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The Nobel Prize in Physiology or Medicine 1963 - shared with Alan Hodgkin and Andrew Huxley, "for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane."
Neural Darwinism - Theory of Neuronal Group Selection
Topobiology - Molecular Embryology
The Immune System as an Ideal Model for Studying Evolution in a Selective System
"Two major developments have profoundly altered immunological research in the last decade: the theory of clonal selection and the chemical analysis of antibody structure... As a result of these developments, it has become clear that the central problem of immunology is to understand the mechanisms of selective molecular recognition in a quantitative fashion. Aside from evolution itself, there are few such well-analyzed examples of selective systems in biology or in other fields for that matter. For this reason, the immune system provides a unique opportunity to analyze the problem of selection under defined and experimentally measurable conditions that have so far been hard to achieve in other Eukaryotic systems. It is fortunate that the characteristics of the molecules and cells mediating selection in the immune response are known or can be known, and above all, that the time scale of the selective events is well within that required for direct observation and experimentation."[1]
Recognition and Memory in the Immune and Nervous Systems
"[I]t is not difficult to see that both the brain and the immune system are recognition systems. Both can recognize and therefore distinguish positively among different objects in a set (in the one case via sensory signals, in the other via molecular complementarity between the shapes of antigens and the combining sites of antibodies). By positive recognition I mean that they do not merely exclude an object by subjecting it to a match with a fixed pattern, but rather that they can name or tag an object uniquely. This is a much more powerful kind of recognition than the exclusive one embodied, say, in the construction of a combination lock. Furthermore, both systems have the capacity to store a recognition event ("memory" and "immunological memory") as well as the capacity to forget."[6]
Pre-existing Diversity is the Engine of Adaptive Creativity
"It is clear from both evolutionary and immunological theory that in facing an unknown future, the fundamental requirement for successful adaption is preexisting diversity."[7]
Gerald M. Edelman (1978)
The Regulator Hypothesis
"According to the regulator hypothesis, the genes force adhesion molecules (CAMs) are expressed in schedules that are prior to and largely independent of those for cytodifferentiation. The expressed CAMs act as regulators of the overall patterns of those morphogenetic movements that are essential for inductive sequences or early milieu-dependent differentiations. It is proposed that, during evolution, natural selection eliminates those organisms in which variants of CAM gene expression or of morphogenetic movements or of both result in interruptions in the inductive sequence. Under this assumption, more than one (but not all) combinations of these two variables will lead to stabilization of the order of inductive sequences and of the body plan in a variety of species. Moreover, small variations in the pattern of action of regulatory genes for CAMs in those organisms that are not selected against could lead to large changes in animal form within relatively short periods of evolutionary time."[8]
Gerald M. Edelman (1984)
The Requirements of a Selection Theory
"[T]he abstract general requirements on any selection theory are (1) a source of diversification leading to variants, (2) a means for effective encounter with or sampling of an independent environment that is not initially categorized in any absolute or predetermined fashion, and (3) a means of differential amplification over some period of time of those variants in a population that have greater adaptive value."[9]
"The key idea may be summarized roughly as follows: These molecules link cells into collectives whose borders are defined by CAMs of different specificity. The binding properties of cells linked by the CAMs are dynamically controlled by the cells themselves as a result of signals exchanged between collectives. Cell binding in turn regulates cell motion and further signalling, and thus the ensuing forms. Control of the expression of CAM genes by the specific biochemistry affecting CAM regulatory genes at particular morphologic sites assures constancy of form in a species. But because the main function of CAMs is to regulate dynamic cellular processes and not specify cell addresses exactly, variability is also introduced during development."[10]
Gerald M. Edelman (1987)
Perceptual Categorization
"An individual animal endowed with a richly structured brain must also adapt without instruction to a complex environment to form perceptual categorizations or an internal taxonomy governing its further responses to its world"[11]
