Dr. Gerald Schochetman

Gerald Schochetman

CHAMBERLAND: This is Dr. Mary Chamberland, and I'm here with Dr. Gerald Schochetman at the Centers for Disease Control and Prevention [CDC] in Atlanta, Georgia. Today is Thursday, July 7, 2016. I'm interviewing Dr. Schochetman as part of the project to document CDC's Early Response to the AIDS [acquired immune deficiency syndrome] Epidemic. Dr. Schochetman, do I have your permission to interview you and to record the interview?

SCHOCHETMAN: Yes, you do.

CHAMBERLAND: So, Gerry, you first came to CDC in 1985 to take on the position of Chief of the Laboratory Investigations Branch in the AIDS Program. This was an exciting time, as the HIV [human immunodeficiency virus] virus had been identified only a couple of years before, and diagnostic testing for the virus was in its early stages.

However, before we talk about your CDC work, let's talk a little bit about your background. Could you tell us where you grew up and a little bit about your 00:01:00early family life?

SCHOCHETMAN: Yes, I grew up in New York, basically in Brooklyn, New York. My parents were immigrants from the Ukraine and came to the U.S. in the very early years of the 20th century, roughly around 1920 to 1930 or so. They had enough of an education to be able to read and write and do basic arithmetic, but always had a great interest and desire in having their children get a good education and be able to make something of themselves in this country. And so that's what we were able to do.

CHAMBERLAND: Where did you go to college and graduate school, and what did you study there?

SCHOCHETMAN: I went to undergraduate at what's called CCNY, or the City College 00:02:00of New York, which is now part of the City University of New York. I originally started out and went through almost my full four years studying electrical engineering. By the time I finished, I decided that really was not what I wanted to do. I stayed on a little bit longer and was able to get a Bachelor's of Science in Biochemistry and Molecular Biology. I always had an interest in biomedical research, and that's what I wanted to do. So from there, I went on to eventually go to the University of Pennsylvania, where I received my PhD in--it was actually a special program in molecular biology, which drew upon faculty from various divisions within the university, so anywhere from biochemistry to biophysics to molecular biology, et cetera. So it was a very interesting 00:03:00education, and I valued it very much.

I did my PhD research at a place in Philadelphia called the Fox Chase Cancer Center, with somebody who was a member of the National Academy, and it was tremendous training. I actually learned to become a real scientist, as they say, being able to think through a project and being able to then actually write a real manuscript, and that was very helpful in doing my thesis et cetera. From there, I went on to do my postgraduate work at the Medical School at McGill [University] in Montreal, and moved on to work on infectious agents. Particularly, I was working on a virus in those days called reovirus. It was an interesting virus for many reasons, which is not necessarily so important these 00:04:00days. Then from there, I went on to a number of positions, both in research and in the private sector, all in biomedical research, mostly associated with infectious diseases.

CHAMBERLAND: You say you always had it in the back of your mind that you wanted to be a biomedical researcher. Do you know who or what influenced you to want to take that on as a career?

SCHOCHETMAN: Actually, nobody seemed to really--I can't remember anybody influencing me, but I always had a great interest in trying to understand medicine and the science behind it. So I just seemed to naturally gravitate towards biomedical research. I thought about going to medical school, but I wasn't sure I really wanted to get involved with clinical medicine and dealing with patients on a daily basis. I was more interested in research itself.

CHAMBERLAND: Now, I don't know about the electrical engineering part, but certainly in the years before you came to CDC in 1985 you mentioned that you were involved in a variety of research positions that included work in retroviruses and immunology, immunoassay development. Looking back on all of that experience, how helpful were these work opportunities in your job as head of CDC's HIV Laboratory?

SCHOCHETMAN: I think it gave me the experience, the varied experience, which I think is actually necessary to be able to tackle a project such as running the AIDS laboratory. When I came [to CDC] in 1985, we were really in the heart of the epidemic; lots of public scrutiny, lots of important work to be done to tame the epidemic. I really pulled on all the background I had, all the scientific 00:06:00skills, the people skills, [and] knowledge of the field. I don't think it's a matter of just book knowledge. It's a total accumulation of knowledge that you have to bring to bear to deal with such a large and vast project as this.

CHAMBERLAND: So what made you decide to leave the private sector to work for the U.S. government, and specifically for CDC?

SCHOCHETMAN: I really didn't have that in mind about working either for the government or the CDC. I had been in research for a number of years. I was in the Washington, D.C., area working at the Frederick Cancer Center, working on viruses and cancer for a number of years. Then over the next several years, I went into the field of biotechnology, [which] was burgeoning. I went into the 00:07:00private sector there and was involved in two start-ups. One was Amgen [Inc.], which is now a very large company. I worked on the development of--one aspect of the development of their first product, erythropoietin, known as EPO, which was a very successful project.

