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Fauci: We got our first boost before Rock Hudson died. Certainly Rock Hudson's illness and death had nothing at all to do with our assessment of what was needed. I believe that Rock Hudson died after the Congress was already aware of the need for increased AIDS research funds.
Harden: Had Congress already agreed to support your budget?
Harden: We discussed with Dr. John Gallin the expansion of AIDS research in the NIAID Intramural Program. He suggested also that you were instrumental in assisting that expansion, especially in acquiring the Twinbrook Facility. Would you talk about that?
Fauci: We have a superb intramural research program apart from AIDS. We had it prior to AIDS. We have people whom we have to support and allow to grow–young people coming up, and established investigators. You are very well aware of the history of the program. It is a sensational program. It was also clear to me that we needed to expand AIDS research intramurally. One of the great strengths of the intramural program is that we are able to move quickly in certain areas and do high risk types of research. We had people there who were willing to do that.
Now in order to do that, we needed to expand. But I did not want to expand at the expense of the other established non-AIDS investigators; therefore, we acquired the Twinbrook facility to provide space. We got money from the Congress, and we started to get people who had not been previously involved in AIDS research get involved all of a sudden. There was [Dr.] Bernard Moss, [Dr.] Malcolm Martin, and others, and the expansion of my own group. We had a number of people who were peripherally involved in AIDS research, but fundamentally it was Malcolm Martin, Bernie Moss, and myself, and then a few other people. [Dr.] Tom [Thomas] Kindt started his rabbit model and a few other people were doing some part-time, less intense, but nonetheless qualitatively quite good science in AIDS.
In order to accomplish this we had to expand the intramural program, because the science in the non-AIDS area was too good to phase out all of a sudden just so that AIDS research could grow.
Harden: I understand that justifying and acquiring the Twinbrook Facility was quite a coup?
Fauci: Yes, it was.
Harden: Do you want to talk more about that?
Fauci: It involved a lot of very aggressive negotiation, aggressive in a good sense. We had to be very persuasive that this was what we needed. Thanks, I think, to the insight of Jim Wyngaarden we were allowed to have that space. I had a very good relationship with Jim. Although many people look upon him as a very staid, conservative person, he is brilliant, but he is also very flexible in many ways. I remember sitting down with him. He is the kind of man who is not very animated in discussion. You have to know him; he listens to what you say and then he says yes or no. When we went in there, Mike [Michael] Goldrich handled it from his side with the Executive Office and I handled it one-on-one with Jim Wyngaarden. Jim said, “Okay, go with it. It is yours.”
Harden: One other budget question. We graphed the extramural budget data, which I am sure you are familiar with, and in the projected figures for 1994 we see AIDS research outstripping everything else. As NIAID Director, do you think that is wise?
Fauci: Actually, that is not the way I wanted it. But I think that money on AIDS research will be very well spent. What happened is that because the resources are very restricted, AIDS was targeted in the 1994 budget by the new Clinton Administration to be an investment area. The budget was built from the top down instead of from the bottom up. What I wanted to do was to have the non-AIDS area grow proportionately while still increasing AIDS research. I still feel that way. As it turned out, AIDS research got a major increase, 18 percent from 1993 to 1994 for NIAID; the problem was that the non-AIDS areas, because there was not enough money around, plateaued. Support even dropped by as much as 7.5 percent in some areas. That is something I was very concerned about and objected to, to Dr. [Bernadine] Healy.
What happened was that the streamlining or cuts that all the institutes underwent were done on a formula with which I disagreed. The formula was that the amount of cut that the Administration wanted to effect across the institutes would be proportional to how big an institute was. NIAID's cut was based on $1.065 billion dollars, which was the 1994 budget, but the cut would be taken only out of the non-AIDS research. The amount of cut taken would be based on the totality of the institute's budget, but since they wanted to protect AIDS, all of the cut would come out of non-AIDS research.
As much as I am, have been, and will always continue to be an AIDS advocate, I thought that this was not an appropriate way to make the cuts. In fact, the Congress agreed with us on that. However, they were not able to correct it as much as I would had liked to have seen it corrected. So the reason that the budget graphs criss-crossed is that non-AIDS research took the hit while support for AIDS research went up. The gospel that I keep preaching to the American public, to the Congress, and to the Administration when they will listen is that we must make a major commitment to all of biomedical research. What now is AIDS was non-AIDS awhile ago. We would not have had the basis for immunology, for molecular biology, for microbiology, for retrovirology, if we had not done basic science in those areas. My concern is that we need to correct this problem. We need to have a little correction in midstream here and make sure that non-AIDS research grows proportionately to the opportunities.
Clearly, the scientific opportunities in AIDS research are there and the money is well spent. In fact, scientific opportunities are greater than the resources we have in AIDS. But opportunities are also greater than the resources we have in non-AIDS research.
Harden: I was talking with one of your staff members in the Division of AIDS at one point, and he remarked to me, “AIDS has changed the way we do business at NIH.” Would you comment on this statement with particular reference to the involvement of activist groups?
Fauci: I do not think there is any question about it. What has happened is that the devastating public health catastrophe of AIDS disproportionately–initially selectively–affected a certain population, gay men. Gay men had just emerged within the last couple of decades in their empowerment and identities, and they are articulate, for the most part very well organized, and politically savvy. They became very interested in what we did with the money that we got both for clinical trials and for basic research. I think a major part of my work in this epidemic has been opening the doors and breaking down the barriers between the activist groups and the scientific community. I took a big chance in doing that because I received much criticism from the scientific community. However, it allows us to see the impact of the disease at the grassroots level.
