albright had done some experiments at the MGH to develop means of providing the body’s total nourishment through a needle intravenously. I picked this up from him and used it a good deal, describing this approach in my book on metabolic care in 1959. However, we did not study it adequately, nor did we spread the word successfully. The credit for priority in all of science should go to
those who are the first not only to perceive a discovery but also to make public the message. In this case it was the group under Jonathan Rhoads, Douglas Wilmore, Henry Vars, and Stanley Dudrick in Philadelphia who did experiments of this type in dogs. They showed that giving the entire (total) nourishment intravenously could support normal growth and the ability of the bitch to whelp and nurse puppies. Since the mid 1960s the giving of total nourishment by this method has been accepted throughout the world. This is vitally important in taking care not only of certain types of surgical patients, but also of many babies born with an inability to eat as well as older patients who are wasted or starving with disorders that preclude normal food intake. This sort of feeding is called total parenteral nutrition (usually abbreviated as TPN).
From this picture of convalescence came a better understanding of a matter of major importance in surgery: the chemistry of confidence. Fear and apprehension add to the intensity of the injury. One of the jobs of the surgeon is not only to repair the injury but also to “hang in there” with the patient; explain what is going on; offer solid reassurance; do the little things that help with pain, such as morphine or special positioning and splinting; and bear with the questions of the family, as companion and mentor. When the patient enjoys the surgeon’s visits, seeks his touch and his care, and rests secure in trust, a sort of stress-free basal state is established. This is why a capable and understanding surgeon (as well as nurses and hospital helpers) contributes so much to recovery. Mental stability and emotional calm are engines of recovery, just as the stressed and shocked mind is an injury in itself and continued anxiety an impediment to recovery. “Doctor” means “teacher.” Part of the doctor’s job is to teach patients about their troubles, what is needed, what will happen, how the future looks, and what to expect.
During those years our research was very expensive. The institutions in which we were working—the Harvard Medical School, the MGH, and the Peter Bent Brigham Hospital—gave us the facilities, the opportunities, and the moral support. We were fortunate in obtaining generous grants from the National Institutes of Health, the Navy, the
Commonwealth Fund, the Hartford Foundation, and the Atomic Energy Commission. It was under contract with the Army that many of these studies were done and my teaching in this field extended to the army courses at Walter Reed Hospital. I became consultant to the Surgeon General of the Army. We did our best to bring the message from our whole laboratory group directly back to the cause for which it was supported: the care of the wounded. Our most intensive research covered the period of World War II and Korea, with later application in Vietnam.
Friends in other institutions worked in this field of study with us. Sometimes they learned from our example, especially with regard to isotopic methods. In other cases we learned from them. These colleagues included Henry T. Randall of New York, William Abbott and William Holden of Cleveland, George Clowes of Boston City Hospital and Brown University, David Hume of our department and later Virginia Commonwealth University in Richmond, Everett Evans at Richmond, and the brilliant group of officers at the Surgical Research Unit at Brooke Army Hospital in San Antonio, Texas. John Kinney, originally a member of our unit and later on the faculty at Columbia, was particularly interested in the energy sources and overall energetics of trauma metabolism. Because of the particularly congenial nature of this group, we formed the Surgical Biology Club in 1954 to get together and talk about these problems. This club soon expanded to include many other features of surgical biology, especially cardiac surgery and transplantation. And before long, similar discussion clubs were formed by our younger colleagues in surgical research.
In 1947 I asked my chief laboratory technician, Margaret Ball, Radcliffe graduate and chemist, to join me as coauthor of a monograph that described the results of our early studies of water and salt changes, nitrogen metabolism, and energy exchange in surgical patients. It was called The Metabolic Response to Surgery and it was intended to present the plain facts about metabolic change in surgery. No pretentious conclusions.
Several years later, in 1959, the W.B. Saunders Company published Metabolic Care of the Surgical Patient. This also was a monograph—a
clinical and research monograph—based on our work, including chemistry and endocrinology, body composition, and certain important surgical operative steps. This became my most widely read book, translated into Spanish, Polish, and Japanese. There was said to be a Russian translation, but since the Soviets did not follow our copyright laws, we knew little about it. For a while it was one of the more quoted books in the surgical literature. We were all pleased by the interest shown in this book by the surgical public both here and abroad. I never wrote a second edition, but other authors, including particularly Douglas Wilmore (who took over my laboratory upon my retirement), published several books on these topics in collaboration with one of our graduates, Murray Brennan (now of Cornell University and the Memorial Sloan-Kettering Cancer Center).