Then I met somebody there, and we formed another company involved in biotechnology. I always wanted to come back to the East Coast. Amgen was out in California, specifically Thousand Oaks, California, and my wife and I wanted to return to the East Coast where friends and family were. So we came back to the Washington, D.C., area and formed another company called IGEN, Incorporated. Based on the technology we developed, it was eventually bought out by Roche, the company Roche. At that time, I was looking around to decide what it was I 00:08:00specifically wanted to do, and a friend of mine mentioned an opportunity at the CDC related to AIDS. I really was not interested in working for the government or necessarily working on AIDS at the time, but I said I would be happy to look at it. Since CDC was in Atlanta and my mother and sister had moved from New York to Atlanta, I said, "Well, I'll at least look into it." I remember [Dr. Walter R.] Walt Dowdle and I met in Washington, and we had a conversation. Then I believe I came to Atlanta and [Dr. James W.] Jim Curran and I--Jim was head of the AIDS Task Force at the time--we had dinner, and I said to my wife, "Well, let's give it a shot." So we decided that we would move to Atlanta, and at least 00:09:00I'd be close to family. It turned out to be a tremendous move.

But I have to say, and you touched on some elements of it, when I came to CDC at the end of 1985 to work on AIDS, I did not believe that would be a long--lived project. By the end of '85 when I arrived, the virus had already been discovered and reported on in 1983. In March of 1985, the first FDA-approved test was available, the first clinical trials for a drug, namely, AZT [azidothymidine], were already in progress, and there were predictions of an AIDS vaccine in two years. So I said, well, I wonder what I'll be working on in two years from now, and then 30 years later, one of the projects I was working on was HIV and AIDS.

CHAMBERLAND: So you thought you were going to be a short termer.

SCHOCHETMAN: That's what I thought.

CHAMBERLAND: Okay, so you said you arrived at the end of 1985. I want to try and get a sense of what the laboratory environment was like at CDC at that time. So just maybe a few questions: How big an operation was the Laboratory Investigations Branch that you were now chief of? Were there a lot of people working in the branch? Who were some of the people? What were the major areas of HIV laboratory work that they were involved in? Do you remember?

SCHOCHETMAN: It wasn't a terribly large group of people. I think there were probably four or five. I don't remember exactly--PhDs and several technicians or so. One of the labs, which at that time was a critical lab, was the HIV Testing Lab. It was the diagnostic lab that was providing laboratory screening for epidemiologic investigations run by the CDC, as well as providing reference 00:11:00laboratory capabilities for various public health laboratories, both state and local health laboratories. The other PhDs were working on a variety of projects, which were really more research oriented. Over time CDC wasn't necessarily a research organization doing essentially basic research; that was probably more NIH's [National Institutes of Health's] responsibility. CDC was really more involved in more applied research related to specifically dealing with the epidemic, from developing tests to figuring out how to culture the virus and providing laboratory support for the epidemiologic investigations here at the CDC.

CHAMBERLAND: Now, not all of the HIV-related laboratory work that was going on 00:12:00at the time was in your branch, because I'm thinking [of] the immunology group and other laboratories. There were probably some collaborations going on with other groups within CDC?

SCHOCHETMAN: Yes, where we could. We always tried to coordinate and work with the various other groups. I think probably initially the first couple of years, a good part of the work was really related to a lot of the testing, diagnostic testing, involved with the various epidemiologic investigations. Over time we branched out a little bit more, and we can go into that, you know, as the field burgeoned and the science of HIV and the epidemic grew. Actually, the complexity of the epidemiologic investigations ensued.

CHAMBERLAND: What was your overall initial reaction as you took stock of the Branch? Did you have ideas about the sort of priorities that you thought the Branch needed to take on in this newly evolving area?

SCHOCHETMAN: Initially when I first came, for the first several months it was really trying to learn the field, learn the players, try to understand CDC's role and who its constituents were: basically the state and local public health laboratories and what CDC's role was. For the most part, I had been either a basic researcher or had worked in industry with product development. So this was a new aspect of the science that was necessary for this field. It was kind of an 00:14:00evolution. It wasn't that you just walked right in and said, "Oh, I know exactly what we need," because, as I said, I figured in two years, I was pretty sure in two years we wouldn't need this anymore. It would become pretty routine. We will probably get into this as we talk later, when we get into the molecular biology and our more basic understanding of the virus and the evolution of this virus, that led to many opportunities as well as complications. Some of that became apparent as time went on.

CHAMBERLAND: You said that the real focus then, at least for that first year or two, was really a lot about diagnostic testing for HIV, that this was a big part of CDC's mandate: to develop testing and push it out to state and local health 00:15:00departments. So maybe to give us a starting point, can you describe what the state-of-the-art HIV diagnostic testing was in 1985? What types of tests were available? How good were they? What were their limitations?

SCHOCHETMAN: Sure. Basically there were two types of tests. One was the ability to culture virus from cells, blood cells, of suspected individuals who were patients. The other was in March of 1985, as we mentioned earlier, the first HIV test was FDA [Food and Drug Administration] approved, and it was a test for antibodies to the virus in an individual. Pretty much that's what we had available to us. Prior to March of '85, it was really looking at things like 00:16:00somebody's CD4 count, CD4, T lymphocyte count, or whether you could culture virus from those individuals. Those were not the kinds of simple routine tests that were absolutely necessary at that time. So when the first FDA--approved test came along in March of '85, more routine kinds of testing could be done, not only on an individual basis but on a larger population basis. We could now screen the population.

Certainly, I think of real importance was the ability now to screen the blood supply, transfused blood. To give you a sense of the impact of the tests at that time, in 1983--this had already been published--the risk of getting an HIV [infected] transfusion in a city like San Francisco was about 1 in 90. One year 00:17:00after the introduction of the test, that dropped to 1 in 40,000. Today, with the addition of molecular biologic tests and the serologic tests, it's probably somewhere around 1 in 1.5 million to 1 in 2 million. So things moved very rapidly. Just the introduction of that antibody test had a major impact on identifying infected individuals and going a long way to protecting the blood supply.

