Dr. Thomas Spira



Dr. Tom Spira

MILLER: This is Dr. Bess Miller, and I’m here with Dr. Tom Spira. Today’s date is November 6, 2015, and we are in Atlanta, Georgia, at the Centers for Disease Control and Prevention. I’m interviewing Dr. Spira as part of the AIDS Early History at CDC project. We are here to discuss your experience during the early years of CDC’s work on what would become known as AIDS[acquired immune deficiency syndrome]. I must ask, Dr. Spira, do I have your permission to interview you and to record this interview?

SPIRA: You do.

MILLER: For this oral history of the early years of AIDS at CDC, we’ll be focusing on the first several years, beginning with June 1981 with the publication of the first MMWR on the five cases of PCP [Pneumocystis carinii pneumonia] pneumonia among homosexual men. I know you worked on many aspects of the disease, but for this interview we’ll focus on your earlier work. Let’s begin a little bit with your background. Can you tell me about where you grew up 00:01:00and your early family life, and then where you went on to college?

SPIRA: For most of my life I was raised in Detroit, Michigan. My parents had come there with me originally from Czechoslovakia, where I was born. We left there when the communists took over. We were refugees in Paris, France, for a couple of years and were able to get in as immigrants through Canada. After a couple of years in Canada, we were able to get into the United States. So as I say, I was raised primarily in Detroit, Michigan. I went to elementary and high school there, and then I went to the University of Michigan for undergraduate school, followed by Wayne State University for medical school. Then I went to Chicago, Illinois, to do my training at Michael Reese Hospital, doing an internal medicine residency and then an infectious disease fellowship in the joint Michael Reese/University of Chicago program. Then after that I came down to CDC in 1975.

MILLER: Can you remember who inspired you about going into medicine? Was that from early childhood or just came up with a major in college?

SPIRA: I think earlier I wanted to be an archaeologist, because I was very interested in ancient history and that sort of thing. But I realized I wanted to make more of an impact in the world than I think an archaeologist does, so I decided on medicine. I didn’t have any real role models. I had an uncle who was a psychiatrist, but I always said he was crazy, so I don’t think he was a role model. But as I went on, I was interested in sciences, in high school, though less so, but more in college. I did a major in cellular biology, although I was also taking courses in Near Eastern Languages and Literature, so I was maintaining that at the same time. I think I shocked the Chairman of the Department of Near Eastern Languages and Literature by asking for a 00:03:00recommendation for medical school, because I was taking a seminar course with him with three of us in Ancient Babylonian and Assyrian Cuneiform.

MILLER: Fascinating.

SPIRA: It was fun. It was a busy schedule. I was taking like 27-1/2 hours per semester, but that’s what I wanted to do, so I did it. In medical school, or even in undergraduate school, I was interested in genetics as one of my science areas. I took a lot of courses in genetics, human genetics, microbial genetics, and the like, but when I got to medical school the person who was doing genetics there wasn’t the one I wanted to work with. So I got involved with infectious diseases with [Dr.] A. Martin Lerner, who was a big herpes expert in Detroit at the time. From there I went on and kept up that interest in infectious diseases. While I was doing my residency, I was going to infectious disease conferences and ultimately was offered a fellowship there as part of the program as well. 00:04:00I’ve been doing infectious diseases since then, along with immunology.

MILLER: Somewhere along the line it looks like you did an immunobiology fellowship at Memorial Sloan Kettering.

SPIRA: That was I think just before this period, in ‘79 to ‘80.

MILLER: What got you interested in immunobiology?

SPIRA: I was also interested in immunology, because even while I was doing infectious diseases I was interested in congenital and acquired immunodeficiency diseases, because they predispose people to opportunistic infections. So I had done work in medical school on that during my fellowship. Then in the years before this I was involved in the pediatric immunodeficiency clinic at Grady Hospital with Dr. Andre Nahmias. One of the researchers, one of his fellows, who 00:05:00went on to be a practitioner in Newark, New Jersey, [Dr. James] Jim Oleske, was involved with the early pediatric AIDS patients. We reconnected there when we went up to investigate the early pediatric cases in New York City and New Jersey.

[Dr. Stephen] Steve Schwartzman, one of the infectious disease practitioners at Emory, founded an adult immunodeficiency clinic at the Emory Clinic. So about once a month I was going over there to see patients with him, although there were a lot fewer patients with adult acquired immunodeficiencies, at least at that time, compared to the pediatric cases we saw down at Grady as part of that immunodeficiency clinic. When I came to CDC, I was working in an immunology-related lab with Dave Gordon as part of, at that time, parasitic immunochemistry. Later it became its own Immunology Division and then part of a Host Factors Division along with hematology and pathology. So it was then, in 00:06:001981, that the first AIDS cases hit. My sabbatical in New York at Sloan Kettering was working with [Dr.] Robert Good, and he was like the grandfather of immunodeficiency diseases here in the United States. At that time Jim Oleske was sending over some patients with possible Nezelof syndrome, which I think were some of the early pediatric AIDS cases that he was seeing there. So I did work in the Immunodeficiency clinic while I spent a little over a year at Sloan Kettering as well, and I’ve continued that interest.

MILLER: It’s almost like you were primed to work on AIDS, but who could have known.

