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.”

Gerald Edelman in his Army uniform, August 1955 at Fort Sam Houston in San Antonio, Texas.

Gerald M. Edelman (1929–2014).

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 10⁸ 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 came home early to the cold water flat they were living in in the Village to discover his rival. He looked in the closet, he looked under the bed, he started shouting, and his girl denied everything. She said, “You're crazy, there is no other guy! Forget it, you're just nuts! You're paranoid!” He soon found himself at the back window of the apartment, trembling with rage, when out of the corner of his eye, he saw a guy on the fire escape below, loosening his collar and wiping his brow. At that point, he flew into an even greater rage, grabbed hold of a huge refrigerator, smashed it through the window, aimed it, and dropped it on this man's head. The man dropped dead. Now, the scene switches to heaven, and Saint Peter is admitting three men, saying, “You fulfilled all the criteria to enter heaven, but you have to tell me how you died for the records.” The first fellow said, “Well, I thought there was some hanky-panky going on, so I came home early to catch my rival. My girl said he wasn't around, but I finally saw him on the fire escape below. I must have had an adrenaline fit, I got an enormous superhuman surge of strength, grabbed this massive refrigerator, and dropped it on his head, and then I must have had a heart attack.” The second man said, “I don't know, it was hot. I don't have enough money for an air conditioner in my office. I came home early to have a drink. I had the drink and stepped out on the fire escape. I loosened my collar, wiped my brow, and then this damn refrigerator falls on my head.” The third man said, “I don't know, I was just sitting in this refrigerator, minding my own business.”

Once such a story entered Gerry’s repertoire, it was to be perpetuated, and he would tell me this particular story at least once a month over 25 years. I still don’t know if his purpose was to criticize the way I was thinking about this or that problem or if the message was so important it needed to be perpetuated. So let’s assume the latter is the case, and do Gerry the honor of perpetuating his message here because he can no longer do so.