Dr. Bruce Evatt

Bruce Evatt

MILLER: This is Dr. Bess Miller, and I'm here with Dr. Bruce Evatt. Today's date is May 10, 2016, and we are in Atlanta, Georgia, at the Centers for Disease Control and Prevention [CDC]. I am interviewing Dr. Evatt as part of the oral history project, The Early Years of AIDS: CDC's Response to a Historic Epidemic. 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. Evatt, do I have your permission to interview you and to record this interview?

EVATT: Certainly.

MILLER: Thank you. Bruce, you've been a national and global leader in hematology, with emphasis on laboratory research and program implementation for persons with hemophilia throughout your career, with over 200 publications. For this oral history of AIDS at CDC, we are focusing on the early years, beginning 00:01:00in June 1981, with the publication of the first Morbidity and Mortality Weekly Report [MMWR] on the five cases of Pneumocystis carinii pneumonia among homosexual men. You served in several critical roles at CDC during these early years, including Director of the Hematology Division, 1978 to 1982; Director of the Division of Immunologic, Oncologic and Hematologic Diseases, 1982 to 1991; and Assistant Director for Hemophilia Activities, Division of HIV/AIDS, 1991 to 2004. Let's begin with your background. Would you tell me about where you grew up, your early family life, and then where you went to college?

EVATT: I grew up in Oklahoma. I was born actually in a house, in the small town 00:02:00of Wayne, Oklahoma, which had a population of 401. In that little town, I went to a grade school which was right next door and adjacent to the high school and had a classroom that had 28 students in the senior class. I wanted to get out of that small town, and so I dropped out of high school and didn't finish. At that time in Oklahoma, you didn't have to have a high school diploma to go to the University of Oklahoma if you made a high enough score on their entrance examination. So I marched off to the University of Oklahoma, took the entrance exam, and passed. My superintendent at Wayne High School wrote a letter to the 00:03:00university telling them I was not university material, that I was immature, and they should not allow me into the university. I remember the interview with Dean Fellows at the time, who was Dean of Students. He says, "Well, Bruce, the law says we have to let you in, but we won't see you around next semester." So I entered University of Oklahoma and majored in physics and minored in math, although I had not had a single science course in high school.

MILLER: Who or what influenced you to go to medical school?

EVATT: That was somewhat by accident as well. At the time, I was interested in--I wanted to fly. So I had become a part of the Air Force ROTC [Reserve Officers' Training Corps] and had taken advanced ROTC and was their top cadet. I 00:04:00was destined for a regular commission. It was out of a lark in the end of my junior year that I said, "Well, I wonder what it would be like to go to medical school." So I called up the University of Oklahoma Medical School and had not applied or anything, and asked, "What does it take to get into medical school?" They told me that the application deadline was six months before, but they had one remaining interview left and why didn't I come up and interview for that. So I traveled up and interviewed for that and got a call two days later, giving me a position in medical school under the condition that I took the prerequisites 00:05:00for my remaining semester in college, because I'd had no biological sciences at all. They were all physical sciences. So I thought about it and accepted it, but then I had to get out of the Air Force commitment. They let me go in order to go to medical school. I entered University of Oklahoma Medical School the following fall and graduated with an MD in medicine. Unfortunately, I had to drop a Philosophy 1 course. Although I had all the hours and other prerequisites, I didn't graduate from college either, because I lacked three hours of freshman 00:06:00philosophy in order to get the degree. So the only degree I have is an MD degree.

MILLER: You had a very strong clinical and academic training in medicine in hematology at Johns Hopkins Hospital. How did you get interested in hematology?

EVATT: I took an elective in hematology at the University of Oklahoma. There was a professor there that was an extremely dynamic person. He made hematology a lot of fun, and so I got interested in it at that point. Later, at Hopkins, during my internship I took an elective, and I decided to take an elective in hematology with Dr. [C. Lockhard] Conley's department there at Johns Hopkins 00:07:00University. His group was a very exciting group, and I did some research and published a paper. With that paper, I also received a research award from Hopkins. That sort of cemented my interest in hematology, and it just continued to grow from there.

MILLER: What led you to CDC and public health, first as an EIS [Epidemic Intelligence Service] officer, 1968 to 1970, and then back in '76 for the rest of your career?

EVATT: When I went to Hopkins, it was in 1964 that I did an internship at Hopkins. To remain at Hopkins beyond internship, you had to have a deferment. We 00:08:00were not yet committed to the Vietnam War very deeply, but there was still--the draft was going on, and they were drafting all physicians out of their internship. So if you didn't have a deferment, you couldn't stay on for first-year residency at Hopkins. I applied for the Berry Plan [a lottery to allow young doctors to complete residency in a civilian hospital before serving in the military]. The Berry Plan was a random event, and I lost the lottery. But I also applied to the NIH [National Institutes of Health], where you could get a deferment. The CDC actually picked up my application to the NIH. [Dr. Michael B.] Mike Gregg at CDC called me up and said, "Would you like to come to CDC?" I said, "What's CDC, and where is it?" Mike told me, and I said, "Will you give me 00:09:00a four-year deferment?" Mike said, "Yes." And I said, "I'll come to CDC." That's how I initially got to CDC. My interest was not in public health, but I came to CDC for those two years and worked with [Dr.] Clark [W.] Heath, who was marvelous to work with, and I learned a lot and obtained a completely different perspective about medicine from the point of view of practice and population medicine and so forth, working with Clark Heath. It was extremely valuable.

MILLER: What was your emphasis during your EIS training? What types of things did you work on?

