This is Oral History Interview #14. Dr. John A. Pierce, Professor of the Department of Medicine at the Washington University School of Medicine, talks about the life and scientific work of Dr. Alfred Goldman [Class of 1920].
We are talking today with Dr. Pierce about the life and times of Dr. Goldman. Dr. Pierce.
Dr. Goldman was proud of the fact that five boys in his family were encouraged greatly by their father to achieve in scholarly pursuits. Four of the boys actually won scholarships to the Washington University. Dr. Goldman was one of the ones who did attend Washington University on a scholarship. This attitude was reflected in his own accomplishments and career. He was elected to Phi Beta Kappa and AOA [Alpha Omega Alpha] as a result of his outstanding scholarship. So I think it’s not unusual to have expected, even from his early beginnings, that he might have gone farther than most people in his profession, and that he was indeed an exceptional person. Perhaps it was one aspect of this that led him to get interested in investigative work as a medical student, which was really quite unusual for that particular time, but which was done under the warm, but firm, hand of Professor Joe [Joseph] Erlanger, who was then chairman of the Department of Physiology.
That’s interesting. I didn’t realize there was a connection there. We have Dr. Erlanger’s papers in the Archives; we can see how they mesh together.
Yes. Dr. Goldman often spoke about Dr. Erlanger in very warm and friendly places. Actually, it was with two classmates of his, Stuart Mudd and Sam [Samuel B.] Grant [ed. note: Dr. Mudd was a 1920 graduate of the Harvard Medical School], that he began to work on the cold experiments. It was in, as they called Dr. Erlanger affectionately, “Uncle Joe’s” ice box that the fellows took off their clothes and exposed themselves to temperatures around four degrees centigrade or so to complete their investigation.
The topic that was then of such great interest was, “What promotes and produces upper respiratory tract infections and what influence does cold exposure have on these things?” Actually, this is a topic of some current interest today even yet. At those times, before there was any capability in the virus field at all, attention was naturally focused on the bacteria. So, what Drs. Mudd and Goldman and Grant did was to produce a series of papers that have been quoted for many years in literature – was that they did expose themselves to cold and they took cultures of their throats before, after, and during the exposure. They did document the fact that each one of them had somewhat of a tendency to recover organisms of a specific type following the cold exposure. The most commonly-cited finding of theirs was the measurements they did on the temperature in the throat with and following cold exposure and their demonstration that this did, in fact, produce an intense nasal constriction in the nasal and upper nasopharyngeal mucosa. It was their thought that this permitted the multiplication of the bacteria and a relatively more easy invasion of the respiratory tract with the organism. That was the principal subject of the first several papers that Dr. Goldman actually published.
It was an outgrowth of this that really led to Dr. Goldman’s own important discovery and description of the physiology of hyperventilation. What actually happened was that Dr. Grant and Dr. Goldman noticed, as they were measuring a number of things through their cold exposure experiment, actually noted that the urine pattern [yielded] an alkaline pH every time, following cold exposure. They reasoned appropriately that this was due to hyperventilation. One [worry] expressed was that they would find themselves overbreathing without really trying or intending to. This captured their attention because there were some previous experiments or descriptions of altered physiology in hyperventilation, but there was no clear-cut recognition that one could overbreathe to the point of producing tetany. It was this particular finding that Goldman and Grant worked out in very careful detail – meticulous detail. I think that there’s evidence of Dr. Erlanger’s hand in the thing, too, because it’s carefully documented with respect to the earlier literature and, in effect, it’s top-quality research for that time. It’s meticulously done and undoubtedly played a big part in the professional development of some individual experiments.
Dr. Goldman was even cited in a book by the eminent Professor [John Scott] Haldane, who has been called the father of respiratory physiology, because on several occasions during the course of hyperventilation experiments, Dr. Goldman did produce in himself generalized tetany. The way Dr. Haldane expressed it was [that] “Poor Goldman was so vigorous in his investigations that he knocked himself out with overbreathing.” Actually, once they realized they wanted to study hyperventilation, what was done was, they set up a metronome and actually intentionally overbreathed by count as you would to play a drum to play a piano.
