00:00:00Harry Haverkos
MILLER: This is Dr. Bess Miller, and I am here with Dr. Harry Haverkos. Today's
date is April 26, 2017, and we are in Atlanta, Georgia, at the Centers for
Disease Control and Prevention [CDC]. I am interviewing Dr. Haverkos 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].
Dr. Haverkos, do I have your permission to interview you and to record this interview?
HAVERKOS: Yes, you do.
MILLER: For this oral history of the early years of AIDS at CDC, we will be
focusing on the first several years, beginning in June of 1981 with the
publication of the first Morbidity and Mortality Weekly Report [MMWR] on the
five cases of Pneumocystis carinii pneumonia among homosexual men. Harry, you
were one of the first epidemiologists at CDC to work in what would become known
00:01:00as AIDS. You were involved in nearly all of the critical activities during those
early years and in many aspects of AIDS research and clinical care throughout
your career. In addition to your many scientific publications, you later
captured this early work in your book On the Front Lines of the AIDS Pandemic,
published in 2012.
Let's begin with your background. Would you tell me about where you grew up and
your early family life, and then where you went to college?
HAVERKOS: Sure. I was born in January of 1951, the same year as the EIS
[Epidemic Intelligence Service] started, in Cincinnati, Ohio. I was the oldest
of four children. My father was an attorney, and my mother stayed at home until
after we all went off to college. It was a very strong Roman Catholic family. My
00:02:00father was in the seminary for high school and college and then left. I think he
got some vision of women and moved out of the seminary. He got drafted and went
to World War II, fought in the Battle of the Bulge, came back and got a law
degree and then became--hoped to be a politician. I went to Catholic school,
grade school and high school, and then went to [the University of] Notre Dame as
an undergrad and studied. I wasn't sure whether I wanted to be a lawyer or a
doctor or a scientist, and I studied a broad spectrum. I eventually went to
medical school and met my wife, Lynne, who was also in my class.
MILLER: What influenced you to go to medical school?
HAVERKOS: Probably a love of science and the fact that I did pretty well at
00:03:00Notre Dame in biology, and it really influenced me to think about medicine. I've
always liked people and working with people, and I was just fascinated by the
science and the human body. I think that drove me to medical school
MILLER: Where did you end up going to medical school? Did you have a subspecialty?
HAVERKOS: We went to Medical College of Ohio at Toledo. We started in 1973. That
was during the Vietnam War era, so I had a very low draft number. Another good
reason to get into medical school is that it kept me from getting drafted. It
was a three-year school. They were trying to put us through quickly for the war
effort. By the time we graduated in '76, the war was over. They were really
00:04:00trying to groom family docs [doctors], primary care docs. I became fascinated
with internal medicine.
We moved to Akron, Ohio, got married when we lived in Akron, and had our first
child. I did three years of training in Akron but really was interested in
infectious disease and maybe going back to medical school [for further
training]. There was a guy named [Dr.] Bruce Ribner, who is actually now down at
Emory, who was our infectious disease professor. I took an elective with him,
and I was very impressed with him. Everything was science based, evidence based.
He'd send us off to the library to read papers every day. I happened to work in
the medical library as my work-study job, and so I became fascinated with
00:05:00infectious diseases because of him.
Then I went to Akron and did medicine. The chief of medicine there turned out to
be an infectious disease guy from my hometown, Cincinnati. Internship was the
swine flu and Legionnaires, so I started reading the MMWRs and wanted to get
into research. I left Akron, a community hospital, and went to the University of
Pittsburgh and did infectious disease training there. It was a research
fellowship, and I did some epidemiologic studies and some studies with [herpes
viruses]. We had a big transplant service that was doing some research on
opportunistic infections of kidney transplant patients, cancer patients, and I
actually saw my first AIDS patient.
MILLER: Tell me more about that. I guess at that time you didn't know it was AIDS.
00:06:00
HAVERKOS: We didn't know it was AIDS, but it was a very unusual case. It was a
guy in his mid-30's who actually ran a bathhouse in Pittsburgh. He was a big
heavy guy, about 350 pounds, and he started having symptoms about 18 months
before that. This was December of 1980 when I first saw him. He was having
weight loss and fevers off and on, and he actually came into the hospital in
December of 1980. He had a pneumonia that didn't respond to antibiotics. They
did an open lung biopsy on December 30, 1980, and I was the ID [Infectious
Diseases] doc, the fellow on call. I got called down to the micro lab. [It was]
Pneumocystis pneumonia, so we started him on Trimethoprim sulfa. When he didn't
get better, we called the CDC. We got pentamidine from the CDC and we didn't
00:07:00know what was going on. He eventually left the hospital. He came back three
months later with chronic diarrhea that they couldn't control. That's when I
found out he was gay, because he [had gay bowel disease]. I saw him again, the
attending presented him in internal medicine rounds, and I saw him a second
time. Then I actually saw this guy a third time here, down at Emory, in August
of 1981. He had left Pittsburgh. By this time he's down under 200 pounds; [he]
started out about 350. He moved in with relatives in Pensacola, and one night
couldn't find his way home. He was picked up by a psychiatric hospital there,
and when they found he had a fever, they shipped him up here to Emory. He then
got reported as an early AIDS case, and I went down and saw him at Emory. He
then developed Mycobacterium avium intracellulare and died late in August.
00:08:00
MILLER: Do you remember your feeling about that patient?
HAVERKOS: Feeling as far as?
MILLER: Was it upsetting? Was it striking?
HAVERKOS: It was very striking, but as an infectious disease doc taking care of
patients on transplant services and cancer patients, you get consulted on fairly
severe infections. It was a long course. He was one of the few patients I was
able to see multiple times. Normally you see a patient and they go back to their
primary care doc, and here I got to see him in three different settings. When I
read the June 5, 1981, MMWR, I was at Pittsburgh still, I didn't start down here
till July 6th, the first Monday in July. I'd already come down for the EIS
00:09:00[Epidemic Intelligence Service] conference and been assigned to parasitology.
MILLER: Before then, what made you get interested in public health and then CDC?
HAVERKOS: Bruce Ribner, again. I finished two years of the ID fellowship in
Pittsburgh, and I was looking for a job. I wanted to grow up to be an academic
infectious disease guy at a university in the Midwest. At that point I had one
published article and two in press, so I didn't have very many credentials. But
I sent letters off to the University of Cincinnati, Ohio State, University of
Kentucky, and Medical College of Ohio, and basically everybody said, you know
[you are not qualified]. So I called Bruce Ribner up. This was in October or
November of 1980. He said, Harry, you're not quite--have you ever heard about
this program called the EIS? I said, no. I know CDC does some infectious
00:10:00disease. He said, you ought to think about this. There's a number of guys in
academic ID who go through this program. Maybe you'll get lucky, you'll get an
outbreak and you'll get a couple of publications, and then some university might
want to hire you. So I called CDC.
Of course, I was too late for applications for that year. It was supposed to be
in by September. But there was a problem between the University of Pittsburgh
and CDC over Legionella mcdadei, which had been discovered in Pittsburgh.
Pittsburgh wanted to call it Legionella pittsburgensis, but the CDC knew where
to send the data for the name. So there was a big friction. When CDC told me I
couldn't apply because I was too late, a lot of the staff people at Pittsburgh
got on the phone and called. CDC finally said, if you come down, we'll think
00:11:00about you. So I flew down on December 8, 1980, interviewed, and two days later
they offered me a slot in EIS.
MILLER: Terrific. Let's shift our focus to your work on what was to become known
as AIDS. You came to CDC as an Epidemic Intelligence Service Officer. Where were
you assigned, and what were you doing when you first arrived?
HAVERKOS: I was assigned to parasitology, so I'd been there the April before.
