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Interview with Dr. Henry Masur
This is an interview with Dr. Henry Masur at the Clinical Center of the National Institutes of Health (NIH) on November 22, 1989. The interviewers are Dr. Victoria Harden, Director, NIH History Office, and Dennis Rodrigues, senior program analyst.
Rodrigues: Could you begin by telling us about your training and experience and how that led you to your involvement with AIDS patients?
Masur: Actually, I became involved with AIDS in a very indirect way. I had a fellowship at Cornell [University]. I trained under a protozoologist named [Dr. Thomas] Tom Jones, who is an expert on Toxoplasma. I was beginning to work on Leishmania donovani. Tom’s major clinical interest was tropical medicine, and he thought that for somebody training in his laboratory, it would be useful to use some of the techniques he had developed with Toxoplasma [gondii] and Leishmania, and to apply them to a parasite at which no one else was looking. He thought that Pneumocystis carinii would be interesting because I was interested both in immunosuppressed patients and in tropical medicine. Pneumocystis was something that affected both immunosuppressed patients and patients in some developing countries, such as in orphanages following World War II.
At that point, there were very few people in the United States who were interested in Pneumocystis. When I started my fellowship in 1975, the CDC [Centers for Disease Control and Prevention] had just published a review of the occurrence of Pneumocystis in the United States from 1969 to 1971. There were only 70 cases a year documented in the United States. It was a very uncommon pathogen. Only three or four groups across the country were looking at it. There was not very much in the literature. So I started doing some in vitro work on Pneumocystis because Tom thought that it was an organism that would provide a means for me to establish my own identity but still use the approaches he had developed.
Over the next few years, I split my time between three different areas. I did some work with immunosuppressed patients because I was interested in the infectious complications of immunologically abnormal people. That also provided an opportunity to study some Pneumocystis patients, so I did all the consults for a big kidney transplant program at Cornell. I also was working in Brazil on Leishmania. Until about 1978, while I was going back and forth to Brazil, I did some laboratory work on Pneumocystis. From 1978 to 1980, I spent a fair amount of time in the field in Thailand and in Brazil, and some time in the laboratory in New York.
In 1979, after I had been in Brazil, I came back and was on the Cornell faculty when I attended the first patient who came into the emergency room with what turned out to be, after a long work-up, Pneumocystis pneumonia. It was clear to me, because I knew the literature very well, that it was very unusual for someone previously healthy to walk in with Pneumocystis. At that point, we had studied the immunology of the organism, but there was not very much clinical literature. The only patients that one saw were either patients with previously recognized immunosuppression or, occasionally, in the developing world, one saw an epidemic of Pneumocystis in malnourished infants. When I came back from Brazil, however, suddenly we had this patient come in, and we worked him up very intensively. It was interesting. We did not know what to make of the fact that he had Pneumocystis pneumonia. By some simple immunologic parameters, he looked like he was very abnormal. We then looked to see who was interested in working him up with us. There was an immunology group under [Dr. Gregory] Greg Siskind at New York Hospital, which performed some preliminary work on the first patient. Then the person who was doing T- and B-cell analysis was [Dr.] Susanna Cunningham-Rundles, a well-known immunologist at Memorial-Sloan Kettering, and also Dr. Mary Anne Michelis. So, Susanna worked this patient up and, at that point, we thought we had a case report of something that would be interesting but not very important. We presented to Dr. [Robert] Good, who then was one of the world's most famous immunologists and who had recently come as the director of the Memorial-Sloan Kettering Medical Center. Although I guess one should not tell tales out of school, he ran a very imperious conference–a very regimented conference. We presented this case, and he said: “This is clearly a case of malnutrition. You should get hair clippings for zinc.” He had never seen the patient. We did not think the patient looked that malnourished, but we were amenable to his advice. So, we said, “Okay.” We sent off the hair clippings to test for zinc, and they came back normal. So, he said, “Send them to another lab. It must be malnutrition.” So we did it again, and he said, “It's malnutrition.” And that was the end of it. Clearly, we were not going to get very much help from him.
