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Q: Do you know anything more about the nature of the work they were carrying out on pernicious anemia?
Ross: They were trying to evaluate compounds that I believe were given orally to see if they could induce a remission in pernicious anemia. Again, I think this work was prompted by the work of George Whipple, who showed that in hemorrhagic anemia the response of a dog to therapy varied with the substance which was given. He had evidence that it was not only the iron contained in the substance that was given, but that there was probably something else in some substance which accelerated the regeneration of blood even in hemorrhagic anemia, over and above the influence of iron. For example, one of the interesting things that he found was that dried apricots given to his dogs led to a more rapid regeneration of blood than could be accounted for just by the iron contained in the apricots. So far as I know, nobody's ever followed up on that to try to explain that, nor am I sure it's ever been corroborated. But one of the most effective agents in his dogs was liver. Of course, liver had a very high content of iron, but he also thought there was something additional to this which stimulated the formation of blood.
Interestingly, historically pernicious anemia was greatly benefited in the foothills of the Alps by giving what was called liver soup. People who had anemia all got liver soup and it helped some because of the iron, but others apparently were cured of their disease and these probably were people who had pernicious anemia. How much Minot and Murphy knew about the liver soup story in the Alps, I don't know. Ask Bill Castle about that when you talk to him. I've always been curious whether they knew about that when they were doing their studies on liver extract. Certainly the ability to determine within a week whether or not an agent was really effective was of tremendous importance because then you didn't have to give the patient the stuff for a month to be certain whether it was going to have any effect.
Q: Did Murphy and Minot work in the same departments?
Ross: They were in the same department of medicine at the Peter Bent Brigham Hospital initially. What their relative rank was, I don't know. I would imagine that Minot certainly was a professor. Murphy was a professor when I knew him. What he was at the time he was working with George Minot, I don't know.
Q: Do you know anything about the interdisciplinary approach that was taken, for example, the work that was done with Edwin Cohn in trying to identify the factor within liver?
Ross: Edwin Cohn was a very colorful gentleman. I had some contact with him. I was not aware of the fact that he was really working with Minot and Murphy, although he may well have been. When I was with him, he was interested in protein fractionation. It was in that connection that I was trying to do some studies in his department.
Q: Did you have contact with him as a medical student?
Ross: Not as a medical student. This was afterwards when I was an assistant professor, at which time I was trying to crystallize hemoglobin. He was a protein chemist and he welcomed me into his department to try to crystallize hemoglobin. This necessitated working in terribly frigid, cold rooms with warm clothing and at one point I thought actually I had gotten crystallized radioactive iron labeled hemoglobin, but I think the material was merely so cold that it was frozen. So I never succeeded in really crystallizing radio iron labeled hemoglobin. But the president of Harvard College, James Bryant Connant--when he was professor of chemistry he did crystallize hemoglobin and did tremendously important studies on hemoglobin. But I never had any contact with him when I was in medical school.
Q: In your discussions with William Murphy on the state of hematology, did he discuss it in terms of developing a budding discipline, or as an interdisciplinary approach?
Ross: I got the impression that he thought it was a special discipline all of its own. I believe that the work that Minot and Murphy did really was investigative clinical hematology. They did not, the best that I know of, work on the concentration of liver to develop of what was known as injectable liver extract. But their work certainly led to that. I think Dr. Murphy would considered himself really as a hematologist, and I believe that Dr. Minot also considered himself as such, although they were internists and very
good internists!
Again, you ask Bill Castle because Bill Castle, as you know, did absolutely tremendous investigative studies isolating the so-called intrinsic and extrinsic factors. He did this with considerable self discomfiture, as he will tell you, by ingesting raw meat and then pumping it out with a stomach tube and giving the product to pernicious anemia patients. It's absolutely tremendous research!! Bill Castle certainly should have been given the Nobel prize. Why it was never awarded, I don't know. I suppose it's the fact that Minot and Murphy and Whipple had received the award in this area. I suppose that was an inhibition to awarding it to another man in the same field, but Bill Castle's work really was fundamental, actually clinical investigation of the highest possible caliber. Minot and Murphy employed an empirical approach to solve a problem. It worked! Most of medicine, still is empirical, although it's not as empirical as it used to be. It was giving a patient a substance and finding out what happened and being astute enough to tell whether it worked or didn't work. But Castle' work really was a planned and expertly executed elegant investigation.
Q: Were there any departments of hematology at this time? Is there anybody that called themselves a hematologist?