Actually, our daughter, Katie, was born the Sunday before EIS conference. I
didn't get down here till Wednesday. I listed parasitology fifth and got my
fifth choice. I was not overly happy. I thought, how is this going to get me
back to the Midwest as an ID guy? I came down on July, whatever that Monday was.
00:12:00We all got together in class. My boss was [Dr.] Dennis Juranek, who ran the
protozoal part of parasitic diseases, which at that time was headed by [Dr.
Myron G.] Mike Schultz.
On my first day Dennis said to me, there's this guy, [Dr. James W.] Jim Curran.
He's looking for people to work on this new outbreak, and I want you to talk
with him tomorrow, Tuesday. So I went over and talked to Jim Curran on Tuesday,
and Jim asked me if I'd heard anything about Kaposi's sarcoma [KS] or
pneumocystis. I told him about my patient from Pittsburgh and that I'd read the
MMWR on June 5th and that my case was like those guys in Los Angeles. I told him
about my work doing open lung biopsies and pneumonias and immunocompromised
patients. Then he saw on my resume that, like him, I went to Notre Dame, so we
00:13:00talked a little Notre Dame football at the end of the interview. He told me he
was talking to a few other people and he'd let me know. The next day he called
me, and he offered me a position. I accepted, and he said, your job is to set up
AIDS surveillance.
MILLER: What was your reaction to that? It was a little different than maybe
what you thought you would be doing when you first arrived. Were you excited?
HAVERKOS: I was excited, yes. I mean, it's a disease I'd seen, it is right up my
line of thinking, and I was very excited. So what do I know about surveillance?
What is surveillance?
MILLER: What was the atmosphere at CDC then among people working on the disease?
00:14:00How did CDC organize those of you working on the disease?
HAVERKOS: Of course, I didn't find that out for a couple weeks. I was in class
with you. You and I were in class, right. Jim called me up the second week on
Monday or Tuesday, and he said, have you got a case definition yet? Are you
ready to go? I said, well, well, well, I've looked over my class notes, and I
talked a little bit to Dennis about what surveillance is. So he was not happy.
But I hadn't interacted. I hadn't yet met [Dr.] Harold Jaffe or [Dr.] Mary
Guinan, or [Dr.] Paul Wiesner or any of the [Task Force members]. I was
interacting with Dennis Juranek.
He [Jim Curran] called me back later that day--I don't know if was Monday or
Tuesday of the second week. He said, you know, you're going to need more time to
work on this. You don't have to go to class the third week. I was a little bit
disappointed. I thought the classes were quite interesting. On the other hand,
00:15:00he said, you've got to have this case definition, because we have to be ready to
go by the end of the third week. So I went in the third Monday [to his office],
and he told me, you've got to come up with a case definition. I suggest you read
over these reports. They had about 40 cases at the time, case reports [of
patients] that Dennis and Jim had seen in New York. I don't know if there were
some reports from San Francisco as well. We had [Dr. Michael] Mike Gottleib, who
had sent in some case reports through [Dr.] Wayne Shandera out in LA [Los
Angeles], so I read those. He told me that I had to explore the Pentamidine
registry. I knew the Pentamidine registry because I'd used it at Pittsburgh, so
I met Sandy Ford [technician in CDC Drug Services] and others.
MILLER: Tell me a little bit, for those viewing as students, what was the
significance of coming up with a case definition?
00:16:00
HAVERKOS: If you're going to count cases, if you're going to find out what the
problem is, you've got to define what you're looking at, and it was not clear.
These reports of cancers and infections and-- of course, as I learned later on
and in class, case definition is-- I don't remember if we did the foodborne
outbreak exercise, but you know they have the list [12 Steps of Outbreak
Investigation]. You've got to develop a case definition, develop a systematic
way to collect cases, and then do a line listing and an epi[demic] curve.
MILLER: What did you come up with?
HAVERKOS: I came up with a three-part definition. The first part was, you had to
have a disease diagnosed that was at least moderately predictive of immune
00:17:00suppression. How I defined that was if you reviewed the literature--and I spent
the first two days in the CDC library reading about all these diseases, many of
which I'd read about before as an ID fellow, at least the infections. The
cancer; Kaposi's that was another story. What I did is, I started tabulating
case reports, what percentage of cases reported in the literature were among
immunocompromised patients with cancer or steroid use or transplants, and which
were in healthy individuals. Going back to my father's legalese, you know,
probability is 50 percent or more; possibility is 50 percent or less.
I counted case reports--well, pneumocystis, if you read the literature.
00:18:00Essentially every case in the literature is an immunocompromised patient, except
for my patient in Pittsburgh and the patients in Los Angeles. The only
exceptions were some cases in orphanages in Eastern Europe and a few neonatal
cases, where they hadn't, in my mind, done a complete workup for congenital
immunodeficiency. So pneumocystis was a no-brainer. Cryptococcal meningitis I
came up with right about 50 percent, so it just barely made the list. Toxoplasma
of the brain was clearly in that 50-75-80 percent range. Tuberculosis, which
turns out to be the biggest opportunistic infection in Africa and Asia, was only
about 10-15 percent by my calculation, so that didn't make it. Just cold sores
wouldn't make it. I did quite a bit of work with herpes simplex, but extensive
00:19:00mucosal infections, again, were more commonly reported in immunocompromised
hosts. I thought we'd see a lot of Strongyloides, which we didn't see, so that
became on the list.
The second part was the age range, and, of course, it [Kaposi's sarcoma] had to
be biopsy-confirmed, and the patient had to be [15-60 years of age]--I learned
quite a bit from [Dr. Kathryn Nugent] Kathy Shands in toxic shock syndrome and
some of the problems she had with this clinical diagnosis and passive system.
But anyway, that was the first part of the definition. Moderately predictive of
immune suppression. Now, I included Kaposi's sarcoma. For Kaposi's sarcoma,
there were about 300 cases estimated in the U.S. each year, but they were in
00:20:00older men or transplant recipients, so we basically took that in the second part
of the definition. I said, [the patient] had to be between the ages of 15, which
in many ways I naively thought was an early age for sexual activity, and 60, to
cut off the elderly men with Kaposi's sarcoma. So the second part was an age restriction.
The third part was, you couldn't have any evidence of immune suppression,
couldn't have steroids, couldn't have a transplant. If you go back and read Mike
Gottleib's five cases, It turns out one of the cases was diagnosed with a
lymphoma two years before, so we threw that case out. There were cases that
didn't meet the definition. That's how I came up with the definition. Jim seemed
to like that when I presented it to him, so that's what we went with.
MILLER: What kind of forms did you use for these--you know, this is the dark
00:21:00ages for those now, with no computers, we didn't have--were these handwritten forms?
HAVERKOS: We had a secretary, and then we had to develop a plan. We had to
decide how we were going to do surveillance, active or passive. But a form--he
[Jim Curran] said to me, we're going to need a form. Why don't you draft a form.
So I went back to my office, and it took me about an hour. It was a
check-the-box form. I know when you call clinicians, you don't want to say, wait
up, wait up. We had our diagnoses, how was it confirmed, culture, you know,
check the box. We had to have the name of the patient, we had to have the name
of the reporting doc, we had to have onset of symptoms, dates the biopsies or
whatever were done, if the patient died, and when they died. But it was a 2-page
00:22:00form. We asked about sexual orientation. We had listed homosexual, bisexual,
[according to] reports of the physician. We'd ask the physician, and the
physician would say, I think this guy is gay, or I think he's straight. We
didn't have anything about injecting drug use. We didn't know about that. But it
was a 2-page form, and I got our secretary to type it so I could check the box.
I think we collected a little data on immunology, the white count or CD4 count
[T-cell test]. Then, of course, we had to get names and addresses of the
physicians reporting. We had to go back [to them] if we're going to do a study.
