HIGHWAYS AND BYWAYS: 50 YEARS OF RESEARCH AT THE CLINICAL CENTER

Michael Gottesman

This year we celebrate the 50th anniversary of the opening of the NIH Clinical Center. On October 14, 2003, a symposium was held in Masur Auditorium to recognize the scope and depth of research accomplishments that represent some of the history of the Clinical Center.

Those who attended—whether newcomers to NIH or longtimers who were here when the doors to the Clinical Center first opened—could not help but be impressed by the enormous impact the Clinical Center has had on the practice of medicine, from developing the current paradigm for the chemotherapy of cancer, to changing the way in which ischemic heart disease is treated, to creating new approaches to the treatment of multiple sclerosis.

This kind of occasion also inspires reflection on the constellation of causes of past success to assist us in imagining how best to ensure continued success in the future.

In listening to the presentations and reviewing other contributions made at the Clinical Center, I was struck by the fact that some of the major paradigm-shifting research was accomplished in the face of great resistance and with enormous investment of time, staff, and resources.

In keeping with the current road map metaphor, Clinical Center research built the major highways, bridges, and tunnels that have transformed the face of medicine.

Vince DeVita’s recounting of the need for protracted persuasion of influential skeptics in the development of multiagent chemotherapy of cancer—and the involvement of so many physicians and patients over so many years—illustrates the kind of major effort to which I am referring.

Similarly huge efforts informed NIH contributions to cardiac surgery (the first implantation of an artificial mitral valve), to the treatment of manic-depressive illness (demonstration of the dramatic effect of lithium), and to identification and control of HIV infection.

So, too, will current and future undertakings related to major public-health problems require a large commitment of resources and energy. The payoff, however, is certainly larger. We are now in the process of planning a major initiative to better understand the physiological causes and consequences of obesity, an effort that will require a substantial trans-NIH commitment.

But the success of clinical research at NIH is as much written in the shortcuts and scenic byways as in its major highways. When we study rare diseases, we never know at the outset where research will take us, but the results are invariably useful and frequently have profound effects on human health. To paraphrase the novelist E.L. Doctorow: Research "is like driving a car at night. You can only see as far as the headlights, but you make the whole trip that way."

The history of the Clinical Center has many examples of circuitous trips without maps that have arrived at unexpected and far-reaching destinations. For example, studies of the rare human embryonic cancer choriocarcinoma, by Roy Hertz and Min Chiu Li, led to a need to follow success of treatment by measuring human chorionic gonadotropin. Judy Vaitukaitus developed the first radioimmunoassay for this hormone—and this assay became the basis for the home pregnancy test, which, needless to say, has had profound social consequences.

Tom Waldmann, in searching for a way to diagnose and treat a rare form of T-cell leukemia, developed an anti-TAC antibody to the a-chain of the interleukin-2 receptor. This antibody blocks T-cell activation and has found important use in the treatment of several autoimmune disorders at the Clinical Center, including multiple sclerosis and autoimmune uveitis.

Finally, our courageous patient volunteers and the observations made by astute clinicians have led to new pathways to discovery. The combined observations of Isaac Asimov and Dr. Seuss summarize the NIH research terrain. Asimov put it this way: "The most exciting phrase to hear in science, the one that heralds new discoveries, is not Eureka!, but Hmm, that's funny." And from Dr. Seuss, we append a key road map legend: "From there to here, and here to there, funny things are everywhere." We need to continue to be accessible to patients with a large variety of disorders, and observe them carefully as we care for them, to learn more about human health and disease.

We are awaiting the imminent recommendations of a Blue Ribbon Panel on Clinical Research at the NIH, co-chaired by Ed Benz, president of the Dana-Farber Cancer Center in Boston, and Joe Goldstein, professor at the University of Texas Southwestern Medical Center, Dallas, on how best to ensure that the new Clinical Research Center has as much impact as the Clinical Center has had in the past.

I am confident that NIH will be asked to continue to take on important public health issues—but not eschew the rare diseases that have led to so many important insights about human pathophysiology.

If you are interested in watching and listening to the many outstanding presentations given at the Clinical Center 50th anniversary symposium, they are archived here, as are the special 50th-anniversary series of Clinical Center Grand Rounds.

—Michael Gottesman
Deputy Director for Intramural Research

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