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Q: During the fourteen years that you spent at Boston University, did you see a change in the types of diseases that a hematologist would examine?
Ross: Yes, I think it's quite fair to say that during that period of time the capacity to modify the course of neoplastic hematologic disease, really began. Before that the only way to treat somebody who had lymphoma or leukemia was with radiation therapy, which wasn't terribly satisfactory. But with the advent of nitrogen mustard and the antifolic compounds, it was possible to modify things very quickly. Consequently, hematologists began to see and take care of more and more neoplastic disease. The advent of cyanacobalamine [Vitamin B-12] replaced liver extract as the therapeutic agent for P.A. and progressively diminished the referral of patients with pernicious anemia to hematologists because good physicians were able to take care of these patients without referring them to a specialist. Also, the recognition of iron deficiency anemia and the ways to treat this, decreased referrals. At one time iron deficiency anemia was a very common referral to hematologists. With the improved training and experience good physicians could recognize the cause of this type of anemia and could treat it. It no longer was necessary to send iron deficient patients to see a specialist. So, gradually over a period of time the hematologist's primary concern has become with neoplastic disease, with certain types of hemalytic anemia that cannot be easily modified, and with certain kinds of hemorrhagic disease which also could not be modified by the techniques used by most physicians.
This has led, unfortunately, to a specialty in hematology which increasingly is general oncology. This, unfortunately, as I say, is apt to be disappointing because usually you can't cure people with these diseases. You can take care of them, which is in marked contrast to pernicious anemia, iron deficiency anemia, and other illnesses which can be, in effect, controlled for a prolonged periods of time without the patient going ahead and dying. But it has changed the complexion of hematology. Unfortunately, hematologists years ago were not alert enough to recognize that they should expand their sphere of concern in neoplastic disease outside that of hematologic neoplasia. This then led to the development of what are now called oncologists, who use the same modalities of treatment in other tumors such as carcinoma of the breast, the colon, the liver, the lung, et cetera. The side effects that occur consequent to the treatment of these patients with oncolytic agents primarily are those related to the hematologic system involved and it's unfortunate that most of the current oncologists have not had a firm, basic education and experience in the field of hematology. Consequently, and not infrequently, we see very bad reactions in patients who have treated for carcinoma without sufficient attention having been paid to the effects of these agents on the bone marrow!
Q: Was there a similar change in the diagnostic equipment made available to clinical hematology during this period?
Ross: During the period that I was at Boston University everything still was done by hand--by technicians in a very laborious fashion. Subsequent to that time, the development of automated procedures on machines can perform these tests in a few seconds with greater accuracy than can be done by a technician looking through a microscope. At one point, we used to teach medical students how to do all the hematological procedures with a hemacytometer, hemoglobinometer, et cetera. Now, that's no longer necessary. When I directed the courses in hematology for medical students, I felt they ought to know how to be able to do a hemoglobin and a white blood count and differential in the middle of the night if they were out in a small hospital and didn't have a machine available, but even white counts are not taught any more to medical students. Those are all done by machine and most places now have technicians who are on call they have to be done. So doctors don't any longer know how to do all these technical procedures that once upon a time seemed so very important. They pretty much have been abandoned in terms of teaching.
Q: When did this change begin to take place?
Ross: This began to take place, in the 1970s--in the early 1970s when a couple of brothers named Coulter, working with Eugene Cronkite designed the so-called Coulter Counter, which initially was rather limited in what it would do, but now it's been expanded to the point at which it will do practically all hematologic studies very quickly in an absolutely magnificent fashion. The machine is not too expensive, and I believe it is probably present in most of the hospitals and laboratories in this country.
Also, it used to be that all of the white cell differential counts were done by eye and microscope but now, there are instruments that will do most of these automatically. This again has displaced technicians from doing the procedures. I'm not sure that these automated differentials always are as good as those done by technicians but if there's nothing really wrong, or expected to be wrong in the differential leukocyte count, I think the machine is quite adequate.
Q: Were there changes in blood banking following the World War II period, based on the experiences gained in the World War II period?
