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JACOB FURTH 169 EARLY YEARS IN RESEARCH, 1918-32 Jacob had an inquiring mind and a love of learning that attracted him to research, even while a medical student. Under the guidance of Edmund Weil, one of several great scientists who, he acknowledged, had an important influence on his career, Jacob began research in microbiology and immunology, directed to whether bacterial species could be characterized antigenically. This work required keeping open plates for one or two weeks in search of mutants, and these were subject to fungal contamination. In his autobiographical essay,1 Jacob wryly confessed his chagrin at his presumption that the "damned fungi were preventing growth of the bacteria by depriving them of essential nutrients. The possibility that the fungi secreted a bactericidal substance did not cross my mind." He also regretted that he did not write up or follow up on work he started at that time on bacteriophage, just discovered by D'Herelle, recalling the statement by his dean and department chairman Oscar Bail that "this may be the greatest discovery of our period." However, a lasting contribution of the period was Jacob's introduction of the agar plate, which has now become standard practice in microbiology. A turning point in Jacob's career was the sudden death of his mentor, Edmund Weil, and his senior associate, F. Breinl, from typhus, and his own illness and recovery from the same disease. Facing the dilemma of whether to choose a career in clinical research or stay in the laboratory, and weighing his future in postwar Europe, Jacob accepted an offer from Eugene L. Opie of the Henry Phipps Institute of the University of Pennsylvania in Philadelphia. He remained there for two productive years, 1924-26, working on acid-fast organisms and their antigens. Jacob acknowledged with gratitude (naming one of his
JACOB FURTH 170 twin sons Eugene) the profound influence of Opie and an outstanding group of young scientists on his career. During his two years at the Phipps Institute he established immunologic relationships among acid-fast organisms, the antigenicity of microbial lipids, and at the suggestion of Opie he confirmed the observation of Zinnser that new antigens could be created by heat. This last work caught the interest of Karl Landsteiner, the discoverer of the blood groups, who invited Jacob to the Rockefeller Institute as his assistant. His two years there, from 1926 to 1928, were a profound learning experience. From Landsteiner and daily contact with other great scholars at the institute, Jacob learned both the philosophy and strategies of research. It was at the institute that he was introduced to the cancer problem by the brilliant work of Peyton Rous, James Murphy, and especially Alexis Carrel, through whom he was introduced to tissue culture, a tool he used continuously in his future work. With Landsteiner he attempted to transform saprophytic vibrios to cholera vibrios and to transform Drosophila strains. They chose the wrong organism. It was Avery who several years later successfully transformed pneumococcal strains, thereby revealing the hereditary role of DNA! Under Landsteiner's instruction Jacob demonstrated differences in the blood groups among the anthropoid apes, and Landsteiner asked him to stay on to take on Philip Levine's work on minor blood subgroups. Restless to do independent work, however, Jacob accepted an offer in 1928 from Opie to return to the Phipps Institute in Philadelphia. A return to this institution was not without some regret. In his autobiographical essay1 he points out ruefully, ''Now that Philip Levine has attained greatness by the discovery of the Rh factor . . . I see what I have missed."
JACOB FURTH 171 Opie had accepted a generous grant from E. Mallinkrodt, Jr., for experimental work on leukemia and placed Jacob in charge. It was here that Jacob began a long, wide-ranging, and uniquely productive study on leukemia, for which he received widespread recognition. He frequently expressed his gratitude to Mr. Mallinkrodt, who required no reports and even kept his support anonymous until 1957, when he relented on Opie's urging. Jacob took two independent approaches simultaneously. One was to obtain leukemic mouse strains. He succeeded by inbreeding mice in which leukemia occurred spontaneously or was induced by radiation. One strain, the AKR mouse, carries a leukemia virus and has become one of the most common and widely used animals in many diverse experimental studies. The second approach was to attempt to isolate viruses from the various types of leukosis then available. Five leukosis viruses were isolated and studied, one of which was the fowl neurolymphomatosis virus, the agent of Marek's disease, an economic scourge of the poultry industry until its conquest by a vaccine in 1970. Other notable findings of this period were the transmission of avian leukosis by blood-sucking insects, the occurrence of high concentrations of leukemia virus in the serum of leukemic chickens, and the viral nature of the common venereal sarcoma of dogs, transmitted through copulation. It was in Philadelphia that Jacob's twin sons were born. He somehow found time to be a good father. Both sons emulated him and became physicians. One is now in North Carolina, the chairman of the Department of Medicine at East Carolina Medical School, and the other, a coauthor of this memoir, is a professor of pathology at the University of Pennsylvania in Philadelphia.