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Interview with Dr. William A. Blattner

This is an interview with Dr. William A. Blattner, Chief, Viral Epidemiology Section of the National Cancer Institute (NCI), National Institutes of Health (NIH), at his office in the Executive Plaza North Office Building, Bethesda, Maryland. The interview was conducted by Dr. Victoria A. Harden, Director of the NIH Historical Office, and Dennis Rodrigues, program analyst, NIH Historical Office, on 2 March 1990.

Rodrigues: Would you tell us about your training and your professional background before you came to the NIH, how you came to the NIH, and how you became involved with HIV disease?

Blattner: I did my undergraduate medical school training at Washington University in St. Louis. I had my first experience in epidemiology during summer rotation through [Dr.] Lou Allen Sale, who was the head of preventive medicine at Washington University. He arranged for me to go to Mexico as a COSTEP [Commissioned Officers Student Training and Extern Program], which is a PHS-sponsored [Public Health Service] activity. I spent three months in Mexico City working at a children's hospital, trying to assist in some studies of nutritional determinations, particularly measuring red cell enzyme assays in children with malnutrition. It was not scientifically productive, because we spent most of the summer trying to get reagents shipped down to Mexico to run the assays. The problems we experienced in trying to get a fairly routine substrate for an enzyme assay taught me a lot about the prolonged delays that can occur in international research programs. If I had been in St. Louis, I could have gotten the substrate in twenty-four hours. It took me two months to get it in Mexico City. There were the problems of transportation, customs, and living and working in the Third World environment. I think that often we do not appreciate what our overseas colleagues have to put up with–they do not have things we take for granted. It has helped me, subsequently, in my efforts in the international arena, to be a little more sympathetic about why things do not happen pronto.

After graduating from Washington University, I went to Rochester, to the Strong Memorial Hospital at the University of Rochester in New York. I did two years in internal medicine, and from there I went to Cornell [University] to do my third year as assistant chief resident at Cornell and the [Memorial] Sloan-Kettering [Cancer Center] in New York. During my time in Rochester, I can remember getting a call from Joe [Dr. Joseph] Fraumeni. He had done some archaeologic work in the Commissioned Corps Office over in Building 10, looking for potential applicants for the epidemiology program. He had come across my folder, and for whatever reasons, invited me to the NIH for an interview. That set the stage for my coming to the NIH in 1973, after my year at Cornell. At Cornell, I had the good fortune of working frequently at Sloan-Kettering, which provided me with my first experience in oncology as it should be practiced. I think it focused my attention on the idea that cancer is an important disease, and it poses a challenge similar to that of AIDS, because it is a multi-system disease that involves the totality of the patient. To be a good oncologist, you have to be a complete physician, because cancer has so many complications.

Harden: Is this what you mean by “oncology as it should be practiced?”

Blattner: Yes. At Sloan-Kettering there was an attitude of optimism and a belief that cancer was a treatable, potentially curable disease. When I first arrived, because of my previous experience, I did not have such an optimistic and hopeful attitude. I am basically an optimistic person; in the face of adversity, I look for the positive potential in the situation rather than the “down” side. The Sloan-Kettering experience thus oriented me toward a career in cancer.

Cornell also introduced me to a very strong infectious disease community. Tony [Dr. Anthony] Fauci had come to the NIH from Cornell a year or so before, and Henry Masur interned, I think, under me. I made a lot of contacts that would subsequently be important in my interactions here at the NIH. Dr. Warren Johnson was the director of the International Health Care Services at Cornell, and working with him was a very positive experience.

The years at Rochester and Cornell provided balancing experiences in the development of my career. Rochester was more of the city-hospital type of environment. There I learned to treat a lot of common diseases in my sleep–so to speak. Cornell was much more of a referral center, and the staff saw a lot of unusual diseases. It also has a large international clientele, which enabled me to see some disease problems that are common in overseas countries but rare here-for example, parasitic infestations. There are various diseases you usually do not see in a lifetime, unless you work in a place like Cornell. These two experiences, I think, laid the foundations for my career.

