Gerald Maurice Edelman
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RETROSPECTIVE Gerald Maurice Edelman Richard A. Lerner1 words were written over half a century ago. Department of Molecular and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037 Even Pauling appeared intrigued. After one of Edelman’s early presentations of his work, Professor Gerald Maurice Edelman died in became a house officer at the Massachusetts Pauling approached the podium. He passed a cryptic note that said “Edelman—send La Jolla, California, on May 17, 2014, at the age General Hospital. He then served as a Cap- ” of 84. His wife, Maxine Morrison Edelman, tain in the US Army Medical Corps at the reprints. Although the 1959 experiment and those and three children, Judith, Eric, and David, American Hospital in Paris. (Leave it to that followed did not solve the generation of survive him. We, of course, remember him Gerry to get stationed in Paris.) In 1957, diversity (GOD) problem, they did provide for his brilliant scientific career. However, I Edelman was accepted as a graduate student the chemical parameters of the antibody have received many comments from people at Rockefeller Institute, and he received his molecule that gene action had to explain. who, upon hearing of his death, remarked PhD in physical chemistry in 1960. This pointed the way to the solution of the alonglinessimilartothese:“It’stheendofan Because of his clinical background and ” “ ’ chemical training, Edelman not only recog- GOD problem. This solution came from the era ; They don tmakethemlikethisany- work of Susumu Tonegawa and other geneti- ” “ ” nized an interesting medical question, but more ; We shall not soon see another ;and cists, who determined in the 1970s that the “ ” was also in a position to solve the problem. The world is more empty now. genetic basis for generation of antibody di- In his teens, Edelman was conflicted as to Hisinsightsledhimtoasimpleexperiment that changed the course of immunology and versity relied on a combinatorial mechanism whether he should become a professional that uses somatic recombination between a ultimately resulted in his sharing the 1972 violinist or pursue medicine. As happens so rather limited set of germ-line genes to encode Nobel Prize with Rodney Robert Porter for often with mothers, his stepped in and with about 108 different antibody molecules. their work on the structure of the antibody the turn of a phrase decided his fate. She told Later, Edelman turned his attention to molecule. There are, of course, two main him that a performing musician was not a developmental biology, particularly to the components to an acquired immune reaction: proper career and was more “like juggling.” study of cell adhesion molecules (CAMs) the antibody and the antigen. In the early Gerry replied that it certainly wasn’t juggling, and then to the study of the brain, with 1950s, the nature of the antibody molecule to which his mother countered “Ihavetwo particular emphasis on consciousness. The was considered to be opaque, and thus words for you—Jascha Heifetz!” hallmark of his chemical and biochemical research focused on the nature of the antigen. After receiving his MD degree from the studies had been their “surgical strike” na- Experimentsonlargeantigenssuchaspro- University of Pennsylvania in 1954, he ture: a methodology that does not easily teins were carried out in the same way as the lend itself to the study of consciousness. earlier experiments of Landsteiner on small Thus, he presented his ideas in a series organic molecules such as substituted aro- of five books wherein he proposed a gen- matic systems. Only in this case, enzymatic eral theory of brain function. Their titles, proteolysis rather than organic synthesis was such as Neural Darwinism and Bright Air, the main tool. Brilliant Fire: On the Matter of the Mind Oneprevailingtheoryofantibodyinduc- are classic Edelman. tion was Linus Pauling’s instructional theory. Edelman was famous for his jokes that This suggested that the antigen acted as a opened every lecture. However, they are template around which the antibody folded, not jokes in the standard sense. Each one and thus the antigen itself played the domi- is carefully chosen and used to illustrate a nant role in the specificity and diversity of the major intellectual construct. For instance, immune system. However, after Edelman’s when he was railing against reduction- 1959 Journal of the American Chemical Soci- ist thinking, he would open with the ety paper entitled “Dissociation of γ-globu- following story, which I quote from the lin,” everything changed (1). The antibody Creando documents (www.creando.org/data/ problem had become tractable from a chem- Ressources/1321360630-the_challenge_of_ ical point of view, and much research was creative_leadership_7.pdf). I reprint the now focused on the antibody molecule. story here because, as much as anything Edelman’s results suggested that the antibody else, it tells us a lot about Edelman’sthought molecule had subunits and/or domains con- process. nected by disulfide bonds. The 1959 paper The story is about a young man in New opens with the simple statement “Sir: Reac- γ York who thought his girlfriend had left him tion of -globulin with sulfhydryl compounds for somebody else. One hot summer day, he sulfite or performic acid resulted in marked Gerald Edelman in his Army uniform, August diminution in the sedimentation coefficient 1955 at Fort Sam Houston in San Antonio, and molecular weight.” This work sounds The author declares no conflict of interest. Texas. obvious today, but remember that these 1Email: [email protected]. 10900–10901 | PNAS | July 29, 2014 | vol. 111 | no. 30 www.pnas.org/cgi/doi/10.1073/pnas.1410861111 Downloaded by guest on October 1, 2021 there is no other guy! Forget it, you’re just know, it was hot. I don’thaveenoughmoney RETROSPECTIVE nuts! You’re paranoid!” He soon found him- for an air conditioner in my office. I came self at the back window of the apartment, home early to have a drink. I had the drink trembling with rage, when out of the corner and stepped out on the fire escape. I loosened ofhiseye,hesawaguyonthefireescape my collar, wiped my brow, and then this below, loosening his collar and wiping his damn refrigerator falls on my head.” The third brow. At that point, he flew into an even man said, “Idon’t know, I was just sitting in greater rage, grabbed hold of a huge refriger- this refrigerator, minding my own business.” ator, smashed it through the window, aimed Once such a story entered Gerry’s reper- it, and dropped it on this man’shead.The toire, it was to be perpetuated, and he would man dropped dead. Now, the scene switches tell me this particular story at least once a to heaven, and Saint Peter is admitting three month over 25 years. I still don’tknowifhis men, saying, “You fulfilled all the criteria to purpose was to criticize the way I was thinking enter heaven, but you have to tell me how you about this or that problem or if the message died for the records.” The first fellow said, was so important it needed to be perpetuated. “Well, I thought there was some hanky- So let’sassumethelatteristhecase,anddo Gerald M. Edelman (1929–2014). panky going on, so I came home early to Gerry the honor of perpetuating his message catchmyrival.Mygirlsaidhewasn’t around, herebecausehecannolongerdoso. but I finally saw him on the fire escape below. came home early to the cold water flat they I must have had an adrenaline fit, I got an ACKNOWLEDGMENTS. I thank Einar Gall for trading reminiscences with me. were living in in the Village to discover his enormous superhuman surge of strength, rival. He looked in the closet, he looked under grabbed this massive refrigerator, and drop- the bed, he started shouting, and his girl ped it on his head, and then I must have had 1 Edelman GM (1959) Dissociation of γ-globulin. J Am Chem Soc denied everything. She said, “You’re crazy, a heart attack.” The second man said, “Idon’t 81(12):3155–3156. Lerner PNAS | July 29, 2014 | vol. 111 | no. 30 | 10901 Downloaded by guest on October 1, 2021.