| 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 |
Q: During this period, what were the sources of funds for both research, the clinical services, as well as traineeships?
Ross: There were no funds from the federal government at that time. The Thorndike, I think, supported its people with a private grant that had come with the establishment of the laboratory, and other grants from the pharmaceutical industry for the development of liver extract for the treatment of pernicious anemia. I think it was from Eli Lilly Company. The staff at the Thorndike Laboratory tested liver extract to insure its efficacy, and were provided some funding. Max Finland got support from the Lederle Laboratories and other agencies interested in the development of chemotherapeutic and antibiotic agents. Chester Keefer--I don't know where he got his support. It might have been that Dr. Minot paid his support from the funds of the Thorndike endowment. At the Evans Memorial, Dr. Keefer had funds to provide all the support for his staff. When the war came along the government became interested in funding research, and research grants became quite common. There was never any pressure to obtain grants brought by Chester Keefer, but most of us at the Evans felt it desirable to obtain a federal grant to support our research. My primary research support came from the National Science Research Development [NSRD] during World War II. After the war I received support from the NIH and the AEC. I don't know what's happened to the Evans' funds, I imagine they're still supporting research there in addition to establishing the laboratory at Boston University. The Robert Dawson Evans fortune also endowed the whole Evans Memorial wing of the Boston Museum of Fine Arts--the one that fronts on the muddy river.
Q: You had an eighteen and a half month internship at the Thorndike also?
Ross: My internship was served on the second Medical Service at the BCH, which was on of the two Harvard clinical services there. The Thorndike Laboratory was the Harvard research institute at the Boston City Hospital whose staff had surveillancy over the two clinical services. The visiting physicians on the clinical services were all Harvard professors some on the Thorndike staff and some on the Harvard clinical faculty. It was a wonderful system. On one day we would have a visiting physician who was a full-time academic at the Thorndike. The next day there'd be an excellent clinical professor from the community who'd make rounds on the same patients. This provided a wonderful opportunity to see the different ways in which these different kinds of physicians confronted the clinical problems that they were encountering. A very, very excellent system that I don't believe exists anymore.
Q: Did you carry out research at the time, while you were at the Thorndike?
Ross: I was in the second medical service. I was not a resident at the Thorndike. I was on the clinical service. No I did not. I had all I could do to provide medical care to the eighty patients on the service. Maybe I wasn't smart enough or vigorous enough to do any more than take care of the patients. That was a pretty full job.
Q: Seminars during that period also?
Ross: There were continuing seminars of all types at all times. We had excellent rounding physicians, there were clinical pathological conferences that we participated in. There were conferences on every subject that you could imagine, hemanologic conferences, infectious disease conferences, cardiovascular conferences, social service conferences. They kept life very full.
Q: You mentioned before during this period, that there was the introduction of sulphamid—
Ross: Yes. I was an intern on the second medical service when the drug "MB 67" [or something like that name] first was used. This was one of the first sulphanilamides used clinically and was obtained from England. The drug did absolutely magical things to people who had infections! We'd give them these little white pills and the disease would go away! I was working for Chester Reefer at the Evans when penicillin came in. During World War II there was a great limitation on the amounts of penicillin available and that was available was pre-empted by the military for the treatment of gonorrhea and syphilis. The military set up special clinics at the Mass. Memorial Hospital where Chester Keefer was the Chief just to treat people with syphilis! There were people in this country that believed that to do this was immoral. Here you were treating a disease--a social disease acquired by illegal "immoral" activity, and they believed it was too damn bad to use the medication to treat syphilis rather than to use it in taking care of some nice lady who had some other condition. At that time Dr. Keefer had six teletype machines installed at the Evans that were in continuous absolutely a thunderous communication from all the people seeking to get penicillin for other purposes. On one occasion some of the material was freed up by the military and used to treat a case of sub-acute bacterial endocarditis in an important patient. The disease was cured. It was absolutely amazing! It was the first time, as far as I know, that this disease had ever been cured! And the consequence of that--this got in the papers both medical publications and the lay press. The pressure to grow penicillin was even greater! There was a great stimulus to increase the production of penicillin and this was done. But Chester Keefer was responsible for a long time for allocating all the supplies of penicillin that became available in the United States. He did a very good job! He was a judicious gentleman and when a patient needed it as an absolute necessity he made the material available.
Q: Following you stay in Boston you made your way to Rochester to work with George Whipple.
