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Harden: Why don't we talk now about the NIAID intramural AIDS program. I identified a group of areas in which NIAID worked, including epidemiology, pathogenesis, antiviral and immunological therapy, vaccine work, molecular biology, and animal models. What did I leave out?
Gallin: There were a few things you left out about those early days. One is the work of [Dr.] Tom [Thomas M.] Folks, now at the Centers for Disease Control, who was working initially with Mal Martin and with Tony Fauci. Tom was a very important person in helping to appreciate [Dr. Robert] Gallo's observation, to relate it to the patient, and to the beginning of looking at what cells became infected.
The other thing that was going on in parallel, which was also very important and which you touched upon, was Projet SIDA in Zaire. That was a unique interaction among a number of agencies in the government: the CDC, the NIAID, and later Walter Reed [Army Medical Center]. It was actually international. People from Belgium played a major role in it and also some people from Germany. The Germans set up a modern blood banking facility in Kinshasa in Zaire, which I have visited. Kinshasa is a third or fourth world setting. It is very primitive. The people from Belgium had set up an infrastructure for interacting with the health care delivery system that existed in Zaire. But it was the CDC and their people, together with NIAID, that set up a modern investigative research effort in this environment. Drs. Thomas Quinn and Skip [Henry L.] Francis, working with Ms. MaryAnn Guerra, played a major role setting up the NIAID research component at Projet SIDA. It was amazing to me how all the events related to AIDS that occurred in Africa turned out to be an incredible predictor of what was going to happen in the United States. It was sort of a preview as to what was going to happen here with us. You could look over there and say, “We know that in the next four or five years we are going to have this problem," and it happened.
Harden: That was very early on, was it not? People keep saying that there were other people who had connections with what was happening in Africa. It took a while before we found out who they were.
Gallin: You have them. Tom [Dr. Thomas] Quinn was also a major person. [Dr.] Chris [Christopher] Brown was also over there.
[MaryAnn Guerra joins the interview at this point.]
Harden: We were interested in the information on budget and FTEs that you gave us. We looked into it in some detail, and I came up with a graph on FTEs. I was trying to figure out what was happening with the budget and when Congress started to appropriate additional money for AIDS. I knew that at some point there was a quantum leap in the budget for AIDS. I was interested in how you remember this event and what kind of impact it had on the intramural program?
Gallin: Let me start and then MaryAnn [Guerra] can fill in. Your graph shows that fiscal year 1986 is when the tremendous influx of resources started. I can still remember the fears that MaryAnn and I had at that time as to how we were going to spend all this money and where were we going to find the space to put the people. An interesting thing happened. I hired a technician, Lee Tiffany, who had worked at the Smithsonian out at a place called Twinbrook in Rockville. He told Cliff Lane–he did not tell me initially–that space was becoming available there because the Smithsonian was moving to a new location. Dr. John Gerin, who was managing a Georgetown University contract we had on our hepatitis research that was located at Twinbrook, also notified me about the availability of the Smithsonian laboratories at Twinbrook.
It never occurred to me that we could get it, but I went to Tony Fauci and said, “Tony, we need some space. There is 50 thousand square feet of space in this building. It has a greenhouse on the top which would make a great cafeteria.” Tony said, “Let me see what I can do.” To make a long story short, what he did, through whatever magic he had, and I do not know how he did it exactly, was to convince Senator [Lowell] Weicker that we had to have this resource to tackle the AIDS mission. Virtually single-handedly, I am told, Weicker made it possible for us to have the budget that made the resources available to the institute and the budget to renovate the building. We were able to acquire this space from the Smithsonian. MaryAnn and I had some great visits out there looking at pre-Revolutionary era pianos and all sorts of things the Smithsonian had stored there. We undertook a massive renovation which was done at an unusually rapid rate through a contract we had with Georgetown University. I think from beginning to first phase, it was only months.
Guerra: We procured the renovations through the Georgetown contracting who did Phase 1 for us very quickly. After NIH acquired the direct lease of the entire building NIH Division of Engineering Services did the renovations for the next phases. We used a contract mechanism that we already had in place and moved the project forward rapidly.