EVATT: Clark was head of the Leukemia Unit and Congenital Defects as well, so my assignment was with--because of my interest in hematology, my assignment was 00:10:00with tracking down leukemia clusters and lymphoma clusters. That was a unique experience. While I was here, I got interested in developing different kinds of statistical analyses of clusters, because cluster analysis was a very difficult science mathematically and there were no good statistical methods for doing that. I got very interested in databases and computers. In those days, the computer--we had the IBM mainframe here, and the computer people were very good. They would loan me--at night the computer was idle, and so they would loan me their IBM mainframe to come in and play with it all night. I'd spend many a 00:11:00night up here in the middle of the night, just trying to develop methods of doing cluster analysis that would be more fruitful. The experience was an extremely good experience.

MILLER: Moving into 1976, can you tell us a little bit about the areas of focus at CDC before the AIDS epidemic began?

EVATT: When I came back to CDC in '76, shortly thereafter CDC reorganized. Before it had been the Bureau of Labs and the Bureau of Epidemiology as the two major areas. They functioned somewhat like silos. Dr. [William H.] Foege thought that by combining them so that each area had its own laboratory associated with 00:12:00it, [there] would be a closer working relationship between the laboratories and the epidemiology groups and would be a more fruitful kind of experience. So the organization that CDC became was to organize a disease entity associated with its own laboratory that would then function to serve the epidemiology and laboratory working together.

Now, there were a number of labs, though, that were somewhat orphaned. They were hematology, immunology, and pathology, that really didn't belong to any kind of association with any specific disease. They were general. So that group of laboratories, and they were mainly laboratories, was put into a Division of Host 00:13:00Factors. They were to serve as a general kind of support for the whole CDC. There was essentially no epidemiology associated with that group initially until AIDS came along. The individuals in the Division of Host Factors were more clinically oriented than some of the other divisions. They were the kind of groups that you would see in a major hospital, so that it was somewhat unique in terms of being a division of virology, a division of bacteriology, and so forth. So that's how the Division of Host Factors was organized. From that point of 00:14:00view, the Division of Host Factor interests were focused more on clinical kinds of problems and unique reference laboratories and reference diseases for the country and supporting other divisions, rather than being a specific kind of disease orientation.

Hematology was looking after rare diseases in terms of looking for ways of prevention. Hematology was--I mean, hemophilia was one of those diseases, bleeding and clotting disorders. Thrombosis was another. Immunology was looking at arthritis and ways to prevent arthritis. And pathology was a general pathology support, for not only our division but also other divisions. That was 00:15:00the kind of setting at the time that the AIDS epidemic hit.

MILLER: Do you remember some of your main focuses when you first came to that Host Factors Division?

EVATT: As head of the--I had headed the--I originally came back to CDC in '76. The reason I came back to CDC is I loved Baltimore, but my wife did not. She really wanted to leave. She had been a social worker and she'd started the law school, and she didn't want to stay in Baltimore. So a job came up to establish a national reference laboratory at CDC in '76 in hemostasis--blood clotting. I took that job as a temporary job because Mary loved Atlanta. I came down to let 00:16:00her finish law school, and then I had considered--I was planning on staying only a couple of years and then going back into academic medicine. At the time we came, I had grants at Hopkins and I was on the faculty. But then the AIDS epidemic hit and changed everything.

MILLER: Moving on to your work on AIDS, as a reminder, can you start by explaining the management of hemophilia in the early eighties?

EVATT: In the early eighties, management of hemophilia had progressed rapidly from about 1960. [During] the first four decades of the 20th century, hemophilia 00:17:00was a horrible disease to have. There was no management. The children often did not live. The average life expectancy was about 29. The children were all crippled by the time they were in their teens, and employment rates were 85%-90%. It was a life of misery. The transfusion progress that the military had made during World War II was rapidly changing everything, because the ability to infuse fresh frozen plasma into children with hemophilia had greatly changed the 00:18:00disease prognosis, so that they were living to be about 39 by 1960.

But with the discovery of cryoprecipitate and then rapidly, the use of lyophilized cryoprecipitate--it was a form of concentrate. It wasn't cryoprecipitate but a modification. During the sixties, it allowed patients with hemophilia to travel, to carry the medicine with them, and to improve the ability, so that life expectancy climbed dramatically. The problem was that concentrates were made from four to five [thousand], as many as 20,000 donors. During that period of time, there was such a need for plasma products that 00:19:00people didn't worry much about blood-borne diseases. Even though everybody got hepatitis from the concentrates, it produced such a dramatic change in outcome for the patients, nobody paid much attention to it. They thought it was expected. Most of it was hepatitis B and non-A, non-B hepatitis. At that time, they didn't know that non-A, non-B hepatitis was the worst, because it was hepatitis C in reality. So that was accepted, and there was not much progress in terms of trying to inactivate the virus in the concentrates. The difficulty with the proteins needed for hemophilia is that they're very labile, very sensitive, 00:20:00and so any kind of inactivation that you would use for viruses would most likely destroy the effectiveness of the protein. So people just accepted this.

Now, there was a whole system of care [that] grew out of the care for hemophilia, with comprehensive hemophilia treatment centers. These were centers that concentrated patients with hemophilia and delivered not only their medical care for bleeding disorders but cared for their psychosocial needs, as well as other disorders. Patients were doing fabulously, except they got hepatitis. But it was a system where you had most of the patients in the US attending hemophilia treatment centers and receiving treatment with concentrates that were transmitting blood-borne diseases. That's the setting that we were in with the 00:21:00start of the AIDS epidemic in 1980.

MILLER: In July of 1982, the MMWR reported on cases of Pneumocystis pneumonia in three persons with hemophilia A. Can you describe when you first heard about Pneumocystis in patients with hemophilia, and what the earliest thinking was about this at that time? Who were some of your colleagues and so on?