So I put it together in about an hour, tried to make it a check-the-box, and
00:23:00took it back in to Curran. Curran seemed a little surprised that I could turn it
around that quickly, but that's what we went with.
MILLER: What was the relationship at that time between CDC and all these
clinical and academic physicians that were reporting cases?
HAVERKOS: I actually think it was pretty good. Most of it. They were as alarmed
about this as we were. We had pentamidine down here. I spent the whole day on
the phone basically, and physicians would call. They'd tell me about their
cases. I'd fill out the reports, and they'd ask me questions. I got a couple of
calls from the press, but they weren't too interested. Patients could call, and
health departments would call. I can remember we didn't have speaker phones in
those days, so I would--my ears would just burn. I mean it was hot. It generates
00:24:00quite a bit of heat. I'd change to this ear and that ear. I was on the phone
constantly. But they were looking for information, just as we were.
I think relations with academic docs were very good except for a few. There were
a couple of groups who I won't mention, who were going to write their cases up
for the New England Journal, so they weren't going to call us until it got
published. But that resolved after publication. I thought our interactions with
people went very well. I enjoyed--I liked talking to people, so for me it was a
lot easier taking a call than going into the intensive care unit back at the
University of Pittsburgh. It was a lot of fun.
MILLER: This was leading up to a case-control study, one of the earliest efforts
00:25:00to try and get more of a handle on the disease, and you were quite involved with
this. Can you tell us a little bit about the case-control study and your
particular role?
HAVERKOS: Actually, while I was doing surveillance and [talking] on the phone
with the docs, Harold and I think [Dr. William] Bill Darrow were deciding about
the case-control study. I was in the dark on that aspect until I guess early
September, when they decided there were going to be eight of us to do the
interviews and that I was going to interview in New York City. Then they had to
train us. They had to tell us, you don't lead the patients, and you try to treat
cases and controls the same way. They gave us the interview [form], which was
about 25 pages. [It included] a lot of sex, a lot of drugs, a lot of more
00:26:00standard things, chemicals and other things that might cause immune suppression.
MILLER: Was the case definition used, the one you had developed in your initial
surveillance, or had it been modified by then?
HAVERKOS: No, no. Harold didn't want to take these cases like 50-60 percent. For
example, cryptococcal meningitis, he didn't think was specific enough, so you
had to have Kaposi's or pneumocystis, period. Any of these other cases, brain
lymphomas, the chronic disease people wanted me to include, which I did.
Extensive herpes viruses, they didn't count. Many of these patients who had
pneumocystis also had cryptococcal meningitis and esophageal candidiasis and
00:27:00crypto [cryptosporidiosis]. Some later had TB [tuberculosis]. It was a more
specific case definition.
MILLER: Was that controversial? Did you agree with that?
HAVERKOS: Oh yes. No, I could understand. I'd studied a little statistics and
study design at Pittsburgh. It was a research fellowship, so, you didn't have
to--no, that was not a problem. That was not a problem at all.
MILLER: Was it difficult deciding on who the controls should be?
HAVERKOS: Yes, it was. Harold ended up selecting a spectrum of controls so that
the first one--and he was going to match them by age, race and residence. The
first control was, when we interviewed a case, we were to have them identify for
us a friend who was matched by age and race and a friend of theirs, but one who
they'd never had sex with. We would ask them to call and set up the interview,
00:28:00and sometimes we'd do the interview in the home of the case, or wherever that
friend control [lived]. We got two controls from STD [sexually transmitted
disease] clinics. After I'd interview a case and I didn't have interviews
scheduled, I'd spend a day or two in the VD [venereal diseases] clinics nearby
and I'd look, again, for a matched control who came in for any STD. [The
control] clearly had to be gay, just as the cases had to be gay, the friends had
to be gay. These had to be gay controls. We had two for each case matched,
again, and we picked them up, either Jim Monroe in New York City, who was the VD
rep at that time, or one of his docs would identify them for us and set up an
00:29:00interview with us.
The next group, we went to private practitioners in the four cities. We did this
in New York, San Francisco, Los Angeles, and here in Atlanta. We identified
physicians who had predominantly gay practices who were, of course, very
interested in helping us out. They were to randomly select a control from their
patient population. We didn't want a volunteer. We didn't want them to get the
most interested, so we randomly selected them by taking a letter out of the
Rolodex. [If] it was the letter "R," that was the letter that was selected, so
across all these four cities the docs were to-- We told them, okay, I
interviewed a 34-year-old white New York City resident. Find me a matched
00:30:00control within 3-5 years of that age. I think the age restriction was broader
for one category and looser for another.
MILLER: But also gay?
HAVERKOS: Also gay.
MILLER: All the controls were gay?
HAVERKOS: No, no. I didn't get to the last group, the fourth group. The fourth
group was a straight control, so the doctors, whether it was [Dr. Michael] Mike
Tapper or whoever the doc was in New York City, would be told, I need an [age]
34 plus or minus 3 Hispanic, white resident. Go to your letter "R" and start
with "R-A." Go down to the first patient you find to match, and call him up and
ask him to participate. If he says yes, hook him up with Harry or Jim or whoever
is doing the interview. If he says no, go back until you get one that agrees.
For the last group, we tried to get heterosexual controls. We went to different
practices in the four cities and talked to docs who had predominantly
00:31:00heterosexual patients and did the same thing. Letter "R" again; match, call up
this guy. We had a lot more trouble getting heterosexual controls. We had a lot
of trouble getting friend controls.
MILLER: Can you tell us a little bit about the thinking of why so many control groups?
HAVERKOS: We had no idea what control group to use--I mean, what are you going
to do? Do a telephone survey? Call up in New York and say, are you gay? Go knock
door to door? Maybe you could do that in San Francisco, but surely you couldn't
do that in New York or Atlanta or Los Angeles. So we weren't sure how we could
get a representative sample of gay men in the study. Harold--again, the
designers of the study argued that we can't pick a perfect control group. Let's
00:32:00pick a spectrum, and this is the spectrum they picked. I thought it was
brilliant-- I teach field epi and I think it was-- I was so impressed with the
case-control study. It changed me from wanting to go into clinical medicine. Now
I want to figure out the cause of every disease that I come in contact with.
MILLER: Were you involved at all with the analysis of the data?
HAVERKOS: Yes, for a while.
MILLER: How did that go?
HAVERKOS: Not very well. The problem was, yes, I was very interested in the
analysis, and so [were] Harold and a guy named [Dr.] Keewhan Choi, the
statistician who was assigned to work with us. I worked with them for several
months, but they did not agree on so many things, and I just saw myself as
getting in the way. Harold, I think, argued as a biologist. He was saying, all
00:33:00these variables are confounded with each other; numbers of partners, rates of
STDs, drug use. We need to group these variables to lead us to an infectious
agent. Is it a toxin? Keewhan Choi was kind of rigid--I see him as a
statistician, and so I described them as two artists. Harold's an impressionist,
and Keewhan Choi is a photographer. Choi basically was going to look at the
data, and let the numbers speak. They couldn't agree, and so they grouped them
different ways. The analysis took forever because they couldn't agree on how to
do it. So I backed out of it after a while. I had other things to do.
MILLER: When you say forever, are we talking months?
HAVERKOS: It took months. We didn't publish that work until October of '83. We
00:34:00had preliminary data by December of '81. We spent the whole month of October of
'81 in the cities. I spent the whole month in New York City, October of '81. By
December we had the first printouts, percentages that did this or that. But I
don't think the results--I don't think we announced the results to the general
public until sometime in late '82. It was over a year afterwards, because Harold
and Keewhan couldn't agree on the results. I don't know what happened. I'm sure
there were much higher levels than I involved in those discussions.
MILLER: What were some of the early hypotheses?