I came to the NIH without any real training in epidemiology. In 1973, I planned to spend two years at the NIH, after which I would go back to New York and do sub-specialty training in infectious diseases, or whatever I might end up doing. When I came to the NIH, I spent a lot of time on the cancer wards and also on the infectious diseases wards on rounds with Tony Fauci. I was interested in the interrelationships of the immune system with cancer. I had an interest in an interdisciplinary approach to research, and I was brought by Joe Fraumeni and Bob [Dr. Robert] Miller into the study of families at high risk for cancer. I had a strong interest in developing the application of laboratory approaches to cancer etiology, which has now become popular as the field of biochemical epidemiology and is the “approach du jour” in epidemiology. But I was taking a lot of courses through the FAES [Foundation for Advanced Education in the Sciences, Inc.] evening graduate school at the NIH. I took subjects beyond those that one might expect someone in epidemiology to take, particularly courses focusing on the immune system. My basic approach was to study families at high risk for cancer, believing that an interdisciplinary method bringing laboratory and epidemiological techniques together would uncover the pathogenic and etiologic mechanisms that underlie the process of development of cancer.

In 1974, Joe [Fraumeni] had a call from Bob [Dr. Robert] Gallo, who, at that time, was over on Pearl Street, where the Air Rights Building is now–the old Bionetics facility. Gallo's laboratory was working with the HL23 virus which was then thought to represent the first human retrovirus but subsequently was shown to be an animal contaminant. This circumstance was the source for a lot of grief for Bob, but it was a useful time for me from a certain perspective. I established a close relationship with Bob that has gone on since then. I think that in dealing with Bob Gallo an important aspect of the relationship is trust. We developed a trusting relationship at that point despite the adversity of the time for Bob. My role in this Gallo laboratory project basically was to interview and to collect information on the patient from whom the leukemia bone marrow containing the HL23 virus had been obtained by Gallo. In January 1975, I made a trip to visit the woman and her relatives in her home town in Kansas to get additional material. That material was used in subsequent attempts to isolate the virus. We never succeeded. We still have material from this woman and her family members in the freezer. In 1974 I had gotten married, and on this trip to Kansas in 1975, I took along my bride. We planned to visit some of my relatives in the area after completing my work. My wife is a nurse, so she drew the blood and collected information from the patient's family.

During this time I recognized the need to establish a repository of biologic materials. The specimen from the woman in Kansas was added to that repository. I had a little table top centrifuge in my office in which I would spin the specimens down. In retrospect, with all that we now know about biosafety, many of the things that we did in those days as house officers, blood smears, for example, were done without much concern for biosafety. I got tired of spending my evenings labeling tubes, so later we developed a more formal repository which now houses thousands of samples.

To return to my early work with Gallo, when we became interested in the relationship of the Gibbon ape leukemia virus to the woman from Kansas's virus, I tried to track down the apes that had been the source of the animal virus isolate. That led me subsequently to Sacramento and the Bay area, where there was an “ape lady” who was famous for keeping primates in her home. In fact, she was on the cover of the local Sunday magazine from a Sacramento newspaper, holding up her Gibbon ape. Interestingly, another species of monkey was also in the picture. This Sacramento woman had all these apes and monkeys living together in her backyard. The importance of this was that one of her animals was the source, as I understand it, of the Simian sarcoma virus discovered at Davis [University of California, Davis]. One of her animals was probably cross-infected from a different species. That led to a different type of malignancy in a different species of monkey. These were the interesting background things that Gallo really appreciated. I did not get anything scientifically out of this work except Bob's friendship and good will.

After the blow-up over acceptance of HL23 [as a retrovirus], for reasons that are recorded–presumably contamination–I returned to my studies of families, focusing primarily in the area of immunology. I made my first contacts with Sam [Dr. Samuel] Broder. He and I were clinical associates together in 1975 on 12 West [in the NIH Clinical Center]. Subsequently, I worked with him in the immunologic evaluations of some families in collaboration with colleagues from Tom [Dr. Thomas] Waldmann's group. After I arrived at the NIH, I can remember [Dr. Costan] Berard's first lecture on the concept of T- and B-cells. I would go every year to hear the update on the progress made in understanding the relationship between the immunopathology that was going on and the immunology that was being characterized. It was a very exciting time. I learned a lot about fundamental biology and immunology, which proved useful later on. Also, I established an association with [Dr.] Dean Mann, whose future work was very important in defining immunogenetic aspects of cancer and familial cancer. I also met [Dr. H.] Uchiyama, who was from [Dr. Kiyoshi] Takatsuki's group in Japan and who had come over to Sam Broder's laboratory. At that time they were working with HUT102 and had established B-cell lines from one of the patients who was the source of the first isolate of HTLV [Human T-cell Leukemia Virus]. Uchiyama was critical to Dr. Waldmann's and Sam's development of anti-tac antibody, which was the monoclonal to the interleukin-2 receptor. There was a lot of networking and interaction going on at this time. This was when I first heard about T-cell leukemia.