EVATT: I think that in terms of my own division, when the AIDS epidemic started, of course the first people noticed were individuals that were homosexuals. The immunology division was very interested in the immune disorder, because it was an immune disorder and what was causing it. [Dr. Thomas J.] Tom Spira was 00:22:00working in some of the clinics, collecting blood and seeing patients, and he began collecting blood from some of these just to study the immunologic abnormalities. As far as the hematology was concerned, we knew what was going on, but we weren't really studying it until we got a call in the spring of 1982 from a physician in Florida, who said that he had a man, an elderly man who was a hemophilia patient who had died with Pneumocystis carinii pneumonia. He was wondering whether or not the Pneumocystis could have been transmitted in a vial of concentrate. The processing of concentrate would not have eliminated 00:23:00Pneumocystis, and I assured him that. But it raised my curiosity, because what hemophilia patients were sensitive to were blood-borne diseases.

Now, at the same time [Dr. James W.] Jim Curran's group was identifying patients who were Haitians who had AIDS and also finding drug abusers who were developing AIDS. Those three groups were coming down with AIDS. The leading theories for AIDS at that time--it was unfortunately named for a homosexual disease. Unfortunately, that made people focus on homosexuals as the focus of the disease. What that did in effect is lead to major theories that it was either 00:24:00anti-sperm antibodies, which were the leading theories, or that it was caused by something--some contaminant of amyl nitrites, which homosexuals used to maintain prolonged erections. The focus was not on a blood-borne disease. If it appeared in hemophilia patients, that would completely change how we thought about the disease, AIDS.

Now, being the most clinically oriented division, we had responsibility for managing orphan drugs at CDC. We managed the orphan drugs that were not licensed. One of those was pentamidine, which was used to treat Pneumocystis. Sandy [Sandra L.] Ford was the clerk that managed that, so I went down to Sandy Ford, and I said, "Sandy, any request for pentamidine that comes in, find out if 00:25:00it's a hemophilia patient. And if it is, please tell us because we will then go investigate it." And so in June and July we had a case in Colorado and then one in Ohio. Requests came in for pentamidine. [Dr.] Dale [N.] Lawrence was sent out to investigate those because he had been an EIS officer, and although he was in the Immunology Division, he was the closest thing to an epidemiologist we had at the time. He went out and investigated those. Both those cases turned out to be cases of AIDS. The physicians in those places did not know they (the patients) had AIDS, but Dale informed them.

Those were the three cases that we had. One case didn't necessarily mean anything, but three were very highly significant, especially when these patients 00:26:00did not have other risk factors. We immediately informed Dr. Foege, and wrote a letter under Foege's signature to the Hemophilia Foundation that this might be a blood-borne disease. At the same time, Foege wanted a meeting in Washington, DC, in July to discuss this and present this to the blood banking industry and the recipients of blood, such as the hemophilia organizations and so forth that would discuss this.

MILLER: Before that meeting, did you call around to find out about other cases? What was FDA [Food and Drug Administration] thinking? What was NIH thinking?

EVATT: Definitely. First of all, we were concerned because one of the theories 00:27:00was that blood transfusions modified the immune system. This was used against this (AIDS) being a blood-borne disease for a long time. We searched the literature, we did a massive literature search to see if we could find other cases reported in the literature of patients with hemophilia who had developed Pneumocystis carinii pneumonia, because I'd never heard of it and I'd been treating hemophilia patients since medical school.

We didn't find any except one case--there were two cases reported, but it turned out to be a single case reported in the Czechoslovakian literature. After we had it [the report] translated, it was in a patient who had received ACTH [adrenocorticotropic hormone]--a steroid--it's not a steroid, but it stimulates 00:28:00steroid production. That case had come down with--but no other cases were found anywhere. I called the FDA. The FDA has a registry so that unusual events that occur in patients following treatment are supposed to be reported to the FDA. It's a passive system, and it's not the greatest in the world. But they'd never heard of it. They had no reports of Pneumocystis infections ever in patients with hemophilia.

So, armed with this kind of information and no reports, we also called all the hemophilia treatment centers and learned they had not seen any Pneumocystis cases. Armed with that, we thought this was a new disease occurrence, and three cases ought to be reported. The situation ought to be raised. But the key to finding these cases was the pentamidine file, requests for pentamidine. This is 00:29:00how we found all our cases, because most of the time medical personnel did not even suspect AIDS in these patients. Patients came down with Pneumocystis, requested pentamidine, and were investigated and found to have AIDS.

MILLER: Then later, on July 27th of 1982, the meeting that you mentioned was held in Washington, where you presented the case histories of these three hemophiliac patients with Pneumocystis pneumonia. Attendees there included Federal officials, the blood banking industry, the National Hemophilia Foundation, university researchers, and community activists. Tell us what happened during that meeting.

EVATT: Well, we presented that information, but we received somewhat of a cold 00:30:00shoulder. The blood banking industry is a very stable industry. Changes occur over long periods of time. They were not interested in three cases needing any modifications. The homosexual community were extremely good donors. They thought they were very civic minded in donating blood. They thought it was their duty to donate blood and to be good citizens. In some cities they made up as much of a third of the donors or donations in those cities, such as San Francisco. In fact, there were blood drives in some of the gay bath houses, because they were 00:31:00such good donors and they could get lots of blood. The blood banking community wasn't interested at all in raising any kind of hassle about the fact that some of their donors may be donating and may be causing this disease. And three patients with hemophilia they felt was no proof at all.

The hemophilia community was interested, but there were not--they saw this drug as being a major life-changing event for patients with hemophilia. And to raise the possibility that maybe it was transmitting this new disease, when there were only three cases, it was so rare that they didn't want patients stopping the medicine. They were not interested in hearing of it as a risk either, and there 00:32:00was still no proof. At that point in time, you still had lots of people believing that it was something else causing AIDS. It wasn't really a disease, that it was a reaction to amyl nitrites. The FDA didn't believe it was a disease. They were not particularly interested.