Gerald M. Edelman (1987)
Essential Components Of TNGS
"The essential components [of the TNGS theory] are (1) the existence of a source of connectional diversity during ontogeny; (2) a set of selection rules for changes in synaptic efficacy within synaptic populations leading to selection and additional variations; (3) the existence of functional reentrant circuits between maps to provide spatiotemporal continuity; (4) the parallel arrangements of such maps to yield classification couples or n-tuples for sampling of independent attributes; and (5) the final construction of global mappings containing motosensory ensembles that are the smallest units capable of perceptual categorization. If our assumptions about the need for any one of these major components are falsified, the theory will be severely weakened."[12]
Gerald M. Edelman (1987)
The Central Features Of TNGS
"A central feature of the theory of neuronal group selection is that the mechanisms leading to the formation of both the primary and secondary repertoire are epigenetic: while bounded by genetic constraints, events occurring at both developmental and experiential stages of selection lead to increases with time in both the heterogeniety and spatial diversity of cells and cellular structures. Such events depend upon the prior occurrence of other events in time courses that are long compared with those of intracellular events, and the cells involved exhibit interactive and cooperative spatial orderings that could not have been stored directly in the genetic code."[13]
Gerald M. Edelman (1987)
Transmitter Logic
"...instead of dividing input into only two classes - excitatory and inhibitory - and thinking of neuronal operations in Boolean terms, we might rather consider a kind of 'transmitter logic' in which each transmitter (in association with its post-synaptic partners) can lead to characteristic modifications of synapses receiving only certain other transmitters and located only on certain other parts of the dendritic tree."[14] - Gerald M. Edelman (1987)
Topobiology
"Topobiology - The study of the place-dependent regulation of cells resulting from interactions of molecules at the cell surfaces with those of other cells or substrates. In the context of this book, such place-dependent molecular interactions can regulate the primary processes of development and lead to changes in morphology by epigenetic means. The fundamental problem of topobiology is to determine how cells of different types are ordered in time or place during development to give species-specific tissue pattern and animal form."[15]
Gerald M. Edelman (1988)
The Developmental Genetic Question
"How does a one-dimensional genetic code specify a three-dimensional animal?"[16]
Gerald M. Edelman (1988)
The Evolutionary Question
"How is an answer to the developmental genetic question (q.v.) reconciled with the relatively rapid changes in form occurring in relatively short evolutionary times?"[17]
Gerald M. Edelman (1988)
The Morphoregulatory (MR) Hypothesis
"The Morphoregulatory (MR) Hypothesis - A hypothesis linking control of epigentic primary processes to a set of genetic elements (morphoregulatory, historegulatory, and selector genes) in order to account for morphogenesis. The linkage occurs via morphoregulatory proteins acting in CAM cycles and SAM modulatory networks. If confirmed this hypothesis would provide the basis for an answer to the developmental genetic question (q.v.)."[18]
Gerald M. Edelman (1988)
Prelinguistic Conceptual Categorization
"The conceptual categorization that emerges prior to language is obviously richer than perceptual categorization but is also enormously enhanced by language. Nonetheless, concepts are about the world..."[19]
Gerald M. Edelman (1989)
Memory in a Somatic Selection System
"Each memory reflects a system property within a somatic selection system. And each property serves a different function based upon the evolution of the appropriate neuroanatomical structure. These higher-order systems are selective and are based on the responses to environmental novelty of populations of neuronal groups arranged in maps. They are recognition systems."[20]
"I have made a distinction, which I believe is a fundamental one, between primary consciousness and higher-order consciousness. Primary consciousness is the state of being aware of things in the world - of having mental images in the present. But it is not accompanied by any sense of a person with a past and future. ...higher-order conciousness involves the recognition by a thinking subject of his or her own acts or affections. It exhibits direct awareness - the non-inferential or immediate awareness of mental episodes without the involvement of the sense organs or receptors."[21]
