Office of NIH History
In Their Own Words: NIH Researchers Recall the Early Years of AIDS
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I was doing some work on genetics of families and had visited an investigator in the Auburn Building in Bethesda. The Red Cross used to have a laboratory in the building. I went into this doctor's office to see if he would run some sort of red cell genetic markers on some families. Although I did not know it, he had been doing a study with Dr. Michael Crawford of Kansas University Medical Center, who is an anthropologist, on sera from the Caribbean. I told him about my idea of a link between the Caribbean and cases of leukemia and lymphoma. He said, “Isn't that an interesting coincidence? I'm studying sera from people in the Caribbean Islands.” Our conversation led to a collaboration and subsequently the first epidemiologic paper linking the virus to the Caribbean and ATL. Most people focus on the Catovsky paper, which is in the Lancet. It did not present any HTLV testing data, however. Catovsky had written a pathology paper, and I had added some things to the discussion about the link of HTLV to these cases–to scoop myself, in a sense. But Catovsky had the paper almost written and it was important to get the information out.

At that time, there were some fairly unpleasant things going on with Professor [Yorio] Hinuma in Japan, who was really giving Bob Gallo a hard time. Bob had gone to Japan in 1981 at the invitation of Professor Yohei Ito to speak and to try to set up a collaboration. Bob had gone with the idea that he was going to give reagents to the Japanese and that there was going to be an exchange. Greg [Dr. Gregory O'Conor] was involved in this. Bob told me that Dr. Hinuma was in the audience for his talk, and that Hinuma was scheduled to talk about EBV [Epstein Barr Virus] and the related work he was doing. Gallo presented his paper and according to Dr. Gallo, Dr. Hinuma went ashen because he had gotten these cell lines from Dr. Kyoshi and had been doing immunofluorescence with these ATL sera while Gallo had already discovered the virus. It created a very unpleasant and nasty interaction.

The Catovsky paper turned the focus away from Japan and provided another venue, so to speak, for this virus. I published the first paper later that year [1981] describing the Caribbean as a viral endemic area and I reported the first sera on the ATL cases from the Caribbean, as well as from the normal population. That was an important first chapter for me. One of the jokes I made at the time of the London meeting's close was: “Maybe, we should have a meeting about this in Jamaica next year.”

In the fall of 1981, we met with Greg O'Conor, and we went down to PAHO [Pan American Health Organization], where Bob Gallo and I met with Dr. Allayne and some other people. Dr. Allayne gave me the name of the head of the pathology department at the University of the West Indies, [Dr.] Nigel Gibbs, who is now at WHO [World Health Organization]. I was aware that the department had published in the cancer research area, and I hoped there were people on the faculty with whom we could work. I wrote to Dr. Gibbs, essentially inviting ourselves to his campus. I said, “We are interested in this syndrome; here are some features of it.” He wrote back politely and said, “You're welcome to come. We don't have any of that kind of problem down here, but I would be glad to meet with you.” Bob and I went to Jamaica in January 1982 and established contact in what became an ongoing research project with the University of the West Indies, supported since 1983 under a contract mechanism. Lo and behold, as we went on clinical rounds, we found two ATL patients. I took some serum from them back with me to the NIH. Within a year, we accumulated sixteen to twenty cases of ATL and showed that over half of the newly diagnosed lymphoma patients there had ATL.

Harden: You were able to identify Japan and the Caribbean as sites for this virus. Does it exist in other places, too?

Blattner: Oh, it is in a lot of places. We were also surveying other populations at this time. Some of our data were false positives and some were true positives. The assays were tough. It was also a critical time in terms of developing assays for retroviruses. We started out with insensitive and nonspecific assays, but we were able, through the availability of reagents and sera, to work with [Dr.] Carl W. Saxinger and [Dr.] Marjorie Robert-Guroff to purify the antigens and develop assays. Carl Saxinger had a contract with BioTech and Dr. Ann Bodner. That group worked to develop an ELISA [Enzyme-Linked Immunosorbent Assay] assay. In the course of this, we developed a close relationship. We developed computer links to allow us access to the data to promote analyses of results and so on. These are some of the important little details.