SPIRA: Fated or cursed, whichever way you want to put it.

MILLER: What actually made you decide to go to CDC?

SPIRA: At the time it was somewhat of an ulterior motive. There was the Vietnam 00:07:00War and there was the possibility of being drafted, although my draft number I think was 365, so the likelihood would have been low. At the time I looked into Public Health Service fellowships under the CORD Program [Commisioned Officers’ Residency Deferment], getting a deferment for that for two years. There were options of doing it at NIH [National Institutes of Health]. In medical school I had done a three-month immunology elective at NIH, working in the different institutes there, so that appealed to me. I didn’t know as much about CDC at the time, but I ended up coming to CDC and working in an immunology-type laboratory. I came in the Bureau of Laboratories as opposed to Bureau of Epidemiology, which were the two divisions at that time. I took the EIS, the Epidemic Intelligence Service, course along with the others, but there were I think five of us in my group that went into the different aspects of lab work.

MILLER: So you were in the Lab division or the Lab Bureau.

SPIRA: Bureau of Labs at the time.

MILLER: Bureau of Lab Services. Was that part of another center or those were the bureaus--

SPIRA: They didn’t really have centers at the time. That’s a later development.

MILLER: So in the very early days, weeks and months when CDC started working on what was the Task Force just after June of ‘81, how did you get involved in that and what were you exactly doing?

SPIRA: Well, it became clear early on that these manifestations, the opportunistic infections and Pneumocystis, even the Kaposi’s sarcoma, were things associated with immunodeficiency. At least in the past, the only patients that were requiring medications from CDC for a Pneumocystis infection were 00:09:00people who were immunosuppressed, either naturally, or more commonly, because they had diseases for which the diseases themselves were immunosuppressive, or they were receiving immunosuppressive therapy that knocked out their immune systems. So early on I saw, when we first got the reports, that this was something that might interest me, so I volunteered for the Task Force that was forming at that time. I was, I think, the sole immunologist for a long time on that Task Force.

MILLER: Who were you working with?

SPIRA: At the time [Dr. J. Steven] Steve McDougal was one of my colleagues. He started at CDC about a year before I did, and we worked very closely together. We shared a lab together in the early years. He was involved later on in some of the other aspects of this, which we may discuss later. Dave Gordon, as I mentioned, later left CDC and went on as a hematologist oncologist; he went on 00:10:00to do some work at Emory University. Those were the main people. Then there were certain lab techs that we worked with. Marjorie Hubbard was here for many years, and [Dr.] Linda Martin. Those are the two early ones.

MILLER: How did you connect with those working on the epi [epidemiology] side?

SPIRA: I can’t tell you exactly how, because I don’t remember, but I became interested, and I contacted them or my supervisor contacted them. They were more than accepting at the time, because this was more manpower to work on this and also more expertise. So I actually looked back at my calendar. I began to be involved and went to the first meetings in the middle of July of 1981, and I think I saw my first AIDS patient here in one of the hospitals in late July of 1981.

MILLER: So what was your initial reaction as you’re starting to work on this 00:11:00new disease?

SPIRA: I could say in retrospect that I said this is obviously an infectious agent that’s causing this immunodeficiency, but I don’t think any of us were that smart at the time. As time went on, itbegan looking more like something that was transmitted like hepatitis B, as we began seeing different risk groups, IV drug users, recipients of blood transfusions, and patients with clotting disorders, as we used to call them, hemophiliacs, but we can’t do that anymore. It began looking more like a hepatitis B-like illness, at least by transmission, although we were still looking at other possible routes, other possible causes. In the early years we were involved in some studies with people at NIOSH [National Institute for Occupational Safety and Health] looking at nitrous oxide, which was used in poppers, which were used by MSM [men who have 00:12:00sex with men] as a sexual stimulant, just to see whether they would depress the immune systems. We did a fairly complex study with immunologists in NIOSH in Morgantown and people in NIOSH in Cincinnati, looking at exposure of mice to nitrous oxide for I think six hours a day for several weeks, and looking at their immune systems to see if it did cause any problems. Luckily it didn’t, and if anything it was better, but at least it ruled out one of the potential theories of what was causing this epidemic.

MILLER: So NIOSH being the National Institute for Occupational Safety & Health, part of CDC, located both in Cincinnati and Morgantown [Pittsburgh and Spokane]. Can you describe the atmosphere at CDC among colleagues working on this disease?

SPIRA: Well, with any epidemic I think everyone’s excited when they’re doing 00:13:00it. Very often when we send people out on epidemic investigations, by the time they get out there it’s over. This was not the case. I don’t think anyone of us predicted that we would still be working on this epidemic, and now we’re in the 30-something year of it. I used to joke that we had a disease development branch, and every few years the Office of Management and Budget was thinking of closing it down, but CDC would come up with a new disease. You know, they came up with Legionnaire’s and any number of things. I said with this one they put themselves out of business, because we don’t need that office any more. Apparently I was wrong, because they came up with SARS [Severe Acute Respiratory Syndrome] and MERS [Middle East Respiratory Syndrome] and a number of other things since then as well.

MILLER: How did CDC organize people working on lab aspects of this disease? Did you eventually become a defined unit?

