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Curran: Yes, I saw the draft in May of 1981. These articles are published rapidly. I cannot remember whether there were four or five cases discussed in the draft. There were five that were published.
At that precise time, we were conducting national STD conferences in San Diego and Atlanta. Between the date on which I saw the draft, and when it came out on June 5, we had our first conference which Harold Jaffe and I attended. We had both seen this draft. And we talked to some of our West Coast colleagues in the gay community and people who were at the meeting. A few weeks later we had a meeting in Atlanta and we did the same thing. In our discussions in California, Harold and I learned that there were other similar cases to those in the MMWR that had been seen by some of the physicians. There were some unusual illnesses going on in the gay community. It was more than the rampant enteric diseases and hepatitis and STDs in the gay community. There actually was a case of Kaposi's sarcoma that somebody had seen in San Francisco, but nobody knew the significance of that then.
So, after the article came out on June 5, a task force was formed at the CDC after a meeting was convened in the CDC director's conference room. People from all parts of the CDC got together, merely a day or two after the MMWR was published. We had scientists from Cancer, Parasitic Diseases, STDs, Viral Diseases, and other people. We talked about what this meant and what we thought it was.
Harden: Expand on that a little, would you?
Curran: The CDC had dealt with two other major epidemics in the preceding five years. One was Legionnaire's disease, and there was considerable experience with Legionnaire's disease in the CDC. The other one was toxic shock syndrome. These unknown problems eventually were found to be linked directly or indirectly to bacteria. The CDC specializes in epidemic responses as an institution. One of the things the CDC does best is rapid mobilization and response to public health emergencies. So, initially, it was thought that these unusual cases might be the next epidemic for the CDC to address. Scientists from different disciplines convened to talk about what was going on from different perspectives and to speculate about what the cause could be. Initially, there was not a lot of unique insight. It was agreed that we needed to find out more.
Harden: So your personal contacts across the country became very important.
Curran: Yes. We took a lot of different approaches. We agreed to form a task force with representatives from different centers in the CDC involved. The Task Force on Kaposi's Sarcoma and Opportunistic Infections was initially comprised of scientists in their late twenties and thirties.
At the first meeting, the group elected me as the chairman or coordinator of the task force. First of all, at the very first meeting, there had been a call about some cases in New York. The man who was in charge of the research in the Parasitic Disease Division, who had supervised the people putting together the first article on Pneumocystis, was scheduled to go to New York to follow up on case reports from there of PCP and Kaposi's sarcoma. I went along.
So three days after the MMWR article came out, [Dr.] Dennis Juranek and I flew to New York to visit [Dr.] Alvin Friedman-Kien and [Dr.] Linda Laubenstein at New York University. They had a patient who had Kaposi's sarcoma, an actor from Detroit. He graduated in 1962, from a Catholic high school in Royal Oak, not too far from my high school. I went to Notre Dame and he went to Yale. The differences between us were not great, but he was gay and I was straight. He was in New York, an actor, and he had these unusual purple lesions all over his body. None of us knew what they were. They did not look very serious. None of us had ever seen a case of Kaposi's sarcoma. And Dr. Friedman-Kien had only seen a couple of cases in elderly men. He was a professor of dermatology. Dr. Laubenstein and one of her fellows, a man named [Dr.] Kenneth Hymes, had written a paper on Pneumocystis and they submitted it to the Lancet at the time, and they shared a draft of that with us. Some of these people with Pneumocystis also had Kaposi's sarcoma. That was the first time that I really felt that these two conditions must be related. That gave us, I think, one of the most important fundamental clues that this was a similar epidemic with an underlying problem.
Subsequently, over the next year I made about 40 more trips to New York, and I saw this man deteriorate over time. He was treated with chemotherapy and things that probably did not help him, and I eventually watched him die. This was all before the virus was discovered. I realized that there was a certain unfairness to this, because our paths in life were not separated by much, but he died while I lived.
Hannaway: One of the questions that we were wanted to ask was about the CDC's experience with swine flu. Some people have complained that it had an effect on the way the CDC responded to AIDS. What are your thoughts on that?
Curran: Well, swine flu and Legionnaire's disease came at the same time, in 1976.