Later on in the HIV [Human Immunodeficiency Virus] story, these links were really key, because we had the direct ability to do testing quickly and get results back directly once the AIDS virus was identified. I think the key thing about this period was summarized in an Annals of Internal Medicine Clinical Conference on ATL and HTLV. It was published in 1982 or 1983. Sam Broder was the editor. It was Vince [Dr. Vincent] DeVita who introduced that program and said, “This discovery was really the culmination of one of the eight original objectives of the Cancer Institute when it was established in 1937: define human retroviruses associated with cancer.” In many respects, however, this major discovery was overshadowed by AIDS. Retroviruses, of course, had first been recognized at the turn of the century.

Harden: Except for one thing. At the turn of the century, there was no way to differentiate viruses into groups as there is today.

Blattner: Yes. I do not think viral differences were appreciated until the work of Dr. Ludwik Gross in the 1950s, when he was able to start actually characterizing different types. When you go back to the turn of the century, there were filterable agents with the ability to cause leukemias, which later served as reagents in the virus-cancer program.

Harden: Have DNA or RNA non-retroviruses been linked with cancer?

Blattner: Some have, but they are ubiquitous. The thing that distinguishes HTLV from EBV and some others is that the retroviruses are very restrictive. It just shows the diversity of how viruses cause trouble. This was a major discovery. Gallo had invested much time and effort in this issue, and in some respects, I think it is a tribute to him that he even got into AIDS. You have to recognize that he has made a major discovery, a tremendous breakthrough, after all these years of negative data. There were very lonely days for Bob, when he was searching alone for cancer-causing retroviruses in humans. He was the laughing stock of science at one point, but he persisted in looking for these retroviruses. I was there for some of that, and I know that people have very selective memories for these things. During this time, he was very successful in characterizing this virus and its genes. I think it is important to realize the background–where were all the Nobel laureates when AIDS came along? They were off doing whatever they wanted to do.

Bob Gallo was one of a very small handful of people who had any competence to look at the AIDS problem, and he got involved without having to be pushed into it. All the things that are going on related to this [John] Crewdson's claims are tremendous distortions. That article [John Crewdson, “The Great AIDS Quest,” Chicago Tribune, November 19, 1989, Section 5, pp. 1-16] and the Shilts book [Randy Shilts, And the Band Played On: Politics, People, and the AIDS Epidemic, 1987] are the sources of all the nasty stuff going on. There is a total lack of appreciation for the fact that this man could have spent the rest of his career focusing on HTLV and could have made contributions of a tremendous caliber by themselves.

Anyway, while all of this work was getting started in the HTLV area, I was the head of the Family Studies Section at NCI; Jim [Dr. James] Goedert was in my section and Bob [Dr. Robert] Biggar was coming in at this point, having returned from Ghana. Jim was basically doing clinical epidemiology; he made important observations about the relationship of certain congenital anomalies to the risk for testicular cancer and about familial cancer. We would go on ward rounds at Georgetown [Hospital], I think, where he had recently come from. Goedert is a very gifted guy. He is one of these people with no formal training in epidemiology who nevertheless has a “green thumb” for etiologic research. [Dr.] Elizabeth McKeen introduced me to him.

He was at Georgetown going on ward rounds; this was in December 1980, as I remember. Jim was alerted to the case of a young medical student with Kaposi's sarcoma, which was an oddity. We did not see Kaposi's in that age group and so were drawn to studies of people with unusual ages of onset of cancer and so forth. In May and June of 1981, we went to the ASCO [American Society of Clinical Oncology] meetings, and I think there was some discussion of unusual occurrences of Kaposi's. The CDC [Centers for Disease Control] was working with people in Los Angeles. During that time, I was personally embarking on the HTLV path. There was a convergence and coincidence of events taking place, with Jim Goedert recognizing one of the first patients with AIDS. In fact, Jim is a co-author of the MMWR [Morbidity and Mortality Weekly Report] report of the first cluster of Kaposi's sarcoma. The memo that you may have seen from Joe Fraumeni–I do not know what the date of it was–was a reflection of the people within my branch stirring to address intertwining sets of issues. In some respects Joe helped us all begin pulling in the same direction.