SPIRA: I think that was much later. We did a lot of this work under our existing 00:14:00organizational structure. I personally participated in the Task Force meetings. I was involved with the first case-control study and subsequent studies as well. This was an unfunded mandate at the time, so there wasn’t the ability to set up separate units or even the knowledge in advance that we would need this in the long run. We sort of went at it with the resources we had.

MILLER: How was that? I mean you were the sole laboratorian working on this,

SPIRA: With the support staff, but there were other laboratorians. I was the only one in immunology, but we had virologists involved with this, we had pathologists involved with this, and they did a lot of work. Even some of the laboratory workers, one of them was [Dr.Donald P.] Don Francis, who came from Phoenix where our hepatitis lab used to be, that was closed out and moved to 00:15:00Atlanta. [Dr.] Paul Feorino was another prominent virologist who was working on this at the time. Among the pathologists, there were [Dr.] Ed Ewing and [Dr.] Francis Chandler and others. So there were quite a few of us involved. There were other people in virology who were looking at serological tests trying to develop assays, trying to find an infectious agent in terms of the pathologists and looking at electron microscopic analysis of material from either biopsies or autopsies from infected patients, trying to see whether we could see anything that would suggest an infectious agent.

MILLER: Was there a collaborative atmosphere between all the different laboratorians? It sounds like it was very complex bureaucratically.

SPIRA: It was. As we went along there was someone, [Dr.] Gary Noble possibly if I remember right, who was put in charge of this on the laboratory side. I think 00:16:00there was an atmosphere of trying to work together to get to the bottom of this. I didn’t feel that we were really competitive in any real way.

MILLER: You mentioned the case-control study, and that was a big event for the very early years, and you were involved in the lab component. Can you describe your role in the study as the immunology expert?

SPIRA: We were doing the studies on the immune systems of patients, primarily looking at CD4 cells and CD8 cells, the normal cell markers that we use to identify different cells of the immune system. At the time we knew from some of the early studies that CD4 cells were depleted in these patients, at least the AIDS patients. Then later as we studied other, earlier forms of disease like lymphadenopathy syndrome, we saw that they had lesser degrees of abnormality. The case-control study studied AIDS cases from one of four cities: Los Angeles, 00:17:00San Francisco, New York, or Atlanta. In Atlanta we only had two cases, and actually I saw those cases and was involved in interviewing them for the study and drawing materials from them for our laboratory studies. There were others from the epi side that went out to the various cities. I think [Dr.] Harold Jaffe went out to San Francisco and [Dr.] Peter Drotman went to Los Angeles, if I remember right, and [Dr.] Mary Guinan went to New York City. They were involved with some more extensive investigations because there were more patients there.

My lab was looking at using some of the early techniques that we had for identifying these subsets of lymphocytes and also looking at other things like immunoglobulin levels in these patients. The virologists were at the same time looking at the virological testing and serology for various things. Since there 00:18:00were a lot of patients, there was a large data set that needed to be analyzed, so we had some data managers and statisticians working with us; Dennis Bregman was one of them at the time. So all of us were working together on this over a period of time.

MILLER: Can you comment a little bit on what was the state of the art in clinical immunology at that time? I mean so much has changed, partly due to the AIDS epidemic.

SPIRA: It was just the beginning of flow cytometry being used for identifying subsets of lymphocytes. Before, when I first came to CDC in ‘75, we had to use very tedious tests: erythrocyte-rosetting, erythrocyte antibody complement [EAC] rosetting, and surface immunoglobulin staining to identify B cells from T helper and T suppressor cells. It was lucky that this was the beginning of more common 00:19:00use of flow cytometry, which made these cells much more easily identifiable. So we geared up to do many more patients, and over those first few years we did quite a few. I can’t remember the actual numbers, but there was a real increase in terms of the numbers of tests we were doing. It kept the laboratory technicians very busy.

MILLER: So were you primarily working with blood, or you mentioned lymph node tissue?

SPIRA: Initially it was primarily blood, but then later we were receiving reports of patients with what we call lymphadenopathy syndrome. They had disseminated lymph node enlargement in the neck, under the arms, in the groin. It was happening in the same populations as were being infected with, I mean being diagnosed with what we now call AIDS. These were men who had sex with men [MSM], sometimes IV drug users, but primarily MSM. We were getting reports from 00:20:00some clinicians who were seeing these patients in San Francisco, I can’t remember their names offhand, but [Dr.] Donna Mildvan in New York at Beth Israel Hospital was one. I gave a grand rounds there on the early years as part of going up there to look at some of these cases. I was beginning to see some of these patients in our immunology clinic and from referrals from local physicians who had large populations of MSM in their clientele. Similar patients were being referred to me, so we were studying them as well. In some cases when they were going to be biopsied, we asked for fresh biopsy material from them, which then went into being studied. Primarily we were doing electron microscopy in some of those patients, but also regular pathology, looking for possible infectious agents. We found some structures which I think were associated with infection, 00:21:00and we published on that back at the time. We didn’t see clear virus in those cells, unfortunately, so it was easier to say we should have found something in retrospect.

MILLER: So can you describe some of the thinking as far as what was happening immunologically? You were looking at T lymphocyte subsets.