Ross: It expanded tremendously! It employed the preservation techniques that I've already discussed. Also the recognition of the numerous different types and groups of blood came to the fore, and explained some of the peculiar reactions that were observed that could not be accounted for on the ordinary [Landsteiner] four blood groups. I think that the major developments really have been in terms of matching and typing and the processing of the blood to ensure compatibility between the donor and the subject. The preservation procedures--that is, the actual places in which the blood is stored--demands a constant temperature in the refrigerator. These have been refined and made more elegant but they aren't much different from the refrigerators that used to be used.
The technique of taking blood, which used to be placed in a bottle with a liquid, has been supplanted now by the use of plastic devices, which are much less expensive, and safer. They can be disposed of after use. You don't have to wash them and worry about the bottles like we used to do. That was a great development which, interestingly, occurred as a consequence of the work of a physician named Carl Walter, a most interesting gentleman! While he was a surgical resident at Peter Bent Brigham Hospital there was a terrible series of fatal accidents consequent to the administration of intravenous fluids. It turned out that instead of having dextrose in some of the fluids, boric acid got into the solutions and killed the patients. Carl was assigned the problem of trying to solve this terrible situation and he solved it in one afternoon by insisting that a paper cup be put on top of every bottle of fluid that was going to be given to a patient and the nurse or the doctor had to take a drink out of the fluid before it was given to the patient. That stopped the trouble right away. He got interested in the subject, and went on to develop a very elegant series of bottles and systems for making intravenous fluids and taking blood for transfusion called the Fenwald system. In addition to being elegant it was quite expensive since the equipment was all Pyrex. Then when the war came along and it was necessary to ship blood from here to Timbuktu, he developed the plastic container which could be dropped from aircraft without rupturing or bursting. This was very wonderful.
He's an interesting gentleman. He was an engineer who had designed the valves that controlled the de-icing equipment used the in all military aircraft at one point. He was already an extremely wealthy man before he came to medical school and he subsequently continued with these innovative engineering developments in medicine. His work greatly expedited and improved the facility of blood transfusion and kept the costs down appreciably.
Other aspects of blood transfusion, haven't been particularly striking or different except for the capacity to precisely cross-match, and ensure that blood is properly used. An exception is the fractionation of blood elements. It's now becoming rather unusual that a patient is given a transfusion of whole blood. A patient more likely will be given a fraction. He may be given red cells. He may be given platelets, or leucocytes. He may be given plasma, but not often is he given the whole works together. This has been economically advantageous as well as improving the therapeutic use of blood.
[recorder turned off and on]
Q: Dr. Ross, I was wondering if you could say something about the development of consultation services in hematology at Boston University?
Ross: When Dr. Keefer recruited the members of the Department of Medicine, it was understood that they would be able to supplement their income--which was not very great from the University or from the Evans Memorial--with income from private practice and consultation. All of the members of our group engaged in consultation practices. It was part of the ground rules that the office space was provided gratis for this endeavor. All of the members of our group engaged very actively in consultation practice with certain limits in terms of the amount of time that was spent. Most of us spent one afternoon a week or maybe two afternoons a week doing this. We were able to supplement our salaries from this endeavor probably one hundred percent or even more. It wasn't very long before all of the members of our group were receiving very interesting referrals for consultation from all over New England, which led to the addition of fascinating cases to the patients admitted to Massachusetts Memorial Hospital of Boston University. These patients almost invariably were able to pay the cost of hospitalization as well as the cost of medical services. These patients were admitted to the teaching services of the hospital, and were a very valuable adjunct to the teaching, complementing the experience with the so-called ward charity patients. It was most advantageous for medical students and residents to deal with patients who were not impoverished and who usually were quite well educated and intelligent people. Although not all of our consultations were such, many of them were.
It used to be the usual practice that the consulting physician would charge each day the patient was in the hospital at the rate that the patient was paying for his hospital room, which was about fifty dollars. In retrospect, that was not too small a fee and probably not too large a fee. Now, with the cost of hospital rooms going up to four, five, or six hundred dollars a day, the consultation fees that the physicians charge are only a fraction of what the hospital charges.
