EDELMAN, GERALD M. (1929- )
American biochemist
For his "discoveries concerning the chemical structure of antibodies," Gerald M. Edelman and his associate Rodney Porter received the 1972 Nobel Prize in physiology or medicine. During a lecture Edelman gave upon acceptance of the prize, he stated that immunology "provokes unusual ideas, some of which are not easily come upon through other fields of study.... For this reason, immunology will have a great impact on other branches of biology and medicine." He was to prove his own prediction correct by using his discoveries to draw conclusions not only about the immune system but about the nature of consciousness as well.
Born in New York City to Edward Edelman, a physician, and Anna Freedman Edelman, Gerald Maurice Edelman attended New York City public schools through high school. After graduating, he entered Ursinus College, in Collegeville, Pennsylvania, where he received his B.S. in chemistry in 1950. Four years later, he earned an M.D. degree from the University of Pennsylvania's Medical School, spending a year as medical house officer at Massachusetts General Hospital.
In 1955, Edelman joined the United States Army Medical Corps, practicing general medicine while stationed at a hospital in Paris. There, Edelman benefited from the heady atmosphere surrounding the Sorbonne, where future Nobel laureates Jacques Lucien Monod and François Jacob were originating a new study, molecular biology. Following his 1957 discharge from the Army, Edelman returned to New York City to take a position at Rockefeller University studying under Henry Kunkel. Kunkel, with whom Edelman would conduct his Ph.D. research, and who was examining the unique flexibility of antibodies at the time.
Antibodies are produced in response to infection in order to work against diseases in diverse ways. They form a class of large blood proteins called globulins—more specifically, immunoglobulins—made in the body's lymph tissues. Each immunoglobulin is specifically directed to recognize and incapacitate one antigen, the chemical signal of an infection. Yet they all share a very similar structure.
Through the 1960s and 1970s, a debate raged between two schools of scientists to explain the situation whereby antibodies share so many characteristics yet are able to perform many different functions. In one camp, George Wells Beadle and Edward Lawrie Tatum argued that despite the remarkable diversity displayed by each antibody, each immunoglobulin, must be coded for by a single gene. This has been referred to as the "one gene, one protein" theory. But, argued the opposing camp, led by the Australian physician Sir Frank Macfarlane Burnet, if each antibody required its own code within the DNA (deoxyribonucleic acid), the body's master plan of protein structure, the immune system alone would take up all the possible codes offered by the human DNA.
Both camps generated theories, but Edelman eventually disagreed with both sides of the debate, offering a third possibility for antibody synthesis in 1967. Though not recognized at the time because of its radical nature, the theory he and his associate, Joseph Gally, proposed would later be confirmed as essentially correct. It depended on the vast diversity that can come from chance in a system as complex as the living organism. Each time a cell divided, they theorized, tiny errors in the transcription—or reading of the code—could occur, yielding slightly different proteins upon each misreading. Edelman and Gally proposed that the human body turns the advantage of this variability in immunoglobulins to its own ends. Many strains of antigens when introduced into the body modify the shape of the various immunoglobulins in order to prevent the recurrence of disease. This is why many illnesses provide for their own cure—why humans can only get chicken pox once, for instance.
But the proof of their theory would require advances in the state of biochemical techniques. Research in the 1950s and 1960s was hampered by the difficulty in isolating immunoglobulins. The molecules themselves are comparatively large, too large to be investigated by the chemical means then available. Edelman and Rodney Porter, with whom Edelman was to be honored with the Nobel Prize, sought
methods of breaking immunoglobulins into smaller units that could more profitably be studied. Their hope was that these fragments would retain enough of their properties to provide insight into the functioning of the whole.
Porter became the first to split an immunoglobulin, obtaining an "active fragment" from rabbit blood as early as 1950. Porter believed the immunoglobulin to be one long continuous molecule made up of 1,300 amino acids—the building blocks of proteins. However, Edelman could not accept this conclusion, noting that even insulin, with its 51 amino acids, was made up of two shorter strings of amino acid chains working as a unit. His doctoral thesis investigated several methods of splitting immunoglobulin molecules, and, after receiving his Ph.D. in 1960 he remained at Rockefeller as a faculty member, continuing his research.
