Medicine beyond magic bullets: a formal case for multilevel interventions

Western medicine's paradigmatic search for 'magic bullet' interventions is facing increasing difficulty: Between 1950 and 2010 the inflation-adjusted cost per USFDA-approved drug has increased exponentially in time, a draconian inverse of the famous Moore's Law of computing. A sequence of empirically-oriented statistical models suggests that carefully designed synergistic multifactorial and multiscale strategies might evade this relationship

Metabolic constraints on the evolution of genetic codes: Did multiple 'preaerobic' ecosystem transitions entrain richer dialects via Serial Endosymbiosis?

A mathematical model based on Tlusty's topological deconstruction suggests that multiple punctuated ecosystem shifts in available metabolic free energy, broadly akin to the 'aerobic' transition, enabled a punctuated sequence of increasingly complex genetic codes and protein translators under mechanisms similar to the Serial Endosymbiosis effecting the Eukaryotic transition. These evolved until the ancestor to the present narrow spectrum of nearly maximally robust codes became locked-in by path dependence

Empirical predictions of an intrinsically disordered protein theory approach to glycan/lectin reaction kinetics

Newly-developed methods from the theory of intrinsically disordered proteins can be applied to the flexible glycan structures that coat cellular surfaces and provide rich channels for biological information transmission. Extension of a mechanistic 'arm-in-sleeve' model via a nonrigid molecule symmetry analysis leads to expectation of empirical observation of punctuated 'spectral' classifications in glycan/lectin interaction, parameterized by an appropriate index of glycan frond length or other index of topological complexity, possibly requiring groupoid classifications analogous to quasicrystals

Beyond the fuzzy lock-and-key: spontaneous symmetry shifts and glycan/lectin logic gates

Changes in the molecular topology of glycan/lectin interaction may explain observed reaction punctuation driven by experimental gradients in reactant concentration. Adoption of a 'biological renormalization' perspective from statistical physics for the analysis of such phase transitions suggests, in marked contrast to conventional physical systems, a broad spectrum of possible universality class behaviors. This spectrum may, in typical perverse biological manner, be of central scientific interest. Generalization, via formalism abducted from coevolutionary theory, suggests that glycan/lectin molecular switches instantiate logic gates that may be as sophisticated as those characterizing basic neural process, if on a different scale

Immune cognition and culture: implications for the AIDS vaccine

We examine the implications of IR Cohen's 'cognitive principle' address of the immune system [1-3] for the HIV vaccine program. This approach takes on a special importance in the context of recent work by Nisbett et al. [4] showing clearly that central nervous system (CNS) cognition is fundamentally different for populations having different cultural systems, and in the context of a growing body of evolutionary anthropology which suggests that such effects are inevitable, since culture is as much a part of human biology 'as the enamel on our teeth'

Crosstalk and the spectrum of biological global broadcasts: Toward generalization of the Baars consciousness model across physiological subsystems

Once cognitive biological phenomena are recognized as necessarily having 'dual' information sources, it is easy to show that the information theory chain rule implies isolating coresident information sources from crosstalk requires more metabolic free energy than permitting correlation. This provides conditions for an evolutionary exaptation leading to dynamic global broadcasts of interacting cognitive biological processes analogous to, but slower than, consciousness, itself included within the paradigm. The argument is closely analogous to the well-studied exaptation of noise to trigger stochastic resonance amplification in physiological systems

A modular network treatment of Baars' Global Workspace consciousness model

Network theory provides an alternative to the renormalization and phase transition methods used in Wallace's (2005a) treatment of Baars' Global Workspace model. Like the earlier study, the new analysis produces the workplace itself, the tunable threshold of consciousness, and the essential role for embedding contexts, in an explicitly analytic 'necessary conditions' manner which suffers neither the mereological fallacy inherent to brain-only theories nor the sufficiency indeterminacy of neural network or agent-based simulations. This suggests that the new approach, and the earlier, represent different analytically solvable limits in a broad continuum of possible models, analogous to the differences between bond and site percolation or between the two and many-body limits of classical mechanics. The development significantly extends the theoretical foundations for an empirical general cognitive model (GCM) based on the Shannon-McMillan Theorem. Patterned after the general linear model which reflects the Central Limit Theorem, the proposed technique should be both useful for the reduction of expermiental data on consciousness and in the design of devices with capacities which may transcend those of conventional machines and provide new perspectives on the varieties of biological consciousness

Machine Hyperconsciousness

Individual animal consciousness appears limited to a single giant component of interacting cognitive modules, instantiating a shifting, highly tunable, Global Workspace. Human institutions, by contrast, can support several, often many, such giant components simultaneously, although they generally function far more slowly than the minds of the individuals who compose them. Machines having multiple global workspaces -- hyperconscious machines -- should, however, be able to operate at the few hundred milliseconds characteistic of individual consciousness. Such multitasking -- machine or institutional -- while clearly limiting the phenomenon of inattentional blindness, does not eliminate it, and introduces characteristic failure modes involving the distortion of information sent between global workspaces. This suggests that machines explicitly designed along these principles, while highly efficient at certain sets of tasks, remain subject to canonical and idiosyncratic failure patterns analogous to, but more complicated than, those explored in Wallace (2006a). By contrast, institutions, facing similar challenges, are usually deeply embedded in a highly stabilizing cultural matrix of law, custom, and tradition which has evolved over many centuries. Parallel development of analogous engineering strategies, directed toward ensuring an 'ethical' device, would seem requisite to the sucessful application of any form of hyperconscious machine technology

On biological homochirality

Generalizing Landau's spontaneous symmetry breaking arguments using the standard groupoid approach to stereochemistry allows reconsideration of the origin of biological homochirality. On Earth, limited metabolic free energy density may have served as a low temperature analog to 'freeze' the system into the set of simplest homochiral transitive groupoids representing reproductive chemistries. These engaged in Darwinian competition until a single configuration survived. Subsequent path dependent evolutionary process licked in this initial condition. Astrobiological outcomes, in the presence of higher initial metabolic free energy densities, could well be considerably richer, perhaps of mixed chirality. One result would be a complicated distribution of biological chirality across a statistically large sample of extraterrestrial stereochemistry, in contrast with a recent prediction of a racemic average

Extending the Modern Synthesis: The evolution of ecosystems

The Modern Evolutionary Synthesis formalizes the role of variation, heredity, differential reproduction and mutation in population genetics. Here we explore a mathematical structure, based on the asymptotic limit theorems of information theory, that instantiates the punctuated dynamic relations of organisms and their embedding environments. The mathematical overhead is considerable, and we conclude that the model must itself be extended even further to allow the possibility of the transfer of heritage information between different classes of organisms. In essence, we provide something of a formal roadmap for the modernization of the Modern Synthesis