Zanvil A. Cohn

Ralph M. Steinman was awarded the Nobel Prize in Physiology or Medicine on October 3, 2011, only three days after his death. After his October 10 memorial service, the Steinman and Cohn families agreed to the establishment of a Zanvil A. Cohn-Ralph M. Steinman Professorship. Explaining why the two scientists merited this recognition, Rockefeller University noted that "Their intertwined scientific legacy is enormous, and their work in the Laboratory of Cellular Physiology and Immunology constitutes one of the most important scientific-cultural threads in the history of immunology – and of the University." The professorship was funded by $500,000 from the Steinman family and $2.6 million from 129 other donors, with the Steinman family's portion coming out of Steinman's Nobel Prize money. "It was Dr. Steinman's wish during his life," Rockefeller University pointed out, "to honor his mentor and collaborator, Zanvil A. Cohn, with whom he discovered dendritic cells and made scientific discoveries that transformed the field of immunology."

In a 2009 biographical memoir, Carol L. Moberg and Steinman wrote that "Zanvil Cohn may be most remembered as the founder of modern macrophage biology and for leading the shift in mid-twentieth-century research from bacterial cells to host-parasite relationships."

Cohn was appointed Rockefeller University's vice president for medical affairs by President Torsten Wiesel in 1992. During the last seven years of his life, Cohn was also the Henry G. Kunkel Professor at the university. In addition, he held the title of senior physician at Rockefeller University Hospital. For a long period, ending only two years before his death, moreover, he was principal investigator at the Irvington Institute for Medical Research.

In 1989 he paid tribute to Dubos on the 50th anniversary of Dubos's discovery of the antibiotic gramicidin by organizing a symposium on "Launching the Antibiotic Era." At the event, he spoke of the importance of "supporting young investigators and global research, the opportunities afforded single investigators working in small laboratories, the efficacy of personal involvement at the bedside, and a moral climate that led to patents for the general good."

No one in Cohn's family had a medical or academic background. Moberg and Steinman say that he was motivated by Paul de Kruif's book Microbe Hunters and by Sinclair Lewis's novel Arrowsmith, as well as by his experiences with penicillin on the Liberty ships, to become a doctor and medical researcher. They also suggest that his interest in medicine, and particularly in the study of infectious diseases, might be traced back to a childhood "brush with death from scarlet fever that quarantined the whole family" and/or to his experiences with "the caring family physician who looked after his father, bedridden nearly a year following a severe bout of pneumonia." (Cohn's father died at 57 while Cohn was in high school.) A 1983 profile of Cohn indicated that "While he was still in medical school, his interest in research had been spurred by a series of technological advances that were dramatically expanding the scope of cell biology. His interest in Rockefeller stemmed from the fact that many of the advances, in electron microscopy, cell fractionation, and immunology, were happening there."

Moberg and Steinman describe the situation in the Dubos Laboratory of Bacteriology and Pathology, as follows: "Dubos fostered investigators, not mere problem solvers, thus allowing newcomers independence to plan experiments and progress at their own pace. As [Cohn] said in a 1983 interview, Dubos had a habit of talking to newcomers 'for the first two days, and if he thought they could get along on their own he would not talk to them again for another year. I was terribly upset, I must say.'" Cohn worked at Rockefeller for the next 35 years, "most of them on the fourth floor of Bronk Laboratory."

"Dr. Cohn's experiments," reported the Times in his obituary, "threw light on the functions of T-cells, made in the bone marrow, and macrophages, large cells that can surround and digest foreign substances like protozoa and bacteria. He applied these insights to patient-oriented investigations of leprosy, tuberculosis and AIDS. He also established that macrophages can release a multitude of biologically active products. Since the mid-1980s he used hormone-like products of the immune system to increase patients' resistance to microbial infections. This work took him to parts of Asia and Latin America where leprosy and tuberculosis are endemic."