The NIH took some interest. Two important things came out of that meeting: one is that the disease was named AIDS, which was great because it took the emphasis off the homosexual community [and] being a homosexual disease. Second of all, the NIH gave my division $285,000, I think, for an epidemiologist to just do some epidemiology on it. That was a godsend, because this was in a time of 00:33:00tremendous financial restrictions for CDC. In fact, that worked against CDC, the financial restrictions, because it was said that CDC had invented the disease in order to get more financial resources out of Washington, DC. That rumor spread about that. Those are the two important things that came out of that meeting, but we didn't get much support from the rest of the community that it was going to be blood-borne.

MILLER: At CDC, within your colleagues, there was already some strong belief that it was blood-borne, right?

EVATT: I think my division was thoroughly convinced that it was blood-borne. The reason was if you lined up the four groups that had been affected: homosexuals, 00:34:00drug abusers, Haitians, and now patients with hemophilia--and we began to accept that patients with hemophilia were an affected group--and you looked at the causes, the only thing that fit was, they were all patients that were at high risk for blood-borne infections. With that kind of logic, we thought it was bound to be shown, that it was just a matter of time before we showed it to be blood-borne. So we were convinced. The rest of the world wasn't, but we were convinced it was going to be blood-borne.

Throughout the rest of 1982, more and more patients with hemophilia came in. By the time we got to December, we had about eight cases, I think. We also started looking, working with Jim Curran's group, looking for possible 00:35:00transfusion-associated cases. We would go out, we'd try to track these down, and we'd go out and try to locate the donors and find out what went on and so forth. One of the problems was that most people--about half the people who get a transfusion die just after the transfusion, just because they're really ill. So finding a case that gets a transfusion that isn't causing underlying disease that might cause some immune suppression like cancer or something like that was very difficult. We repeatedly had to go out and do that.

The blood banks also were not extremely helpful. They would claim patient 00:36:00privacy, and so they wouldn't give us the names. One case where we knew that a possible transfusion case had occurred was in Boston, and they wouldn't give us the name of the donors, but one person had slipped and we got the last name. The last name was a common name, and Dale Lawrence called every last name in the phone book, every person with the last name in the phone book to see if he had donated blood. We never found the patient in Boston, but we found the mother, who said that her son had donated and had moved to St. Louis. We tracked that 00:37:00patient down, Dale did, tracked that patient down through an STD [sexually transmitted diseases] clinic, looking if they had that, they might have some other STD. He tracked that patient down and found out that the person had donated blood and also belonged to a risk group. This is the kind of shoe-leather epidemiology it took to get through the barriers that were set up by the blood banks, who were resisting investigation of possible transfusion cases. Finally, the first one was reported in December of 1982, which was a 20-month-old baby in California, I believe. Then we had one sure transfusion case and eight patients with hemophilia, and that's when the January 4th 00:38:00meeting, 1983, was called.

MILLER: Were the health departments involved in tracking down patients or in assisting with tracking down donors at that time?

EVATT: I think the health departments did all they could, but I think this was a very labor intensive, very focused kind of investigation so that--from Jim Curran's group, he worked more closely with the health departments. My group didn't really work with health departments. It really worked with universities and hospitals and with patient organizations. So it was a different approach. I think we were coming at it from two different angles. Jim Curran would probably be able to tell you what assistance the health departments were able to add, but 00:39:00we didn't really interact with them that much. They were helpful in St. Louis when we were tracking down that donor, and when we had specific questions that dealt with their clinics, they were helpful. But it was really a one-on-one kind of detective work that we were doing, trying to locate these patients. Many of the times, as I say, the pentamidine file [was key].

One of the things that has occurred since the AIDS epidemic is the inability to get patients' names and records. Today it would be very difficult to do the kind of work that we did back in 1982, because of those rules and regulations and laws regarding release of medical information, if not impossible.

MILLER: So for the hemophiliacs it would be especially difficult, since they got 00:40:00pooled concentrate?

EVATT: Yes, they were much more the canary in the mineshaft, because really a transfusion recipient got exposed to one or two donors at most. But patients with hemophilia would be exposed to four to 40,000 at a time. So you get a dose of that, and many of these vials would have multiple donations that were infected, [and that many] people['s donations] could have gone into that. So the level of difference was incredible. If you look at the percentage of infected units that were calculated later, blood donations from, say, San Francisco, you find that as much as one half or two percent of the units at the height [of the 00:41:00epidemic] might have been infected. But half the patients with hemophilia got infected with HIV.

MILLER: What effect did this have among the major stakeholders, once there was a case in this child who had a blood transfusion, in thinking about blood-borne transmission? Did that right away change people's minds?

EVATT: No. In fact, the January 4th meeting was probably one of our most frustrating. I think everybody at CDC thought this will be a slam-dunk meeting, that we would go and present the data and everybody can obviously see it's blood-borne, and the obvious way is to eliminate high-risk donors from donating blood. So eliminating high-risk groups had been done as a common practice for 00:42:00improving safety of blood control. Then Tom Spira's lab and [Dr. John Steven] Steve McDougal's lab had done studies on looking at possible surrogate tests, and 90% to 95% of these groups were positive for hepatitis B core antibody, and they could just screen hepatitis B core antibody as a possible screening test. There were also some immunological studies, but this test was licensed and could be used. We recommended using this as a surrogate test for possible donations and to eliminate high-risk groups. And we thought everybody would see the same thing. Well, the meeting was held here in Atlanta in the old auditorium. The press were there and--

MILLER: Who else was there? Who was in that meeting?

