Thursday, May 29, 2014

A00067 - Gerald Edelman, Nobel Laureate and "Neural Darwinist"


Dr. Gerald M. Edelman at Rockefeller University in 1972, in front of a gamma globulin model.CreditDon Hogan Charles/The New York Times
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Dr. Gerald M. Edelman, who shared a 1972 Nobel Prize for a breakthrough in immunology and went on to contribute key findings in neuroscience and other fields, becoming a leading if contentious theorist on the workings of the brain, died on Saturday at his home in the La Jolla section of San Diego. He was 84.
The precise cause was uncertain, but Dr. Edelman had Parkinson’s disease and prostate cancer, his son David said.
Dr. Edelman was known as a problem solver, a man of relentless intellectual energy who asked big questions and attacked big projects. What interested him, he said, were “dark areas” where mystery reigned.
“Anybody in science, if there are enough anybodies, can find the answer,” he said in a1994 interview in The New Yorker. “It’s an Easter egg hunt. That isn’t the idea. The idea is: Can you ask the question in such a way as to facilitate the answer? And I think the great scientists do that.”
His Nobel Prize in Physiology or Medicine came in 1972 after more than a decade of work on the process by which antibodies, the foot soldiers of the immune system, mount their defense against infection and disease. He shared the prize with Rodney R. Porter, a British scientist who worked independent of Dr. Edelman. The Nobel committee cited them for their separate approaches in deciphering the chemical structure of antibodies, also known as immunoglobulins.
Dr. Edelman discovered that antibodies were not constructed in the shape of one long peptide chain, as thought, but of two different ones — one light, one heavy — that were linked.
From this, he and a research team at Rockefeller University in Manhattan determined the structure of an entire immunoglobulin molecule. Their advance, as well as Dr. Porter’s, “incited a fervent research activity the whole world over, in all fields of immunological science, yielding results of practical value for clinical diagnostics and therapy,” the Nobel committee said.
From the mid-1970s on, Dr. Edelman was largely concerned with the brain and the nature of consciousness — “how the brain gives rise to the mind,” as he put it. He rejected the prevalent notion that the best model for the brain was a computer.
Rather, he took a lesson from his earlier work in immunology. He had helped establish that antibodies work according to a process akin to Darwinian selection, and he now postulated a theory of the brain called neuronal group selection, which came to be known as “neural Darwinism.”
Within the dense thicket of nerve cells in the brain, known as neurons, are a vast array of neuronal groups. Dr. Edelman believed that when something happened in the world — something encountered by one of our senses — some neuronal groups responded and were strengthened by a series of biological processes. Those groups, he concluded, became more likely to respond to the same or a similar stimulus the next time, and thus did the brain learn from its own experience and shape itself over the course of a life.
Dr. Edelman discussed neural Darwinism and his theories connecting biology and consciousness in four books, including “Bright Air, Brilliant Fire: On the Matter of the Mind” (1992). They were received with both admiration and skepticism, praised as visionary by some and judged incomprehensible by others.
Gunther Stent, a pioneer of modern biology, expressed his frustration, saying: “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.”
Since then, however, elements of Dr. Edelman’s work have been supported by experimental research.
“To some degree, it’s still an intractable subject,” said Peter Vanderklish, a neuroscientist and professor at the Scripps Research Institute in La Jolla, where he and Dr. Edelman were colleagues. “There isn’t going to be any kind of theory of the brain that doesn’t involve elements of his ideas. The brain is never — never has been or ever will be — in the same state twice, and will never encounter the same environmental cues twice. What’s attractive about his model is that it tries to address that reality.”
Gerald Maurice Edelman was born on July 1, 1929, in the Ozone Park neighborhood of Queens. He grew up there and in Long Beach, N.Y. His father, Edward, was a doctor; his mother, the former Anna Freedman, worked in the insurance business.
As a boy, he studied violin and considered becoming a professional musician. After graduating from Ursinus College in Pennsylvania, he earned a medical degree from the University of Pennsylvania and interned at Massachusetts General Hospital in Boston. From 1955 to 1957, he served in the Army Medical Corps in Paris, after which he began his research on antibodies at the Rockefeller Institute, now Rockefeller University.
There, in 1981, he founded the Neurosciences Institute. Much of its study of the brain is based on the theory of neuronal group selection and computer simulations of nervous systems. The institute later moved to the Scripps campus and in 2012 separated from Scripps and relocated nearby.
In addition to his son David, Dr. Edelman is survived by his wife, the former Maxine Morrison, whom he married in 1950; a second son, Eric; and a daughter, Judith.
Dr. Edelman was the author of hundreds of articles and papers. His books include “A Universe of Consciousness: How Matter Becomes Imagination” (2000), written with Giulio Tononi, a psychiatrist and neuroscientist at the University of Wisconsin.
Dr. Tononi described Dr. Edelman in an interview as a major thinker whose ideas pushed science forward. “When he started doing this, thinking that the brain might work by selection, as the evolution of species does and the immune system does, the way people were looking at the brain was completely different,” Dr. Tononi said.
As to the durability of Dr. Edelman’s ideas, he added: “The overall spirit has been vindicated. That’s how I would put it.”