SPIRA: We saw that CD4 cells were being depleted, and this is the major subpopulation of T lymphocytes. We know that these cells are important in terms of helping B cells make antibody to various things. They’re also important in fighting off many of the opportunistic infections that we see in these patients as well. Pneumocystis is one, certain fungal infections, toxoplasmosis, or other parasitic infections. So the lower the numbers of CD4 cells, the less likely 00:22:00they are to be able to prevent the reactivation of these infections if you have been exposed to them in the past. Many of these infections were reactivation infections, which normally wouldn’t cause any problem in a person with a normal immune system but just manifested themselves when the immune system was depressed.

MILLER: Was this new? Had this been seen in other diseases and syndromes?

SPIRA: Well, there are other T cell deficiencies. There’s DiGeorge syndrome, which is a specific T cell deficiency in children who are born without these cells, where they come down with similar infections. There’s combined immunodeficiency, that has defects both on the T cell side and the B cell side. So it wasn’t unknown before, but to see so many people having the same thing out of the blue, without any family history, without any manifestations in childhood, was very unusual, and certainly without any other underlying causes.

MILLER: It sounds like you handled a lot of specimens; blood and tissue and so on. Were you or your colleagues worried about handling these lab specimens?

SPIRA: At the time I don’t think we were smart enough to worry about it. As time went on and it became clear that there was an infectious agent involved, some of the technicians became more concerned. I remember one of them became pregnant, and she was concerned about any risk to her newborn or developing child, I should say. We did a lot of things that in retrospect we might have been more careful about. I remember when I started my lymphadenopathy study I was doing physical exams on patients, feeling under their arms for lymph nodes. We weren’t using gloves at the time, and later as the virus was identified, we 00:24:00were worried about where it might be found, whether it could be found in things like sweat. I even wanted to do a study in gay men just to see if we could find it in sweat. We were trying to get a sauna or a place where we might be able to collect it in an efficient fashion, but none of the places we approached were willing to volunteer. I think they didn’t want to be involved. But we knew it was in blood. Later there were studies on saliva, showing that saliva was not that infectious, because there were antibodies in the saliva that would inactivate or prevent it from causing infection.

MILLER: So some of the academic centers and, of course, NIH were working on the 00:25:00immunology of this disease as well.

SPIRA: I think that was a little later. The first time that we were involved, at least that I remember being involved with NIH, I think it was in ‘82, if I remember right. We had a conference at NIH on Kaposi’s sarcoma that the National Cancer Institute sponsored. A number of us went up there to discuss these cases. I think they were at the time more interested in the KS [Kaposi’s sarcoma] side of it because it was a malignancy, than they were in the epidemic aspect of it or the infectious side of it. It was only later that more people became involved, in terms of similarities between this and other tumors that are associated with retroviruses.

MILLER: How was the interaction with NIH? Was there collaboration there?

SPIRA: I wish there had been more collaboration at the time. There were times when we sent up to them large groups of specimens from our patients that we collected serum specimens from for testing, but often we didn’t get back the results. Alternatively when they did publish the results, they published other people’s results, other people that submitted specimens to them, but not including ours. We had much more collaboration with the French group, Luc Montagnier and his colleagues there. When we sent material to them, they were more readily responsive and sent back results, and that was very useful.

MILLER: Can you describe CDC’s contribution to, we’ve got the 35-year “retroscope” here. How do you see CDC’s contribution in those early years on immunology?

SPIRA: I wouldn’t restrict it to immunology. Maybe that’s my area, but certainly in epidemiology CDC was the primary institution working on that. As we’ve done in other epidemics, I think we were very good at that. We also were good in terms of identifying the risk in terms of blood transfusions, and we were trying to push the blood bankers to screen patients once the tests were available. That wasn’t always easy. Even at the conferences we had here in the early years, presenting to blood bankers cases that we had collected that seemed to have acquired the infection or acquired the disease through blood transfusion, they didn’t want to believe it. I think there were a number of issues, maybe cost and others that I may not be as aware of, that influenced them. But it was even later, I remember giving a talk at Yale, where one of the heads of the blood group, blood bankers, Dr. Bove, was located, that there were 00:28:00still some issues. They didn’t want to believe that this was caused by an infectious agent that could be transmitted through blood transfusions.

MILLER: You mentioned working with the French, Luc Montagnier. How did that come about?

SPIRA: I’m not sure who made the first contact. I don’t think it was myself, and I know that for a fact, but I know we sent them a lot of material. I gave a talk, I think in ‘83, at the Institut Pasteur on epidemiology when I was over there, and they were very welcoming and very supportive. I think there was just good relations between the two groups.

MILLER: There was a meeting at WHO [World Health Organization] I think in the early years that you attended.

SPIRA: WHO?

MILLER: Yes.

SPIRA: I remember a WHO-sponsored meeting on this that Dr. Maxime Seligmann of Paris organized. I remember it was in, I’m trying to remember the first one. There were actually two of these meetings. One was in a chateau outside of Paris, and there was a lot of discussion on these cases. That wasn’t the only thing being discussed, but we came up with a document of recommendations that WHO supported on the immunology of this disease. Certainly, I was in a group of very eminent immunologists at the time, so it was very exciting to have these discussions with them.

MILLER: Was some of the U.S. work path finding, or was there quite a bit of work being done in Europe at the time?