CHAMBERLAND: Now, the antibody test, certainly that first generation, as good as it was--that's actually very striking just to see in that very short period of time the reduction in risk of transmission through the blood supply. But it too was not ideal, because it took quite a while for antibodies to develop. Someone could be infected on day one, but there would be a period of time where there 00:18:00was no test that could catch evidence of the virus. That's correct?

SCHOCHETMAN: Yes. It takes about three to four weeks for the antibody to appear. So in those first three or four weeks somebody could be infected but would come up negative on the antibody test. This is actually quite important. That's a very important period, those first three or four weeks. It's called the acute or window phase. Once they [the patients] developed antibodies, they had been infected for a while. We then called that the chronic phase. Over the last few years, CDC has been able to understand that the epidemic, 30 years later, is still with us. That is, there are still 50,000 to 60,000 new infections in this country each year. Up to 50 percent of new infections are actually caused by people in that window period, that acute phase, those early three to four weeks. It's at that time they're the most infectious, and their-- what we call viral 00:19:00titers, or the level of virus in their blood, are actually at the highest. So, it was really critical, although we didn't completely appreciate it back in '85, '86, '87, the importance of how significant it was in terms of helping to stem the epidemic, but over the years that became very important.

In the early days in the 80's, we tried to close that window [when] we introduced in this country something called the antigen test. The antigen test was really a test to detect the presence of one of the proteins of the virus, called the p24, and that would be positive in those first three to four weeks. So, before antibody developed, the antigen would be positive. You weren't 00:20:00testing for the body's response to the virus, which would be the antibody. You were actually looking more directly for the virus itself in one's blood. That assay did go a long way to assisting in the early detection of HIV. Subsequent to that, it was shown that the use of a genetic-based test or a nucleic acid-based test we call an NAT test, N-A-T was really more sensitive than the antigen--based test. So, the FDA then mandated that all blood in this country should be tested by an NAT test as well as an antibody test for HIV.

CHAMBERLAND: So on this topic of molecular testing and this real need to try and 00:21:00identify different approaches to close that window period, if you will, to find evidence of infection earlier, you were the senior author on a 1988 paper published in the journal Science, that reported on a new testing technique called polymerase chain reaction or PCR. I wonder if you could briefly describe what PCR testing is, and why it was a significant advance in this whole area of diagnostic testing.

SCHOCHETMAN: Yes. Let me give you a little background to that and why we got involved in this new area, which was quite new at that time. It was about 1987 or so when we first got involved with it, and it came out of a question that one of our epidemiologists asked me. It happened to be Dr. [Timothy] Tim Dondero, 00:22:00who was with the [HIV] Epidemiology Branch. Tim asked me, "Gerry, we have a number of patients who are antibody positive for HIV but from whom we cannot culture virus. Are they infected? Why can't we culture virus from them?" Of course, there could be many reasons: either they were exposed to the virus but really were not infected, or they were truly infected but for whatever reason the virus was unculturable. There could be many technical reasons for that that we didn't understand. So we thought about that, and somebody else in the lab and I, one of the colleagues who worked for me, Dr. Chin-Yih Ou, we talked about this. Then we decided that probably the best way to do this would be to look for the virus itself, particularly using genetic means. The reason we felt we had to use genetic means was because we thought that the amount of virus in the 00:23:00patient's blood during that period of time would be relatively low and that we probably would have to use some sort of amplification technique.

It was sort of the needle in the haystack: the haystack was the human blood in a patient, and the needle was looking for this virus in there. The question was, was the current nucleic acid technology sensitive enough to find that needle, and the answer was probably no. So we had to look for a way of trying to amplify all those needles to make many, many copies of that needle and then hope that we could detect the presence of the virus, or that needle.

Just at that time, a paper had been published from a scientist, from a corporation called Cetus in California that developed a technology which allows 00:24:00for the amplification of the nucleic acid, basically making many copies of that needle. That subsequently came to be known as polymerase chain reaction [PCR]. We contacted the people out in Cetus and asked for their help. We went out and learned the technology from them. They were kind enough to supply us with an important instrument that we needed that could cycle temperature, which was needed to run the reaction, which would have been very difficult to do without that, and [they] made available other reagents to us. Within short order we were able to be successful in amplifying HIV from patients' blood and being able to detect it. That was really the first time that this technology, the ability to 00:25:00directly detect genetic information of the virus within a patient's blood cells, was achieved.

That publication came out in Science, I believe in 1988, and at that time it was extremely revolutionary. Today it's kind of matter of fact, but it actually won the [Dr.] Charles Shepard Award here for the best scientific paper in CDC. Interestingly, the technology became extremely useful, and we worked with many of the epidemiologists here. One of them was Dr. Martha Rogers, who was working on pediatric AIDS and particularly HIV infection in newborns. One of the real problems with detection or determination of infection in newborns was [to 00:26:00determine] which of the infants born to HIV-positive mothers were truly infected, since it was felt that only about 25 percent of infants born to positive mothers actually became infected. So when one looked at a patient, it was difficult to decide which was [in] the 25 percent and which was [in] the 75 percent uninfected.

