Neural Darwinism

Neural Darwinism is a biological, and more specifically - Darwinian and selectionist, approach to understanding global brain function originally proposed by American biologist, researcher and Nobel-Prize receipient[1] Gerald Maurice Edelman (July 1, 1929 – May 17, 2014). Edelman's 1988 book Neural Darwinism[2] introduced the public to the Theory of Neuronal Group Selection (TNGS) - which is the core theory underlying Edelman's explanation of global brain function.

Due to the book title, TNGS is most commonly referred to as the Theory of Neural Darwinism, although TNGS has roots going back to Edelman and Vernon Mountcastle's 1978 The Mindful Brain: Cortical Organization and the Group-selective Theory of Higher Brain Function.[3] The development of Neural Darwinism was deeply influenced by Edelman's work in the fields of immunology, embryology, and neuroscience - as well as, his deep commitment to Charles Darwin and the ingenuity of selection as the unifying foundation and grounding of all biology.

Neural Darwinism is really the neural part of the natural philosophical and explanatory framework Edelman employs for much of his work - Somatic Selective Systems. Neural Darwinism is the backdrop for a comprehensive set of biological hypotheses and theories Edelman, and his team, devised that seek to reconcile vertebrate and mammalian neural morphology, the facts of developmental and evolutionary biology, and the theory of Natural Selection into a detailed model of real-time neural and cognitive function that is unmistakably biological - and, built from the bottom-up, utilizing the variation that shows up in nature, rather than trying to explain it away as algorithmic noise in a computational system of logic circuits.

Neural Darwinism was the first book, in a trilogy of books, that Edelman wrote to delineate the scope and breadth of his ideas on how a biological theory of consciousness and animal body plan evolution could be developed in a bottom-up fashion in accordance with population biology and Darwin's theory of Natural Selection - as opposed to the top-down algorithmic and computational approaches that dominated cognitive psychology at the time.

The other two volumes are Topobiology - An Introduction to Molecular Embryology [4] with it's morpho-regulatory hypothesis of animal body plan development and evolutionary diversification via differential expression of cell surface molecules during development; and The Remembered Present - A Biological Theory of Consciousness[5] - a truly novel biological approach to understanding the role and function of "consciousness" and it's relation to cognition and behavioral physiology.

In the course of laying out the case for Neural Darwinism, or more properly TNGS, Edelman delineates a set of innovative concepts for rethinking the problem of nervous system organization and function - all-the-while, demanding a rigorously scientific criteria for building the foundation of a properly Darwinian, and therefore biological, explanation of neural function, perception, cognition and global brain function capable of adequately supporting Primary and Higher-order consciousness.

Neural Darwinism is a tour-de-force of biological thought and philosophy as well as raw science; Edelman being well-versed in the history of science, natural philosophy & medicine, as well as, robotics, cybernetics, computing & artificial intelligence. The multidisciplinary aspects of Neural Darwinism require a great deal of patience to absorb because of the scope and breadth of what it is trying to encompass.

The theoretical approach was conceived of in opposition to top-down algorithmic, computational, and instructionist approaches to explaining neural function. Edelman seeks to turn the problems of that paradigm to advantage instead; thereby highlighting the difference between bottom-up processes like we see in biology vis a vis top-down processes like we see in engineering algorithms. He sees neurons as living organisms working in cooperative and competitive ways within their local ecology, not computer chips or logic gates in a larger machine.

Among other things, Neural Darwinism posits that the evolution and behavior of cell populations in the body of an organism, operating over the lifetime of the organism, are determined by the rules of natural selection operating in the local cellular and physiological context. Just as the development and evolution of cooperative and competitive interactions between populations of organisms in the ecology are governed by the rules of natural selection - for cell populations in the body, the body is their ecology and their interactions within that context is still governed by the principles of population biology and natural selection.

