A doctor’s son in Queens
Gerald Maurice Edelman was born on July 1, 1929, in Ozone Park, Queens, New York, to Jewish parents. His father, Edward Edelman, was a practising physician; his mother, Anna Freedman Edelman, worked in the insurance industry. He grew up in New York’s public schools and graduated from John Adams High School.
As a boy and young man he studied the violin seriously, and for years he imagined a career as a concert violinist. In the end, he later said, he realised he lacked the inner drive a performer needs, and he turned to medical research instead. Music stayed with him for life, and one of his children would become a professional musician.
From medicine to a mystery
Edelman attended Ursinus College in Pennsylvania, graduating magna cum laude in 1950, and received his medical degree from the University of Pennsylvania in 1954. After a year at the Johnson Foundation for Medical Physics and a year as a house officer at Massachusetts General Hospital, he joined the U.S. Army Medical Corps as a captain in 1955 and practised general medicine at a station hospital attached to the American Hospital in Paris.
In Paris he read a medical textbook that said remarkably little about antibodies, the proteins the body makes to fight infection. Antibodies were among the most important molecules in medicine, yet no one knew what they looked like or how a seemingly uniform group of proteins could recognise an almost unlimited range of invaders. Edelman resolved to find out. In 1957 he joined the laboratory of Henry Kunkel at the Rockefeller Institute in New York as a graduate fellow and earned his doctorate in 1960.
At Rockefeller Edelman stayed on after his doctorate, becoming assistant and then associate dean of graduate studies while running his own laboratory, and in 1966 a full professor. Beyond antibodies, he pioneered the use of fluorescent probes to study proteins and developed new ways of separating molecules and cells, techniques that other laboratories adopted widely.
Taking an antibody apart
Antibodies are giant molecules, and Edelman’s strategy was to break them into smaller pieces that could be studied one at a time. He guessed that, like many proteins, an antibody might be built from several chains held together by chemical cross-links made of sulphur. Using chemical solvents to break those disulphide bonds, he succeeded in splitting the molecule into separate chains. Working independently in Britain, Rodney Porter cut antibodies a different way, with an enzyme. Together their results showed that the commonest antibody, immunoglobulin G, is made of four chains: two identical light chains and two heavy chains about twice as long.
Edelman found an ingenious source of pure material. Patients with multiple myeloma, a cancer of antibody-producing cells, make huge quantities of a single antibody, and many pass a puzzling protein, known since the nineteenth century as Bence Jones protein, in their urine. In 1962, with Joseph Gally, Edelman showed that Bence Jones proteins are the light chains of the patient’s own myeloma antibody. That gave researchers a plentiful supply of identical chains to analyse.
Reading the whole molecule
Through the 1960s Edelman’s team cut the chains into fragments and determined the order of their amino acids, the building blocks of proteins. In 1969 they published the complete sequence of an entire immunoglobulin G molecule, more than 1,300 amino acids long and at the time the largest protein ever fully sequenced. They also mapped every sulphur bridge holding the chains together.
The sequence revealed the secret of antibody diversity. Each chain has a constant region, much the same from antibody to antibody, and a variable region that differs greatly. At the tips of the Y-shaped molecule, the variable parts of one light and one heavy chain fold together to form a unique pocket that grips a particular target. The stem, made of the heavy chains, links up with the rest of the immune system. In 1972 the Karolinska Institutet awarded Edelman and Porter the Nobel Prize in Physiology or Medicine for their discoveries concerning the chemical structure of antibodies.
The comparison of different antibody sequences explained one of the great puzzles of biology: how a nearly uniform population of proteins could recognise a nearly unlimited range of foreign invaders. The answer lay in the variable regions, whose endless variety gives each antibody its own target while the constant regions keep the overall machine the same. The 1969 sequence also showed that the constant part of the heavy chain is built from repeating units that resemble the constant part of the light chain, a clue to how antibody genes had evolved.
How it changed medicine
The Nobel committee said the work laid a firm foundation for truly rational research in immunology, something previously largely lacking, and immediately set off research around the world yielding results of practical value for clinical diagnostics and therapy. Knowing exactly which part of an antibody binds a target and which part summons the immune system is the starting point for designing antibodies as medicines.