Ross: There were no departments of hematology. Hematology was part of the department of medicine. There were emphases on the study of hematologic disease, but this was part of the department of medicine. However, Dr. Minot used to give us a series of lectures at the Thorndyke Memorial Laboratory at the Boston City Hospital, usually late in the afternoon. It was a voluntary course in which he discussed various aspects of hematology. This course was pretty much unique! I don't recollect that there were similar courses in endocrinology or nephrology or anything else. So I think the emphasis was really on a developing field, which became a coherent, recognized specialty. There were no departments in hematology. I think still, as far as I know, hematology is a division of internal medicine in most cases. That's of interest because there was great opposition to the establishment of a separate society of hematology by the people who came from Thorndyke Memorial, primarily George Minot and Bill Castle. They thought it was an error to try to segregate this specialty from the general field of medicine.
Q: Dr. Tullis apparently also opposed it.
Ross: Yes, I think he did. They were not enthusiastic about this. On the other hand, there was another fine gentleman in Boston named William Dameshek. Unfortunately he's now dead. He had a traumatic end. However, Bill Dameshek was a sort of a flamboyant guy and he thought hematology ought to be a separate activity, and he worked to accomplish this. As a consequence of his interests and also the interests of Castle and several other people, there was established what was called the Blood Club. It used to meet in Atlantic City in conjunction with the Society of Clinical Investigation and the Association of American Physicians.
Q: Perhaps we could talk about that a little later on just to try to keep chronological order here.
Ross: Okay.
Q: Dr. Ross, I was wondering if you could add any more about the course work and experience you had as a Harvard medical student?
Ross: It was interesting that during the first two years of medical school the lectures were complemented by the laboratory work to a very large degree. For example, in physiology, we were stimulated to have ideas about what was going on in the body. I remember we used to make these smoked Kymograph drums to record physiological events and we'd burn our fingers and get soot all over us, which was sort of annoying, but it was the encouragement that you had an idea rather than just a recording of the contraction of nictitating membrane. If there was something you could do extra, this was encouraged and it also was stimulating, and ultimately led me to study and to write and publish a paper in the American Journal of Physiology about the influence of certain drugs on the nictitating membrane of the cat when I was a tutorial student in my senior year. Those interests and those approaches really began as a freshman medical student in the laboratory course in physiology.
Q: Your laboratory course itself was taught by Cannon?
Ross: It was under the jurisdiction of Professor Cannon and there were other distinguished people who were in the laboratory, but he was around all the time. And he'd visit the laboratory when the boys were burning their fingers smoking the Kymograph drums etc. and lending encouragement and telling them he used to that himself, which made it a little bit more tolerable.
There were other distinguished people. There was a man named William Forbes, Will Forbes, who was a distinguished physiologist who was there also to help. Rosenblueth I've already mentioned, participated in laboratory instruction. Then there was a man named Hallowell Davis, who was a very distinguished physiologist, and became chairman in Philadelphia who also was there. It was a very great stimulus for medical students to work under the direction of these people who we recognized as scientists and physicians of great distinction. This was very advantageous.
Also, in anatomy, in my second year, I became what was called a prosecutor. In essence, we did the dissection for the professor to use in the demonstrations to the class. That again was conducive to scientific concern. You could look for things that you wouldn't ordinarily see in the ordinary class dissection. There was every encouragement to proceed in that direction.
My chemistry course under Professor Otto Folin was pretty classical. We didn't do anything other than what had to be done and that was hard enough to do correctly, goodness knows.
The pathology that we studied was primarily histological pathology, although we saw some autopsies. They were pretty shocking to young medical students, particularly the way that they were presented. The first one we saw was done by a very distinguished lady pathologist who I think was out to shock the boys and she was pulling out the intestines and cutting them off and she broke them. The man had been dead in the refrigerator for a month and the intestinal contents sprayed all over the medical students and a couple of them got very ill. That was quite a lesson! Subsequently, I became a pathologist for a while. I never wanted to do anything like that. That was a good learning experience. However our instruction was just classical pathology at that point. It did stimulate a lot of interest in pathology and the morphological aspects of disease.
You asked something about the balance between lectures and laboratory work. I say that the major emphasis really was on the lecture aspects of our courses, although the laboratory work certainly was emphasized, too. But the amount of time that we dedicated really to laboratory work at that point was not the equivalent to what was dedicated to lecture courses. But in my first year in medical school, there was a tutorial group in physiology in which various things were discussed at an advanced level in an informal seminar type of procedure with Professor Cannon, Professor Bard. Professor Bard was a man who was chiefly responsible for the seminar activity. As I remember it, there were only eight or ten students involved in this. How they selected them I have no idea, but this certainly was very stimulating to advanced thought. I remember that one of the students subsequently became a quite distinguished molecular geneticist in the seminar. He was talking about the things that determine the function of organisms on a hormonal basis. I cannot remember his name, unfortunately. I think he left our class and went to some other school where he continued his work. Rut that type of discussion also stimulated people to think, to look forward, to look at other approaches and how we might do something more than just accept the rote learning which many schools at that time prescribed.