SPIRA: I think the group in the Institut Pasteur was very active in the early 00:30:00years and subsequently. They were very interested, and I was involved with a group of pathologists from Europe that were interested in some of our work with lymphadenopathy syndrome and the earlier manifestations. So I had gone to a meeting in Hamburg, I think that was also in ‘83, where we had discussions of that and how to approach the problem. They had a future colleague who visited us here in Atlanta in those years, a pathologist from the Tropical Medicine Institute in Hamburg who helped set up that meeting, Dr. Racz. He was Hungarian, which I could relate to because I speak Hungarian from my background; we spoke Hungarian at home. So we formed a friendship. He and his wife were both pathologists in Hamburg, so I visited with them there, too. And I remember giving a talk at the Robert Koch Institute in Berlin. No, it was at the 00:31:00Bundesgesundheitsamt in Berlin, which was the Federal Health Office there. The Koch Institute was in Munich, where I also gave a talk on one of my trips there. But I think there was a lot of interest at the time and certainly in France. They were beginning to see cases in other countries as well, in people who had contact with Africa, or indigenous cases who had contact with the United States, or other places where there were cases.

MILLER: You were fairly young. That must have been quite an exhilarating time.

SPIRA: It was, and it was very different from our previous work in the lab. Usually lab people stay in the lab. At least at CDC, they were lucky if they got to go to one meeting a year, and that wasn’t always a given. This allowed a lot more interaction with people at a number of meetings. We had our first 00:32:00AIDS-related conference here in Atlanta in those years, and then they began the international AIDS conferences. I went to a number of those. Unfortunately, I was one of the ones canceled by Congress in the Florence AIDS meeting, when they decided too many people were going and they canceled 200 people at the last minute. Te following year I gave my presentations at the International Immunology Conference in Budapest rather than going to the meeting in Amsterdam, and what I was working on at the time was the big topic of interest in Amsterdam. It was idiopathic CD4 T-lymphocytopenia, which looked like HIV but wasn’t.

MILLER: You also worked on pediatric cases. In December of 1982 there was an MMWR published on four possible cases of question mark pediatric AIDS from New York, New Jersey, and California. Can you describe a little bit about the early 00:33:00work on pediatric AIDS?

SPIRA: We worked with [Dr. Pauline A.], Polly Thomas who was working at the New York City Health Department at the time, plus others, [Dr.] Gwen Scott was a pediatrician in University of Miami. I’d say it was probably after that first MMWR we went to New York to collect further cases of pediatric HIV/AIDS. These were often children born to mothers who were infected. When we were up there, there was a case at Cornell. Her mother was an IV drug user who died of HIV, but her child was infected or was showing signs of infection. We went to Newark to collect the cases that [Dr. James] Jim Oleske had there. We went to the Bronx to the Albert Einstein College of Medicine, where Arye Rubinstein collected some pediatric cases, and we put those all together and summarized those. Polly Thomas was instrumental in doing that.

Then I went down to the University of Miami to try to get data on their cases, and they had cases in Haitian children at the time. Unfortunately, I spent a day down there while they were deciding whether they would release the information to us, and they finally decided they didn’t want to. So it wasn’t a very pleasant interaction. I had better interactions with the people there studying adult HIV, with [Dr.] Art Pitchenik and [Dr.] Margaret Fischl and some of the others, [Dr.] Gordon Dickinson. They were much more forthcoming, and we received a lot of material from them from Haitian patients in Miami, along with similar patients in Brooklyn from SUNY Downstate Medical Center. We did a lot of the early work in terms of the immunological testing in the early Haitian patients who were involved in papers that both the institutions published on that.

MILLER: So now in 1982 before the virus has been identified,

SPIRA: Not till ‘83.

MILLER: So what was the thinking? You know, all these kids, they’re not primary immunodeficiency syndromes that you might see. But why not, and why in Haitian young children? So what was the thinking? It’s easy in retrospect to say, well yes, but how did it start formulating itself?

SPIRA: I can’t give you details, because my mind is not detailed, but as time went on there was just more and more evidence that it was something transmissible that could be transmitted vertically from mother to child, as well as horizontally between individuals through certain routes. That all started to fit together, and we were just trying more and more to find that agent. It wasn’t until the French first reported on their LAV, Lymphadenopathy-Associated Virus, that it all came together and became much more clear.

MILLER: You talk about your work with the Haitians and primarily in Florida, but I guess they were also in New York.

SPIRA: In Brooklyn.

MILLER: Can you talk a little bit about the collaboration that you had with the folks in Brooklyn and Miami on the Haitian patients?

SPIRA: Well, at the time they didn’t really have the immunological support that they needed to study these patients well, so we volunteered our services for doing that. We received material, blood samples primarily, through overnight delivery from these patients from the clinicians in both of these areas. We were also receiving some material from Haiti itself. Peter Drotman had made a trip to Haiti to try to see if there were cases there as well, and he brought back serum specimens from there that were later tested. We also developed collaboration 00:37:00with one of the clinician pathologists there in Haiti, Dr. Elie, who continued to send us patients over a period of time that he thought were infected. We did immunological studies on those patients. So I think that was a very profitable to both sides, a win-win situation for collaboration there.

MILLER: Can you talk a little bit about the atmosphere among the Haitian patients and community at that time?

