GENESIS Framework R20.4–R21.2: A Drift‑Modulated Bistable Dynamical World Model for Chronic Disease and Sequential Topology Modulation

The GENESIS Framework R20.4–R21.2 documents the development of a drift‑modulated, bistable dynamical model for chronic disease stabilization, intervention testing, and disease‑landscape analysis. The core architecture is a three‑variable nonlinear ODE system (S,R,D) , where S denotes stress/symptom activation, R regenerative capacity, and D accumulated allostatic damage as a slow drift variable. A cubic sensitization term produces genuine multistability with a healthy attractor, a chronic attractor, and a saddle‑type separatrix. Damage‑dependent sensitization and regeneration terms implement allostatic fatigue and neuroinflammatory amplification.Version R20.4 (Reference Architecture 1.1) establishes a structurally robust baseline: the functional chronification threshold D_func, a three‑tier hierarchy of parameters (topology‑dominant r0 and k, basin modulators e and η, trajectory‑only δ, ε, β), and the Delta Paradox, i.e. the structural separation of topology‑modulating and purely dynamical interventions. Monte‑Carlo validation confirms bistability and topology stability under broad parameter variation.The R21.x series adds three principal advances. R21.1 introduces sequential intervention dynamics and shows that therapeutic topology is sequence‑invariant: drug order and staging gaps up to 120 days leave D_func, separatrix position, and healthy basin volume unchanged, establishing a Delta‑Paradox analog for sequential protocols. R21.2 provides a structural analysis of the system’s curl field and quasi‑potential landscape, characterizing GENESIS as a dominant‑gradient bistable system with a small rotational component and enabling an approximate disease energy landscape. An Altfall deep‑dive demonstrates that accumulated damage D acts as a slow separatrix modulator rather than an acute attractor switch, with direct implications for pacing‑based management of ME/CFS and Long COVID.The documentation positions GENESIS as a mechanistic world model in the sense of LeCun’s energy‑based framework: an explicit, interpretable energy landscape over disease states that can be extended towards patient‑specific, learning digital twins via future data‑assimilation layers. All code and analyses are provided as open‑access notebooks.