Edelman was inspired by the successes of fellow Nobel Laureate[6] Frank MacFarlane Burnet and his Clonal selection theory of acquired antigen immunity out of a finite pool of pre-existing lymphocytes within the immune system. Edelman elevates the Darwinian foundations of Burnet's theory and generalizes the process to all cell populations of the organism. He also sees the problem as one of recognition and memory from a biological perspective, where the distinction and preservation of self vs. non-self is vital to organismal integrity. Neural Darwinism, as TNGS, is a theory of neuronal group selection that retools the fundamental concepts of Darwin and Burnet's theoretical approach. Neural Darwinism describes the development and evolution of the mammalian brain and it's functioning by extending the Darwinian paradigm deep into the body and nervous system.

Edelman was a medical researcher, physical chemist, immunologist, and aspiring neuroscientist when he was awarded the 1972 Nobel Prize in Medicine or Physiology (shared with Rodney Porter of Great Britain). Edelman's part of the prize was for his work revealing the chemical structure of the vertebrate antibody by cleaving the di-sulfide linkages that join the component chain fragments together, revealing the constant and variable chains.[7]

The work of Porter and Edelman provided the molecular and genetic foundations underpinning how antibody diversity was generated within the immune system. Their work supported earlier work by Frank MacFarlane Burnet describing how lymphocytes capable of binding to specific foreign antigens are differentially amplified by clonal multiplication following antigen discovery. Edelman would draw tremendous inspiration from the mechano-chemical aspects of antigen/antibody/lymphocyte interaction in relation to recognition of self-nonself; the degenerate population of lymphocytes in their physiological context; and the deep bio-theoretical foundations of this work in Darwinian terms.

After a foray into molecular embryology and neuroscience, in 1975, Edelman and his team went on to isolate the first neural cell-adhesion molecule N-CAM, one of the many molecules that hold the animal nervous system together. N-CAM turned out to be an important molecule in guiding the development and differentiation of neuronal groups in the nervous system and brain during embryo-genesis. To the amazement of Edelman, genetic sequencing revealed that N-CAM was the ancestor of the vertebrate antibody[8] produced in the aftermath of a set of whole genome duplication events at the origin of vertebrates that gave rise to the entire super-family of immunoglobulin genes.

Edelman reasoned that the N-CAM molecule which is used for self-self recognition and adherence between neurons in the nervous system gave rise to their evolutionary descendants, the antibodies, who evolved self-nonself recognition via antigen-adherence at the origins of the vertebrate antibody-based immune system. If clonal selection was the way the immune system worked, perhaps it was ancestral and more general - and, operating in the nervous system.

Degeneracy is a key concept in Neural Darwinism. The more we deviate from an ideal form, the more we are tempted to describe the deviations as imperfections. Edelman explicitly acknowledges the structural and dynamic variability of the nervous system. He likes to contrast the differences between redundancy in an engineered system and degeneracy in a biological system; and, demonstrates the how the "noise" of the computational and algorithmic approach is actually beneficial to a somatic selective system.[9]

Edelman's argument is that in an engineered system, a known problem is confronted, a logical solution is devised and an artifice is constructed to implement the resolution to the problem. To insure the robustness of the solution, critical components are replicated as exact copies. Redundancy provides a fail-safe backup in the event of catastrophic failure of an essential component but it is the same response to the same problem once the substitution has been made. This is great if the problem is predictable ahead of time and the solution works, but biological systems face an open and unpredictable series of spacetime events they have no foreknowledge of; and, redundancy fails when its designed to answer to the wrong problem.

Variation fuels degeneracy - and degeneracy provides somatic selective systems with more than one way to solve a problem; as well as, the ability to solve more than one problem the same way. This property of degeneracy has the effect of making the system more adaptively robust in the face of unforeseen contingencies, such as when one particular solution fails unexpectedly - there are still other unaffected pathways that can be engaged to result in the comparable final outcome. Early on, Edelman spends considerable time contrasting degeneracy vs. redundancy, bottom-up vs. top-down processes, and selectionist vs. instructionist explanations of biological phenomena.

Edelman's commitment to the Darwinian underpinnings of biology, his emerging understanding of the evolutionary relationships between the two molecules he had worked with, and his background in immunology lead him to become increasingly critical and dissatisfied with attempts to describe the operation of the nervous system and brain in computational or algorithmic terms.