We had rote learning, too. We had a course in physical diagnosis. I remember this was taught by Professor Henry Jackson, Jr., who also was a very colorful character. It was a very interesting course. I remember I made outlines of what he had told us about physical symptoms, etc., etc., and put them on the back of my closet door and memorized them in the morning when I was getting ready to go to work. That also was a part of learning which I think was really quite valuable. Henry Jackson, Jr., his primary interest was in the white cell, not the red cell, and he and Professor of Pathology Henry Parker, Jr., became very distinguished for laying the foundations for the classification of the lymphomatous diseases by relating the clinical symptomatology to the anatomical findings. This classification was advanced by a gentleman named Gall, who worked at the Massachusetts General Hospital, but almost simultaneously Parker and Jackson developed this classification at the Boston City Hospital [an affiliate of Harvard].
Q: How do you spell Gall?
Ross: G-A-L-L. He subsequently became dean and Vice Chancellor at the University of Cincinnati’s School of Medicine. He was a pathologist who worked at the Massachusetts General and I think he had the first publication attempting to make a classification of lymphomatous diseases. Except for Hodgkins' disease, they have been considered pretty much all similar when they're really vastly different. Rut, again, this impact of knowing that people were advancing the field of knowledge and not just being satisfied to learn what had gone on in the past was a very beneficial stimulus to medical students.
Q: The tutorial system itself was apparently established first by Lawrence J. Henderson? Did you have any dealings with--
Ross: Lawrence J. Henderson is extremely distinguished. He, when I was there, was working primarily at Harvard College, across the river at Cambridge. He gave tremendously elegant lectures. I heard just one of them which was wonderful. Also there was a gentleman named Alfred Whitehead who gave his final lecture at Harvard, when I was a student, I went to hear that! That also was tremendously stimulating. But I confess I couldn't really understand some of the things he was talking about. He was far too advanced intellectually and philosophically for me to completely grasp what it was he was talking about.
But the tutorial system existed at Harvard Medical School and I was privileged to participate in this as a freshman medical student and then again as a fourth year medical student, I opted to take four months as a tutorial student in the physiology department. I think there were at least two others in my class that also did this. That was tremendously stimulating to thought and to trying to advance knowledge by learning new things. That had existed before I went to Harvard, for how long I don't know, and whether Professor Henderson had a hand in establishing that or not, I do not know. It was emphasized primarily by the physiologists, although the biochemists also had a similar program, and I don't know whether microbiology and pathology had that or not. I wouldn't be surprised, but I cannot remember that.
Q: Apparently David Edsall, who's headed Harvard Medical School had wanted to establish a tutorial in biochemistry.
Ross: Dr. Edsall was the dean of the medical school when I was there. He had two sons, Geoffrey and John. They both became extremely distinguished physicians. One in the field of immunology and the other in physical chemistry. They both were splendid gentlemen. I had the very unfortunate experience of providing medical care to former Dean Edsall at the time he died. He had a neoplastic disease and developed torula meningitis for which there was no curative agent at that time. He expired. It was a very, very sad experience having known him as a dean and then seeing him pass away. There wasn't anything that could be done except take care of him. Nothing seemed to help him much.
Q: Were you aware of the various attempts of reforming the different disciplines in the medical school at that time under Dean Edsall?
Ross: Not really. Medical education undergoes an attempt at revolution at least once every ten years and usually it ends up about the same as it was before with a different name. No, I did not know about Edsall's attempts to modify this except that the whole tutorial system was extremely valuable and if he initiated that, why, God bless him some more!! I didn't know that. The tutorial system was very fruitful, and other people did tutorials in other areas. I was fortunate, I believe, in doing mine in physiology which eventuated in two publications as a medical student, which is not too bad. They both were based on experimental approaches rather than a review of literature, etc., etc. That was really very stimulating and every encouragement was given me to do that.
Q: Is there a reason why you chose physiology as opposed to perhaps biochemistry or some other field?
Ross: I confess that dealing with the organism as a whole and the Various things that it was doing were more attractive to me than dealing with test tubes, flasks, and bottles. I suppose that was probably the reason. Again, I would say that Professor Folin was a categorist whereas Professor Cannon's department was more dynamic and interested in the kinetics of life. They were just completely different. Professor Cannon's approach appealed to me more than did Professor Folin's.
Q: There was apparently some friction between Folin and Cannon over the question of establishing these different disciplines. Did you ever pick up on that?
Ross: That I didn't know about. Thank God, I didn't. There was enough dissension in the world without thinking about things that your respected professors were fighting about. Let them fight but don't tell the medical students about it. They never told us about it. I'm glad they didn't.