HAVERKOS: We had four major hypotheses. Basically, everybody thought CMV
00:35:00[cytomegalovirus] was it. CMV was a herpes virus. I had done some work with CMV
at Pittsburgh, and CMV had been found in all five cases of Mike Gottleib's. We
found evidence of CMV in our patient in Pittsburgh. There was a guy named
Gaetano Giraldo in Italy who did a lot of work in KS in Africa, and in the '70s
he saw a herpes virus in electron microscopy of Kaposi's patients in Uganda and
then did serologic studies. At that time we knew of five herpes viruses: herpes
simplex 1, herpes simplex 2, CMV, EBV [Epstein-Barr virus], and varicella zoster
virus. Giraldo collected serum on KS patients [and] controls in Europe and
00:36:00Africa, and he thought he saw a little higher rate of CMV in the cases than in
the controls in his studies. He thought it was most consistent with CMV, so he
thought it was CMV. That was the leading hypothesis.
The second hypothesis was these drugs called the poppers or nitrites, which were
used by gay men. They're actually the forerunner of Cialis and Viagra. They
cause vasodilation, and they were [in] widespread use in the gay community in
the major cities. We did a quick survey of the STD clinics, asking patients
coming in with STDs whether they used poppers or not. About 85% of gay men in
the STD clinics had used poppers at least once, and I forget what range, 6
months, 2 years, 5 years, and about 15% of heterosexuals. So poppers-- there was
00:37:00an earlier outbreak, what was it, tryptophan, and a year or two earlier one of
the CDC investigations, so [that hypothesis involved] drugs or toxins.
The third theory was that it was some kind of immune overload, that it was just
multiple infections. These guys would have syphilis and gonorrhea, and they'd
overwhelmed the immune system. That was the third hypothesis we looked at. The
fourth was that there's some new agent out there. Again, herpes viruses, if it
was CMV, maybe it's another herpes virus, maybe it's a new herpes
virus--hepatitis-B like viruses. That's how [Dr. Donald] Don Francis and the
hepatitis people got involved, especially after within months we were seeing
cases in drug users. The pattern of gay men and drug users was very reminiscent
00:38:00of hepatitis B surveillance. Then there was actually a mention of retroviruses.
I heard about retroviruses that first summer, though of course I'd never heard
of them before being down at CDC. So those were the four leading hypotheses, and
we tested for those in our case-control study.
MILLER: You were one of the early persons working on cases in injection drug
users in a prison, for example, in upstate New York. Can you tell us a little
about that investigation?
HAVERKOS: Yes. Actually, in February of '82, there were essentially four of us
working full-time on AIDS up till then, plus a secretary. It was Jim and Harold
and a guy named [Dr.] Alex Kelter, who was from Chronic Diseases [Division,
CDC]. He was the sacrificial lamb from Chronic Diseases, and I was from
00:39:00Parasitology. In February of '82, Paul Wiesner went back and got more people to
work full time. He got [Dr.] Peter Drotman, [Dr. James] Jim Goodrich, and [Dr.]
Doreen Kramer. Mary Guinan, who was kind of dabbling with us, came on. Even I
think [Dr.] Martha Rogers got moved in at that point, so we had more players.
Jim gave me a choice. He said, do you want to continue doing surveillance--oh,
[Dr.] Richard Selik was the other one that came in. Do you want to continue
doing surveillance--we like what you're doing--or do you want to go out and see
patients? It was a no-brainer. I mean, my ears were burning. I was bored sitting
in the office. It was fun talking to people, but one of my first trips then was
to go to upstate New York. There were three patients that were in Ossining,
00:40:00"Sing Sing" prison in New York that were diagnosed with pneumocystis within a
couple of months of each other by [Dr.] Gary Wormser, ID clinician at New York
Medical College, I think in Valhalla, NY. Mary Guinan, who had a lot more
outbreak investigation [experience] than I, went up, and we met with John
Hanrahan, who was the EIS officer in our class assigned to Albany, New York. We
interviewed these three prisoners, who actually had spent some time previously
about a year and a half earlier at the same center, at the Taconic Correctional
Facility [NY] facility, a smaller center. It was 85% black, and it only had
about 200 inmates. These were three white prisoners, so 15% of the total. So we
thought, we're going to get the incubation period, we're going to get routes of
00:41:00transmission. We went up and interviewed these three guys and their wives. They
claimed they didn't know each other at all, hadn't seen each other, and it was a
fruitless effort. I think they also were not very likely to talk to us, because
how is this going to play out with your parole officer, telling us about their
sexual behavior and injecting drug use. It was a very fruitless--.but that was
my first experience. We basically didn't do as much--at least I didn't--as much
with drug users until I got to NIDA [National Institute on Drug Abuse] in 1986.
00:42:00
MILLER: Certain diseases were beginning to be predominant among the early
patients, as you mentioned when you said Pneumocystis carinii pneumonia and
Kaposi's sarcoma. What was the early thinking as to why some patients were
getting one disease or another? I know that's an area that you have had a
particular interest in as time went on.
HAVERKOS: After we finished the case-control study and we got the early results,
we did three follow-up studies. First, [Dr.] David Auerbach noticed that a
couple of patients in Los Angeles that he interviewed knew each other and were
sexual partners with each other. He called Bill Darrow and said, maybe we can
find out who's connected to whom and how it got from New York to Los Angeles.
They did a follow-up study, and eventually, with the help of a little black book
00:43:00from an airline steward from Montreal, were able to link 40 cases in 10 cities.
That further suggested that this was a sexually transmitted agent, not a toxin
or whatever. That was the first study.
The second study Mary Guinan started, saying, let's look at cases among drug
users and heterosexuals. We'd actually interviewed a couple of men in New York
City and in Los Angeles who claimed they were not gay. We had some cases that
weren't gay: heterosexuals, and some used drugs, and some didn't. Mary did a
follow-up study, and what we found from that was very interesting. We found
evidence of cytomegalovirus in over 90% of the cases in the case-control study.
We couldn't find evidence of cytomegalovirus as often in the injecting drug
00:44:00users and in the heterosexual men and women that we followed later. We also
found nitrite [inhalants] was used by almost all the [gay] men. It was not found
in the heterosexuals. Again about a 10% use of poppers [nitrite inhalants], and
maybe 15% antibodies or evidence of cytomegalovirus. So it pushed -- the first
two confirmed that that wasn't it [nitrite inhalants and cytomegalovirus were
not the cause of the syndrome].
The third study I did with Dennis Juranek's help, and we were surprised. It
turns out it was the first study. There were 50 patients included. Only 8 of
them [had] pneumocystis alone. Thirty-nine had Kaposi's sarcoma, and 3 had both
Kaposi's and pneumocystis. If you looked at that data, splitting it out that
way, it turned out the guys with pneumocystis were less sexually active. The
numbers of patients, of contacts, was much lower for the pneumocystis patients.
00:45:00So Dennis and I said, hey, let's get more pneumocystis patients, and let's
compare the data, all the data, the laboratory data of the men who developed
Kaposi's and the men who developed pneumocystis. Let's also follow these men
over time that are still alive that we've interviewed and see if they develop
the second disease. If they had pneumocystis, did they develop Kaposi's,
Kaposi's and pneumocystis. Peter Drotman and I would go out and interview new
cases of pneumocystis. We were focusing on pneumocystis in men. If they were
heterosexual, we'd give all the analysis to Mary for her study. If they were
gay, we took them into our study. After about October of '82, we had almost 90
00:46:00patients overall, and we had 20 in the-- 20 with pneumocystis alone, 20 with
both Kaposi's and pneumocystis, that's 40, and we had 47 with Kaposi's. We went
back and analyzed their results and then compared them to the controls also. Lo
and behold, we find the guys with Kaposi's were much more sexually active, used
much more drugs, recreational drugs, marijuana, and had more non-B hepatitis.
