Many aspects of health and disease are modeled using the abstraction of a “pathway” – a set of protein or other subcellular activities with specified functional linkages between them. This metaphor is a paradigmatic case of a deterministic, mechanistic framework that focuses biomedical intervention strategies on altering the members of this network or the up/down-regulation links between them – rewiring the molecular hardware. However, protein pathways and transcriptional networks share important properties with neural networks and related dynamical systems, which implies that they can exhibit interesting and unexpected capabilities such as trainability (memory) and information processing in a context-sensitive manner. Specifically, they may be amenable to manipulation via their history of stimuli (equivalent to experiences, in behavioral science). If true, this would enable a new class of biomedical interventions that targets aspects of the dynamic physiological “software” implemented by pathways and gene-regulatory networks. Here, we propose an expanded view of pathways from the perspective of basal cognition. We review clinical and laboratory data supporting the idea that a broader understanding of pathways (and how they process contextual information across scales) is a limiting factor for progress in many areas of physiology and neurobiology. We argue that a fuller understanding of the functionality and tractability of pathways must go beyond a focus on the mechanistic details of their structure, to encompass their physiological history and embedding within higher levels of organization in the organism, with numerous implications for data science addressing health and disease. Exploiting tools and concepts from behavioral and cognitive sciences is not just a philosophical stance on biochemical processes; at stake is a new roadmap for overcoming the limitations of today’s pharmacological strategies and for the inference of future therapeutic interventions impacting a wide range of disease states.

No abstract

No abstract

No abstract

No abstract