"There are, grossly speaking, two kinds of nervous system organization that are important to understanding how consciousness evolved. These systems are very different in their organization, even though they are both made up of neurons. (...) The two systems, limbic brain-stem and thalamocortical, were linked during evolution. The later-evolving cortical system served learning behavior that was adaptive to increasingly complex environments."[22]
"The first [type of nervous system] is the brain stem, together with the limbic (hedonic) system, the system concerned with the appetite, sexual and consummatory behavior, and evolved defensive behavior patterns. It is a value system; it is extensively connected to many different body organs, the endocrine system, and the autonomic nervous system. (...) It will come as no surprise that the circuits in this limbic-brain stem system are often arranged in loops, that they respond relatively slowly (in periods ranging from seconds to months), and that they do not consist of detailed maps. They have been selected during evolution to match the body, not to match large numbers of unanticipated signals from the outside world. These systems evolved early to take care of the bodily functions; they are systems of the interior."[23]
"The thalamocortical system consists of the thalamus and the cortex acting together, a system evolved to receive signals from the sensory receptor sheets and to give signals to voluntary muscles. It is very fast in its responses (taking from milliseconds to seconds), although its synaptic connections undergo some changes that last a lifetime. (...) Unlike the limbic-brain stem system, it does not contain loops so much as highly connected layered structures with massively reentrant connections. In many places these are topographically arranged. The cerebral cortex is a structure adapted to receive a dense and rapid series of signals from the world through the sensory modalities simultaneously - sight, touch, taste, smell, joint sense (feeling the position of your extremeties). It evolved later than the limbic-brain stem system to permit increasingly sophisticated motor behavior and the categorization of world events."[24]
Rejection Of Computational Models, Codes, & Point-to-point Wiring
"One conclusion we can draw (...) is that, while there are close similarities in certain regions, there are no absolutely specific point-to-point connections in the brain. The microscopic variability of the brain at the finest ramifications of its neurons is enormous, making each brain unique. These observations provide a fundamental challenge to models of the brain based on instruction or computation."[25]
Gerald M. Edelman (1998)
The Ubiquity of Degeneracy in Biological Systems
"Degeneracy, the ability of elements that are structurally different to perform the same function or yield the same output, is a well known characteristic of the genetic code and immune systems. Here, we point out that degeneracy is a ubiquitous biological property and argue that it is a feature of complexity at genetic, cellular, system, and population levels. Furthermore, it is both necessary for, and an inevitable outcome of, natural selection."[26]
Edelman, Gerald M. (1974). "Origins and Mechanisms of Specificity in Clonal Selection". In GM Edelman. Cellular Selection and Regulation in the Immune Response. 29. New York: Raven Press. ISBN 0-911216-71-5.
Edelman, Gerald M. (2005). From Brain Dynamics to Consciousness (IBM Research's Almaden Institute Conference on Cognitive Computing - A Prelude to the Future of Brain-Based Devices). (0:52:08)
Crossin, Kathryn L.; Edelman, Gerald M. (1986). "Mechanisms of cell adhesion in epithelial-mesenchymal transformations". Progress in Clinical and Biological Research226: 81-92. PMID 3543970.
D'Eustachio et al.
D'Eustachio, Peter G.; Rutishauser, Urs S.; Edelman, Gerald M. (1977). "Clonal selection and the ontogeny of the immune response". International Review of Cytology, Supplement5: 1-60. PMID 413803.
↑Description: Scanning Electron Microscope (SEM) image of leukocytes, red blood cells platelets circulating in the human bloodstream.
↑Description: Illustration of disulfide bridges (red) linking the light (L, green) and heavy (H, purple) chains of Immunoglobulin G (IgG) antibody. The variable (V) regions are located at the antigen-binding end; and, the constant (C) domains form the primary frame of the IgG molecule. Another disulfide bridge holds the two symmetrical units made up of a light chain (VL+CL) and a heavy chain (VH+CH1+CH2+CH3) together to form the completed antibody. Work by Rodney Porter with the enzyme papain resulted in cleavage of the antibody into Fab and Fc fragments, while work by Gerald Edelman lead to the reduction of the disulfide bridges so as to separate the molecule into light- and heavy-chain fragments. Together, this work allowed the antibody structure to be sequenced and reconstructed, resulting in the awarding of the Nobel Prize in Physiology or Medicine in 1972.