EVATT: Well, of course all of the--there were a number of divisions involved in this at CDC. Certainly, Jim Curran's division, the Viral Disease Division, the Division of Host Factors, and we had representatives from the different federal agencies who were here, the different blood banking organizations, AABB [American Association of Blood Banks], ABC [America's Blood Centers]. Also the gay group organizations, as well as affected groups like the Hemophilia Foundation. All of those were here in a massive organization. So we presented the data, which we thought was straightforward. I believe it was a total of eight [cases] at the time. I'd have to go back for the exact number. It could have been one or two more than that. But eight definite cases with hemophilia, 00:44:00one transfusion case, and then all the data on the fact that these groups were highly infected with other blood-borne diseases. And then we were met with a wall of criticism, that we were jumping the gun, we didn't have an agent, we hadn't shown Koch's postulates. That we were jumping to conclusions, that we were bad scientists, and we wanted them to spend millions of dollars introducing tests and eliminating a lot of their blood donors, stigmatizing a group of American citizens and so forth.

We looked at it entirely differently. They thought they were being, I'm sure at 00:45:00the time, they were being careful scientists. The problem is nobody knew how extensive this disease was already in the population. Even we underestimated it. They said, "Why do all this for eight patients with hemophilia?" The reason is that nobody realized that this disease had already extensively infected the donor population, as well as the other populations. With that underestimate, no one really knew what the extent of the problem was. So the problem was underestimated. They thought they were being careful and cautious. We thought it was somewhat of an ethereal way they were approaching things, and practically they should adopt these things immediately.

So it ended up with nothing really coming out of that January 4th meeting, 00:46:00except it did change the focus. That was the beginning, when people began the process of the paradigm shift [away from] thinking this is a gay disease and putting more and more emphasis on blood. This was such a shift in thinking, [because] at the time this occurred, people thought all infectious diseases were conquered. There were actually people advocating that CDC be closed, because we didn't need a federal agency when we knew all the infectious diseases that were going to occur. And here out of nowhere comes this strange disease that's completely underestimated and that many people believe CDC invented, and they wanted to close CDC. Then we're telling them they should spend millions of 00:47:00dollars to prevent something, when they don't even know what causes [it]. This was the situation we were in in January, but it did start the shift in thinking.

MILLER: Were there particular individuals that stand out in terms of what their arguments were? Specific people from the blood banks or personalities that dominated the thinking?

EVATT: Well, I think Dr. Bovey was one from the blood banking industry that felt that CDC was overstepping its bounds. The other thing is that normally the FDA would have been the person or the agency responsible for holding these kinds of meetings that the CDC was somewhat out of bounds in terms of where the 00:48:00responsibility lay. FDA had the legal ability to regulate blood banking, and for CDC to be stirring up this kind of trouble outside of the other agency was ruffling feathers at that time. The other thing is that the FDA didn't really believe in this disease, so they weren't convinced it was anything but a syndrome. That it might be caused by something else rather than an infectious agent. It's much different now when we know all about it, but if you go back to 1982, when the scientific community thinks about this disease completely differently and that it's a syndrome, it's not an individual disease. You get 00:49:00effects, but that might be caused by anything. Besides, we hadn't seen an infectious disease anywhere that does anything like this. And so the FDA wasn't convinced. It really wasn't convinced it was a real disease.

MILLER: What about the clinicians? New York, San Francisco--were they more alarmed, more in line with CDC's sense of the disease?

EVATT: The hemophilia community, which had been affected, was greatly split on this. You had advocates for CDC, such as Dr. Jean Lusher and Dr. Harold Roberts at Chapel Hill, who strongly supported CDC's position. You had other physicians that were great leaders in the hemophilia community, like Dr. Lou Aledort, who 00:50:00greatly opposed CDC's involvement and really tried to keep the NHF [National Hemophilia Foundation] from working with CDC on this issue, because he thought that it was not really a disease that was a major effect on the hemophilia community. Within the community themselves, you had this split based upon their belief. When you don't have absolute proof, you always have that kind of inner fighting that often, in terms of recommendations, what comes out of these organizations are compromises. So you had CDC on one side, you had the naysayers 00:51:00on the other side. So CDC would make a recommendation for the NHF to recommend to its community, and you would get a compromise. You'd get somewhere in the middle.

So that occurred everywhere. You had major people in the leaders of the homosexual community that were totally against the stigmatization of the gay community. These organizations were fighting for civil rights and for recognition that they were good American citizens. And here you had a disease that was going to be blamed on them if all of this turned out to be correct. This is one of the problems: that it got labeled initially by the media as a gay 00:52:00disease rather than a blood-borne disease. If it had been labeled as a blood-borne disease so that the gays were victims just like everybody else, it might have had a different progression in the beginning. But since it got labeled as a gay disease, it created an atmosphere that was difficult to overcome, and it took a great deal of effort in future years for people to overcome that.

MILLER: By March of 1983, CDC, FDA, and NIH agreed on a set of guidelines published in the MMWR, and they were--I guess a compromise--where recommended members of groups at increased risk should avoid donating blood. Was that effective? How was that?

EVATT: That was very interesting because what happened was, after we recovered 00:53:00from that January 4th meeting, because all of us were--as I say, I can't emphasize [enough] how deflated we were after that meeting. The patients with hemophilia kept piling up and so forth, and so we got together in Dr. [Walter] Dowdle's office and decided CDC couldn't issue guidelines, but the Public Health Service could. So we got together a draft for recommendations to come out of the Public Health Service. [Dr.] Ed Brandt was Assistant Secretary of Health at the time, and Ed Brandt is, by the side, my wife's cousin. So we put together those 00:54:00guidelines and shipped those off to the other agencies and to Ed Brandt's office. Well, a firestorm hit, of course.

