Halberg Franz, Cornélissen Germaine, Katinas George, Syutkina Elena V, Sothern Robert B, Zaslavskaya Rina, Halberg Francine, Watanabe Yoshihiko, Schwartzkopff Othild, Otsuka Kuniaki, Tarquini Roberto, Frederico Perfetto, Siggelova Jarmila
Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA.
J Circadian Rhythms. 2003 Oct 29;1(1):2. doi: 10.1186/1740-3391-1-2.
Afew puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-one-goes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individual's needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal.
本文总结了与我在20世纪50年代所做的一小部分工作相关的几个谜题,并回答了主编的几个问题,以表明时间变异性规则作为空间中的生物变异性对遗传学规则起到补充作用。我主张摒弃诸如相对恒定或内稳态等陈词滥调,这些概念在很长时间里对生物科学起到了很好的作用。然而,它们从未打算在日常生理学上拉上一层无知的帷幕。在拉开这些帷幕时,我们揭示了一系列动态变化,这些变化可通过越来越小的设备中内置的计算机在数据收集和实时分析中得到解决,用于持续自我监测正常情况并个性化检测异常情况。当前基于参照无时间限定的正常范围进行解读的抽查的医学技术,能够发展成为一门时间序列科学,其测试能够以推断统计学的方式针对个体。对于血压情况这已经可行,但最终对于如今仅基于群体临床试验的流沙般不可靠依据来解读的许多其他变量也应该成为可能。这些忽略了个体差异,从而也忽略了个体的需求。时间组学(绘制时间结构)主要目的是通过动态参考值量化正常情况以检测最早的风险升高,它还带来了让分子生物学既关注正常情况也关注严重异常情况的好处。