ASH Oral History: Lockard Conley
ASH provides the following oral history for historical purposes. The opinions expressed by the interviewees are not necessarily those of ASH, nor does ASH endorse or make claim as to the accuracy of any of the information included here. This oral history also is not intended as medical advice; you should always seek advice from a qualified health provider for your individual medical needs.
The following oral history memoir is the result of one tape-recorded interview with Dr. C. Lockard Conley, conducted by Eric Hoffman on October 28, 1987, at the Johns Hopkins University Hospital in Baltimore, Maryland. Dr. Conley has reviewed the transcript and made corrections and emendations. The reader is asked to bear in mind that the following oral history is a verbatim transcript of spoken, rather than written, prose.
Q: Dr. Conley, I was wondering if you could provide some background, biographical information. I have you as being born in Baltimore in 1915. I was wondering if you could, perhaps, provide some information about your early schooling, early awakenings toward science or medicine as a career.
Conley: I attended the public schools including high school in Baltimore; became quite interested in science in the last year or two of high school particularly in biology where I had an excellent teacher. I grew up in the years of the Great Depression. I attended college at Johns Hopkins and majored in biology, not knowing at that point what I was going to do with it. And in fact, it was not until the third year of college that I decided that I wanted to be a pre-medical student. I hadn't made that decision until that point. I graduated from Hopkins in 1935 as a pre-medical student.
Q: There's quite a bit of interest in the early developments of biology at Johns Hopkins, going back to the turn of the century. I was wondering if you could supply some information about what sort of courses were offered, which professors you studied with, during the 1930s.
Conley: My introduction to biology was by a young instructor named Charles Brambel. He was an interesting man who in effect teased a lot of the students. For example, I remember in our very first session, he had us draw the yeast cells that we saw under the microscope. A yeast cell under the microscope simply looks like a disc and there is no way you can draw it, except to draw a circle or perhaps to fill it in. He would go around and shake his head as if we hadn't drawn it correctly. So that was sort of an amusing introduction to biology in my first year. But I got quite seriously interested in biology and studied the biology of that era, which was largely organismic, and included embryology, comparative anatomy and histology. Histology was given as an elective course taught by Dr. Emmart, a woman who had been working with Dr. Warren Lewis, one of the pioneers in the development of tissue culture. So I had a little introduction to at least medical histology as a college student but a very minimal one. I learned something about the techniques of making sections and looking at them. The eminent professors, H.S. Jennings, E.A. Andrews, S.O. Mast and C.W. Metz, did not teach any of my undergraduate courses.
Q: There is much being made about the fact in history of biology right now, that there was a transition that took place between earlier morphological studies and later experimental studies.
Conley: Yes, this was very much organismic biology, with very little physiology or function. We were looking at specimens, dissecting animals, that sort of thing. I studied chemistry. My chemistry professor was Neal Gordon, whose name is famous because he established what are now called the Gordon Conferences. Neal Gordon had these conferences originally at Gibson Island, here. They were then called the Gibson Island Conferences but subsequently, they've become known to all medical scientists as the Gordon Conferences held in New England. Neal Gordon was my professor of inorganic chemistry and I later studied organic chemistry. Alsoph Corwin was attempting to synthesize hemoglobin. He is still one of my friends. I got very little physical chemistry. My education in science, by current standards, was very deficient. It was all pretty standard, fairly elementary kind of material. Joseph Sweetman Ames, then President of the Johns Hopkins University, gave us a few lectures on elementary physics.
Q: Were there courses offered at the time in bio-chemistry?
Conley: I'm quite sure bio-chemistry was not taught in the undergraduate school. There has been a great change in what young people learn now. Just as many high school students learn calculus, much of the pre-clinical teaching that was provided for medical students, they've already had now before they get to medical school.
Q: This was in the medical school or undergraduate?
Conley: I was an undergraduate.
Q: Undergraduate, okay. Were there any other courses that stood out? Did you have courses in genetics at that time?
Conley: Yes, I had a course in genetics by Alexander Weinstein, who was an impressive teacher. I learned a good deal from him about Mendelian genetics, as known at that time.
Q: Was there-- you said that it was in your third year that you became interested in the study of medicine?
Conley: Medicine, yes.
Q: Was there a particular event or particular study--
Conley: I think it as probably a practical decision. What else could I do with that kind of background, particularly at that particular time, when there wasn't very much future in anything. There didn't seem to be.
Q: And you decided on going to Columbia, to Physicians and Surgeons?
Conley: No, I didn't go to Columbia. I was very impecunious, and I applied to only one medical school: the University of Maryland. I went to the University of Maryland for my first year of medical school. There, as a medical student, I met Magnus I. Gregersen, the Professor of Physiology, who had newly arrived from Harvard and who was a student and a protégé of Walter Cannon. Dr. Gregersen invited me to drop out of medical school for a year, and to spend a year in physiology. This was long before research grants; I was called a teaching fellow. Although I did participate in some research, I did not accomplish anything very meritorious at that time.
But that experience changed my own thinking from my, up until that time, anatomical approach, to thinking physiologically and subsequently, pathophysiologically. I think it was that experience that made me ask why? What's going on? Rather than what is it? There is no question that it had a great influence on my life.
Then I went to Columbia where Magnus Gregersen became the Professor of Physiology. He invited me to go there as a medical student, and I was able to get a scholarship. So I went through Columbia with a scholarship and kept my fingers in the Physiology Department.
Q: Magnus Gregersen worked in the Department of Physiology in the Medical School itself?
Conley: He was the Professor of Physiology, he was our professor.
Q: What particular area did he work in?
Conley: He was interested in measurement of blood volume.
Q: That's the research project that you, yourself--
Conley: That's what I was involved in and I learned the techniques. But more important than that, I became very interested in mechanisms, and in physiology as it is applied to medicine. I went to Columbia, at what I consider to be the peak of its excellence. There were just extraordinary people there. The surgeon was Allen O. Whipple, who was himself a physiologist; he thought in terms of mechanisms, had a very unusual and interesting approach to medicine, and was a superb teacher. There was an excellent Pathology Department. And here again, we were not just looking at dead material, but trying to understand what had happened to it. But the Department of Medicine was really spectacular. My teachers included Robert F. Loeb, Dana Atchley, Franklin Hanger, Randolph West, William Thompson and many others. These people were real medical scholars.
Q: This was a period when biochemistry itself was finding a niche within the medical school?
Conley: When science was very much being applied to medicine. And the people whose names I mentioned, were very much scientists. Robert Loeb was an incredible figure in terms of his approach to medicine. He was a superb clinician, had a photographic memory, and his approach to clinical problems was very much physiological.
Q: Can you give some examples of the work that Loeb did?
Conley: Dr. Loeb was the one who discovered the nature of the electrolyte disturbance in Addison's disease. He was an authority on serum electrolytes. And his colleague Dana Atchley was similarly involved. During my last year in medical school, I was invited to meet after breakfast with Dr. Loeb and Dr. Atchley. Atchley was primarily a clinician, but a very scholarly one, and Loeb was a full-time professor. They would meet in Dr. Loeb's office every morning between eight and nine and discuss the issues of the day. It was a very exciting experience to sit with these giants--and they were giants in medicine-- to hear them and to participate in discussions of pathophysiology in medicine.
Q: What would be the nature of the discussions? Was it on recent experiments?
Conley: Yes, they discussed the work that was going on, that they were involved in. But anything that had come along-- this was not a scheduled meeting, it was an after breakfast get-together before the work of the day started when they might discuss the news events of the day. But usually the conversation related to something that was evolving in medicine. Something that was going on.
Q: Were there connections between Columbia Presbyterian and the other medical research institutes of the city such as Rockefeller, such as--
Conley: They were not intimately connected. Columbia Presbyterian Medical Center is out at 168th Street, really quite far removed from these other centers. There was an affiliation with the old Bellevue Hospital. There was a Columbia service at Bellevue where we had some of our clinical instruction. There, for example, I met Andre Cournand, who much later won the Nobel Prize for his work on cardiac catheterization.
Q: Was there any interest awakened in you in hematology while you were at Columbia?
Conley: Not at all. In that day, all of the routine blood counts, urinalyses, gastric analyses were performed by medical students, so I did many, many blood counts along with all of the other medical students. But I can't say that I had any intention of doing that beyond medical school.[laughs]
Q: It might have been after you graduated, but I believe that at Columbia P&S they started to do work in terms of developing plasma collection and plasma analysis for a blood bank program that they were developing.
Conley: The blood bank evolved while I was there. Blood banking, blood transfusion was extremely primitive when I was a medical student and intern. We had a large square plate, a sheet of plate glass, on which with a red crayon we drew nine squares and we would type and cross match blood using blood of known type that had been stored in the laboratory. The blood typing and cross matching were done by the interns. There was no blood bank. John Scudder was the man who established the blood bank.
Q: Did you have any context with him?
Conley: I surely did, as an intern. All of us interns drew blood from the blood donors when they came in to be bled. And of course, we then obtained blood from Dr. Scudder's bank. He had some interesting ideas that we were exposed to. He was a very dynamic man
Q: Did you come into contact with his associate?
Conley: Dr. [Charles] Drew? Yes I knew Dr. Drew.
Q: Could you supply some information on--
Conley: No, not very much. Dr. Drew was very much on the scene working with Dr. Scudder in developing the blood bank. They developed their own blood bank storage bottle, which was sort of a figure-eight shape bottle with a narrow section between the top and the bottom to keep the potassium that was released from the blood cells out of the plasma. That didn't last very long. This was an age of pioneering and there is no question that they were pioneers.
Q: Through the offices of people such as Walter B. Cannon, and Alex Carrel from Rockefeller Institute, it was suggested that Columbia University develop a pilot program for blood banking, to be used in defense of Britain. I think that was the name of the program actually--Blood for Britain. Do you know anything--
Conley: I don't know anything about that at all. I do remember that Dr. Richard Bing was working in the Pathology Department before I left, and Charles A. Lindbergh by that time was working with Dr. Carrel, at a time when they were being looked upon with some disfavor. And Lindbergh would come out to the medical school in the evening, when he was not likely to be seen, to work with Dr. Bing in developing a perfusion apparatus-- to perfuse excised organs and that sort of thing. That had nothing to do with the war effort. I was not in any way associated with Dr. Carrel, and my only recollection of him, except from knowing about him in his tissue culture work and so forth, was his work with Dr. Bing and Charles A. Lindbergh.
Q: Do you know what happened to the blood banking program at Columbia? It seems to be a lost chapter in lots of the accounts of--
Conley: I don't know about the blood bank per se, but there have been people at Columbia who have been very, very important in studies of the red cell, red cell immunology, and other fields applied to blood banking. But I had no contact with those people. Incidentally, I left Columbia before I finished my training in May of 1942, to enter the military service.
Q: Perhaps if we talk about your military service-- was there, did you continue with your medical training work in the military?
Conley: I volunteered for the military service after Pearl Harbor. I remember I had to send three letters of recommendation to get into the military service. It took from December until May until I was called up, reflecting the disorganization of that period, when the military forces were being expanded rapidly. But in May, I had applied to the Air Forces, and was accepted into the Air Forces as a Lieutenant in the Medical Corps, and was assigned to what was called Hunter Field in Savannah.
I was there for about a month when the Air Forces opened a new base at Greenville, South Carolina. The man who was selected to be the Surgeon--the Surgeon is the term for the medical officer in charge--took me and two other of his then colleagues along to establish the medical unit of this new base in Greenville. And although I was very young and very inexperienced, I guess I was more experienced than some of the others. So I became the Chief of the Medical Service in the station hospital. We had really quite a good little medical service there, and some very good doctors.
