DR. EARL PHILIP BENDITT, Professor Emeritus in the Department of Pathology at the University of Washington School of Medicine, died on May 27, 1996 at the age of 80.
Earl had long been acknowledged as a preeminent experimental pathologist of the twentieth century. His working career, spanning some 50 years, was characterized by two notable features: a chemical quantitative approach and a fantastic ability to recruit capable acolytes to advance his quest for answers to a wide range of pathological problems, most particularly inflammation, atherosclerosis, and amyloidosis.
Earl's career had deep roots in histochemistry. Indeed, it is a continuous thread that can be traced through Earl's opus. Early in his distinguished scientific career, Earl had three noteworthy publications in Volume 1 (1953) of the Journal of Histochemistry and Cytochemistry: a paper with George Gomori on the precipitation of calcium phosphate in the histochemical method for phosphatase localization (-chymotrypsin. Later studies established that the mast cell enzyme was a protease, and the enzyme and a second mast cell protease were christened chymase and tryptase. In another seminal paper in 1970 (
Earl's career as an experimental pathologist began at the University of Chicago as a member of Paul Cannon's group, working on deficiencies of essential amino acids. Not all the connections in Earl's work are obvious, and by no means did all of his inventive hypotheses yield scientific gold. There was, however, a connection between his work on serotonin in mast cells and then in chromaffin cells and that on one of his highly productive scientific forays, amyloid. His work on serotonin interested him in the possibility that some pathological deposits might arise by a process akin to the tanning reaction responsible for the hardening of insect cuticle. George Martin worked for a while on possible oxidizing enzymes that might participate. The histochemical observation that amyloid was relatively rich in tryptophan fitted in a general way with the hypothesis. The death and autopsy of a patient with ulcerative colitis and enough amyloid in her organs for several years of work led to the isolation of amyloid A protein and all that followed. In the early experiments, Adams' method for staining tryptophan residues was used as the most convenient marker to follow the extraction process. Needless to say, amyloid turned out to have nothing whatsoever to do with tanning.
There may be other versions of the story of how Earl came to study atherosclerosis, but one creditable possibility is that it had its origins in the early stages of devising a grant renewal strategy. Earl had brought with him to the University of Washington an NIH grant entitled "Vascular Response To Injury"; it supported his extended laboratory throughout his 24-year term as Chairman of Pathology and beyond. Ed Smuckler working on liver cell injury, Russ Ross on wound healing, David Lagunoff on mast cells, and George Martin on serum oxidases all benefited from the largess of the grant. When it came time for a renewal application, Earl decided that a unifying theme justifying the grant title was in order. He fixed on the study of the proliferative response of endothelium to injury. Not much on this theme was done in the first years after the grant was funded. Then, following up on Stan Gartler and David Linder's brilliant demonstration of the monoclonality of uterine leiomyomas, Earl proposed to use the approach to test his hypothesis that the plaques of atherosclerosis were like benign tumors. He used vessels from African-American women who were heterozygous for glucose-6-phosphate dehydrogenase. It was not a simple study, either technically or interpretively, and Earl did much of the initial work by himself, spending hours dissecting out individual plaques in the cold room in an arctic parka. John, his eldest son, helped him and was a co-author of the seminal paper in the Proceedings of the National Academy of Science (
Writing in an editorial in 1971 (
Earl presided over the Department of Pathology at the University of Washington from 1957 until he relinquished the Chair in 1981. The department was by no means committed exclusively to his own research and that of his students. Buster Alvord, Rich Prehn, Bernie Wagner, Karle Mottet, Victor Gould, Ben Trump, Gary Striker and their programs prospered in the academic environment Earl created. The department spawned some seven chairs of pathology during Earl's tenure as chair, including Russell Ross, Earl's successor. The continuingly vital Department of Pathology at the University of Washington, which he created, developed, challenged, and inspired is a true legacy of Earl's. Over his scientific career, Earl received accolades that are too numerous to list, but the highlights certainly include membership in the National Academy of Sciences and the Rous-Whipple and Gold Headed Cane Awards from the American Association of Pathologists. Earl is survived by his wife, Marcella, and his four sons, John, Alan, Joshua, and Charles.
On a final personal note, both of us feel a deep sense of loss with Earl's death. Throughout our careers he never ceased to be both supportive and challenging. His memory and his standards for experimental science will stay with us, as it surely will with the many pathologists, histochemists, and other scientists who benefited from his work and from working with him.
David Lagunoff and Allen M. Gown
Literature Cited
Benditt EP (1971) Pathology and the future. Hum Pathol 2:337-339 [Medline]
Benditt EP, Benditt JM (1973) Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Natl Acad Sci USA 70:1753-1756 [Medline]
Benditt EP, Eriksen N, Berglund C (1970) Congo red dichroism with dispersed amyloid fibrils, an extrinsic cotton effect. Proc Natl Acad Sci USA 66:1044-1051 [Medline]
French JE, Benditt EP (1953a) Histochemistry of connective tissue: I. The use of enzymes as specific histochemical reagents. J Histochem Cytochem 1:315-320
French JE, Benditt EP (1953b) The histochemistry of connective tissue: II. The effect of proteins on the selective staining of mucopolysaccharides by basic dyes. J Histochem Cytochem 1:321-325
Gomori G, Benditt EP (1953) Precipitation of calcium phosphate in the histochemical method for phosphatase. J Histochem Cytochem 1:114-122