The consultation practice was really very useful. To me, as a hematologist, many referrals came from other hematologists, such as Dr. William Castle of the Thorndike Memorial, who strictly limited the number of "private" patients that he wanted to see. He'd refer many of them to me, as also did Dr. George Minot and some of them from Dr. William Dameshek of Tufts Medical School. This was very much appreciated! This brought us very interesting cases and, interestingly, these were some of the best subjects for our clinical investigation. They were intelligent and we explained to them what was being done and, almost without exception, they were willing to cooperate completely.
Q: Are there any particular cases that stand out that you would care to comment on?
Ross: I remember one poor lady came to see me who had an anemia the cause of which the local physician couldn't figure out. She was studied and she had severe iron deficiency anemia. We did a barium enema on the lady and, at that point, I got lobar pneumonia and very, very ill. I did not review the X-rays of her colon. She was treated with iron, went home, got better and then she came back just as anemic as when she'd first been seen! At that point, I went and looked at the X-ray and she had a carcinoma of the cecum, which had been missed by the radiologist! Hers was a very good illustrative case not only for me but for the fellows, the residents, and the medical students that the doctor in charge of a patient has got to look and be familiar with everything that goes on relative to his patients!! This woman's cecum was resected and she is completely well, even at this time some twenty-five or thirty years later. That was a very educational and gratifying case!
I've mentioned the man that developed quadriplegia temporarily as a consequence of being treated with folic acid. And I had a very significant number of patients who had Hodgkins disease and we made an early attempt to eradicate this disease with radical dissection of the site of the tumor. I remember many of these cases. Unfortunately, we didn't cure any of them. That was a terrible ordeal for the patient to bear because the surgery was very disfiguring and it was very disillusioning because we didn't have any other therapy except X-ray and we didn't cure these patients. Now, the resection is implemented followed with and radiation and then chemotherapy, and we're able to cure about half of the cases with Hodgkins disease. Those are examples.
Q: Dr. Ross, I was wondering if you could review some of the major research efforts that you made while at Boston University as well as talk about the sources for funding for research in the post-World War II period.
Ross: Yes, in addition to the investigations that I carried out relative to blood preservation, iron metabolism, erythropoiesis, and blood destruction, I also was interested in applying radioactive iodine to the diagnosis and treatment of thyroid disease. This was a fruitful endeavor and as you may know, this modality of therapy and diagnosis of thyroid disease still is very widely utilized. In addition to this, I became interested in zinc, and we had radioactive zinc and were studying zinc metabolism. I had the idea that possibly polycythemia rubra Vera might be related to some abnormality of zinc metabolism. We did a great deal of work on that but zinc metabolism didn't seem to have any relationship to polycythemia. As a consequence of the use of these various isotopes, the Atomic Energy Commission expressed interest in subsidizing our investigative efforts and they took over the funding that had previously been granted by O.S.R.D. The AEC funded our investigations quite adequately for many years. This was extremely helpful since they were generous with their funding and we were frugal with our use of it. These are examples of the type of investigations that I did while I was there.
We were also interested in trying to study the mechanisms by which neoplastic disease produced anemia. It was always believed that anemia was caused by the bone marrow being crowded out by the cancer. We were sure that was not the case. We showed that the anemia in patients who have cancer is attributable to two factors. There's an increased rate of senescence of erythocytes, that is the red cells grow older more rapidly than they usually should, and the bone marrow is unable to compensate for this with an appropriate increase in the rate of formation of red blood cells. This was not related to any replacement of the bone marrow by neoplastic tissue. We tried very hard to find out what the actual mechanism of the increased rate of senescence of red cells was, but we never succeeded in clarifying what it really was that makes the erythocytes grow older more rapidly, except the fact that they circulate in a person who has cancer. To the best of my knowledge, this has never been explained. It's a fruitful field for future investigation.