I didn't get Keewhan Choi to work with. I worked with Dennis Bregman and his
young [co-worker] [Dr.] Paul Pinsky. Paul, I think, did a lot of the work, but
anyway, they came out with a single variable that separated the gay men with
00:47:00Kaposi's from the gay men with pneumocystis. It was nitrite inhalants, which was
a startling discovery, I thought, and it made a lot of sense to me. It [nitrite]
causes blood vessels to dilate, and it [Kaposi's sarcoma] is a blood vessel
tumor. Kaposi's is predominantly in gay men, and nitrites are used more by gay
men than heterosexuals. It turns out if you reviewed the cancer studies, the
research studies that had been done on poppers, it caused cancer in the Ames
Test. This made just total sense to me. It was like a eureka moment. But the
problem was-- I got these results, so we stopped in September-October of '82. We
stopped enrollment, and we finally got the data analyzed. I came back from a
00:48:00meeting in Italy in June of '83, and Paul Pinsky told me what the answer was.
Nitrite inhalants. This is now June, July of '83, and I am excited. This is like
"hot stuff."Anyway, I presented to the Task Force, and the Task Force was --unimpressed.
MILLER: What did you do with this?
HAVERKOS: Jim Curran sent me back to re-analyze, break it out by groups, male
interviewers, female interviewers, length of interview. Anyway, it turned out,
in the secondary analysis, every analysis was higher [for] Kaposi's, whether you
split it up by any of these groups. These results were incredibly robust.
00:49:00
MILLER: What was the reason, from your point of view, for the controversy or
lack of interest in accepting that?
HAVERKOS: CDC was under the gun from PHS [Public Health Service] because we
hadn't found the virus yet. When they put in their budget request--I think [Dr.
Walter] Walt Dowdle told me this later, in August or September of '83--it turns
out CDC listed their number one accomplishment in their fiscal year 1984 budget
request, their major accomplishment was ruling out a role of nitrites as the
cause of AIDS. So I presented this to the Task Force. I couldn't present this. I
had a big lecture in San Francisco at the end of August, and Curran made it
00:50:00perfectly clear if I said a word about this study, he'd can me. Emotions were
high. There was a lot of tension going on.
MILLER: This was just before the virus was found?
HAVERKOS: The virus had already been found, actually, by the French. The French
found the virus and reported it in January of '83 at Cold Spring Harbor [New
York]. I heard about it at that meeting that I went to in Italy. The French,
Jean-Claude Chermann, presented the virus. I was convinced they had the virus. I
actually got them to send the virus to CDC. The problem with the French virus
was, they didn't grow it in a cell line that was easily propagating the virus.
00:51:00They'd send it to everybody, and no one could grow it because it would die in
transit. Bob Gallo [found virus in AIDS patients and found a cancer cell line to
grow the virus efficiently] -- found it in lymphadenopathy patients. So the
virus was already found.
I don't know how much Curran and Jaffe felt about the virus at that point. It's
hard to know. Of course, Jim was tied up in many things. Harold and I went
separate ways. We had new EIS officers coming in. [Dr.] Ken Castro came in, and
[Dr.] Ann Hardy came in. [Dr. Michael E.] Mike Gorman came in and wanted to work
on AIDS, but they wouldn't let him work on AIDS. I mean the Task Force was now
40 or 50 people. I had to make an appointment to get on the slot to give a
discussion at the staff meetings. I was now investigating blood transfusion
00:52:00cases. It was crazy. I've got a wife and two kids at home, you know, when am I
going to spend some time with them? It was a hectic time. I don't know all that
went on, but I know that I thought this was a startling finding and thought it
was important, but I wasn't able to talk to anybody about it.
MILLER: In retrospect, with 35 years of hindsight luxury, what's your thinking
now as to the role of poppers?
HAVERKOS: I actually think it plays a major role in Kaposi's sarcoma. The big
rap against HIV causing Kaposi's-- actually, Gaetano Giraldo went back and took
all his cases of Kaposi's and tested them for HIV [human immunodeficiency
00:53:00virus]. He found that only recent Kaposi's cases in Africa were HIV positive. So
we knew HIV wasn't the cause of Kaposi's sarcoma. Similarly, I said, if it's the
nitrites, we've got to find nitrites in Africa. I contacted [Dr] John Ziegler.
Anyway, long story short, I now think the cause of Kaposi's sarcoma involves
three steps. There was a herpes virus found in 1994 by Chang and Moore that we
can find evidence of in all four types of Kaposi's sarcoma, four types meaning
elderly men that Kaposi described in 1872; the African cases, both in young
black men and children reported from 1914 on; then the immunosuppressed renal
transplant recipient steroid use group that was discovered in the '50s, when
00:54:00transplants really grew in numbers; and in gay men we can find HHV8 in 95% of
Kaposi's patients worldwide.
MILLER: HHV AIDS?
HAVERKOS: Yes, human herpes virus 8. That's the virus found by Chang and Moore
in 1994, which in retrospect is probably the virus that Gaetano Giraldo found in
1972 and saw on electron microscopy, though I haven't been able to confirm that.
The second factor that plays in Kaposi's is immune suppression. For gay men it's
HIV, for organ transplant recipients it's the rejection drugs, for elderly men
some argue it may be some kind of senescence of the immune system, or it may be
00:55:00that some of those patients are also treated with other drugs or chemicals that
are immunosuppressive. In Africa it's HIV late, but early on it's parasitic infections.
There's a third factor, and this is where nitrites come in. It's the factor that
affects the blood vessels. Remember, it's a blood vessel tumor. I contacted John
Ziegler, who was doing work on Kaposi's in Africa. He did two very nice
case-control studies in Africa: one in HIV-positive Kaposi's and one in
HIV-negative Kaposi's. In the two case-control studies he found a link to
geography and a link to walking barefoot in volcanic soils. He proposed that
it's aluminous silicates or iron oxides in the soil that get in the breaks in
the skin in the feet, with some epidemiologic data, again, on barefoot farmers,
00:56:00etc. Then lower leg disease and actually lymphadenopathy in kids, in these
youngsters, from sitting them out in the farms and probably getting this
absorbed through diapers when you're out working with your dad when you're two
or three and your mother's got you out with your dad. Anyway, so he thinks that
aluminous silicates is that blood vessel variable.
It turns out there are a number of anecdotal reports in the literature among
renal transplant patients and others about the use of ACE [angiotensin
converting enzyme] inhibitors, [such as] Captopril and Lisinopril. These are
anecdotal reports that people get a transplant, they get hypertension, they get
treated with an angiotensin [converting enzyme] inhibitor, and they develop
Kaposi's. There have been several reports [showing that] when they change to
another agent and stop the ACE inhibitor, the Kaposi's goes away. Now if you
00:57:00diagnose Kaposi's, one of the first things is if they're on an ACE inhibitor,
they take them off. I think the nitrites still play a role. Actually in my
career I was able to get nitrites banned [from being] manufactured and sold in
the United States for my work at the National Institute on Drug Abuse. A
congressman from San Francisco, Mel Levine, and a gay activist named Hank
Wilson, who was a proponent of my work and thought that nitrites were bad for
your health, got laws passed in '88 and '90 and banned it. Nitrite use, of
course, in the U.S. has plummeted. We've since developed Viagra and Cialis,
which don't seem to have the same oncogenic effects. Kaposi's has plummeted in
00:58:00the U.S. Now where I'm looking, it turns out well. Where'd these nitrite
manufacturers go? They're selling their product in Asia. I just got a paper to
review two years ago among gay men in Beijing; 50% of them are using poppers,
and we're seeing some reports of Kaposi's sarcoma out of China. I think it still
plays a role, and I have continued to pursue this.
