Office of NIH History
In Their Own Words: NIH Researchers Recall the Early Years of AIDS
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Harden: We have talked to Dr. Waldmann.

Broder: So he must have described the same thing.

Harden: Yes. He has described it.

Broder: So you know I am not making it up!

Harden: No, no. The only problem was that the medical records for that first patient were lost, misplaced, something happened to them. But we have heard about this patient from a number of people.

Broder: You see, it is part of the conspiracy to downplay the contribution of the NIH intramural program!

Harden: Dr. Waldmann said that people are going to think that.

One person with whom we talked said, “I remember there was a large group of people in this room. Everybody wanted to see this patient that Dr. Waldmann had.”

Broder: There is no question that this was an unusual patient. His medical history showed that he had visited Haiti, he ultimately had a lymphoma of his GI tract, and he had many unusual infections. Basically, all I remember saying was that we had never seen anything like this before, and I hope we never see anything like this again.

Hannaway: But had you read newspaper accounts or heard from colleagues about AIDS?

Broder: Oh, yes, sure. It was not called AIDS, but as part of the work-up, we discussed anecdotal reports of a new immunodeficiency disease in otherwise healthy gay men. The junior staff had done a very good job of reviewing the literature and came across some unusual cases, sporadic cases of gay men, primarily in New York and San Francisco, who seemed to have very unusual things happening to them, especially a kind of global immunologic failure.

There were two indicia that something very strange was happening. First, they were young men starting to get ill, and their doctors were having to call the CDC [Centers for Disease Control and Prevention] for the release of pentamidine, which was then used for Pneumocystis carinii. Ironically, one of the world’s repositories for knowledge about Pneumocystis carinii was in the intramural program of the National Cancer Institute, where Vince DeVita was one of the world’s authorities. Same goes for Tony Fauci, whose lab was about four floors above the ward. So there was an enormous realm of expertise. [Dr. Philip] Phil Pizzo was here and was able make a number of contributions. There was an enormous wealth of expertise all within a few floors in one building.

Harden: Do you remember the conversations of people talking, “What on earth is this?” I do not know whether, how...

Broder: Sure, sure. There was an enormous sense of pressure and urgency, because there was so little known and so little we could do.

As additional cases became known, there was a substantial level of stress and a certain level of public distrust and confusion, all of which made everyone’s life more difficult.

The situation temporarily gave a level playing field to all sorts of crazy people who, in the Andy Warhol sense of the term, could obtain not only 15 minutes worth of fame but possibly build a career, promoting ideas without a scientific foundation. This greatly confused the public and to some extent damaged science. In part, the sheer complexity of AIDS, and the inability at that time to determine its cause or treatment, made things much worse. The only way you can block a very bad idea is to put forth a good idea. At the very beginning, scientific community was not able to do that. We really did not know what was going on. So the only honest thing we could say is, “We need more research.” Many of the theories put forth at the time essentially blamed the victim and greatly complicated many issues related to public education about disease transmissibility.

Some of the issues of lifestyle became a big issue, and Tony Fauci once, when it came to maternal-to-fetal transmission, asked a critic, “What lifestyle did the fetus undertake to acquire the disease?” I do remember feeling a sense of sadness that a number of scientists, who had great power and great prestige, were delighted to stay completely out of these issues in that era.

Harden: Did you see any homophobia among the scientists at the NIH who stayed out of it or got into it or...

Broder: No. I know of no scientist who refused to enter the AIDS research arena on the basis of homophobia.

My only point was that there were a number of scientists who basically said, “I am doing my own research. You do your thing, but I am not switching to this. I am not going to spend any time on AIDS.” I do not know if I am the only person who has expressed that view.

Hannaway: No. A few people have. Some have been quite dismayed, I think, by some people wishing to stay away from AIDS research.

What we wanted to ask you about now is that, after the AIDS retrovirus was identified, you decided to pursue research into treatments for AIDS in your laboratory. Could you describe how you came to this decision, who was in your laboratory, and how you initiated and organized this research?

Broder: This is a complicated question. It was clear that we needed a focused laboratory that was used to drug discovery and was willing to work with live AIDS virus. The only institute in the NIH that historically had focused heavily on new drugs is the Cancer Institute. Other institutes certainly played a role, and other institutes have made wonderful contributions to the therapeutic armamentarium. But the Cancer Institute is the only group at the NIH that actually had become a “pharmaceutical company” working for the public, in difficult areas where the private sector either could not or would not make a commitment. Ironically, one of the drugs synthesized for the National Cancer Institute was one by [Dr.] Jerome Horowitz under an NCI grant working at what was then called the Detroit Cancer Institute, I believe, and is now called the Michigan Cancer Foundation. This drug was AZT, and it was initially created and tested as a possible anti-cancer drug.

Hannaway: During the 1970s or...

Broder: During the 1960s and 1970s....