CHAMBERLAND: If you did an antibody test on a newborn infant, all of them born to an HIV-infected mother, that wasn't helpful.

SCHOCHETMAN: No, and that's exactly what I was coming to. That is because all the infants born to positive mothers would be antibody positive, because of passive transfer of antibodies from the mother to the child. So it really wasn't helpful. It could tell you something about the status of the mother, and that technology was used in one of the surveys, the large population survey called 00:27:00"Family of Surveys" at that time, which was involved at looking at the prevalence of infection in childbearing women. You could look at the infant, and if the infant was positive, then obviously the mother was positive. But to determine which infant was actually positive, you actually had to wait until the antibodies from the mother would decay in the baby. That could take anywhere from six to eighteen months, and that really was not very helpful.

So we decided to put the PCR test, the genetic amplification technology, to use. What we were able to show was that really within a week or two, a matter of days after an infant was born, we could take a tiny amount of blood from that infant and actually use the PCR technology to determine which of the infants born to 00:28:00the positive mothers were truly infected and carried the virus from the mother. That paper, to me, was also a real landmark paper, and that was published in the New England Journal of Medicine, I believe, in 1989. I think those two papers, the use of PCR in the Science paper in '88 and the use of PCR in newborn infants, were really I think two of the most important landmark studies that we did.

CHAMBERLAND: This is really within just a few years of your arrival. CDC, it sounds like, was doing cutting-edge research and diagnostic test development. So CDC was actually then the first to develop a PCR test for HIV, and also it sounds like the first to use it in an applied way, as you were describing, in these newborn infant studies that were done.

SCHOCHETMAN: Right, that's correct.

CHAMBERLAND: What was the reaction in the scientific community among your colleagues? I mean, what was the reaction?

SCHOCHETMAN: I think it was certainly recognized as major breakthroughs here. Then it was quickly followed by other studies, which demonstrated that what we had done was absolutely correct. Although initially it was hailed as real breakthrough technology and research, within in a few years it became routine kind of work. So the excitement waned, as everybody was now using it [PCR] routinely in the laboratories. But the use of PCR was really the basis for other kinds of critical studies that were done. One of them, maybe you'll touch on in a little while, is the Florida dentist case.

CHAMBERLAND: Yes, I definitely want to go there.

SCHOCHETMAN: That was actually a confluence of the use of that technology with some other understanding about particularly HIV and how rapidly HIV evolves. Those things we put to use to really begin to sort out how we could track the virus or the epidemic, I should say, from individual to individual--not tracking infection but actually tracking the virus and the change in the virus.

CHAMBERLAND: So the study that you and Martha Rogers collaborated on with a host of other investigators strikes me as a really good example of the teaming up of epidemiologists with laboratorians and coming out with a fantastic result. In your experience at CDC, was that hard to do? Oftentimes these two groups can 00:31:00develop a bit of a silo mentality and work in separate parallel work streams. So, I was just curious about what your experience was over the years, about teaming up with epidemiologists and vice versa, the epidemiologists teaming up with you?

SCHOCHETMAN: To me it was always natural. It was the way it should be done. To me, the power of the research was the combination of the two. The technology itself, the PCR technology and its application, was one thing, but to make it really useful one needed access to the appropriate specimens. It was really critical to get access to patients from the important studies that were being done, and with those samples then we could apply the technology, this cutting-edge technology. The combination of the two led to the importance of the usefulness of the technology. It wasn't simply the technology itself; it was 00:32:00applying it to the individuals who were doing the epidemiologic investigations. It was that combination of laboratory and epidemiology, I think, that was most powerful and led to the highly successfulness of CDC during those years.

CHAMBERLAND: Another thing that you mentioned in passing, another application if you will, was the work that was done in collaboration with Tim Dondero in the so-called "Family of Serosurveys." Can you just expand on that a little bit, and tell us about what that was all about, because that was a pretty ambitious undertaking as well.

SCHOCHETMAN: It was. There were several studies, and the one that really comes to mind and the one we were involved with pretty extensively was the Family of Surveys of childbearing women. One of the questions that was being asked, I 00:33:00guess it was the early '90s--I've lost track of the exact dates when those studies were going on--was to try to understand the prevalence of infection in childbearing women in this country. The question was, how do you get at that? It was known that infants, all infants born in this country, virtually all infants, have a test for metabolic diseases. One of them is called phenylketonuria. The way it's done is, there is a heel stick on the newborn child, and a little drop of blood is then spotted on a special filter paper, which is actually FDA--approved, or was at that time, and the test for phenylketonuria was run.

Then it became, I think, obvious to us and certainly to the epidemiologists that 00:34:00that was a way of collecting blood from the newborns. That was being routinely done, and the filter paper on which the baby's blood was collected wasn't all used for the metabolic disease testing. There was leftover filter paper, and we felt that, together with the laboratory, it was already becoming clear that we could remove some of the blood off the filter paper, what we call "elute off" enough of the material. We now had a collection of the baby's blood, which we could now run in the antibody test. But it wasn't the routine way of running the antibody test. Normally one draws blood from a patient, an adult, and then runs it in the standard test. We were now modifying that test, and so we then had to modify our technology to make the antibody test work in this new sample that we 00:35:00were now collecting. We spent a lot of time really working out the technology.