But in 1943, the Air Surgeon General's office, apparently detected my previous experience in physiology. I was transferred to what was called the Altitude Training Program, at Randolph Field, Texas. I was at Randolph Field to take a course in what was then considered to be High Altitude Physiology.
Q: Could you give some more information on the altitude training program?
Conley: Yes. It consisted primarily of teaching air crew members the risks of high altitude flight and what precautions were required to protect them against these dangers. In World War II, there were virtually no pressurized air craft. I think there may have been some photo-reconnaissance planes that went up high, but the bombing flights over Europe, the B-17 flights were under 25,000 feet, which at that time was considered to be high altitude. As a matter of fact, at any flight above 10,000 feet, it was required that oxygen be used.
In those days, you had to use oxygen masks and there were two types that were sequentially developed. We had to teach the air crew members the importance of using these masks, how to use them, and to expose them to simulated flights in low pressure chambers, demonstrating along the way by having certain of the participants not use oxygen and letting everyone else see them pass out. We would tell them, now be sure to turn on your oxygen before you pass out, but they never did. So it was a very convincing demonstration. We were dealing with young, very cocky people. You know, the kind of people who say, "Maybe you need oxygen but I don't." And the fact is, you don't sense the need for oxygen, so we had to give these dramatic demonstrations, hoping to convince them that they really should use oxygen at these altitudes. We unnecessarily took them to much higher altitudes, to 35,000 feet where they might experience bends, which is the agonizing joint pain that occurs when bubbles of nitrogen are extruded.
Conley: I was only involved in the program for a year or so. I was sent to Maxwell Field in Montgomery, Alabama to participate in the activities of the altitude training unit. But then I was transferred to the medical service of what was an excellent hospital, where I sat out the war, involved in internal medicine. I had really quite a good clinical experience at the Maxwell Field Hospital until I left the military service at the end of 1945.
Q: One quick question about the altitude training program at Randolph Field. Were you involved in actual research, physiological research or was it more of a clinical and training program?
Conley: It was theoretically a research unit, but there was very little research going on there, in contrast to the Naval Unit in Pensacola, which was very actively engaged in research.
Q: And then, one quick follow up. Was there any discussion at that time about involving aviators in these experiments, for instance, experiencing bends and things of that nature?
Conley: Was there any?
Q: Was there any concern or discussion over the question of--
Conley: The civilian head of the Air Forces Altitude Training Program, was Dentlev Bronk, who became the president of the Johns Hopkins University. He was the one who, I am told, specified that flight personnel should be exposed to 35,000 feet. The very junior ones among us thought it was pretty silly since nobody was flying to that altitude. Maybe Dr. Bronk thought that they would be sometime. Of course, long before flights to that altitude became common, aircraft were pressurized. But that was after World War II.
Q: In 1946, following your war experience, you received a Lipman Fellowship?
Conley: That's an interesting story. I told you that I had not completed my clinical training at the Presbyterian Hospital. So as soon as I returned from the military service, I went back to the Presbyterian Hospital to see Dr. Walter Palmer, who was at that time Chairman of the Department of Medicine. He said, yes, of course, you do need another year of house staff training, and I was about to go back there.
My parents lived in Baltimore. I discovered that one of my medical school classmates was here at Hopkins on the medical service as a resident. He'd been a good friend of mine. We got together and he said, "Why don't you come to Hopkins?" I had had absolutely no connection with Hopkins Medical School at all. I didn't know anyone here. He said, "Come on down and talk to Dr. Longcope. Dr. Longcope was the Chairman of the Department of Medicine. So I did. I went in to see Dr. Longcope, and to my amazement, Dr. Longcope offered me a fellowship. That seemed very attractive to me, because although I had had a very good time in New York in earlier years, now that I was married and had a small child New York didn't seem to be a very attractive place to live. So I liked the idea and I accepted this fellowship, which was without specification as to exactly what I was to do, but was intended to round out my clinical training, in fact to complete the training which I had not completed. Dr. Longcope said, "I'm retiring at the end of June and you'll have to see Harvey." A. McGehee Harvey was the appointee as his successor. And so Dr. Harvey took over the department in July.
In the meantime, I had made quite a number of friends and associates here. Dr. Elliot Newman, who had been the chief resident for some time, impressed me as being a tremendously scholarly person. On leaving the residency, he was going to establish a laboratory. He was particularly interested in fluid and electrolyte balance, the sort of thing that I had been involved in before. So I was all set to join him in the laboratory.
Q: This laboratory that he was going to establish was within the medical school?
Conley: Yes. You see, during the war years, the department of medicine, in fact all of the departments had withered away. Almost everyone had gone off to the wars and the place was being held together by older people. Research was pretty quiescent. Elliott Newman was going to be one of the first bright young people to get things going with his new laboratory. I was scheduled to join him, among others. Dr. Harvey took over, with a necessity really to start from scratch and build a department with virtually no full-time people here.
Q: What was the state of research then with few full-time people?
Conley: It was low.
Q: What about in terms of equipment and--
Conley: It was antiquated. The buildings were antiquated. There had been no new building. My recollection is that the last new building had been built in 1927. The place was sort of dirty, run down, decrepit and needed a lot of restoration, rebuilding. So Dr. Harvey, the new young Chairman of the Department of Medicine, had this great responsibility and of course opportunity, to start from scratch. He recruited a whole group of relatively young people to fill slots.
Q: And the philosophy that was followed by this Dr. Harvey was that there should be basic bio-medical research?
Conley: He thought that was very important.
Q: And that was a change from what existed before the war or was that a continuation?
Conley: Oh, there had been research going on here, important research. But I think the war years, per se, devastated research activities. Hematology, of course, was well represented by research activity because Dr. Wintrobe was here and he had many accomplishments. But Dr. Wintrobe left in 1943, and really left virtually no trace of the Department of Hematology.
Q: Was it actually functioning as a Department of Hematology?
Conley: Oh, there had been research going on here, important research. But I think the war years, per se, devastated research activities. Hematology, of course, was well represented by research activity because Dr. Wintrobe was here and he had many accomplishments. But Dr. Wintrobe left in 1943, and really left virtually no trace of the Department of Hematology.
Q: Could you give an idea of what doing research under Max Wintrobe would have been like?
Conley: No, I was not here. You see I didn't meet Max Wintrobe until years later. So I had no knowledge or feeling for him except that he was a very hard working man and was doing experimental work. He was interested in nutrition, was using pigs as models and made some very, very significant discoveries. He was also, of course, greatly interested in clinical hematology. He wrote the first edition of his book here, it was published in 1942. That was a significant force, you know, in making hematology a branch of clinical medicine. There was a tremendous hematologic slant here when he was here. When he left, there was nothing.
Q: So, where did hematology come from then?
Conley: I'll tell you about that. When Dr. Harvey took over, he was looking for people to do various things to fill in the vacancies. He called me in and said we don't have an anticoagulant therapy program here. We're not using anticoagulants. Would you be willing to set up a little laboratory and develop a program? I knew that blood clotted, but that's about all I knew about it. So I was given a tiny room with an antique copper water bath and a Bunsen burner and a very minimum amount of equipment. My old biology teacher at Hopkins, Dr. Brambel, was running an anticoagulant therapy laboratory at the Mercy Hospital. So I went over to see him to find out how you did it, and learned the simple methods that are employed-- Learned to take rabbit brains out of the rabbit heads, which you have to do to make the thromboplastin. I set up a little laboratory--and that wasn't very hard to do--and for a period prescribed all of the anticoagulants that were used in the hospital. Initially I had no help. Ultimately, a technician was employed to help me. But I found that this didn't take much of my time, and purely for the fun of it, did some research. I was fortunate to make some very significant discoveries.
Q: This was on the prothrombin time, did that come in at this point?
Conley: The prothrombin time, developed by Armand Quick, was a method that we used to control anticoagulant therapy. It was a standard method which I learned. But this got me interested in blood clotting and so I started doing simple experiments. In those days, as Dr. Castle may have told you, it was possible with your own hands and a high school education to make significant discoveries. And that is what I did. In a relatively short period of time, I was able to make some discoveries and write some papers. Young people came to work with me, initially volunteers, then fellows. Things went so well that in January of 1947, six months after Dr. Harvey took over, he said we don't have anybody running a Hematology Division here. Would you be willing to do it until we can recruit somebody? I didn't know any more about hematology than I did about blood clotting. That was the sort of thing that was done in that era but couldn't conceivably be done now. I learned hematology all by myself, by doing it. And things worked out well.
Q: A number of questions on this. It was during this period that anticoagulant therapy was coming into vogue. Could you say something about the state of the art?
Conley: Well, anticoagulant therapy-- heparin had been discovered here at Hopkins in about 1915, but did not fall
into widespread clinical use until many years later. It was being used to some limited extent in the
The discovery of Dicumarol, by Karl Paul Link, at the University of Wisconsin, derived from a study of the toxic agent in spoiled sweet clover hay that had caused epidemics of hemorrhage in cattle. Herds of cattle that had eaten spoiled sweet clover hay bled to death. It had been known for some time that the spoiled sweet clover hay was responsible, but Karl Paul Link--an agricultural chemist at Wisconsin--isolated the toxic material, which was called dicumarol.
At the University of Wisconsin, I think the clinicians didn't appreciate his suggestion that this toxic agent might be given to man as an anticoagulant. But the people at the Mayo Clinic were more venturesome, and this material had a very extensive trial. And by the time I came here in 1946, dicumarol was being widely used. Dr. Harvey wanted it available here.
Q: Under what circumstances was dicumarol used?
Conley: It's used to prevent thrombosis in any situation where patients are thought to be predisposed to thrombosis, or where they have already had thrombosis and want to prevent new ones or extensions.
Q: And do you know what led Link to believe that it could be used as an anticoagulant, dicumarol?
Conley: Well he knew that it impaired blood coagulation, of course. He knew quite a bit about how it did it. And I guess it was fairly logical reasoning that something that impaired blood coagulation, --if degree of impairment could be regulated,-- might be effective in reducing the probability of thrombosis.
Q: So the work you were given to develop, was actually to work in the area of thrombosis?
Conley: All I was asked to do was to set up this program, so that doctors who wanted to give dicumarol would have the test available and I actually regulated the dose. In other words, we did prothrombin times at frequent intervals, and depending upon those prescribed the dicumarol.
Q: Did you find time to do research in other areas?
Conley: I became interested in coagulation in general, so that my research initially, for the first couple of years, was related to coagulation, but not to dicumarol.
Q: Was there a push to develop this research?
Conley: No, I did it for the fun of it. That's the way to do it, of course. I didn't have to. I wasn't thinking of staying at Hopkins. I came here with the thought of being here for a year, probably, or two, and had no thought that anything like this would happen. And even after I was asked to head the non-existent Hematology Division because there was no one else here, there was no thought in my mind that I would be doing this for very long. One thing led to another, and this is the story of my life actually.
Q: So there was no attempt, as there were at other Universities, to find some link between basic research and preclinical, or clinical studies?
Conley: Johns Hopkins was the first research university in the United States. Its medical school has been the prototype for all of the medical schools in the nation following the Flexner Report in 1910. There has never been a time when there were not close interactions between clinicians and preclinical scientists. I call your attention to the fact that the DNA restriction enzymes, essential for all DNA technology, were discovered here by Drs. Nathans and Smith, who were awarded the Nobel Prize for that discovery. Both Nathans and Smith were trained as clinicians, but work in a basic science department. The history of hematologic research at Hopkins is particularly rich. Hopkins celebrated its Centennial in 1976 and during that year a number of symposia were held, one, the "William Osler Symposium on Hematology." All of those who participated had been or were Hopkins physicians and scientists spanning a period of 50 years. I should like to quote my summary of this Symposium, which reflects but by no means includes all of the research activity at Hopkins in the area of hematology.
