Interview with Dr. Samuel Broder

Harden: Dr. Broder, we would like to start the interview by asking you to tell us a little about your background, where you grew up, where you went to college, where you went to medical school, and how you got into medicine.

Broder: I grew up in Detroit, Michigan. I went to the University of Michigan as an undergraduate, and then I went to the University of Michigan Medical School. I graduated from medical school in 1970. I went to Stanford University in Palo Alto, California, right after graduation, did my internship and residency in internal medicine, and came to the National Institutes of Health (NIH) as a clinical associate in the National Cancer Institute (NCI) in the early 1970s.

Harden: What was it that made you go into medicine? Were there any particular family influences, for example, that made you want to become a doctor?

Broder: That is complicated. I think basically I was interested in a combination of science and scientific activities and an ability to help either people individually or from a public health perspective. I acquired that interest probably when I was in my early teens. It is hard for me to pinpoint any one force that did that. It just seemed like a very logical thing to do, and things unfolded thereafter.

Harden: When you came to the NIH in the 1970s, with whom were you working and what were you doing?

Broder: I worked initially with Dr. [Thomas] Tom Waldmann in what was then called, and probably still is, the NCI Metabolism Branch. I moved briefly to the NCI Medicine Branch, and then moved back to the Metabolism Branch. In approximately 1980, an opening occurred as the head of the Clinical Oncology Program at NCI. It seemed like a good opportunity, so I became the head of the Clinical Oncology Program.

Harden: That is a rapid rise. Tell us about your earlier research. What were you doing in those years before you became head of the Clinical Oncology Program?

Broder: I was interested in immunodeficiency disorders and was particularly attracted to the relationship between immunology and cancer. Tom Waldmann’s group had a number of very interested and focused individuals who were studying diseases like ataxia telangiectasia, the Wistkott-Aldrich syndrome, hypogammaglobulinemia of different types, intestinal telangiectasia, and other things like that. They seemed to personify what I was interested in doing in that most of the people in Tom Waldmann’s group were doctors, M.D.s, but they were interested in generating knowledge and learning from patients, both as individuals and as part of the clinical trials activities.

In fact, that was actually a very interesting time, because [Dr. Robert] Bob Good in that era had extolled the virtues of studying “experiments of nature.” The theory was that there were certain clinical syndromes which, despite their rarity or seeming uniqueness, actually taught broad lessons in medicine and science; and that these syndromes often resulted from inborn errors of the immune system, or sometimes from certain acquired injuries to the immune system. These clinical syndromes “performed,” if you will, experiments of nature that were more interesting than what a scientist in that era, or maybe in any era, could have designed.

Harden: This was the period when molecular immunology was flowering. Do you recall feeling as though you were learning something new every week?

Broder: I think there was a lot of excitement. The molecular revolution actually had not quite taken off when I first got to the NIH. It was in its infancy, and probably the questions being asked were, at one level, removed from the kind of elegant molecular biology that now informs immunology, informs everything.

But I think, ironically, I did catch the wave of the National Cancer Program, which then was still very new. This program was very controversial, and I think, in some ways threatening to some members of the scientific community, both inside the intramural program and throughout the country. But, actually, the National Cancer Program was an engine that drove almost all biological research and provided unbelievable benefits to the NIH generally and to intramural scientists and to those who received grant support.

I think it was a very interesting time, because the public’s commitment and vision in favor of cancer research were applied across the board to virtually every institute within the NIH. Many of the ideas that we take for granted–cloning and sequencing genes, expressing novel, new proteins, understanding the molecular basis of genetic regulation, and so on–were derived from the commitment to study things in the context of cancer research. I think that was a bargain for the public at large, and I think we are still seeing the aftershocks and residuals of that era. There is still much misunderstanding and perhaps even occasional anger about the National Cancer Program.

I joined the NCI at a time when many ideas could be pursued freely, particularly in the clinical arena, without necessarily worrying about clinical costs and the limitations of third-party payers. This was a marvelous, and alas, now vanished time.

Harden: You were always involved in clinical research?

Broder: That is correct.

Harden: I would like to hear your comments on being a young investigator in the NIH intramural program. What was unique about this? And what were the limitations?

Broder: I can look at it only from the standpoint of what I like to do and what I thought was being done in the intramural program. In the intramural program, scientists can make a serious commitment to clinical activities at the same time that they have their own laboratory activities. Even more important, they can use the clinic as a vehicle for generating hypotheses that can then be taken back to the laboratory. I think there are some profound misunderstandings of how important this is, primarily amongst scientists who spend their entire lives in a conventional laboratory and may not appreciate how important the clinic can be in generating knowledge for the laboratory to pursue. Being able to make observations in patients and then using those observations, based on the skill and acumen of a great clinician, to go back into the laboratory and to answers research questions, is a wonderful feature of the intramural program. However, I fear that the importance of the intramural clinical programs may now be under-appreciated. In other words, the people who founded what is the modern version of the NIH took great pains to locate laboratories in juxtaposition to a hospital ward or a clinic. Sometimes a laboratory would actually be on a ward–a research laboratory, not a clinical laboratory–and that juxtaposition between scientists and clinicians, allowing a clinician to see patients and walk a few steps back and forth to exchange samples of tissue or blood, was invaluable for progress. The free flow of knowledge and the encouragement of ideas based on that principle were unusual and perhaps unique.