Edelman explicitly rejects computational approaches to explaining biology as non-biological. He amasses an impressive array of arguments against the concept of computation or logical circuits based upon codes and point-to-point connectivity, showing how inconsistent the concepts are with the actual architecture of the nervous system. What some would call noise, Edelman calls natural variation.

He gradually began to understand that the problematic and annoying "noise" of the computational "circuit-logic" paradigm could be reinterpreted from a population biology perspective - where that variation in the "signal" or architecture was actually the engine of ingenuity and robustness from a selectionist perspective.

Edelman reflects upon what he calls Darwin's Program for obtaining a complete understanding of the rules of behavior and form in evolutionary biology.[10] He identifies four necessary requirements:

• An account of the effects of heredity on behavior - and behavior, on heredity.
• An account of how selection influences behavior - and, how behavior influences selection.
• An account of how behavior is enabled and constrained by morphology.
• An account of how morphogenesis occurs in development and evolution.

Edelman is interested in completing "Darwin's program" by reconciling the relationships between genes in a population which lie in the sperm, egg, and fertilized egg; and the individuals in a population who develop a particular phenotype as they transform from an embryo into an adult who will eventually procreate if they are adaptive enough. He would like to follow the process uninterrupted as we move through evolutionary time, one generation after another.

Darwin's program seeks a complete description of the transformations (T) that take us from:[11]

• Genome-) genes in a fertilized egg, thru development (T1) to
• Phenotype -) the embryo, which develops (T2) within the ecology into
• Phenotype-) an adult, who procreates (T3) with another individual to bring together
• Genome-) sperm and egg, which combine (T4) their...
• Genome-) genes into a fertilized egg.

In the early 1900's, the Neodarwinian Synthesis had unified the population biology of Mendelian Inheritance with Darwinian Natural Selection. By the 1940's, the theories had been shown to be mutually consistent and coherent with paleontology and comparative morphology. The theory came to be known as the Modern Synthesis on the basis of the title of the 1942 book Evolution: The Modern Synthesis by Julian Huxley (June 22, 1887 – February 14, 1975).[12] The Modern Synthesis really took off with the discovery of the structural basis of heredity in the form of DNA. The Modern Synthesis was greatly accelerated and expanded with the rise of the genenomic sciences, molecular biology, as well as, advances in computational techniques and power to modeling population dynamics. Edelman, and his team, were positioned in time and space to fully capitalize on these developments as his research progressed.

Edelman's first theoretical contribution to Neural Darwinism came in 1978, when he proposed his Group Selection and Phasic Reentrant Signalling: A Theory of Higher Brain Function.[13] Edelman lays out five necessary requirements that a biological theory of higher brain function must satisfy.[14]

• The theory should be consistent with the fields of embryology, neuroanatomy, and neurophysiology.
• The theory should account for learning and memory, and temporal recall in a distributed system.
• The theory should account how memory is updated on the basis of realtime experience.
• The theory should account for how higher brain systems mediate experience and action.
• The theory should account for the necessary, if not sufficient, conditions for the emergence of awareness.

Edelman recognizes that animal nervous systems operate fundamentally in terms of adaptive pattern recognition rather than logic. They are finite structures with a finite resolution on reality and their experience. They cannot know an effectively infinite reality in it's totality, therefore they don't attempt to do so because it would be impossibly costly in terms of time and resources. Animal nervous systems are not logic devices, nor are they Truth-seeking devices. Instead, animal nervous systems evolved a strategy of adaptive pattern recognition that allows for the environment to be cognitively sampled and approximated, or "imagined", based upon the finite nature of it's experience. The nervous system is capable of constructing a seemingly infinite variety of cognitive approximations that are of greater or lesser degree of correspondence to the actual features of reality that they are experiencing. They are not primarily interested in those models with the closest correspondence to reality, but rather to those models meeting their primary adaptive and/or hedonic needs at any particular point in time and space.

In Neural Darwinism, Edelman addresses the problem of neuronal ignorance, and the fact that most neurons know nothing about the outside world as we conceptualize it - they experience the world at the cell-membrane and, that is a local affair that occurs well within the environment of the body.

