Abstract
Ideas of homeostasis derive from the concept of the organism as an open system. These ideas can be traced back to Heraclitus. Hopkins, Bernard, Hill, Cannon, Weiner and von Bertalanffy developed further the mechanistic basis of turnover of biological components, and Schoenheimer and Rittenberg were pioneers of experimental approaches to the problems of measuring pool sizes and dynamic fluxes. From the second half of the twentieth century, a biophysical theory mainly founded on self-organisation and Dynamic Systems Theory allowed us to approach the quantitative and qualitative analysis of the organised complexity that characterises living systems. This combination of theoretical framework and more refined experimental techniques revealed that feedback control of steady states is a mode of operation that, although providing stability, is only one of many modes and may be the exception rather than the rule. The concept of homeodynamics that we introduce here offers a radically new and all-embracing concept that departs from the classical homeostatic idea that emphasises the stability of the internal milieu toward perturbation. Indeed, biological systems are homeody- namic because of their ability to dynamically self-organise at bifurcation points of their behaviour where they lose stability. Consequently, they exhibit diverse behaviour; in addition to monotonic stationary states, living systems display complex behaviour with all its emergent characteristics, i.e., bistable switches, thresholds, waves, gradients, mutual entrainment, and periodic as well as chaotic behaviour, as evidenced in cellular phenomena such as dynamic (supra)molecular organisation and flux coordination. These processes may proceed on different spatial scales, as well as across time scales, from the very rapid processes within and between molecules in membranes to the slow time scales of evolutionary change. It is dynamic organisation under homeodynamic conditions that make possible the organised complexity of life.