Edelman, Gerald M. (1929- )

views updated May 21 2018

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.

See also Antibody and antigen; Antibody formation and kinetics; Antibody, monoclonal; Antibody-antigen, biochemical and molecular reactions; Antigenic mimicry

World of Microbiology and Immunology

Edelman, Gerald M.

views updated May 29 2018

Gerald M. Edelman

American neuroscientist, professor, and author Gerald M. Edelman (born 1929) won the Nobel Prize in Physiology or Medicine in 1972 at the age of 43. He went on to achieve equal prominence for his pioneering theory of mind, referred to as "Neural Darwinism" or "Neuronal Group Selection" (NGS). While his conclusions about the fundamental workings of the human brain were often controversial, they were never dull. Edelman's publications on the subject included Neural Darwinism: The Theory of Neuronal Group Selection, Bright Air, Brilliant Fire: On the Matter of the Mind, and Wider than the Sky: The Phenomenal Gift of Consciousness. He founded the Neurosciences Institute in New York City in 1981, and moved it to La Jolla, California, in 1993.

Education and Training

Edelman was born on July 1, 1929, in New York City. His father, Edward, was a physician and his mother, Anna, a homemaker. As he was growing up in Ozone Park, Queens, and Long Beach, New York, science was not foremost in his mind. Instead, he trained to be a concert violinist with noted teacher/performer Albert Meiff. Music was to remain a consuming passion of Edelman's over the years, but it was not to become his career.

After attending public schools in New York City through high school, Edelman went to Collegeville, Pennsylvania, to study chemistry at Ursinus College. He graduated magna cum laude in 1950 and then headed off to the Medical School of the University of Pennsylvania, from which he received an M.D. in 1954. In 1955 Edelman became a medical house officer at Massachusetts General Hospital. Next up, he joined the U.S. Army Medical Corps as a captain, and practiced general medicine at a military hospital connected with American Hospital in Paris, France, for two years.

Upon his discharge from the army in 1957, Edelman returned to his hometown to pursue a Ph.D. in biochemistry and immunology from the Rockefeller Institute (now Rockefeller University). It was there, under the guidance of Dr. Henry G. Kunkel, that Edelman began the research in immunology that would lead to his Nobel Prize. His thesis explored methods of splitting immunoglobulin molecules, or antibodies, and he received his doctorate in 1960.

Won Nobel Prize

After earning his Ph.D., Edelman stayed on at Rockefeller University as assistant dean of Graduate Studies. In 1963 he became associate dean of Graduate Studies, and in 1966 he became a full professor. He continued his research in his own laboratory, and was soon making some groundbreaking findings.

In the 1950s and 1960s, the understanding of the nature of antibodies was scant. Their role in combating foreign substances, or antigens, in the body was known, but their chemical structure and the way in which they were able to recognize antigens was less clear. English biochemist Rodney R. Porter was investigating the matter, as was Edelman. Throughout the 1960s each scientist came up with independent research, sometimes drawing on one another's research, in order to explain the properties of antibodies more fully. By 1969 Edelman and his team at Rockefeller had succeeded in creating a precise model of an antibody molecule, which was made up of a four-amino-acid-chain (two light and two heavy chains) structure comprised of more than 1,300 amino acids. This enabled the team to identify exact locations of antigenic binding. Edelman's group had just narrowly beaten Porter's in achieving such a goal, and both researchers were awarded the Nobel Prize in Physiology or Medicine in 1972 for their efforts. Their work had many far-reaching effects in medical therapy, including preventing organ rejection in transplant situations. But Edelman, just 43 years old at the time, had even more to offer the world of science.

Neural Darwinism

After winning the Nobel Prize, Edelman changed his focus from immunology to developmental biology and neuroscience. Specifically, he began to investigate how the human body, and especially the brain, operates, by honing in on cellular interactions in early embryonic development and the formation and function of the nervous system. He quickly made innovative inroads into this new area as well, beginning in 1975, when he discovered cell adhesion molecules (CAMs). CAMs bind neurons together to form the brain's fundamental circuitry, thereby guiding the basic processes through which an animal achieves its shape and form and by which nervous systems are constructed. While seminal in its own right, this work also led to the larger theory for which Edelman is likely most famous, that of "Neural Darwinism."

In 1981 Edelman founded the Neurosciences Institute as an independently supported part of Rockefeller University (relocated to La Jolla, California in 1993). Its mandate was to emphasize the scientific "big picture" and investigate creative theories on the workings of the brain, particularly as to higher brain function. Within this organization, Edelman formulated his notable theory of mind.

