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Interview with Dr. Harvey G. Klein

This is an interview with Dr. Harvey G. Klein, Chief, Department of Transfusion Medicine at the Warren Grant Magnuson Clinical Center at the National Institutes of Health, Bethesda, Maryland, on 29 January 1993. The interviewers are Dr. Victoria A. Harden, Director of the NIH Historical Office, and Dennis Rodrigues, Program Analyst. The subject of the oral history is the NIH response to AIDS.

Harden: Please start by giving us a brief summary of your education and career up to the time that you became aware of AIDS. I would also like you to comment on why you decided to go into medicine and medical research.

Klein: I went into medicine probably because my uncle was on the faculty of the Harvard Medical School. He was a pediatrician, and throughout my childhood he was more or less a role model for me. He was my great uncle. He was one of the first professionals in the family, and that motivated me to look toward medicine. But, as an undergraduate at Harvard, I was a German literature major. I simply did enough science at Harvard, and at MIT (Massachusetts Institute of Technology) to satisfy the requirements for entry into medical school.

When I went to medical school it was with the object of becoming a physician, but not necessarily a researcher. I do not think that I, as a graduating senior from a liberal arts college, really knew what the various opportunities were, and what they meant, in medicine. But, looking at the various medical schools available and the geographic area that I wanted to be in, I applied to, and was accepted by, the Johns Hopkins Medical School. As it turned out, Hopkins was one of the most research-oriented medical schools, if not “the” most research-oriented medical school, in the United States. As a first-year medical student, there was an elective period, and during that elective period, I became interested in research, beginning with a small project in a laboratory at Hopkins. From that point on I felt that that was more or less what I wanted to do in medicine. I wanted to see patients, I wanted to practice clinical medicine, but I wanted to be doing something that brought new information to the medicine discipline.

I spent four years as a medical student at Hopkins. I was interested in internal medicine, so I stayed in Baltimore to be on the house staff at Hopkins. It was the house staff named after Sir William Osler, and it had quite a long tradition of clinical investigation.

While on the house staff, once again, I think my decision to go into the blood area was molded by an individual who was generally considered to be one of the best clinicians at Johns Hopkins. That was Dr. C. Lockard Conley who, as it turned out, was the Head of the Hematology Division. He was my attending physician and my mentor, to some extent, and was very much oriented toward investigational studies. No matter what you did, whether you were a private practitioner or a full-time clinician at a medical center or a laboratory researcher, Dr. Conley always thought that you ought to think in a research mode, make and record observations, and try and interpret them.

After my residency I became a fellow in Dr. Conley’s division. This was at the time of the Vietnam War. Hopkins had all kinds of close ties to the National Institutes of Health. I had actually already applied to the Commissioned Corps of the Public Health Service and had been assigned as a senior medical student, as a first-year intern, and as a first-year resident, to the Centers for Disease Control in the Infectious Disease Division, Venereal Disease Branch. I had been to Atlanta and looked around. It was only when I decided to go into hematology that I thought that perhaps studying venereal diseases for two years of government service was not in the best interest of my career. I talked to Professor Conley about it. He said, “Why don’t you see some people at NIH,” and he gave me the name of a Dr. Ernst Simon. Ernst Simon was the first Director of the Blood Division of what was then the National Heart and Lung Institute. He had just arrived. I think he arrived in April of 1973. I was scheduled to enter the Commissioned Corps on 1 July 1973. I interviewed with him. He had very few physicians working for him–certainly no young hematologists–and he said, “I would be delighted to have you with Dr. Conley’s recommendation for two years in my division.” So I came to the National Institutes of Health, in the Blood Division, for two years after my hematology fellowship at Johns Hopkins.

Harden: As a part of the Commissioned Corps?