Eventually I believe there were something like 40 to 50 different laboratories that were doing the testing around the country as part of the Family of Surveys. We had to ensure that all of those laboratories were doing the testing correctly and that they knew what they were doing and that they knew how to do it, and they could do it on a consistent basis month after month after month. So we set up protocols, and we trained the various laboratories around the country in the technology. We then set up panels of positive and negative samples, which we sent out to those laboratories and tested their proficiency in doing that testing, and we did that multiple times. Then we made both positive and negative 00:36:00controls, which we disseminated to all those laboratories. Once we were convinced that the laboratories knew how to do the testing and had demonstrated the appropriate proficiency, then we felt comfortable that they could do the testing on a regular basis, although we did come in from time to time and look at this.

With the positive and negative controls we gave them, we were always monitoring them. Every time they did a run of samples, they would batch them and then run them. They would always run one positive and one negative [control], and we kept watching the results of the positives and negatives. If there was anything aberrant in that positive or negative result, then we felt that something could be wrong, and we sent CDC staff in to investigate what was going on. In some cases, a lab would decide to change the protocol a little bit because they thought it was better. That messed things up, needless to say, and then we said, 00:37:00please don't do that without informing us first, so that we could check it out to see whether that was critical or not. So, there was a huge amount of work to ensure the quality of the results that were coming through those laboratories. I think, speaking just from the laboratory standpoint, that was one of the reasons the survey was so successful over the years. I believe there were millions of tests done on a yearly basis, and the quality of the data was superb.

CHAMBERLAND: That does sound like a huge, huge operation.

SCHOCHETMAN: It was, and we were only a handful of people carrying this out.

CHAMBERLAND: That raises a question. I was thinking about that FDA is obviously responsible for the licensure of diagnostic tests, and you were using this as a diagnostic test, if you will. I was just curious about the interaction with FDA. Did FDA have to, in any way, license this, or how did this work out from that perspective?

SCHOCHETMAN: FDA, I believe, was aware of the studies that were going on. The testing was really done on a population basis, and it was not used to diagnose any specific patient. It was not used to manage the treatment of a patient, so I don't think it really fell into the category of requiring FDA approval.

CHAMBERLAND: Because, as you say, the results of an individual infant's tests were not provided to the mother, for example. You were just studying on a population basis.

SCHOCHETMAN: Right.

CHAMBERLAND: And being able to say that in such a state or on a national basis, the rate of seropositive women giving birth was thus and such.

SCHOCHETMAN: Right. If I remember correctly, I think most of the identifiers were actually removed from the sample, so there was really no way to get back to 00:39:00those patients.

CHAMBERLAND: Right. Just another really fantastic application of technique and, as you say, modification as needed. It also raises that--and I'm sure there are other examples--the HIV lab at CDC really became a resource for training and educational purposes, training laboratories. Were laboratorians actually brought into Atlanta? Did you go out and train in the field? How did that work?

SCHOCHETMAN: I think that some of the training was actually done, I think, by some other groups within the CDC, but there were people who came in from time to time. We actually even had people come in from the FDA to learn PCR, the polymerase chain reaction, technology from us, and [they] went back and could introduce that into their laboratories.

I don't know if you're going to touch on this, but as we think about testing, 00:40:00one thing to keep in mind is that, as we test for HIV, we have to realize that HIV is not a single virus, but actually is a group of viruses. Even within a single individual there's what we call a "swarm" of viruses. This virus evolves continuously, with evolution in real time. So it became kind of---it dawned on us that this was going to be an issue, but also could end up being a useful observation from our standpoint.

The difficulty was that, I believe, It was in '86 or '87, another HIV was detected, HIV-2. Although it wasn't as prevalent as HIV-1, which was responsible for the worldwide pandemic, it was clear that the current HIV-1 test could not 00:41:00detect all the HIV-2 specimens that were circulating. It became clear that the assay was going to have to be modified, and reagents from the HIV-2 virus were going to have to be incorporated into the new assay.

A few years later it became clear that there were other variants, one called HIV-1 Group O. The HIV-1 Group O was also not completely detected by the current assays, so there had to be again modification of the test. After I left CDC and went on to take on the responsibility of being in charge of all the R&D for the Infectious Disease Diagnostics Group at Abbott, it became clear to us that here was a virus that was evolving in real time all over the world. Wherever you 00:42:00went--and this was work we actually had started at CDC [in] understanding the genetic variation of this virus, and that is on a geographic basis--there were all these different strains, or what we would call variants of HIV. The U.S. and Europe in the early days had what we would call HIV-1 Group M, for the "major group," subtype B. If you went to Africa, you had subtype As and Bs and Cs and Ds, a variety of subtypes. As you went to different parts of the world, e.g., if you went to Thailand, you would have A, C and some other subtype B.

So it became clear to us that if we were going to have one assay, one antibody assay that was going to detect all infected people anywhere in the world at any time, that i the assays would have to be robust enough. At Abbott, and I don't 00:43:00mean to get away from CDC, but it became clear to us that this was going to become critical. Abbott was a diagnostic manufacturer, it was a test manufacturer, and it couldn't afford to have tests that it sold on a global basis miss infected individuals anywhere in the world. Then Abbott, at that time when I was still at CDC, the two groups formed a collaboration, what we called the "Global Surveillance Program." We started to look for all of the variants--or as many [as] we could detect--of HIV globally, around the world: Africa, Asia, Latin America, the U.S., basically anywhere, Europe, wherever we could get access to samples. Then we had to make panels from those samples and 00:44:00use those to challenge our assays. In other words, if we collected samples from Africa or Asia or Europe, all those samples had to score positive in our assay. If not, then the assay would have to be modified.