Gallin: We had two things then. We had this space and we had some money. We had to decide what to do with it. There was one very important memo that I received from [Dr.] Bob [Robert] Chanock. The subject of this memo was “Areas of Research in the NIAID AIDS Program Which Require Immediate Increase and Support.” He wrote me pleading that we rapidly establish an SIV [simian immunodeficiency virus] program within the institute. He said that everybody has now at this point heard about the AIDS virus, and everybody is trying to get a quick fix to make a vaccine. He said that it will never work. It did not work in polio, and it is not going to work now. He said, “You have to go back to the ABCs,” which means you have to have an animal model. You have to evaluate systematically a model of the disease to develop a vaccine. Then, from those lessons, you learn to develop the human vaccine. I can still remember going to Tony Fauci at that time and we had an exciting discussion about Bob Chanock's proposal. We decided that we would be foolish not to proceed with his proposal.
Originally with [Dr.] Bob [Robert] Purcell, who was a section chief in Bob Chanock's laboratory, and Bob Chanock, we set up an SIV model. We also set up a feline immunodeficiency virus model out at Twinbrook. That was one of the first uses of Twinbrook. A young investigator named [Dr.] Phil [Philip] Johnson was brought in. He very rapidly emerged as a real mover and shaker and took charge of that model. Bob Purcell, after setting it up, gradually went back to his hepatitis work and drifted out. Phil Johnson stayed until he became a professor at Ohio State. [Dr.] Vanessa Hirsch, who was working with him, is now overseeing, with Bob Chanock, the SIV model, which has been very successful. This intramural program is one of the few centers in the country that is pursuing that model. Dr. Harry Ginsberg, an emeritus professor from Columbia University, is now an expert on this group.
At the time of the setting up of this Twinbrook facility, we had to figure out whom else to move there. At first we had a virologist, [Dr.] Niza Frenkel, a full professor from the University of Chicago who had joined Bernie Moss. Initially she thought she might work on HIV, so she came to work with Bernie Moss's group but was stationed at Twinbrook. Then we recruited two viral immunologists from the Wistar Institute, [Dr.] Jack Bennink, and [Dr.] Jonathan Yewdell. We began to have a nucleus of virologists and viral immunologists with an interest in AIDS. Bernie Moss decided to relocate another adenovirus person who had an interest in the potential use of adenoviruses as vectors to transmit genes that might render cells resistant to HIV infection. This was [Dr.] Jim [James] Rose and he moved out to Twinbrook too. That was the nucleus initially.
Then it became very clear that Bernie Moss was having a lot of trouble with some of his people being out at Twinbrook and some of his people being in Bethesda. He did not like that. I was very sympathetic to his wanting everybody under one roof, so we brought all of Bernie Moss's people back to Bethesda. We decided to move a whole laboratory out to Twinbrook, and the choice was [Dr.] Tom [Thomas] Kindt's [laboratory]. The rationale was that Tom Kindt was developing a rabbit model for AIDS, so we decided to have all our animal models for AIDS at the Rockville Twinbrook facility. Kindt needed to interact more with the virologists. We thought that with Vanessa Hirsh and Bob Chanock there, they would have a very sensible proximity interaction and that indeed has happened. That has been a positive move. Tom Kindt has no desire to move back. He is now my Associate Director for Twinbrook operations. So Twinbrook has been developing nicely since then, and other scientists have been recruited.
About that same time–around 1986 or 1987 as all this was happening–it became clear that we needed to be thinking about the whole AIDS effort, about what the entire intramural program was doing in some sort of coordinated and logical way. If, for no other reason, than to be able to explain to Congress and to other people what we were doing with all the money that was beginning to come in. It was in those circumstances that we decided to create, at least on paper, what we call the AIDS Vaccine Development and Treatment Center. The NIAID intramural activity was still at that point an intramural program. Subsequently, as we grew intramurally, it became a Division. The growth of the NIAID intramural program illustrates one of the impacts of AIDS. Our budget increased from about 53 million to 119 million dollars in less than six years.
