Presentation of the Julius M. Friedenwald Medal to Jerry S. Trier, M.D

GASTROENTEROLOGY 1999;116:1457–1460

AMERICAN GASTROENTEROLOGICAL ASSOCIATION Presentation of the Julius M. Friedenwald Medal to Jerry S. Trier, M.D.

Jerry S. Trier, M.D.

he Julius M. Friedenwald medal is the most prestigious award given to a member by our Association. Named for a distinguished Baltimore gastroenterologist and eighth AGA president, the Friedenwald medal is conferred in recognition of outstanding lifetime achievement in and contribution to the field of gastroenterology. Given the many distinguished contributions we shall review here, it is fitting that Jerry S. Trier, M.D., is our 1999 Friedenwald medalist.

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The Formative Years Born in Frankfurt, Germany, in 1933, the youngest child of Kurt and Alice Trier, Jerry spent his early childhood in Germany, where his parents were retail merchants before the family emigrated to the United States in 1938. Initially, the Trier family settled in Chicago, remaining there for 10 years during which time

Jerry received his elementary education at public school and then entered the University of Chicago Laboratory High School. Leaving Chicago in 1948, the family resettled in Seattle where Jerry completed the final 2 years of high school and subsequently enrolled in the undergraduate program at University of Washington. Shortly after entering medical school in Seattle in 1953, Jerry’s career in academic medicine began to take shape. On the verge of completion of the Human Genome Project, it is remarkable that less than 50 years ago, the ultrastructural anatomy of tissues remained largely unexplored. There was a pressing need for information regarding the organization of cells and their structural relationships within tissues. Clarification of molecular contributions to processes ranging from inflammation to digestion were in their early stages. Central to this line of inquiry was a need for clearer understanding of the

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microanatomy of tissues. The advent of the electron microscope permitted rapid progress, even though this major advance in imaging was exceedingly complex to use in the 1950s (and indeed early 1960s), because fixation, processing, sectioning, and other preparatory techniques were not yet defined. There was much meticulous science to be done to elucidate how subcellular elements that were visualized ultrastructurally related to the life of the cell. Amidst this excitement, Jerry met the late Dr. H. Stanley Bennett, then Chair of the Department of Anatomy at this young medical school. Bennett was a remarkable teacher and role model for Jerry and many other budding academicians. Working weekends, summers, and any spare moment, Jerry pushed on toward defining the ultrastructure of the parathyroid gland under Bennett’s wise tutelage. This remarkable preceptor allowed serious students such as Jerry to exercise wide latitude with design and execution of experiments and was always there to offer sage advice and constructive criticism. Despite his contributions to his students’ studies, Bennett selflessly refused to append his name to the resulting publications. The late Dr. Robert H. Williams, the Chair of Medicine at the time, was also an influential role model. Williams, like Bennett, combined the skills of scientist, educator, and administrator but was also a superb clinician, attributes on which Jerry has built a distinguished career. After obtaining his M.D. degree with high honors in 1957, Jerry served as an intern and resident at Strong Memorial Hospital in Rochester and then moved to the National Cancer Institute as a clinical associate, where his academic interest, the structure-functional relationships in the alimentary tract, emerged. With support of Dr. David Rall, head of the Clinical Pharmacology and Experimental Therapeutics Service at the National Cancer Institute, Jerry characterized the influence of methotrexate on the mucosa of the small intestine. The result was a clearer understanding of the partitioning of the proliferative compartment to the crypt, the ability of undifferentiated crypt cells to phagocytize dying neighbors (used today in evaluating graft-versus-host disease), and the influence of cytotoxic therapies on ultrastructurally defined surface area.