So this was done very scientifically?
Oh, yes. They sustained this for a very lengthy period. The end result, sometimes after fifteen minutes or after twenty minutes, was, on a few occasions, tetany. Most of the times they didn’t reach the tetany point, but they did measure serial changes in pH and they did demonstrate for the first time that it was the marked reduction in carbon dioxide from the lungs that led to the marked alkalosis. They inferred in their discussion that it was likely that ionized calcium had a role in this thing. Of course this has been the subsequent story that as it became possible to measure ionized calcium, the alkalosis decreases the ionized calcium and tetany is produced.
They did some study on mass hyperventilation, too, didn’t they? I thought I noticed in Dr. Goldman’s description of his work that it hadn’t been recognized that such a thing could exist up to that point.
Yes. I don’t remember an experiment that went with that, but I think that it was common experience in the years following their description as medical school experiments were designed for people in classes in physiology, which required sustained hyperventilation, it was common experience to run on to one or two medical students per class that had a kind of a “runaway” hyperventilation that couldn’t be stopped. After the class was over they couldn’t just simply stop overbreathing and go back to the normal state. Of course, this is the kind of overventilation that was really Dr. Goldman’s largest scientific contribution. This is the hysterical hyperventilation that he recognized in the emergency room. He probably would not have been so quick to recognize it, if he hadn’t personally participated and done the self-experiments that made him intimately familiar with all the details of hyperventilation. I believe it is accurate that his was the first clinical description of what is now called the hyperventilation syndrome, which is more or less hysterical overbreathing.
He also talks in his papers the hyperventilation following muscular exercise. Of course, there’s always been intense interest among physiologists, in fact still today, trying to sort out the various contributory factors to the hyperventilation of exercise. This is a subject that was of interest to Dr. Goldman, too. I think that he recognized the kind of treatment that was indicated, namely, reversing the process by rebreathing. No one has really improved on this sort of an immediate solution to the clinical problem, so it’s still rebreathing that’s done today. I think that Dr. Goldman also recognized when the problem was at an end, so I think he reasoned his way through this, and at later periods of time he didn’t work additionally [on it]. He dropped it when the time was right to drop it.
That’s very true. He went on to other things, other interests.
One of the [things] he went on to that was of much interest to me (anyway) was the early cytology study. He did present one of the earliest papers – not the first, but one of the earliest papers – to detect the presence of malignant cells in pleural fluid. He wrote two papers at a widely-spaced interval, maybe ten or fifteen years apart, illustrating that he had sustained an interest in this connection. One was in the cytology of sputum at a later time, when that form of cancer diagnosis seemed reasonable as the cells were better-recognized and the other one with malignant cells in the pleural fluid.
I think that he has to be given credit for, certainly, stimulating local interest in the cytologic diagnosis of cancer because he published his earliest paper, I think, around 1921 on that particular subject. His work was always close to the patient, from the early days on. After he finished the experiments that he did for which he received a master’s degree in physiology, practically all his investigations stemmed from problems with which he was confronted through his patients.
After he earned his master’s degree he had a full patient load of clinical work and he was doing this also, in addition to his full-time responsibilities in medical practice.
That’s right. I heard him talk a number of times about his interest in lung disease and the fact that he was very interested in tuberculosis. Like myself, with this same interest, he was one of the relatively few people at that time that did not have tuberculosis. And he had not had tuberculosis himself. So many of the early chest physicians had developed an interest in chest diseases and lung diseases by a personal experience with tuberculosis. Dr. Goldman had not had tuberculosis himself. In fact, I heard him say a number of times that at the early meetings of the College of Chest Physicians and the American Thoracic Society he was one of the very few people around who didn’t have some sort of personal clinical experience with tuberculosis. I don’t know how he happened to take such a sustained interest in lung diseases. Perhaps it was the contact with the hyperventilation, but I believe [that] of the three classmates that worked on the problem in the cold, he was the only one that stayed professionally in academic thoracic medicine throughout his professional life.