During the war Edward Churchill, my boss during my internship, was surgical commander in the Mediterranean theater. The Excelsior Surgical Society formed by his colleagues in the war established the Churchill Lectureship. In 1952 I was asked to give the Churchill Lecture, where for the first time I discussed publicly my theory of the four phases of convalescence and of surgical convalescence as an integrated natural process similar to pregnancy and normal growth.
Then, in 1956, I was invited by the Harvey Society to give one of their lectures. As a surgeon I was flattered by this invitation because these lectures are usually given by scientists in the basic fields such as chemistry, physiology, biochemistry, or endocrinology. It was on this occasion that I first discussed our growing knowledge of the endocrine changes after surgical operations and postulated the existence of a “wound hormone.” By that I meant a circulating substance from the wound itself that could stimulate the endocrine glands directly. Many years later George Clowes showed that a newly discovered lymph-cell stimulator called interleukin-1 (IL-1) could act in exactly that way. Much remains to be learned about this wound stimulus to bodily change.
The awards, distinctions, and honorary degrees that came my way over the years were recognition of the work of our laboratory group in surgical metabolism and the biology of convalescence. As I made clear on so many occasions, this was not a solo effort. My many colleagues in the lab, as well as some of these honors and appropriate bibliographic references, are set forth in the Notes and References section later in the book.
During medical school Laurie and I had moved from the walk-up on Longwood Avenue to a house up on Corey Hill overlooking Boston Harbor (in the far distance). A few years later we moved down the hill to a place near Brookline Village called Griggs Road. This was a circle of small row houses, facing a central playground. In these houses dwelt several friends of ours, doctors and medical students, including, particularly, Reed and Faith Harwood, John and Sally Adams, and the older man I would come to admire so much, virologist John Enders, and his wife. All our children played together out in the middle of the playing field. I was supposed to mow the lawn in front of my house but became too engrossed with other activities to do it as dutifully as I should have. Once the grass grew so long that Henry Swan, another friend who lived nearby, came with his mower and mowed “MOORE” in the long grass as a gentle reminder that I was the owner and (delinquent) mower of that particular bit of greenery.
By 1944, entering practice and feeling a little more affluent, and because we had three children and were about to have a fourth (Caroline), we needed a bigger house. As always, Laurie was the person who found
our new house. I was too busy working at the hospital. She found a marvelous big old New England house up on the Walnut Street hill in Brookline, across from the First Unitarian Church.
In 1947 we purchased a few acres on Marion Harbor about 60 miles south of Boston, where the wind blew hard and the sailing was wonderful. The children’s summers were spent in Marion learning to sail. We built a small house there to which we added another bubble every now and then. I took a couple of weeks off each summer, but Laurie and the kids lived down there all summer.
By the middle and late 1940s our work in surgery seemed to be going well, and people in other centers were interested in it. I had been elected to some surgical societies and national organizations. I was pushing along with our projects and did not worry too much about exactly where it would all lead. My practice was growing and I enjoyed the whole bit immensely: Laurie, the family, research, practice, teaching at the hospital and the medical school.
In the summer of 1947, before we built our house in Marion, we rented a small cottage in Sippewisset, across Buzzards Bay, north of a small summer colony called Quisset. One August day (the 16th to be exact), we turned on the radio for the news, as we did every morning. To our surprise, we learned that Elliott Cutler had died.
Cutler, as I have said, had been one of the most important teachers of our class at medical school. Because my internship was at the MGH, I saw him but rarely after the war, since he presided over surgery at the Brigham. I admired Cutler and the surgical tradition at the Brigham and visited that hospital occasionally, even though not many residents at the time did this sort of visiting to learn what was going on at nearby hospitals. Many friends of mine were in residency training there. When we heard of Cutler’s death, Laurie and I had no idea at all that I might be asked to become his successor. Somehow the myth has been started that I was pointing for this job ever since childhood. Nothing could be further from the truth. Originally, I had planned to return to practice in Chi-
cago. Now I was perfectly satisfied with the wonderful opportunities given me at Harvard and the MGH.
Fred Ross, our friend and classmate, was Cutler’s chief resident at that time and helped care for him through his final illness. Cutler was a young man, still under 60, when he died of metastatic cancer of the prostate.
We heard little of search committees or other rumors until 7 months later, when, in March 1948, Dr. Churchill called me into his office at the MGH to tell me that I was on the list of candidates for appointment as the Moseley Professor and Elliott Cutler’s successor as Chief of Surgery at the Brigham. He asked me what I would think about such a thing. I told him I hadn’t thought much about it at all, and that I was very happy where I was, working in his department.