MILLER: Talk a little bit about your work with Haitian cases. During the fall of
'81 and ongoing, there were reports of opportunistic infections and Kaposi's
sarcoma among Haitians living in the United States. Early reports were coming
from Miami. Tell us a little bit about your work with these cases.
HAVERKOS: I didn't notice them until it was March of '82, maybe early April of
00:59:00'82. I'd been on the road; I'd been interviewing prisoners in upstate New York
and pneumocystis patients in other places. I had a couple--there was an
investigation in Miami of a lion they thought might have been exposed to HIV. I
saw the first cases in the states of South Carolina and West Virginia. I think
they wanted to see if I'd come in a spacesuit or how I'd interact with patients.
I was supposed to have a week to get ready to prepare for the EIS meeting in
April of 1982. I was going to present the case definition. Jim Curran and Dennis
Juranek came to me and said, hey, we're seeing some cases of Kaposi's sarcoma
01:00:00and toxoplasmosis in Miami. We'd like you to go down and investigate it. They
were going to send [Dr.] Jim Goodrich, our newly minted guy, and they were going
to send [Dr.] Bruce Weniger, who was a second-year parasitology [EIS officer].
They said, you've seen these cases, why don't you go? I said, sure, why not.
It turns out there was a pathologist in Miami, a guy named [Dr.] George Hensley,
who had made a diagnosis of toxoplasmosis of the brain in two Haitian patients.
He reported the first one in September of '81. [Dr.] Mike Malison was the EIS
officer in Tallahassee who reported the case. The second one came in, but then
01:01:00what Hensley did, he had some other cases with brain abnormalities and fever
that he thought was tuberculosis of the brain. He sent the biopsies to a guy
named [Dr.] Jack Remington, a big infectious disease guy, big Toxoplasma guy at
Stanford [University]. Jack reviewed the brain biopsies from Miami and made a
diagnosis in [an] additional five patients as toxo [toxoplasmosis]. They weren't
TB; they were toxo. Jack, who had a good relationship with Dennis Juranek in
parasitology, said, not only that, I've got two other biopsies among Haitian
men, one from Montreal and one from New York City. Don't you think that's a
little strange? Nine cases. I mean, this is a fairly rare disease in the U.S.
01:02:00They sent me down to Miami, and I think only one of the toxo patients was still
alive at that point.
They had a couple of cases of pneumocystis among Haitians; they had one case of
Kaposi's. But it's another group almost like the drug users. They're not going
to talk to me because many of them didn't speak much English. Many of them were
illegal immigrants, and there were some real issues with Haitian immigrants at
that time. But I saw the cases, looked over the medical records, and met the
docs in town. I came back and said, yes, this is it, this is what I've seen in
gay men, the immune function studies are the same. This looks like the cases I'm
seeing. I got back in about a week. It turns out Peter Drotman had gone to Haiti
01:03:00the same time I'm in Miami, because there were reports out of Haiti of the same
thing, or somebody explored in Haiti. I got back, and Curran said to me, hey,
there's a group from NIH [National Institutes of Health]. [Dr. Richard M] Dick
Krause, who was the head of NIAID [National Institute of Allergy and Infectious
Diseases], has taken three of his medical officers down to Port-au-Prince,
Haiti, to see some of the cases in Haiti. You ought to go with him; you've seen
the cases in Miami. So, I went down to Haiti with [Dr. Thomas C.] Tom Quinn,
another Notre Dame grad, [Dr. Alfred] Al Saah and [Dr. H. Clifford] Cliff Lane,
[Dr. Anthony S.] Tony Fauci's right-hand man, Cliff Lane. The four of them went
down, and I met them in Port-au-Prince. I was down there for about ten days and
saw a number of their patients on their ward. The cases were a little different.
I didn't see any toxo, but they had Candida esophagitis, they had extensive
01:04:00herpes virus infections, they had tuberculosis in addition to some pneumocystis,
and had a lot of Candida esophagitis, a little cryptococcal meningitis and a
couple of cases of Kaposi's sarcoma. It was a little different spectrum.
MILLER: Were they all men?
HAVERKOS: No. No, it was mainly men, probably 2/3 men, 1/3 women. There were
more women than we'd seen. We had a couple of women who were drug users in New
York, a couple in other places. But yes, some women. I was down there about two
weeks and came back and actually was impressed. Of course, the Haitian
government really wanted two things. They wanted money for research. CDC was now
01:05:00reporting Haitians as a risk group, and it was costing them quite a bit of
tourist money, stigma, Haitians in Haiti. So they wanted Haitians removed as a
risk group. Interestingly, they meet with Krause, the head of NIAID, who has
quite a bit of money, right? CDC, we don't give out much money. Krause promised
them money, and they asked Krause, can't you do something about changing this
designation? Krause said, hey, I'm not from the CDC. Talk to Harry. So I was
just bludgeoned. It was almost as bad as the first meeting when I went up and
told the FDA [Food and Drug Administration] that we had three blood transfusion
cases. These guys were just nasty-- it was not a very pleasant trip, to say the least.
01:06:00
MILLER: How was your relationship with the NIH folks doing the investigation
down there?
HAVERKOS: The investigation was great. In fact, that's how I got my job at NIH.
In February of '84, after Curran told me he can get three new EIS officers or
make me a staffer, I gave him a deadline, and he went beyond the deadline. I
called up NIH, called Henry Masur, and asked him if he's got a job for me. Henry
didn't, but he told me about [Dr. Robert R.] Bob Edelman, and Bob Edelman worked
for Dick Krause. When Krause found out, I got offered a job on the spot. This
interaction with NIH in Haiti-- Tom Quinn is a Notre Damer, so again, we can
talk Notre Dame football. I thought our relations were very good with NIH and
01:07:00used [that] as a springboard for my move up to NIH.
MILLER: When you came back and saw the cases in Haitians, what was the response?
What happened as a result of that?
HAVERKOS: CDC was very interested. I didn't think we could do much research in
Haiti myself, but the Haitians then wanted to present their cases, and they
wanted somebody from CDC to go back. Jim asked me if I would go back to this
research meeting. I told him I didn't think I was the appropriate guy to send
back, so they ended up sending [Dr.] Joyce Johnson, who was another new recruit.
She went down to the research meeting in Haiti, and I basically shortly
thereafter got involved in the hemophiliacs and the blood transfusion cases and
never really got back to the Haitian cases.
01:08:00
MILLER: What were some of the hypotheses as to why this syndrome was showing up
in Haitians?
HAVERKOS: In Haiti, they were trying to say this is gay men, and some of the men
were gay, it turns out. There was a concern about voodoo practices, sex in some
of these rituals. There was some concern about malnutrition. There were even
some that raised the issue of mosquitoes. Of course, it turns out it was
heterosexual transmission, which eventually developed. These were probably the
first clusters, other than the injecting drug users, that were clear evidence
01:09:00that this was an STD like other STDs. That was shown over the next couple of
years by studies the CDC did in Miami and New York, by Ken Castro and Joyce
Johnson and others, and [Dr.] Jean Pape down in Haiti, linking it to
heterosexual transmission. We saw a lot of kids. This was one of the first
groups where we saw children diagnosed during '83 and '84. That's another marker
of heterosexual transmission, perinatal transmission resulting from infection to
women and back and forth. But yes, some of these other hypotheses were put
forward, which talked about voodoo practices and stigma.
MILLER: Can you tell us a little more about voodoo practices or what those
01:10:00involved, or the thinking about those?
HAVERKOS: Yes. I came back and did a lot of reading about voodoo practices,
several books, and it's not like the Catholic mass or going to a Seder or
whatever. Voodoo practices are very independent. The shaman does whatever he
does and puts people in trances, and it turns out there's sex, there's drug use,
there's chicken blood. There's all kinds of different rituals that play--
MILLER: .Did it include any component of needles?
