How does homeostasis happen? Integrative physiologic, systems biologic, and evolutionary perspectives.

Homeostasis is a founding principle of integrative physiology. In current systems biology, however, homeostasis seems almost invisible. Is homeostasis a key goal driving body processes, or is it an emergent mechanistic fact? In this perspective piece I propose that the integrative physiologic and systems biologic viewpoints about homeostasis reflect different epistemologies-different philosophies of knowledge. Integrative physiology is concept-driven. It attempts to explain biological phenomena by continuous formation of theories that experimentation or observation can test. In integrative physiology, "function" refers to goals or purposes. Systems biology is data-driven. It explains biological phenomena in terms of "omics"-genomics, gene expression, epigenomics, proteomics, metabolomics-depicts the data in computer models of complex cascades or networks, and makes predictions from the models. In systems biology "function" refers more to mechanisms than to goals. The integrative physiologist emphasizes homeostasis of internal variables such as pCO2 and blood pressure. The systems biologist views these emphases as teleologic and unparsimonious in that the "regulated variable" (e.g., arterial pCO2 and blood pressure) and the "regulator" (e.g., the "carbistat" and "barostat") are unobservable constructs. The integrative physiologist views systems biologic explanations as not really explanations but descriptions that cannot account for phenomena we humans believe exist although they cannot be observed directly, such as feelings and, ultimately, the conscious mind. This essay reviews the history of the two epistemologies, emphasizing autonomic neuroscience. I predict rapprochement of integrative physiology with systems biology. The resolution will avoid teleological purposiveness, transcend pure mechanism, and incorporate adaptiveness in evolution-"Darwinian medicine."