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: Dr. Wintrobe was sort of a single operator. He had many collaborators who were not members of a hematology division. George Cartwright, who went with him to Salt Lake City, and became his successor, worked with him here. And I think Cartwright was probably a resident when he was doing that. But there was certainly no department or division.

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 1940s.
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.

[Tape Interruption]

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.

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