Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland.
Am J Physiol Regul Integr Comp Physiol. 2019 Apr 1;316(4):R301-R317. doi: 10.1152/ajpregu.00396.2018. Epub 2019 Jan 16.
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 physiological and systems biological 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"-i.e., genomics, gene expression, epigenomics, proteomics, and metabolomics-it depicts the data in computer models of complex cascades or networks, and it 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 Pco and blood pressure. The systems biologist views these emphases as teleological and unparsimonious in that the "regulated variable" (e.g., arterial Pco and blood pressure) and the "regulator" (e.g., the "carbistat" and "barostat") are unobservable constructs. The integrative physiologist views systems biological 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, i.e., "Darwinian medicine."
稳态是整合生理学的基本原则。然而，在当前的系统生物学中，稳态似乎几乎看不见。稳态是驱动身体过程的关键目标，还是一种涌现的机械事实？在这篇观点文章中，我提出整合生理学和系统生物学关于稳态的观点反映了不同的认识论，即不同的知识哲学。整合生理学是概念驱动的。它试图通过不断形成可以通过实验或观察进行检验的理论来解释生物学现象。在整合生理学中，“功能”是指目标或目的。系统生物学是数据驱动的。它根据“组学”——即基因组学、基因表达、表观基因组学、蛋白质组学和代谢组学——来解释生物学现象，它用复杂级联或网络的计算机模型来描述数据，并根据模型进行预测。在系统生物学中，“功能”更多地指的是机制而不是目标。整合生理学家强调 Pco 和血压等内部变量的稳态。系统生物学家将这些重点视为目的论的和不简约的，因为“调节变量”（例如，动脉 Pco 和血压）和“调节者”（例如，“碳平衡”和“血压平衡”）是不可观察的结构。整合生理学家认为系统生物学的解释不是真正的解释，而是描述，不能解释我们人类认为存在的现象，尽管它们不能直接观察到，例如感觉，最终是意识。本文回顾了这两种认识论的历史，重点是自主神经科学。我预测整合生理学与系统生物学的和解。这种解决方案将避免目的论的目的性，超越纯粹的机制，并将进化中的适应性纳入其中，即“达尔文医学”。