Neural Darwinism, or Neuronal Group Selection (NGS), was first presented in Edelman's 1987 book Neural Darwinism: The Theory of Neuronal Group Selection. The idea is described in his biography on the Cajal Conference website (citation below) as: "the theory that populations of neurons develop individual networks through a Darwinian selection process. [Edelman] thinks that the converse opinion, that neurons are genetically coded to make specific connections, just as transistors are wired in a preset pattern, is untenable given the very limited size of eukaryotic genomes in relation with the explosive number of neuronal connections." Further, Edelman argued against the traditional concept of a fixed human nervous system, suggesting instead that neural systems continuously change. That is, the human brain has variations unique to each individual and modifies itself constantly in response to each new incoming signal.

The forgoing explanation is, necessarily, an extremely simplified and streamlined definition of a multi-faceted and complicated theory. Indeed, some of its controversy stemmed from its very complexity. Edward Rothstein of the New York Times quoted the 1988 comment of biologist Gunter Stent on NGS as, "I consider myself not too dumb. I am a professor of molecular biology and chairman of the neurobiology section of the National Academy of Sciences, so I should understand it. But I don't." Other critics found the theory either derivative or based on incorrect interpretations of other models of the mind. But Edelman ignored the naysayers and quietly continued his pioneering work.

Preeminent Neuroscientist

After his first book on NGS, Edelman went on to write several others elucidating his ideas for both the scientific and lay communities. He started by writing the two volumes that completed his initial trilogy, Topobiology: An Introduction to Molecular Embryology (1988) and The Remembered Present: A Biological Theory of Consciousness (1989). He followed those up with Bright Air, Brilliant Fire: On the Matter of the Mind, published in 1992, A Universe of Consciousness: How Matter Becomes Imagination (2000), which presented new data on the neural correlates of conscious experience, and Wider than the Sky: The Phenomenal Gift of Consciousness (2005), which included a model of the biology of consciousness. It was in the latter book that Edelman, unenviably, attempted to articulate his ideas for a lay audience. Additionally, he had authored more than 500 research publications by 2006.

By 2005 Edelman had added other responsibilities to his resume besides heading up the Neurosciences Institute. Those included serving as chairman and professor of neurobiology at the Scripps Research Institute, scientific chairman of the Neurosciences Research Program, and president of the Neurosciences Research Foundation. His institute was thriving on its own campus in La Jolla, with 36 research fellows studying nearly every field of neuroscience. Each fellow was fully funded by the institute for up to four years, in order to insulate him or her from the vagaries and distractions of grant writing and laboratory politics, as Edelman felt such independence was necessary for proper original research. And the institute itself was an interesting reflection of its founder: one building devoted to theory, another to experimentation, and a third (a concert hall) to music.

Edelman's unique and significant contributions to science garnered him many accolades, honors, and awards throughout the years. In 1954 he received the Spencer Morris Award from the University of Pennsylvania; in 1965, the Eli Lilly Award in Biological Chemistry of American Chemical Society; and in 1969, the Annual Alumni Award from Ursinus College. He gave the Carter-Wallace Lectures at Princeton University in 1965, the National Institutes of Health Biophysics and Bioorganic Chemistry Lectureship at Cornell University in 1971, and the Darwin Centennial Lectures at Rockefeller University in 1971. He was the first Felton Bequest Visiting Professor at the Walter and Eliza Hall Institute for Medical Research in Melbourne, Australia, in 1972, and became a Vincent Astor Distinguished Professor at Rockefeller University in 1974. Other awards included the Albert Einstein Commemorative Award, the Buchman Memorial Award from the California Institute of Technology, and the Rabbi Shai Schaknai Memorial Prize. And he held memberships in numerous professional and scientific societies. He was one of the few international members of the Academy of Sciences, Institute of France.

Despite the controversy surrounding his theories, and perhaps even because of it, Edelman was indisputably one of the preeminent neuroscientists of his time. His advocates found his ideas breathtaking. His adversaries rarely dismissed him out of hand. And the potential impact of his ideas, whatever one felt about them, was enormous. As Rothstein wrote, "(Edelman's) vision can also spur discomfort, because it implies that there is no supervising soul or self—nobody is standing behind the curtain. This, for Dr. Edelman, is Darwin's final burden."