ASH Oral History: Samuel Rapaport

Q: I would like to ask you first about your childhood and early education experience, and how that might have influenced your choice of professions.

Rapaport: I was born in 1921 in Los Angeles. I have lived my entire life in Southern California except for: 21 months of military service (1946/1948) at the Aero-Medical Laboratory at Wright-Patterson Air Base in Dayton Ohio, two years in Norway in Oslo at Rikshospitalit (the primary hospital of the Oslo University School of Medicine) with Drs. Paul Owren and Peter Hjort-the first, in 1953/54, as a Fulbright Research Scholar in Medicine and the second, in 1964/65, on a sabbatical supported by an NIH grant, and 6 months in 1983 in Israel on a second sabbatical as a member of the Mortimer and Raymond Sackler Institute of Advanced Studies at Tel Aviv University in order to give a postgraduate course on Hemostasis and Thrombosis and to work with Dr. Uri Seligsohn.

I became a physician because my father was a physician. I respected and admired him. He was available for his patients 24 hours a day of every day for many years. I was also influenced by a book I had read as a teenager: Arrowsmith by Sinclair Lewis. Its protagonist was a doctor devoted to medical research. I decided that I wanted to be a doctor who cared for patients, like my father, but who also did medical research.

At age 15, I enrolled at the University of California at Los Angeles (UCLA) as a premedical student. I liked my time there; in the late 1930's, the campus was small and beautiful. After three years at UCLA, I applied to and was accepted at two California medical schools: the University of California's Medical School in the San Francisco Bay area and the University of Southern California's (USC's) Medical School in Los Angeles. I chose the latter because my father had experienced a myocardial infarction that had left him in congestive heart failure and I wanted to remain close to my family.

In my second year of medical school, the United States entered World War II. Many of the physicians from The Los Angeles County General Hospital, which was the medical school's teaching hospital, were in a medical unit that was sent to the India/Burma border theater of operations.

This stressed the medical school's small Department of Physiology. For one thing, the department chair, Dr. Douglas Drury, had changed how physiology would be taught in the next medical school year. He would no longer give lectures to the entire class. The class would be divided into three smaller groups. Each student would receive a syllabus that contained the essence of his lectures and a schedule of the reading assignments. The students were to have read the assigned reading before attending his/her small group to discuss what had the read as guided by a faculty member assigned to supervise the group. That faculty member would also supervise the members of the group in the course's laboratory experiments.

But a woman member of the Department who was also a physician had been sent full time to the Los Angles County Hospital to buttress its teaching and patient care activities. Dr. Drury's way to handle this was to expand his planned three student groups into four smaller student groups. This would reduce stress upon two "inexperienced instructors" who would replace her. He needed to find them and quickly. In order to hasten the supply of doctors for the armed forces, the medical school year had been shortened to nine months. The next "medical school year" would begin in July 1942--only a few months away.

There was a second perhaps more pressing problem. USC had accepted a contract from the Office of Science and Development of the National Research Council, Division of Medical Science for two war-related research projects in Aviation Medicine. The School of Medicine had created a new department, an Aviation Medicine department, in order to carry out these projects. The Dean of the Medical School agreed to provide funds to recruit two new teaching/research assistants who would be members of both the Physiology and Aviation Medicine departments.

I was asked to be one of the two new teaching/research assistants and I dropped out of school as a student at the end of the school year. The school administration obtained a draft deferment for me as an employee of the School of Medicine who would work on an aviation medicine project for the Army Air Corp and also serve as an instructor in an important medical school course.

I felt challenged to serve as an instructor in a course that I had just completed and to work in a field of research I knew nothing about.

Q: Can you tell me something about the aviation medicine projects?

Rapaport: One project involved the risk to the lungs of an "explosive decompression" of an airplane with a pressurized cabin. The other project was to determine the effect on the body of G (gravity) forces stemming from acute acceleration and deceleration. A "human centrifuge" was built on the campus for that project.

I worked on the first project as low man on the totem pole of a team of four more senior but less available persons. A rat with a thermocouple in its nose was put inside a small chamber at sea level pressure. The small chamber was then placed into a much larger chamber pressurized to an altitude of 40,000 feet. The thermocouple's temperature, which was continuously recorded during the experiment, served as an indicator of the phase of the rats' respiratory cycle. The temperature would fall when the rat inhaled air from the chamber and would rise as the rat exhaled air that had been warmed in its lungs. A person recording the thermocouple's temperature could open the door of the small chamber within and so "explosively decompress" the rat at any phase of its respiratory cycle.

The rat was then removed from the chamber, euthanized, and dissected. If the chamber had been opened at the end of expiration, then the rat's lungs appeared grossly normal. If the chamber had been opened at the peak of inspiration, then the rat's lungs were grossly hemorrhagic. A report of these findings was dispatched to the Office of Science and Development of the National Research Council.

After 18 months of teaching and research, I became a medical student again. I graduated in June of 1945 and began a general medical internship at the Los Angeles County General Hospital. The war ended in August of that year and the internship, which also had been shortened during the war to nine months, was lengthened to its former one year. I had planned to go east after my internship to enter an internal medicine residency but instead of heading east I was called up for military service.

Near the end of my internship Dr. Drury arranged for me to be interviewed by an Army Air Corp officer. Because of that, when I was called up for military service the end of my internship I was sent directly, as a first lieutenant in the Army Air Corps, to the Aero-Medical Laboratory at Wright Patterson Air Base in Dayton, Ohio.

At Wright Patterson I worked on a project to investigate if it would be possible, for fighter pilots flying in artic weather, to pilot the plane without wearing heavy gloves. It turned out, after many months in which I was both an active investigator and the research subject, that the answer was yes.  

On my discharge from military service, I returned to Southern California and began an internal medicine residency at the Birmingham Veterans Administration Hospital, a new temporary VA Hospital located in the San Fernando Valley. It was named not for its location, as is usual with a VA hospital, but to honor an Army General. I chose that hospital for my residency instead of going back to the Los Angeles County General Hospital, where I had also been accepted for a residency, for a major reason. 

Q: Did you think based upon your military experience that the VA Hospital would be a more interesting place to work?

Rapaport: That wasn't the reason. A classmate of mine from USC, Mortimer Morton, had used radioisotopes in medical research while obtaining a PhD before entering medical school. We became good friends. He was now in the process of setting up a nuclear medicine unit at the Birmingham Veterans Administration Hospital. He said that if I came to the VA for my residency, he would teach me radioisotope techniques that would be useful in medical research. And he did. I used external counting of radioactivity after injection of radioisotope-labeled albumin into calf muscle to measure the effect of different conditions---exposure to cold, smoking a cigarette, a sympathectomy ---upon nutritive blood flow in limb muscle. These experiments yielded enough data for two medical publications.

Going to the Birmingham V.A. Hospital proved a fateful decision for me for a more important reason. I met two doctors there who would greatly influence my professional life. One was Dr. Gurth Carpenter, a pioneer clinical hematologist in Southern California, who was a consultant to the hospital. The other was Dr. Thomas H. Brem, who was then on the hospital's Medical Service Staff.