The William Osler Symposium on Hematology, celebrating the Centennial of The Johns Hopkins University, was presented in the Turner Auditorium in May by 56 participants, all former or present members of the Hopkins family. The diversity of the program reflected the indefinable limits of hematology and its interweaving with many other scientific and clinical disciplines. The speakers, x-ray crystallographer to clinician, demonstrated that development of useful knowledge has been as much the result of passage of information from the clinic to the basic science laboratory as in the opposite direction. A surprising number of early Hopkins men and women, most not identified as hematologists, made noteworthy contributions; some of these were reviewed during the Symposium in conjunction with descriptions of recent investigations. Osler's own work was summarized by one of his successors as Physician-in-Chief, Dr. A. McGehee Harvey. Osler's last senior year class at Hopkins, the Class of 1905, included two students destined to become Nobel laureates: George Hoyt Whipple, regarded as the father of experimental hematology in the United States; and Peyton Rous of fowl sarcoma fame, credited with devising a preservative fluid for blood and developing the first blood bank. The names of some Hopkins figures have been incorporated into the language: Dorothy Reed cells, Howell-Jolly bodies, Auer bodies, Duke bleeding time, Felty's syndrome. "Wintrobe" has become virtually synonymous with "Hematology." The work of others is indelibly written in the history of hematology: Franklin P. Mall, Florence R. Sabin, Charles A. Doan, Warren H. Lewis and many others. Heparin, streptokinase, cold agglutination and cryoglobulinemia were discovered at Hopkins, where "infectious mononucleosis" and "sickle cell anemia" were named.
The three-day William Osler Symposium will not be published in its entirety. The Symposium on Thalassemia which follows is representative, bringing together developments of historical interest and current investigative work.
Conley: Wintrobe also was self-educated. He said that his interest in hematology evolved from an interest in pernicious anemia, and that his principal research interest had started out to be trying to identify the anti-pernicious anemia principle. He did animal experimentation here, a lot of it. And he collaborated with investigators in other departments, notably in pathology and the School of Hygiene. That kind of collaboration was going on. But Dr. Wintrobe had left, and many other people had left and I think that whatever had been going on before was at a low ebb at the time that Dr. Harvey took over. It was a time then for rejuvenation. Dr. Harvey, had a lot of research experience and he had his own research unit.
Q: In which area did he--?
Conley: He was interested primarily in neuromuscular transmission, and was involved with Edgewater Arsenal that was studying nerve gas agents that block neuromuscular transmission; so he was interested in those diseases in which those phenomena were important. He was concerned with laboratory research and the people working with him had a very active laboratory from the word go, from the time he came back after the war. But he was in the war too, you see. He didn't get back until after the end.
Q: So the neuromuscular transmission research, in his case, also came out of wartime interests with nerve gases and also--?
Conley: He'd been interested in this long before. He worked in England with Sir Henry Dale and had a really quite remarkable research experience at Cambridge, as part of his pre-war training. He had established a substantial reputation as an investigator before he came here as a chairman.
Q: Did he hold this out as his model of doing research in a clinical setting--
Conley: Absolutely. He wanted everybody with any responsibility here doing research. There was no question about that.
Q: So that became like, the Hopkins model or the Harvey model?
Conley: Absolutely, yes. In that era, and until recently, the traditional three-legged stool was in vogue. In other words, every successful member of the full-time staff was expected equally to be a teacher, an investigator and a clinician.
Q: And this was a philosophy that seems to have come from Dr. Harvey?
Conley: He very much felt that way.
Q: Some of the work that you did early on, I believe you published on this by 1949, was on the surface effects in coagulation.
Conley: Yes, that was one of my very first interests, at a time when it was generally believed that blood clotted when it was shed because the platelets disrupted. Although others had suggested that that was not so, it was an almost universally held belief by senior coagulationists at that time. We did some definitive experiments to demonstrate that the platelets were not the factor, that there was a plasma factor, which we did not then identify. But one of my early collaborators after we had done this original work, was Dr. Oscar Ratnoff, who went on to become one of the world's leading coagulationists. Dr. Ratnoff is the man who encountered a patient whose blood didn't clot normally on contact with glass, and led him to be able to identify the factor that we always knew was there, and which came to be called Hageman factor.
Q: Hageman, after the patient that--?
Conley: Yes, Oscar Ratnoff had a prepared mind, of course, because he had worked here and was convinced, that glass contact activated a plasma factor.
Q: Could you supply some more information on what types of equipment and approaches would be required to find a soluble component with the plasma itself?
Conley: I can tell you research equipment was very primitive in those days. This was before research grants. I met the president, I guess the owner, of a local ice cream company, and he gave me an ice cream freezer which we used for our refrigerated centrifuge. And I borrowed a centrifuge that we put into this freezer. That was our original refrigerated centrifuge. I found investigators who were using rabbits for their research. When the rabbits were discarded we cut off their heads to make thromboplastin. We were so lacking in funds, that I actually redistilled the acetone that we used to extract the thromboplastin rather than buy a new bottle. You can't believe how tough times were in those early years. I obtained my first NIH grant in 1948.
END OF SIDE ONE, TAPE ONE; BEGINNING OF SIDE TWO, TAPE ONE
Conley: The first research grant that I received from the NIH in 1948 was still being supported when I retired in 1980, and, beyond that I had many additional grants. But that first one was must be one of the longest term grants that the NIH issued. With some financial support we were able to have designated fellows. Thereafter, I had a training program which was very much research oriented. We had a small program in which we would take, at the most, two or three fellows per year. Everyone who was appointed recognized that he was going to spend a large fraction of his time doing research. During my tenure, we never had a clinical hematology program. The fellows learned clinical hematology by osmosis but not through a formal structured program.
Q: Was Max Wintrobe's book used, CLINICAL HEMATOLOGY?
Conley: Max Wintrobe's book was used by every hematologist extensively, in large part for its extraordinarily complete bibliography. Since I was a newcomer to the field, every time I encountered a patient with a disease I didn't know much about, I would not only read Dr. Wintrobe's chapter, but I would go to the library and read all of the original references. I built up a substantial collection of reprints over the years. Soon after we had fellows, we started having a journal club. In those years, it was possible to review the hematologic literature in total in a once-per-month session. At those meetings we would send for reprints and so I rapidly built-up a large reprint collection.
Q: How would hematology at that time be defined? Who would be counted as a hematologist?
Conley: That is a very good question and a very important one, because there was almost no such thing as a hematologist. There was no hematology organization. There was no journal of hematology until 1946, when Blood, the journal of hematology, was founded. Hematologists included all kinds of people, who were interested in the blood. And at various informal meetings, and many meetings were informal, participants included non-clinicians: biochemists, and biologists. This is one of the marvelous things about hematology, its multiple interfaces. Hematology was considered to be the queen of the clinical sciences, in fact the first branch of clinical medicine to have a solid scientific basis.
Q: Who is it that considered hematology as the queen of the clinical sciences?
Conley: I don't know who first introduced that term but it has been often repeated. And it was certainly true. There are certain reasons for that. Everyone mentions the availability of the blood. Something that you can get and study much more easily than you can other tissues or organs. But hematology, meaning examination of the blood-- blood counts--were done routinely by all doctors. In this medical school, in the second year, there was a major course in what in those days was called clinical microscopy. And for many, many hours, students learned to perform blood counts, to examine the urine, to examine other body fluids and so forth. And they had to do this because when they went on the wards, they were entrusted with this responsibility. So every medical student learned a lot of hematology. In that era, students were less involved with cardiology or gastroenterology.
Q: What about other areas such as bacteriology?
Conley: Bacteriology, of course, was taught as a formal course in the pre-clinical sciences. But in terms of clinical medicine, the clinical microscopy course was taught by clinicians to students who were going to be using these methods to examine patients.
Q: Was the emphasis in this clinical microscopy more of a morphological?
Conley: It was more on methodology as it started out, but as information evolved, as it rapidly did, pathophysiology was incorporated into the teaching. Then as pathophysiology became interesting in other branches of medicine, and particularly after students no longer did routine blood cell counts, hematology was squeezed out and largely displaced. So whereas students, had a couple of months of hematology, now they got maybe ten sessions.
Q: Perhaps we could return to that question of how hematology got squeezed out, a little later on. But I was wondering if you could identify more of the content of hematology at that time. At what point did there seem to be a shift from morphological studies to this what you're calling pathophysiology?
Conley: I think the big influence was in changing hematology from a branch of pathology, where it had been and still is some places, where bone marrow and blood examinations were done by pathologists, not by clinicians. The driving force, I would say was the discovery of the treatment of pernicious anemia. The discovery that an anemia, which was incurable and fatal, diagnosable by morphologic methods could, in fact, be treated. This stimulated all kinds of interest in the mechanisms of anemia. And it interested people who were not just looking at dead, fixed tissues.
Q: But there is a gap of time between the late '20s when the liver factor was being isolated [not isolated at Harvard], for treatments in pernicious anemia and this later period that you are talking about.
Conley: Things were going on but hematology was not a block of science. For example, what preceded the discovery of liver therapy was the discovery of the vitamins. That goes back before the turn of the century. The big discoveries, in the early part of the century, were the vitamins. And those vitamins included folic acid. But preceding the discovery of folic acid, it was well known that patients with pellagra were anemic. Pellagra was rife in the rural South. When I went to medical school, we learned about the three p's -the pellagra preventing principle, the three d's -dementia, diarrhea, dermatitis, when pellagra was known to be a nutritional disease, but its cause hadn't been identified. So this was a very exciting era and this impinged on hematology, too, because these patients were anemic and it was known that certain concentrates, yeast for example, cured the anemia but it was not until 1946, that folic acid was identified.
In other areas vitamin K was discovered by Dam. K stands for coagulation's vitamin if you spell coagulation with a K as they do in Dam's country. When I was an intern, patients with obstructive jaundice who were going to be operated on were given alfalfa juice, because alfalfa juice contained vitamin K. You see, I've seen some of these things evolve.
The nature of the bleeding in jaundice, was explained by Dr. Armand Quick, who was able to do this because he invented the prothrombin time test. And you see, the discovery of the prothrombin time test totally opened up the field for anti-coagulant therapy.
So all of these things were going on simultaneously, but unrelated in a sense that most of the investigators were not hematologists. But all of this was hematologic. And at a meeting, where these things were discussed, there were groups of people with varied basic knowledge and interests, but all bringing together their knowledge on a subject. When it was proposed, years later, that a society of hematology be formed--Henry Stratton and Bill Dameshek and others said we ought to have a hematology society-- this was actually opposed by some. Dr. Carl V. Moore who was one of my idols and one of the great hematologists of the time, said we don't want a society. If we have a society, then we'll be defining what a hematologist is, then we'll be having boards. He so appreciated, as I did, the non-disciplinary, or inter-disciplinary nature of hematology that we hated to see that destroyed by creating, as it were, a walled-in specialty.
Q: I'd like to talk about that a little later too. There seems to have been very widespread opposition to forming a society. People such as Bill Castle-
Conley: Yes, exactly, Castle never joined. Castle is an honorary member but he never joined the Society. Wintrobe didn't join it, I think for several years. I didn't join it-- at first.
Q: It was based around this notion of keeping hematology open to basic research in an inter-disciplinary fashion rather than getting caught in the standardization of boards.
Conley: Let's take the one disease, the study of which has produced more basic information than any other. Do you know what that is? Sickle cell anemia. I have written an account of the development of knowledge about that disease because I'm so fascinated by it: the sequential developments and who made the great discoveries. It's a very remarkable story because most of the people who made the discoveries, were not people that you would have thought would have done so.