Programs in other parts of the country and in other academic centers could perhaps do the same thing, but I think they tended not to. Even when I arrived at the NIH, the seeds of managed care were already planted, and while they had not completely taken root, other academic centers lacked the freedom to do what NIH could do. We are now obsessively focused on third-party payers and making sure that revenue targets are met. As the 1970s and 1980s unfolded, we saw a compartmentalization of clinicians versus laboratory scientists. Part of this was based on the reality that laboratory science became extremely specialized, requiring skills in molecular biology not available to the ordinary physician. But many of the individuals at the NIH, nevertheless, made a very effective transition into the new world of molecular biology. I had the good fortune to work with many such people, people like Tom Waldmann and a number of other people who were very effective at bridging the gap.

I think that that this bridging function was extremely valuable, and my suspicion is that much of it may have been lost My fear is that the intramural program does not function at that same level in terms of the interplay between the lab and bedside, and probably no place in the country now does. I think the NIH leadership clearly has not assigned full value to this function historically, in part because of practical necessity , costs, and in part because of a lack of an appreciation or respect for the process.

Hannaway: To follow up on that, do you believe now that the emphasis on laboratory research has become predominant at the NIH in terms of where discoveries will be made?

Broder: I think that is basically correct. I do not want to be misunderstood on this point. It is a basic principle of anyone who has ever led the NIH and anyone who has ever held a senior position at the NIH that basic, fundamental, unrestricted laboratory research has an indispensable and cardinal role in the activities of the NIH. I certainly do not disagree with this philosophy. However, the process of generating ideas for science does not follow a simple trajectory, involving a simple process in which a scientist thinks of an hypothesis, generates all the laboratory data that might be necessary, identifies a gene and molecular pathway that is relevant and then, by essentially a black box, knowledge gets applied in the clinical arena. I think it is quite the opposite in many situations. Sometimes an astute clinician, or a set of clinical observations, drives the basic research in fundamental ways.

It was once very common to see individuals who could traffic in both scientific and clinical ideas. When I first got to the NIH, this was still very common. It is becoming less and less common and less and less respected or valued, in my view. The NIH is potentially allowing a two-class system in the intramural program: there are the crème de la crème basic scientists, and then the clinical scientists are an afterthought or are tolerated as a necessity. Perhaps this critique is not totally fair, but I think there has been drift in that direction.

Harden: I know that [Dr. James] Jim Wyngaarden was very concerned about the situation with clinical investigators when he was director and was trying to encourage more people going into clinical research. Perhaps it is just very difficult to do clinical research, find the funding, and have the expertise in the laboratory.

Broder: I think that is true. Institutions are often defined by how they reward individuals, and I am not talking about simple financial reward. I am talking about a culture of respect and giving positive reinforcement. I think that people who can function in basic and clinical research perhaps receive less respect than they did in an earlier time.

I think that, on balance, for example, the NIH of today might find it difficult or impossible to respond to the AIDS epidemic in the same way that it did in the early 1980s. Getting answers very quickly would be very difficult, in my view. Providing the necessary resources and administrative flexibility might be very difficult.

I do not think it is an accident that much of the critical work for perhaps the first three to four years of the AIDS epidemic originated within the NIH intramural campus.

Harden: I recall seeing an NCI memo dated 1981 or 1982 to [Dr. Vincent] Vince DeVita saying, “This new disease looks really serious. I think the Cancer Institute needs to commit money.” This memo shows a grassroots response to AIDS–an investigator bringing it to the attention of the NCI director, rather than the other way around. Would you agree that this is what happened?

Broder: You asked an interesting question, because you are describing a situation in which the National Cancer Institute is responding to what looks like an infectious disease in a public health emergency. In fact, that is a strength of the program. The National Cancer Institute was criticized for doing that. But at the beginning of the AIDS epidemic, NCI resources had to be placed in the service of identifying a cause of AIDS and possible prevention and treatment.

There is a potential lack of corporate memory. Some scientists and organizations, that might have made a contribution, did not respond to the AIDS emergency. I am not being critical. I am merely stating a reality, that a scientist in a laboratory doing wonderful work may not feel that he or she has any obligation, in such situations. It may not appear to be an important problem to that person. The NIH, and its unique team of scientists and clinicians, and especially a core of individuals who could wear both hats, made a profound difference. In my opinion, there were no counterparts to Bob Gallo or Tony Fauci outside the NIH.

Hannaway: Can you remember when and how you first learned of AIDS. Do you have a recollection of that?

Broder: Well, we had a case on Tom Waldmann’s service, in 1981. This was an individual who basically was a walking synopsis of what AIDS turned out to be. It was not then even called AIDS. There were various names being given.

Hannaway: GRID.

Broder: The GRID syndrome, that’s correct. There were all sorts of complicated names attached to it. I do not think the name AIDS had actually come into play at that point. We admitted this man, who was referred to the NIH because he had a profound immunodeficiency, a very dramatic reduction of lymphocytes, a very strong susceptibility to opportunistic infections of various types–viral, bacterial, Pneumocystis, a number of things–that were not very clear and in some ways, did not fit the definition of any then-known immunodeficiency disorder.