Q: This goes back a number of years, before you'd been there also. It dealt with the question, once again, if there's to be a program in biochemistry coming out of physiology or clinical biochemistry, who should have control over it.
Ross: Really? I didn't know that. Did Cannon want to control it?
Q: Cannon was friends with L.J. Henderson, who had ideas for developing it as a physical chemistry.
Ross: I see. I didn't know that.
Q: Folin was more, as you're saying, into the categorical approach.
Ross: That's very interesting. That sort of bears out what I was thinking but I hadn't known the facts.
Q: Is there anything more you'd like to add on the course work that you've gone through at this point?
Ross: I would say that we had magnificent texts. For physical diagnosis, there was a text called Norris and Landis, which has never been equaled. That would describe and illustrate in diagrams the physical findings that one would find and document it with cross sections of the body from the patient who had actually had those diseases. Again, this was structural and formal but to me it made realistic what it meant when you detected dullness in a certain area of the chest you could see a section of the lung that showed where the dullness was and what cause it and what it looked like. That was just wonderful. Gray's Anatomy was complemented by a handbook of anatomy by Professor Robert Montraville Green, who was our primary lecturer in anatomy. It had beautiful illustrations of anatomical structures and that was extremely valuable and complemented the dissections we were doing. The physiology text was pretty standard, by the Englishman Starling. It was a good text but nothing particularly striking. In pathology, we had a wonderful textbook written by a Canadian named Phillip Boyd. He had insomnia and he wrote his textbooks in the middle of the night when he couldn't sleep. He was an exquisite writer who had a style that attracted the attention of students. All the texts that we had were really valuable and I'm very appreciative of them!
Q: In 1936, you became Student House Officer at Huntington Memorial Hospital. I was wondering if you could describe--
Ross: No, I became Student House Officer at the Huntington Memorial Hospital in my junior year of medical school. I graduated from medical school in the class of 1936. So in 1934-35 I was the Student House Officer in the Harvard Cancer Commission’s Hospital called the Huntington Memorial. Incidentally, it was endowed and named for the same Huntington who established the museum, library and hospital over in Pasadena, California. He contributed the money that made the hospital and laboratory possible.
The house officership at the Huntington Hospital at Harvard was a tremendous experience and it really changed my life remarkably, because up to that point in my education I really had been, I would say, a bookish person who learned from his lectures, text books, and laboratory instruction, but as a Student House Officer at the Huntington hospital, another third medical student and I were the only medical people in residence there at any time. There were about twenty to thirty beds. All the patients had cancer and the other student and I were "holding the fort" with the nurses. I remember I started work there on July the first, 1934, and on July fourth one of the patients who had had a radical electrocautery dissection of the tongue and cheek for cancer of the mouth "sprung a leak" at 2:00 a.m. He just bled like nothing I have seen before or afterwards. All over the place. All over me, the nurses, the floor, the roof and everything. I couldn't stop it. So I called a gentleman named Professor Charles Lund, who'd done the operation. He came in and ligated the carotid artery. I had never known that you could do that. But that is a sample of the type of serious illness that was hospitalized in the Huntingdon. The staffs of the hospital were all professors of surgery or medicine at Harvard and they encouraged the student house officers to assist at the operations. You're pretty young as a junior medical student to start assisting at a radical mastectomy, radical neck dissections, hysterectomies etc., etc. As a consequence of this "golden opportunity" to "practical" management of patients I didn't go to any more lectures. I stayed in the hospital and worked there rather than doing what I probably should have been doing and going to the lectures, but I didn't. I began dealing with actual, clinical medicine at a very practical level while I was still medical student, presumably still learning things from books and lectures. However, the instruction and supervision at the Huntington was superb!
To some extent, this experience may have been deleterious since I spent so much time at the Huntington rather than doing some of the things that medical students were supposed to do. I think the experience at the Huntington changed the course of my life from becoming what you might call a fundamental, scientific investigator to becoming a more or less clinical doctor trying to apply scientific methods to clinical medicine.
As part of my job at the Huntingdon, I was responsible for calibrating all the radon and the radium that was used for cancer therapy at Harvard Medical School. I was provided with great big, thick, heavy lead gloves and aprons for protection as I handled the radioactive material to calibrate it in an electrometer. But in the morning when it was early and I had something else to do, sometimes I didn't use the lead gloves. I got enough radiation exposure to the dorsum of my hands to cause skin carcinomas which have to be resected from time to time. I've got one right there now that's got to be taken off. That was also the beginning of the radiation exposure that lead to the development of radiation cataracts. I was exposed to much additional ionizing radiation over the subsequent years, but that's when and where the exposure began, and I think that's where the cancers of the skin of my hands began.
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