Q: This is a very interesting picture that is developing for early stages of hematology. We have people working in other disciplines or sub-fields contributing to a later stage of professionals becoming self-conscious and saying this is what we would consider research with hematology. But a more particular question arises then: in numbers of the cases that you were listing, such as the work that went on with pellagra, the work with pernicious anemia, these involve nutrition and vitamins--how important was the study of vitamins itself as a model for doing research within the hematology? In other words, were vitamins seen as almost a magic bullet for hematologic disorders? Did that attract people to look into it?
Conley: One of the big nutritional items in hematology is iron and certainly people interested in iron metabolism were interested in nutrition as part of iron metabolism. As a matter of fact, the nutritional aspects of iron metabolism, I think, have been greatly over-emphasized. But there is no question about its very important role. Iron deficiency is said now to be the most common deficiency in the world. But I don't think that Carl Moore, for example, who was a great student of iron metabolism, could be said to have been a nutritionist. He was interested in iron, per se.
Q: I wasn't thinking so much in terms of actually developing a grand theory for hematology but having a working model. What are the sorts of things that you would do research on. The reason I'm asking this is that Dr. Nathan has raised this as an issue. That because of the similarities in bone marrow morphology between leukemia and anemia, it was thought in the early '50s that there might be a model, that there might be--
Conley: Well a lot of people, particularly nutritionists--
Q: Well, he thought people practicing in hematology also.
Conley: One of my medical school classmates was Bob Williams, and his father, R. R. Williams, was the man who isolated, identified and synthesized vitamin B1--thiamine. Dr. Williams had been in the Philippines, where he--he was not a physician-observed nutritional deficiency and became very interested in it. He came back to the United States and maintained his interest in nutrition. My recollection is that he was director of the chemical laboratories of the Bell Telephone Company. He lived in Summit, New Jersey and had a laboratory over his garage where he was doing his nutrition research. I had met Dr. Williams, actually we sailed together for several days, so I had a chance to talk with him. He was sure that nutrition was the key to disease and that we would find a vitamin that would be curative for everything. Not one vitamin that could cure everything, but that we'd find multiple vitamins, that disease had its origin in nutritional deficiency, and I think many nutritionists have had that feeling.
Q: But you don't think this might have been a view held by people practicing as hematologists?
Conley: I don't think so. When you talk about practicing hematologists, that's something else again, because there weren't very many people who were designated, or considered themselves to be practicing clinical hematologists. There aren't very many people now, who practice hematology apart from oncology. As a clinical specialty, hematology, I think, is concerned mostly with the treatment of oncologic disorders. Initially, hematologists were the persons who used nitrogen mustards and folate antagonists in the treatment of leukemia and lymphoma. As chemotherapy became more elaborate and complicated, oncology split off as a separate specialty. Most neoplasms are not hematologic ones.
Q: Would it be fruitful to talk about the split between oncology and hematology as well as some of the other areas that--that ASH seems to have not had as much influence in as might have been suggested by some of its members? Perhaps together as a most definite topic of discussion. This time just continue with talking about the early training in hematology at Johns Hopkins.
Conley: Progress, of course, has its perils and disadvantages, but you can't complain about progress. It was possible in Dr. Wintrobe's day, to know all there is to know about everything, that touches on hematology. I told you that when I began, we could review the total hematologic literature--surveying all the journals across the world--in one meeting a month. Now you can't do that anymore. So a hematologist was expected to know about blood banking and how the blood clotted, and how to take care of patients with leukemia or polycythemia or anemia. But as knowledge evolved, there were a number of mitotic divisions.
For example, blood banking split off quite early on. What made blood banking become such a specialty? Several things, the existence of the blood bank per se. You needed a unit where blood was stored and somebody who knew how to handle it. But then blood bank serology became very complicated following the discovery of the Rh factor and the cause of erythroblastosis fetalis. When I was a medical student, there was a prize given to the student who wrote the best paper on erythroblastosis fetalis. Of course there wasn't anything to write about. And then we suddenly find the cause of what was previously an untreatable and fatal disease. In the mid-1940s the Coombs test, which made it possible to detect antibodies that previously had been undetectable, made cross-matching a science, and made it possible to detect all kinds of allo-antibodies that previously had not been recognized. So blood banking rapidly became a special field. And because it was largely a service function, it tended to become more divorced from academic medicine than other branches.
Q: But there were certain connections in the sense that you had co-fractionation for the, within the blood component.
Conley: It was the plasma that was fractionated. Dr. Cohn was the one who fractionated liver extract that Dr. Minot had found effective in pernicious anemia. It was Dr. Cohn who did the early fractionation of the plasma. So that's another aspect of hematology that was developing quite independently.
Q: Is the fractionation of--?
Conley: Yes. The fractionation of plasma. I don't know how Dr. Cohn got to be the first chairman of the NIH Hematology Study Section, because I would not have thought in that period that plasma fractionation would have been thought to be primarily hematologic.
Q: He also wrote the first article published in Blood-
Conley: He was a very important figure.
Q: He was apparently personal friends with George Marshall who for a year was President of the American Red Cross and during that time made various connections in Washington.
Conley: Well Dr. Cohn was very well connected; there was no question about that. He was a force unto himself.
Q: How much do you think, what role you think that plays, the connections that people have and the sources of funding that people have as opposed to solving problems of diseases or pathologies.
Conley: I don't think you can draw any conclusions, any generalizations about that. Some of the most humble people make the greatest discoveries. Look at Dr. James B. Herrick. You know his name, you know what he did? A practicing physician, he discovered two new and important diseases within two years: sickle cell anemia and myocardial infarction. That had nothing to do with his connections. He was just a very astute clinical observer.
Q: But in the sense of people coming to, at a later stage, coming to see themselves as hematologists or belong to a society of hematology, what would you feel would be more important, the sorts of connections that people had or the sorts of research that they did?
Conley: Well I would like to think that in academic medicine, certainly in a place like this, research accomplishment would be very important. I can't imagine that political connections are vital.
Q: We, go back to the original question that you raised. How did Cohn become head of the NIH session?
Conley: He was a very dynamic person and he was doing important things. His ethanol fractionation of plasma proteins was new. This was exciting work. How he got to be the chairman of the study section. Why wasn't Wintrobe the first chairman of the Hematology Study Section? Here was a man who was known around the world as a great hematologist but that didn't happen that way. I have no idea how that all worked out.
Q: What sort of relationship was there between Wintrobe and Cohn, do you know, at that stage?
Conley: Well I suspect there wasn't any. I doubt that their paths crossed very much. But I don't know.
Q: You were saying in a once monthly meeting, the sum total of literature published on hematology could be covered. Where this literature might be found? In the Journal of Clinical Investigation?
Conley: We reviewed all of the general medical journals, of which there were relatively few in those days, the important foreign journals as well as American ones. Scanned the titles, picked out papers that seemed pertinent to hematology. Each member of the group was assigned a group of journals. And then we could scan these or review them in detail, depending on their importance, in the course of a meeting. In this way it was possible for us to be really broadly knowledgeable across the board in hematology.
Q: So you must have had some knowledge of what goes into hematology. Would it cover things such as blood banking? Would it cover work in sickle cell anemia?
Conley: Oh yes, we tried to cover the waterfront. And it was reasonably possible. You know when I was a medical student; we all read original papers with great excitement. I remember reading Dr. Castle's papers when I was a medical student. But few medical students read an original paper now. That's not exactly fair. But the fact is that medical students now complain about reading textbooks. They all demand handouts. They want a summary. The infinite detail is so overwhelming that everything has to be condensed. And that's a fact of life. There is just that much more to learn than there was, and I guess I'm glad that I had my career when I did and didn't have to contend with this enormous morass. I think it was rather fun being broadly based which no one can hope to be now in the same way. I don't think in this medical school or any other, it's any longer believed that the traditional three-legged stool is feasible. You just can't do that. You're going to have people who do basic research, and you're going to have clinicians, who are going to talk to each other, but they are not going to be equally competent in each other's fields.
Q: What would have been the hottest areas in hematology, let's say, when you first began your tenure as head of the division here?
Conley: The quest for the missing agent in pernicious anemia. Vitamin B-12 was discovered in 1948. And that was soon after I arrived, and so I got deeply involved in vitamin B-12 research. We had a huge hematology clinic by then, with I guess more than a hundred patients with pernicious anemia. I for a number of years was the Secretary of the Anti-Anemia Preparations Advisory Board. When liver was used to treat pernicious anemia, you remember that Dr. Minot gave a diet rich in liver. And then Dr. Cohn by 1929 had produced a fraction which was infinitely more potent. But it took from then until 1948 to find out what it was in liver-- that turned out to be vitamin B-12. One of the reasons that it took so long was that the only assay for this material was administration to patients with pernicious anemia in relapse. So the drug companies that sold liver extract had to have their preparations tested. They had to find doctors around the country who saw untreated patients with pernicious anemia who were willing to use this test material to treat their patients. They would give an injection every day and if the patient got what we considered being the optimal reticulocyte response then we would, as a board, approve. The data would be submitted to this board on which Dr. Castle, Dr. London, Dr. Bethel, others and I were members. I was the secretary so I handled the paperwork, would review these data and if the patients responded optimally, then we would approve the preparation.
Q: This was a nationwide society?
Conley: It wasn't a society. It was a board of the US Pharmacopoeia. But there was no other way. No animal assay.
Q: Who originally organized this board?
Conley: I can't tell you. It was organized by the United States Pharmacopoeia. I presume it was done in the 1930s but I really don't remember. It was very much a going concern when I joined. But every patient who was treated with liver extract received USP liver extract which was designated in units. One unit was that amount which, when injected daily to a patient with pernicious anemia in relapse, produced an optimal reticulocyte response. So you see, I was very interested in pernicious anemia and when B-12 became available, we were among the first investigators to be provided with vitamin B-12 and specifically with radio labeled vitamin B-12. We did the early experiments on the absorption and excretion of vitamin B-12. The observations that we made here on the urinary excretion of B-12 formed the basis for the so called Schilling Test.
Q: Was Hopkins one of the few sites where actual pool of patients was-
Conley: No-- you see you had to have untreated patients. Our pool consisted of patients who were treated. Patients came in every month to get their injections. For the assay you had to have new patients who came in with anemia. In those days, you did not get informed consent. You just went ahead and gave the stuff. The drug houses, of course, were scouring the countryside trying to find doctors who were willing to do this. And if the doctors were willing, then they were paid so much for doing it. And when a patient with pernicious anemia came in, they'd notify the drug house. The material would be provided and they would submit the necessary forms to the USP-- to our board which would then certify the preparation as being up to snuff.
Q: Were you primarily responsible for organizing this pool of patients?
Conley: No, No, No. All we did was receive the data.
Q: You just received the data? And this was something--
Conley: Yes, the drug manufacturers had to find the doctors who would test the material, get the results and submit them to the board.
Q: But they were doctors at Hopkins--
Conley: No they were doctors anywhere. No one institution would see enough patients with pernicious anemia --
Q: So the data that you had came from everywhere?
Q: What would be some of the other areas of early concern? You had pernicious anemia, you have--
Conley: My personal situation was that I suddenly became head of a non-existent division with no training in this at all. There was no hematologist here. So I had to really learn by doing. And this is one of the few places where that could be done, because we had such a wealth of clinical material and such a close inter-relationship among doctors. There was no jealousy, and I was welcome to see anyone who came along. Very quickly, I built up clinical experience. And with every new case that came along, I was quick to read the literature. I had to. Not just a textbook, to really read original papers. And in doing this, of course, my curiosity was wetted. Instead of being as a current investigator would almost necessarily be, having interest confined within narrow limits, my interests were very broad. So I was involved in all kinds of things.
Q: Did coagulation remain--
Conley: That was my primary interest for, oh, five years, I guess. But then my colleagues who came along and I had some very distinguished ones, took over and increasingly did the work and finally supervised it. I became less and less the authority on blood coagulation, to the point where in recent years I have been totally out of it.