In the late spring of 1950, the Veterans Administration acquired the beautiful multi-story Naval hospital in Long Beach, California. Patients and personnel in the wooden barracks of the temporary Birmingham VA hospital became the patients and personnel of the new permanent Long Beach Veterans Administration Hospital. Its medical service wards were divided had medical subspecialty wards: a Cardiology Ward, a Pulmonary Ward, a Gastroenterology Ward, an Endocrinology Ward (primarily for diabetic patients) and an Arthritis Ward.

There was also one other ward. There were not enough hospitalized patients with hematological disorders to fill a full ward and there were also patients who did not require hospitalization on a subspecialty ward. So there was a hybrid ward: the General Medicine and Hematology Ward. Dr. Thomas Brem had been the physician had been responsibile for the care of patients on the General Medicine and Hematology Ward. But just as I was finishing my residency, Dr. Brem was selected to be the new Chief of the Medical Service. He asked me if I would like to replace him as the medical staff physician responsible for the care of patients on the General Medicine and Hematology Ward. I jumped at the offer.

Q: What year was that?

Rapaport: That was in 1950. I soon realized that I had a decision to make. Should I accept the responsibility only for the care of the hematology patients on my ward? Or should I broaden my responsibility and try to become an on-site readily available consultant in hematology for patients throughout the hospital? With youth's boldness, I accepted the challenge of the second option and stepped onto a path leading to where I am today.

Q: How did Dr. Carpenter influence your career in medicine?

Rapaport: When I took over the General Medicine and Hematology Ward of the Long Beach V.A. Hospital, Dr. Gurth Carpenter became my mentor. I will always hold this complex, eclectic, erudite man in high esteem for what he taught me in weekly consultative visits over many months. And I would like today's hematologists to "meet him" through my words.

Born in Great Brittan, he was a Graduate of the Edinburgh School of Medicine, and spent five years at the Royal Infirmary in Edinburgh in positions equivalent to an internship and medical residency in the USA. In 1936 he immigrated to the USA, to Chicago to begin a residency and teaching fellowship in Pathology at the Presbyterian Hospital and Rush Medical College. After he finished his fellowship, he joined the Department of Medicine at the University of Chicago as an instructor.

Illness in one of his children caused him to move, in 1942, to the warmer climate of Los Angeles. In the late 1940's and the 1950's, he was the premier hematologist in clinical practice in Southern California. He held a part time appointment in the Department of Medicine at USC and also served as a consultant to the Laboratory Service of the Los Ageless County General Hospital. He was one of a handful of physicians who, after World War II, founded the Western Society for Clinical Research (now renamed the Western Society for Clinical investigation). As its president, he chaired the first scientific meeting of the Society in San Francisco in 1947.

He remained a valued friend for many years after I left the Long Beach V.A. Hospital. I felt bad when my recruitment in 1958 as the full time hematologist of the Department of Medicine at the USC School of Medicine cost him part time faculty job. When he died in 1988 at age 79, I wrote his obituary for the journal of the Los Angeles County Medical Association.

Q: How did Dr. Brem influence your medical career?

Rapaport: I also became a close personal friend of Dr. Thomas H. Brem. I considered him my "professional father" during the years I worked with him in the Department of Medicine at USC.

Dr. Brem had spent almost four years during World War II with the Los Angeles County Hospital Unit at the India/Burma theater of operation. Upon returning to Los Angles, he began a private practice but soon decided that it wasn't for him and he joined the medical staff at the Birmingham VA Hospital. As I have already mentioned, by 1950 he had become Chief of the Medical Service of the Long Beach Veterans Administration Hospital.

Tom Brem was an outstanding clinician and an outstanding human being. In 1954, while I was abroad in Norway on leave from the VA Hospital as a Fulbright Research Scholar in Medicine (see later), he wrote to let me know that he was moving to USC as the designated Chair of Medicine when the current Chair retired. And that when that happened he would want me to join the department as its full time hematologist.

Tom Brem was fair in everything he did and had not an ounce of pretence, prejudice or pomposity within him. Happiness for him was making it possible for people in his Department to achieve their professional goals. He taught all who interacted with him how high one must aim to become and remain a good physician.

He was one of the early persons pushing for the passage of Medicare against the resistance of many doctors in Southern California who considered that "socialized medicine." They considered him a "traitor" for supporting it. That did not bother him; I remember him saying "Why should I care if people I dislike dislike me?" He treated every patient he encountered on medical rounds on the wards of the USC Service at the LA County General Hospital, even the most down and out street person recovering from an alcohol binge, with courtesy and concern.

He was the icon of a generation of internists in Southern California who trained as residents in medicine at the Los Angeles County General Hospital. In later years he served as a President of the American Board of Internal Medicine and also of the American Board of Medical Specialties.

He died, coincidently as had Dr. Carpenter, at age 79. I felt privileged to be asked to speak at his memorial service. As I spoke a thought soothed my sadness. My wonderful friend Tom had helped me not just to become a high quality physician. He had also tried to help me in another way. He loved to fish and he would hire a boat each year for members of his department to spend a summer's day fishing together on the blue Pacific. And by example, he had tried to teach me how to catch a 35 pound albacore using 25 pound test line.

Q: Would you like to go back now in our conversation to the 1950's?

Rapaport: All right. After two years of experience as a hematologist at the Long Beach VA Hospital, I thought that I had become reasonably competent. But one day in the fall of 1952, I discovered that I had more to learn. My ward was adjacent to the cardiology ward. In our hospital, as in many hospitals then, a patient with a myocardial infarction was confined to strict bed rest for six weeks. During that time the patient usually received an oral anticoagulant (Dicumarol®). Pothrombin times were used to monitor its dosage. One day I accidentally met one of the cardiologists in the hall between our wards and he greeted me with these irritated words: "Tell me, why are the prothrombin times in this hospital so erratic? That question altered my profession life. I replied: "I don't know but will try to find out".

Q: What's a prothrombin time?

Rapaport: I wasn't sure myself. The test was performed in our clinical chemistry laboratory and I asked its supervisor to tell me how it was done. I learned that it was the time it took for a mixture of plasma and thromboplastin to clot after calcium was added to activate clotting.

(An aside. Thromboplastin is a complex of a membrane protein released from certain cells, including a white blood cell called a monocyte and an associated anionic phospholipid released usually from other cells, particularly platelets. It forms at sites of tissue injury and also other pathologic circumstances. It preferred name now is tissue factor and, it triggers what is now referred to as the tissue factor pathway of clotting. It can form a complex with an activated form of a plasma protein, called Factor VIIa, which is the usual way blood starts to clot in vivo.)

The supervisor hadn't known that prothrombin time tests from his clinical laboratory were unreliable. Our reading together the instruction insert of the commercial thromboplastin reagent the laboratory used provided no clue. Nor did my subsequent reading in the hospital's library a rather quarrelsome literature about prothrombin times.

On a consultative visit soon afterwards, Dr. Carpenter brought a visitor with him. His name was Dr. Paul Owren. He was a professor of medicine at the University of Oslo School of Medicine and the head physician of one of the two medical floors (Medical Department A) at Rikshopitalet, which was the school's major teaching hospital and the premier hospital in Norway.