Gerald Maurice Edelman (July 1, 1929 – May 17, 2014)[2] was an American biologist who shared the 1972 Nobel Prize in Physiology or Medicine for work with Rodney Robert Porter on the immune system.[3] Edelman's Nobel Prize-winning research concerned discovery of the structure of antibody molecules.[4] In interviews, he has said that the way the components of the immune system evolve over the life of the individual is analogous to the way the components of the brain evolve in a lifetime. There is a continuity in this way between his work on the immune system, for which he won the Nobel Prize, and his later work in neuroscience and in philosophy of mind.
Education and career[edit]
Gerald Edelman was born in 1929 in Ozone Park, Queens, New York, to Jewish parents, physician Edward Edelman, and Anna (née Freedman) Edelman, who worked in the insurance industry.[5] After being raised in New York, he attended college in Pennsylvania where he graduated magna cum laude with a B.S. from Ursinus College in 1950 and received an M.D. from the University of Pennsylvania School of Medicine in 1954.[5]
After a year at the Johnson Foundation for Medical Physics, he became a house officer at the Massachusetts General Hospital and then practiced medicine in France while serving with US Army Medical Corps.[5] Edelman joined the Rockefeller Institute for Medical Research as a graduate fellow in 1957, working in the laboratory of Henry Kunkel and receiving a Ph.D. in 1960.[5] Rockefeller made him the Assistant (later Associate) Dean of Graduate Studies until 1966, when he became a professor at the school.[5] In 1992, he moved to California and became a professor of neurobiology at The Scripps Research Institute.[6]
After his Nobel prize award, Edelman began research into the regulation of primary cellular processes, particularly the control of cell growth and the development in multi-celled organisms, focussing on cell-to-cell interactions in early embryonic development and in the formation and function of the nervous system. These studies led to the discovery of cell adhesion molecules (CAMs), which guide the fundamental processes that help an animal achieve its shape and form, and by which nervous systems are built. One of the most significant discoveries made in this research is that the precursor gene for the neural cell adhesion molecule gave rise in evolution to the entire molecular system of adaptive immunity.[7]
Edelman founded and directed The Neurosciences Institute, a nonprofit research center in San Diego that between 1993 and 2012 studied the biological bases of higher brain function in humans. He served on the scientific board of the World Knowledge Dialogue project.[8]
Edelman is a member of the USA Science and Engineering Festival's Advisory Board.[9]

Nobel Prize[edit]