Ross: I completed my internship on the Harvard Medical Service at the BCH, and I was still enamored with pathology. I knew that George Whipple had been one of the Nobel laureates in hematology, and in the meanwhile my mother had died of agranulocytic angina, a disease caused by the failure to form leukocytes and consequently the patient develops terrible and usually fatal infections. Incidentally, Dr. Jackson and Dr. Parker recognized that this disease was related to the use of a certain drug called pyramidon, a drug used to alleviate pain and suffering. This also was discovered at about the same time by a hematologist named Kracke, who was a professor at the University of Alabama. This was appropriately published in the medical literature but the doctor taking care of my mother in Covina, California didn't know about this. He spent all his time taking care of the sick. He gave my mother pyramidon for a broken leg every day for a month and wiped out her bone marrow and she died as a consequence. This was really quite hurtful and then again, made me want to go and continue a more intensive approach to the field of hematology. So I went to Rochester and worked for Dr. Whipple for a little over a year. While I was there I became enamored of the use of radioactive iron to study blood formation and worked there with a very fine biochemist Dr. Paul Hahn. We did lots of work in terms of the rates of hemoglobin formation in different circumstances and what factors would change the rate of hemoglobin production. While I was there I was also privileged to work with another biochemist Dr. Leon Miller. In this work we were interested in the toxic effects on the liver of toxins such as chloroform. It's of interest that if you starve a dog from the standpoint of protein nutrition and deplete his protein stores, a half an hour of chloroform anesthesia, would destroy the liver and he would die. We observed that if you fed the dog a pound of hamburger an hour before we gave him the anesthesia he survived. Then we showed that giving the dog methionine and sulphur containing amino acid in place of the hamburger the dog also survived the chloroform anesthetic. The dog didn't even get sick! This was a very fascinating field! One of my major jobs in this research was making up the protein free diets for the dogs, giving them anesthesia, administering the methionine and so forth. That was a very stimulating experience!
Dr. Whipple was on the board of trustees of the Rockefeller Foundation which funded the initial construction of the cyclotron at the University of California, Berkeley by E.0. Lawrence. He was a wise man who said, "Look, if you're going to make this instrument, how about making me some radioactive iron so that I can start an investigation of iron metabolism." So the first radioactive iron from the Berkeley cyclotron went to Dr. Whipple and Dr. Hahn, with whom I was studying the formation of hemoglobin. The radioactive iron was in such terribly short supply that we used to collect the feces of the dogs and recover the radioactive iron from the feces and use it again for experiments. I had a very menial task there. I didn't do the collection of feces, but took the collected feces and digested them chemically in a Kjeldah flask and then extracted the iron from the digestate with ether and alcohol. A terrible job!
Q: At this time were you aware of the work of Rudolph Schoenheimer and David Rittenberg at Columbia, using radio isotopes for labeling?
Ross: Yes, I was. They published a very fine book and one of them an expert--was it Schoenheimer or Rittenberg? I can't remember which who was that was interested in the porphyrins, a fascinating subject! They were among the first who were able effectively to use isotopic tracers to study the metabolism of these materials.
Q: Was also work being done in Baird Hastings labs at that time?
Ross: I don't know. They probably were using isotopic tracers but I wasn't aware of what they were doing. When I returned to Boston I was named a Welch fellow by the National Research Council. I held my Welch fellowship while I was an associate professor of medicine at Boston University School of Medicine as a research fellow in Baird Hastings department. I cannot remember whether or not isotopic tracer work was conducted in Dr. Hastings' department.
Q: Could you comment about George Whipple himself?
Ross: George Whipple was a wonderful old man. He was a sort of an elderly fellow when I was there. He wore half moon glasses so he would read through the glasses but did not need refraction in the upper part. He had trouble hearing, so these half moon glasses would sit on the end of his nose as he wandered around the laboratory. He was the Dean of the University of Rochester School of Medicine and he hated dirt! He had the corners of all the stairwells painted white so if there was any dirt in the corners he could see it. And then he'd make the janitors clean it up immediately! He walked around the hospital and the medical school--and if found any dirt he'd put in an emergency call to clean it up right then. He ran a very good department of pathology. His pathology activity, in terms of instruction, really was quite old fashioned. He used to have teaching sessions every week of collected anatomical specimens from autopsies that were of particular interest. He would stand up and demonstrate and talk about these. The bad aspect of this was that we did many autopsies at the County Tuberculosis Sanitarium. We were instructed to bring back slices of these T.B. lungs, kidneys, etc. I shudder to think of it, but students used to pick them up and squeeze them and look at them close to their faces and inhale the bugs!! Interestingly a very high percentage of the residents in pathology and also the faculty came down with tuberculosis. I'm sure it was acquired as a consequence of this exposure. I remember I did three autopsies at the T.B. Sanitarium one day and came back to the path