Churchill then asked me if I would like to stay on at the MGH and take charge of all the surgical research there, a sort of administrative promotion. That he should bring up such a counteroffer should have given me a hint that matters had already progressed pretty far. I told him that I appreciated this handsome and generous offer. Fortunately, I was tactful enough not to mention that I couldn’t think of anything worse, since I had trouble enough managing my own research, getting the money for it, and keeping all those granting agencies happy. I had no desire to start worrying about a lot of other people’s research, controversy over research space, and raising even more money.
By 1948 our four children were all in Park School, next door to our home. Our friends included doctors at all the Harvard hospitals, about our age, also with children, many of them living nearby in Brookline. From college and other associations we enjoyed friends who were in business or the other professions, especially law and teaching.
I was not anxious to change jobs, and we certainly did not want to move. I began to weigh the alternatives. If something came up that led me to be appointed to the Peter Bent Brigham Hospital, we certainly were well situated. The Brigham was only 2 miles from our house. By this time my lab at the MGH was well financed and several research grants had come through, so I no longer had to rely solely on the generosity of Oliver Cope and Edward Churchill. My private practice was coming
along pretty well, aided a good deal by my interests in duodenal ulcer and burns.
The MGH was large and strong at that time, while the Brigham was small and much weakened by the war and an aging senior staff. It had only 250 beds, compared with the 850 beds at the MGH. And the surgical department was taking some hard hits. Not only had Elliott Cutler died, but other prominent surgeons there, notably David Cheever and John Homans, were close to or at retirement age. Nobody was doing cardiac or thoracic surgery, and there was no one in charge of several of the other surgical specialties (gynecology, ophthalmology) at the Brigham. Some specialties (neurosurgery, orthopedics) were shared with nearby hospitals. Bob Zollinger had left to take over the service at Ohio State.
On the other hand, the Brigham could hold its head up pretty well. While much smaller than the MGH, it had been responsible for many advances, ranging from the introduction (under Harvey Cushing) of an entirely new field, neurological surgery, to the publication of a new, richly illustrated how-to book, the Atlas of General Surgical Operations by Cutler and Zollinger. This bestseller was used extensively (surreptitiously even by the residents at the MGH) and avidly read by other surgical residents throughout the world. The Brigham was a haven of learning for students and residents. And in 1948 it had a young, brilliant, newly appointed chief of the Department of Medicine, George W. Thorn. The possibility of working as Thorn’s opposite number was very attractive.
Despite some reservations, I was impressed by the opportunities the position offered and was flattered to be—as Dr. Churchill told me— on the short list. I realized that now I really had to get off my chair and start thinking about this proposition more seriously. I went for a visit to the Brigham, taken there by William Quinby, the head urologist, whose assistant, Hartwell Harrison, was a longtime friend. Quinby had been acting chief of surgery since Cutler’s death. We made rounds and saw the laboratories. The remarkable gap between those who did and did not go to the war was pointed up by the fact that Fred Ross, my classmate who had been away in the army for 5 years, was still the chief resident in
surgery while I was being offered the professorship. He took this with good grace. I knew there were plenty of people at the Brigham who were candidates for the job. They also greeted me warmly. I told Dr. Churchill I would accept the job if it were offered.
In May I was told that I had been selected for nomination as Moseley Professor at Harvard and Surgeon-in-Chief at the Brigham. Dean Burwell took me to visit the President of Harvard University, James Bryant Conant. He had been our university president during my last 2 years at college and was a member of the same undergraduate club, so I knew him slightly. He asked if I would accept the offer and take on the job, offering me a ridiculously low salary. After a little bit of negotiation, I accepted the post.
The hospital board needed to approve this new joint appointment of university and hospital. I met with the Board of Trustees of the Brigham Hospital, the most vocal member of which was Robert Cutler, the younger brother of Elliott Cutler. Bobby Cutler was to become the President of the Board, later Chairman of the Board, and finally Honorary Chairman. He and I became well acquainted. I operated on him and took care of him when he was sick. A close friend of President Dwight Eisenhower, he migrated to Washington a few years later where he served in the Eisenhower White House as the first director of the National Security Council. He was also an author, a humorist, a blythe spirit, and by far the best raconteur of off-color stories that I have ever heard. The women of the ladies’ board blushed and were suitably shocked but tried their best to remember the stories. The Board seemed enthusiastic about my decision to accept the job.
In June, Laurie and I went to Marion to take a vacation before the new job began. For the first time we moved into the small portable house that we had bought, to which we had added a living room and a dormitory for children. On July 1 I would take on new responsibilities. My 35th birthday was still a couple of months away.