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Vol. 22 No. 5 Contents
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Neuroendocrinology Letters incl. Psychoneuroimmunology & Chronobiology

NEUROENDOCRINOLOGY LETTERS
including Psychoneuroimmunology, Neuro
psychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology
ISSN 0172–780X

NEL VOL. 22 No. 5
REVIEW
GALLERY OF CHRONOBIOLOGISTS


full text pdf (1257kb)

2001; 22:359-384
pii: NEL220501X01


Essays on chronomics spawned by transdisciplinary chronobiology

Witness in time: Earl Elmer BAKKEN
by Franz Halberg, Germaine Cornélissen, Kuniaki Otsuka, George Katinas & Othild Schwartzkopff

Submitted: September 12, 2001
Accepted: September 14, 2001

Foreword

Technology allows the monitoring of ever denser and longer serial biological and physical environmental data. This in turn allows the recognition of time structures, chronomes, including, with an ever broader spectrum of rhythms, also deterministic and other chaos and trends. Chronomics1 thus resolves the otherwise impenetrable "normal range" of physiological variation and leads to new, dynamic maps of normalcy and health in all fields of human endeavor, including, with health care, physics, chemistry, biology, and even sociology and economics. The authors plan to describe initiators of modern mapping of our make-up in time, with focus on mechanisms and applications. Earl Elmer Bakken, to start the planned series, is also to serve as a local time-witness (Zeit-Zeuge) of concerns about chronomics in Minnesota.

Introduction

Genetics, as a quantitative science, took a long time to develop into genomics and proteomics. Gregor Mendel, and even those who rediscovered rules to inheritance long buried in Mendel's original findings were all dead by the time the mapping of the human and other genomes was initiated. By comparison, the development of chronobiology as an inferential statistical science resolving variability in time was fast. Rather than being viewed by a few others, [1-7; cf. 8], here preference is given to assays that may be checked by those described themselves.

Karl-Heinz Bernhardt (9) quotes Goethe: "… die Geschichte der Wissenschaft die Wissenschaft selbst, die Geschichte des Individuums das Individuum ist" ("The history of science, the science itself, is the story of the individual, is the individual"). This view applies not only to those sharing Goethe's view of nature, which again according to Bernhardt emphasized what is obvious to the naked eye, such as the classification of clouds by Luke Howard, to whom Goethe dedicated a poem (9). Precisely as in dealing with the form of clouds, as a pertinent example, Goethe focused on what can be seen with the naked eye - that is he sought primarily what he presumed not to have been able to find in numbers and signs ("Goethe, in seiner Naturbetrachtung immer vorrangig auf das dem Sinne der Augen Erfaßliche fixiert, griff die Howardsche Wolkenklassifikation enthusiastisch auf, eröffnete sie ihm doch einen seiner Neigung und Lebensweise angemessenen Zugang zur Witterungskunde, den er über Zahlen und Zeichen nicht hatte finden können, wie er in der Wolkengestalt nach Howard ausführte.") This time-macroscopic approach can be a starting point for chronomics but is not our concern herein.

We take a view that neither may be improperly labeled as diametrically opposite, nor does it deprecate either Goethe's incontestable genius or the stature of many opinion leaders in the field of clocks. We echo Alexander von Humboldt, who courted Gauss (10) by presuming first that everything in science is to be expressed by at least semiquantitative numbers and signs. We add that these numbers (the point estimates) are at best accompanied by estimates of their uncertainties, such as 95% confidence intervals. This is neither to say that intuition and/or a keen observation without numerical support is inappropriate: it is often the best start of an investigation. We will also elaborate on the merit of responding to a problem promptly, with the first available tool, as by the use of a metronome in an initial application to cardiac pacing (11). Eventually, improvements are to be guided by the results of numerical analyses (12-15), but again one must not rely on inferential statistical analyses alone. Furthermore, whenever the transformation of an observational series from the time into the frequency or phase domain is required, the back-transformation into time is desirable (16-20).