Today laboratory-made antibodies are among the most important drugs in the world, used against cancers, rheumatoid arthritis and other autoimmune diseases, and infections, and they are engineered by swapping and reshaping exactly the variable and constant regions that Edelman’s sequence first revealed. Antibody-based tests are used every day to diagnose disease, and measurements of antibody light chains help doctors diagnose and follow multiple myeloma. The Rockefeller University credits the work with improving disease diagnosis and informing strategies to prevent the rejection of transplanted organs.
Myeloma cells, which had given Edelman pure antibodies to study, also became part of the next breakthrough. In 1975 Georges Köhler and César Milstein fused antibody-producing cells with myeloma cells, creating cell lines that make a single chosen antibody in unlimited amounts: monoclonal antibodies. The structural picture drawn by Edelman and Porter explained what those antibodies were and how they grip their targets.
From immunity to the brain
After the Nobel Prize, Edelman moved on to how a single fertilised egg grows into a complex animal. His laboratory discovered cell adhesion molecules, proteins that let cells recognise and stick to one another, which guide how tissues take shape and how the nervous system is wired. He found that the gene for one of them, the neural cell adhesion molecule, belongs to the same ancient family as the genes of the immune system.
He then turned to the brain itself. In Neural Darwinism (1987) and later books he proposed that the brain develops by a kind of selection, strengthening the networks of nerve cells that prove useful, much as the immune system selects the antibodies that work. He wrote popular books on consciousness, including Bright Air, Brilliant Fire (1992) and Wider than the Sky (2004), and built robotic brain-based devices to test his ideas. He founded and directed the Neurosciences Institute, and in 1992 he moved to California, where he chaired the Department of Neurobiology at The Scripps Research Institute in La Jolla; from 1993 to 2012 his institute studied the biology of higher brain function in San Diego.
Late in his career, according to his own account for the Nobel Foundation, his laboratory also developed methods to build synthetic gene promoters and to make cells read genes more efficiently, findings that The Scripps Research Institute said could be broadly useful in making biological medicines.
Jewish background
Edelman was born into a Jewish family in Queens at a time when the sons and daughters of Jewish immigrants were moving in large numbers into American medicine and science. His father’s practice and his own path through New York public schools to medical school followed a pattern shared by many of his generation.
He spoke little in public about religion; his books argued that the mind is a purely biological phenomenon. He served on the Board of Governors of the Weizmann Institute of Science in Israel, and he is listed among Jewish Nobel laureates in medicine.
The man
Edelman married Maxine Morrison in 1950. They had two sons, Eric, a visual artist, and David, a neuroscientist, and a daughter, Judith, a bluegrass musician and writer. Colleagues described him as an independent and creative thinker with a true passion for knowledge. He wrote more than 500 research papers.
His career was unusual in its sweep, crossing biophysics, protein chemistry, immunology, embryology and the study of consciousness. He liked to point out the thread that tied them together: both the immune system and the brain, he argued, are recognition systems that work by selection among enormous variety.
He served on the National Institutes of Health’s biophysics study section from 1964 to 1967, gave the Darwin Centennial Lectures at Rockefeller in 1971, and in 1972 became the first Felton Bequest Visiting Professor at the Walter and Eliza Hall Institute in Melbourne. Before the Nobel Prize he had already received the Eli Lilly Award in Biological Chemistry from the American Chemical Society, in 1965.
Last years and legacy
In later life Edelman developed prostate cancer and Parkinson’s disease. He died in La Jolla, California, on May 17, 2014, aged 84.
His theories of the mind remain debated, but his work on antibodies is settled science and part of every immunology textbook. By showing what an antibody is made of and how its parts work, Edelman helped turn immunology into a precise molecular science, and opened the way for the antibody tests and antibody medicines that now help millions of patients.
Sources & further reading
Gerald M. Edelman, Biographical, NobelPrize.org · Press release: The Nobel Prize in Physiology or Medicine 1972, NobelPrize.org · Gerald M. Edelman: Nobel Prize, The Rockefeller University · In Memoriam: Gerald Edelman, The Scripps Research Institute · Gerald Edelman, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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