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Harden: I have two or three questions about the development of these drugs and treatments. First: The idea of using supercomputers and other technologies to do designer drugs has not yet resulted in a useful drug. Do you think it is possible? Second: Is there great promise from cytokine regulation as possible therapeutic interventions? Third: Would you describe what NIAID is doing about these and any other approaches?
Fauci: With reference to the first question, targeted antiviral therapy is certainly the way of the future, and even the way of the present because it is being done already. You could computerize the design of a drug by finding out what the structure of the molecule that you are trying to block is, and then getting a computer analysis of what the right conformation of a molecule to block that molecule would be. That is very much akin to what we are doing in taking highly purified components of the virus, getting the crystallographic structure, and determining what small peptide would block the conformation or the function of something like protease or TAT. Those agents are already in clinical trials. We do not have any information right now, in June of 1993, about whether or not these agents will turn out to be effective, but they hold promise because they are very specific for the virus. That responds to your first question.
The second question relates to our work back in the mid-1980s on cytokines. It is clear that cytokines play a major role in the regulation of HIV expression. In the test tube you can block cytokines and block virus expression. Therefore, the rationale exists to test drugs in vivo that have an impact on cytokine production and cytokine induction of HIV expression. There are ongoing clinical trials with substances like pentoxiphylline, thalidomide, IL-1 receptor antagonists, and a number of other drugs, that can block cytokine expression.
Harden: Is NIAID supporting both of these kinds of research?
Fauci: Both intramurally and extramurally, the NIAID is supporting them.
Harden: Do you have a hunch as to what might be most successful?
Fauci: I think that the modification of cytokine expression will be an important part of the ultimate armamentarium of HIV therapy. I think that therapy for HIV disease will ultimately consist of a combination of blocking the virus, interfering with inappropriate immune activation, blocking cytokine induction of HIV expression, and ultimately reconstituting the immune response either by tissue transplants or by cytokines which actually can build up the immune response.
Harden: I have one more question. As you have been in the public eye so much you have had to conduct your affairs under more intense scrutiny perhaps than any other scientist/administrator ever has. How do you handle this? How do you decompress? I read things on occasion and I note in the margin, “This is Fauci-bashing.” How do you personally handle the potshots?
Fauci: You have to keep your eye on the ball, and never forget what it is you are trying to do, what the goal is and what is your scientific pathway to that goal. You also have to adopt an attitude. I borrow the line from The Godfather–it is in both the book and the movie–“It's nothing personal. It's strictly business.” You have to understand that even though frustrated people who are in pain attack you, it is because you are a visible person. If I reach out to them, they see me, they hear me, I am there. I am not off in a closet somewhere.
When someone is in pain and suffering, he or she needs–and it is almost an instinctual need–to blame or to attack someone for the lack of speed or success of the scientific enterprise. The person who is most visible out there becomes the target. I learned very early on in this epidemic that as I became more of a spokesman, as I became someone who was leading the charge, as it were, that I was going to be the target. Once you accept that that will happen, and if you do not take it personally, then you can go on with your work and you are able to function.
Harden: I recall that when you talked to the NIH Alumni Association you mentioned the function that your sister serves in keeping you in touch with the public's views on AIDS. Can you comment more on that?
Fauci: I have a sister, Denise, who is three years older than I. She is a well-educated woman, a college graduate, a former schoolteacher, who left her profession to raise her family. She represents what I would consider the middle class, the upper-middle class, intelligent person in America. There are many misperceptions about HIV, such as the ones seen in the newspapers that are media-driven misperceptions, the ones that are scientist-driven misperceptions, things that inevitably will be misinterpreted. I get a good handle on how the general public is interpreting information by my sister's response to me and to anything else that is in the newspapers on HIV.
For example, I knew that people were wondering seriously about whether HIV was the cause of AIDS, when [Peter] Duesberg was campaigning intensively trying to convince people that HIV was not the cause of AIDS, because my sister would call me up and say, “Anthony”–she is one of the few people besides my father who calls me Anthony now–are you sure that HIV causes AIDS?" When she calls and asks me that, I know that the general public is wondering about that.
When there was talk about incidents like some of the scares we have had about children getting AIDS in school, and whether they can get it from their classmates, I would say, “No. All the data show that a child would not get it from his or her classmates.” My sister would call and say, “I am worried about my grandson, or my granddaughter, who is in kindergarten. Can they get AIDS from someone who has a cut?" If she is worried about this, then so is the rest of country. Denise has served as a nice barometer for me of what people are sometimes afraid to say, but what they really worry about.
Harden: One more question. What about your own family? When someone makes a threat against you or your family, how do you handle that?
Fauci: The days of the overt threats are over. One thing I can say about ACT UP is that ACT UP has never personally, physically threatened me or my family. They have insulted me, and one activist in particular, Larry Kramer, who has, in fact, become a very good friend, wrote an article that insulted my wife. He had never even met her. He just said awful things about her out of anger and frustration. He felt so guilty about that that he is still very contrite about it. Incidentally, my wife and Larry Kramer have since become friends with mutual respect.