While working as a physician at Rikshospitalet during World II in Nazi occupied Norway, Dr. Owren had encountered a patient with a congenital bleeding disorder and a prolonged prothrombin time. Her prolonged prothrombin time could not be accounted for by an abnormality of the then known four coagulation factors thought necessary for a normal prothrombin time. After the was ended and scientific communication became possible again, he published a scientific paper in Lancet describing a new plasma clotting factor required for effective hemostasis and for a normal prothrombin time test. He called this new factor proaccelerin; in today's numerical nomenclature it is Factor V.

(An aside here about Dr. Arnold Ware.In the late 1940's Drs. Arnold Ware and Walter Seegers, while attempting to purify prothrombin, had found that their semi-purified material contained a contaminant that accelerated blood clotting. They named it plasma accelerator globulin (Plasma Ac Globulin). Plasma Ac Globulin also turned out to be factor V. Dr. Ware later moved to Southern California and he and I worked for many years at the USC School of Medicine and Los Angeles County General Hospital.)

In 1952, Dr. Owren was invited to America to participate in the 5th International Conference of the Josiah Macy Foundation on Blood Clotting and Allied Problems. It was held on the East Coast but before returning to Norway, Dr. Owren wanted to see more of America. Dr. Carpenter was his host in Los Angeles and brought Dr. Owren with him on his weekly visit to the Long Beach V.A. Hospital. He had arranged for Dr. Owren to give a lecture to the VA Hospital's medical staff on recent advances in the understanding of blood coagulation.

Dr. Carpenter also needed to make a private consultative visit to a patient in Long Beach before returning to his Beverly Hills office. He left Dr. Owren with me while he did so and I had the unexpected privilege of talking for quite a long time with an internationally distinguished man about how blood clots.

That night at a party for Dr. Owren in Dr. Carpenter's home, I learned about the Fulbright program. Senator Fulbright had sponsored a bill in Congress in which funds from World War II debts owed to the US by countries devastated by the war could be used to support international cultural and scientific exchange visits of scholars to and from these countries. I also learned from Dr. Owren that no one had yet applied for an open Fulbright grant for a Research Scholar in Medicine in Norway.

The next day my wife, Joyce, knowing that I wanted to be both a clinician and a medical researcher, urged me to apply for it. Her persistence overcame my initial resistance. A little irritated, I told her I would apply if she would type the application. She did and "we" got the grant. Off we went in the late summer of 1953 on a slow boat to Norway.

Q: Was Norway then known for its contributions in Oslo to blood coagulation research?

Rapaport: I want to begin with a comment from a recent telephone conversation that I had with my long time Norwegian friend, Dr. Peter Hjort. He told me that the United States through its Fulbright program had rescued Norway from the catastrophic effects upon its cultural and scientific activities of the Nazi occupation of Norway during World War II. This comment adds another perspective to what I wish to say next. I want people to realize how important Fulbright Grant support meant not just for me, but for many young Americans seeking an academic career in a variety of disciplines. I honor the memory of J. William Fulbright, a senator from Arkansas, for his worldly wisdom and persistence of purpose in getting Congress to approve the bill establishing those grants.

I want also to clarify why it was not just Paul Owren's guidance that resulted in Oslo being the city where several early important contributions were made to the understanding of how blood clots. It was also a byproduct of Norway's system of medical education, and the Oslo University School of Medicine was the Norway's prime medical school. One graduated from a 6 year curriculum in medical school as a physician (Lege in Norwegian). A Lege seeking a career in academic medicine then had to spend from 2 to 3 years in research to produce, defend, and usually publish a dissertation (essentially a PhD thesis) before becoming a Doctor of Medicine. That explains why Paul Owren had reported his discovery of factor V in two separate 1947 publications: one a 300 page dissertation published as a supplement in Acta Medica Scandinavia and the other a 5 page paper published in the British journal Lancet.

In 1951 in Boston, a second new clotting factor was discovered during the study of a patient with a bleeding tendency and an unexplained prolonged prothrombin time. Soon afterwards a patient with a deficiency of this second new clotting factor was discovered in Oslo. It was referred to in Oslo as proconvertin. In today's numeral nomenclature it is called Factor VII. When I arrived in Norway in late August of 1953, Dr. Knut Aas, the Avdelingslege, the second in rank and responsibility in Medical Department A, had published his thesis on the properties of proconvertin and, his evidence of its stoichiometric reaction with thromboplastin in the presence of calcium to form a complex that was called convertin.

In 1957 Dr. Peter Hjort, the closest friend I made in Norway, published his thesis for a Doctor of Medicine degree. Its title was "Intermediate Reactions in the Coagulation of Blood with Tissue Thromoboplastin." He mailed me a published copy of his thesis three years after I had returned to the USA from my Fulbright year; It meant much to me then and still does now. For he had inscribed in it: "To Sam Rapaport - my first teacher in coagulation! Your Friend Peter." In his thesis, he described the properties of an inhibitor of tissue factor-triggered clotting that he had named anticonvertin. (His work proved important for a major project in my laboratory more than three decades later.)

A third person, Dr. Bjarne Waaler, published a paper from work that he later included in his Doctor of Medicine dissertation. That paper also became important for in a later project of mine for it contained this sentence: "Tissue thromboplastin is shown to initiate both clotting systems when added to normal plasma". This was one of the first clues that a tissue factor/ Factor VIIa complex might activated not just factor X but also Factor IX.

A surprise awaited me three weeks after I arrived in Oslo to begin blood coagulation research Paul Owren's guidance. A vicious hepatitis epidemic had spread through Scandinavia after World War II and, Crown Princess Martha of Norway was one of its victims. She had developed chronic hepatitis and by the late summer of 1953 was in bad shape. The fall months in Norway can be dreary with many cold, rainy, dark days before snow begins to brighten things up as Christmas approached. The American Ambassador to Norway had a home in South Florida; he offered it to the Crown Princess for the months before Christmas and she had accepted the offer. Paul Owren, in addition to his eminence in blood coagulation research, was considered Norway's finest internist. At royal request he was suddenly off to Florida to serve as the personal physician of the Crown Princess. And I found myself six thousand miles away from home on my own in a research laboratory on the sixth floor research laboratory in Rikshospitalet.

I needed quickly to decide what I wanted to do. There was a freezer in the laboratory and when I opened it I discovered a treasure. There were multiple small test tubes of frozen plasma from Paul Owren's original patient with proaccelerin (Factor V) deficiency, from the patient discovered in Oslo to have proconvertin (Factor VII) deficiency, and from a patient with hemophilia.

There was also a unique piece of equipment on the laboratory bench: a metal block about a foot and a half long and a half foot wide that had holes in its top surface into which test tubes could be placed. When an electric cord extending from the box was connected to an electric socket the temperature of the box rose to and was maintained at a constant temperature of 37 degrees Celsius. Gone was the need for a cumbersome water bath in order to study blood clots at body temperature.

Q: How did you decide upon a project to work on?