Porter's method of splitting the molecules used enzymes that acted as chemical knives, breaking apart amino acids. In 1961 Edelman and his colleague, M. D. Poulik succeeded in splitting IgG—one of the most studied varieties of immunoglobulin in the blood—into two components by using a method known as "reductive cleavage." The technique allowed them to divide IgG into what are known as light and heavy chains. Data from their experiments and from those of the Czech researcher, Frantisek Franek, established the intricate nature of the antibody's "active sight." The sight occurs at the folding of the two chains, which forms a unique pocket to trap the antigen. Porter combined these findings with his, and, in 1962, announced that the basic structure of IgG had been determined. Their experiments set off a flurry of research into the nature of antibodies in the 1960s. Information was shared throughout the scientific community in a series of informal meetings referred to as "Antibody Workshops," taking place across the globe. Edelman and Porter dominated the discussions, and their work led the way to a wave of discoveries.
Still, a key drawback to research remained. In any naturally obtained immunoglobulin sample a mixture of ever so slightly different molecules would reduce the overall purity. Based on a crucial finding by Kunkel in the 1950s, Porter and Edelman concentrated their study on myelomas, cancers of the immunoglobulin-producing cells, exploiting the unique nature of these cancers. Kunkel had determined that since all the cells produced by these cancerous myelomas were descended from a common ancestor they would produce a homogeneous series of antibodies. A pure sample could be isolated for experimentation. Porter and Edelman studied the amino acid sequence in subsections of different myelomas, and in 1965, as Edelman would later describe it: "Mad as we were, [we] started on the whole molecule." The project, completed in 1969, determined the order of all 1,300 amino acids present in the protein, the longest sequence determined at that time.
Throughout the 1970s, Edelman continued his research, expanding it to include other substances that stimulate the immune system, but by the end of the decade the principle he and Poulik uncovered led him to conceive a radical theory of how the brain works. Just as the structurally limited immune system must deal with myriad invading organisms, the brain must process vastly complex sensory data with a theoretically limited number of switches, or neurons.
Rather than an incoming sensory signal triggering a predetermined pathway through the nervous system, Edelman theorized that it leads to a selection from among several choices. That is, rather than seeing the nervous system as a relatively fixed biological structure, Edelman envisioned it as a fluid system based on three interrelated stages of functioning.
In the formation of the nervous system, cells receiving signals from others surrounding them fan out like spreading ivy—not to predetermined locations, but rather to regions determined by the concert of these local signals. The signals regulate the ultimate position of each cell by controlling the production of a cellular glue in the form of cell-adhesion molecules. They anchor neighboring groups of cells together. Once established, these cellular connections are fixed, but the exact pattern is different for each individual.
The second feature of Edelman's theory allows for an individual response to any incoming signal. A specific pattern of neurons must be made to recognize the face of one's grandmother, for instance, but the pattern is different in every brain. While the vast complexity of these connections allows for some of the variability in the brain, it is in the third feature of the theory that Edelman made the connection to immunology. The neural networks are linked to each other in layers. An incoming signal passes through and between these sheets in a specific pathway. The pathway, in this theory, ultimately determines what the brain experiences, but just as the immune system modifies itself with each new incoming virus, Edelman theorized that the brain modifies itself in response to each new incoming signal. In this way, Edelman sees all the systems of the body being guided in one unified process, a process that depends on organization but that accommodates the world's natural randomness.
Dr. Edelman has received honorary degrees from a number of universities, including the University of Pennsylvania, Ursinus College, Williams College, and others. Besides his Nobel Prize, his other academic awards include the Spenser Morris Award, the Eli Lilly Prize of the American Chemical Society, Albert Einstein Commemorative Award, California Institute of Technology's Buchman Memorial Award, and the Rabbi Shai Schaknai Memorial Prize.
A member of many academic organizations, including New York and National Academy of Sciences, American Society of Cell Biologists, Genetics Society, American Academy of Arts and Sciences, and the American Philosophical Society, Dr. Edelman is also one of the few international members of the Academy of Sciences, Institute of France. In 1974, he became a Vincent Astor Distinguished Professor, serving on the board of governors of the Weizmann Institute of Science and is also a trustee of the Salk Institute for Biological Studies. Dr. Edelman married Maxine Morrison on June 11, 1950; the couple have two sons and one daughter.