Q: What was some of the early work you did in coagulation? There was work for example in hemorrhagic--
Conley: Well the very first paper that we published here was published with William I. Morse, who was here as a fellow in general medicine working in the outpatient department. I met him and asked him to come and work with me in the laboratory and he did. We discovered that in doing the prothrombin time test, the non-specificity of the test was such, that there was no way to compare the results of a test done here with the results of a test done at the Mayo clinic. This turned out to be very important, and has been, in very recent years, re-emphasized so that now in Europe, in particular, a standardized thromboplastin preparation is used. But that was the first thing we did.
And then we became very interested in patients, I've already mentioned our studies of how blood clotting was initiated, and the discovery of a plasma factor that we did not identify but was involved with surface induced clotting reactions. We became very interested in anticoagulants that occurred in the blood of patients, and discovered what came to be known as the "lupus anticoagulant." That's had quite a big flair in recent years. So these turned out to be important things that we were doing, diddling in the laboratory, with our hands and a few test tubes. And that's the way it went.
And then as times became more sophisticated, we did more sophisticated things. Dr. Robert C. Hartmann, who was actually the first fellow who got paid to be a fellow, carried on a lot of coagulation research. He was interested in the role of platelets in coagulation and other things. In his era we discovered the anti-heparin activity of the platelets, later designated "platelet factor 4." He went on to become head of the Hematology Division at Vanderbilt. His successor in coagulation was Dudley P. Jackson who continued, and was very important in demonstrating that living platelets, that is to say, metabolizing platelets were necessary for haemostatic function, and that dead platelets or platelet fractions were no good. And that was an important-
Q: Did he work with radiation injury?
Conley: Yes, he produced thrombocytopenia with radiation and then showed what it took to correct the hemorrhage, and nothing short of living platelets was any good. At that time, various people were giving ground up platelet extracts and all sorts of things and claiming that they worked. In fact, they don't. So that was a very important observation that Dudley Jackson made. And so it went. Dudley Jackson was here for quite a few years and went on to become the Chairman of the Department of Medicine at Georgetown.
Q: You mentioned earlier that you did some of the early work on circulating anticoagulants that was later, later had, or more recently has a greater interest in lupus for example.
Conley: An anticoagulant as a cause of a defect in blood coagulation had rarely been reported when we came along. I think there were no more than three or four reported cases in the world. We discovered that one of our hemophiliacs had one of these anticoagulants which is now thought to be an antibody. But at the time that we discovered it, there were only two published reports documenting this. And there was no report of the anticoagulant which is now known as the lupus anticoagulant which we discovered, which had different properties.
Q: Interest waned or never picked up on this until--
Conley: Oh no, it's attracted interest all along the way. But there has been a great flare of interest recently. The lupus anticoagulant is very well known. There is enormous literature on it, but I don't think many people remember where it was discovered. That was a long time ago.
Q: Would you like to say some more about it?
Conley: No, we discovered it and described it, and I became very interested in lupus. Lupus was a little known disease back in those days and the discovery of the LE [Lupus Erythematosus] cell at the Mayo Clinic is what crystallized interest in lupus because it facilitated diagnosis. And so in this institution, we very rapidly accumulated a large number of cases. I studied the hematologic aspects. We did the so called LE cell preparations in our laboratory and in fact invented a new and improved method for demonstrating LE cells. The big monograph on lupus that really brought clinical knowledge together was co-authored here by Dr. Harvey and a group of his associates including me. I wrote about the hematologic aspects.
Q: When was that monograph--?
Conley: That was published in Medicine, in 1954.
Q: So once again this is interest in doing research that arises from clinical concerns.
Conley: This has been my life. Having questions asked by patients that we go to the laboratory to answer. And I lived during an era when it was possible to do that.
Q: Do you think that's how hematology developed in other settings?
Conley: Oh, I think there's no question about it. That that's how it evolved, and it was possible in hematology, more readily than in other fields to do this.
Q: The work for example of Dudley Jackson on radiation injury, where did his interest in radiation injury come from? Was that from World War II?
Conley: He was graduated from medical school after World War II, but that was a time when all young physicians had to do military service. He was lucky enough to do alternate military service with Gene Cronkite.
Q: At ________________?
Conley: Cronkite was then in the Navy. So that's where he did the radiation work.
We had a large population of patients with sickle disorders, so I followed with very great interest the discovery of Linus Pauling's group of the electrophoretic abnormality of the hemoglobin. We were desperately anxious to use his methods. But between 1948 and 1952 the only person who could do this, really, was Dr. Itano, at Pauling's laboratory. And they used the tremendous Tiselius apparatus which meant very few specimens could be examined.
Then Ernest Smith in 1952, came to work with me as a fellow. Ernest Smith had had no prior laboratory training or experience at all, but he knew about the work Henry Kunkel and his colleagues had done on zone electrophoresis using filter paper. I had been to talk to our biochemists here, to chemists at Homewood, trying to develop a method by which we could do what Pauling's group was doing. They all shook their head, they didn't know what to do. And this young fellow with his own hands built electrophoresis tanks out of plastic. We put together a Heathkit apparatus and in no time at all were able to electrophorese hundreds of samples of hemoglobin with much more beautiful separations than you could get with the Tiselius apparatus. That led to one important discovery after another. Any number of new abnormal hemoglobin was discovered here. We found that hemoglobin C involved two percent of the black population. We described the clinical syndrome produced in persons who were heterozygous for both hemoglobin S and C. So this was a very exciting period here.
Q: How was the program in sickle cell anemia research set up then?
Conley: It was initially a clinical program. But when Dr. Smith came as a fellow, he built this little apparatus. It didn't take as much room as this desk top. But it was marvelous. You just take drops of red cell hemolysates, and you could put a dozen of them on a single strip of filter paper, turn on the current, and four hours later you had these perfectly beautiful separations. We had people coming from all over the world to see this, you know. It was so simple. But for four years it hadn't been done.
Q: And the prototype for that was the Tiselius apparatus?
Conley: The original apparatus that was used by Itano in Pauling's laboratory was this big Tiselius apparatus. That was how electrophoresis was first done.
Q: So where did Smith get his ideas for it?
Conley: From Henry Kunkel's publications. They were separating serum proteins. The method was there, but it just hadn't been applied to hemoglobin. By the time the method was published, we'd had a tremendous experience in discovering new abnormal hemoglobins including a very important one that was called Hopkins II hemoglobin. It was the first hemoglobin that was not produced by a gene that was allelic with hemoglobin S. And that was the first evidence that there were two genes involved in hemoglobin synthesis. It turned out that there are two polypeptide chains, the alpha chain and the beta chain, determined by two non-allelic genes. But the first convincing evidence for that was the discovery of Hopkins II hemoglobin in a family in which there was also hemoglobin S. These two hemoglobins did not behave as alleles.
Q: On the methodological side, did the electrophoretic apparatus then diffuse back to biochemistry and chemistry departments here?
Conley: Oh yes, that method and subsequently its variants came to be extremely important across the board in enzymology and all kinds of protein analysis.
Q: So this is a case where clinical science actually _________ in basic research.
Conley: Oh, yes. Henry Kunkel was an eminent immunolologist. As a matter of fact, when I was the chairman of the Hematology Studies Section, he was a member. He would never have called himself a hematologist but his contributions to hematology were very great. And that's what hematology has been like, you see. Quick, who invented the prothrombin time, was in no sense a hematologist. He didn't know anything about anemia, I don't think, or leukemia. Warner, Brinkhous and Smith, who invented the two stage method for measuring prothrombin were pathologists at the University of Iowa. Brinkhous became the professor of pathology at the University of North Carolina.
END TAPE ONE, SIDE TWO; BEGINNING OF TAPE TWO, SIDE ONE
Q: Dr. Conley, we've been talking about how hematology was defined in your early years as head of the Division of Hematology at Johns Hopkins. I was wondering if you could perhaps recount some of the early split-offs, people who might have been considered as important to blood work, but did not end as hematologists.
Conley: In the 1940s, hematology encompassed all of what is now oncology, I think you could say, except surgical practice. The few chemotherapeutic agents that were then available were managed by hematologists. Blood banking, to the extent that it was academic, was done by hematologists, but it was not largely an academic specialty in those years. The performance of routine laboratory tests was handed down as medicine advanced from pathologists increasingly to hematologists. Then as developments took place, blood banking evolved as a very large clinical service, and the blood bankers were predominantly non-academic. They were providing blood and not terribly interested in hematology apart from that service function. There were, of course, distinguished persons studying blood group serology and that sort of thing, often not directly related to operating a blood bank.
As laboratory medicine developed, clinical pathology developed as an increasingly important branch and clinical pathologists took over the laboratory aspects of hematology that formerly had been done primarily by pathologists. So clinical pathology became a specialty within pathology. As that happened, hematologists began to lose a lot of their livelihood because hematologists prior to that time had been the physicians who ran hematology laboratories. In Baltimore for example, a distinguished physician had his laboratory to which his internist colleagues sent their patients for blood cell counts and various other tests. He was not a clinical pathologist; he was an internist, himself, a hematologist. So that the clinical pathologist increasingly took over routine laboratory work, to the very great distress of hematologists. And of course, it threatened their livelihood. It made being a practicing hematologist much less lucrative than it had been.
Q: What years would this have been?
Conley: This was, I guess, well under way in the 1950s and had reached crisis proportions I think in the 1960s.
Q: But you've already had NIH study sections on hematology itself. What role did the NIH play?
Conley: Hematology, as the queen of the sciences, evolved as an academic specialty. And the noted hematologists that became known around the world were academicians. They were doing laboratory research. Although some laboratory research in early years was relatively unsophisticated compared to present day investigation, it was very important in revealing scientific principles. And it became increasingly sophisticated to the point now where many of the people who're doing the very finest laboratory research never see a patient. They don't know very much about hematology outside of their own very special fields. That has been the big change. Hematology was a significant clinical specialty, particularly after Dr. Wintrobe's textbook was written. Now I think of hematology as an academic specialty, really, i.e. hematology apart from clinical pathology and apart from oncology.
Q: Once again, is that a creation of the NIH for example and their funding policies or is a creation, more of the content matter of study?
Conley: There is absolutely no question that the availability of funding has made this remarkable research achievement possible. What happened in hematology very early on, was that hematologic research was really very basic science oriented whereas in gastroenterology or cardiology, it was mostly clinical studies. The NIH was very excited about funding basic research, which hematology increasingly became with the discovery of coagulation factors; the better understanding of how blood clotted; the serology of the blood groups; the abnormal hemoglobins; all of these things opened whole new fields; for literally swarms of investigators to do very important basic scientific research, which in fact, in many instances, had implications that ranged far beyond clinical hematology. So this gave hematology a great advantage, really, in competing for research funding and for making great scientific contributions. It's no accident that in mid-century, many chairmen of department of medicine were hematologists, despite the fact that hematology as a clinical specialty is minute in relation to gastroenterology or cardiology.
Q: You're saying this was because of the influence of the basic research--
Conley: Because these people were doing research and medical schools wanted people who were doing productive, innovative research and these were hematologists. So look, who were the chairmen of departments of medicine? UCLA, there was John S. Lawrence, a hematologist of great distinction in that era. Max Wintrobe became chairman of the department at Utah. Charles A. Doan, chairman of the department at Ohio State, a noted hematologist. Carl Moore at St. Louis. Who else. Any number of people. Sydenstricker at Georgia, he was a great pioneer of the study of sickle cell anemia. And I'm sure many others that don't come to mind.
Q: Well there is Lawrence Young.
Conley: Lawrence Young, of course, at Rochester, a very important figure whose work on hemolytic anemias, particularly hereditary spherocytosis, made him famous. So these were all people who were doing very creditable laboratory research. And it was hard to find people in other branches of clinical medicine who were equally pushing forth the frontiers of science, you may say. So this is why hematology was the queen of the clinical sciences in that era.