↑Description: The immune system has an ancient history within animals. All animals have an innate immune system, but only vertebrates have an "active" antibody-based immune system. The innate (left branch) immune system is ancient and anchored around the phagocytic white blood cells discovered by the pioneering biologist, embryologist, zoologist, immunologist, gerantologist Élie Metchnikoff (May 15, 1845–July 15, 1916).[2]. The antibody-based system (right branch) arose at the origin of vertebrates and is associated with the genome duplication events[3] that provided the duplicate copies of NCAM which eventually resulted in the emergence of genetically recombinant antibodies.[4][5] Paul Ehrlich (March 14, 1854–August 20, 1915)) was the discoverer of antibodies - and, along with Elie Metchnikoff, is considered to be one of the founders of Immunology. In 1908, they would share the first Nobel Prize in Physiology or Medicine. 64 years later, Edelman and Porter would share this very same prize.
↑Description: Clonal selection theory (CST) - hematopoietic stem cells (1) differentiate and undergo genetic rearrangement to produce a population of cells possessing a wide range of pre-existing diversity with respect to antibody expression (2). Lymphocytes expressing antibodies that would lead to autoimmunity are filtered from the population (3), while the rest of the population represents a degenerate pool of diversity (4) where antigen-selected variants (5) can be differentially amplified in response (6). Once the antigen has been cleared, the responding population will decrease, but not by as much as it was amplified, leaving behind a boosted capacity to respond to future incursions by the antigen - a form of enhanced recognition and memory within the system.
↑Description: 1) Degeneracy is the source of Robustness. 2) Degeneracy is positively correlated with Complexity. 3) Degeneracy increases Evolvability. 4) Evolvability is a prerequisite for Complexity. 5) Complexity increases to improve Robustness. 6) Evolvability emerges from Robustness.
↑The ingenuous 1964 Nirenberg and Leder experiment would identify the mRNA codons, a triplet sequence of ribonucleotides, that coded for each amino acid; thus elucidating the universal genetic code within the DNA when the transcription process was taken into account. Changes in the third position of the codon, the wobble position, often result in the same amino acid, and oftentimes the choice comes down to purine or pyrimidine only when a choice must be made. Similar, but variant, codon sequences tend to yield similar classes of amino acid - polar to polar, non-polar to non-polar, acidic to acidic, and basic to basic residues.
↑The twenty biological amino acids breakdown into four major classes of biological amino acids - polar (hydrophilic), nonpolar (hydrophobic), acidic, and basic side chain residues. The amino acid backbone is an amino group linked to an α-carbon, on which resides the side chain residue and a hydrogen atom, that is connected to a terminal carboxylate group.
![Cells in the Bloodstream[c]](https://anichin-myid.netlify.app/host-https-en.wikiversity.org/wiki/File:SEM_blood_cells.jpg)
![Immunoglobin Antibody[d]](https://anichin-myid.netlify.app/host-https-en.wikiversity.org/wiki/File:AntibodyChains.svg)
![Vertebrate Immunity[e]](https://anichin-myid.netlify.app/host-https-en.wikiversity.org/wiki/File:Hematopoiesis_simple.svg)
![Clonal Selection Theory[f]](https://anichin-myid.netlify.app/host-https-en.wikiversity.org/wiki/File:Clonal_selection.svg){kind=small}
![Relationships between degeneracy, complexity, robustness, and evolvability.[g]](https://anichin-myid.netlify.app/host-https-en.wikiversity.org/wiki/File:Relationships_between_degeneracy,_complexity,_robustness,_and_evolvability.png)
![The degeneracy of the genetic code buffers biological systems from the effects of random mutation.[h]](https://anichin-myid.netlify.app/host-https-en.wikiversity.org/wiki/File:06_chart_pu3.png)
![A large number of degenerate sidechain residue combinations form the tertiary structures that make the protein globular.[i]](https://anichin-myid.netlify.app/host-https-en.wikiversity.org/wiki/File:Overview_proteinogenic_amino_acids-ENG.svg)