department and had speckles of dried material all over my glasses. I scraped these specks off and did a tuberculosis stain. They were just loaded with tubercle bacilli!! I'd had tuberculosis as a child and conceivably that might have given me a little immunity to the disease, and I didn't catch it again, thank God! Dr. Whipple was a great fisherman. He used to take a month off every year and go up to Nova Scotia to fish for salmon. He also was an avid hunter. He'd go and shoot birds. Even up into his eighties he still could see well enough to hit a partridge on the wing. He was an experimentalist of profound astuteness. If you did an experiment in which one or two dogs that didn't come out the same way as the others, he'd always explain it by saying, "Well, some dogs can run farther and faster than other dogs." That was the explanation for the aberrancies that occurred in the experiments that he did. He made great contributions in terms of protein nutrition, the mechanisms of anemia, the regeneration of blood. He kept a special breed of dog that he used for his work. They were the ugliest looking mutts you ever saw! They were a cross between an English bull dog and something else, I don't know what. They had those pink rimmed eyelids, blue eyes, and white skin. Dr. Whipple had a whole animal house built to house these creatures. They were used very gently and humanely for the conduct of his experiments. Most of his experiments were related to rates of regeneration of protein and hemoglobin. He was a very stimulating and interesting man. He at one time was a professional baseball player. He debated whether he should become a continuing professional ball player or go to medical school, and of course he made the decision to go to medical school. He worked at the University of California Medical School in San Francisco at one time where he was the director of the Hooper Foundation, a well endowed research institution. As I recollect it, he became dean at [?] Medical School in San Francisco for a while and then was appointed dean to establish the new medical school at the University of Rochester, which was heavily subsidized by the Rockefeller Foundation. At one time during his career, he worked as a pathologist in the Canal Zone. He described certain tropical diseases and the consequences of these diseases. He was a very benign fellow, and used to entertain us at his home. He was a very great influence on those privileged to be associated with him!!
Q: In the conjuncture between Whipple's work in research and his role as Dean of the medical school, do you think he imparted a different path to development of biomedical sciences at Rochester as compared to what, maybe, was done at Harvard?
Ross: I think so. He selected all of the senior faculty and his faculty was uniquely concerned with fundamental experimental research at a laboratory level, not only in pathology but also in medicine, pediatrics, anatomy, physiology and chemistry. Dr. John R. Merlin, one of the professors working there probably had the explanation of diabetes and its relationship to insulin almost simultaneously with Banning and Best, but he hadn't published his results. This poor fellow was embittered the rest of his life because Banning and Best had beaten him out for recognition as the discoverers of insulin, when he'd actually had it first!
Dr. Whipple placed great emphasis on investigative endeavor and this lent a tremendous flavor to the whole institution. The University of Rochester medical school started with this emphasis, while Harvard started one hundred fifty years before basic research existed and when research was clinical observation and therapy. The impact of basic research came at a later date and was grafted on clinical research. Dr. Whipple started a school in which the emphasis was on fundamental research and clinical research followed.
Q: Whipple being a co-recipient of the Nobel Prize along with Minot and Murphy. Did they maintain contacts of any sort?
Ross: I don't really know. I don't think so. I don't think they had a very close relationship. I seldom heard them talk about each other. I just don't know about that.
Q: Did you decide more in favor of hematology while you were working under Whipple?
Ross: Yes. I would say that, although I had a very great interest in hematology as a consequence of my experience at Harvard. Some of the most exciting lecturers at Harvard were the people that talked about hematologic subjects. That gave me great interest and working in pathology stimulated and solidified this interest. Joining Dr. Whipple's group made it even more certain, and I decided that I would really like to be a hematologist, at that point and I continued in that specialty since. I would say that my idea of becoming a clinical hematologist was probably formulated when I was in Dr. Whipple's department. Then when I was appointed by Dr. Keefer I was head of the division of hematology. I expanded the clinical activities, and continued using radioactive tracers to study the kinetics of blood formation and destruction and used radioactive iron as a labeling tool to study the preservation of red blood cells during World War II. This was a fruitful endeavor. Using erythrocytes labeled with radioactive iron, I stored them under different circumstances and with different preservative solutions, and then transfused them into subjects to observe how long they survived in the recipients' circulating blood. This ultimately eventuated in the development of preservatives that were effective in maintaining erythrocyte viability for about three weeks. With slight modifications these preservatives are still used in blood banks all over the world. A few more items have been added to the solution and it now preserves satisfactory viability for four weeks. I'd rather transfuse fresher blood but stored blood is widely used at this time.
Q: We'll come back to that in a short while. Could you comment some about Paul Hahn?