Rapaport: At that time in Norway patients throughout the country with an acute myocardial infarction were given an oral anticoagulant called Dicumarol® and they continued to take it from then for it was thought to diminish the risk for a second myocardial infarction. At that time it was known that taking Dicumarol® decreased the activity of two plasma factors-- prothrombin and proconvertin (Factor VII). Its dosage had to be monitored, and this was done for the whole country in a central clinical laboratory on the sixth floor of Rikshospitsalet. That laboratory was only about 15 yards away from the research laboratory in which I would work. I could easily obtain left over plasma samples.

It was after talking to the nurse/technician in charge of the monitoring laboratory that I decided what my research project would be. The prothrombin time described in the 1930's is the usual test used to manage oral anticoagulant therapy but it could not be used to monitor Dicumarol® therapy in Norway. Although proaccelerin (Factor V), is not affected by Dicumarol® it is labile and could contribute to lengthening the prothrombin time of plasma that had to wait too long before being tested. Some of the patients lived far away from the hospital; it might take a day after a blood sample was drawn before it arrived to be tested at the laboratory in Rikshopitalet.

A new test, therefore, had been designed in which a patient's plasma that was to be tested for its prothrombin and proconvertin activity was first diluted 1/10 with an aliquot of an undiluted ox plasma. The ox plasma had been adsorbed to remove its prothrombin and proconvertin activity. This provided both a high stable proaccelerin activity and also the fibrinogen needed for a prothrombin time. Then thromboplastin was added to the mixture and the tube was incubated at 37 degrees to bring it to body temperature. Finally, pre-heated calcium was added to trigger the calcium dependent reactions necessary to generate thrombin and the test tube was tilted back and forth to detect the first insoluble fibrin that formed.

The test had been named a P&P (prothrombin and proconvertin) test. Its use, however, had created a new problem. The P&P test time was shorter if a patient's plasma had been standing for a long a time before being tested than if the plasma had been tested soon after the patient's blood had been drawn. But the nurse/technician in charge of the laboratory said that now all was well. A trace of heparin had been added to the oxalate anticoagulant used for the test and this had eliminated the problem. I was intrigued; I wanted to know why. It was related, after all, to the query about prothrombin times that had triggered my interest in blood coagulation.

In September 1953, I thought that the reason why a P&P time decreased if a blood sample stood for a long time in a glass test tube before it was tested had to stem from an increase in activity of either prothrombin or proconvertin or both. (It would be 3 years later that a third plasma factor, Factor X, was discovered and that Dicumarol® also diminished its clotting activity.

The freezer in the research laboratory contained plenty of proconvertin deficient plasma. I improved the assay for its activity then in use by adding adsorbed ox plasma to make the assay more specific. I had my research project; to determine if contact of plasma with a glass surface could increase proconvertin activity. I found that adding crushed glass to a dilution of normal plasma would quickly increase the proconvertin activity of a test sample in my new assay. This could account for what happened when normal plasma stood for a long time in a glass tube before assay in the P&P test.

I published my data in a paper that I wrote with Dr. Owren and Dr. A as as coauthors and it was published in the January 1959 issue of the Journal of Clinical Investigation. It turned out to be an important paper but for a different reason. Its summary included these words: "Proconvertin has been defined as inactive proconvertin or active proconvertin rather than as a plasma activity or a serum activity." In the later numeral nomenclature the words would have been: "Factor VII has been defined as inactive Factor VII or active Factor VIIa." I had provided first evidence that plasma could contain not just inactive Factor VII but also Factor VIIa.

(Another aside. Recombinant Factor VIIa has now been found useful in controlling bleeding in patients withHemophilia A and an inhibitor of factor VIII, on Hemophilia B with an inhibitor of Factor IX. It also appears to be useful in controlling bleeding in other disorders.)

Sometime late in my year in Oslo, I read an important paper from Dr. Brinkhouse's group at the University of North Carolina. It was about a new procedure for the assay of anti-hemophilic factor (the factor lacking activity in Hemophilia A). They did not use the complete protein/anionic phospholipid complex in their assay that had thromboplastic activity in a prothrombin time test, but just its anionic phospholipid component. In the text of the paper they referred to their new test as a partial thromboplastin time. I used a four part modification of the Brinkhouse group's test to determine what would correct the prolonged partial thromboplastin time (PTT) of the plasma from the patient with hemophilia that was stored in the laboratory's freezer. Would an aliquot of added adsorbed plasma rich in antihemophilic globulin (Factor VIII) correct the patient's prolonged PTT; which would mean that the patient had Hemophilia A? Or would an aliquot of serum rich in plasma thromboplastin component (Factor IX ) correct the patient's PTT, which would mean that the patient had the newly recognized form of hemophilia referred to as Hemophilia B? I believe that the patient was the first patient in Norway known to have Hemophilia B.

Q: What was it like socially to live a year in Oslo?

Rapaport: During Paul Owren's stay in Florida, Paul Owren's wife Marit and my wife Joyce became good friends. Marit Owren had discovered that Joyce Rapaport was a school teacher who taught English in a high school in the USA. And she asked Joyce if she would mind teaching English to her daughter Ingrid. The Owren family lived about a block away from Rikshospitalet. Joyce would go each Monday afternoon to their apartment to tutor Ingrid. I would come over to the apartment after finishing my afternoon's work at Rikshospitalet and the three of us would eat a delicious dinner that Marit had cooked.

The first words of the first meeting I had with Professor Owren on his return to Oslo were not to ask about the research I had done in his absence. They surprised me: "Have you and your wife bought your skis yet?" I said no because we lived in Southern California and didn't ski. Paul Owren's reply revealed who was in charge: "If you do not, I will do it for you". So we bought skis and Joyce and I became Norway's worst skiers. Paul Owren discovered this during the week of Eastern Vacation, when we were his guests at quite a luxurious hotel located on a mountain still covered with snow. He then had the opportunity to observe it for himself.

There was a microscope at the far end of the laboratory room I used at Rikshospitalet. A young doctor would sometimes use it to count red blood cells for a study on the survival time of transfused red blood cells. His name was Peter Hjort; we would talk with each while we worked---not about science but about the culture and politics of our two countries. Over the year we became good friends and have remained so ever since.

It was in a late month of my stay in Oslo that I received the letter I mentioned earlier from Dr. Brem telling me that he would want me to become the full time hematologist for the Department of Medicine at USC. That was great news.

Q: What would you do when you first returned to the USA?

Rapaport: When I returned I rejoined the Medical Service staff of the Long Beach VA hospital. My ability to use the original partial thromboplastin time test as described above to distinguish between Hemophilia A and Hemophilia B became important for happened next. I knew that I would have to wait until Dr. Brem could find the funds needed for me to join the faculty of the USC School of Medicine in a tenure track position. And I suspected that it might be a long wait.

But I had been "hooked" in Oslo and wanted to establish my own Coagulation Research Laboratory. I decided that I would start it while I was still at the Long Beach VA Hospital. I had a good friend there who was a biochemist on the Research Service of the hospital. He told me that he had a room in his laboratory that I could use, and that I could also use one of his freezers and some of other laboratory equipment. Yet I knew that I would be unable to begin meaningful coagulation research with my one hands alone; most of my time would be needed to fulfill my clinical duties. I had to find a source of money to hire a research technician.

