Abstract
AbstractFor a broad spectrum of low level cognitive regulatory and other biological phenomena, isolation from signal crosstalk between them requires more metabolic free energy than permitting correlation. This allows an evolutionary exaptation leading to dynamic global broadcasts of interacting physiological processes at multiple scales. The argument is similar to the well-studied exaptation of noise to trigger stochastic resonance amplification in physiological subsystems. Not only is the living state characterized by cognition at every scale and level of organization, but by multiple, shifting, tunable, cooperative larger scale broadcasts that link selected subsets of functional modules to address problems. This multilevel dynamical viewpoint has implications for initiatives in translational medicine that have followed the implosive collapse of pharmaceutical industry 'magic bullet' research. In short, failure to respond to the inherently multilevel, multiscale nature of human pathophysiology will doom translational medicine to a similar implosion.
Highlights
1.1 Magic bulletsThe collapse of pharmaceutical research productivity (e.g., Paul et al, 2010) has spawned attempts to speed the ‘bench to bedside’ translation of basic re-search into therapeutic instruments, usually seen as new magic bullets, drugs or otherwise.The context for this effort can be seen in figure 1, adapted from Bernsetin (2010)
Baars’ global workspace model of animal consciousness attributes the phenomenon to a dynamic array of unconscious cognitive modules that unite to become a global broadcast having a tunable perception threshold not unlike a theater spotlight, but whose range of attention is constrained by embedding contexts (e.g., Baars, 1988, 2005; Baars and Franklin, 2003): 1. The brain can be viewed as a collection of distributed specialized networks
We provide a minimal formal overview that will be reexpressed in more complex form, much like Onsager’s nonequilibrium thermodynamics, and using these ideas, examine recent initiatives on ‘translational medicine’ (e.g., Littman and Krishna, 2011) that seek to overcome the recent collapse of pharmaceutical industry productivity (Paul et al, 2010)
Summary
The collapse of pharmaceutical research productivity (e.g., Paul et al, 2010) has spawned attempts to speed the ‘bench to bedside’ translation of basic re-. As phospholipid composition determines the quaternary structure and function of a high proportion of a cell’s proteins, and determines signal transduction responses to most protein changes, it is likely that the functions of proteins in vitro will be, for the most part, somewhat different from the functions of those same proteins in vivo. In some contrast to current biomedical ‘magic bullet’ ideology, we will attempt to lay a foundation for the development of multilevel, multiscale ‘magic strategies’ that may, at least in their initial stages, better fit the inherently complex underlying patterns of multifactorial human pathophysiology. This is not an effort for the faint of heart, and we must begin far afield
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