HAVERKOS: There can be components of needles. Actually, the needle component was
picked up by [Dr.] Jean Pape in his case-control studies. It turns out needles
are used in two ways in Africa and in many third-world countries, and among
01:11:00immigrants in the United States and other places: for vitamins and antibiotics.
People will go to a HCW [health care worker] or other-- if you go back and look
at, for example, Jean Pape's case-control study in Haiti, yes, there are clear
links to needle use, more so by cases than controls. His controls were family
members that didn't have AIDS. Whether they were HIV infected at that time-- Ken
Castro's study found a link, among the women, that they were friends with
shamans. They didn't have data [on] sex with shamans, but women Haitians with
cases in Miami and New York were more likely females and more likely to be
offered money for sex, though very few of them reported getting money for sex.
01:12:00They also were statistically reporting friends who were shamans [more] than the
control group. There were some links there, and these were probably all
confounding variables for sexual interactions. That would be what I propose, 40
years later.
MILLER: There was so much you were involved in. One of the things I wanted to
ask you about is one or two areas of the blood product and blood transfusion
cases. What were some of your major efforts in that area?
HAVERKOS: I investigated one hemophiliac case [in Ohio]. There was one trip to
Los Angeles in January of 1984 that I think was for me a very important trip. It
01:13:00turns out there were four children in Los Angeles, one of whom was a son of a
very prominent attorney in LA who was a big [President Ronald] Reagan supporter,
and he wanted to know who the blood donors were to his son. I went to the Los
Angeles Health Department, and they said they didn't have the resources to deal
with this. Then they went to the Reagan Administration, and the Reagan
Administration called CDC and said CDC will send someone to Los Angeles to
investigate these cases. I drew the short straw, which was my lot in life, and
they sent me out to Los Angeles. My first meeting was with the attorney, and the
01:14:00health department gave me a car, a parking space at the health department and
the names of 42 donors to these four kids. From the donors I picked men and
those that were unmarried or certain ages or lived in certain parts of town, and
I interviewed 14 of them. I tracked them down, drove to their homes and
interviewed them in their homes throughout Los Angeles. I identified at least
one patient, one gay male, some of whom already had some symptomatology, for
each case.
As I was getting prepared to come back to Atlanta--I'd already checked out of my
01:15:00hotel--I got a call from an old friend of mine, Mike Gottleib. Mike said, I hear
you're in town. He and I had heard about the French virus over in Naples, Italy,
whenever that was, that was the '83 meeting I went to, in the summer of '83.
Mike said to me, I've just had two patients with AIDS: one a woman I just
diagnosed in December of '83 with pneumocystis, who claims no risk factors but
had two blood transfusions ten months earlier. She had a hysterectomy. It turns
out when I went to the Los Angeles Health Department to get the donors, one of
the two donors was one of my patients who I diagnosed just three months earlier.
01:16:00Michael and I said, oh, this could be the third and fourth steps of Koch's postulates.
What if we can get these people-- we were trying to grow the virus. We were all
interested in retroviruses by then. Don Francis was already running the lab
component. He came in September of '83. So Michael--I remember I slept in his
home over the weekend, because I had checked out of my hotel, on his fold-out
couch. I called CDC, called Harold and said, hey, can you send down [Dr.] Paul
Feorino and Donna Warfield (I think her last name was Warfield) to start the
samples rather than ship them? So Paul and Donna came out and started the
cultures on Monday, and then we all came back to Atlanta Monday night or Tuesday morning.
01:17:00
It turns out they were two of the first three patients that CDC grew retrovirus
from, and we ended up publishing that work in July of 1984. Gallo published in
May, and we published in July. We made the mistake, according to PHS, of naming
the organism LAV [lymphadenopathy-associated virus], because it matched the
virus that we finally grew from the French. Bob Gallo went ballistic because we
didn't call it HTLV III-LAV, which is what he and the Public Health Service
agreed the name of the virus would be.
MILLER: That is a fascinating story about linking the transfusion to the cases.
That had to have been really--.
HAVERKOS: Right. Of course, that was--by the time Don Francis came to me and
01:18:00told us, it was May of '84. I was already packing my gear and getting ready to
head up to NIH. But yes, that was probably the most memorable two weeks of the
blood transfusion series.
MILLER: You mentioned the conference in Naples, Italy, that took place in the
spring of '83. Can you tell us a little bit about that time?
HAVERKOS: It was set up by Gaetano Giraldo. This was an oncologist, a husband
and wife team; actually his wife was also an oncologist. They had done a lot of
work with Kaposi's sarcoma in Uganda in the '70s, and, as I said, they had
linked it to CMV. They became very interested, and cases started coming in from
01:19:00Italy and France and Germany. We were getting European cases, and he wanted to
hold a meeting, and he got some money for a meeting to bring together
researchers in Europe to talk about these cases. He thought it would be good.
But he also promoted his theory that CMV caused Kaposi's sarcoma and that this
was something out of Africa. Also about the same time we were starting to see
AIDS patients in Belgium from Zaire.
He had this meeting, and it turned out CDC gets invited to Europe for two
things. One, WHO wanted Jim Curran to come over and help them plan for their
first meeting, which they ended up holding in October of '83 in Aarhus, Denmark.
01:20:00Also they wanted Jim Curran to come talk at the meeting in Naples. Jim Curran
couldn't go. Walter Dowdle came to me and asked me if I would like to go to this
meeting in Naples, and he told me I could take my wife if I wanted. I had to pay
her own way, of course, but anyway Lynne and I went to that meeting in Naples.
At that meeting not only did I meet Giraldo and give a presentation on our
data-- in fact Giraldo and I dealt with the press, but in the afternoon--it was
a one-day meeting-- Jean-Claude Chermann presented the one patient they had.
They grew this retrovirus from lymph nodes of their patient in Paris. So I met
01:21:00the French. They had a dinner following the meeting. Lynne and I got there a
little late, but the French saved us a spot at their table. They were toasting
CDC for all our work suggesting it's a virus, and I was toasting them for
finding the virus that we were all looking for. It was quite an exciting night.
MILLER: What was the early thinking in Europe about the cause of the virus or
the source of the virus?
HAVERKOS: I think they were following the same lines we were, and they were
looking for retroviruses. Bob Gallo was the preeminent retrovirologist in the
United States. He was part of the discovery of HTLV1 and HTLV2, the human
01:22:00retroviruses first found associated with cancers. There were virologists around
the world working with retroviruses, including the French, so they were trying
to grow it. [Dr.] Willy Rozenbaum was the clinician in Paris, who I still keep
up with. Willy was the one who brought the lymph nodes over to Luc Montagnier,
and Jean-Claude Chermann was the director of the lab. The technician, Françoise
Barré-Sinoussi, was the one that actually did the work. They found a virus a
year before Gallo and a year and a half before we did, and then San Francisco
01:23:00came out with it.
MILLER: You mentioned the Belgians were seeing cases in persons who had been in
Zaire. Can you talk more about that, and was the connection being made that the
source of the virus might be from Zaire?
HAVERKOS: Again, Giraldo was the one pushing that this might have been a disease
around for a long time, because he saw Kaposi's in Africa and did a lot of work
in Kaposi's in Uganda. I didn't have as much direct experience with [Prof.