Bob [Biggar] was not in the section at that point. He was newly back from Ghana when he said that he wanted to fly to Denmark. Contrary to the portrayal in the Shilts book, it is difficult when you have someone new come into your program. Biggar was new; he had come from the Viral Cancer Program. Foreign travel in the Cancer Institute at the NIH is not something that you take lightly. There has to be a lot of justification for it. Bob's request was not turned down, as Shilts suggested, because AIDS was of no interest for NCI. Rather it was because of bureaucratic requirements to justify overseas trips, which are a politically sensitive issue given all the talk about government “junkets” etc.

Another piece of the puzzle was discovered during our collaboration with Dean Mann. We had set up a fairly high powered immunologic capability through an interagency agreement with the Uniformed Services University [for the Health Sciences] with Mike [Dr. Douglas Michael] Strong, who ran a transplantation service. One of the things that we were able to do through this mechanism was to develop a lot of immunologic assays. We also bought a FACS [Fluorescence Activated Cell Sorter] machine. A FACS machine is used for identifying T-cell subsets and, in retrospect, was one of the key instruments that helped us recognize the extent of the problem caused by AIDS.

Harden: When did you first start thinking of AIDS as a separate disease–something that was not just a curious phenomenon?

Blattner: By the fall of 1981 we had a pretty good idea from work that Jim [Dr. James] Curran reported at that infamous meeting in 1981 when he came up here to the NIH. I cannot remember whom he was briefing. It was September 1981, as I remember it, when everyone was talking about the ground work that the CDC had been doing. There were many potential grantees at the meeting. There was a fellow–a Kaposi's sarcoma researcher from New York. I cannot remember his name right now.

Rodrigues: Dr. Alvin Friedman-Kien?

Blattner: Yes, Friedman-Kien was there. He had lunch with Curran. I was very gung-ho on getting the wheels going on this thing, because it seemed pretty important, especially from a cancer research point of view. Kaposi's sarcoma seemed like a very important lead to pursue. During this period, Bob Biggar made his trip to Denmark. Through [Dr.] Peter Ebbesen, he began collecting materials from one cohort of gay men in Denmark. The concept behind that project was that in order to understand the dynamics of an epidemic, it would be best to be at the leading edge. If you are in the middle of the epidemic, you are swimming in a sea of information.

Inspired by Bob's concept, Jim Goedert went to New York and laid the groundwork for studying cohorts of New York and, subsequently, Washington, D.C., gay men. The first eleven patients of the fifteen studied for our February 1982 Lancet paper provided a lot of information. They were, as far as I know, the first group of clinically normal gay men that were immunologically evaluated. We wrote a somewhat misdirected paper on these people, however. It had the right information but some conclusions were misinterpreted. Maybe we overstated the association between a significant level of immune suppression in these people and their exposure to amyl nitrite. That information was available because of the FACS machine. Jim Goedert can tell you more details about his trip to Atlanta in the course of these cohort follow-ups. He was the first person to provide a population estimate of the severity of the AIDS epidemic. My recollection is that 30 to 40 percent of the hundred or so gay men evaluated had substantial immune deficiency.

We went wrong in our analysis in that paper because we were looking at the various behaviors, and one of the behaviors associated with immune deficiency was the use of amyl nitrite inhalants. In retrospect, we can think about this differently. It was a mark of a high risk behavior for HIV infection. You have to understand that when you are going through this kind of process and living it, as opposed to looking back on it, things were not that clear. There were very few of us who were living it, because there were not very many people working in the area. It is very clear to people in retrospect how “stupid” we were, but ultimately the problem got solved through the process of scientific research.

continued on page 03

 

 

 
 
 
       
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