SPIRA: Obviously we weren’t talking to them directly. I think later as this became more political and the stigmatization of Haitian patients was occurring, it became more of an issue. Then CDC reclassified that risk group from patients coming from countries where there was heterosexual transmission of HIV, rather than make them a single group. In the same way hemophiliacs didn’t like to be classified as a risk group by itself, so it became patients with blood 00:38:00disorders. I think it wasn’t until the hemophiliacs came onboard that this became much more a noticeable issue, because they were much more connected politically and could get more resources applied to this problem through the government and other sources as well.

MILLER: So the patients receiving blood products, were they wealthier or just more politically connected?

SPIRA: I think they were just more politically connected. It wasn’t an out group, if you will. It wasn’t a stigmatized group like IV drug users or MSM or sex workers or the like. I think it was then that it became much more well known and wasn’t given names like GRID or Gay Related Immuno-Deficiency, which was not a very useful way of describing it.

MILLER: Do you recall discussions as to the early thinking as to why these 00:39:00Haitians were a risk group early on?

SPIRA: I can’t say how early I remember, but I think it just fit together. At that time we didn’t realize that this may have come from overseas. It was only later when we began to do some studies from Africa from our group in the Congo. We had a lab there. The connections became a little more clear as time went on, but I don’t think in those early years we could really make the connection.

MILLER: One of your major efforts in the early years was studying patients with lymphadenopathy syndrome, and you were involved in the longitudinal study of homosexual men with the syndrome of unexplained lymphadenopathy. Can you describe the syndrome a little bit and why you did a longitudinal study on this group?

SPIRA: At the time we were getting reports and actually seeing patients here in Atlanta of men who were MSM who had developed lymphadenopathy out of the blue without any other illness necessarily, although some of them were symptomatic when they first developed it. This was noticeable to them or even noticeable to people who were looking at them, you know, pointed out by others, because it was often in the neck. Sometimes these were very massive, 2-3 inches in diameter sometimes, and they weren’t happy having them. So some of them consulted their physicians to see what was going on. This was happening at the same time as the HIV AIDS cases were occurring elsewhere in the same cities. I mentioned that we were getting reports from some of the clinicians in San Francisco and New York City of similar cases. We thought it would be useful to try to see what the 00:41:00natural history of this syndrome at the time was, beyond doing the immunological studies to see if their immune systems were suppressed. They were to varying degrees, some of them were not so much, some of them were more so. But we wanted to see what would happen over time.

We weren’t doing a Tuskegee syphilis study type thing, because as agents became available to treat these patients, they did go on those treatments. We didn’t do anything to prevent that. In fact, one of my patients in the study became the first patient on DDC [Zalcitabine [2?-3?-dideoxycytidine, ddC], also called dideoxycytidine, the third antiretroviral to be approved by the Food and Drug Administration, which was one of the early HIV drugs, and he developed a massive rash. This was up at NIH where we sent him for that care. But at that time we just weren’t sure what was going on; was this something different, or was this something similar, part of the same spectrum of disease. So we began studying these patients. Over a year and a half or so, I began in November of 00:42:00‘81 enrolling these patients in the study, and there were seventy-seven in the study. Of those seventy-five were HIV positive when the first test became available. So our case definition which we used at the time was very good I would say, and we followed these patients. About every three months they would come in to see me at CDC. At first I was seeing these patients by myself, and then some others joined me. [Dr. Daniel B.] Dan Fishbein was one, and [Dr.] Robert Janssen helped in terms of doing, he was a neurologist by training so he did some neuro-psych testing, psychometric testing of these patients to show that there were aspects of mental involvement with these patients as well, and he published some papers on that. [Dr. Jonathan] Jon Kaplan, who I still work with now, was also helping me for a period of time following these patients as well.

MILLER: So what were you collecting on these patients? Was it doing routine exams?

SPIRA: We were doing routine exams, physical exams, looking certainly at the lymphadenopathy but also looking at things like splenomegaly, hepatomegaly, going through a symptom review with them to see if anything else had come up. Some of these patients did go on and develop HIV/AIDS with an opportunistic infection or Kaposi’s. We were doing immunological studies of CD4 and CD8 cells, the spectrum there. We were also doing some serological studies when viral load tests became available. We were looking at the crude or viral load test that we had at that time. We were doing P24 antigen, which was one of the early tests as well. There was a variety of things that we had available over time, and we followed these patients for about 12 or 14 years. Over that period 00:44:00of time a lot of the patients unfortunately succumbed to the infection, because we didn’t have the best of agents at the time. Of the others, some of them left town, went on to other places, as you might expect in a mobile population.

MILLER: So were you seeing them in an office at CDC or did you move to a clinical setting?

SPIRA: We had an occupational medicine clinic here at CDC in Building 1--well, it wasn’t in Building 1, it was in one of the smaller buildings. We got permission, although a grudging permission, from the staff there, the doctor in charge there, to use one of their examination rooms and schedule patients there. So that’s where we saw them later as it built up. I think originally I saw them in my office.

MILLER: So you must’ve gotten to know these patients quite well.

SPIRA: Very well.

MILLER: So how was that in terms of the early years? There must have been a lot 00:45:00of patients that died, especially in the early years.