It is interesting how life is serendipitous. One of the people whom I have mentioned was working on putting this data together. Her work was delayed by a pregnancy, so, as a result, she was slow completing her portion of the case report, which would have been the first documented AIDS case, but would also have been buried in some obscure journal. Every month I would call her up asking about where all the immunologic data on this one patient was. But she dragged her heels so much that by the time she got the data together, we had seen two more patients. By then, we were planning to write about three patients. We thought that it might be a more interesting report. Actually, at that point, I called the CDC (which they subsequently denied), and I talked to the people who do Pneumocystis serology and asked them if they would do Pneumocystis serology [on these three cases] because this was very interesting. These three cases were unprecedented. The people in the serology laboratory were not interested. At that point, I was sufficiently naive and I did not realize that the CDC was a big place and that talking to the serology laboratory was not talking to the epidemiology people. So, they did not want to do anything more than just run the serologies. I said, “It would be very interesting to give us some follow-up. Are you interested in doing anything more”? They said, “No.” That was the end of it. Again, this person who was putting together some of the immunology data on the three patients was so slow that by that time she got the immunology prepared on the three patients together, I was ready to strangle her. We presented one of the cases at intercity infectious disease rounds in New York, and several people came up to us and said they had similar cases. So, we went around and we collected a dozen cases. These cases were being seen at a variety of different hospitals.
Harden: What year was this?
Masur: This was 1980. Again, the work was slowed down by the fact that I had gone back to Brazil at some time in the middle of this. When I came back from Brazil, we had 12 cases, and we got all the data together. But unbeknownst to us, one of our co-authors at Memorial was also working with [Dr. Frederick] Fred Siegal from Mount Sinai Medical Center on chronic perianal herpes, which, I guess, he did not realize was a similar issue. He was simultaneously working up some men with chronic herpes simplex plus Pneumocystis. We did not know about it although he was a co-author on our paper. Also, we did not know about [Dr. Michael] Mike Gottlieb's cases in Los Angeles. So, at this point, it was clear to us that we had seen about a dozen men with Pneumocystis, but it not clear whether they were immunosuppressed because they had been infected with a virulent strain of Pneumocystis, which had somehow altered their immunity, or whether they had somehow become immunodeficient due to something else. It was not at all clear that this was a major public health problem. It seemed to be an unusual issue, and the major focus was whether or not there was some kind of an environmental exposure. We did not know that they were all gay or intravenous drug users.
The first evidence we actually had that our initial case was gay came when I was in a room about a third the size of this one, and he suddenly leaned over and said, “Give me a kiss.” I just looked at him. In retrospect, it was clear that he was gay and he was demented: he had a red bandanna in his back pocket and wore an earring, but being naive like most physicians, I had not put all that together. Not as many people knew about the gay culture then as they do now. At least I had not read that much. We really did not know anything about the sexual orientation of the other patients. A couple of them were drug users, but a lot of the people who go through the infectious diseases rounds come from hospitals that serve that kind of clientele and have them in their ward populations. It was not clear to us until later that these people shared drug abuse and homosexuality, or that there was a connection between the two.
At this point, we knew that there were 12 cases. We submitted that information to the New England Journal of Medicine on the assumption that this was probably something involving a very small number of people and that it would turn out to be scientifically very interesting. But, at that time, there was no suggestion that it might reflect a public health problem. I went off to Brazil again. When I came back, we got a call from the CDC indicating that the New England Journal of Medicine was, in fact, considering two other similar manuscripts and that the CDC wanted to put something in Morbidity and Mortality Weekly Report. It is interesting how things have evolved since then. We were concerned that putting the information in Morbidity and Mortality Weekly Report would preclude publication in the New England Journal of Medicine. We talked to the New England Journal. They were very adamant that “prepublication” [elsewhere] would prohibit publication in the New England Journal. Again, history seems to have changed over the subsequent time. We decided that we should not put our material in Morbidity and Mortality, which probably was not the right decision in retrospect, but neither was the New England Journal's decision correct, either. In any event, Gottlieb reported his cases in Morbidity and Mortality Weekly Report. I do not actually know who had seen the first case, or who had submitted the first manuscript to the New England Journal. However, three articles were published in the New England Journal of Medicine, which thus became, simultaneously, the first peer reviewed reports of AIDS.