Gastroenterology as a Career In 1961 Jerry returned to University of Washington for Gastroenterology fellowship training with Dr. Cyrus Rubin. Probably more than any other, Cy’s group pioneered the concept that small pieces of mucosal tissue from the alimentary tract could be retrieved from patients through the use of long biopsy tubes and, using analyses of the anatomy of the mucosal surface, generated insights into the management and diagnosis of disease. Jerry flourished in this intellectual climate while honing his formidable clinical skills and publishing classic studies of the ultrastruc-

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tural anatomy of the mucosa of the small intestine. For example, our medalist provided convincing evidence of exocytic secretion by Paneth cells and undifferentiated crypt cells. He beautifully described the pathology and response to antibiotic therapy of the intestinal mucosa in patients with Whipple’s disease. Perhaps most fundamentally, Walt McDonald and Jerry explored the mechanisms of epithelial cell renewal along the axis of the gut—studies that linked his earlier work on methotrexate to later work detailing mucosal responses during ex vivo studies.

The Peripatetic Early Faculty Years In 1963 fresh from his fellowship, Jerry moved to the University of Wisconsin, where he took up the position as Chief of Gastroenterology at the V.A. Hospital. In Madison, he met another new faculty member, Robert M. Donaldson, Jr., who was recruited to direct the Clinical Research Center. These two future Friedenwald Medalists (Donaldson received the Friedenwald Medal in 1987) became colleagues and collaborators and ultimately developed a close lifelong friendship. Utilizing the new approach of cellular fractionation, Trier and Donaldson (in collaboration with Ian MacKenzie and William Kopp) demonstrated that cyanocobalamin–intrinsic factor complex bound selectively to the brush border of ileal enterocytes as a fundamental step in absorption of this essential nutrient. Pursuing his well-developed interest in intestinal epithelial renewal, Jerry and colleagues discovered megaloblastic and hypoproliferative states of the epithelium in patients deficient in cyanocobalamin (all patients had pernicious anemia) and those who had received abdominal irradiation. During this period, Jerry and collaborators also presented evidence that the Paneth cells lining the base of the crypts participated in regulated secretion. The nature of the secreted products has only slowly emerged, an elusive problem foreseen by Jerry Trier in his 1966 review entitled ‘‘The Paneth Cells: an Enigma.’’ In 1967 Jerry joined the University of New Mexico at Albuquerque as Associate Professor of Medicine and Anatomy and Director of the Gastroenterology Division. Although Jerry remained in New Mexico less than 2 years, he initiated studies of Barrett’s esophagus and epithelial renewal in celiac sprue that combined ultrastructural and other cell biological approaches with a powerful organ culture technique described below. Bob Donaldson, who had succeeded the late Franz J. Ingelfinger as director of the Gastroenterology Section at Boston University (BU) about the time Jerry moved to New Mexico, persuaded Jerry to join him at BU’s Department of Medicine as director of the Cell Biology Section. There, Jerry spent 4 extraordinarily productive years. Jerry also befriended one of the writers of this piece, then a fellow, and an era of amazingly collegial scholarship

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ensued. Building on the Ingelfinger tradition, Bob made BU into a gastroenterological powerhouse, with the help of such luminaries as Phil Kramer, Lauran Harris, Roger Lester, Don Small, and of course Jerry. As Jerry recounted in his panegyric to Bob Donaldson during the Friedenwald medal ceremony in 1987, 80% of the section’s fellows went on to academic positions. Several of Jerry’s most important contributions emerged also during this time, many utilizing organ culture for analysis of alimentary tract mucosal explants. This technique helped investigators examine crucial aspects of the biology of intestinal epithelial cells in vitro (mapping the proliferative compartment, determining the influence of disease states on epithelial kinetics, examining the influence of ‘‘toxins,’’ such as gliadin in celiac sprue, on epithelial cell biology, defining parameters of protein and mucin turnover in the epithelium, etc.). Our honoree’s influence extended beyond these substantive contributions to the primary literature. He published a multitude of chapters and reviews, for example contributing six chapters to the first edition of Sleisenger and Fordtran’s standard text, Gastrointestinal Disease ( Jerry has now written many chapters in all six editions).