You never want to compromise the integrity of the science that you do, but, quite frankly, the way we approached clinical trials had a degree of rigidity in it. Some flexibility was needed and has now been installed. You could have a pristine clinical trial that was so user-unfriendly that no one would participate in it. Patients with AIDS would get drugs in the guerilla clinics, as it were, or get them in a manner that was not standard. They would also be on all different types of drugs. By changing the way that we do business at NIH, the constituency which has the disease for which you are scientifically responsible has some positive, productive, contributory input to some of the elements of how you do the science–not all, but some.
When the gay activists were demonstrating, predominantly against the FDA but also against the NIH, and being very strident in their criticism, I challenged them. I said, “Okay, come on in, sit down, and let's talk about it. What is it that you want?" That was when we developed relationships with them that are now very productive. We have activists who are important members of our advisory councils. We consult back and forth with them all the time. AIDS changed the way we do business at NIH in that, when appropriate, the constituencies play a major role in some of the policy and decision-making processes. You cannot just cave in and let people tell you how to do science the wrong way, but there is a lot you can learn from understanding how the disease is affecting a particular population, somewhat removed from the bench, and removed from the “ivory towers” that we have here.
Harden: Let us follow up with the case study of AZT [3'-azido-2', 3'-dideoxythymidine]. The trial of the drug, as I understand it, was halted perhaps too soon because of activist demands that, “It looks good, let's go with it.” Is this a morality tale?
Fauci: No, actually it is difficult to say what was the right or wrong thing to do. It was a situation where there was only one drug available–it was not like trying out one amongst many antibiotics–and the activist community and the constituents were suffering. They demanded that they have access to anything that could give them even a little hope. Pressure was put on the FDA. They responded appropriately for rapid expedited approval of AZT, making drugs available that normally would not have been available for years and years.
Harden: Do you think this delayed understanding of AZT?
Fauci: I do not think it delayed understanding of AZT. I will tell you the reason why. The studies of AZT went on after the approval. First of all AZT was approved, and we should get this historically correct as long as this is a historical document. AZT was approved first for HIV infection with AIDS and ARC [AIDS-related complex]. Everybody agrees–all of the studies–that there is benefit from AZT, which is unequivocal, if you are sick with HIV disease. The debate is over whether there is any lasting benefit if you start treatment very early, namely at 500 T4 cells or fewer, as opposed to waiting until somebody gets symptoms.
We knew from our trial that if the drug was started early and the results compared to those from a placebo, the people who were getting AZT did better, at least for the first year. It was at that point that the pressure to approve AZT for people with early HIV disease built up on the grounds, that, “It is unethical to continue the study. There is a benefit. Approve the drug–which was already approved for AIDS–change the package insert and say the drug is now usable for people who have fewer than 500 CD4+ cells, even if they do not have symptoms.”
What subsequent studies have shown is that, if these people were followed for three years, the initial benefit, which looked as though it was going to be significant, disappeared after that time and there was no real long-term benefit. After the recent June 1993 state-of-the-art conference looking at the data from the Concorde Study, which was the U.K./French study, and at a number of other studies, the recommendation now is that AZT should still be given if someone is symptomatic, no matter what the T4 count is. However, if a patient is without symptoms and has between 200 and 500 CD4-positive T cells per cubic millimeter [(mm3)], it is not an absolute recommendation to treat that person with AZT. The physician and the patients have the option of deciding between themselves whether they want to have the “possible” benefit of AZT. There is no long-term benefit on the average, but there are some patients who will benefit. The “possible” benefit is a better quality of life for a year or so weighed against the cost and the potential toxicity of the drug. This is a change from the previous recommendation to treat everyone with CD4-positive T-cell counts less than 500 per cubic millimeter [(mm3)], even those who are without symptoms.
The approval of the early use of AZT was, in fact, particularly influenced by the great pressures exerted in the country by constituency groups to make drugs available very rapidly.
The British were able to carry out a study that we would never have been able to do in the United States. There are different styles in different countries. There is virtually no chance in the U.S.A. that a study that shows some early benefit could have gone on without giving drug to the placebo group, and that is the reason why the study was stopped. We are pleased that the British were able to keep their study going. We have now modified the recommendation somewhat, but not dramatically. The bottom line in all of this–we might as well get it out in the open–is that we need better drugs than AZT and ddI and ddC. Certainly there is a benefit to these drugs that is discernible, and significant, after someone gets sick. But when someone is well, we do not have a drug that will prolong the disease-free state and the life of an individual significantly enough that we could make the statement that everybody should be on the drug as soon as they are infected.
The pathogenesis work that we did in the lymph node studies showed that one can detect virus burden and replication very early in the asymptomatic stage of HIV disease. Thus, we have the scientific basis when safe and truly effective drugs are available to treat a patient as soon as possible, from the moment it is known that he or she is HIV-infected. That rationale is sound. What we do not have, in 1993, are drugs good enough to justify treating somebody that early. What we need to do is to develop better drugs, and to work with the combinations of drugs that we already have, to determine whether if, in fact, someone is treated early, their disease-free state is prolonged significantly.continued on Page 05
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