You can't make a million different assays; that's virtually impossible. You can make one, and you have to make millions and millions of tests each year, and that has to be done on a continuous basis. It's virtually impossible to manufacture multiple tests. So, it was important for us to understand the structure of the virus, the genetic variability of the virus, and to ensure that the tests were robust enough to not miss any infected individuals anywhere in the world at any time.

CHAMBERLAND: So this Global Surveillance Program that you were doing in collaboration with Abbott while you were still at CDC--obviously, you're 00:45:00collecting, you're getting lots of specimens, you're finding modifications, changes. Who then would be working to tweak the assays, if you will? Is that something that CDC would do or Abbott would do, or would you both do it and collaborate and see your results? I'm just curious, because it seems to me you're constantly chasing your tail trying to modify the test.

SCHOCHETMAN: It turned out that the appropriate choice of reagents for the tests was made correctly, so that we didn't have to change the assay on that regular [a] basis. Once we got to understand the major variants of HIV, the major groups, then it was pretty clear that the assays that had been developed were doing quite well. But that's an ongoing project, an ongoing problem, and so 00:46:00it's critical for CDC, as well as all of the manufacturers, as well as the FDA.

I touched on earlier that the evolution and variation of this virus is enormous, in that on the one hand it's a problem, which we just discussed--the ability to develop a single assay that could detect all these different strains. But that information could also be put to very good use, because if the virus is evolving, the question then is, if person A transmitted to person B, would the virus be sufficiently similar in person B to demonstrate [this]? Or would it be similar but different than [the virus in] patients C,D,E,F and G, to suggest that person A was the individual who transmitted to patient B, but not to, at least not immediately, to C, D, and E? [Transmission was] probably indirect, since all patients eventually, if one goes back far enough in time, probably 00:47:00were all infected from the original infection. So that really was--

CHAMBERLAND: I think I know where you're going with this.

SCHOCHETMAN: That was really what we started to use at the CDC, actually in the late '80s.

CHAMBERLAND: To do these transmission studies?

SCHOCHETMAN: Yes. We understood the genetic variation, and we decided at that time, by about 1989 to 1990, we were thinking about whether we could track the virus, in the laboratory anyway, could we track the epidemic in a different way? Not just by who gets infected and what [were their] risk categories, et cetera, but could we follow the virus in all these patients? And could we understand the movement of the virus and understand the growth of this epidemic from the virus' standpoint? It might give us an understanding of risk factors and what the future may hold in terms of transmission patterns. So we started to work on 00:48:00that, and using the genetic technology, PCR, we could amplify the virus, [and] we then could use genetic sequencing capabilities. We could sequence the viral genetic information, and then we could compare genetic sequences from patient A to patient B to C, to D, to E. That's what we were beginning to do, and we started to look at cohorts from various cities, from New York to Boston to other cities. Just about that time the epidemiology--

CHAMBERLAND: Can I just ask, were you finding differences?

SCHOCHETMAN: We were.

CHAMBERLAND: I mean, was it clear that the virus circulating in New York City was slightly different than maybe [in] San Francisco?

SCHOCHETMAN: Yes and no. I mean they were all similar in many ways, but they were all somewhat different. None of them were exactly the same, and it was those differences that were really key to the whole thing. Not only did we have the ability to amplify the genetic information so that we could sequence it, but 00:49:00what we were lacking at the time was the ability to analyze the genetic information from one patient to the other. Could we demonstrate similarity or differences and then link patient A to patient B? That really was the next phase of this, to work out what we call the phylogenetic analysis, the relationship of viruses from one individual to the next. That came up very strikingly in the famous Florida dentist case.

CHAMBERLAND: The Florida dental investigation.

SCHOCHETMAN: It was about that time, 1990 I believe, was the very first case, patient A. Our Epidemiology Branch came to us and said, we were approached by the Florida Department of Health about an AIDS case, a young woman who was HIV positive but did not seem to have any HIV risk factors, no identified risk 00:50:00factors, other than she was a patient of a dentist who had AIDS, clinical AIDS. Could we make the match that the dentist had transmitted to patient A? Of course, this had never been done before. This was really, truly the prototype case. We scratched our heads and looked at each other, and I said, we're on the verge of being---- we think we're able to do this, so we'll give it a try and see how that would pan out. We were fortunate to get a sample of blood from the dentist as well as patient A, and eventually we got other patients who were infected within the dentist's practice.

CHAMBERLAND: Who were HIV-infected?

SCHOCHETMAN: Who were HIV-infected.

CHAMBERLAND: I think there ended up being about eight HIV-infected patients in the practice. Some of them had other risks, the classic risks like IV drug use, 00:51:00but most of them did not.

SCHOCHETMAN: Right. That was very critical to us. So, we enlisted the aid of other people in the community, in the scientific community in the U.S., to assist us, particularly with the analysis of the information. People that had more experience in doing--

CHAMBERLAND: The molecular analysis?