While in Paris serving in the Army, Edelman read a book that sparked his interest in antibodies.[10] He decided that, since the book said so little about antibodies, he would investigate them further upon returning to the United States, which led him to study physical chemistry for his 1960 Ph.D.[10] Research by Edelman and his colleagues and Rodney Robert Porter in the early 1960s produced fundamental breakthroughs in the understanding of the antibody's chemical structure, opening a door for further study.[11] For this work, Edelman and Porter shared the Nobel Prize in Physiology or Medicine in 1972.[3]
In its Nobel Prize press release in 1972, the Karolinska Institutet lauded Edelman and Porter's work as a major breakthrough:
"The impact of Edelman's and Porter's discoveries is explained by the fact that they provided a clear picture of the structure and mode of action of a group of biologically particularly important substances. By this they laid a firm foundation for truly rational research, something that was previously largely lacking in immunology. Their discoveries represent clearly a break-through that immediately incited a fervent research activity the whole world over, in all fields of immunological science, yielding results of practical value for clinical diagnostics and therapy.[12]

Disulfide bonds[edit]

Diagram illustrating the disulfide bonds (red) that link the light (green) and heavy (blue) protein subunits of Immunoglobulin G (IgG)molecules. This diagram also illustrates the relative positions of the variable (V) and constant (C) domains of an IgG molecule. The heavy and light chain variable regions come together to form antigen binding sites at the end of the two symmetrical arms of the antibody.
Edelman's early research on the structure of antibody proteins revealed that disulfide bonds link together the protein subunits.[4] The protein subunits of antibodies are of two types, the larger heavy chains and the smaller light chains. Two light and two heavy chains are linked together by disulfide bonds to form a functional antibody.

Molecular models of antibody structure[edit]

Using experimental data from his own research and the work of others, Edelman developed molecular models of antibody proteins.[13] A key feature of these models included the idea that the antigen binding domains of antibodies (Fab) include amino acids from both the light and heavy protein subunits. The inter-chain disulfide bonds help bring together the two parts of the antigen binding domain.

Antibody sequencing[edit]

Edelman and his colleagues used cyanogen bromide and proteases to fragment the antibody protein subunits into smaller pieces that could be analyzed for determination of their amino acid sequence.[14][15] At the time when the first complete antibody sequence was determined (1969)[16] it was the largest complete protein sequence that had ever been determined. The availability of amino acid sequences of antibody proteins allowed recognition of the fact that the body can produce many different antibody protein with similar antibody constant regions and divergent antibodyvariable regions.


Topobiology is Edelman’s theory which asserts that morphogenesis is driven by differential adhesive interactions among heterogeneous cell populations and it explains how a single cell can give rise to a complex multi-cellular organism. As proposed by Edelman in 1988 topobiology is the process that sculpts and maintains differentiated tissues and is acquired by the energetically favored segregation of cells through heterologous cellular interactions.

Theory of consciousness[edit]