Neurons live a life that is driven by what Edelman describes as the primary processes of cellular development. He breaks them into two categories, Driving Processes and Regulatory Processes:[15]

Driving Processes -

• Cell Division
• Cell Motion
• Cell Death

Regulatory Processes -

• Cell Adhesion
• Induction
• Differentiation

Neurons can communicate as organisms do, but within the range of their experience and capacity. Any perception of reality on the scale that we know it is a collectively embodied endeavor on their part, but no individual neuron is ever aware of or dedicated to anything more than their survival within the ecological and physiological environment they find themselves in. Collective action is adaptive because it serves the physiological well-being of the organism, but neurons as individuals do not cognize the world the way we do, their world is communicated to them at the level of the cell membrane and it's surface molecules.

There is quite an evolutionary journey from cells to vertebrates and mammals. In Neural Darwinism, Edelman will pick up the picture at the vertebrate grade. Edelman envisages a vertebrate nervous system organized into a somatic division dedicated to the ecology and a visceral division dedicated to the hedonic needs of the organism. His view is similar to that of the great American vertebrate anatomist and paleontologist Alfred Sherwood Romer (December 28, 1894 – November 5, 1973) and his vision of the vertebrate as a dual animal.[16]

Romer proposed a situation where the chordate ancestor of vertebrates was a tunicate-like organism that expressed two different bodyplans over the course of it's life as it metamorphosized from it's larval form to it's adult form. He describes a mobile larval bodyplan with a notochord, central nervous system, segmented musculature, and head senses that is responsible for dispersal in the environment such that it can find a place to settle down and metamorphosize into an adult; and, a sessile filter-feeding adult anchored to the seafloor with a bodyplan that has pharyngeal gill slits and a visceral nerve net that runs along the GI tract. Romer saw the adaptive evolutionary challenge of vertebrates as one of somatovisceral integration.

Romer hypothesizes that at the origin of vertebrates these two bodyplans, which were sequentially expressed, came to be expressed simultaneously - and fused only at the hindbrain-gill slits and the sacral nerve. Originally, the only points of communication between the two "animals" was via the unmyelinated neurons of the parasympathetic nervous system. The rest of vertebrate evolution revolves around adaptions that allow the integration of these two bodyplans. Romer describes the gradual emergence of the myelinated sympathetic nervous system and it's increasingly sophisticated development of control of the viscera by the somatic division as we move along the evolutionary progression of vertebrate anatomy and physiology.

Interestingly, although Edelman makes no references to the Polyvagal Theory of Stephen W. Porges (1945-present), Porges work adds an additional layer of nuance to Romer's picture of vertebrate organization with respect to mammals; and, the neuroanatomical basis of a social-engagement system constructed out of the remodeled pharygeal arch system, a newly emergent neocortex with inhibitory outflow, and the myelinated division of the parasympathetic nervous system.[17][18][19]

Edelman describes the neuroanatomy of the somatic division, the central nervous system (CNS), as organized into a structure that is made up of nerve tracts as well as nuclear, laminar and columnar cell populations - and in contact with the external world via the primary sensory sheets and muscle ensembles. Since Edelman focuses on the operation of the neocortex, his hedonic feedback systems emanate from the world of subcortical structures that have roots deep in the brainstem and connections to the visceral body via the autonomic nervous system.

Communication between the two divisions can occur via the autonomic, endocrine, and immune systems but, the key neural integration point is where the reticular network of the brainstem ties together the cranial nuclei of the pharyngeal arch system, the general and special tracts of the peripheral nervous system, and the global neurotransmitter fountains that diffusely project upward to the midbrain, thalamus, and cortex, as well as back down the spinal column. This is the point of hedonic feedback between somatic and visceral divisions that communicates adaptive value to the central nervous system and its perceptual-behavioral action networks in accordance with how the needs of the visceral body are being met.

Edelman's background made him well aware that the most fundamental distinction an organism can make is between self and non-self. He considers the key problem for cells, organized into mesencyhme and epithelia within a multicellular animal, is how to organize themselves such that they can act as a unified whole, or "self" within a broader ecology when survival necessitates it. With his understanding of duality of vertebrate anatomical architecture, he focuses on how the nervous system might give rise to a unified sense of "self" from it's structure and dynamic interactions with the environment.

