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Discovering the Molecular Structure of Antibodies and Elaborating the "Sciences of Recognition"

Antibodies are proteins made by the immune system. They seek out specific antigens-toxins, the cell walls of bacteria, or the outer coats of virus particles, for example-to disable these invaders or signal other cells to remove them. For decades, immunologists puzzled over the amazing specificity of antibodies for the antigens to which they bind. In the late 19th century Paul Ehrlich proposed that the the answer lay in their molecular structure. But only in the mid-20th century did methods become available to study large proteins such as antibodies.

Edelman, Gerald

Gerald Edelman (1929- ) began working to decipher the structure of antibodies, also called immunoglobulins (IgGs), when he joined the Rockefeller laboratory of Henry Kunkel in 1958 as a graduate student. Over the next several years, and after joining the university's faculty, he showed that IgG molecules were composed of two types of polypeptide chains, known today as light and heavy chains. At the same time, Rodney Porter at the University of Oxford, UK, used a complementary approach to chemically split apart the IgG molecule and deduce its Y-shaped structure. Edelman went on to determine the complete 1,300 amino acid sequence of an immunoglobulin, the longest amino acid sequence to be worked out at that time.

"For their discoveries concerning the chemical structure of antibodies," Edelman and Porter shared the Nobel Prize in 1972. This research launched the field of molecular immunology, and opened the door to the wide-ranging use of antibodies in diagnostic testing-from home pregnancy tests to tests for allergies and infectious diseases such as hepatitis-and as therapies, for example to control the rejection of organ transplants, treat autoimmune diseases and cancers, and inhibit blood platelets from causing heart attacks..

Edelman has described immunology as a "science of recognition," and in the 1970s he shifted the focus of his research to another such science: the mechanisms of cell-cell interaction in the early development of the embryo and in the formation and function of the nervous system. These studies led to the discovery of cell adhesion molecules (CAMs)-molecules that glue cells together to form tissues, and that guide the fundamental processes of development, including the formation of the nervous system. It was, in fact, the discovery of a specific antibody that allowed Edelman in 1974 to isolate the neural cell adhesion molecule (NCAM), the first cell-cell adhesion molecule to be purified and characterized.

One of the most significant insights provided by this work is that the precursor gene for the neural cell adhesion molecule gave rise in evolution to the entire molecular system of adaptive immunity. Expanding on this discovery, Edelman formulated a detailed theory to explain the development and organization of higher brain functions in terms of a process known as neural Darwinism, or neuronal group selection. He then extended this theory into a new, biologically based theory of consciousness.

Gerald M. Edelman received the BS from Ursinus College (1950), the MD from the University of Pennsylvania School of Medicine (1954), and the PhD from the Rockefeller Institute (now University; 1960). He did research at the Johnson Foundation for Medical Physics (1954-1954), and served as medical house officer at the Massachusetts General Hospital (1954-1955), as captain in the U.S. Army Medical Corps (1955-1957), and as assistant physician at the Rockefeller Hospital (1957-1960). In 1960 he joined Rockefeller's faculty and served as assistant dean of graduate studies, rising to professor in 1966. In 1974 Edelman was named Vincent Astor Professor at Rockefeller. He founded the Neurosciences Institute in 1981. In 1992 Edelman moved to the Scripps Research Institute, where he is today professor and chairman of the department of neurobiology. Edelman also remains director of The Neurosciences Institute in La Jolla, California. In addition to the Nobel Prize (1972), Edelman's achievements have been recognized by The Warren Triennial Prize (1992), the Medal of the Presidency of the Italian Republic (1999), the C.U. Ariens-Kappers Medal (Netherlands Institute for Brain Research, 1999), La Medaille de la Ville de Paris (Echelon Vermeil, 2002), and the Santiago Grisolia Chair Prize (2003). He has received honorary degrees from many universities, including The Rockefeller University (2008). Among other learned societies, Edelman is a member of the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, and the Academy of Sciences of the Institute of France.

Selected Publications

Edelman GM. Dissociation of γ-globulin. J Am Chem Soc, 1959, 81: 3155-3156

Edelman GM and Poulik MD. Studies on structural units of the gamma-globulins. J Exp Med, 1961, 113: 861-884
http://jem.rupress.org/cgi/reprint/113/5/861

Edelman GM, Benacerraf B, Ovary Z, and Poulik MD. Structural differences among antibodies of different specificities. Proc Natl Acad Sci USA, 1961, 47: 1751-1758
http://www.pnas.org/content/47/11/1751.full.pdf+html

Edelman GM and Gally JA. The nature of Bence-Jones proteins: Chemical similarities to polypeptide chains of myeloma globulins and normal gamma-globulins. J Exp Med, 1962, 116: 207-227
http://jem.rupress.org/cgi/reprint/116/2/207

Schwartz JH and Edelman GM. Comparisons of Bence-Jones proteins and L polypeptide chains of myeloma globulins after hydrolysis with trypsin. J Exp Med, 1963, 118: 41-53
http://jem.rupress.org/cgi/reprint/118/1/41

Bergaird I and Edelman GM. Normal counterparts to Bence-Jones proteins: Free L polypeptide chains of human gamma-globulin. Proc Natl Acad Sci USA, 1963, 49: 330-337
http://www.pnas.org/content/49/3/330.full.pdf+html

Edelman GM, Cunningham BA, Gall WE, Gottlieb PD, Rutishauser U, and Waxdal MJ. The covalent structure of an entire ?G immunoglobulin molecule. Proc Natl Acad Sci USA, 1969, 63: 78-85
http://www.pnas.org/content/63/1/78.full.pdf+html

Edelman GM. Covalent structure of a human ?G-immunoglobulin. XI. Functional implications. Biochemistry, 1970, 9: 31973205
http://pubs.acs.org/doi/abs/10.1021/bi00818a012?journalCode=bichaw&quickLinkVolume=9&quickLinkPage=3197&volume=9

Edelman GM. Antibody structure and molecular immunology (Nobel Prize address). Science, 1973, 180: 830-840

Edelman GM. Surface modulation in cell recognition and cell growth. Science,1976, 192: 218-226

Brackenbury R, Thiery J-P, Rutishauser U, and Edelman GM. Adhesion among neural cells of the chick embryo. I. An immunological assay for molecules involved in cell-cell binding. J Biol Chem, 1977, 252: 6835-6840
http://www.jbc.org/cgi/reprint/252/19/6835

Thiery J-P, Brackenbury R, Rutishauser U, and Edelman GM. Adhesion among neural cells of the chick embryo. II. Purification and characterization of a cell adhesion molecule from neural retina. J Biol Chem, 1977, 252: 6841-6845
http://www.jbc.org/cgi/reprint/252/19/6835

Edelman GM. Cell adhesion molecules. Science, 1983, 219: 450-457

Cunningham BA, Hemperly JJ, Murray BA, Prediger EA, Brackenbury R, and Edelman GM. Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science, 1987, 236: 799-806

Links

The Neurosciences Institute
http://www.nsi.edu/

The Scripps Research Institute - Neurobiology
http://www.scripps.edu/nb/chair.html

The Nobel Prize in Physiology or Medicine, 1972
http://nobelprize.org/nobel_prizes/medicine/laureates/1972/

Hospital Centennial

Discovering the Molecular Structure of Antibodies and Elaborating the "Sciences of Recognition"

Selected Publications

Further Reading

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