MILLER: And the guidelines were basically?

EVATT: To defer high-risk groups and to do surrogate testing. A firestorm hit, because we were overstepping our bounds once more, even more than the January 4th meeting. The FDA was absolutely furious. Absolutely furious. They flew down and met with Walt Dowdle, who was my boss and Jim Curran's boss.

MILLER: He was the Head of--

EVATT: Head of Infectious Disease. Walt and his diplomatic ability smoothed that over. But anyway, it got reviewed by three different agencies, and it got 00:55:00watered down quite a bit, so it got published in March.

MILLER: So they left out the surrogate testing.

EVATT: They left out the surrogate testing, and they watered down the elimination of homosexual donors, watered that down to men that had had multiple sex partners or something like that. So that got published. Still, the FDA was reluctant to believe that it was a blood-borne disease, but they went along with those recommendations. So that got published. But again, you're progressing into the change. Now, if you go back and look at the infectivity of units of blood, which an investigator by the name of Bush has done in San Francisco blood banks, 00:56:00you'll find that that did have a major impact on blood transfusion infectivity, so that it fell fairly dramatically. So that by the time the test was actually introduced in mid-1984, the infectivity of individual units had dropped considerably.

MILLER: Just from the recommendations that urged members of high-risk groups to abstain from donating blood voluntarily.

EVATT: Voluntarily. So that was effective in terms of producing a lowered risk for transfusion recipients. The effectiveness for hemophilia is difficult to say, because so many donations go into a unit that probably--that was not what 00:57:00affected the hemophilia. What affected hemophilia was the heat treated--

MILLER: Can you tell us a little bit about that? You and colleagues at CDC, Steve McDougal and others, did quite a bit of research on inactivation of virus with heat treatment, as was done a few years before, looking at hepatitis B. Can you describe that a little and what the impact was?

EVATT: Surely. Well, in 1983, Baxter introduced heat-treated factor. It was lyophilized [freeze-dried] material they stuck in an oven and heated, and it was licensed by the FDA for prevention of hepatitis B transmission. They 00:58:00unfortunately charged three times market price for a regular factor. This medication is so expensive anyway that nobody would buy it.

MILLER: So Factor VIII cryoprecipitate, now you're heating it and it's tripling its cost?

EVATT: It's purified. It's beyond cryo. It's purified factor. So they take cryo and purify it. Out of the cryo they purify Factor VIII. Then they heat it in an oven. They put it on the market for hepatitis B prevention. Well, at that point in time, people didn't even know anything about whether or not it was effective against HIV, so nobody would buy it. Nobody would pay three times--

MILLER: And how much are we talking about in dollars at that time?

EVATT: Factor VIII I think at that time was selling for about 15 cents a Factor VII unit. Now Factor VIII unit, a patient receives a thousand units at a time or more, depending on how big they are. So 15 cents per unit is a lot of money. But you raise that to 50 cents a unit, and you really have--you're really producing some increased cost, especially if you're bleeding twice a month and you had to treat for two or three days.

MILLER: Was insurance paying for that?

EVATT: Yes, but there's a lifetime cap on insurance. Many times, the patients had to pay 15% or 20% of the cost, so nobody would buy it. The question is, was 01:00:00it effective? Well, when the French found LAV [lymphadenopathy-associated virus], they sent it to [Dr. Robert C.] Gallo.

MILLER: At NIH.

EVATT: At the NIH. Gallo was not one of my favorite people, and he certainly wasn't one of [Dr. Donald P.] Don Francis's favorite people. Gallo suddenly discovered it at the same time and called it HTLV III [human T-lymphotropic virus], I think. So we requested some of the material of Gallo's to work with at CDC. Gallo refused and wouldn't send it to CDC. The French were very helpful, and the French actually sent Steve McDougal some LAV, so we had LAV in our 01:01:00laboratory. McDougal ran my immunology lab. Very bright guy. Very careful. But he was an immunologist. This didn't make the viral disease people very happy, that we were working with LAV. But McDougal worked out an assay for LAV and could quantitate it. So he could grow up tons of this stuff in his laboratory. So I went to Steve, and I said, "Steve, look, let's try some of this stuff in concentrates and heat it and see what happens to the titer." Steve says, "Sure, that's easy to do." So Steve grows up the thing. I get him some concentrates. He 01:02:00spikes the concentrates and then we heat it. First of all, we wanted to heat it both in a liquid state, because there was one company in Germany that heated it in liquid state, as well as the dry state in [as done by the] American companies. We wrote to the Germany company, and they wouldn't give us their method of doing it. It didn't make any difference. We just got it from the patent office and copied the patent. So he did these things.

MILLER: So you're heating up concentrates of the HIV virus, LAV.

EVATT: Concentrates of, clotting concentrates that would go into hemophilia patients, but we spiked them with the virus and then we heated them. Then the 01:03:00liquid one, we had to re-lyophilize.

MILLER: Lyophilizing is--

EVATT: Means freeze drying. So we tried to find somebody at CDC that would let us use their lyophilizers to lyophilize LAV. That was not an easy thing to do. Finally, we found a discarded one over in the basement of the virology building. We wrapped it up in HEPA [high-efficiency particulate air] filters and everything and lyophilized the liquid stuff. We then heated the freeze-dried material in the dry state. Then Steve McDougal looked at the titers, and we had about a six-log diminution of the titer. So we thought this was fantastic. I was 01:04:00going to the World Congress of Hemophilia, which was being held in Rio. I went down there and I presented this to the congress down there, where it had countries from all over the world, that heat inactivates this stuff. It was fantastically received, but nobody wanted to use the Factor yet. So we were able to put it through the commercial companies' processes. Alan Brownstein, who was Executive Director of the US Hemophilia Foundation, got four manufacturers together. I had lunch with Alan and those four manufacturers. Two of them, Alpha and Cutter, agreed to put the virus through their processing plant. We got back, 01:05:00they sent us the material, we spiked it, we sent it back to them, and they put it through their processing and sent it back to Steve McDougal. He tested it, and same results. Extremely--

MILLER: That was brave of them.