Edelman describes the central nervous system as a set of topological maps of the body periphery and muscle groups that become increasingly plastic as we move up from the base of the spine all the way to the midbrain and thalamus. From there the thalamus maps to the neocortex. The maps are able maintain their topological integrity due the way traveling nerve bundles in development largely preserve their spatial relationships they migrate to contact other cell groups in the body. The maps are formed in development via the neural transmission from the periphery traveling inward and stimulating the release of growth factors and synaptic reinforcement amongst the cells and neurons involved - thereby, consolidating and stabilizing the maps.

A second critical component in establishing a sense of self vs. non-self is the motor-ensembles which underlie the posture of the organism. Cognition has two primary components - sensory and motor. Posture is how the organism orients itself in the environment based upon it's hedonic state and the ecological context. Posture is mediated by the motor ensembles responding to the hedonic evaluation of perceptual experience. These motor ensembles are topobiologically mapped, just as the sensory maps of the periphery - indeed, the sensory maps are intimately tied to the motor groups that move them.

These systems of embodied interactive topobiological maps and postural motor ensembles interact at all levels of the CNS, are increasingly plastic as we move up the CNS to the cortex, and are ultimately tied to hedonic pathways emanating from the subcortical and brainstem centers that receive feedback from the viscera and play an important role in an evolving sense of "self" coalescing around a hedonic center as the system adapts to everything else that is non-self.

One specific goal of the theory is to demonstrate how the subject of consciousness can approached scientifically and in a manner that is consistent with the underlying principles of Darwinian biology. Neural Darwinism ties the process of consciousness directly to the cognitive architecture of the organism and the need to assimilate previously un-encountered phenomena into the organisms repertoire of adaptive responses. Edelman acknowledges that human consciousness appears to have evolved a broader range of potential than our animal cousins and he takes time to divide the process of consciousness into Primary and Higher-order so that he can address the uniqueness of linguistic consciousness vis a vis the remembered present of mammalian consciousness more broadly.

In Edelman's view consciousness is a sub-component of cognition more broadly. Consciousness functions to deal with novel aspects of our experience which have not been previously encountered and adapted to. Edelman reasons that consciousness is dedicated to the assimilation of novelty and attending to hedonically-salient ecological con-specifics.

Once the novelty has been adapted to and assimilated as habituated reflex, or the basic hedonic need met, the novelty ceases to be novel - and, consciousness is freed up to attend to further novel aspects of the organisms perceptual experience and the ongoing adaption to it's environment.

By restraining the definition of consciousness in this manner, the term acquires a very specific, finite, and biologically defineable form as a psycho-physiological process with an underlying anatomical architecture and evolutionary history, allowing it to be scientifically tested, categorized, and examined. He seeks to ground the process in the anatomy and physiology of the organism - specifically to neuronal groups within the nervous system and how they perform the task of perceptual categorization from an initially nebulous wave of world signals being received by the sensory sheets in conjunction with hedonic feedback systems.

The thalamo-cortical system is of particular importance since the neocortex is thought to play an important role in higher order consciousness - and, this is the primary sensory gateway that connects the neocortex to the rest of the sub-cortical system. The connections from the paleo- and archi-cortex provide important input as well. The neocortex itself, will send out a shower of inhibitory outflow that modulates and refines sub-cortical motor actions as it travels down the central nervous system to the distal neuro-muscular motor groups along each tract.

Edelman organized key ideas of the TNGS theory into three main processes:

Primary Repertoire - how the phenotype emerges from the genotype via genetics and epigenesis operating at the cellular level under the influence of the primary processes of development;

Secondary Repertoire - how behavioral selection occurs among globally-ignorant local neuronal groups in response to the influence of cognitive and hedonic feedback systems;

and Re-entrant Mapping - how neural tracts "map" the surfaces they connect to, thereby providing topological relations between neuronal groups that make possible sustained physiological entrainment of local and distant neural groups into temporally stable global behavioral units of action or perception.