SPIRA: It was very depressing. Certainly with the study patients I built up a relationship over many, many years. It was very difficult not to be able to give them something that would help them. I think one of the reasons they came in to CDC was the expectation that being part of the study would be beneficial to them, although obviously we couldn’t guarantee that up front. Even within that population, plus I was seeing patients at the VA [Veterans Administration hospital] and the infectious disease clinic, in the early years it was very depressing because patients were coming with opportunistic infections. You could treat those to the extent that we could, but they would often die of other things that we couldn’t treat.

MILLER: So some of these illnesses were quite complex. I guess then patients were admitted to the hospital.

SPIRA: We did not do any primary care of these patients here. They all had their 00:46:00private physicians who took care of their care. Obviously, we don’t have a clinical facility here like the clinical center at NIH, so we can’t do workups and hospitalize patients here. We did report out the basic findings to the clinicians on a routine basis after we saw the patients, so they had that information as well.

MILLER: So this went on and then the virus was identified and then slowly there began to be treatment protocols. So I guess you saw the whole spectrum.

SPIRA: We saw the beginning with AZT [zidovudine, a nucleoside analog anti-retroviral drug, the first HIV/AIDS drug] and then some of the other nucleoside reverse transcriptase inhibitors. Later, as more drugs became available and multidrug therapy became useful, we saw that the AZT patients sometimes after eight or nine months would develop resistance to that drug. We didn’t do resistance studies. We didn’t get that far, but we did see that 00:47:00their immune systems wouldn’t improve after that. That was disappointing, I must say.

MILLER: Again, I assume you were drawing blood from these patients. At that time were you concerned about your own risk for acquiring the disease?

SPIRA: Up front I wasn’t. I think we were all in denial. I did have some needle sticks I think on two occasions, which was worrisome. There were certain things I didn’t do for a period of six months after that, just because I didn’t want to risk exposing anyone else to this. So it was worrisome. It wasn’t hazard free.

MILLER: Was the Public Health Service testing for HIV when you had routine exams?

SPIRA: We didn’t have routine exams, but being in the lab at some point, I can’t remember exactly when, they would collect baseline serum or blood on us 00:48:00and freeze it down, in case there was any exposure later on, to see whether we were positive before the exposure or if anything untoward developed it was only after exposure.

MILLER: You worked also with colleagues, I think you mentioned this, to try and find an infectious causative agent in lymph node biopsies. Can you describe what was involved in doing that?

SPIRA: I think primarily the pathologists were doing electron microscopy. Dr. Gorelick was involved in that. He was the electron microscopist here. As I mentioned, they found some tubular structures that were found in some other diseases that maybe might have been associated with this that were in the patients and not in other normal tissue. But we didn’t unfortunately find the virus itself. On the other hand, we were also doing studies in animal models 00:49:00with the virologists. We were exposing marmosets and also some retired chimpanzees from the hepatitis studies that came in from Arizona. They were brought here, and these were giant chimpanzees. I don’t know how old they were but,

MILLER: But we know they were retired.

SPIRA: They were scary. I actually had my finger squashed when the cage gate came down on my thumb or something. But when we had to get blood on them, we didn’t do the actual draw, but I was there to get it immediately. It was not an easy thing to do. The marmosets we followed over a period of time to see if they would show any immune deficiency over time. Unfortunately, they didn’t. This virus didn’t seem to affect them. It was only later that we found out that chimpanzees, although they are probably the source of this, don’t show 00:50:00any manifestations. What we did originally was inject them with infectious material from patients, infected cells, to see if we could replicate the disease in that model.

MILLER: Can you say more about that? Were others doing this as well? Was CDC sort of filling a niche that wasn’t filled elsewhere?

SPIRA: I’m not aware of anyone else doing it at the time, but I may not have been aware of everything going on elsewhere. But it was one of the ways CDC was trying to see if we could show an infectious agent as well.

MILLER: Very exciting.

SPIRA: It was interesting, if not exciting.

MILLER: So where were these chimps kept?

SPIRA: These were actually kept here. There were two floors in, I forget the 00:51:00building number since it’s no longer there, where they had animal facilities, mainly mice and rats and maybe some rabbits. I think they had to make special provisions for these. They had two chimpanzees and I can’t remember their names, though I should.

MILLER: You just had two?

SPIRA: Only two. Chimps are very expensive to keep up, and I think for whatever reason there were only two.

MILLER: Okay. So looking at the lab in general, how would you say the early work on AIDS affected the labs? First of all, there musthave been budgetary constraints. Were there necessary supplies? How did that work?

SPIRA: Luckily we were able to cover what we needed in terms of getting reagents for doing this work. I don’t remember any time when we were short, although where the money came from and what budget it came from I’m not sure. There 00:52:00wasn’t a specific mandate at the time for that, but somehow someone was allocating the funds for this.

MILLER: So you had test tubes and gloves and reagents.

SPIRA: We had no shortages.

MILLER: Did the labs grow under the demands of AIDS?

SPIRA: It had to. Originally there were just a few of us working on it, but then it expanded and more people were drawn into this. That’s both, not just immunology but virology as well. I’m not sure if pathology had additional individuals, but certainly more of their time was spent on this. We also had people in our group. Linda Martin was involved in looking to see what would deactivate the virus, once it was found that it was a viral disease, because there were concerns about surfaces in the lab. You know, could you get it from 00:53:00being around a place where blood had spilled. So there were some very nice studies done there to address that issue as well.