Also I studied the blood volume in congestive heart failure in patients and in experimental animals with Dr. Clifford Berger, professor of physiology at Harvard. We proved that contrary to accepted belief there was no increase in circulating red blood cell mass in that condition.
Q: During this period you, no doubt, also had to develop new forms of instrumentation. For example, in following the use of radioactive iodine, I was wondering if you could comment on the development of some of this investigation.
Ross: At the time we began to apply radio-iodine in human subjects, the equipment was very crude and we designed an interesting thing that looked like a cannon. We got special kinds of lead and steel that didn't have any radioactive materials in them and fabricated them in to a very effective tool to localize the uptake of radio-iodine in the thyroid gland. This equipment was emulated elsewhere. There are more sophisticated techniques now available, but at the time it was a quite unique and a very useful instrument. Also, in our studies of radioactive iron, to quantitate the radio-iron in blood specimens we had to electroplate the iron derived from the blood onto a copper plate solution. That necessitated acid digestion in a Kjeldahl flask of red blood cells and then appropriately treating the digestate chemically, and electroplating the iron from the destroyed red cells onto a little copper disc. This made possible, really quite sensitive determination and quantification of the amounts of iron which were contained in the sample of blood. Also, we developed the technique of using radioactive chromium to determine the survival of red blood cells and not only the survival of these cells, but also using these labeled cells to determine the volume of red cell mass in the body. Interestingly enough, this again is a technique which is widely used even at this time. It is quite feasible to quantitate very accurately the length of time that red blood cells will survive. Take the individual's own cells, label them with radioactive sodium chromate, then puts his own labeled cells back in his body, so you're actually finding out what happens to his own cells in his own environment. It's interesting, you can compare that with what happens with the donor cells from some other individual in the transfusion into the same person who's got his own cells back and compare the two, which is an interesting approach to solving certain problems.
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Q: Dr. Ross, I was wondering if you could say a few words about the contribution of your wife and the rest of your family during your medical career?
Ross: During the time that I was a young physician, it was the habit of people in my position to spend all their time, efforts, and concerns working on the medical problems at hand. And I confess I failed to spend an adequate amount of time in other pursuits. However, in December 1942, I married a lovely lady named Eileen Sullivan, who was a microbiologist head of the bacteriology lab at the Peter Bent Brigham Hospital of Harvard University. She always was a tremendous support and help to me in my endeavors. We had five children, and they were all born while I was in Boston. I confess, in retrospect, I feel guilty at not having spent more time with my wife and my children, but they never complained, and they made it possible for me to do things which otherwise I could not have done. I shall be everlastingly grateful for these facts. My wife died three months ago after a six year battle with carcinoma of the breast during which time she never complained. My children were a tremendous support to her and also to me subsequently. I am very glad that I was privileged to have such a marvelous wife and such wonderful children!
None of my children wanted to go into the field of medicine. They said you had to work too hard to be a doctor like I was and they could think of better ways to spend their lives. I'm sure being a physician takes a lot of work, but I'm not sure they'll find any better way to spend their time.
Q: Dr. Ross, during the World War II period, 1944 to be exact, an individual by the name of Henry Stratton met another person, Siegfried Tanhauser, and expressed an interest in beginning a journal in the field of hematology. It was Tanhauser, apparently, who introduced Stratton to William Dameshek in 1944. I was wondering if you could give some details first about Stratton, and then about Dameshek's role in founding the journal which was to he called Blood.
Ross: Yes. What's the name of the gentleman again?
Q: Tanhauser.