Klein: As a part of the Commissioned Corps. I was one of what was then called the “Two-Year Wonders.” I had thought, since it was an option at that point in the Commissioned Corps, that I would probably stay for three years. The program, as it had been outlined to me, was part administrative, but the Intramural Program had been described to me and I had actually gone over and talked with Dr. W. French Anderson at the time. Dr. Arthur Nienhuis had just arrived. Dr. Albert Deisseroth, who is now at M.D. Anderson Hospital, had just arrived. French Anderson was a molecular hematologist who had just arrived. I had thought that I would be playing a significant role in the Intramural Program of the Institute. As it turned out, since Dr. Simon was brand new, he did not realize that there was quite a separation between the intramural and extramural programs in the Heart, Lung, and Blood Institute. My role in the Intramural Program in 1973-75 was almost as an observer. I was welcome to go to rounds, to see what was happening, but my actual responsibilities were entirely administrative–those that I was paid for and judged by–in Building 31. So I stayed there for only two years. I did not elect to stay a third year.

But during those two years I was involved in several interesting, and subsequently important, areas. As a classical hematologist I had not given very much thought to blood transfusion. I trained as a coagulationist. I had been involved in some hemophilia studies at Johns Hopkins. When I came to NIH, two of the large programs that were being established at the Heart, Lung, and Blood Institute were in the hemophilia area, in what was then called Blood Resources, which was really blood transfusion. NIH had commissioned a study by Booze, Allen and Hamilton of blood resources in the United States in the early 1970s. Because the system of collecting, delivering, processing, and using blood in the United States was felt to be sub-optimal at best, a major effort was made by NIH, centered in the Heart and Lung Institute, to develop safe, available, cost-effective transfusion services for the United States. They established a Blood Resources Program.

In the Blood Resources Program were studies of post-transfusion hepatitis, since that was the major risk incurred in blood transfusion at that time. The figures indicated that as many as 30 percent of all subjects transfused with blood in the United States developed hepatitis in the late 1960s and early 1970s. There was a Hemophilia Program as well, which was fine for me because I had done some hemophilia studies earlier.

For the two years that I was there, two of the things that I was assigned to do involved blood resources with post-transfusion hepatitis and hemophilia. In fact I was instrumental in two of the large contracts that were let. One was a multicenter prospective study of post-transfusion hepatitis called the TTV Study, or Transfusion-Transmitted Virus Study. The second was in establishing a chimpanzee breeding colony in the United States for hepatitis research. The chimpanzee was the only animal model for post-transfusion hepatitis, and importation of chimpanzees from Africa was becoming difficult, bordering on impossible. Chimpanzees were very expensive, but even at any cost, the animals were not to be had. That was really limiting our transfusional hepatitis studies. As it turned out, both of those subsequently were key elements in the AIDS epidemic.

I stayed for two years, and at the end of 1975 I was looking for a clinical research position. I was very interested in blood transfusion services and was looking at programs around the country, one of which was a very small program here at the National Institutes of Health. I talked with Dr. Paul Holland, who had just become Director of the Program here, and he told me that there were no more positions available. One of their positions they had committed to a young man who had trained with me in medical school and had been on the house staff with me at Hopkins. He had come to NIH two years earlier. This was Dr. Peter Tomasulo. But, at the last moment, Dr. Tomasulo decided to go to a training program in Milwaukee. A position became available in the Clinical Center, in what was then the Clinical Center Blood Bank, and I took it.

Today, Dr. Tomasulo is Medical Director of the American Red Cross, so he stayed in this area. He is back in Washington and is Director of Blood Services across the country. As I said, he was a classmate and he is a close friend of mine.

So I came to the Clinical Center in 1975, to spend one year learning the hands-on laboratory aspects of blood transfusion. It was a small, but very exciting program at that time because it had probably one of the most important studies of post-transfusion hepatitis. This was something that I had been exposed to at the Heart and Lung Institute. Dr. Harvey Alter, who had spent his prior career primarily in post-transfusion hepatitis, was now here. He was the co-discoverer of the Australia antigen, which is now known to be the hepatitis B virus. He had continued prospective studies of patients in the Clinical Center who had undergone open heart surgery, collecting specimens from donors, and from the patients after transfusion for years, and freezing them away for prospective studies. Dr. Paul Holland, who was also interested in post-transfusion hepatitis, was here. He has published numerous papers primarily on the clinical aspects of post-transfusion hepatitis. Then there were several other individuals, who were among the best serologists in the country, interested in serology of blood. But the major research interest was in transfusion-transmittted disease, and in 1975 that meant hepatitis.