Q: And yet there are areas that go beyond the realm of hematology itself. We're talking about blood banking, which does not go into, reach into the academic niche that hematology found, but also areas such as oncology.
Conley: Well, oncology, of course, has evolved much later than clinical pathology and was the next great threat to hematologists. As soon as tumors other than hematopoietic neoplasms were being treated by physicians other than surgeons, oncology opened up as a special field. Oncology was initially done by hematologists but then rapidly expanded beyond hematology. And oncologists, in many instances, in most instances I think, are not primarily hematologists. I think there was a big split, and so classical hematologists, the people who were investigating anemias and treating non-oncologic disorders, don't have very much left. So there are relatively few hematologists, classic hematologists, who are now practicing.
At the annual meeting of the American Society of Hematology, a group of these people get together and rub their hands and sympathize with each other. But the fact of life is that there is no way to change this. It's the nature of the beast. So oncologists and hematologists have joined hands and they have now overlapping specialty boards. In many programs there is an effort for oncologists to learn some hematology, and hematologists to learn some oncology. But in the terms of the practice of clinical medicine, outside of academic medical centers, the practice is oncology and there is little opportunity for a non-oncologic hematologist to survive.
Q: Do you think this has something to do with the government funding through their war on cancer from the '60s onward?
Conley: I think hematology is an academic specialty. And I would not personally advise a young physician to join the hematology training program in an academic medical center that was not oncologically based, unless he planned an academic career. There is a tremendous opportunity for research in hematology. And if you plan an academic career, then hematology is a rich, promised land.
Q: It seems that this split between hematology and oncology didn't extend as far as pediatric hematology, for of course, you still have to deal with leukemias.
Conley: I think that's true. I think it has been possible for pediatricians, for pediatrician hematologists to cover the waterfront more satisfactorily because of the relative rarity of pediatric neoplasms and the more uniformity of their approach.
Q: So you would see this split coming more from the growth of knowledge, so called, rather than--?
Conley: Yes. The impossibility for any one physician to have sufficient expertise across the board, to handle these things well. Now classic hematology has also undergone mitosis. So a specialist in blood coagulation, the real contributing specialist, really is not likely to know very much about treating leukemia nowadays, or running a blood bank for that matter.
Q: What about the programs in sickle cell anemia, also, is that another area that's--?
Conley: There are several types of programs in sickle cell anemia. When Nixon was President, he designated sickle cell anemia the disease of the year, and Congress was pressured to make the funds available, not only for research in sickle cell anemia but also in patient care programs, the establishment of sickle cell centers and clinics which were primarily related to patient care.
Q: Did research money, however, flow to--?
Conley: There was research money, but hemoglobin research was progressing apace, without that. Nixon in his speech when he announced this said that we, I don't remember his words, had been shamefully negligent in supporting research on sickle cell anemia. In fact, at that point this was one of the most exciting research areas there was. And things were moving along very rapidly. Investigators, who were studying abnormal hemoglobins, were being generously funded, because that was a very promising, productive area of research.
Q: But you don't mean to move research monies away from--?
Conley: There is no question that the availability of funding for sickle research brought people into the sickle cell research area who hadn't given sickle cell anemia a thought before. So x-ray crystallographers, who hadn't thought a thing about sickle cell hemoglobin, or didn't even know about it, suddenly were very interested in studying the crystal structure of polymerized hemoglobin S and so forth.
Q: Was there any sense that hematologists lost out in the race for funds?
Conley: Oh no, I don't think so. I think that for hematologic research, across the board, there has been no shortage of outstanding investigators. And I think that hematology has been generously funded. Now, let me put it this way. That to get funded to do hematologic research, you have to do very good research. If you're doing cancer research, it doesn't necessarily have to be that good. I think that's a fair statement. I think there's been lots of money to support cancer research of a nature that would not have been funded, research of the same character wouldn't have been funded for hematologists. Which means that you can't be funded as a hematologist to do a clinical study of pernicious anemia or that sort of thing. It's increasingly sophisticated research. But I think people who are doing good, sophisticated hematologic research are probably doing pretty well. I think that if there is any criticism, it would be the support of less good research in other areas which have a great appeal because of the popular concern about such diseases as cancer and heart disease.
Q: Could we go back to your experiences at Johns Hopkins, in light of these last comments, and talk about the genesis of the hematology program here.
Conley: I didn't have any prototype to follow and I did what came naturally. I told you that I became interested in research in coagulation as a pastime and it was great fun. And it was productive. As new things came along I tended to ask questions and either to get involved myself or to get other people involved. And so as we evolved a training program that was inevitably research oriented. I've never had a clinical training program. So that every young physician who came to work with me knew before he came that he was going to be involved in a research program and he knew what he was going to do. In other words before he joined the group, we had selected some research activity. And this worked out extremely well, as you can see from what happened to these trainees.
What impressed me was that if you had very good people, they did not have to have six weeks in the blood bank, six weeks in the coagulation laboratory, six weeks here, which is now almost required by the boards. If you have an acceptable program now, you have to do this sort of thing. This is one of the reasons why I was opposed to boards, because I didn't want to have a standardized program. We were doing very well with our program. And as I told you, Dudley Jackson who came here to do coagulation research, ended up as Chairman of a Department of Medicine. Julius Krevans not only became Chairman of a Department of Medicine, but now is Chancellor of the University of California at San Francisco. So these people did all right. Sir David Weatherall, who did superb hemoglobin research here, is Nuffield Professor of Medicine at Oxford and the Editor of the two volume Oxford Medicine.
So you see I didn't have any reason to think that there was anything defective about my program, in terms of clinical training. These people were very good people and they did very well. So I was not only not impelled to set up a rotational program, where the fellows would be assigned here there and everywhere in sub-specialties of hematology, but I fought against it, because I thought it would destroy our research program.
Q: I guess the experience of David Weatherall might be a good case in point for this--
Conley: David Weatherall is a good, is a fine example. We had similar ones. They haven't all reached his distinction, although some of them are quite distinguished. David Weatherall came here with virtually no research training. He made use of our clinical resources and the hemoglobin research program that we had set up. But he also made a close affiliation with our bio-physics laboratory, Howard Dintzis and his people.
What Howard Dintzis had done was to study the assembly of the protein molecule to show that the amino acids are added in sequence to ribosomes. Well how did he do that? He used reticulocytes. And why did he use reticulocytes? Because Irving London, years ago, was studying heme synthesis. And he found that when he added N15 labeled glycine to the blood of normal people it didn't get incorporated into heme. But when he did this to the blood of patients with sickle cell anemia it did. This led to the discovery that reticulocytes synthesize hemoglobin. So reticulocytes all of a sudden become a treasure, because now you have easily available cells that synthesize protein. And so they were used by all kinds of people who were studying the nature of protein synthesis. David Weatherall went over and learned the techniques, used their facilities and resources. This is what I like, an open ended division with collaboration, and we've done this many times. He couldn't have learned that from me, certainly, or from anyone in our division. But in a great university, this is what's good. This is again why I detest an enclosed program.
Q: He also came in originally on his initial fellowship to work with--
Conley: He joined Victor McKusick's group but he immediately discovered that if he was going to do what he wanted to do that they didn't have the resources. So he transferred in just a few months to our division. And he did collaborate with Ned Boyer who is a member of the genetics division but all of his subsequent work was done here in this division and with collaboration of Dintzis's group. He set up some of the techniques here. He was a very hard working, very intelligent, very ingenious worker and his productivity is even now incredible to me. With the responsibilities he has, I don't know how he does it all. But he started out doing it here at a great facility.
Q: Which techniques did he bring from biophysics?
Conley: He learned out to incorporate radioactively labeled amino acids into evolving hemoglobin molecules, to feed amino acids to reticulocytes. And that led to the study of hemoglobin synthesis in thalassemia. His monograph on thalassemia was largely based on his experience here. The book was published after he went back to England, but the work was largely done here.
Q: You said there were other examples similar to Weatherall who would serve to shape this picture of hematology being this hybrid discipline and formation.
Conley: Ronald Rieder did pretty much the same thing. Ronald Rieder is now Professor of Medicine and Head of the Hematology Division at Downstate. He had had no training in hematology until he came here. He learned some things from David Weatherall but also from collaboration with others including Dintzis's group and went on to make significant discoveries. Many of these fellows have been rewarded by election to elite research societies, the American Society for Clinical Investigation, and the Association of American Physicians, which I think reflects their accomplishment.
Q: Did Oscar Ratnoff also have similar type role?
Conley: Oscar Ratnoff was in medical school with me. I knew him slightly as a medical student. Actually he was a class ahead of me, although he is a year younger than I am. He's very precocious, I guess. He lived in New York, so he did not live in the medical student dormitory, and I didn't get to know him well. But then when he joined the army, which he did after I did, he was also assigned to Randolph field, to the altitude training unit. We got to know each other very well then, and we thereafter kept in contact with each other. After the war, he came to Hopkins sometime after I had been here and joined the division that was newly headed by George Myrick, which was called the Biological Division, but really was the microbiology division.
Oscar looked with great interest on what I was doing, and although he published a paper or two from the Biological Division, he spent most of his time working with me. This was after I had done the work on surface contact and he got very interested in that. We published a number of papers together here. I think this is where he really got firmly established in coagulation research. He's a brilliant scholar and he went on to Cleveland, and has continued this work until this very day. He has a lifetime scholarship that supports him as long as he wants to work in research. He's been very fortunate that he's been able to devote his professional life to research, which he's done with extraordinary productivity. I can't count him as one of my fellows, because he was a fellow in another division, but the fact is that he spent most of his research time working with me. And we did some rather significant things together.
Q: Was there a point at which, as you began to acquire more knowledge of the hematologic field itself, that you looked for models, research, clinic relationships at other universities? Were there other prototypes for what you were doing, or did you feel confident that what was unfolding at Johns Hopkins was--?
Conley: I think our program was a little bit off beat in its unstructured nature, that we never had clinical fellows, that everybody who came's primary responsibility was to do research and anything he learned beyond that was sort of incidental. But the wealth of clinical cases was well-organized in a hematology clinic with just unbelievable patients. In a few months we would see more of everything than most people would see in a life time. Really, it was like that.
One of my interests in life from the word go, has been the study of the natural history of disease, so I never let go of a patient. I'm still seeing patients that I first saw 40 years ago. You learn a great deal by doing that. Even now I have a clinic where current residents work with me. I see new patients, but most of the patients are old patients, many of whom I've been following for years. There is no better way than that to learn about the natural history of disease.
Q: Was this; is this a concept that you feel that you have played an important role in developing? Is it a certain approach to organizing the department of hematology for example?
Conley: I don't think I've had very much influence on other training programs.
Q: You wouldn't think that Hopkins has played a role in say colonizing or organizing other younger hematology departments, as fellows leave from here and go elsewhere, and they carry forward a Hopkins model or a Hopkins approach?
Conley: Well, it's hard to generalize on that. We've had diverse people, who've done really quite different things. Oscar Ratnoff, for example, I'm sure held on to all of his coagulation type patients, as long as he's able to. But he didn't originally head a division as such across the board. David Weatherall has very broad interests. After all, he's a chairman of a department of medicine. He's interested in everything and he's made significant contributions in fields rather far removed from hematology. He's a geneticist of very great distinction. But if you ask me does he follow up his patients forever, I simply don't know. I don't know how they work.