Ross: Dr. Tanhauser was a very distinguished German physician who was expelled by the Nazis and came to the United States and became a professor of medicine at Tufts University. In that capacity he contributed greatly to mankind's knowledge in the United States. He was a very interesting man in relationship to certain types of pigment metabolism as it related to hematology. Dr. William Dameshek was the hematologist at Tufts and they became very close friends. There was another immigrant from Germany, a man named Henry Stratton, who had known Dr. Tanhauser in Europe. He had worked for Springer-Verlag, a publishing house which was, I believe, located in Munich. Everything that he had in Springer-Verlag was bombed out during the war, so he came to this country to start another publishing career. He, for some reason, wanted to start it in hematology. I don't know quite why, but he was a very astute gentleman. So he wanted to start a journal of hematology and Tanhauser, I guess, put him in contact with Bill Dameshek and between the two of them they decided to publish the journal, Blood. This was a joint ownership at that time. There was another gentleman named Grune, who I believe also was a refugee from Germany, but he had a significant amount of money and he provided the funding to start the journal, Blood. Subsequently, Mr. Grune, I think, was bought out by Doctor Dameshek and Henry Stratton, but Mr. Grune was tremendously effective in initiating the publishing activities of Henry Stratton. The company was known as Grune and Stratton. The journal Blood, I believe, was initiated in 1944. I can't be terribly sure about that--
Q: 1945, I believe, is its founding date.
Ross: --with Bill Dameshek as the editor. He got a group of associate editors and an assistant editor. I was the assistant editor and my job was to develop an abstract section of the publication, which I worked at for some years and which I think was very helpful to many hematologists. I became an associate editor along with Charlie Doan, Max Wintrobe, and two or three others--Carl Moore and some other distinguished individuals. At the time that the publication was begun Bill Dameshek used to put annotations at the foot of the articles which appeared in the journal saying that he disagreed with what was being said by the author or amplifying what the author had said. This was distinctly unusual in American scholarly journals and exception was taken to this activity both by Max Wintrobe and by Charlie Doan. At that point, we learned that Bill Dameshek owned a sizable portion of the journal Blood, and he allowed as now he was going to do what he saw fit as the editor and part owner of the journal. At which point all the associate editors resigned en mass. At that point, Bill decided maybe he'd better rethink the situation, which he did, and he agreed that that policy would be abandoned in the journal Blood, and that he was going to be much more amenable to the suggestions of his associate editors in the future, which he was. He was really a very great gentleman, scholar, and physician, and he had his way of doing things, but he was willing to modify it if other people thought he should.
Another interesting thing that he did--he was interested in international aspects of hematology and medicine and he was able to print the abstract of every article of the journal in Esperanto for a long period of time. I was never sure how really valuable this was since I always figured that anybody who was going to take the journal Blood could read it in English without having to resort to Esperanto. However, this was done for some years and then, I think because of the cost, it was abandoned. It no longer is done in the journal Blood. But the journal Blood was really a very successful publication. There are other publications in the field like Vox Sanguinis and other publications in Europe and also now in Japan, and they complement the activities of Blood: The Journal of Hematology. On the other hand, being biased, I would say that Blood: The Journal of Hematology, was one of the formative influences on the establishment of hematology as an effective discipline and brought coherence to the field.
Initially, the articles published in Blood, almost all of them, were clinically oriented. With the advent of new editors and new advisory boards, there is now much more basic science published in Blood than there used to be. I think that it probably outweighs the clinical articles at this time.
Interestingly, another journal has sprung up in an attempt to compensate for that. This new journal is called the American Journal of Hematology, and it concentrates on clinical presentations. I think that's good. There ought to be an opportunity for publication of any article which is good on any subject. It seems to me, unfortunate that good clinical articles are left out of Blood in order to publish basic science articles and vice versa in the American Journal of Hematology.
Both of these journals, I believe, are flourishing as are the journals published in Europe and also in Japan about hematology.
Q: Do you know if the European journals or the Japanese journals predated Blood?
Ross: I believe one of the European journals did. I can't tell you now which one, but I'm not even sure about that. I just don't know. Now there's a Scandinavian journal of hematology, there's Vox Sanguinis, which I think originated in Switzerland and there's a European Journal of Hematology. I know that most of those came after Blood, but how many of them antedated it, I don't know.
Q: The American Journal of Hematology, do you know when that started?
Ross: This started four or five years ago, I believe, and I don't think it has the stature nor does it have the excellence of the journal Blood, but nevertheless it's a good publication.
Q: Were the early articles in Blood determined by Dameshek's own idiosyncratic feelings of how hematology should develop, or was there some other policy underlying that decision?