EVATT: Yes, extremely effective. Baxter didn't and Armor didn't. Baxter came back later and asked us to do it, and we did it once more. But we got the same results in all. Then I flew up to meet with the head of the Medical Advisory Council for the National Hemophilia Foundation, along with [Dr.] Jeanine Jason, and we presented this data to the Foundation. They immediately recommended that 01:06:00all--that people switch to heat treated. Although we still had two vigorously opposing physicians on that council that opposed the switch.

MILLER: So that heat treatment then did not inactivate the protein you had originally been concerned about?

EVATT: No. Well, it may have partially heated it, may have partially inactivated it, but not enough that it was still extremely effective therapeutically and that it inactivated. Well, if you go back now and look when that switchover occurred, which was the end of '84, you go back and look at birth cohorts in patients born in years '85, '86, '87, '88, none of the patients were infected with HIV after that. So that switch to heat treated stopped the epidemic. That 01:07:00was before the testing was introduced in July of 1985. So that switch was extremely effective in stopping an epidemic.

MILLER: In December of '83, the Blood Products Advisory Committee of the FDA met to discuss options of surrogate marker testing, and testing was proposed but not recommended again.

EVATT: That's correct.

MILLER: Finally, in January of '85, when an antibody test for the virus was available, provisional PHS [Public Health Service] recommendations for screening donated blood and plasma for antibodies of the virus were established. It is said that many, many hemophiliacs and recipients of blood transfusions were infected during the two years between 1983 and 1985 (1983 and 1984). Is there an 01:08:00estimate of how many were infected?

EVATT: The estimates are difficult, because you had so many who died. We went back and tried to look at the estimation of the number of--there were at least 50% of the patients, and it may have been closer to 60%, 65% infected. But they were all estimates. We don't know for sure. A lot of the patients didn't--the disease didn't show up till later. So we know from birth cohorts that the infections stopped at the end of 1984. So nobody got infected after the end of 1984. But we've continued to find cases through 1985, '86, '87, '88 that didn't 01:09:00know they'd been infected back prior to 1984, but they'd all received factor back in those early days. This made it difficult, because when that recommendation was made in 1984, this was a surveillance problem.

When that recommendation was made in 1984, we had no in vivo [taking place in a living organism] data that said it would prevent the infection. All we had was the in vitro [taking place outside a living organism] data on the inactivation, so that we had to set up a surveillance program that followed after that. Now, one of the problems that occurred in that surveillance program is that you have so much noise, because you have patients that have never been tested that are coming down with AIDS during the next several years, because of that long 01:10:00incubation period of up to ten years before they came down with one of these identifying conditions. Without a prior test, we couldn't determine whether or not someone that came down with a new infection was a possibly new case or not. But we did manage to find some, because one of the manufacturer's processes was inadequate. Not enough heat, not long enough.

MILLER: In terms of looking at numbers of even hemophiliacs, are we talking about tens of thousands or are we talking--

EVATT: Well, there's about--the number of hemophilia patients in the US, there's about a total of 15, 16, 17,000 total in the United States. In a number of Factor VIII [deficient patients] that became infected, I would approximate it as 01:11:00probably between 6,000 and 8,000 total. Because [out of] all of those hemophilia patients, some of them are Factor IX, which didn't get as high a dose because they don't take as much factor. So that if you look, there's probably 14,000 to 16,000 patients with hemophilia A, Factor VIII deficiency, and those were most heavily infected.

MILLER: Then their partners.

EVATT: Yes.

MILLER: So additional cases that were created from them. With the luxury of hindsight, could we have responded differently? What were some of the barriers to responding differently?

EVATT: I think for transfusions, I think that if we had had--if you look from the time that transfusions--[when] the gay population started becoming infected 01:12:00to the time that the restriction of high-risk groups [was in place], it was a period of ten years. So ten years of exposure of transfusion recipients with increasing frequency occurred up until the ban on high-risk donors donating. Had the same thing occurred--if you go back historically and look, the same thing occurred in the 1960s and 1970s with hepatitis. But then they--at that point in time, there was such a demand for plasma and blood products that they were 01:13:00bringing in blood from foreign countries, they were bringing in blood from prisons, they were bringing in blood from--they were paying for blood, they paid donors. They were paying, they were buying blood everywhere, and half the patients, 25% to 50% of the patients from those paid donors in some studies would become infected with hepatitis. So it was a major hepatitis epidemic. That developed the all-volunteer donations. What they were doing in essence was screening out high-risk donors for blood-borne infections.

They focused on the wrong thing. They focused on the philosophical question that blood is a gift, and so it shouldn't be paid for. Now, if they'd focused on the factor, screening out high-risk donors and the paid donations for blood-borne 01:14:00infections, they could have had that already in place. The one thing that was missing in that group were the homosexual donors, who are also a high-risk group but weren't identified with the paid donors because they voluntarily gave. But that was the first time, and that long lag time infected tons of people with hepatitis C and hepatitis B. I think that was the first exclusion, but it became a religion of paid versus voluntary. But it wasn't--that wasn't the issue. It wasn't the fact that you paid a donor that made it infective. It was the fact you were drawing it from populations at high risk. Now commercial blood banks pay for donations for plasma products, but they do an extremely extensive screening process, and their background rates of these blood-borne infections are lower than the voluntary donors. So if they'd focused on the right thing, 01:15:00they could have eliminated a large portion of that population. They would still have missed it for this epidemic though, because of the year--high-risk donors, you had a major population of high-risk donors that were voluntary donors, so it wouldn't have held for this particular epidemic.