In the early 1980s, wanting to discover "why in certain diseases the macrophages, after ingesting pathogens, not only fail to kill them but instead provide a hospitable environment for them to thrive, multiply, and reactivate disease," and thus develop therapies, Cohn and other members of his team began visiting hospitals in Brazil, and later in Colombia, Ethiopia, India, Nepal, and the Philippines, to study patients with leprosy and various other diseases, including tuberculosis and AIDS. "For some reason," Cohn said in a 1983 interview, "no one had ever really looked very hard at the local skin lesions of leprosy patients. Diagnosis has usually been based on analysis of cells in the blood stream. So when we first went to Brazil, we decided that we would examine the cells in the skin. In the virulent lepromatous lesions we found bacteria-filled macrophages together with a large number of suppressor T cells. As we studied patients in the intermediate stages of the disease and on to the tuberculoid form, we found that the number of so-called helper cells began to increase relative to the number of suppressor T cells."

In 1977, Cohn was one of nine Rockefeller University professors to visit the People's Republic of China as part of one of the earliest U.S.-China cooperate ventures in science and culture following the death of Mao and the end of the Cultural Revolution. In 1988 he spent a sabbatical at the Dunn School at Oxford University.

Cohn was elected to the National Academy of Sciences in 1975, was appointed to Rockefeller's first Henry G. Kunkel Professorship in 1986, and received honorary degrees from Bates College (1987), Oxford University (1988), and Rijksuniversiteit in Leiden (1990).

In 1972, Cohn, along with Hirsch and Alexander Gordon Bearn, organized at Cornell University Medical College "one of the first medical scientist training programs for the combined M.D.-Ph.D. degree." Cohn also "fostered interactions of young people with physicians at Rockefeller, Weill Cornell Medical College, and Memorial Sloan-Kettering Cancer Center, the three biomedical research and educational institutions across the street from one another," establishing "the Tri-Institutional Biomedical Forum, an informal sherry-and-lecture series reminiscent of his happy 1988 sabbatical at the Dunn School in Oxford, where young scientists could get to know their counterparts at these three institutions." He also brought new life to the Clinical Scholars program, which trained new doctors "to care for patients on a daily basis while conducting bench research to better understand their diseases."

Ralph Steinman joined the Cohn-Hirsch laboratory in 1970, and eventually it became the Cohn-Steinman laboratory. In 1973, in the course of studying macrophages, Steinman and Cohn discovered "an entirely distinct class of immune cells" which differed "in structure, appearance, and function from macrophages" and which would come to be recognized as "powerful initiators of the immune response and major controllers of both innate and adaptive immunity." As one source puts it, this cell, which Steinman named the dendritic cell, would later be found "to be the sentinel cells of the immune system."

Looking into the genesis of macrophages, Cohn and his colleague Ralph van Furth "used a radiolabeled isotope to label blood monocytes and trace their production and development. They identified the blood monocyte as the precursor for tissue macrophages and the bone marrow as the source of monocytes." At the same time, electron microscope studies he performed with Hirsch and Martha Fedorko provided further insight into macrophage formation and differentiation. This work, according to Moberg and Steinman, "illuminated a pivotal pathway to host defense and captivated the minds and spirits of innumerable scientists," resulting in five international conferences on mononuclear phagocytes held at Leiden between 1969 and 1991.

In 1966 Cohn was made full professor at Rockefeller, which had just changed its name from the Rockefeller Institute for Medical Research to the Rockefeller University, and, with Hirsch, formed a Laboratory of Cellular Physiology and Immunology. There they explored macrophages, about which little was known. Cohn's "adroit tissue culturing of macrophages made it possible to observe, challenge, and manipulate them to figure out how they worked." He showed how "the cell's outer membrane folds around the captured material, forms a sac or vacuole that is pinched off from the cell surface and enclosed within the cell, and fuses with the lysosome where the contents are then digested." The result, as Moberg and Steinman put it, was the transformation of endocytosis into "a central field of cell biology, because it is pertinent to all cells for extracting from their surrounding environment the nutrients needed for survival as well as for capturing and destroying toxins and pathogens." A Rockefeller University source puts it this way: "Cohn's discoveries on endocytosis in macrophages have proved fundamental to cell biology, since endocytosis is a process universal to all cells, and is the mechanism by which cells digest materials from their surroundings, ranging from microbes to proteins carrying nutrients."

A number of films were made to illustrate the processes Cohn studied, including Phagocytosis and Degranulation (with Hirsch, 1962) and Pinocytosis and Granule Formation in Macrophages (1967). The Journal of Experimental Medicine later noted that Hirsch and Cohn's "elegant films of live phagocytes...remain an ideal component for many courses in biology."

