Kutschera Ulrich
The Systems Biology Group Inc, 374 California Avenue, Palo Alto, CA, 94306, USA.
Institute of Biology, University of Kassel, 34132, Kassel, Germany.
Theory Biosci. 2018 Nov;137(2):117-131. doi: 10.1007/s12064-018-0265-6. Epub 2018 Jun 14.
The founders of modern biology (Jean Lamarck, Charles Darwin, August Weismann etc.) were organismic life scientists who attempted to understand the morphology and evolution of living beings as a whole (i.e., the phenotype). However, with the emergence of the study of animal and plant physiology in the nineteenth century, this "holistic view" of the living world changed and was ultimately replaced by a reductionistic perspective. Here, I summarize the history of systems biology, i.e., the modern approach to understand living beings as integrative organisms, from genotype to phenotype. It is documented that the physiologists Claude Bernard and Julius Sachs, who studied humans and plants, respectively, were early pioneers of this discipline, which was formally founded 50 years ago. In 1968, two influential monographs, authored by Ludwig von Bertalanffy and Mihajlo D. Mesarović, were published, wherein a "systems theory of biology" was outlined. Definitions of systems biology are presented with reference to metabolic or cell signaling networks, analyzed via genomics, proteomics, and other methods, combined with computer simulations/mathematical modeling. Then, key insights of this discipline with respect to epiphytic microbes (Methylobacterium sp.) and simple bacteria (Mycoplasma sp.) are described. The principles of homeostasis, molecular systems energetics, gnotobiology, and holobionts (i.e., complexities of host-microbiota interactions) are outlined, and the significance of systems biology for evolutionary theories is addressed. Based on the microbe-Homo sapiens-symbiosis, it is concluded that human biology and health should be interpreted in light of a view of the biomedical sciences that is based on the holobiont concept.
现代生物学的奠基人（让·拉马克、查尔斯·达尔文、奥古斯特·魏斯曼等）都是研究生物体的生命科学家，他们试图从整体上理解生物的形态和进化（即表型）。然而，随着19世纪动植物生理学研究的兴起，这种对生物世界的“整体观”发生了变化，并最终被还原论观点所取代。在此，我总结了系统生物学的历史，即从基因型到表型将生物理解为整合生物体的现代方法。据记载，分别研究人类和植物的生理学家克劳德·贝尔纳和尤利乌斯·萨克斯是这一学科的早期先驱，该学科于50年前正式创立。1968年，路德维希·冯·贝塔朗菲和米哈伊洛·D·梅萨罗维奇撰写的两部有影响力的专著出版，其中概述了“生物学系统理论”。文中给出了系统生物学的定义，涉及通过基因组学、蛋白质组学和其他方法分析的代谢或细胞信号网络，并结合计算机模拟/数学建模。然后，描述了该学科对附生微生物（甲基杆菌属）和简单细菌（支原体属）的关键见解。概述了稳态、分子系统能量学、悉生生物学和共生生物（即宿主 - 微生物群相互作用的复杂性）的原理，并探讨了系统生物学对进化理论的意义。基于微生物 - 智人 - 共生关系，得出结论：人类生物学和健康应根据基于共生生物概念的生物医学科学观点来解释。