Hannaway: The claim basically is that the CDC overreacted to swine flu, and reacted more appropriately, let us say-this was in some of the literature-to Legionnaire's disease. The literature says that the CDC overreacted in advocating that a more dramatic vaccine program be developed and so on. Did this ever come up in your discussions relating to AIDS? Did anybody ever say, “Oh dear, we overdid it with swine flu. Maybe we should not be so vigorous?
Curran: I mentioned the two things that I thought were more relevant, and that was Legionnaire's disease and toxic shock syndrome. We were in the mode of investigating AIDS at the time, not implementing prevention programs. The swine flu vaccine initiative was a program of protection, which is more like the national immunization program or polio eradication or smallpox eradication. When swine flu came along, it was a calculated-risk issue. Gerald Ford was president, [Dr.] David Sencer was head of the CDC, and Jimmy Carter became president shortly afterwards. After Guillain-Barré cases associated with swine flu vaccine and the absence of a major flu epidemic, Carter and [Joseph] Califano fired David Sencer as director of the CDC and appointed [Dr. William] Bill Foege, currently one of our faculty members at Emory, to be director of the CDC. Foege was director when AIDS came along.
More important from a political standpoint, I think, was the advent of the Reagan Administration and the reduction in force in the Public Health Service; the closing of Public Health Service hospitals; and the initial threat both to the NIH and the CDC, probably more to the CDC, of a reduction in budget and reduction in force. A sort of a pall settled over the government when Reagan first came in. It affected many of my initial interactions, which were with the National Cancer Institute and [Dr. William] Bill DeWys and his boss, [Dr.] Bruce Chabner.
Harden: We are not as familiar with the administrative structure of the CDC as we are with that of the NIH, and so you may have to set us straight on this from time to time.
Curran: Each center at CDC is most like an institute at NIH, from an administrative point of view.
Harden: But then you have preventive programs that the swine flu episode would have fallen under, and that is a different kind of administrative initiative from the response to diseases like Legionnaire's.
Curran: Parts of the CDC are scientific units, but there are also programmatic units. A center may have both. For example, the National Center for Chronic Disease Prevention and Health Promotion has cancer prevention programs, but it also has nutrition research groups, cancer research groups, and so on.
For the infectious diseases, in the early 1980s, there were really two centers. There was the Center for Prevention Services and also a Center for Infectious Diseases, where laboratory research and a lot of the epidemiological research were done. It was not all cut and dried, though, because STD research and tuberculosis research and immunization research were in the Center for Prevention Services. But the laboratories were in the other center.
Every July 1, a new bolus of young physicians and other scientists come into the CDC as epidemic intelligence officers, and they are really anxious to go and tackle the world's epidemics. They are very smart young people. They are like the new people that come to the NIH. They are usually physicians, who come in for two years of training, and then most leave.
Hannaway: They are idealistic and dedicated.
Curran: Yes. They wanted to go jump on AIDS. Everybody wanted to work on this problem, but the Reagan administration was cutting back support. We could not get any staff support or secretaries or computers. But every EIS officer wanted to work with us, so we had that resource available.
Now some of them had actually seen cases. There was one who had been a fellow with [Dr.] Henry Masur and others in New York. And it was said that the people in New York said, “If you go to the CDC, do not tell them about this problem because we do not want the CDC to scoop us on this.” So we did not learn about the New York cases, even though requests from New York for pentamidine had come in earlier than those from California.
The first thing we did after we organized the task force was to gather some EIS officers to work on AIDS. Some of the original EIS officers were [Dr.] Martha Rogers, who was still at the CDC in 1998, and [Dr.] Harry Haverkos, who has since been at the NIH and the FDA. He had been an infectious disease fellow in Pittsburgh and had seen a patient with Pneumocystis. He came to the CDC because he wanted to study Pneumocystis. When he came to Atlanta, it happened that his patient was transferred to Emory.
There was also [Dr.] Ida Onorato, who is now with the HIV division, but at that time she was a fellow with Masur in New York. So we had a few people who had actually seen patients as new EIS officers, and they joined our task force. We had a Cancer EIS officer join the task force. Martha was in Viral Diseases and Harry was in Parasitic Diseases. They were assigned to me as task force coordinator.
Also, over the next few months, a few of my STD branch scientists were reassigned to the task force. I was assigned permanently for three months to head this.
Hannaway: For three months. That was optimistic.
Curran: Yes, three months became fifteen years! The task force initially operated out of the Center director's office, and then it operated out of the CDC director's office; so we would get more visibility, and hopefully more resources.