I turned my laboratory to trying to look for drug discoveries in that arena, knowing that we could have at our disposal all of the things necessary for early drug development, including a ward right down the hall, with the backup of the entire infrastructure NCI had established for new drug discovery and development. In effect, we had a “skunkworks.” We did not cure AIDS, but we did deliver many specific drugs in real time: real drugs, not theoretical things, not promises to develop a drug in the future, not the basis of an RFA or an RFP–real drugs. Some of them were patented on behalf of the government, some of them not, some originated in collaboration with private sector partners, others not. But a large number of candidate therapeutic drugs emerged from the NCI programs. Some were successful, others not. However, even those that were not successful stimulated important further research and, in my opinion, were an antidote to the sense of therapeutic nihilism that was very common in that era.

We had superb clinical investigators like [Dr. Robert] Bob Yarchoan, who was available and ready to do the things we needed to do. We had [Dr.] Hiroaki “Mitch” Mitsuya, who was exceptionally gifted, and could grow anything in tissue culture. He was able to set up mass screening systems that were very effective and reliable. That attracted the attention, of course, of what was then Burroughs Wellcome in developing AZT. Then we were able to develop analogs, some of which are still out there, or at least stimulate the development of other analogs. [Dr.] Jan Balzarini joined me from Belgium. He was an exceptionally good medicinal chemist/pharmacologist. And we were able to tap on many of the people like [Dr.] Dave Johns, [Dr.] John Driscoll, in fact, all the people in the intramural program. They were able to do structure-activity relationships with us. There was a two-year period of time where everything sort of clicked in and the bureaucracies were not there to do what bureaucracies usually do. I do not think it could be done now, quite frankly.

Hannaway: Was Dr. Mitsuya already in your laboratory?

Broder: He was absolutely already there.

Hannaway: Was he a postdoctoral fellow?

Broder: He was a postdoctoral fellow at that time. He subsequently has become a permanent staff member of the NCI...

Harden: And this window, you are saying, is 1984 to 1986?

Broder: I would say from about 1984 to about 1987 There was a two- to three-year window of time where the bureaucracies were not well established yet. Quite frankly, among the reasons why I think bureaucracies stayed away is that there was a strong presumption that the project would fail quickly or self-destruct.

Harden: I would like you to elaborate on this because of two things. I am very interested in how scientists thought about AIDS when it first appeared. Were they all thinking within the same paradigm, or were, for example, basic scientists thinking about the disease as a molecular phenomenon while physicians were thinking more of the whole patient?

Broder: I do not think there was one simple viewpoint. In my case, I was influenced by the fact that I was trained as a medical oncologist and, therefore, in some ways was able to take advantage of similarities in the way a retrovirus replicates and the way a tumor cell replicates. I was also willing to accept that it is better to make some progress quickly than hold back and wait for a cure before acting or before trying to implement a new therapy.

A starving man or woman cannot turn down a slice of bread because it is not a full loaf, and I think that, on balance, many of the scientists involved, perhaps from a combination of well-intentioned but naive analyses of the situation, were really saying, “A cure or nothing. Give me 20 years and I’ll give you a cure.”

In addition, there was a lack of appreciation, an ineradicable lack of appreciation, for the role that certain types of clinical advances play in the basic research agenda. Once there was at least a recognition that one could make certain partial advances with a single agent, AZT, then one could bring in things like didanosine, or the other products. One could bring in non-nucleoside inhibitors. One could be more confident that viral protease inhibitors would work and were worth pursuing.

Hannaway: Did Dr. DeVita support your ideas of going for the slice of bread if you cannot have the whole loaf?

Broder: Yes. But he also did more than that. He had a belief that you can do things without having to wait for perfect knowledge, and he was not afraid to act. There was a destructive level of skepticism at one point. Some scientists forgot that skepticism is a tool of science; it is not a replacement for science. It is a tool that allows you to analyze, to weigh and consider, not to be fooled, not to let your emotions run away with you. But what was happening, in my view, in some portions of the scientific community was that skepticism became the format of science: it was very unhelpful. There was a curious belief that nothing would work. When we had our first reversal of dementia, which subsequently became a common thing, especially in children, some scientists said that they would not believe it. We would show them PET [positron emission tomography] scans. They just refused to believe it.

Hannaway: Did Dr. Bruce Chabner, who was the chief of the Division of Cancer Treatment at the time you started this work, believe that AIDS drug discovery was an important part of his division’s mission?

Broder: Yes, and he made major contributions in his own right. He was interested in a drug called trimetrexate which turns out to be a very good agent for certain opportunistic infections–this drug was originally developed for cancer, but it has value in other clinical settings.

Harden: In 1986 the Technology Transfer Act became law. It represented a tidal shift in attitudes towards patenting within the government. Do you want to comment on it?

Broder: The federal Technology Transfer Act of 1986 and subsequent iterations of it proved to be very valuable from a scientific point of view. This act provided a framework for working with industry and for making it the policy of the NIH and other federal laboratories to concern themselves with the practical applications of research, and getting the fruits of research to the places where the public good could be served. The Act provided an incentive and a legal framework for getting products developed and for collaborating with the private sector in ways that would otherwise be impossible.

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