Herman Eisen (1918–2014) Immunologist and Educator Who Discovered Fundamentals of Antibody Binding
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COMMENT OBITUARY Herman Eisen (1918–2014) Immunologist and educator who discovered fundamentals of antibody binding. erman Eisen made fundamental an ultrasensitive method to measure the contributions to our understand- strength of binding — the binding con- ing of how the body’s immune stant, or affinity — of antibodies for Hsystem recognizes foreign structures. chemical entities such as dinitrophenol. In an almost 70-year career, he showed He showed that binding becomes stronger OF MIT COURTESY how antibodies bind to antigens (surface the more time has elapsed since the first molecules on viruses and bacteria) and exposure to an antigen, because cells pro- measured how and why such binding ducing more tightly binding antibodies are strengthens, a concept that now domi- preferentially stimulated as the amount of nates the field of vaccine design. antigen diminishes. After repeated expo- Eisen died in Cambridge, Massa- sure to the same antigen (‘booster’ immu- chusetts, on 2 November. He was born nization) the tightly binding antibodies are in 1918 into the Jewish community of synthesized without delay. Brooklyn, New York, one of four chil- In 1973, he was recruited as a founding dren, to parents who had emigrated from member to the newly established Center Eastern Europe. “I grew up with a sense for Cancer Research (now the Koch Insti- that anti-Semitism in the world around tute for Integrative Cancer Research) at us was pervasive, regarded as a fact of the Massachusetts Institute of Technol- life, like birth and death,” he later wrote. ogy in Cambridge. His research inter- At age 16, he was interested in chemistry ests broadened to include recognition but enrolled as a premedical student at by receptors for antigens on blood cells New York University (NYU), persuaded known as T lymphocytes. He contributed by his father that “large companies in the to the discovery and characterization of chemicals industry did not hire Jews. In the elusive T-cell receptor, and provided medicine, however, a somewhat related field, US$3,600 per year, freeing him to do full- experimental and conceptual tools to show one’s destiny was in one’s own hands.” time research and to marry Natalie Aronson, the extraordinary sensitivity of ‘killer’ T lym- While recuperating from tuberculo- a paediatrician, and start what became a phocytes, capable of responding to the pres- sis during his university years, Eisen was family of five children. Working in the bio- ence of even a single antigen molecule as a deeply affected by two works: Sinclair Lewis’s chemistry department at NYU, Eisen, with means of eradicating a virus-infected cell. Arrowsmith (1925) and Charles Darwin’s On Fred Karush, showed that antibodies typi- At his house near Woods Hole, Massachu- the Origin of Species (1859). He was inspired cally possess two active sites that can bind setts, Eisen indulged his passion for garden- by a seminar in which he learnt that moving antigens. This permits the formation of ing, enjoying the biology and the aesthetics of a hydroxyl group on a benzene substituent aggregates that are eliminated from the body. what he nurtured. The author of an influential from one carbon atom to another dramati- However, if such complexes lodge in joints or textbook, General Immunology (1990), Eisen cally changed the compound’s effect on a cat’s in the kidney, they can cause disease. was a sought-after mentor for students, post- blood pressure. It revealed to him the connec- Next, Eisen moved to NYU’s department doctoral fellows and sabbatical visitors. tion between molecular structure and bio- of industrial medicine to explore allergic With his unwavering curiosity and com- logical function. As a resident in pathology at skin reactions to dinitrobenzenes. Working mitment to research, he was always available Columbia University in New York from 1944 on his own skin and that of guinea pigs, he to discuss science, scheduling lunch dates to 1946, Eisen was introduced to immunol- discovered that only those chemicals that are to catch up with research areas in which he ogy in the laboratory of Michael Heidelberger, capable of forming covalent bonds to skin was interested but not necessarily active. whose work had enabled the first demonstra- proteins cause the characteristic itchy rash. Herman Eisen remained at the frontier of tion that antibodies were proteins. These studies led to his appointment in 1955 immunology: he was working on a manu- During his time as a medical resident at as professor of dermatology at Washington script and e-mailing coworkers the day that Bellevue Hospital Center, NYU’s main teach- University in St. Louis, Missouri; he became he collapsed en route to the gym, aged 96. ■ ing hospital, Eisen worked as a ship’s surgeon chair of microbiology there in 1961. on a voyage to South America. Between min- Eisen was one of the handful of like- Lisa Steiner is professor of biology at the istering to crewmen with minor injuries or minded pioneers intent on understanding Massachusetts Institute of Technology syphilis, Eisen read Karl Landsteiner’s superb immune recognition who met periodically (MIT) in Cambridge, Massachusetts, USA. 1936 summary of what was then known in a series of ‘antibody workshops’. These She worked under Herman Eisen as a about immunology, The Specificity of Sero- advanced the problem of antibody diver- postdoctoral researcher between 1962 and logical Reactions. The monograph argued for sity — how the body raises defences against 1965, and they were friends for more than molecular complementarity as the basis for different invaders — much as the RNA 50 years. Hidde Ploegh is professor of biology antigen recognition, a concept that inspired Tie Club, founded by James Watson and at MIT, and worked with Eisen at the MIT much of Herman’s later work. George Gamow, coalesced the pioneers of Center for Cancer Research from 1992. In 1948, Eisen received a senior National molecular biology. emails: [email protected]; Institutes of Health fellowship grant of At Washington University, Eisen developed [email protected] 38 | NATURE | VOL 516 | 4 DECEMBER 2014 © 2014 Macmillan Publishers Limited. All rights reserved.