I don't remember how I met a well established pediatric hematologist named Madeline Fallon. Her somewhat gruff manner hid a heart of gold. She was shepherd of a flock of about 150 hemophilic patients - children and adolescents living in Los Angeles or its suburbs. She wanted to know what kind of hemophilia each member of her flock had - Hemophilia A or Hemophilia B. And rightly so for that would be essential when different plasma concentrates would become available: one specific for Hemophilia A and the other specific for Hemophilia B.

She had approached a pathology laboratory group in Los Angeles. It would do that for her flock of patients for $25,000. That was pretty; big money in the mid 1950's. I told her I would do it for free if I could find the money to pay a research technician to work in a Coagulation Research Laboratory that I was trying to set up at the Long Beach V.A. Hospital.

Dr. Fallon had a friend who was a prominent Los Angeles cardiologist. He convinced the Research Committee of the Los Angeles Affiliate of the American Heart Association to give me a $5000 grant to establish my Coagulation Research Laboratory. (It was a far-sited group that recognized the relevance of blood coagulation research to cardiology - to for example understanding the ways thrombi might form within blood vessels.)

I used a small amount of the money to have a metal constant temperature box made similar to the one I had used in Oslo and to purchased reagents, glassware and two stop watches for measuring the clotting times of functional blood coagulation tests. I hired a research technician with the rest of the money.

And so it was, with the permission of a hospital administration that understood supporting medical research was part of the of the overall mission of the Veterans Administration, that I drove on Friday afternoons to Dr. Fallon's office in Los Angeles. She had a small laboratory room in her office that had a laboratory bench and a small centrifuge on it. I brought with me the reagents and glassware I would need and some dry ice to take back plasma samples that I might want to test further.

She would ask several hemophilic patients and their families to come to her office. She would obtain permission to draw a blood sample from each hemophilic patient into a test tube containing a buffered anticoagulant that I had brought with me. Then I would run the test to determine which reagent - adsorbed plasma or serum - would shorten a sample's prolonged partial thromboplastin time. After many, many weeks, we had determined which kind of hemophilia (A or B) each member of her flock had.

Although a pediatric hematologist, Dr. Fallon was asked to see in consultation a policeman who had no known history of a bleeding tendency, but who had developed a large inguinal hematoma after a hernniorrhaphy. He now needed a cholecystectomy and she asked me to perform some coagulation studies on him for her. I asked her patient to come down to see me as a research subject in my Coagulation Research Laboratory at the Long Beach VA Hospital. Which he did.

He told me that he had played on his high school football team and had never noticed abnormal bruising or bleeding. That impressed me because that be a rough game. I found that he had a normal prothrombin time but an abnormal partial thromboplastin time that could be corrected both by adsorbed normal plasma and by normal serum.

R.L. Rosenthal, E.D. Dreskin, and N. Rosenthal had described in a paper in Blood in 1955, about their study of two sisters and a maternal uncle who had a milder hemophilia-like disease, a normal prothrombin time, and lacked a plasma factor that was present in both normal adsorbed plasma and in normal serum. They named the lacking factor plasma thromboplastin antecedent; in the numerical literature it is Factor XI. Some had been skeptical of their report, but now not me. [The patient] had what they had described. This turned out to be important for me. [The patient] became a source of Factor XI deficiency plasma for my coagulation research laboratory and enabled me to begin research early related to Factor XI deficiency.

So that's how I opened my independent coagulation research laboratory and began my independent research care. It was supported by successive research grants from the National Institutes of Health (NIH) until I retired in the mid-1990's.

I also continued to be an active internist, clinical hematologist and medical teacher: first briefly at the UCLA School of Medicine, then until late 1974 at the USC School of Medicine and since then at the UCSD School of Medicine. At the last I was Chief of Medicine of the newly opened at the affiliated San Diego VA Hospital, but soon changed jobs to became the Head of the Hematology Division of the Department of Medicine of the Medical School (Its Chair was Dr. Helen Ranney who had also been a President of ASH and is a much valued friend of now many years.)

At my research at these institutions, I avoided involvement in clinical research trials concerned with the management of patients with bleeding or clotting disorders. This was because of the major responsibilities I have always had, independent of research, in the care of patients as a clinical hematologist and internist.

Q: While you were waiting to return to USC, how did you become involved with hematologists at UCLA?

Rapaport: The hematology scene in Southern California bloomed in the late 1940's when the University of California opened a new medical school at UCLA and a beautiful new hospital was built on its campus. The Chair of the Department of Medicine, Dr. John Lawrence, had been recruited from the Rochester University School of Medicine and had there were three talented hematologists I knew of who were in his Dapartment: Dr. William Valentine, who would become nationally distinguished, Dr. Charles C. Craddok, who was interested in white cell kinetics, and Dr. William Adams who was interested in multiple myeloma. Moreover, Dr. Joseph Ross, who was amongst the first to use radioactive iron in the study of iron metabolism and radioactive chromium-labeled erythrocytes in studies of the life span of circulating red blood cells, had joined the UCLA School of Medicine as a Professor of Medicine and as the Associate Dean of the School. Who would have thought that the UCLA Medical School could use another hematologist - but they did.

Treatment of hematological malignancies had become more complex and clinical trails of efficacy were needed. Funds became available in 1956 from the federal government for cooperative trails involving several of the western medical schools. A group was formed, called the Western Cooperative Chemotherapy Group, with headquarters in Seattle at the Washington University's School of Medicine. Dr. William Adams was the responsible investigator for the clinical trials to be carried out at UCLA. And he had funds to support a junior person to be the hands on clinical hematologist for the trial.

I applied for and got the position, and moved to UCLA in December of 1956. It was with the proviso that I was would be given a room to set up my Coagulation Research Laboratory at the UCLA Hospital and sufficient time off from my clinical duties to pursue coagulation research. My technician from the Coagulation Research laboratory in Long Beach moved to Los Angeles to continue working with me. I had enough residual funds from my "$5,000 dollar grant" to continue paying her salary for a while, after which I obtained some small grants from local California Foundations.

I submitted a grant to the NIH in the spring of 1958. It was approved but "without funding". In late September, however, to was funded from residual unspent money in the federal funding year which that had to be used before the funding year ended on the first of October.

The clinic I ran for the clinical trials was at the nearby Wadsworth V.A. Hospital, which was affiliated with the medical school. There was enough money in the grant for a fellow, and I chose Dr. Charles Chapman, who had finished an internal medicine residency at the Long Beach VA Hospital and wanted to become a hematologist. He was a very good doctor, we became good friends, and he took over my responsibilities at UCLA when I moved to USC. I think of him as my "first fellow."

