The Evolution of Large Organism Size: Disparate Physiologies Share a Foundation at the Smallest Physical Scales

Life is defined by self-governing networks of molecules changing conformation cyclically to convert thermodynamic motion into directional work that creates structure. A spectrum of scale, from nanoscopic to macroscopic, involves a shift from intracellular thermody-namically driven processes (thermal agitation ultimately rooted in quantum phenomena) to intercellular bulk flows described by classical physics; from short-distance transport involving diffusion and cytoskeletal transport to long-distance pressure fluxes in hydrau-lic networks. A review of internal transport systems in macroscopic eukaryotes suggests that a key evolutionary step favoring large size and multicellularity involved exploiting molecular-scale stochasticity to generate organized bulk flows (e.g. motor proteins collec-tively generating mechanical pressures in metazoan tissues such as cardiac muscle; within tracheophytes, active and passive phloem loading/unloading inducing pressure gradients, and active regulation enabling passive xylem function and hydraulic reliability; sieve-like conduction in heterokonts; peristaltic shuttle streaming in myxogastrian plas-modia). All macroscopic physiologies are underpinned by Brownian dynamics and thus quantum mechanics. Although well documented separately, acknowledgment of the role of quantum mechanics as the foundation of physiology unites the smallest single cells with the largest multicellular organisms across the tree of life; demonstrating how all large biological organisms represent an outgrowth of the smallest scales of physics.