He took a great interest in – and I think it’s purely and simply related to his strong attachment to his patients and his genuine and deep interest in the problems that they had – he took a great interest in industrial diseases and occupational exposures and served as a consultant for a number of companies locally. And [he] was always intent on making as accurate and impartial a judgment as he could about what the situations really were.
He seems to have had a real skill in delineating new diseases, recognizing a set of symptoms as being different from other symptoms.
Yes. I think this is attributable to his extremely careful scholarship and his tenacity to stay after a problem until he really had wrestled it down to his own satisfaction. He was fairly demanding of himself and so, when he saw something that was different he stayed with it until he saw it all the way through to the end.
That would take a great deal of work, not only recognizing it but studying it.
To insure that you know what you say is where you are – this is the hard part.
That’s true, because he was busy with his patients at the same time.
It’s very easy to let time go by and to not put these things in the literature that are important. I think this is much to his credit, and I think it really certifies and documents his academic capacity as very great indeed.
Was he ever tempted to go into full-time academic work in the fields he was interested in?
I think that he had taken on the clinical load in his private practice at such an early time that he never seriously considered dropping that at a later time. Although, I really never did talk to him about that transition. He was, without question, deeply involved in the medical group, deeply committed to the medical school and had such a great attachment to his students at all levels that I’ve had many of them in the last several years approach me at the meetings around the country and inquire about Dr. Goldman and express their appreciation and gratitude for his efforts.
How much contact would he have with students? How did he meet them?
He participated in the student teaching program in the Department of Medicine over an extremely long period of time. In fact, [Dr. Carl V.] Moore told me one time that Dr. Goldman was one of his teacher when he was medical school. His period of time on the faculty was really fifty years. Since 1967, when I took over the directorship of the pulmonary disease division, Dr. Goldman had attended conferences two or three times a week almost without fail, for the whole time until after his illness forced him into retirement in 1973. So his exposure was really quite sustained and he was a frequent discusser at conferences. Whenever questions arose about industrial diseases or things that he had had experience with he always spoke up. As a consultant in the hospital, he was often called on to evaluate [in] clinical situations. He always, in that situation, gave his information to the resident and medical students, so he [maintained] individual contact through that mechanism all through these last years, and I’m sure for the fifty years before.
His heart really was in the medical school, I think, from the time he entered private practice on. He never ceased to be a very strong participant in our clinical teaching program. He had a number of topics in fact, x-rays and things that he gave me. I know personally he gave other [individuals] some of the other things; that he was anxious to see some of the young people get interested in and work on. He didn’t figure [that] all the problems were solved; he knew where the problems still were and he was hoping that he could interest somebody in doing some work on them.
So from the time he graduated from medical school he maintained his close connection with the school and his interest in the students, which is certainly shown by his weekly participation.
That’s right. He has a very strong following from a large number of the graduates of our school.
It’s intriguing, too, that Carl V. Moore was his student and he knew him from that point on. Would you like to talk about his clinical work with patients?
I would; I’d like to say this – and it’s very typical and characteristic of the genuine nature of Dr. Goldman’s interest in people. He approached all the patients that I saw him with – and that I saw in contact [with] him – with the same sort of attitude of respect and almost affection, and with a sincere interest in their problems and taking their problems as his problems. It really didn’t matter what the patient’s background was, who he was or what sex or color [the patient] was, Dr. Goldman had the same deep, genuine interest. His clinical judgment was uncanny and something of a conversation point around the school. Because no matter how obscure or difficult the patient’s problem might be, it was generally conceded that you couldn’t trick or fool Dr. Al Goldman. In my years with him, this has certainly been true.
He did have a deep interest in tuberculosis and a lot of patients with tuberculosis. As he retired from practice, he took great pains and care to refer each patient to a colleague that he felt might be sort of characteristically suited for that patient’s needs. Of course, I got several of his patients and it almost continues today; each time I see one of those patients they have something additional to tell me or say about Dr. Goldman. They were all very concerned with his health before he passed away and all inquiring about this. There was an almost unbelievable aura of love and affection that his patients had for him, not only as their physician but as a man. They respected him. I think this has to emanate from the heart; one can’t sort of fake this. Either you have it or you don’t.
We already talked about his relationship with Carl V. Moore. Would you like to talk about some of his other colleagues?
