Abstract Modern biomedical science has achieved extraordinary success in identifying the molecular, genetic, inflammatory, metabolic, and cellular mechanisms associated with disease. Yet beneath these advances lies a fundamental question that remains comparatively underexplored: why do many diseases repeatedly emerge in specific anatomical locations rather than being distributed randomly throughout the human body? Across diverse pathological domains, stable spatial patterns are observed. Osteoporotic fractures cluster within characteristic skeletal regions. Atherosclerotic plaques preferentially develop at arterial bifurcations. Osteoarthritis disproportionately affects specific joint compartments. Disc degeneration concentrates within limited spinal segments. Male pattern baldness follows reproducible anatomical trajectories. Cancer metastases demonstrate organ-specific preferences. This paper proposes the concept of Spatial Vulnerability as a systems-level framework for understanding these recurring anatomical distributions. Spatial Vulnerability is defined as the non-random tendency of specific anatomical regions to accumulate biological risk as a consequence of persistent local exposure conditions operating across time. A four-layer conceptual model is proposed: Structure → Exposure → Adaptation → Pathology. Within this framework, disease emerges not solely from molecular mechanisms but from the interaction between disease-generating mechanisms and long-term spatial conditions, including mechanical loading, fluid dynamics, neural regulation, tissue architecture, and adaptive history. Rather than replacing existing biomedical explanations, the framework seeks to integrate them into a broader understanding of the geography of human pathology.
Israel Don (2026) studied this question.