A home at Peter Bent Brigham (Brigham and Women’s Hospital) In 1972, Dr. Eugene Braunwald moved to Boston from San Diego as Chairman of Medicine at Peter Bent Brigham Hospital (Brigham and Women’s Hospital since 1980). There he recruited a series of scholarly, energetic, and ambitious division chiefs and began to build what became one of the most remarkable departments of medicine in the country. Jerry Trier was recruited to lead the Division of Gastroenterology in 1973 and labored unremittingly to build a nationally prominent division noted for keen scholarship and scientific innovation. Forthwith, one of the writers of this piece joined Jerry’s division and a few years later the other followed as a research fellow in Jerry’s laboratory. The latter, a freshly minted pathology trainee, focused on gastrointestinal pathology and decided to pursue training in experimental gastrointestinal pathology. For this kind of work, the Trier laboratory was obviously the place to be—one only need examine the detailed, beautiful visual presentations and the insightful scientific papers emanating from Jerry’s group. By that time, the laboratory extended its line of inquiry to include analyses of fetal intestinal development and the interactions of viruses with the small intestine. For example, Trier and colleagues mapped the processes by which multilayered epithelium that lines the fetal intestine is remodeled into the crypt-villus structure characterizing adult mucosa. Other contributions from his laboratory outlined structure-function

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relationships of epithelial cell junctions, identified the M cell as the pathway of reovirus penetration of the epithelial barrier, and defined key aspects of M cell biology, such as the demonstration that they possessed the machinery necessary for antigen presentation as well as antigen transport. Strikingly, many molecular questions posed by today’s investigators rely on Jerry’s broad portraits of mucosal structure and biology. Jerry also focused significant effort on mentoring fellows and young faculty. This role has always been important to him. Both of the authors have benefited greatly from his encouragement and career counseling. Many of his trainees have evolved their own successful academic careers including some who now serve as deans or department chairs. Several others who did not directly train with Jerry have greatly benefited from his wise counsel, and our field has benefited from his leadership. Perhaps one of the reasons he impacted so greatly on others was his internal compass that always pointed the way to scholarship, impeccable honesty, and personal integrity—the seeming guiding principles of the man. Indeed it is these traits that those of us close to him so admire. Although Jerry excelled at the bench his entire career, he displayed equal adeptness in all phases of his professional life. From the perspective of a faculty member (M.C.C.), Jerry was an ideal chief, one who offered continuous intellectual support and encouragement but also who knew the benefits of protecting young faculty members from the more pragmatic interferences that plague many academic settings. Jerry led the Division at Brigham and Women’s until 1987, and in 1997 became Professor Emeritus at Harvard University. Renowned as an astute clinician, Jerry is the physician most often looked to at clinical conferences and on rounds for clear guidance on how to treat patients with particularly puzzling or difficult-totreat alimentary disorders. His teaching skills are so refined and his thoughts so well organized that it seems possible to merely transcribe his spoken words as gospel. In 1997, the Gastroenterology Fellows at Brigham and Women’s Hospital established the Annual Award for Excellence in Teaching in Jerry Trier’s honor. This award is given to a faculty member by the fellows on completion of their clinical training, and represents proof of Jerry’s commitment to clinical education. In a note to the present coauthors, Jerry emphasized that the establishment of this award was something that made him particularly proud. Aside from these skills, Jerry is also a top drawer gastrointestinal pathologist; his clinical contributions to the field of Gastrointestinal Pathology (Barrett’s esophagus, celiac sprue, Whipple’s disease) are well recognized.