That is how I arrived here. Although my primary interest had been in coagulation, because of my experience at the Heart, Lung, and Blood Institute and because of the interest in post-transfusion hepatitis here, I became first peripherally, and then directly, involved in transfusion-transmittted disease.

Harden: I noticed in looking over your publications that you have many methodology papers. Have you been very interested in developing new techniques, methodologies, or instruments, in this specialty?

Klein: I have always seen myself more as a clinician, but I think it is fair to say that a number of the things I did had to do with technologic ways of managing patient care–cell separation, collection and processing of blood components. The Clinical Center was the ideal place to do that at the time, first of all because of its unusual patient population, and secondly, because of excellent engineering support in this hospital. Third, in the mid-1970s money for equipment was not nearly as scarce as it is now at NIH, and it was certainly much easier to obtain than it was at the university hospitals, for example. So you could do a number of things here yourself if you wanted to. Staff were hard to come by, but equipment was relatively easy. If you wanted to do studies of modification of existing equipment for therapeutic purposes that was doable.

Harden: You became Chief of the Department in 1983?

Klein: That is correct.

Harden: We are jumping ahead here a little. But I would like to ask one question. This was the Clinical Center Blood Bank before 1983 and then it became the Department of Transfusion Medicine. Why did the name change?

Klein: I wrote an editorial on that for JAMA in 1987 on the fiftieth anniversary of blood banks in the United States. The first blood bank in the United States and in the world was established at Cook County Hospital in Chicago in 1937. The individual who established the American Blood Bank was a clinician-pharmacologist-internist, and blood banking at that point was more or less a clinical specialty. Prior to that, if you wanted to transfuse blood you needed a surgeon, because you connected vein to vein. So, surgeons and obstetrician-gynecologists did most of the transfusion around the world.

The advent of being able to anti-coagulate and store blood meant that you could get rid of the surgeon and have a new kind of individual in charge. Initially the individual was a clinician responsible for knowing when a transfusion might be necessary, finding donors, and then putting the blood into the proper anticoagulant preservative solutions. Much research during the 1930s and 1940s was done in that area. But gradually the specialty was taken over, almost by default, by the pathologists who ran laboratories, because it seemed as if the important part of blood transfusion was cross-matching and compatibility. What was needed was to have a group of skilled technologists who would take blood from the donor and from the recipient and then find ways in the test tube of predicting their compatibility. So transfusion sciences shifted to the laboratory run by a pathologist and were taken care of by technologists and technicians.

By the 1970s and early 1980s, it seemed to me that things had shifted away from that. We were pretty good at doing the technical things and crossmatching, and that was not much of a problem. The major problems in blood transfusion were clinical problems. It was transfusion-transmitted disease; it was collecting large numbers of single donor components, possibly collecting components from a sick individual for their own use, so-called autologous transfusion. There were therapeutic procedures. To lower the white count in a leukemia patient acutely using a machine, you had to feel comfortable taking care of patients. Mostly the pathologists did not want patients in their blood bank. They would rather just draw units of blood from healthy people and then test them in the laboratory.

It seemed to me that blood transfusion was becoming more of a clinical discipline again. It was shifting back. That is why I wrote the editorial and used the phrase “transfusion medicine.” I did not originate the phrase–it comes from the German–but this was the first Department of Transfusion Medicine in the world. We felt that departments of transfusion medicine would have a blood bank–they would not be a blood bank, they would be more than that–they would preserve, crossmatch, test blood for compatibility, but they would also be clinical consultants for the use and collection of blood, and for therapeutic treatments with all kinds of blood components. That was the reason for the name change. It was very well thought out.

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