Gerald Maurice Edelman.

Professor Gerald Maurice Edelman died in La Jolla, California, on May 17, 2014, at the age of 84. His wife, Maxine Morrison Edelman, and three children, Judith, Eric, and David, survive him. We, of course, remember him for his brilliant scientific career. However, I have received many comments from people who, upon hearing of his death, remarked along lines similar to these: “It’s the end of an era”; “They don’t make them like this anymore”; “We shall not soon see another”; and “The world is more empty now.” In his teens, Edelman was conflicted as to whether he should become a professional violinist or pursue medicine. As happens so often with mothers, his stepped in and with the turn of a phrase decided his fate. She told him that a performing musician was not a proper career and was more “like juggling.” Gerry replied that it certainly wasn’t juggling, to which his mother countered “I have two words for you—Jascha Heifetz!” After receiving his MD degree from the University of Pennsylvania in 1954, he became a house officer at the Massachusetts General Hospital. He then served as a Captain in the US Army Medical Corps at the American Hospital in Paris. (Leave it to Gerry to get stationed in Paris.) In 1957, Edelman was accepted as a graduate student at Rockefeller Institute, and he received his PhD in physical chemistry in 1960. Because of his clinical background and chemical training, Edelman not only recognized an interesting medical question, but was also in a position to solve the problem. His insights led him to a simple experiment that changed the course of immunology and ultimately resulted in his sharing the 1972 Nobel Prize with Rodney Robert Porter for their work on the structure of the antibody molecule. There are, of course, two main components to an acquired immune reaction: the antibody and the antigen. In the early 1950s, the nature of the antibody molecule was considered to be opaque, and thus research focused on the nature of the antigen. Experiments on large antigens such as proteins were carried out in the same way as the earlier experiments of Landsteiner on small organic molecules such as substituted aromatic systems. Only in this case, enzymatic proteolysis rather than organic synthesis was the main tool. One prevailing theory of antibody induction was Linus Pauling’s instructional theory. This suggested that the antigen acted as a template around which the antibody folded, and thus the antigen itself played the dominant role in the specificity and diversity of the immune system. However, after Edelman’s 1959 Journal of the American Chemical Society paper entitled “Dissociation of γ-globulin,” everything changed (1). The antibody problem had become tractable from a chemical point of view, and much research was now focused on the antibody molecule. Edelman’s results suggested that the antibody molecule had subunits and/or domains connected by disulfide bonds. The 1959 paper opens with the simple statement “Sir: Reaction of γ-globulin with sulfhydryl compounds sulfite or performic acid resulted in marked diminution in the sedimentation coefficient and molecular weight.” This work sounds obvious today, but remember that these words were written over half a century ago. Even Pauling appeared intrigued. After one of Edelman’s early presentations of his work, Pauling approached the podium. He passed a cryptic note that said “Edelman—send reprints.” Although the 1959 experiment and those that followed did not solve the generation of diversity (GOD) problem, they did provide the chemical parameters of the antibody molecule that gene action had to explain. This pointed the way to the solution of the GOD problem. This solution came from the work of Susumu Tonegawa and other geneticists, who determined in the 1970s that the genetic basis for generation of antibody diversity relied on a combinatorial mechanism that uses somatic recombination between a rather limited set of germ-line genes to encode about 10 different antibody molecules. Later, Edelman turned his attention to developmental biology, particularly to the study of cell adhesion molecules (CAMs) and then to the study of the brain, with particular emphasis on consciousness. The hallmark of his chemical and biochemical studies had been their “surgical strike” nature: a methodology that does not easily lend itself to the study of consciousness. Thus, he presented his ideas in a series of five books wherein he proposed a general theory of brain function. Their titles, such as Neural Darwinism and Bright Air, Brilliant Fire: On the Matter of the Mind are classic Edelman. Edelman was famous for his jokes that opened every lecture. However, they are not jokes in the standard sense. Each one is carefully chosen and used to illustrate a major intellectual construct. For instance, when he was railing against reductionist thinking, he would open with the following story, which I quote from the Creando documents (www.creando.org/data/ Ressources/1321360630-the_challenge_of_ creative_leadership_7.pdf). I reprint the story here because, as much as anything else, it tells us a lot about Edelman’s thought process. The story is about a young man in New York who thought his girlfriend had left him for somebody else. One hot summer day, he