At the beginning of 1980, Bob Gallo brought me back into the fold, so to speak, with the question of a new virus that they were in the process of characterizing. They were focusing on the relationship of this HTLV virus to mycosis fungoides, which was the clinical diagnosis on the patient, CR, from whom the virus was isolated. Bob told me about his work and I helped him get samples from cases of mycosis fungoides. We ran a lot of tests, but none of the cases were positive.

Mr. Gordon Piller, who runs the Leukemia Research Fund in the U.K., had come over to the NIH a few times in the preceding years. Bob Gallo had brought me over to his laboratory a few times to meet Mr. Piller, because Piller was trying to develop in the U.K. a front-line, field-oriented approach to epidemiology modeled after the approach I was pursuing. At that time, most of the epidemiology in the U.K. was being run out of armchairs in Oxford, by looking at statistics, and not really “pressing the flesh” in a certain sense. Mr. Piller was an important contact, because in May 1981, the Leukemia Research Fund sponsored a one-day meeting in London, and I was invited to it. That was really, for me, a watershed event. I was fairly successful at what I was doing in family studies and had a lot of ideas and many projects going on. I had not given the HTLV story as much attention as perhaps I should have.

I went to this meeting in London, which had a rather interesting format. Sir John Dacie, a famous hematologist from the U.K., had developed an approach to such meetings in which he got rid of all the props that scientists use, such as slides, blackboards, and charts. He put us into a fairly barren, quite old amphitheater in the Royal College of Pathology, which was established around 1853. The scientists sat around a table–a few French, a few from the U.K., myself and Bob Gallo, talking about leukemia research without any slides or any other props.

The night before this meeting, Bob had given a talk, which was one of his usual whirlwind tours of the field looking at where things stood with HTLV. The talk was inspirational. Dr. Gallo has a beautiful way of synthesizing things. He came down from the lectern after his talk. I was standing there with him when a dermatologist from one of the local hospitals came up to him afterwards, and said that he did not think that the patient, CR, had the diagnosis he was said to have. He did not think the patient had mycosis fungoides. For me, that was a real red flag. We had been looking at mycosis fungoides but had not been finding anything. So, I was primed somehow, with that little comment, to start thinking about the HTLV problem again.

As a consequence, the next day Gallo revealed a little more of the unpublished data, in which he had a few positive cases from Japan with this ATL [adult T-cell leukemia/lymphoma] syndrome that he had gotten from Professor [Yohei] Ito. He revealed that all of several hundred mycosis fungoides cases were negative. Danny [Dr. Daniel] Catovsky presented some cases of West Indians, three or four, who had an unusual form of clinical lymphosarcoma cell leukemia of T-cells. This information jelled in my head. I went back to my hotel room and I wrote a four page letter, of which I still have a copy, outlining my next three years of research. It was really extraordinary for me, because I had not done that sort of thing before. I had a series of hypotheses: (1) HTLV-1 caused the ATL disease in Japan; (2) it was causing this disease in the West Indies; and (3) it also caused other unrecognized immunologic aberrations.

We started a collaboration with Catovsky, who sent over some serum from these West Indian cases. This was the first time that Gallo's people started getting clear positives. In the meantime, they made a second isolate from a black woman from New York. I went up to New York and spent the day in the record room at SUNY [State University of New York] Downstate State Hospital, where I reviewed a huge chart. There was not very much there. I flipped over the nursing notes and there was the information I was looking for. This woman was from the Caribbean. She was from Saint Lucia, and that provided another confirmation of a Caribbean connection.

continued on page 02

 

 
 
 
       
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