The Vaccine Development and Treatment Center plan outlined the interaction of the various elements of the intramural activities for AIDS. By then, more and more laboratories were doing something in AIDS. Now, in virtually every laboratory in the institute someone had a project on AIDS. In some laboratories it was 100 percent, or nearly 100 percent, and in some less. Overall, our activity is about 50 percent on AIDS for the intramural program in 1993. You can see we have a molecular microbiology group, which included [Dr.] Bruce [W.] Chesebro and Mal Martin; a clinical immunology group, which was led by Tony Fauci and Cliff Lane; an antiviral agent group, which was led by Cliff Lane and Mal Martin; a vector development unit, which was led by Bernie Moss and which focused on his vaccinia work.
More recently, Bernie Moss has worked with [Dr.] Ira [H.] Pastan of NCI [National Cancer Institute] to develop an antiviral agent using a CD4 Pseudomonas exotoxin. This was really the idea of Dr. Ed [Edward] Berger, who was a tenure-track scientist in Bernie Moss's laboratory. Ira Pastan had the technology to couple the various elements like CD4 to Pseudomonas exotoxin, which he had been using in chemotherapy for cancer. He wanted to target therapies to cancer cells and he had this marvelous toxin, Pseudomonas exotoxin. Bernie Moss suggested that we could use the same approach to annihilate cells that were infected with HIV and that express CD4. That is now under clinical evaluation.
During this period [Dr. Herbert] Sandy Morse developed a mouse model which has been very interesting. It is called mouse acquired immunodeficiency syndrome [MAIDS], which initially we thought was going to be a great model for HIV. It is caused by a different retrovirus, but one somewhat related to AIDS. Sandy Morse developed this together with [Dr.] Janet Hartley. She had worked very closely with [Dr.] Wally [Wallace P.] Rowe, who made some of the initially important studies on retroviruses. The mouse model is teaching us many lessons about the pathogenesis of retroviral infections, but is probably not a good model for human AIDS.
Harden: I believe that only Bruce Chesebro from NIAID's Rocky Mountain Laboratories [RML] was listed as working on AIDS. Is anyone else there doing AIDS research?
Gallin: There is another group at RML that works on AIDS. It is led by Dr. Seth Pincus, who works in the Laboratory of Microbial Structure and Function. [Dr.] John L. Swanson is the laboratory Chief. Dr. Pincus is a senior staff fellow who has been working on antibodies against AIDS, as well as on some HIV immunotoxins. This is somewhat related to what Bernie Moss and Ira Pastan were doing. Dr. Pincus has done some nice work there.
Guerra: Dr. Pincus's research was funded through the AIDS targeted antiviral program.
Gallin: That has been a important program for our Institute. Initially we were very skeptical when Building 1 [the NIH Office of the Director] received AIDS targeted monies to distribute to institutes. I was very nervous because I feared that we would get programs started with Building 1 soft dollars, but we would not have institute dollars to continue them. Building 1 dollars might disappear one day, and then what would we do with all these people and their projects? So far that has not happened. In actual fact we have been able to nourish a lot of young programs and to bring them to a point of importance. That has worked out well.
Harden: You are talking now about young people who are just beginning their careers. I would also like to know about your senior people who might have looked into how their research might be related to AIDS. I would guess that they would spend a year or two working on it and then say that they had done all they could. That would be the end of it. Did you have many people like that?
Gallin: We had a few. One pair was Jack Bennink and Jonathan Yewdell. When they arrived at NIH they intended to work on AIDS, but subsequently their science led them to other areas. Bob Purcell was very interested in setting up this SIV program out at Twinbrook, but once it was set up, he felt that his priorities were back in hepatitis. He let the Twinbrook program take its own course. Niza Frenkel first came here saying that she was going to do some work on HIV, but it never panned out. She, in the meanwhile, discovered a new virus, human herpes virus 6, which turns out to be the cause of roseola, a childhood infection. Instead of HIV, she pursued that virus, which has turned out to be extremely important. She subsequently moved to Israel.
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