SCHOCHETMAN: The phylogenetic analysis. We had people from the Los Alamos database, we had an expert in phylogenetic analysis from the University of Texas, I believe, and we had somebody else out in California who also had some experience in this area, and we used them as consultants to guide us. Eventually, we were able to sequence the individuals. It was critical that we develop really good technique within the laboratory. We could not 00:52:00cross-contaminate samples, and so we developed technology and a procedure and a protocol for keeping everything separate. We had to maintain chain of custody, and as samples came in, we immediately amplified those samples. When we amplified them, which means we made copies of them, on the copies for each individual patient we added a few extra nucleotides, a few extra bases, that were unique to that particular patient. So, we put a signature on each sample, and we did this for each patient so they're all different, all the signatures were different. When we were starting to do the sequencing, we were pretty sure when we'd see that signature in the sequence, we knew who we had and that we had not cross--contaminated the samples. We didn't think the dentist's sample was one of the patient's or vice versa; we knew that they were all distinct. That was critical, so we knew we had done the work properly.

Eventually we were able to get genetic sequences for all of them and work out the phylogenetic analysis of them. As you were saying, some of the individuals who were HIV-infected in the practice had high-risk behavior. They were gay men who obviously probably had contracted their infection through some sort of risky behavior. What was interesting was those two--there were two individuals, if I remember correctly, their viruses did not match each other, nor did they match [those of] the other patients nor the dentist. Whereas the six, those with no identified risk factors--

CHAMBERLAND: I think there were five [in addition to Patient A].

SCHOCHETMAN: Five, whatever that number was.

CHAMBERLAND: Who had no other risk factors.

[NOTE OF CLARIFICATION: A total of 10 patients were found to be HIV-infected in the Florida dental practice. Of these, six had no identified risk factors for HIV and were infected with an HIV virus which closely matched that of the dentist; four patients, each of whom had a risk factor for HIV, were infected with HIV viruses which did not match that of the dentist.]

SCHOCHETMAN: No other risk factors. Those individuals all matched each other. The virus was very close, and all matched the dentist's. So we said, that was 00:54:00the first indication that we probably had transmission from the dentist to those patients, and we had internal controls. The other thing we were concerned about was, was there a particular strain of HIV circulating in the local community that could cause this, [that] would be a confounder for what was going on?

CHAMBERLAND: Because people would say, well, this is just common in the community?

SCHOCHETMAN: That's correct. So, we went out and collected, in the local community, specimens from about 40 different patients [in] various risk groups, et cetera. I think we were able to sequence something like three dozen, about 36 of them, something like that. It turned out that we could not match any of those samples to each other, nor to the dentist, nor to the patients who matched the dentist. It became clear to us that, however it occurred, there was transmission from the dentist to those six patients, and the other four patients who had true 00:55:00risk behavior had somehow obtained their infections outside the practice.

So, that was really the first case, and of course, there was lots of controversy about it. As we were generating the data, we kept having regular reports, and the media and everybody else was saying, you're being premature, you're being premature. Well, we had two choices. We could either be what they would consider premature, or we could withhold the data until the study was completed. Then we always felt we could be accused of suppressing the information. So, we said, better to make the information available. Eventually, it was all published, I think it was in the Annals of Internal Medicine and somewhere else, I don't remember the publication at the moment.

CHAMBERLAND: Yes, I think there were two publications, one focused on the epi and one focused on the molecular epidemiology work that your lab had done.

SCHOCHETMAN: On the molecular, right, that we did. Although there was lots of 00:56:00criticism early on, eventually a lot of the results were repeated by other labs. Eventually it became the prototypic case for how you do this. Then people were applying it to rape cases and a variety of other transmission cases. But I think that was another real landmark use of the technology: one, developing the technology, and then, together with the epidemiologists, applying it to really important issues and trying to understand what was actually going on in the transmission of this virus.

CHAMBERLAND: Yes, the stakes were incredibly high, and this had been something, as part of CDC's routine surveillance, CDC was looking for "unusual" or "infrequent" modes of transmission--

SCHOCHETMAN: Right.

CHAMBERLAND: There had always been a concern out there: could healthcare workers somehow transmit the virus to their patients? It certainly had happened for 00:57:00hepatitis B viruses; for example, surgeons in the past had been known to transmit through whatever, accidental needle sticks or blood exposure. Absolutely, although we're at least in years of time not strictly speaking part of the early response, as you say, absolutely this was an historic landmark where CDC was out there and really led the way from a laboratory perspective.

SCHOCHETMAN: Yes, it goes back to what you said earlier: when I came to CDC in '85 did I have an understanding of the direction we had to go. The answer was, I'd like to say I did, but it was actually an evolution. As our understanding of the epidemic grew and the understanding of the science of HIV grew, and as new 00:58:00technology was being developed for a variety of reasons other than HIV, it became clear to us what the path forward was. A lot of these discoveries were really our being prepared and being knowledgeable enough to be able to apply the technology. Then the rest is history, as they say. But remember, a lot of this was 25-30 years ago. Today we take it as second nature, but in those days we didn't have a clue as to where this was leading us.

CHAMBERLAND: Let me ask you, because you've worked both in the private corporate sector as well as the federal government, so you've had a foot on both sides, if you will. What are some of the things that a CDC can do well that are harder for the corporate sector, and vice versa? Can you look back and sort of compare and contrast?