Ross: Paul Hahn was really a wonderful gentleman! He came from a Rochester German family. His father had been responsible for developing the Crossman air rifle. I don't know if you knew anything about that or not. It was not an ordinary B.B. gun. It was an air rifle that propelled a pellet that was strong enough to kill a deer, and a man, and it was an analog of the rifles used by the Japanese in World War II. They were light. They were, in essence, almost noiseless. They were impelled by a charge of carbon dioxide gas in a tank or they could be pumped up by hand. His family had considerable financial resources and Paul had a large number of brothers and sisters. I think there were six or eight. Paul was interested in chemistry and after he got through college, he worked for Dr. Whipple. He wanted to go to medical school but Dr. Whipple told him it wasn't necessary, not necessary at all. He was a good biochemist and he should work in the field of biochemistry for George Whipple, which Paul Hahn did to his everlasting discomfiture, sadness, and sorrow, and ultimately to his death. He wanted to do clinical research on patients. Since he was not a physician, presumably he was not competent to do this, and he became a very unhappy man. So he went to Vanderbilt University where he pursued chemical studies using radioactive tracers. He had trouble there because he wanted to do experiments on humans, so he moved to Meharry Medical College where he carried out observations on humans. He never got in trouble for this. He was interested in trying to develop therapeutic applications of radioactive materials. He had various kinds of particular radioactive materials which he coated with gold which would stay where they were put in the lung. He had some effectiveness in treating people with carcinoma of the lung with this material. He was never really able to step out and become a clinical investigator. Although the work that he did was innovative and imaginative and potentially very fruitful, he could not use it clinically which is what he wanted to do. Consequently, he became a substance abuser for material known as whiskey and he drank large quantities of this material. He developed diabetes and ultimately expired as a consequence of alcoholism and diabetes which is heartbreaking! He had six children. He was such a bright and nice guy that it's too bad he had to do this and that he died as a consequence. He was very innovative, imaginative, a very good investigator, and a wonderful preceptor for me! I spent about a year and a half working with him. This again, was a great opportunity!!
Q: It seems that many of the personalities that we've discussed, even those that went in to do fundamental research actually began as M.D.s. You have Cannon, you have various other people that we talked about here. We have Whipple. Of course, Murphy, Minot. Was there a change that was going on at that time where people would leave medical practice to go into research, or did they seek a balance between these areas?
Ross: I don't think so. I think the individuals that you've mentioned and that I've mentioned became medical investigators as their role in academic medicine. I don't know, personally, of any people at that time who had been in practice, who abandoned practice to come back to do fundamental or even clinical research. Some of the professors that I had at Harvard were competent enough to write clinical papers analyzing four hundred cases of this or that or the other, which was a definite contribution, but this was distinctly a by-line to their practice. The people that I had contact with, primarily, had gone into investigative medicine as a continuum of their medical education. At that time, such occupation paid very poorly. At one time I as told by Soma Weiss that the most one could ever expect to make as a clinical investigator was about five thousand dollars a year. Of course, that was a long time ago. That might be worth about twenty five thousand in 1986 dollars, but some people get paid more than that and some don't, even to this day. These were people who were dedicated to trying to advance knowledge at the fundamental level and it was a fascinating opportunity because there were lots of things that hadn't been discovered then. If you were diligent you could find things and make contributions. Most of the people that I had contact with were clinicians. I mentioned Paul Hahn who was a Ph.D. biochemist. There was another gentleman at the Thorndike named Laskey Taylor. He was involved in the evaluation of different kinds of proteins. He was a Ph.D. He had the same problems as Paul Hahn. He wanted to do clinical research and he couldn't. He became an alcoholic which was a terrible tragedy. I think he died inadvertently at a relatively early age. However, not all the people that I know that are alcoholics are Ph.D.s! I also have very good M.D. clinical friends who are alcoholics as well. One of my best friends was a gentleman who studied blood volumes. He made great contributions! He had the misfortune to have two children who were criminally insane which drove him to drink. They were in an asylum outside of Boston and he'd have to booze up for a week before he went to see them, and it'd take him a week to taper off after he'd seen them. He was an innovative, very brilliant, wonderful man. His name was John G. Gibson III. He was a professor of medicine at the Peter Brigham Hospital who made his primary mark in studying blood volumes with dyes in disease states. He was an influence on my life, because I was studying blood volumes with radioisotopes.
Q: Are you aware of other groups that were beginning to use radioisotopes during this period? The Columbia group. The Rochester group.
Ross: The Columbia group, the Rochester group, and than there was also a group in Berkeley. They were using it therapeutically, and diagnostically. There was a man there named Low Beer who was I think a Viennese, who used radioactive phosphorous in the therapy of leukemia. He and Dr. John Lawrence used this agent.
Q: Do you know how to spell Low Beer's name?
Ross: L-0-W capital B-E-E-R. It's two words. Both the L and the R are capitalized. He probably got too much radiation exposure and he died of leukemia as a consequence of this. Also in San Francisco there was Mayo Soley who was investigating the use of radioactive iodine in the treatment of hyperthyroidism. He was a very nice guy! He went to the University of Iowa to become Dean. He [committed] suicide on a hillside with a rifle one sunny afternoon in autumn, which was, again, a terrible loss.
Q: Schoenheimer, himself, committed suicide also.
Ross: I did not know that. Did he really?
| 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 |