Contemporary biomedicine has achieved extraordinary explanatory and therapeutic power in acute disease, trauma, infection, and organ-specific pathology. Yet its prevailing architecture remains less adequate for chronic, multisystem, stress-mediated, and environmentally contingent illness, where symptoms and dysfunctions frequently span conventional specialty boundaries. This white paper argues that such limitations arise not only from incomplete data but from a fragmented explanatory framework that treats the organism as a collection of discrete systems rather than as a nested continuum of dynamically coupled processes. Drawing on convergent work in fascia and interstitium research, biotensegrity and mechanotransduction, endothelial and microvascular medicine, mitochondrial stress biology, mast-cell and innate immune surveillance, and interfacial-water theory, the paper advances an integrative model of physiology organized around substrate, flow, sensing, exchange, defense, and recovery.
In this framework, fascia and interstitium constitute a body-wide mechanosensitive and fluid-linked substrate; endothelium and microcirculation serve as distributed exchange interfaces; mast cells and related sentinels monitor tissue boundaries and perturbation; and mitochondria function as executive regulators that allocate energy between adaptive function and defensive lock-in. Interfacial water is introduced as a candidate substrate-level explanatory layer that may help unify otherwise disconnected observations concerning hydration, charge separation, transport conditions, and interface-dependent biological behavior. The paper does not claim equal evidentiary status for all components. Rather, it distinguishes between strongly supported findings, integrative inferences, and exploratory hypotheses, thereby preserving transparency while enabling higher-order synthesis.
On this basis, chronic illness is reframed not simply as local lesion, isolated pathway dysfunction, or prolonged exposure to insult, but as a state of impaired organismal coherence in which mechanobiological strain, disturbed exchange, altered energetic allocation, persistent innate activation, and incomplete healing become mutually reinforcing. Healing, correspondingly, is reconceived not merely as suppression of downstream symptoms but as the restoration of conditions required for salugenesis: the active re-establishment of adaptive flow, exchange, signaling, and recovery. The paper further argues that the political economy of knowledge has favored fragmented, profit-compatible models over substrate-level and preventive integrations, and that a renewed epistemic commons is required if physiology is to develop toward a more transparent, preventive, and non-coercive science of health.