Nathan] Clumeck and with [Dr.] Peter Piot and the Belgians. I did have some
connections with the French, and the French had seen a couple of cases from
01:24:00Africa as well. That meeting in '83 was the first time I heard about cases from
Africa. I'm giving you my information from reading New England Journal articles
from '83, '84 were basically Nathan Clumeck [Belgian clinician, 1st author of
NEJM Report], et. al. Again, most of these papers have 42 authors. The Belgians
had made some diagnoses, of pneumocystis predominantly, but also other
opportunistic infections. They saw other parasitic infections that we don't see
in the U.S.: schistosomiasis, some other worms and things, I can't remember, but
again, very rare parasitic and fungal and other infections in patients, and many
of them were from Zaire. Either they were Belgian natives who went to work in
01:25:00Zaire, either as diplomats and then came back and the diagnoses were made in
Belgium, or they were immigrants, Zairian natives, because there was a very
strong tie between Belgium and Zaire.
France, I think, their connections were with other countries. Actually Dick
Krause was over at a meeting in Vienna [Austria], and there's this young
clinician named Peter Piot who approaches Krause at an infectious disease
meeting in Vienna. He said--this was after Krause had been to Haiti and seen
patients, and Piot told Krause, hey, I want to go to Zaire--he'd only seen
patients in Belgium-- I want to see what's going on. Krause wrote him a
01:26:00check--this is the story anyway--for ten thousand or something for Piot. It
turns out Tom Quinn, who had also been with Krause in Haiti with me, was at the
meeting in Vienna. So Piot and Quinn go to Zaire. The meeting in Vienna was in
September of '83. They fly down in October of '83, and Krause, when he came back
to the United States, told HHS he was sending an expedition to Zaire. They said,
you ought to send somebody from CDC. I didn't get approached for that meeting.
MILLER: Who went?
HAVERKOS: [Dr. Joseph B.] Joe McCormick, who was already in Africa, met them in
01:27:00Zaire in October of '83, and they found a cluster of cases in the hospital. Then
they actually went back and put together a nice sexual contact chart, linking
men and women to different clusters, four or five patients who had these
opportunistic infections. Then Quinn came back to NIH and McCormick to CDC, and
Piot went back to Belgium. They ended up setting up Project SIDA, which I guess
ended up getting started in February of '84. After I turned down the job offer
to go to Zaire, [Dr.] Jonathan Mann went over, starting in about May of '84.
MILLER: At that time was there any sense of the connection between the cases in
Zaire and the Haitian cases?
01:28:00
HAVERKOS: There was a known cluster of about a hundred professionals from Haiti,
mainly teachers, in the late '70s who went to Zaire. What happened to those guys
in the early '70s is not known. If you talk to Jean Pape and look at his
earliest cases, he claims none of those returned to Haiti. Most people left
Haiti. Under Baby Doc Duvalier, the son [of dictator Francois "Papa Doc"
Duvalier], the economic conditions were [very bad]--so in the early '70s people
01:29:00from Haiti were leaving. Very few were coming back, and we had patient
immigrants through the late '70s and early '80s here in Miami. I think you can
conjecture that transmission from Haiti to Miami and New York, and I could draw
a connection between gay men in New York City and bisexual men in Haiti, from
some of the work from Pape. In fact, I collected all the anecdotes from our case
histories, our case-control study, looking for the New York cases and other
cases. We had a travel history on these, and I found several where they did
travel to Haiti and bought little boys in Haiti, young men.
MILLER: So the question is, to which direction is--.
HAVERKOS: That's speculative, yes. No one will know. There are some interesting
01:30:00migration patterns that if we could go back and follow, we might. Whether it
makes any difference at this point--in fact, it's almost like the stories you
used to hear about syphilis in the 1400's and 1500's. We've already stigmatized
Haitians and a number of other groups, finding out where it's from. I'm not sure
it does anybody any good at this point, but I guess there will always be that curiosity.
MILLER: As we're drawing to a close, I want to ask you: are there any aspects of
CDC's response in the areas you worked on where we fell short or could have done
a better job, in your opinion?
01:31:00
HAVERKOS: I think there are three areas I would talk about. The first area is
recognition of heterosexual transmission. I thought we were rather slow and
really didn't see the writing on the wall. Some of that was due to internal
politics. Some of it was from [Dr.] Alexander Langmuir and [Dr.] David Sencer
and some in New York who really were very resistant to this heterosexual
transmission concept.
MILLER: Why would that be?
HAVERKOS: I don't know. You would probably have to ask them, but they clearly
didn't think men could get it from women for reasons that are-- I can't conceive
of what the reasons could be, being an infectious disease guy who has studied
01:32:00sexually transmitted diseases and never seen one that sexual activity-- once
it's in the bodily fluids, some are cell-associated STDs, some are in the
plasma. I think we were very slow to recognize male-to-female transmission, and
I think we compounded that problem with our hierarchical system of
classification of gay men and drug users. Heterosexuals had to deny all these
[risk factors]. That was a real problem, because 70% of gay men, at least in our
case-control studies, were bisexual. How do we know that if just because a guy
had one homosexual sexual contact as a teenager and he meets Richard Selik's
01:33:00hierarchical breakdown, that he wasn't infected heterosexually later on? How do
we know if drug users were infected by using needles and not through
heterosexual transmission? There's a lot of sex in drug users. I think by that
very restrictive definition, we just compounded this wish that something would
stop the epidemic-- Alexander Langmuir I have great respect for, but if you read
his writings-- anyway, that was one area.
The second area is that we were slow in dealing with cofactors. A little slow.
I'm not sure the CDC has even yet dealt with cofactors. I think stifling my work
[on nitrites] was a major mistake in really understanding the pathogenesis of
Kaposi's sarcoma and the whole disease. It's hard for me not to criticize Jim
01:34:00Curran and Harold Jaffe and Bob Gallo and Tony Fauci and many other people for
not seeing the value in that pursuit.
The third area is that I think we were slow in appreciating [Dr.] Dale
Lawrence's work with the longer incubation period. We really only brought that
to light after we saw that by screening the blood supply, we still weren't
impacting the shape of the [epidemic] curve among blood transfusion recipients.
So if I were going to criticize CDC and others, those would be my three areas of criticism.
MILLER: And Dale Lawrence's finding being?
HAVERKOS: That the incubation period is likely to be five, six, or seven years,
not 24 months or three years, whatever timeframe we were using initially to
01:35:00discourage blood donations. So those would be the three areas I would raise some criticisms.
MILLER: A couple of questions about the personal aspects or impacts of your work
on AIDS. First of all, did you worry about becoming infected yourself? Were you
worried about your family?
HAVERKOS: Not until we saw the first healthcare worker issues. Yes, I had
recapped needles on a case-control study. I went out and drew blood, and I did
get tested. In the Public Health Service we have to have a physical every five
years. By the time I got around to my first physical-- I started in '81, as you
did-- I didn't get my first physical until '87. I was up in the Washington,
D.C., area, where the military was, so I got my first blood test in '87. I
01:36:00remember thinking, if I'm positive, what am I going to tell my wife? What am I
going to tell my kids? Fortunately, I came back negative, but, yes, that was a
concern of mine. I met some healthcare workers who have been exposed, and I took
care of a number of needle stick injuries with my clinical work at the army
hospital that I started in '89, and [I saw] how emotional those situations are.
I wasn't smart enough back in '81 or '82, but yes, that did cross my mind, too
01:37:00late maybe.
MILLER: You were a part of something that changed the history and course of
public health in so many ways. How has that affected you personally?
HAVERKOS: I think I've had a very productive career. Fortunately, my wife has
stayed with me through all this time, and we have three great kids and now six
great grandchildren. I think it was a very interesting career. I worked at NIH,
I worked in drug abuse, I saw patients at Walter Reed [National Military Medical
Center], and I have a lot of friends. I don't think it adversely affected me.
People still have dinner with me; they still talk to me. I wouldn't trade the
01:38:00experience for anything. It was really an incredible ride. I'm glad I got the
opportunity to be part of it.
MILLER: Thank you.
HAVERKOS: Thank you.
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