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In Their Own Words: NIH Researchers Recall the Early Years of AIDS
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Harden: Could you expand a little more on the case of the brother? What kinds of symptoms did he have? Where was he in the disease process?

Goedert: He had a skin lesion on his thigh, and he had a lesion in his palate. Both of these had been biopsied and his doctors could not figure out what was causing them. He had the enlarged lymph nodes, and the question at that moment was should he go ahead with a lymph node biopsy. He had also had, as I recall, some fevers, night sweats, and chronic sinus problems.

Harden: Did he live in Washington?

Goedert: No. At the time he lived elsewhere. The lymph node biopsy was done at a very well known university medical school. He called me back, maybe a week later, and told me, “They said it was Kaposi's sarcoma.” I said, “They must be wrong. That is impossible.” I had, in my whole career, seen one case in an elderly Jewish man whose general practitioner had said, “I think this is Kaposi's sarcoma.” Nobody else ever agreed with him. That was the only case I had ever seen or of which I had heard. I was very familiar with the literature and knew that this cancer just did not occur in young people.

Harden: What year was this?

Goedert: This was February and March of 1981.

Harden: The first publication on AIDS was in June 1981. Is this just before that, rather than a year or more before.

Goedert: No. I do not think so. The first phone call, I think, was in February [1981] and then the second conversation was probably in March. I remember that the man and his whole family ended up coming to Washington to see me. They brought the slides. I took the slides over to the Armed Forces Institute of Pathology and the eminent pathologists at AFIP in the Sarcoma Section said, “No, this is not Kaposi's sarcoma, this is angiosarcoma.”

We worked out a treatment for the man based on that, but it was not appreciably different than what would be done for a Kaposi's sarcoma patient anyway. Actually, when I say we worked out a treatment, this happened just before the annual American Society of Clinical Oncology meetings. I made a number of phone calls and scurried around, as an eager young fellow should do, and I asked all of the sarcoma experts at the time what they would do for this fellow. Nobody really knew for sure. They all had their own ideas, but there was no clear, certain therapeutic approach for him in terms of what should be done.

His sister, meanwhile, who had originally been the one to call me, had been asking around in New York, where she lived, about different possibilities for treatment. She had discovered that there were a number of other young men who were said to have Kaposi's sarcoma. She put me in touch with a physician at the VA [Veterans' Administration] hospital, I think in Brooklyn. I had a conversation with this physician, and he said, “Oh yes, we had–I think he said–six [patients]," or something like that. I said, “That is amazing.” He said, “Yes, and they are all gay. Is your patient gay?" I said, “I don't know.” Times have changed in terms of what we ask our patients. In the end my patient reluctantly acknowledged that he was gay. That was a time, especially for a young professional, when it was not something that was out in the open.

Anyway, the whole family ended up moving to Washington, and the young man was treated indirectly by me. At that point I was at the NIH full-time, so it was one of the junior fellows at Georgetown who was his primary physician. As was true for most AIDS patients at the time–as is true for a Kaposi's sarcoma patient–he had a prolonged but not especially successful treatment experience at Georgetown. Shortly after, on the heels of his occurrence, another essentially openly gay black man appeared at Georgetown, who had Kaposi's sarcoma and a number of other illnesses. I became involved in his case also, since at that point the information was exploding in terms of the immunology and so on.

Harden: This is still mid-1981?

Goedert: July of 1981.

Harden: In July of 1981 you were beginning to hear more and the MMWR [Morbidity and Mortality Weekly Report ] publications and other information were coming out?

Goedert: [Dr. James] Jim Curran [from the CDC] had come by. I do not know exactly how I first got in touch with Curran, but we had a couple of conversations and my initial patient was included in that first MMWR report.

Harden: Right.

Goedert: I contributed some information from NCI's SEER Program [Surveillance, Epidemiology and End Results] in terms of expected incidence rates and so on.

Harden: What was going through your mind at this point? The disease could not possibly be Kaposi's sarcoma, but it was. Were you and your colleagues thinking about a new disease, were you trying analogies with other things, or were you thinking of zebras or horses at this point?

Goedert: This was certainly a zebra. There was no question about that. The first thought, before I heard anything about the other cases, was that the patient probably had some inherited familial susceptibility. We knew at that time that there were cancer families. Joe Fraumeni and [Dr.] Frederick Li had been studying them. They are now well known in terms of the p53 gene. I strongly suspected that the patient was probably a member of one of these cancer families–what we then called a sarcoma family. I drew blood from the other family members–there were two sisters and the parents–with the intention of at least banking it away until the time when we would have something that we could hang our hats on. There were some other tests such as HLA typing and the like.

Once it became clear that this was an outbreak among homosexual men, it completely changed the character of the disease. [Dr. Robert] Bob Biggar arrived in our group at NCI almost at the same time as I did, and Bob came to us with more of an infectious disease orientation. We talked about two essentially different theories as to what the disease might be. We had some, at least for me, eye-opening discoveries as to the gay lifestyle of the time.