Ross: Dameshek selected the articles to be published and rejected the articles not to be published. Initially, he did this as a solo endeavor. Subsequently, with the encouragement of the advisory board, it was agreed that he would send these out for review to other people. Subsequently, each article was sent to two independent observers and to some extent Bill Dameshek was constrained in his selection by the opinions of the reviewers and of his associate editors. Initially, it was some what difficult to obtain enough articles to put out an every other monthly publication of the journal but this didn't last very long. I was on the editorial board for ten or twelve years, and at the time I left the board I think the acceptance rate was about forty percent of those that were submitted.
Q: I was wondering if we could go over some of the names that you mentioned who were among the early associate editors and assistant editors of Blood, and perhaps you could supply some background information. Along with yourself as assistant editor, there was a Steven Schwartz? Do you recall?
Ross: I think he came along a good bit later on.
Q: I had him as one of the original--[tape interrupted]
Ross: In the early days of the publication of the journal Blood, it is of interest that Bill Dameshek, the editor-in-chief and part owner of the journal, operated pretty much on his own in respect to editorial policy as I think I've already commented. He didn't necessarily see fit, originally, to refer articles to review by others but this was changed. He also used to put footnotes in the articles if he didn't agree with what the author was saying and that irritated some of the members of the board, as I commented, but he had a very distinguished group of individuals who assisted him in establishing this journal. For example, there was Dr. Charles Doan, a very distinguished hematologist in Columbus, Ohio, who had worked with Florence Sabin in delineating the reticulo-endotherial system and the vascular system of the bone marrow. He was an active participant and brought great wisdom to the board. There was Thomas Hale Ham, who was an excellent hematologic investigator and a very great stimulant and interested in large measure in improving education in the field of hematology. There was Roy Kracke of Alabama, who had been the individual who recognized the connection between medication with pyramadon and the cause of agranulocytic angina, and Maxwell Wintrobe of Salt Lake City, who authored the first definitive modern textbook of hematology, who was very interested in this journal and always was very critical about the advertisements which appeared in the journal. He was a very great stickler for propriety and he used to protest vigorously that the items which were being advertised in the journal weren't really up to the snuff to the extent that he thought they should be. Finally, it was agreed that any advertisement that was going to be put in the journal was going to be reviewed by Max Wintrobe from the standpoint of its appropriateness to appear in a journal.
Then, of course, George Minot, the Nobel laureate in hematology, initially was a consulting editor who provided great insight and wisdom in the initial stages of this journal. I played a role, initially, as an assistant editor, as also did Steven Schwartz, who at that time was in Chicago. My particular assignment was the development of the abstract section, and it might be that Steven Schwartz was involved with the book reviews. I can't really remember what his actual assignment was.
Then there was a very great group of advisory editorial people, among whom was Russell Hayden of Cleveland, a great hematologist; and Cyrus Sturgess of Ann Arbor, University of Michigan, who had a tremendous reputation and had published definitive textbooks in the field of hematology, prioriented toward clinical endeavor; Laskey Taylor, who as a coagulationist at the Thorndike; Oliver Jones in Buffalo, who was a cytologist; Cecil Watson of Minneapolis, who was interested in pigment metabolism; and Philip Levine, who had a great deal to do with recognizing Rh factors in blood and contributed very greatly to our knowledge about establishing compatibility of blood transfusions.
Every year there would be a luncheon, which was subsidized by Henry Stratton, at which all of these individuals would be assembled. We would have a nice luncheon and discuss things. As time went on, this group really had a considerable amount of persuasive effects on Bill Dameshek in operating this journal. It became, I think, the preeminent publication in the field of hematology in the world. It was extremely valuable to have a place for hematologists to publish their activities together in a coherent fashion. Henry Stratton insured that the publication was done in an excellent fashion. Having been a European, he was able to get absolutely magnificent photo reproductions of the drawings and the photographs of the various blood cells. He saw to it that the photographic and other illustrations in the journal were absolutely superb, as best they could be! The whole effect was of a really excellent publication which has continued since.
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