Edelman is noted for his theory of consciousness, which he has documented in a trilogy of technical books and in several subsequent books written for a general audience, including Bright Air, Brilliant Fire (1992), A Universe of Consciousness (2001, with Giulio Tononi), Wider than the Sky (2004) and Second Nature: Brain Science and Human Knowledge (2007).
In Second Nature Edelman defines human consciousness as:
"... what you lose on entering a dreamless deep sleep ... deep anesthesia or coma ... what you regain after emerging from these states. [The] experience of a unitary scene composed variably of sensory responses ... memories ... situatedness ... "
The first of Edelman's technical books, The Mindful Brain (1978),[17] develops his theory of Neural Darwinism, which is built around the idea of plasticity in the neural network in response to the environment. The second book, Topobiology (1988),[18] proposes a theory of how the original neuronal network of a newborn's brain is established during development of the embryoThe Remembered Present (1990)[19] contains an extended exposition of his theory of consciousness.
In his books Edelman proposed a biological theory of consciousness, based on his studies of the immune system. He explicitly located his theory within Charles Darwin's Theory of Natural Selection, citing the key tenets of Darwin's population theory, which postulates that individual variation within species provides the basis for the natural selection that eventually leads to the evolution of new species.[20] He rejected dualism and also dismissed newer hypotheses such as the so-called 'computational' model of consciousness, which liken the brain's functions to the operations of a computer. Edelman argued that the mind and consciousness are purely biological phenomena, arising from complex cellular processes within the brain, and that the development of consciousness and intelligence can be explained by Darwinian theory.
Edelman's theory seeks to explain consciousness in terms of the morphology of the brain. A newborn baby's brain comprises a massive population of neurons (approx. 100 billion cells) and those that survive the initial phases of growth and development will make approximately 100 trillion connections with each other. A sample of brain tissue the size of a match head contains about a billion connections, and if we consider how these neuronal connections might be variously combined, the number of possible permutations becomes hyper-astronomical—in the order of ten followed by millions of zeros.[21] The young brain contains many more neurons than will ultimately survive to maturity, and Edelman argued that this redundant capacity is needed because neurons are the only cells in the body that cannot be renewed and because only those cells and networks best adapted to their ultimate purpose will be selected as they organize into neuronal groups.

Neural Darwinism[edit]

Edelman's theory of neuronal group selection, also known as Neural Darwinism, has three basic tenets—Developmental Selection, Experiential Selection and Reentry.
  • Developmental selection -- the formation of the gross anatomy of the brain is controlled by genetic factors, but in any individual the connectivity between neurons at the synaptic level and their organisation into functional neuronal groups is determined by somatic selection during growth and development. This process generates tremendous variability in the neural circuitry—like the fingerprint or the iris, no two people will have precisely the same synaptic structures in any comparable area of brain tissue. Their high degree of functional plasticity and the extraordinary density of their interconnections enables neuronal groups to self-organise into many complex and adaptable "modules." These are made up of many different types of neurons which are typically more closely and densely connected to each other than they are to neurons in other groups.
  • Experiential selection -- Overlapping the initial growth and development of the brain, and extending throughout an individual's life, a continuous process of synaptic selection occurs within the diverse repertoires of neuronal groups. This process may strengthen or weaken the connections between groups of neurons and it is constrained by value signals that arise from the activity of the ascending systems of the brain, which are continually modified by successful output. Experiential selection generates dynamic systems that can 'map' complex spatio-temporal events from the sensory organs, body systems and other neuronal groups in the brain onto other selected neuronal groups. Edelman argues that this dynamic selective process is directly analogous to the processes of selection that act on populations of individuals in species, and he also points out that this functional plasticity is imperative, since not even the vast coding capability of entire human genome is sufficient to explicitly specify the astronomically complex synaptic structures of the developing brain.[22]
  • Reentry —the third tenet of Edelman's thesis is the concept of reentrant signalling between neuronal groups. He defines reentry as the ongoing recursive dynamic interchange of signals that occurs in parallel between brain maps, and which continuously interrelates these maps to each other in time and space. Reentry depends for its operations on the intricate networks of massively parallel reciprocal connections within and between neuronal groups, which arise through the processes of developmental and experiential selection outlined above. Edelman describes reentry as "a form of ongoing higher-order selection ... that appears to be unique to animal brains" and that "there is no other object in the known universe so completely distinguished by reentrant circuitry as the human brain."

Evolution theory[edit]

Edelman and Gally were the first to point out the pervasiveness of degeneracy in biological systems and the fundamental role that degeneracy plays in facilitating evolution.[24]


Edelman married Maxine M. Morrison in 1950.[5] They have two sons, Eric, a visual artist in New York City, and David, a professor of neuroscience at Bennington College. Their daughter, Judith Edelman, is a bluegrass musician, recording artist, and writer. 


Edelman was suffering from prostate cancer and Parkinson's disease.[1]
Edelman died May 17, 2014 in La Jolla, California, aged 84.[25][26]

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