Precision medicine has accumulated unprecedented data density through genomics, multi-omics, and artificial intelligence, yet its translation into routine care for complex diseases has lagged behind the pace of data generation. The five tenets for evidence-based precision medicine articulated in Nature Medicine in 2026—heterogeneity in risk, response, and prognosis; signal robustness; structured statistical benchmarking; precision trial designs; and individual and societal risk–benefit—point to a shared methodological gap: beyond oncology, precision medicine lacks an explicit computational language capable of representing living states across biological scales and submitting such representations to stringent incremental testing against competitive benchmark models. This judgment requires a qualification: systems medicine, network medicine, multi-omics integration, and digital twins have each already proposed cross-scale or multi-system state representations. Prim-Lex Medicine cannot establish its originality by denying the existence of these approaches; it can only do so by providing independently verifiable incremental information beyond the space they already cover. A concurrent Nature Genetics perspective on clinical implementation of multi-omics concludes that the central challenge is no longer data generation but the standardization and interpretability of complexity; multiplexing, high dimensionality, and probabilistic interpretation introduce risks to reproducibility and clinical validity. Prim-Lex Theory (Economic Climatology) is a candidate framework situated precisely in this methodological space. Its Fivefold Prim-Fire architecture organizes living states into a cross-scale taxonomy spanning physical energy metabolism, cellular redox state, plant metabolism, neural coherence, and Earth-system coupling. Its two classes of Prim-Lexon—entity/time equivalents anchored in the fluorescence lifetime of NAD(P)H bound to dehydrogenase proteins, and coherence-coupling equivalents composed of criticality, synchronization, information integration, and phase—address, respectively, the “intensity of a single entity’s state” and the “structural coordination among multiple subsystems.” This article reconstructs the international academic expression of Prim-Lex Medicine, rigorously separating philosophical heuristics, mathematical definitions, established experimental measurements, candidate clinical hypotheses, and independently validated findings. It advances a falsifiable validation program built on the clinical operationalization of Five-Element computation, Eight-Dimensional state representation, and Nine-Nexus decision constraints, with pre-registration across multi-specialty clinical data, competitive benchmark models, and external validation of incremental predictive value as the primary criterion. Regarding the mathematics of Five-Element interaction, this article makes explicit that the quadratic form can identify only the symmetric part of the matrix and cannot distinguish the directionality of “generation” from “restriction”; testing directed relationships therefore requires separating a static symmetric interaction model from a dynamic directed coupling model that requires longitudinal data. It does not claim that Prim-Lex Medicine has uncovered a common cause of disease or improved patient outcomes; its academic value depends on independent data testing incremental predictive value, calibration quality, and cross-disease transportability. As the first step in this testing program, the pre-registration protocol and statistical analysis plan (SAP) covering four specialties was publicly frozen through OSF Registries on October 23, 2026 (DOI: 10.17605/OSF.IO/8QPMK), providing an immutable time anchor for subsequent independent validation.
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Shen Xiaowang (2026) studied this question.
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