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News and Publications
Ernest Beutler, M.D.
This annual report is a special one, not only because it is the penultimate report of this millennium but also because it marks the 20th anniversary of my chairmanship of the Department of Molecular and Experimental Medicine. My purpose this year is to compare what is with what was, to describe some of the changes that have occurred and the challenges that have arisen, and, finally, to suggest what may be done in the future to address these challenges.
I joined the Research Institute of Scripps Clinic, as it was then known, in the fall of 1978. By the fall of 1979, I had moved all of my operations to La Jolla, where we had set up our laboratories at the Coast Boulevard site. The Department of Clinical Research, which I chaired, consisted of 3 laboratories: hematology, headed by William Crosby; metabolism, headed by Willard VanderLaan; and clinical immunology, under the direction of John Vaughan, who had been the previous chairman of the Department of Clinical Research. The department had 10 full-time faculty members and 15 full-time clinicians with adjunct appointments. Several of the senior faculty were highly respected in their fields, and among the junior faculty, a few were outstanding and, in my judgment, had great promise. John Vaughan had succeeded in obtaining a grant from the National Institutes of Health to establish the General Clinical Research Center.
However, as a whole, the department appeared quite dispirited for a variety of reasons. A part of the problem was that the research institute had achieved worldwide recognition because of the seminal work in immunology that was being done there, and some of those who were not laboratory-based immunologists felt like second-class citizens. Then, too, the relationship between physicians in the research institute and those in medical practice was beginning to change. At the time that I arrived, each division head had played a leadership role in his clinical specialty in the clinic. Dr. Vaughan had been chairman of medicine and head of the rheumatology division, Dr. Crosby headed the hematology division, and Dr. VanderLaan was in charge of the metabolism division. But Dr. Vaughan had relinquished his responsibilities in the clinic, retaining only the role of program director of the General Clinical Research Center. Dr. VanderLaan was replaced as head of the metabolism division during my first year at Scripps. Replacing Bill Crosby as head of the hematology division in the clinic, I was the only member of the research institute faculty who headed a clinical division in the clinic.
I was not daunted by the disproportionate size of the immunology effort at the institute; rather, I considered that size a strength. I must admit that I was troubled somewhat by the name of the department. I did not know what a department of clinical research was expected to do, but I did not confess this uncertainty to Charlie Edwards, president of the Scripps Clinic and Research Foundation, or to Frank Dixon, director of the research institute. I did not want them to regret having chosen someone who did not know what clinical research was to head the department, and perhaps to change their minds about offering me the opportunity to lead it. (I now feel emboldened to confess this early uncertainty because the National Institutes of Health recently convened a blue-ribbon committee charged with defining "clinical research." The committee encountered the same difficulty that troubled me 20 years ago.)
I certainly had no enthusiasm for a program that consisted essentially of setting up good clinical trials. Such trials are important and need to be done well, but this activity had never been among my main interests. Fortunately, I found that the department was engaged in bench research that was related, in some degree, to human disease. That characteristic was good enough for me, because that type of research is what I had always done.
During the next 2 decades, many changes occurred in our department and in its relationship to the clinic. In 1982, the Department of Biochemistry and the Department of Cellular Biology merged with our department and became divisions within a new department with the very flexible name the Department of Basic and Clinical Research. A division of experimental pathology was created, first under the leadership of Robert Nakamura and then under that of Frank Chisari. A small hemostasis program under the late Ted Zimmerman was augmented by the recruitment of Lawrence Harker and has flourished under the leadership of Zaverio Ruggeri, becoming the largest division in the department. An autoimmune center consisting of 2 divisions, clinical immunology and rheumatology research, was established by Eng Tan. A new arthritis division under Martin Lotz was created recently. Floyd Bloom brought his group from the Salk Institute to form a division of neuropharmacology, which has subsequently become an independent department. Peter Vogt brought us a distinguished program in oncovirology. Jim Koziol, who had been a consultant to our General Clinical Research Center, was recruited from the University of California, San Diego, and formed a division of biomathematics.
Accompanying these changes were changes in the size and location of the laboratories we occupy; the most major change occurred just this year. Our 1980 move from Coast Boulevard had translocated the department into the building that had been the entire home of the research institute when our present campus was built. As the department grew, however, it became necessary to accommodate our staff in other buildings, and by 1999 we had metastasized into 5 buildings. Our new building, constructed to our specifications for Lankford & Associates by Hensel & Phelps, has made it possible to bring our department together once again. As shown in this volume of reports, the original faculty of the department has grown from 10 to 48 members in the past 20 years. Most, but not all, of us are in the new facilities, and the additional space has made it possible to selectively add new faculty to the department for the first time in several years.
The success of a department in the research instituteshould not be measured by the number of faculty members, the size of the members' laboratories, their grant support, or even the number of scientists trained for the future, but rather by the contributions the members make to science. Because science is an incremental process, conveying what progress can be attributed to one laboratory or one department is often difficult, but some contributions stand out. The development of 2-chlorodeoxyadenosine in this department as a valuable therapeutic agent stands out. This drug, developed entirely at Scripps with virtually no industrial support, has been licensed for use in treatment of hairy cell leukemia, for which it is generally acknowledged as the treatment of choice, and is a valuable agent in the treatment of chronic lymphocytic leukemia, lymphoma, and multiple sclerosis. Other important original contributions include recognition that a decrease in intracellular pH is a necessary feature of apoptosis, the role of T cells in the response of humans to hepatitis, the discovery of potentially important new oncogenes, and the importance of shear stress in the mechanism of attachment of platelets to endothelium.
Academic medicine, it used to be said, was like a 3-legged stool. The legs were research, teaching, and clinical care. The "triple threat" academic physician performed all 3 tasks and did them well. In the past 2 decades, clinically competent and active physicians who also do laboratory research have become increasingly scarce. Clearly, we cannot depend on this model in the future as we did in the past. Increasingly, it is becoming necessary to depend on interactions between clinicians and basic scientists to advance research; in the future it will rarely be the same individual who performs the work at the laboratory bench who brings the results of that work to the bedside. At the same time that this trend has developed, the growth of managed care has made it increasingly difficult for clinicians to participate in a meaningful way in research projects. This problem confronts not only us at TSRI but the whole nation. We have been fortunate in obtaining encouragement and funding from the Skaggs Foundation to pursue an innovative approach to overcoming this difficulty.
The Skaggs Scholars in Clinical Science program provides an opportunity to bring together research-minded physicians and TSRI faculty to develop useful collaborations. Funding is provided for some of these collaborative research projects, including, if needed, salary support for the clinician. Because the program was initiated only in 1998, it is too early to tell how successful this approach will be. Clearly, however, if the coming millennium is to bear the type of scientific fruit that we have harvested in the 20th century, we must adapt to a new set of realities.
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