I performed coagulation tests in my research laboratory in the UCLA Hospital on two patients I will always remember. The first was a patient at the UCLA's hospital. She had a history of a persisting bleeding tendency and she turned out to have the same rare disorder that Paul Owren had first described: hereditary factor V deficiency. I was paid handsomely for finding that out; not in money but because she became the donor of factor V deficient plasma for my research laboratory for many years, including one last donation after I moved, in the late fall of 1974, from Los Angeles to San Diego. (I wanted to pay for her train ticket from Los Angeles; but she refused saying she wanted as payment only a kiss on the cheek. Which she got.)

The second patient was a young girl hospitalized at the Los Angeles County General Hospital. Dr. Arnold Ware had moved from Detroit to Southern California and was now a member of the Department of Biochemistry at USC and the Director of clinical chemistry laboratory at the Los Angeles County Hospital. He called me up to ask if I was interested in studying the plasma of a young girl in the hospital whose coagulation laboratory findings were compatible with a diagnosis of congenital hypoprothrombinemia. Indeed I was.

I went quickly across town to the Los Angeles County Hospital to obtain a blood sample from an unfortunate adolescent who looked to me very ill. I was very upset to learn, not too many days later, that she had died from a fungal infection complicating the administration of very high doses of an adrenocortical steroid. She had been given the adrenal steroids in an attempt to stem the aggressive progressive of her disorder, which I later learned was systemic lupus erythematosis. I could not measure any prothrombin activity in her plasma. But when I measured the prothrombin activity of a mixture of equal aliquots of her plasma any my normal plasma, its prothrombin activity was about 50% of normal. She did not have congenital hypoprothrombinemia nor did she have an antibody in her plasma that neutralized the activity of added prothrombin. It turned out that she had an unusual manifestation of an antibody that can bind to a prothrombin/anionic phospholipid complex. Such an antibody is now referred to as a "lupus anticoagulant" a name a younger colleague (Dr. Donald Feinstein) and I had suggested in writing review article. This turned out to be a misnomer, for a lupus anticoagulant usually does not increase the risk for bleeding, but the risk for thrombosis. This patient was an exception. Her antibody was so powerful that she had been at risk for bleeding because of her plasma's prothrombin activity was literally zero. The macrophages of her reticuloendothelial endothelium could clear antibody bound prothrombin/ lipid complexes so rapidly that her hepatocytes could not make enough new prothrombin to raise her plasma level.

Q: When did you finally join the Department of Medicine at USC.

Rapaport: In late 1958, I got the good news that I had been waiting for so long to hear. Dr. Brem had found the funds for me to join the Department of Medicine as a tenured Associate Professor. I abruptly resigned my temporary In Residence appointment at UCLA. I had applied for an NIH research grant in the spring of the year. It was approved, but not funded. It must have had a pretty low priority for in those days the NIH had plenty of money. And indeed, close to the end of the federal funding year, October 1st, the NIH had had enough money to fund my grant. My grant came with me to UCS, as did my research technician now paid from my grant. My coagulation research laboratory at USC could be quickly set up.

But I soon learned that I had a big problem. I would be very busy, teaching medical students and house staff, caring for patients, and setting up my coagulation laboratory in a room in a Medical School building across the street from the hospital. That room would also have to serve as an my medical school office. And the university would provide funds only for my salary, not provide funds for anything other than my salary. Where would I find money for secretarial support or even a telephone for my laboratory/office?

Q: How did you find the money?

Rapaport: I learned from Dr. Brem that the NIH would support training grants designed to increase the number of Academic Physicians in the Subspecialties of Internal Medicine. I quickly applied and was soon awarded one of these grants. It was for support for a two year program to support successive two year fellowships for two trainees. The first year would be a clinical year in which a fellow would participate in the patient responsibilities of the hematology division at the Los Angeles County General Hospital. The second year would be a research training year in my newly named Hemostasis and Thrombosis Research Program with other responsibilities limited to attending the hematology clinic and two clinical conferences. The grant had funds for a secretary, for a part time technician, and for some equipment: a two-headed microscope to teach the morphology of hematology (and a telephone or two to keep everyone functional. This program was maintained for the fourteen years I would be at USC. Five fellows of the program would become Professors of Medicine.

Q: Can you tell me more about your teaching activities at the USC School of Medicine.

Rapaport: In my first several years at USC, I taught hematology as a segment of a course the third years medical students took. Its goal was to relate physiologic and pathologic processes to clinical findings. I used the lectures that I wrote for this course were incorporated into a small hematology textbook that I wrote: " Introduction to Hematology". To my surprise that book became a best seller both at home and in a couple of countries abroad.

In later years the hematology course was revised. The students were organized into several small groups. A series of patient case histories with different hematological disorders were written and microscopic slides were prepared for members of each small group to examine and learn the morphologic findings of each disorder.

My teaching of house staff of the Los Angeles County General Hospital included rounds with house staff (and an accompany student or two) as an attending on a general medical ward for several months of the year. This overlapped with my clinical care responsibilities to assure hematological care in the Medical Department of the Los Angeles County Hospital and in the outpatient Hematology Clinic was nothing less than first class. I was also responsible for the quality of teaching internal medicine house staff who had chosen an elective rotation with the hematology division.

I looked forward to the time that I spent as an attending physician on the general medicine ward: my interest in general internal medicine had remained strong. For I believed and still do now that a competent clinical hematologist stands upon the cement of also being a competent internist.

Two weekly teaching sessions were organized. The first was a one hour structured conference in which the findings of a current hospitalized interesting patient were presented and we discussed not only how the patient should be managed but also the basic hematology involved. This conference was well attended by house staff, fellows, and voluntary clinical Hematology Division faculty.

The second session was a review with those attending the weekly Hematology Outpatient clinic of the findings of the patients we had seen that day. This was a small session held after the clinic was over. We gathered around the double headed microscope in the room the Division had been given in the hospital, looked at blood smears obtained that day from patients attending the clinic, and discussed the status of each patient we had seen.

Should we start now to talk about the American Society of Hematology?

Q: Sure, when did you first become involved with ASH?

Rapaport: Very early. The society was organized in 1958 and Dr. James L. Tullis was its first President in 1959. The first scientific meeting of ASH I attended was in 1960. I remember sitting in a half-filled hotel ballroom hearing its second President, Dr. Carl V. More, declare: "The primary purpose of this organization is to put on a good scientific meeting each year". I remember thinking yes that's what ASH should be about.

ASH is a democratic organization responsive to the needs of its membership. A business meeting is held at the close of each of its national meetings. At one early business meetings someone asked for the floor and said: "You put on a good program for clinical investigators, but you don't provide practicing hematologists with the education we need." The following year an education program preceded the scientific session; ever since an educational program has been a key part of the national meeting.

ASH is also an organization where past service as an officer or as a key member of an important committee does not give one a continuing privileged status. The year after I was President of ASH, I sent in an abstract for presentation at the scientific session. It was turned down; those choosing the program didn't think it was good enough. The fact that I had presided over the meeting the year before didn't matter. I thought: "My God, this is a society I am really proud to be a member of".

Q: No aristocracy?