It's much more difficult for us to do it now. For example, the marvelous hematology clinic that I formerly directed withered away when they started charging big fees for patients to come. So as soon as patients had to pay a large fee to come here to get their treatment for pernicious anemia and they found they could get it from their local doctor at a fraction of the price, they disappeared. So we don't have any patients coming here now to get their monthly injection of vitamin B-12. But for many years we did. Sam Charache, who's taken over the abnormal hemoglobins, still follows many patients with sickle cell anemia and they are still used for research, because he has an experimental treatment program. But it's more difficult than it used to be. Teaching hospitals such as this, years ago didn't have to pay the minimum wage. A lot of the people who worked here were in effect volunteers, including very educated people who came here to work for the fun of it, or worked at very low salaries because they liked the work. That's all changed now, of course. People expect to be paid and you have to pay big salaries for people who aren't necessarily as talented as some of the people we formerly had. Patients do have to pay or have to be paid for. So we can't have patients coming back primarily for our education.
Q: So the approach of upholding this philosophy of natural history of disease actually belongs to a different type of work organization, hospital structure, than could exist today?
Conley: Well, theoretically the HMOs should be able to do this extremely well, but whether they will or not is the question. I have my own detailed clinical records quite apart from the hospital records. Some of these records, I have cabinets full of them, are very thick and so every time I see a patient, the notes in succession are added and then on the front of the chart I have a flow sheet, so that I can quickly look back. When fellows or residents see one of my patients for the first time they can quickly follow the course of the patient's illness. And they find this very instructive because they see patients with important diseases who never get admitted to the hospital, patients that they wouldn't ordinarily see. In a snap shot view, they can view the life history of a patient's illness.
Q: If we could switch gears somewhat--
Conley: I'm afraid we've been doing that right along.
Q: And talk about first year associations with the National Institutes of Health (NIH) and what role this played in shaping a hematological field or discipline.
Conley: I've had continuing associations with the NIH up until the time of my retirement, when I decided I didn't want to do any of that anymore, because I had done so much of it in my life. My first association with the NIH was when I received my first research grant in 1948. And then thereafter, I was continuously funded for research in blood coagulation, and for research in sickle cell disease, and abnormal hemoglobin. I had a training grant when they became available. In 1952 I first became a member of the Hematology Study Section. I will point out to you that I came here as a fellow in 1946, and in 1947 was by appointment the Hematologist in Chief without any prior experience or training. Then in 1952, I was a member of the Hematology Study Section.
Q: What went on the Hematology Study Section?
Conley: This was where grant applications, bearing on hematology were reviewed. The Hematology Study Section was very important to me primarily because it brought me into intimate contact with the other members. The Study Section would meet and review ponderous research grant applications, usually over the course of a couple of days. We would have to spend the night in the vicinity. When I first went to the NIH, the Clinical Center and other large buildings hadn't been built. We used to meet in a hotel in Washington. So we had a rather intimate relationship with the other members of this relatively small panel. The members of the panel were largely very distinguished hematologists, whom I had a chance to meet. When I joined the Hematology Study Section, Carl Moore was the chairman. And such people as Larry Young and Max Wintrobe and Bill Castle, and many other distinguished people served on this rotating board. I think the period of appointment was four years, so in the course of four years, I got to meet many of the leaders in academic hematology. This was great for me, having started without contact with other hematologists. I got to know these people rather personally from these contacts. And I think having a panorama of research before me, as these research grant applications were presented, was very instructive. I got to know what was going on in the world.
Q: Was there a common scope as to, common vision as to how hematology should develop as a field, held by people in this--?
Conley: No, I don't think at that point that the Hematology Study Section was regarded as any kind of a policy forming group. But the Hematology Study Section critically reviewed the applications. Each member of the study section secretly graded each application with a number. These numbers were averaged and then each application was given a rank score, which was basically the average of these grading. It was very well done.
Q: But there still must have been, at least implicitly, some notion of what goes into making up a discipline of hematology.
Conley: I don't think we even considered that.
Q: Is that true?
Conley: I'm sure that was true. We proudly considered that hematology was widely ranging. I think we were pleased that these applications were so very diverse.
Q: Were there any very strong differences of opinion over funding in the early stages, 1952?
Conley: I don't think so. I think that it was in those days, relatively easy to pick out the real pearls, to pick out the really good things.
Q: Would this have been similar at other study sites, in other fields?
Conley: When I joined the Hematology Study Section, the total number of study sections was very small. Maybe half a dozen, I don't know. But nothing like now. It was a very small organization, you see.
Q: And it wasn't required to try to map out where funds should go? It was done much more-
Conley: That was the responsibility of the councils. There were two review groups. The study sections who were the experts, the scientists. The councils included all kinds of people, politically oriented or not. These are political appointees basically. Some of them are physicians or scientists. But a number are not. And they are people who are supposed to have the broad view about funding needs, what kinds of research to support. So it's the councils who would determine where the cut off point would be.
Q: And who have been on the councils in this early stage?
Conley: If you're asking for names, I certainly can't. The Study Section members never met the council members. The study sections would meet, make their decisions and then this would all be passed on to the council that would meet separately. They did not do intimate reviews of the grant applications, nor were they really prepared to do that. But they looked at the big scene. Do we need more research in coronary artery disease, or this that and the other thing? And coagulation research was generally considered to be important because it was related to thrombosis, and anticoagulant therapy was coming aboard. So that was an important discipline. And this was why I was asked to join, because I had done research in coagulation sufficient to attract some notice.
Q: In World War II there was very little research.
Conley: Right, and then it exploded. Exploded. And this was responsible for the explosion of the medical schools. The number of full-time people in this department of medicine at the end of World War II, could be counted on the fingers of one hand, I'm sure. And now there are so many hundreds that I don't know them all. It is like this in every medical school. The NIH is largely responsible for that. Now there are other sources of funding, the Howard Hughes Institute, the Johnson Foundation,-- but those are latecomers. We were supported by other organizations. Our vitamin B-12 research was funded in part by the National Vitamin Foundation, for example. We had support from the Atomic Energy Commission for some of our platelet research.
Q: This would have fit in with Dudley Jackson's work?
Conley: Yes, yes. In those days, you didn't have to do what you said you were going to do. Our early sickle cell research, which was important, was supported by our coagulation grant. But the NIH was delighted because it was productive research. Now they've gotten more restrictive. I think you're supposed to do what you said you were going to do.[laughing] But at any rate, it was a pretty free and easy life in those days. My division was largely supported by research funds. We would not have had a division were it not for those funds.
Q: Was there any input from pharmaceutical houses?
Conley: The National Vitamin Foundation was supported by pharmaceutical houses, by multiple pharmaceutical houses.
Q: Do you remember some of the leading ones that?
Conley: I don't even know. It was a foundation.
Q: You didn't directly deal with the pharmaceutical companies?
Conley: No, but we had a lot of help from pharmaceutical houses. In our vitamin B-12 research, the vitamin B-12 was all provided free. The radioactively labeled B-12 was given to us. The Squibb- Merck people were very helpful to us. But we did not receive funding from pharmaceutical houses.
Q: Was there funding in the post World War II period from the OSRD for example?
Conley: Yes, I was going to mention that next. Apart from my connection with the NIH, I was very importantly connected with the Division of Medical Sciences of the National Research Council. The National Research Council was charged with the responsibility for dispensing research funds from the military to non-military organizations. The Army supported a lot of coagulation research. And I was a member of the Panel on Blood Coagulation. This panel, was made up of the traditional coagulationists--Seegers, Brinkhaus, Quick--and this is where I had intimate associations with those people. We would meet and argue and pass judgment on funding for research in those fields via the military services. That continued for a number of years.
There was a Committee on Blood and a Panel on Blood Coagulation. I ended up as chairman of the Panel on Blood Coagulation, and was also a member of the Committee on Blood, which had broader interests. We sponsored a number of symposia. Very important, for example, were conferences on platelets, which made it possible to bring experts together from around the world.
Q: Would these be mostly people involved in basic research, or were there also representatives from, let's say, industry, from government, from military.
Conley: Well, anybody could be invited, but these were mostly academic investigators, mostly from medical schools. But there was no barrier to having anybody. The military services themselves had research activities. The Walter Reed Institute for Research and the National Naval Medical Center had research programs. That's where Gene Cronkite was. George Brecher was at the NIH. These government institutions were themselves involved in hematologic research and their representatives participated in meetings both at the NIH and at the National Research Council. As funding was largely taken over by the NTH, the importance of the National Research Council in these activities dropped off.
Q: If we could talk about other institutional supports to the new discipline of hematology. I was wondering if you could talk about the journal Blood, itself what role you saw that playing from the '40s onward?
Conley: I think the journal Blood was certainly very important in bringing hematology and hematologists together. Blood, as you know, was initiated by Henry Stratton, who was a publisher, who for some reason was interested in hematology, perhaps because of his friendship with Bill Dameshek who became the first editor of Blood.
[END OF SIDE ONE, TAPE TWO; BEGINNING OF SIDE TWO, TAPE TWO]
Conley: Have others that you've talked to, talked about Dameshek and his important role in hematology?
Q: If you could add something on Dameshek-
Conley: Dameshek was a remarkable man, an imperious presence: at any meeting which he attended, he always sat down next to a microphone and he rarely failed to make a comment on any hematologic paper, any subject. He was really very broadly knowledgeable. These were not unimportant comments. He traveled widely. He got to know hematologists throughout the world. He attracted to his laboratory many young foreigners who worked there. It gave him a sort of international clientele. And when he organized Blood, he made a point of accepting papers from all over. I'm not one of his critics and if you want to read what one of his critics say, you have to read Dr. Wintrobe's The Blossoming of a Science, which I think is perhaps unduly critical of Dameshek. Dameshek certainly made the most of his opportunities, and I think there was a feeling, which I certainly have no reason to support, that in receiving all of these manuscripts, he was pre-informed about things and was quick to write editorials and to get his own people involved.
Q: I've heard such comments.
Conley: I certainly have no information myself. I read this in Wintrobe's book and I've heard other people talk about it. But I think having a journal certainly did help hematology. In 1942, we had a textbook for the first time. In 1946, a journal. So that began to solidify, hematology as a clinical specialty. And most of the original papers were pretty much clinically based. So yes I think Blood has been important.
Now Blood was firmly managed by Dameshek and Stratton for many years, and actually it was about the time that I was the President of the Society when tumultuous decisions were being made. One of them was to take Blood as the official organ of the society. And that was not accomplished without some little difficulty. But in fact, it was ultimately very smoothly accomplished and I think it has worked out very well.
Q: What were the difficulties?
Conley: I think those who had it were not very anxious to let go of it.
Q: Oh, to put it under the aegis of the American Society--
Conley: The American Society of Hematology was not going to take it unless it was the official organ, that the Society would appoint the editor, would appoint the editorial board, would review the manuscripts. And you can imagine that a private journal wouldn't be too happy about that.
Q: Jumping ahead a little bit, would the ASH membership be most likely to publish within Blood or were there other journals just as likely to receive--?
Conley: When Blood first came out, as Dr. Wintrobe points out in his book, a number of hematologists did not submit their papers to the journal because of the feeling that you've heard expressed. But that was long ago. When the proposition was made that there be a society of hematology, this came from the same group from Stratton and Dameshek. At that point, Castle said I'm not going to have anything to do with it. But Hale Ham, who was one of Castle's associates, said let's join them and lick them, or words to that effect. So he got some of his friends to go to the organizational meeting and to play a significant role in how the society was organized, and in constructing the by-laws, and helping to make it the kind of society that it turned out to be.
Q: When was your first association with the American Society of Hematology?
Conley: I'm a totally non-political person, really. I had enough to do to run my own show. I am not a joiner, by nature. I don't go to a lot of meetings. I have never attended a meeting of the International Society of Hematology outside of the United States, for no good reason, except that I just haven't felt, that if I really wanted to learn something, those were not the meetings where really hot new stuff is presented. It's a wonderful opportunity, and I should have taken advantage of it, to meet people and to see various parts of the world. I can now say I should have but I didn't. I did not immediately join the American Society of Hematology, but I didn't have any sense of antipathy.