In October 1957 Cohn was appointed assistant physician and research associate at the Rockefeller Hospital and what was then called the Rockefeller Institute for Medical Research (later Rockefeller University) in New York, where he worked in the laboratory of René Dubos, whose 1954 monograph Biochemical Determinants of Microbial Diseases he considered "visionary and provocative" and "always kept within reach." Dubos's studies in microbiology had played a key role in the development of antibiotics. Yet there was little understanding of how these "wonder drugs" worked. Cohn's first project in Dubos' lab, which he conducted with Steven Morse, was to confirm that it is polymorph leukocytes that kill the bacteria that cause staph infections.

Returning to Bates after the war, Cohn met Fern Dworkin in 1946 in an organic chemistry class. After graduating in June 1948, they married in December of the same year. Unable to gain entrance into Harvard Medical School, he entered Harvard's graduate program in bacteriology in the Department of Microbiology, where he did so well that he was able to enter Harvard Medical School a year later. It was while he was a medical student there that he published his first scientific paper, based on work begun in the Department of Microbiology. He received his M.D. degree in 1953 and was one of an extremely small number of students in that medical school's history to be awarded an M.D. summa cum laude. His thesis concerned host-parasite relationships, which would be the focus of his career.

During World War II, Cohn joined the U.S. Merchant Marine, became a hospital corpsman, and served from 1944 to 1946 "as purser-pharmacist on Liberty ships in the Atlantic and Pacific," where he was sometimes "the only medically trained person among the ship's crew and 1,500 soldiers, with responsibility for preventing epidemics, administering vaccines and antibiotics, and treating wounds."

Zanvil Alexander Cohn (November 16, 1926 – June 28, 1993) was a cell biologist and immunologist who upon his death was described by The New York Times as being "in the forefront of current studies of the body's defenses against infection.", professor at Rockefeller University. There Cohn had been the Henry G. Kunkel Professor for seven years. Cohn was senior physician at the university as well as vice president for medical affairs. Until two years before his death, he also served as principal investigator of the Irvington Institute for Medical Research. Although Cohn never won the Nobel Prize, Ralph M. Steinman, with whom he ran a laboratory at Rockefeller University for many years, was named to win the 2011 Nobel Prize in Physiology or Medicine for the work on dendritic cells done in their lab, eighteen years after Cohn's death.

By way of explaining Cohn's importance, one commentator has noted that macrophages "are scavenger cells of the immune system that engulf and digest invaders, including bacteria and other pathogens, as well as toxins and dead cells. They are central to so-called innate immunity—immune defenses that can act without previous exposure to a pathogen. They are central to inflammation, the responses of the body to infection and injury, and also when inflammation becomes chronic during diseases like atherosclerosis and tuberculosis. When Zanvil Cohn (1926-1993) began studying macrophages in the early 1960s, little was known about them. Immunologists had for decades focused on the chemistry of the second major component of the immune system—the acquired immune response, in which the body produces antibodies in response to exposure to an antigen. In pioneering studies, both at the laboratory bench and with human subjects, Cohn helped launch the new field of cellular immunology."

Cohn was born in New York City, the son of David and Esther (Schwartz) Cohn; he had one sibling, a brother, Donald, who was three years younger. Zanvil, a Yiddish version of Samuel, was a family name. His father had come to New York from Düsseldorf at age 19 in 1905 and after working for some years in his uncle Josef's butcher shop in Manhattan became an owner of Kansas Packing, a meat packing firm in New York. Cohn's mother, born in the United States of parents from Budapest, was raised in Huntington, Long Island, and worked as a buyer for Oppenheim, Collins & Co., a Manhattan clothing store, later becoming a partner in an apparel firm. As a child, Cohn spoke both German and English. He attended public schools in Queens, then Columbia Grammar School in Manhattan, where he played baseball and football, was president of the student government, and played piano at graduation. After graduating from Columbia Grammar at 16, Cohn attended Bates College in Maine, where he majored in biology. He was the first member of his family to attend college.

characteristics and the predominant T-cell phenotypes. N. Engl. J. Med. 307:1593-1597.