Rapaport: That's right. It's also an inclusive organization. Its goal has never been to become a prestigious organization in which one competes with colleagues for the honor of being elected a member. All that election to membership requires is evidence that one is active in some aspect of hematology. I believe members feel "at home" at its national meetings. The only problem for me is that attendance at the national meetings has grown to where it has sometimes been difficult to find a seat in a room of a quite place to eat and talk with colleagues.

Q: Who were its members early on?

Rapaport: Academic hematologists organized the ASH and have been key movers ever since. But from early on, it had members who were primarily practicing hematologists. As I have just mentioned, ASH quickly developed a strong commitment to an education program providing practicing clinical hematologists with the latest information needed for the care of their patients. I particularly remember a slide bank exhibit at the meeting that contained collections of microphotographs of blood and bone marrow smears that one could view and, if one wished, could order as a teaching tool. The education committee of ASH also started printing a booklet that was distributed at the meeting. It contained a summary of the meeting's educational sessions along with references for further reading.

I must say, though, I am beginning to fear that our national meeting has a real problem. It is is at risk of being kidnapped. Pharmaceutical and biotech companies are sponsoring satellite symposia held just before or just after our national meeting. Some have even tried to intersperse a satellite symposium during the actual ASH meeting program time. I worry that these symposia may not be subjected to the same careful peer review process that is required for the content scientific sessions of the society itself.

There is only so much that one can take in at a meeting. If satellite programs continue expanding, then sooner or later some people may spend more time at our national meeting attending satellite symposia than attending ASH-chosen sessions. The tail then may wag the dog.

Satellite symposia must not be allowed to invade the scheduled program time of our national meeting unless invited to do so. But it may prove hard to put the cork back into the bottle.

Q: Can you tell me more about your associations with ASH?

Rapaport: In the late 60's, I served for three years on the Executive Committee. I was a member of one of the scientific subcommittees. For a couple of years, I also gave one of the teaching sessions of the educational program. One year I was chair of the nominating committee one year. And a couple of years later, I was nominated to be a future president. I then went back onto the Executive Committee: as vice president, president-elect, and, in 1977, as president of the Society.

In 1976, when I was Vice President of ASH, our early December national meeting was in Boston. My clinical and research activities in hematology had narrowed to focus upon hemostasis and thrombosis. I was surprised that many of the people I knew with similar interests were not there. They had gone two weeks earlier to a meeting in Florida of the recently formed American Heart Association's Council on Thrombosis. I worried that this might be a harbinger of things to come.

When I became President of ASH, I contacted Dr. Edward Genton, who was Chairman of the executive committee of the Council on Thrombosis and asked him to consider an alternate year arrangement. One year the Council on Thrombosis would put on a full fledged meeting on hemostasis and thrombosis at the American Heart Association meeting and ASH would deemphasize hemostasis and thrombosis at its national meeting. The following year the Council on Thrombosis would have only a token meeting at the American Heart Association meeting but its members would be welcome to attend the ASH national meeting. They could send in abstracts for the meeting, pay the standard ASH member registration fee, and hold their meeting as one of the ASH evening programs. They would plan and run that evening meeting.

After a little arm twisting of executive committee members, both societies accepted this arrangement. I think it helped, at least for that time, to keep intact a cohesive hemostasis and thrombosis research community. I am afraid I don't remember how long this arrangement lasted. I do know that the American Heart Association meeting is so very large and competition for space and time is so intense that people whose primary interested in the hematologic aspects of bleeding and clotting disorders have drifted back to us as their primary meeting.

Q: Would you say that the similar problems arise over the question of leukemia, for instance?

Rapaport: Between hematologists and oncologists?

Q: Yes

Rapaport: If I had a magic wand and could organize the next few years of ASH meetings just the way I wanted them to be, I would organize the ASH meetings to emphasize disorders of hemostasis and thrombosis and other non-malignat disorders one year and emphasis malignant hematological disorders the following year. That second year would be particularly valuable for those persons attending our meeting who are both practicing hematologists and practicing oncologists.

When I was a Governor of the American Board of Internal Medicine some years ago I helped make it easier for a doctor to become both a board certified hematologist and a board certified oncologist by proposing that the Board accept a combined three year hematology/oncology fellowship program as satisfying the Board's requirements to sit for the subspecialty examination in both disciplines. I did push for that but it might not have happened without the support of Chairman of the Board, then Dr. Saul Farber. For a member of the board then who was a prominent oncologist, had proposed that the requirement to be eligible to sit for an examination should be two completely unrelated two years fellowships: one required to take the oncology examination and the other to take the hematology examination.

I thought then and still do now that a combined three year fellowship is the way to go because hematological malignancies were have been a large part of the treatable malignancies. However, as more promising management of solid tumors - breast, ovarian, brain, lung, prostate - has increased. So I don't know how long in the future a combined three year hematology/oncology fellowship program will be the way to go. But I do know this; the real enemy is not a new discipline trying to "take over" what another discipline may think is its exclusive turf. The real enemy is suffering and ignorance. Battling that enemy is what counts.

After my presidency, I became a member of the Advisory Board of ASH for what I believe was three or four years, but it may have been longer. The Board has provided advice to the Executive committee on such issues as should persons in other countries interested in hematology be accepted as members of ASH. As I recall the answer then was yes but for only for a few who had contributed importantly to advancing understanding in some aspect of hematology. The Advisory Board was also involved in giving advice as to who would get the Dameshek prize and who should give Stratton Honorary Lecture at the plenary session of our national meeting. Being selected to give either is an honor. In 1984, I was asked to give the Stratton lecture and this was a high points of my professional life.

Q: Earlier you mentioned Carl Moore's statement that the sole purpose of ASH was to hold a good scientific meeting each year? Do you think that still holds?

Rapaport: No I don't. The Society had to become involved in lots of other things. For example, the Society must play in solving medical "political issues". For example, the issue of what tests a doctor may run in his or her own office and charge for, versus what has to be sent out to a laboratory run by a pathologist, needed to be clarified. The Society was also asked by the American Board of Internal Medicine to decide what the requirements for certification as a hematologist should be. The Society must continue to lobby both Congress and officials of the National Institutes of Health (NIH) for increased hematology research support. It has also become involved, and I hope will become more deeply involved, with other national medical societies in an extremely important present issue---how health care should be delivered in our country. ASH can't sit aside and pretend that there is not a big problem of how patients with hematological diseases are going to be able pay for all the expensive things that are increasingly needed in the treatment of hematological malignancies.

Just putting on a good national meeting is now not enough. The Society's members and staff mjust be involved in the whole gambit of medical care and its relation to society. I suspect it makes the work of someone now sitting on the major committees of ASH a lot harder and less attractive than in earlier days, when the main issues were related to the scientific and education programs. But, I guess, that's modern life.

Q: I suppose that the underlying reason for dealing with these issues is that if one doesn't play a role in it, the -

Rapaport: Others will decide for you. I remember that early on ASH was initially against the idea of there being a subspecialty board for hematologists. But then a representative of the American Board of Internal Medicine came to a business meeting of the society with an ultimatum: "There shall be a board in hematology". To their credit, the American Board of Internal Medicine asked ASH for advice on defining what the eligibility requirements should be for one to sit for a hematology subspecialty examination. As it turned out having board certification in hematology has proven to be of real value to practicing hematologists. They now have a certificate to prove to governmental agencies and insurance companies that they have special competencies for which they should be paid.