But when it turned out to be a nice solid organization, I soon joined and then quickly got involved. I was a member of the editorial board of Blood for two periods of service. I was a member of the Council of the American Society of Hematology twice, and ended up as the Vice President and on up to being President. I was obviously very actively engaged in that society not long after it had been established.
It was, at times, a very contentious society for a while. There were meetings at which there were heated debates, in which people called each other names, and in sessions preceding my presidency--not the immediate preceding ones -- it was pretty uncivilized. But then the Society grew up and it's been nothing like that. It's very high class.
Q: Could you recount some of the significant contentions that took place during the early stages?
Conley: I think that there were great arguments over the by-laws. There were great arguments over the extent to which the Society should be involved in politics, in the sense of trying to influence the Congress on issues. There was great agony about the disputes between hematologists and clinical pathologists and that sort of thing, and attempts to resolve those issues through one mechanism or another in the Society. But of course, those issues didn't get resolved. The Society did decide, as most academic societies decided, that they did have to have an input to the Congress. And our Society immediately preceding and during my presidency, employed Mr. Grupenhoff, who was a highly competent lobbyist in Washington to advise us. We didn't even know what was going on. We didn't read the Federal Register. Very important decisions were being made. For example, there was a proposal published in the Federal Register which was going to require that all laboratories that did hematologic tests had to be headed by a clinical pathologist. That would have killed the hematologists.
Q: And this was at the time when there was this contention with clinical pathology within--
Conley: Yes. And it was just by chance that somebody read this. A non-member of the Society called it to my attention. Nobody in our society was reading the Federal Register, you see. So it was clear that we needed somebody who knew what was going on at least to tell us. So that was done very effectively when Grupenhoff was employed. The society now includes clinical pathologists, oncologists-- it has an enormous membership. I think that within the Society, they meet very amicably. But there were some pretty hot times.
Q: Could you, perhaps, go into a little more detail about the content of the conflict between clinical pathologists and hematologists and how it was reflected in this legislation--
Conley: When I learned of the impending regulations and threats to hematologists, I appointed an ad hoc Committee on Laboratory Standards and asked Frank Trobaugh to serve as its chairman. Frank became very aggressively involved with the appropriate federal agencies. Since that time the Society has had strong representation and has wielded a significant influence. Clinical laboratories have come under the close eye of federal regulatory bodies. The Clinical Laboratory Improvement Act was passed in 1977. Clinical Laboratories are now under the inspection of several governmental agencies. Laboratory tests must be standardized, and the qualifications of laboratory directors and medical technologists are set out. For a time proficiency testing was carried out under the supervision of the Centers for Disease Control. I have had no personal involvement with all of this, and I am unable to evaluate its effect. There is still concern about conflict of interest in the operation of certain clinical laboratories, so all of the issues are not yet settled, but the American Society of Hematology now is kept well-informed about what is going on and is actively participating in the decision-making process.
Conley: Another contentious area related to-the development of specialty boards. Specialty Boards were first invented many years ago. My recollection, which may be incorrect, is that the first specialty boards were in tuberculosis and then gastroenterology. After World War II, as specialties developed as hematology did, there was pressure to form other specialty boards. And hematology was a latecomer.
There were many academic hematologists who didn't think a specialty board was a good idea. I was among those most violently opposed. And the reason that I was opposed, was for the reasons that I've already expressed to you. My training program here would not meet the specifications of any specialty board, you see. We did not have an organized training program in which we guaranteed that each trainee spent two months doing this, two months doing that. I thought that as soon as we did that our very successful training program would be devastated. Maybe it's all right to train people that way who are going to go into practice. But in terms of our program, we were training hematologists to lead the academic life, and most of them have done that. And so I greatly feared what would happen if we had boards and a structured program.
Philosophically, it seemed to me that what you want is a physician who knows how to do what he does. If you're taking care of leukemia patients and you don't deal with a blood bank, it isn't terribly important that you know how to run a blood bank. So the idea that you had to be across the board knowledgeable didn't appeal to me, particularly at this time when already knowledge was so increasing that you really couldn't be fully informed in every field. I was opposed to this and so were many of my friends. I told you that Carl Moore had opposed even the formation of an organization, because it would lead to a definition of a hematologist and then to boards. So he was opposed to it.
But the American Board of Internal Medicine, seemed to have it among their objectives to have every branch of internal medicine codified and sub-specialized. There was some pressure from the Board to develop sub-specialty boards. And there was a faction within the American Society of Hematology that wanted a board for one very special reason and, it was political: the feeling was that if we had a hematology board, we could keep out the clinical pathologists. I don't suppose you'll find that written anywhere. But that was a strong feeling. But when this issue was put to vote to the membership of the American Society of Hematology, they voted weightily against supporting a specialty board.
Q: Which in essence meant they were voting still to maintain ties with clinical pathology?
Conley: Well, they didn't want a specialty board and that's all I can say. The membership voted against having a specialty board in hematology, which promptly evolved nonetheless.
Q: Who were the people behind the legislation for putting clinical pathologists at the head of any lab dealing with blood?
Conley: The clinical pathologists and their organization, the American Society of Clinical Pathology.
Q: They had there own lobby? Is that the--?
Conley: Yes, the pathologists, of course, traditionally did hematology, and as clinical pathology evolved, it evolved within departments of pathology. For example, the Department of Laboratory Medicine here is a hospital department, but academically it's assigned to the Department of Pathology.
Q: In your year-end report as President of the American Society of Hematology you mentioned a high frequency of error in clinical laboratory tests.
Conley: Yes, the CDC, had started to send out unknown specimens to laboratories all over the countryside. And then the laboratory did the tests and reported the results. The results of the tests were distressingly frequently erroneous. I suspect that that's been greatly improved. There's been a revolution, you see, in laboratory medicine because of the development of machines that do all the work. So much of what is done now is done by machines.
Q: Also in your report, your year-end report to ASH, you suggested that ASH should be more active in the problems of the blood transfusion field.
Conley: Yes, because I told you that was a time in which the least academic area of hematology was in blood banking. There were great feuds between the American National Red Cross and the American Association of Blood Banks, which was a more profit-oriented organization. The NIH has assisted in developing research in blood banks, and the current situation is much improved.
Q: This was also at the time, at least in the popular press, where there was a lot of discussion about hepatitis, contamination in blood supplies.
Conley: There was no question about that. There was a commercial blood bank here in Baltimore, in a poverty stricken area, where we were buying blood. The people who were contributing the blood were delighted to have the small amount of money they got to go out and buy heroine or what not. It was a disaster. The organization that ran this blood bank tried to set up a branch over in the commercial district, hoping that people would come in, in their lunch time and give blood. It was a failure. It didn't work. People didn't come. The NIH was getting many of its platelets from this place, I don't know how much hepatitis they spread around. But I think there are good data to show that that's not the kind of blood you want to receive.
Q: So, in a sense, during your tenure as president in ASH there seems to have been a shift away from some of the earlier concerns in ASH. You start to have a ________ put on specialty boards.
Conley: I had a very placid year, when one of the big things that we had decided to develop, and were in fact developing, was our relationship with Grupenhoff, in Washington, the person who advised us and served as a lobbyist for us. Grupenhoff knew the congressmen and the senators and was very effective in introducing representatives of our Society to these people so they could explain what our concerns were. There was no question that that was an entry that we simply didn't have and that other groups did have. So I think it was thought by our Society that that was a very profitable investment.
And we were just taking over Blood at that point, and that worked out very well. The conflicts with the oncologists and clinical pathologists seemed to be, not resolved, but of less concern. We took in the oncologists. Many oncologists are members of the Society, as are clinical pathologists. So I don't hear that feud raging anymore. I think it's a foregone conclusion that things are the way they are; that there's no possibility of changing them.
Q: By way of summation I wonder if we could return to one of the questions we asked early on. And if you could, by briefly eluding to the role that the journal Blood played, the text Clinical Hematology other texts, professional societies. If you could, perhaps, talk about the definition of hematology as a discipline. How you would compare the definition of hematology when you first began, back in 1947, until 1980 or so. Compare those two, the transition from one state to another.
Conley: Well, I think a clinical hematologist, who is not an oncologist, nowadays, is either a pediatrician or an internist, who is delighted to see patients with various kinds of anemia or with those hematologic neoplasm that they are privileged to treat. What else do they do? Deal with hemorrhagic disorders and that sort of thing. Often they work in a group practice with physicians specializing in other areas.
Q: The nature of research itself?
Conley: Now an academic hematologist is something else again. An academic hematologist must be an investigator or at least lead a unit in which there are scientists doing basic research. I don't think he's going to get any support for his work if he doesn't do that.
Q: Would you see a transition having taken place, going from academic hematology being based around morphology, to one that's closer to, maybe, molecular biology?
Conley: Morphology is important--of course, a clinical hematologist must know morphology, in the sense that he knows how to look at a blood smear and a bone marrow preparation and know something about special stains, and certain techniques, sure. Any clinical hematologist would have to know about those things. He doesn't have to know how to run a blood bank and, unless he's further specialized in oncology, he probably is not going to be treating lung cancer and that sort of thing. Hematologists did do that originally, when there were no oncologists, but that's all changed. So a clinical hematologist is what I've just said. Now an academic hematologist, is almost necessarily either a group leader, in which he, by way of being a leader, is in touch with people who are doing various research projects. But the man who is doing the work is almost necessarily a specialist, in a very narrow field.
Q: Such as coagulation, such as--?
Conley: Molecular biology, he's doing DNA technology or protein synthesis or something like that. And it's very unlikely that a person who is going to get big grants from the NIH to do that personally is the doctor that you want to see if you have an undiagnosed anemia. Clinical medicine is just as complicated as research. And the idea that you can work in a clinic one day a week, and be a super doctor is just as fallacious as the notion that you can work in the laboratory one day a week and be a superb researcher. One is as difficult as the other.
Q: And what you have called for, in your own practices, through your own practices, seems to have been, to be able to apply the methods and techniques of basic research to clinical problems.
Conley: Well I started out in the primitive era where a hematologist was supposed to be an internist and I was supposed to know medicine across the board. I started out in 1947, making teaching rounds on the general medical science. We had no specialty units here. So I saw everything that came along, whether it was cardiac disease or nephritis. And I was supposed to know something about all. That went on for a number of years, but no one believes that it's possible anymore. This week, in this quarter, I am making rounds with medical students. But no one really thinks that I'm going to be an expert on all the patients I see. What you teach them, of course, is how to take a decent medical history and approach to diagnosis, but you're not expected to know the details, the ins and outs of complex subspecialty diseases. So, we no longer have the professor who knows everything, who at the same time is doing with his own hands, first class research.
Conley: No chairman of a department of medicine expects to recruit the three-legged stool type person anymore. What Jack Stobo, our relatively new chairman, has designed for a department is that each division head will be primarily a researcher who's going to spend most of his time in the laboratory. And he's going to have colleagues and associates who're primarily clinicians, but who're going to be interested in what's going on in the laboratory and who will bring clinical problems to the bench-- they'll be sufficiently aware of what's going on to know what the questions are. If you have a pure scientist who's never seen a patient, then he doesn't know what the questions are. So you need someone who can tell the investigators what to look for.
During my tenure--in my thirty-three years, can you imagine that?--as head of the Hematology Division here, I never had a fellow who was not an MD. But now my successor has PhD fellows, and that's the way to go, of course. You've got to have those people if you're going to do the kind of sophisticated research which you have to do these days. After all, clinical investigators are now competing with full-time PhD types for research funds. When I was a member of the Hematology Study Section, virtually all the grantees were physicians, and now a majority of them are PhDs. So that reflects an extraordinary change in the pattern of research activity--its complexity and its nature.