MILLER: Can you say a little more about the lab precautions? Were these things done under a hood?

SPIRA: Initially we were doing them out on open counters, and it was only later as it became more likely to be an infectious agent that we started doing work in laminar flow hoods.

MILLER: So there was no discussion of consideration of doing this in higher containment labs, after we’ve all been re-sensitized after the Ebola outbreak?

SPIRA: No. If it had been a more readily transmissible agent, let’s say through aerosol, then we would have seen more cases in people around them that had no direct contact with individuals who had the infection. We weren’t 00:54:00seeing that. In the initial case-control studies, some of our controls were friends with the patients; others were MSM with the same age and from the same city as the patients, so we didn’t see anything like this in necessarily friends. We did see some patients who were MSM but were just the same age from the same city that were likely infected, but earlier on in the disease and weren’t aware of it. So there was no evidence to be worried about anything more readily transmissible at the time.

MILLER: So looking back again now from a number of years later, are there any aspects of CDC’s response where you feel that we fell short or could have done a better job?

SPIRA: Well, you know, the early people that were involved in the Task Force were coming from the sexually transmitted diseases group, who were dealing with 00:55:00gonorrhea and syphilis epidemiology. That was very good. Jim Curran and Harold Jaffe were coming from there. It certainly exposed some of us who weren’t as well versed in those areas in terms of how to ask questions about different types of sexual activity. It was an education for me. I think I had led a sheltered existence before then. But I’m not sure what I would have done to make this work better. I think Jim Curran did a very good job in terms of leading the Task Force and advocating for additional resources and the like, to the extent that not all of us were involved and were aware of what was being done. At least, as I said, we didn’t feel any major deficiencies there. So offhand I can’t say I would have changed things necessarily.

MILLER: Well, in closing I’d like to ask a few questions about the personal aspects or impact of your work on AIDS. You were obviously a huge part of something that changed the history and course of public health. How would you say that’s affected you personally?

SPIRA: Well, I’m still doing HIV AIDS work in the 34th year of this. I don’t think anyone could have predicted that. Certainly I couldn’t have. About eight years ago I switched from the lab, let me take it back a little further. In 2005, I retired after 30 years in the Commissioned Corps of the US Public Health Service, and I had the option of either staying on the domestic side of the lab or going to the international side of it. I decided to switch to the international. But after a couple of years, I decided to go to programmatic side 00:57:00and do adult HIV treatment, since I’m a clinician as well. I’ve enjoyed that immensely. I feel that at this point in time I’m having more of an impact there than I would have if I’d stayed necessarily in the lab. All along I think I’ve worked with a very good group of people, dedicated, hardworking, and I think that always makes things easier. That’s certainly the case now, and there’s never a shortage of things to do. We have had some increase in our staffing which is good. PEPFAR funding is maybe better and more predictable than it was in the past than other areas.

MILLER: PEPFAR being the,

SPIRA: President’s Emergency Plan for AIDS Relief. We’re in our third five-year plan of funding, so that’s I think what was nice to know: that you’re valued and people are willing to put money behind that value.

MILLER: Can you say a little bit more about actually what you are doing now which is so interesting?

SPIRA: I provide liaison for certain countries overseas in terms of their adult treatment program. So I’m liaison for Ukraine and central Asia, which are focal epidemics primarily among IV drug users, and also for Kenya and Tanzania and Mozambique, which are more generalized epidemics. So there are a lot of areas that have been changing over the years in terms of the eligibility for HIV treatment or antiretroviral treatment. Right now the WHO is recommending shifting to ‘test and treat,’ meaning everyone who is found to be infected should be treated as soon as possible, so that’s an exciting time.

Viral load testing, which wasn’t available in the past due to cost and other infrastructure aspects, is now becoming more available in countries and is being 00:59:00recommended as the means of following patients to make sure that their virus is suppressed. WHO came out with a 90-90-90 program, where you want 90% of the people who are infected to know their status, 90% of them to be started on antiretroviral therapy, and 90% of them to have their virus suppressed, meaning have an undetectable viral load. Working to achieve that has been very exciting. Our previous division director, Dr. Birx, is now the Global AIDS Coordinator in Washington, and she’s instituted a lot of major changes in how we approach this, emphasizing the use of evidence to see where we put our funding and using data to evaluate the impact of that funding to try to concentrate on geographic areas where we’ll have the greatest impact. So it’s been an exciting time just in the past year trying to keep up with that and put into practice what 01:00:00she’s been recommending.

So it’s an exciting time here. Because we’re using data much more frequently, there’s much more data to look at and it’s coming in on a quarterly basis. So there’s a lot more work both for our headquarters teams and our in-country teams to keep up with this and also to maintain the quality of the services that we’re providing. We’re doing much more these years to monitor the quality of our programs overseas as well.

MILLER: It’s been fascinating, Tom. Any closing thoughts?

SPIRA: Well, it’s been an exciting 30 or more years. Before I started HIV work, I was working on other immunodeficiency diseases, but those are few and far between. I think that work helped in terms of being easier for me to actually transfer into this area and have some contributions here, and I hope to 01:01:00be able to do that for a few more years.

MILLER: Well, I do too. Thanks very much.

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