Science cannot proceed without figurative microscopes in time as well as in space. The analogy to the need for detecting, for instance, the lurking dangers of infection by unseen microbes before they lead to hard events, including death, applies necessarily to the merits of mapping structures in time, chronomes, to detect disease risk syndromes in blood pressure and heart rate variabilities (19). Cartography in both space and time with the use of tools that extend our senses to resolve "unseen" matter is very often indispensable (6) and is of transdisciplinary theoretical and applied interest (18-20; cf. 5, 16, 17).

Whenever possible, we return to Goethe's position, described figuratively as a spiral, by trying to revisit, visualize and check at a higher, invariably numerical level along the desirable and often indispensable scale of time, whatever was found in the frequency and phase domains. This is the scope of chronobiology, as it developed from intuitive observations of within-day and seasonal variations to the mapping of the time structures, chronomes, in us and around us, that represent the dynamics of everyday physiology, psychology, pathology and even of everyday economics. All human endeavors can benefit from the cartography of transdisciplinary chronomics, Figure 1. The many who contributed to chronobiology and thereafter to the necessary systematic mapping of chronomics in our era and earlier cannot all be singled out again (16, 17); the authors are deeply in their debt.
Ubiquity and relative prominence of biological near-matches of photic and non-photic environmental cycles. The first anthropoids shared with other animals and plants the recurrent, nearly daily periodic need for rest or sleep (21-24) or at least the need for a recurrent change from anabolism to metabolism. Thus, rhythms, if not chronobiology, became obvious before Homo sapiens developed. Circadians characterize most early living matter, bacteria included (25). The endogenous preparation for rest each night, or for each awakening, is a basic feature of our physiology as in the sleep movement of plants (26-29) or in the motor and other rest-activity cycles. Almost every body function of plants and animals may carry genetically coded photic interactions with the earthly daily alternating light-dark environment (30). But non-photic effects are also likely.

Why is the biological week more prominent than the circadian rhythm, e.g., in the electrical activity of a single cell that may have been around on earth 500 million years ago (31)? Again, why is the biological week more prominent than the day early in crayfish, rat, piglet and human ontogeny (32, 33)? Why does RNA formation precede DNA synthesis in each murine circadian hepatic cycle (34, 35)? A budding chronoastrobiology may scrutinize the possibility that such findings constitute a separate line of evidence supporting an RNA-world before a DNA-world. Moreover, the prominence of the week early in ontogeny and phylogeny, is in keeping with the resonant frequency of ions in a weak magnetic field, involving periodicities of about a week (36). Is it also in keeping with an even earlier prebiological, if not primordial biological electrolyte world (32)? In this context, early stages of ontogeny may constitute living fossils (37).

Subtle cosmic/magnetic factors? Human pathology (38), suicides (38, 39), epilepsy (37), heart attacks (37, 40-47; cf. 33), strokes (44, 45, 48) and traffic accidents (49) have been investigated for associations with geo- or heliomagnetics, controversies (41, 42) arising perhaps because of a solar cycle number- and stage-dependence of susceptibility (33). Human morphology, psychology and behavior, normal as well as abnormal, by virtue of cyclic signatures, cross-spectral coherence and remove-and-replace approaches (37) also show associations with non-photic effects of the sun and/or galactic cosmic rays. Planetary magnetics constitute not only an endogenous feature of the earth itself, but also a partial signature of effects from the sun and from beyond it.
Subtle factors are a matter of the unequaled lifetime concern of A.L. Chizhevsky (50-53), Figure 2, whose expressiveness was matched by extensive albeit descriptive statistical data, those in Figure 3 fully confirmed by meta-analyses. Traute and Bernhard Düll (38), and Frank A. Brown Jr., Figure 4 (54-57) and Franklin Barnwell (58) have considered the roles played by subtle factors. Whereas Chizhevsky superposed 11-year cycles in the incidence of cholera, Figure 3, the Dülls used 27-day cycles of other pathology, Figure 5. Their propositions are supported again by time-microscopic tests, as is the work by Stoupel, Figure 6 (40). The time-macroscopic study of chronomes - structures in time - in both geomagnetism and chronobiology, however, has a long, albeit descriptive history (59), with some notable exceptions (60-63).
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