Q: Boards in hematology were started when?

Rapaport: In the late sixties or early seventies. I took the first examination so let me look. I see that my certificate on the wall there was signed in 1972.

Q: Were you personally involved in the functions of the American Board of Internal Medicine?

Rapaport: I became a member of the Board of Governors of the American Board of Internal Medicine in 1973, became a member of its Subspecialty Committee on Hematology in 1974, and became the Chair of the Subspecialty Committee on Hematology in 1978.

Q: How does one determine what a hematologist should be competent to do?

Rapaport: Remember the way I told you how I started. I looked at a sign on the door of the ward at the VA Hospital I was assigned to be in charge of. It read: "General Medicine and Hematology." Ipso facto, I became the hospital's hematologist. Whether or not others in the hospital asked me to consult on their patients depended upon how I performed. If my associates in the hospital thought "Gee, he doesn't know A from Z", then they weren't going to continue to ask me to see patients. But if I learned how to help them with their patients and did a decent job, then my colleagues would accept me as a hematologist. That's all there was to it at that time, either in the hospital or out in the community.

But as time went on the knowledge base in all of the subspecialties of internal medicine began to grow almost exponentially, and the American Board of Internal Medicine decided to set up subspecialty boards. To sit for a subspecialty examination, a hematologist first had to pass the American Board Examination to become a board certified internist. Then, as we have already talked about, he needed to complete a board approved fellowship in Hematology. Initially the board "grandfathered" the fellowship requirement for those of us, like me, who trained ourselves before the days of hematology training fellowships. All we needed to do was to pass the board's Hematology examination to become a board certified hematologist.

Q: How did you feel about the exam you took?

Rapaport: I thought it interesting and not hard for me. After all, I'd been a hematologist and been teaching hematology for a long time before I took the exam. As I mentioned earlier, I had recently written a small introductory hematology textbook. The night before the exam I reviewed my own textbook. That did the trick; I passed.

Two years after that I became a member of the Subspecialty Committee on Hematology of the American Board of Internal Medicine. Serving later as its Chair I was responsible for assuring the quality of two of the hematology subspecialty examinations. I enjoyed that.

Q: Why was that?

Rapaport: There were intelligent, nice people on the hematology subcommittee and it was stimulating interacting with them. We put together a fair examination: an examination that asked the question that a competent hematologist needs to be able to answer.

Q: Would the kinds of questions be different today?

Rapaport: Yes because of advances in our knowledge of molecular biology: the availability of newer agents, such as monoclonal antibodies and growth factors, to diagnose and manage hematological malignancies, and the use of surface marker analysis to identify different blood cells and their precursors. Treatment modalities have also become more complicated. Infusing purified donor stem cells from blood has replaced having to perform a bone marrow aspiration on the donor to get these cells. Newer products have become available for transfusion therapy. I would study hard before taking the hematology subspecialty examination today.

Q: So hematologists practicing today have to take in a broader range of considerations. But are they as broad in their knowledge of medicine?

Rapaport: I don't know. I can't generalize about that. They surely have to know a lot more things directly related to hematological disorders than they had to 20 years ago. Whether someone is able to do that and still keep up a broad basic knowledge of internal medicine is an important question. I think that the answer varies with the individual hematologists. But I think it's probably right to say that for any subspecialty of internal medicine, its becoming harder and harder to have the time to keep current about advances in general internal medicine and still have the time to remain competent in one's subspecialty. The amount of material that one has to know just grows and grows and grows.

It's a lot tougher to remain a competent hematologist than it was 20 years ago. Making a diagnosis is easier because of new imaging techniques and other new test methods. What's harder is deciding what should be done after knowing what a patient has. There are so many more things one can try, for example, various options in different chemotherapeutic regimens, and some of these options are costly and may also with miserable side effects. Some patients want to believe that everything is curable. And the expectation of some patients today is that everything should be curable. They don't want to listen when we say: "We can't do any more." It's a much different practice of medicine today than it was 20 years ago.

Q: Have you been involved in conflicts between hematologists and pathologists?

Rapaport: There can be an issue in training programs about who obtains bone marrow specimens and who evaluates them. I got along very well with the hemtopathologist at USC, Dr. Robert J. Lukes, who is a very nice man. We became good friends and resolved rather easily problems that might arise.

I had a particularly good arrangement when I moved here to the UCSD School of Medicine. I and a younger colleague, Dr. Raymond Taetle, both worn two hats. We had appointments in both the Departments of Medicine and the Department of Pathology. This enabled us to develop a combined teaching program involving both hematology fellows and pathology residents in which both could learn together.

I know there have been problems elsewhere; these have included issues between hematologists and pathologists as to who can run a laboratory and what tests can be performed by doctors who have a laboratory in their office that has not being inspected for formal quality assurance. But clinical hematologists must be allowed prepare blood smears and perform simple tests in their own office laboratory. I know this is becoming "old fashioned" but they must not be told: "You can't do this because you don't have the right kind of certification." I believe that sort of inflexibility can hinder delivery of care.

I know, however, that some sort of control is needed. One can't have people doing sloppy work in office laboratories without somebody checking on them once in a while and saying: "Hey there wait a minute." How to set up regulations to assure careful accurate results is an important issue yet to be addressed. But I'm not sure you are interested in all this.

Q: It is interesting because it provides a picture of the nuts and bolts of how one does hematology, of what the tensions are. I find very interesting who is responsible for what, because it ultimately defines hematology.

Rapaport: Some people would say that hematology is a specialty on the decline. That, in fact, it may largely become an academic specialty of a small number of people doing research in various institutions and seeing a limited number of patients with unusual hematological problems. I think some people believe that oncologists will eventually take over the management of most patients with hematological malignancies. And that there will be a small number of people who will mainly be certified specialists in transfusion medicine. That could be the way it will go.

Q: But as far as you are concerned----

Rapaport: I think it important to let ways of health care delivery grow in a flexible manner that adjusts to change and that allows new treatments to be delivered to patients most efficiently. If you divide subspeicalties into rigid groups that require rigid requirements to get into - well that is the path to atrophy. Biological systems that work like that die out. So would social systems unable to adapt. If it works out best for the delivery of care, I don't care if the number of people, such as me, who call themselves hematologists shrinks drastically.

I do care, though, that there is a history and background of hematology that must not be forgotten. There have been distinguished hematologists who have made real contributions to medicine. And the study of the blood has led to major contributions in understanding human biology. I hope that this continues and believe there are younger people coming along who will continue to use the techniques and tools of hematology to advance biologic research - to wherever it is going. With the advent of powerful methodologies of molecular biology, I can't begin to imagine what may be just over the horizon.

Q: I suppose we can stop here unless you believe there is anything else?

Rapaport: I think I've told you most of what I have to say. I repeat that I think that the American Society of Hematology has been and will continue to be a great organization. I am proud that I was once one of its Presidents.

©2008 Columbia University

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