Bob and I initially took two approaches to this. First, I took the approach of characterizing some of the immune abnormalities. We had, in early to mid-1981, bought into the new technology of flow cytometry by getting a cell sorter. [Dr.] Mark Green suggested that I try to recruit some gay men and see what their cells looked like. I went back to my sister-in-law and asked for her assistance. I knew she had some acquaintances that were gay. In fact, she put me on to a fellow who helped me set up a pilot study of fifteen gay men in Manhattan that we still have going twelve years later. Essentially, we characterized the CD4 and CD8 populations in the first two [AIDS] cases at Georgetown and then in these fifteen gay men in New York. We came up with the startling discovery that half of the asymptomatic New York men were immunologically abnormal and also that there was an apparent association with nitrite inhalant use.

Shortly thereafter, Bob Biggar, who has his own novel way of thinking, with the epidemic breaking out in Los Angeles, San Francisco and New York, hopped on a plane and went to Denmark. His idea was to try to leap ahead of the epidemic. In the end, the studies were complementary. Then we put our heads together in terms of a more complete study of the two theories. Bob, coming from an infectious disease orientation, thought that there was likely to be an infectious agent. I, with a more simplistic approach and having noted the original apparent association of nitrite inhalant use, said, “I think the cause might be these nitrite inhalants.” Bob was right and I was wrong.

Harden: Much may have been made of being right and being wrong, but what we are trying to do is to see what led you to these assumptions?

Goedert: We had a unique disease and a gay lifestyle.

Harden: Are there other examples of environmental substances like the inhalants, which were causing immunological problems? Or were other factors leading to these conclusions and suggestions?

Goedert: There were certainly a number of occupational exposures that led to very uncommon malignancies. It had not been very long before that a pathologist in Ohio had discovered the link between angiosarcoma of the liver and vinyl chloride in the vinyl polymer industry. I think that my orientation was on the toxicology, occupational associations. There was a rather lengthy literature about certain occupational exposures and bladder cancer. But when there is a case of a very unusual cancer, like angiosarcoma of the liver, and then I learned that a nitrite inhalant user had Kaposi's sarcoma, it seemed to me as though the nitrite inhalants were the most likely culprits.

Rodrigues: I imagine there was little information available about the effects of these inhalants with regards to long-time exposure or the way they were being used?

Goedert: Certainly not of long-term exposure. It was clear that they caused marked vasodilatation, and it was clear that the tumor was essentially a vascular tumor. Amyl nitrite had been used as a pharmacologic agent for heart disease patients for a long time prior to nitroglycerine. Essentially, nitroglycerine is a derivative of some of these substances. There was a discussion about whether you could look at elderly men, the classical Kaposi's patients, and see if there was any relationship between nitroglycerine use and pharmacologic prescription of amyl nitrite use. I do not think those studies have ever been done. There is, just now, a case-control study of elderly men in Greece, who have Kaposi's sarcoma, to get at some of these questions. Our opinion is that they probably will not find an association between nitrite-nitroglycerine use and Kaposi's sarcoma.

The other thing we had done for the first publication, since it looked like the amyl nitrite inhalant use was related to Kaposi's sarcoma, was we collaborated with people down the hall here [at NIH] in the National Toxicology Program to have them test for mutagenesis in vitro. They tested rather quickly four or five of these nitrite compounds, including amyl nitrite and isopropyl nitrite, which were the two commonly used ones, and a couple of others. They found what they still feel is sufficient mutagenic activity, suggesting that these substances could be carcinogenic in humans. I think it is by no means a far-out theory; it is just one that can only be disproved.

Harden: There was another theory by another group that had to do with antigenic overload of the immune system. Do you recall your reaction to that? There seemed to be three theories floating around for a period.

Goedert: I have had a lot of feelings about that theory over time, none of them strongly positive. It always seemed a little nebulous and rather diffuse in terms of the number of people that ought to be at risk if antigenic overload was the cause.

On the positive side, the one thing that seemed potentially to support that theory was the experience with non-Hodgkin's lymphomas. There is a fairly good animal model that shows that the combination of immune suppression and antigen stimulation led to malignant lymphoproliferation in rodents. I think there are some human experiences that are somewhat comparable in terms of congenital immune deficiencies and the idea that antigen stimulation, or antigen overload, if you will, can lead to non-Hodgkin's lymphomas.

It was obvious to me that the immune deficiency of the syndrome in general, the KS-PCP [Kaposi's sarcoma-Pneumocystis carinii pneumonia] syndrome, that we now call AIDS, was too restricted in terms of the kinds of populations that got it. It just seemed implausible. Especially, of course, once the transfusion cases appeared, which was not long after–about a year later. Once there were cases in hemophiliacs, and especially in transfusion recipients, I think that theory just completely lost all of its air.

Harden: There was a meeting, I think, at the end of June 1982 in New York where the hemophilia data and the transfusion data on babies were presented. It may have been Dr. Biggar, or Dr. Robert Levine, who went to the meeting.

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