MILLER: Would money and resources have changed the picture? Do you think it was limited resources, both financial and human personnel? Was that a big barrier?

EVATT: I was surprised how quickly--you know, people did all kinds of--afterwards--but I was surprised how quickly these epidemics were resolved in terms of--if you go back and look at the history of things. Especially with such 01:16:00a paradigm shift in terms of how people had to change their way of thinking about infectious disease and blood-borne infections and so forth. First cases appeared--after the first cases appeared, the identification of the groups went reasonably quickly, considering you had a passive system. It wasn't an active system, and the pentamidine file was the most active way we had of finding them [cases]. If we hadn't had that, it may have been delayed another year. But it occurred reasonably quickly. The inactivation--if the switchover had occurred to the heat-treated factor in '83, it would have eliminated a lot of patients with hemophilia. The test occurred later, but already by the time the tests occurred, the elimination of the high-risk groups had already had a major effect on the 01:17:00HIV epidemic. By that time infectious units were quite low, by the time that the test was introduced in terms of screening.

So it really didn't have the effect that the exclusion of groups had had, and that came from the basic epidemiology and recommendations. I think had that been made earlier, you could have prevented a lot of blood transfusion cases. I'm not sure it would have made any difference in hemophilia. I think the inactivation--you had to inactivate the material for hemophilia. That's personal opinion. But if you look at the data, I think it supports it. I think that my recommendation for the future is that high-risk groups for blood-borne 01:18:00infections ought to be excluded, possibly including medical personnel, because they're a high-risk group for a number of blood-borne infections acquired in hospitals and just through what they do. But I think that that should be the--unless you have a blood shortage, then it changes the nature of things.

MILLER: There were a lot of legal proceedings that took place after this. Now, was this involved with persons with hemophilia who developed AIDS and their families suing the blood banks, or what happened there?

EVATT: I think that's important. After something like this occurs, everybody looks around for somebody to blame. There were two. Another cause of the mindset 01:19:00that occurred is as a result of the fights between the volunteer versus non-volunteer in the 1960s, blood banks--there was legislation introduced in most states that blood banks couldn't be sued for transmitting diseases. So they felt protected. Now, the companies didn't, because they had product liability and they were more sensitive to going along with recommendations. In fact, many of them started excluding high-risk groups long before the recommendations came out of the Public Health Service. They wanted to be ahead of the curve because they knew they were going to get sued. Blood banks didn't get sued as much as the commercial companies, and the commercial companies got sued. There was so 01:20:00much money involved in that, that was quite an inviting plum for the lawyers to get into those lawsuits.

MILLER: Were some of them won by the plaintiffs or--

EVATT: What they did, they came to a settlement, a general settlement. The companies all went together and settled across the board with the plaintiffs. So it all got filed, folded into a class action suit. Although individual suits did occur, and those were varied in terms of the outcomes. But it was difficult to do. The companies didn't intend, for the most part, didn't intend to harm their 01:21:00patients. But they made some very bad decisions in some cases. Unfortunately, those decisions probably did end up in some big claims.

MILLER: In closing, I just wanted to get your sense of the personal aspects of your work on AIDS. How did your work at this very intensive time during the AIDS epidemic affect you personally?

EVATT: Well, it was very time consuming. First of all, I think of time. It was extremely busy. Now, it was not my major interest at all. I just wanted to get 01:22:00this thing over with, so I could get back and work on the things I wanted to work on. It was kind of a diversion that being at CDC, you're responsible and you have to do it. I think that was, for the most part, the attitude of my whole division. We worked with it, we tried to solve it as quickly as we could, tried to help wherever we could, but it was not--we did not consider it career enhancing to work in this area.

In retrospect, it probably was more important than the things we wanted to work on, but that's the way it is. In retrospect and if I had to do it again, I'd still do the same thing. It was a major problem, it was confronting the American 01:23:00public, and it had to be solved, and it had to be solved as quickly as possible. If I have any regret or any feeling of failure, it's really that I couldn't convince these people to do what should have been done any faster. I don't know whether it was my communication skills or what it was, but I couldn't convince them to exclude high-risk groups and to think about surrogate testing. Because I think those would have made a difference in the blood transfusion recipients if they'd been done earlier.

MILLER: With the advantage of 35 years of hindsight, do you have any additional thoughts on CDC's response to the epidemic?

EVATT: I think CDC's response was excellent. When I compare it to the other 01:24:00agencies, it's exemplary. Now within CDC, there were clearly turf battles. I'm not going to deny that. That got in the way sometimes.

MILLER: Can you give an example? Or rather not?

EVATT: Rather not give examples, but there were turf battles. It depended on, to some extent, on how people were--what they looked at this condition to do. We looked at it as something as a job we had to get done. Other people looked at it as a career, and they had a different perspective. You had people like Gallo 01:25:00that looked at it as a Nobel Prize, and that changed the way they cooperated and it changed the way their interactions. But that's just normal reactions. But in terms overall of how CDC came out of this, they did a first-rate job. You go back and you can't blame CDC for anything that they did incorrectly in this. That was I think due to the exemplary leadership that CDC had at that time. Working with Walt Dowdle was just fantastic. Walt really directed the overall direction of this AIDS epidemic investigation and processes, and he kept 01:26:00everybody on a level head. He deserves a lot of credit, which I don't think he gets in terms of what he did to keep us all together and working towards this common goal.

MILLER: Thank you very much.

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