Well, I had a sort of chance contact with some of [Dr. Goldman’s] professional colleagues and so forth. I might mention just two little stories that could be of interest. After Dr. Goldman was ill and knew that he had metastatic chondrosarcoma in his lung, the question sort of naturally arose whether cancer chemotherapy might be worthwhile. The local experts are as good as any in the country and they reaffirmed this in the course of the subsequent events, but Dr. Goldman asked whether I would look into this and see what I could find out about it – probably more as an interested friend than as a physician. I went to the library and searched the literature and tried to see what I could find out about it and came up with a list of five or six experts around the country that I thought were eminent in the cancer chemotherapy field. I then consulted with two of the local experts that Dr. Goldman had been in touch with and decided on sending letters off to two of these people at other major medical centers.
It turned out that one of these went to the M. D. Anderson Foundation in Houston, which is now part of the University of Texas. The director immediately referred it to his division chief, who worked in this particular area of connective tissue tumors, [and] who, lo and behold, it turned out as I talked to him on the phone, was a former student of Dr. Goldman. He was very involved with Dr. Goldman, was saddened to hear about his illness and [offered] to see Dr. Goldman at any time that Dr. Goldman would like to come down there. As it worked out, they made the decision – and principally it was Dr. Goldman’s decision – not to try that sort of therapy because the toxic effects seem to be overwhelming and the beneficial effects very questionable. So, Dr. Goldman didn’t proceed down to see his former student and take the therapy. But I thought what a small world it was to have come all the way around full circle and have a referral to one of his own former students, who, in fact, is quite an expert in this therapeutic field.
The other story that I think of right now is that I was visiting another major medical center last week and had occasion to discuss with one of the other site visitors – who is now at a state university in the East – [to discuss] Washington University. As it turned this young man was a graduate of our school and a classmate of Dr. Goldman’s son. They were quite close friends during medical school. Dr. Robert Waldman, [the man] whom I was talking to, had some interesting (new to me) clinical stories to tell about Dr. Goldman [who] was his teacher in medical school – and he finished some ten to fifteen years ago.
This kind of thing continues to happen all along. My point of telling the story about Dr. Waldman is simply to illustrate that many hundreds of physicians around the country who have personal knowledge of and experience with Dr. Goldman as a teacher. He was indeed an expert and dedicated teacher.
When did you first come to know Dr. Goldman?
I first knew him in 1967 and I must say he was extremely helpful from the day I arrived in St. Louis. He was anxious to support the program in any way that he [could]. [You] really could call on him. He went far beyond the call of duty in his support. In fact, I might mention that Dr. Goldman’s family, on the occasion of his birthday [the] year before last, established a permanent book award so that the graduating senior who participates in the pulmonary disease teaching program as a senior student is awarded a rather handsome book allowance if he is chosen as the outstanding student that comes through the division [during] the year. It’s called the Alfred Goldman Book Award.
It’s a perpetual memorial. Do you have any additional comments you’d like to make about Dr. Goldman?
I think that Dr. Goldman was a totally dedicated man. He was intensely dedicated to his family. During the last months of his life I had a large number of discussions with him. He was proud of his parents and the family he was raised in and he did everything to promote the kind of atmosphere and environment that you would want for your children. He saw all three of his children graduate from college and two of them from professional school. He always had a lot of fun living, and always enjoyed a good story, and was an excellent storyteller. I remember on one occasion he mentioned to me that he’d just about been everywhere and he thought he’d just about done everything and he’d had a lot of fun. He didn’t really think that if he had his whole life to go through again he would change anything very drastically at all. He literally lived for his patients and his family.
After he passed away, I remember talking to Mrs. Goldman in some detail about his scientific work and papers that he’d published. It was her comment that he did all of this without any conversation or display at all; he just quietly went about his work and when it was time to print it he just printed it and he didn’t say anything to _____(?) it and he didn’t know very much about it. I think again that illustrates his mature direction of purpose and the way that he was able to channel his efforts in the appropriate channel at the appropriate time.
This oral history interview with Dr. Pierce was conducted on April 3, 1974.
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