The first major contribution to the theory appeared in 1978, in The Mindful Brain: Cortical Organization and the Group-selective Theory of Higher Brain Function by Gerald Edelman and Vernon Benjamin Mountcastle (MIT Press). Mountcastle describes the columnar structure of the cortical groups within the neocortex, while Edelman develops his argument for selective processes operating among degenerate primary repertoires of neuronal groups.

Edelman defines Perceptual Categorization as "the selective discrimination of an object or event from other objects or events for adaptive purposes".[20]

The last part of the theory attempts to explain how we experience spatiotemporal consistency in our interaction with environmental stimuli. Edelman called it "reentry" and proposes a model of reentrant signaling whereby a disjunctive, multimodal sampling of the same stimulus event correlated in time leads to self-organizing intelligence. Put another way, multiple neuronal groups can be used to sample a given stimulus set in parallel and communicate between these disjunctive groups with incurred latency.

Edelman's interest in selective systems expanded into the fields of neurobiology and neurophysiology, and in Neural Darwinism, Edelman puts forth a theory called "neuronal group selection". It contains three major parts:

1. Anatomical connectivity in the brain occurs via selective mechanochemical events that take place epigenetically during development. This creates a diverse primary repertoire by differential reproduction.
2. Once structural diversity is established anatomically, a second selective process occurs during postnatal behavioral experience through epigenetic modifications in the strength of synaptic connections between neuronal groups. This creates a diverse secondary repertoire by differential amplification.
3. Reentrant signaling between neuronal groups allows for spatiotemporal continuity in response to real-world interactions. In "The Remembered Present" (1989) and later, "Bright Air, Brilliant Fire: On the Matter of the Mind" (1992) and "A Universe of Consciousness: How Matter Becomes Imagination" (2001; coauthored with Giulio Tononi), Edelman argues that thalamocortical and corticocortical reentrant signaling are critical to generating and maintaining conscious states in mammals.

With neuronal heterogeneity (by Edelman called degeneracy), it is possible to test the many circuits (on the order of 30 billion neurons with an estimated one quadrillion connections between them in the human brain) with a diverse set of inputs, to see which neuronal groups respond "appropriately" statistically. Functional "distributed" (widespread) brain circuits thus emerge as a result.

Edelman goes into some detail about how brain development depends on a variety of cell adhesion molecules (CAMs) and substrate adhesion molecules (SAMs) on cell surfaces which allow cells to dynamically control their intercellular binding properties. This surface modulation allows cell collectives to effectively "signal" as the group aggregates, which helps govern morphogenesis. So morphology depends on CAM and SAM function. And CAM and SAM function also depend on developing morphology.

Edelman theorized that cell proliferation, cell migration, cell death, neuron arbor distribution, and neurite branching are also governed by similar selective processes.

Once the basic variegated anatomical structure of the brain is laid down during early development, it is more or less fixed. But given the numerous and diverse collection of available circuitry, there are bound to be functionally equivalent albeit anatomically non-isomorphic neuronal groups capable of responding to certain sensory input. This creates a competitive environment where circuit groups proficient in their responses to certain inputs are "chosen" through the enhancement of the synaptic efficacies of the selected network. This leads to an increased probability that the same network will respond to similar or identical signals at a future time. This occurs through the strengthening of neuron-to-neuron synapses. And these adjustments allow for neural plasticity along a fairly quick timetable.

It has been suggested that Friedrich Hayek had earlier proposed a similar idea in his book The Sensory Order: An Inquiry into the Foundations of Theoretical Psychology, published in 1952 (Herrmann-Pillath, 1992). Other leading proponents include Jean-Pierre Changeux, Daniel Dennett and Linda B. Smith. William Calvin proposes true replication in the brain, whereas Edelman opposes the idea that there are true replicators in the brain.

