Alfred North Whitehead’s An Enquiry Concerning the Principles of Natural Knowledge reimagines epistemology by grounding natural science in a relational ontology of events—temporal-spatial nexuses like "a flash of lightning"—as the primary reality, replacing Newtonian matter. He critiques the bifurcation of nature (separating perceived qualities from scientific quantities) and introduces the method of extensive abstraction, defining geometric entities (points, lines) as logical constructs derived from overlapping events’ duration (temporal thickness). Central is the percipient event—an observer’s situated participation in nature—which unifies sense-awareness (direct perception) and causal efficacy (contextual relations) into coherent observation. Whitehead’s theory of objects distinguishes scientific objects (e.g., electrons as inferred patterns) from perceptual objects (e.g., colors as immediate data), mediated by significance—the relational embedding of events in a spatiotemporal manifold. He rejects static substance, framing nature as a creative advance of interconnected rhythms. Though overshadowed by Process and Reality, this work pioneered process ontology, influenced later philosophy of science (e.g., Quine’s holistic empiricism), and laid groundwork for rejecting Cartesian dualism, remaining a cornerstone in relational metaphysics and interdisciplinary critiques of reductionist science.

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