SCHOCHETMAN: I don't know if it's harder. They each have a different mission. When you're in a corporation, the job is to produce a product, because whatever science, whether it's developed by CDC or NIH or any other organization, to be useful it has to be implemented. It has to be developed into something that can be brought to the public and be used. That's really where industry comes into play. For HIV it was, for the manufacturers such as Abbott that I worked for, the development of the test. CDC wasn't going to necessarily develop an FDA-approved test and manufacture it in multiple million amounts and distribute it globally. That was something for the private sector to do.

For CDC, it had worked out; it was doing the public health portion of it. It [CDC] determined that there was an infectious agent, and eventually it was able to put the test to use. We knew that it was being transmitted in the blood, even before the test was developed we knew that. Even before I think the virus was discovered, CDC knew that there was an infectious agent and that it was just a matter of time before it was going to be discovered. So CDC's role is really to understand the epidemiology of the epidemic, the transmission. Its role, eventually--as part of its title is to prevent, it's prevention, control and prevention, I should say. So, CDC's role is a little different, but they're both mutually inclusive, I would think. One thing I learned from being at CDC prior 01:01:00to going to industry was how useful it was to understand public health and the importance of public health, and how to apply our knowledge of that to the private sector, so that it could be successful in what it needed to [do to] protect the public's health.

CHAMBERLAND: You've certainly given us some very good examples of where CDC's lab excelled and was second to none, if you will, in the areas that it worked on. When you look back, are there aspects of CDC's laboratory response where you think we fell short, or we could have done a better job of?

SCHOCHETMAN: No, I don't think we fell short, and one could always do a better job. But you know, this was an evolving epidemic, one that was unprecedented in 01:02:00our time. There was lots of media coverage, lots of reaction to the changing science and environment, et cetera. I actually think we did quite well in trying to understand the epidemic and how to really deal with it and understand the scope of it, and understand how to control it and how to use the technology that was being developed, not necessarily for this disease but for other uses and how to apply that technology to this epidemic.

I think if anything, it's really--I think what this history project is all about is, what are the lessons learned? The lessons learned are that--one, you don't always know the answers when you start out, but as you begin to learn, you 01:03:00should be able to understand what's going on and how to draw upon epidemiology science elsewhere, your own knowledge, and et cetera. And be able to piece that together to be successful in helping to control an epidemic such as HIV.

CHAMBERLAND: So [when] you came to CDC in 1985, you thought it was going to be a short--term project, [but] you've obviously continued to work on aspects of HIV/AIDS your whole professional career, both at CDC and then afterwards in the corporate sector. How has that affected you personally or professionally? I mean the opportunity to work on HIV/AIDS?

SCHOCHETMAN: You know, [it's] different than what I thought when I first came. When I first came, I really wasn't sure I wanted to work on AIDS. As I said, it 01:04:00was an opportunity to come to Atlanta, and I wasn't sure I was going to be working on it in two years. I'd have to say, it was an opportunity of a lifetime. Looking back on it, I feel like I've been rewarded for having the opportunity to work on it, both in the corporate sector as well as CDC. I look back on my years at CDC very, very fondly. My kids used to say to me when I was at CDC, "So Dad, what do you do?" It was always hard to try to explain to them, but as they grew older, they began to appreciate it and realize the role that CDC plays and the part that I was able to play in that over time.

Moving on to the corporate sector, I think that a lot of the training that I got at CDC and understanding of its role and the whole role of public health in this country and globally, it is really critical. One of the last jobs I had at 01:05:00Abbott was dealing with strategic initiatives, business development, et cetera. One of the things that was critical was to assure that Abbott Diagnostics, the diagnostic division, was aligned with public health, both domestically and worldwide. A large company such as Abbott, certainly working in the diagnostic arena and many other arenas, really can't ignore what goes on in public health and what policies are. It has to align itself with public health policy so that it can be successful and do the job it needs to do in protecting the public's health and dealing with customer needs. The appreciation I got of CDC's role 01:06:00initially, what it does in the U.S. and who its constituents are, but then even on a global basis, because even when I was at CDC, we worked in Africa, we worked in Asia, we worked in Europe. That allowed me to really make that transition and be very successful at a company such as Abbott. So, I think they are both important, and they both need to work together. Training in one is absolutely critical to success in the other, whichever way you go.

CHAMBERLAND: It's almost as if we've come full circle. Any closing thoughts, anything that you'd like to add that we haven't covered?

SCHOCHETMAN: Not really. I'm actually excited and happy that a history project such as this is being undertaken. It's useful to record this for posterity. This 01:07:00was one of those epidemics that I think will be one for the millennia. It actually started in the last millennia, as a matter of fact. I think there were lots of things that were learned, both from an epidemiologic standpoint, from a public health standpoint, from dealing with the public and the public hysteria, as well as application from my standpoint, of laboratory and laboratory technology. The ability to put epidemiology and laboratory together I thought was really powerful, and I never completely appreciated it until I came to CDC. I realized, by the time I left, that it was absolutely critical to have the two work closely together. Silos don't work; collaboration and colleagues do work successfully.

CHAMBERLAND: Well, that seems like a great place to end. Thank you so much for 01:08:00sharing your stories with us, and I think we'll call it a wrap. Thank you.

SCHOCHETMAN: Sounds good.

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