The first thing we did was to go back to the source of the information; that is, go back to the pentamidine requests. Pentamidine isethianate was an orphan drug before the term was used. It was a drug that was made by a group named May & Baker of England. It was too much of a hassle for them to seek licensing since the drug was used less than 100 times a year in the United States. As a matter of a fact, there was a professor at the University of Cincinnati named [Dr.] Peter Walzer, who, when he was at the CDC, had written a paper reviewing the pentamidine requests from 1969 to 1978; he found only one case in which pentamidine was used in somebody without an underlying cancer or severe immunosuppression. That gave us a background of essentially no unexplained PCP for nine years through 1978.
So we started following up systematically every one of the recent cases in which pentamidine had been requested. We found a few more in New York, a couple more in California, and one in Atlanta. That was it for the whole country. And they were all PCP cases in gay men, except for a couple of additional cases in New York among men, supposedly drug users.
We sent EIS officers who had finished their initial training to each of the states where there were cases, and to the 18 largest metropolitan areas in the country. We had prepared a case definition for this new syndrome. It was defined as these life-threatening opportunistic infections or Kaposi's sarcoma in people with no case of underlying immunosuppression. That was the bottom line. We had the EIS officers go into the university hospitals and academic centers in each of these 18 metropolitan areas and review all of the pathology records-at the time, Pneumocystis was diagnosed with a lung biopsy-or medical records or tumor specimens for any of these cancers or opportunistic infections back to 1975, and there were none except for the ones that we already knew about and maybe a couple of others in California and New York. Then we kept on doing active surveillance of all the calls coming in. Dr. Friedman-Kien called in and said that he had 20 cases of Kaposi's sarcoma, and we tracked down all of those around the country. There did not turn out to be that many new calls, but there were a few, and a lot of them had been seen at Sloan Kettering by a physician named [Dr.] Bijan Safai, who was a specialist in skin cancers.
We then needed to verify these diagnoses. We sent Kaposi's sarcoma specimens to a dermatologic pathologist, Dr. Bernard Ackerman, in New York to make sure that the diagnosis was accurate. We were trying to piece together answers to the questions: Is this new? Is it increasing? Who has it? Who does not? The most important thing for our case definition was that it was specific. It was not so important that it be sensitive initially. But it was important that it be specific because when you are determining whether a problem is new and looking for the etiology, you have to make sure that you do not over diagnose it. If you think about some of the poorly defined syndromes that we have trouble understanding nowadays, like chronic fatigue syndrome or fibromyalgia, part of the trouble is that the symptoms are not specific. This greatly complicates the search for the etiology.
The first connections with the National Institutes of Health came through the National Cancer Institute. Alvin Friedman-Kien was a dermatologist who had discharged his military obligation as a Clinical Associate at the National Cancer Institute in the Cancer Virology Laboratory, and he had some friends there whom he contacted.
Initially, the NIH was having trouble with the concept of an outbreak of cancer and of infectious diseases being the same epidemic. NCI had more initial insight than the other institutes. It may have been that Bill DeWys and Bruce Chabner had experience in the Uganda Cancer Institute with [Dr.] Greg Donaldson, and that people that were still around from the old Kaposi's sarcoma study days, when they studied epidemic Kaposi's sarcoma in Uganda and were very interested in the viral etiology of cancer.
They were aware of the literature that showed that this was a cancer that also occurred in transplant recipients. As a matter of fact, it was hundreds of times more common in people with kidney transplants than in others; and if you took away the immunosuppressants from the kidney transplant patients, the cancer would sometimes go away. Here you have a cancer associated with immunosuppression and you have opportunistic infections that potentially occurred because of immunosuppression.
NCI also had a lot of money invested and a lot of interest in the viral etiology of cancer, and NCI was the largest institute at the NIH. In retrospect, NCI had several reasons why they were interested in the strange outbreak. So NCI called me-I am trying to remember-it was sometime in the fall when I met with Bill DeWys. Bill DeWys had been a senior resident when I was a medical student at Ann Arbor.
Eventually, NCI planned a workshop. The CDC was also a sponsor. We helped them get it together and organize it. I spoke at it. It was a small workshop, but it was a start. They got recommendations from that to take to the Division of Cancer Treatment's Board of Scientific Counselors to request seed money to do some studies.
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