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Table 1. Selected National Activities Chairman, Steering Committee, Gastroenterology Research Group Chairman, VA Gastroenterology and Nutrition Merit Review Committee Member, General Medicine A Study Section, NIH Member, Human Resources and Research Review Group, NIDDK, NIH Member, Advisory Council, NIDDK Member, Subspecialty Board on Gastroenterology, ABIM Vice-Chairman, Research Report Update Committee, National Digestive Diseases Advisory Board Editorial Boards American Journal of Medicine Anatomical Record Current Opinion in Gastroenterology

Contributions to National Organizations Jerry Trier’s contributions to the science, practice, and pedagogy of gastroenterology are remarkable, but Jerry is equally adept at leadership and administration of many national organizations. Table 1 outlines selected national activities of Jerry’s including service on National Institutes of Health (NIH) Review Groups and the Advisory Council of National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Our organization, the American Gastroenterological Association, was also well served by Jerry Trier. As summarized in Table 2, Jerry has served in one or another editorial capacity for our journal, Gastroenterology, for 25 years. Not only did he give of his precious time to chair committees of our organization but he also was our President in 1985. The first major fundraising drive among the AGA membership, named ‘‘A Case for Research,’’ was initiated by Jerry in 1988. The success of this early effort is not judged in monies raised but in that it contributed to the establishment of the American Digestive Health Foundation.

The Man Approximately 2 years before his decision to become Emeritus, one of the writers ( J.L.M.) remembers being called to Jerry’s office where he spoke of his Table 2. Highlights of Service to the AGA Gastroenterology Editorial Board 1967–1970, 1978–1983, 1993–1998 Chairman, Editorial Board 1988–1993 Associate Editor 1970–1977 Editor, AGA News 1983–1985 Training and Education Committee 1968–1972, Chairman 1979– 1982 Publications Committee 1988–1993 Vice President 1983 President-Elect 1984 President 1985 Councilor 1986 and 1987

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intention to close his laboratory and concentrate on one of his other lifetime professional loves: mentoring students, housestaff, and fellows in his distinctive ‘‘bench-tobedside’’ style. This writer was shocked at first, because Jerry had done so much during his time in the laboratory. Even though he still had some years remaining on his NIH Merit Award, Jerry’s reasoning in making this decision displayed the mixture of cool logic and altruism that so characterizes him. This was a time of severely limited NIH moneys, and Jerry simply concluded that his technical skills had become dated and would no longer prepare trainees for a lifetime career in research. As a result, he found continued funding of his laboratory difficult to justify. As was often the case, his concerns focused on what was best for trainees, young faculty, and our discipline of gastroenterology. Although still very active in teaching, attending, and counseling roles, his Emeritus position now offers him an opportunity to spend more time with his wife Laurel and his children. Knowing Laurel’s good judgment and ability to assess the temperament and character of individuals she meets, we suspect that Jerry has had his own counselor all these years, whom he has likely put to good use. Jerry and Laurel also have the good fortune of sharing interests in hiking (they are particularly fond of mountain terrain) and birding. They have three grown children with whom they remain very close: Stanley, an atmospheric scientist engaged in full-time research; Jeryl, a high school mathematics teacher; and Stephen, an electrical engineer. This brief sketch of Jerry Trier defines the values and attributes that merit the highest award of our organization. In so honoring him, we as an association renew our pledge to keep those values which he so richly exhibits— scholarship, industry, and integrity—as guiding principles of our own organization. Jerry, we are delighted to join our colleagues in acknowledging and honoring your lifetime achievement in gastroenterology. JAMES L. MADARA, M.D. Department of Pathology and Laboratory Medicine Emory University School of Medicine Atlanta, Georgia MARTIN C. CAREY, M.D., D.Sc. Department of Medicine Harvard Medical School and Digestive Diseases Center Division of Gastroenterology Brigham and Women’s Hospital Boston, Massachusetts Address requests for reprints to: James L. Madara, M.D., Department of Pathology and Laboratory Medicine, Emory University Hospital, H-184, 1364 Clifton Road, Northeast, Atlanta, Georgia 30322. Fax: (404) 727-3133. r 1999 by the American Gastroenterological Association 0016-5085/99/$10.00