The Biothermodynamic Evolution Hypothesis: A Predictive Research Programme for Biological Organization Under Constraint

Living systems maintain coherence under constant flux, yet biology still lacks a predictive grammar for determining when biological organization will adapt, reorganize, or fail under constraint. Biological transitions are commonly analysed as changes in genes, pathways, organisms, or environments considered separately, although many such transitions emerge from how energetic, informational, microbial, immune, metabolic, neural, and regulatory layers are jointly organized under changing conditions. The Biothermodynamic Evolution Hypothesis (BEH) proposes that a living system’s regime of encounters constrains its energy–information economy, and that this economy shapes which biological capacities are maintained, simplified, expanded, externalized, or reorganized. Its central claim is not that thermodynamics replaces population genetics or that the holobiont is always the unit of selection. Rather, BEH treats organizational trajectories under load as candidate explanatory and predictive objects: in selected systems, changes in cross-layer integration may precede visible phenotypic, clinical, or ecological transitions and generate directional, falsifiable predictions. We define a minimal operational vocabulary in which χ denotes a candidate descriptor of cross-layer integration and the Biothermodynamic Flux Index (BFI) represents a candidate trajectory model relating load, efficiency, and buffering. Neither construct is presented as a conserved quantity, a universal thermodynamic state function, or a validated biomarker; both must compete against alternative formulations and same-input comparator models. BEH is therefore framed as an active research programme rather than a finished theory. Its value depends on whether it generates preregisterable predictions, survives prospective and cross-domain testing, and adds mechanistic, explanatory, or predictive value beyond established models. By shifting attention from isolated components to the organization of living systems under constraint, BEH offers a common grammar for studying adaptation, resilience, breakdown, and recovery without erasing domain-specific mechanisms.