Criticism of Neural "Darwinism" was made by Francis Crick on the basis that neuronal groups are instructed by the environment rather than undergoing blind variation. A recent review by Fernando, Szathmary and Husbands explains why Edelman's Neural Darwinism is not Darwinian because it does not contain units of evolution as defined by John Maynard Smith. It is selectionist in that it satisfies the Price equation, but there is no mechanism in Edelman's theory that explains how information can be transferred between neuronal groups.[21] A recent theory called Evolutionary Neurodynamics being developed by Eors Szathmary and Chrisantha Fernando has proposed several means by which true replication may take place in the brain.[22] These neuronal models have been extended by Fernando in a later paper.[23] In the most recent model, three plasticity mechanisms i) multiplicative STDP, ii) LTD, and iii) Heterosynaptic competition, are responsible for copying of connectivity patterns from one part of the brain to another. Exactly the same plasticity rules can explain experimental data for how infants do causal learning in the experiments conducted by Alison Gopnik. It has also been shown that by adding Hebbian learning to neuronal replicators the power of neuronal evolutionary computation may actually be greater than natural selection in organisms.[24]

Jean Piaget (1896–1980) often used the concept of the schème (a supposed unit of action-coding), which he left as an abstraction. However, later theorizing led to the hypothesis that such schèmes were probably RNA-like molecules, at least in their simplest cases. Such molecular sites would need to intercommunicate mainly via infra-red signals: messages which would be able to travel through fatty tissue such as myelin, but would be blocked by water barriers (of >20 microns). This "new" [R]-system was proposed as a cooperative alternative arrangement, more concerned with digital signals and data required for advanced thinking—(whereas the traditional [A]-system of action-potentials and synapses would perhaps cope more with activities such as logistics, muscle-control, and pattern-recognition which can probably manage using analogue devices—a division of labour).[25][26][27][28][29][30][31][32]

Whether or not one accepts those actual details, such a molecule-based system offers (i) an obvious scope for clear-cut encoding, (ii) an obvious explanation for any inherited behaviour-traits, (iii) a vastly greater number of candidate-codes from which to select-or-waste in a Darwinian contest; etc. Hence, this might be seen as overcoming Crick's objections, at least partially.

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• Edelman, Gerald M. (December 12, 1972). Jan Lindsten (ed.). Nobel Lectures, Physiology or Medicine 1971-1980 - "Antibody Structure and Molecular Immunology". World Scientific Publishing Co., Singapore 1992. ISBN 978-9810207915.
• Edelman, Gerald M. (1987). "CAMs and Igs: cell adhesion and the evolutionary origins of immunity". Immunol Rev. 100: 11–45. doi:10.1111/j.1600-065x.1987.tb00526.x. PMID 3326819.
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• Edelman, Gerald M. (November 20, 2001). "Degeneracy and Complexity in Biological Systems". Proceedings of the National Academy of Sciences, U.S.A. 98 (24): 13763–13768. PMID 11698650.
• Edelman, Gerald M. (2004). "Wider Than The Sky: The Phenomenal Gift of Consciousness". Yale University Press. ISBN 9780300102291.
• Edelman, Gerald M. (2006). "Second Nature: Brain Science and Human Knowledge". Yale University Press. ISBN 9780300120394.
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• Fernando, C.; Goldstein, R.; Szathmáry, E. (2010). "The Neuronal Replicator Hypothesis". Neural Computation. 22 (11): 2809–2857. doi:10.1162/NECO_a_00031. PMID 20804380. S2CID 17940175.
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• Jessell, T; Kandel, E (2002). "E. W. Maxwell Cowan 1931—2002". Nat Neurosci. 5 (9): 827. doi:10.1038/nn0902-827.
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• Porges, Stephen W. (2001). "The Polyvagal Theory: Phylogenetic substrates of a social nervous system". International Journal of Psychophysiology. 42: 123-146.
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• How Brains Think: Evolving Intelligence, Then and Now by William H. Calvin
• Neurogenesis in the Adult Human Brain
• Johnson, George "Evolution Between the Ears", "New York Times," April 19, 1992, accessed April 16, 2007 (a critical review of Gerald Edelman's 1992 book Brilliant Air, Brilliant Fire)
• Calvin, William "Neural Darwinism: The Theory of Neuronal Group Selection", Science, 24 June 1988, accessed April 16, 2007 (a review of Gerald Edelman's book Neural Darwinism)
• Webpage of Chrisantha Fernando, first author of "Copying and Evolution of Neuronal Topology"
• A Wikiversity course that extensively discusses neural Darwinism
• The basic Neuroscience course at Wikiversity
• The Department of Neuroscience at Wikiversity