By then it was clear that there were three foci of this infection, but the extent of the foci was not clear. There really was no race for space or resources. It was more of an interesting scientific phenomenon. That was just about the time when [Dr. Joseph] Joe Parrillo, who had been a classmate of mine at Cornell, came here to the NIH to be the Chief of Critical Care Medicine. He was looking for senior investigators. He knew that I was interested in infectious disease and in seriously ill patients. He thought that it would be an interesting recruitment tool to be able to say, “If you want to study this strange phenomenon, there are a lot of opportunities. Why don't you come to NIH, and while you are working in the ICU [intensive care unit], you can have laboratory space. We could work something out.” I knew [Dr. Anthony] Tony Fauci from Cornell. Actually, Tony had been the chief resident when Joe and I were fourth-year students. So, we had both known Tony, and Tony had been instrumental in recruiting Joe to come down to NIH. When I came to look at a job, Tony, at that point, was very interested in getting involved in AIDS, but he had not really initiated anything. He was very excited about having somebody who would help bring in some patients so that he could study them. He was very interested in devoting a lot of his laboratory resources to it, and he had [Dr. Clifford] Cliff Lane in his laboratory as a Fellow, who he thought would be a good person to get involved in studying these patients. At that point, it seemed like another unusual disease like Wegener's [granulomatosis], or Sjogren's syndrome, which was scientifically interesting.
The NIH could be a good place to study this unusual disease because we could bring patients in from all over the country and study them. There seemed to be no need for a major initiative. This appeared to be another disease that, with the NIH’s good virology, immunology, laboratory space, and investigators, could be studied at NIH. So I came with that in mind. There was a lot of interest in this new phenomenon. Before I arrived at NIH, however, I disappeared to the tropics again for another few months. By the time I came, in early 1982, these articles had come out, and there was a lot of interest. There were a lot of people who were interested in collaborating on AIDS.
When we first started studying AIDS, we found–just by word of mouth–that there were a lot of people who wanted to look at various aspects of it. It was not an issue of resources because I was by myself in Critical Care. There were other people who, as individuals, had an interest. Tony and Cliff did the immunology. We had a meeting each week that grew larger over time. [Dr. Edward] Ed Gelmann, who is now at Georgetown, was a Fellow in the Cancer Institute [National Cancer Institute, NCI]. He was interested in Kaposi's sarcoma and searching for a viral etiology. [Dr. Phillip] Phil Smith, who was then in the National Institute of Dental Research, was interested in some other immunologic aspects. [Dr. Gerald] Jerry Quinnan, from the Food and Drug Administration [FDA] here on campus, who ran a herpes virus laboratory, was very interested in looking at CMV [cytomegalovirus], HSV [Herpes simplex virus], and VZV [Varicella-zoster virus]. They would come to the meetings each week, and [Dr. Stephen] Steve Straus, who is with NIAID [National Institute of Allergy and Infectious Diseases], was interested in the herpes virus aspects of this. So very quickly we got a group of people, all of whom were interested in different aspects of the problem.
To me, that was what made NIH an exciting, attractive place to work. You could put together a group of people who did not need an organized program because they all had a common interest. They could all pick off a piece of the problem to work on. Somebody could publish on CMV; somebody else could publish on immunology; somebody else could focus on the formative problems. This collaboration worked out very well. Some of the other institutes also quickly got involved. [Dr. Alan] Al Palestine and [Dr. Robert] Bob Nussenblatt very quickly recognized that eye involvement was a common problem in AIDS, so they got involved very early. We had an expert on every organ system and every major category of laboratory abnormality. [Dr. William] Bill Travis was very interested in the pathology of the disease. We were able to use one critical care therapist ([Dr.] Jack Ames, now a radiation oncologist) part time to deliver specimens to all these laboratories. We had a very small number of patients who were from all over the country because treating physicians did not know what to do with them, but there were not very many at that time. We had the patients come in, and while taking care of them, we would try to study them. We had one therapist who would draw blood in the morning and then go around to all these laboratories and deliver the specimens. We would meet once a week, evaluate what was going on, and decide what to do next. That was just at the time in 1982 and 1983 when the CDC data began to show that this was more of a national problem. But it was not until after this that AIDS was recognized as having a retroviral etiology. That was really the beginning of the crunch for resources. Up until then, AIDS was more of a curiosity.
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