I do not really worry, but if I am concerned about anything, it is not about the avowed activists, because they do it to get your attention. The thing that is of some subliminal concern is the real wacko who wants to go after a public figure, because I am a public figure. As a scientist, generally you are not a public figure. There are advantages and exciting things to being a public figure, but there are also burdens. I am a very recognizable face on television and so on. If I have any concern, it is not about someone who is an activist seriously trying to gain my attention about something because activists know they have an open door with me. It is about the person who goes crazy and decides he or she wants to take somebody out or harm someone's family. Obviously, the chances of that happening are very small, but it is still within the realm of possibility.
Harden: Do you have anything else to add before we move to more general questions?
Fauci: No. That is fine.
Harden: I would like to discuss your third role at NIH, that of being the Associate Director for AIDS. It is an even larger public role than the NIAID directorship. You initially accepted the positions of NIH coordinator on AIDS and chaired the AIDS Executive Committee. At that point you were faced with trying to get cooperation among all the institutes. What was your initial strategy?
Fauci: My initial strategy was to get everyone to appreciate–and they did very readily– that we all had a common goal and that was to conquer this epidemic. It was also to use whatever expertise we had–individual institutes had different levels of, and qualitatively different, expertise–and to get people not necessarily to work together, which was important, but to make sure we covered all the bases. We had to check that there was not a gross overlap of people doing exactly the same thing in exactly the same way. There is complementation, and duplication is sometimes very productive, but we also wanted to make sure that there were no big gaps. That was the major charge of the Coordinator of AIDS Research at the NIH, which is what I do at that level.
Harden: Were there any particular obstacles such as people who did not want to cooperate?
Fauci: No. The group was very collegial. Obviously, when there are resources available, people will try to grab as many as they can. When you make recommendations for the allocations of budget requests, it sometimes becomes difficult. The Congress does whatever it wants. Usually they do it within the realm of the recommendations. But the initial budget that goes forward has to be built from the institutes up. Obviously, there are people, who have good and honorable intentions, jockeying to get more, trying to do what they can to get the most resources. In that respect sometimes you have to disappoint people because you have to make the initial request meet a certain level of funding that you got from the NIH Director, or the Assistant Secretary, or the Secretary [of Health and Human Services], and fit in the relative priorities of what that request should be.
Harden: Would you comment on your experiences in meeting with Vice President, and later President, George Bush, and with President Ronald Reagan when they came to NIH. What did they, as presidents, want to know about AIDS, and what did you tell them?
Fauci: Vice President, and then President, Bush clearly got much more involved in AIDS than did President Reagan. Though President Reagan was sympathetic, AIDS certainly was not in the forefront of his attention or interest. He did, however, have a department to handle it. Bush and Reagan wanted to know the extent of the disease, the projections for the epidemic, where we were going with the science, and whether we had as much funding as we needed to perform the science adequately. They were very concerned about getting the right momentum going scientifically.
Bush took much more of a personal interest, and that is how I developed a personal friendship with him. When he came to the NIH, I gave him a briefing of a couple of hours, showed him the wards and some patients, and showed him our laboratory. I thought that was going to be the end of it. But, subsequently, he called me up a couple of times and asked me some thoughtful questions about AIDS. I was very flattered that the Vice President of the United States would do that. He did it not infrequently. As Vice President, he would call me down to a meeting at the White House, ask me to brief him, or if he had someone who was an important person, a foreign dignitary who wanted to know something about AIDS, the Vice President would just get on the phone and ask me to come down there.
I started to get to know him very well. He was kind and generous to me socially, inviting me to the Vice President's mansion for private dinners, Christmas receptions, and occasions like that. As you can see, I was very fortunate.
When he became president, we continued our relationship, and he was very good at listening to what I had to say. He tried, I believe, as best as he could within the constraints of his administration, to do some of the things that he has been criticized for not doing. It is very easy to criticize the Bush Administration, but the man really cared about the country and about HIV-infected individuals. He did much more than he was given credit for. The problem was that some of the measures I would recommend were very difficult for him ultimately to enact or execute because he knew the resistance that he was going to get from the more conservative elements in his administration and in the Congress. It was not a secret, that he was, and is, a moderate person. But I think he was realistic enough to know that he would not be able to get certain programs through.
People who criticize Bush say that he should have exerted more explicit leadership in trying to get programs through. But it is interesting, and paradoxical, that even now President Clinton, who has very noble intentions about getting certain things done vis-a-vis policies for HIV, is running into resistance from some of the same people who would have given Bush resistance. It is surprising that even some of his own people are being resistant to these policies. What that tells us is that there are many other forces besides the President that ultimately determine what is going to get done in this country.
I think Bush's record of supporting biomedical research from the standpoint of resources is very good. So far Clinton has done a good job of highlighting AIDS and the need for more resources for AIDS. I think that both of them have been very good about it, and each of them has gotten unjustified bad press. Bush has gotten unjustified bad press because his administration, in general, was a much more conservative administration than that of Clinton, which is now just in its first six months. President Clinton, who is trying very hard to do the right thing by HIV, has met unexpected resistance from certain elements which have not allowed him to execute what he otherwise would have. Now he is being criticized for not getting it done. It is very easy to criticize the person at the top. I guess the historic bottom line lesson of this for me is that AIDS is a very complex issue, and it is very easy to criticize the people at the top. That is the reason why I think Bush got a lot of unjustified criticism and Clinton has already gotten unjustified criticism.
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