Transdisciplinary unifying implications of circadian findings in the 1950s

Abstract

A few 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-onegoes 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.

Immunometabolism: Is it under the eye of the clock?

“…This illustrated the presence of an endogenous clock separate from the external stimulus of light. The term circadian was first coined in the 1950 s by Franz Halberg [6] who provided some of the first evidence of circadian control of immunity [7]. Although clock mechanisms differ between organisms, conservation of a timer system throughout the evolutionary tree exemplifies its importance.…”

Prokaryotic and eukaryotic unicellular chronomics

“…[6]), dedicated to him and to Pittendrigh [28], who eventually asked, received and published an acrophase chart), may have anticipated what would develop: Aschoff replied in a personal letter (in German) asking something like "Do you wish to take are cord for posterity?" The answer was in the affirmative, as is being done in this paper.…”

“…In LL only, the non-photic/photic amplitude ratio is larger than unity, Fig. 2b-e. Unicellular time structure can be viewed in a still wider perspective of chronomes, consisting of 1. trends, 2. a broader-than-circadian and circaseptan intermodulating spectrum of cycles and 3. probabilistic and any other chaos, the latter evaluable usually in data denser than those discussed herein [6,[42][43][44][45]. Whatever biological variable is investigated, sampling is best planned in the light of what has been mapped and made known about the then-entire available spectrum of rhythms so that once the task of long-term mapping has been done, its essentials can be spotchecked by everybody working in the one domain.…”

“…The brevity of the time series is a grave limitation but an apparent decreasing trend at the outset is reversed toward the end of the series and a cosinor shows the predicted circaseptan component superposed on the circadian component in the luminescence of cyanobacteria, a slight modulation only analyses can exclude in the data of Mihalcescu et al [1]. The issues of 55 years ago, revolving around any endogenicity of circadians, reemerge in biology [6] (cf. [61]) around the often very wobbly and transient circaseptans.…”

“…This reminds us that humans procreate and die faster than the length of an about 500-year cycle (corresponding to the rule of reciprocal cycles in and around us [2]) not only in the emergence of outstanding physicians, historians and poets [3] and in tree rings, but also in cave temperatures recorded in stalagmites [4]. Should it become possible to extend the observation span and/or analyses beyond that in the figures published in [1], a further comparison of broader-than-circadian chronomes in eukaryotes vs. prokaryotes would eventually become possible [5,6]. Before humans came about-before hominization [7]-there had to be a cell, and a heretofore mostly spatial cellular system promptly acquired a chronomic system in time, much broader than circadian, what we attempt to demonstrate herein [4,5] (cf.…”