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THE 24-HOUR SCALE: A TIME DIMENSION OF ADAPTIVE FUNCTIONAL ORGANIZATION FRANZ HALBERG, M.D.* I. Background The literature seems to be more extensive on physiological 24-hour periodicity than on other biologic periodicities. Nonetheless, "time-ofday " effects are viewed mostly as a nuisance to biologic measurement. Caution in accepting such variations as entities in their own right isjusttified ifrhythms are being related, without much qualification, to almost anything within us or without, near or remote, known or unknown. To cite a few examples, activity, feeding, drinking, sun, moon, stars, and weather have all been used, and some continue to be invoked to account for physiological rhythms. Such interpretations are biased when consideration ofany one ofthese factors excludes all others. Furthermore, opinions on how a particular agent brings about some or all physiological periodicity have Varied. Centering all too often around sweeping "either-or" propositions, the perennial dispute "extrinsic or intrinsic " has often been characterized by vague interpretations, variable findings, and, with notable exceptions, by a lack ofanalytical statistics. Is it surprising, then, ifin the era ofnatural sciences, based upon experimental method, various disciplines ofbiology and medicine remain barely influenced by information on daily periodic functions? Pertinent data are mostly omitted from modern texts. * Division of Cancer Biology, Department of Pathology, University of Minnesota; and Cambridge State School and Hospital, Cambridge, Minnesota. This work was supported by the Elsa U. Pardee Foundation, the United States Public Health Service, the American Cancer Society, and the Division ofPublic Welfare, State ofMinnesota. The author is grateful for the encouragement ofDr. Maurice H. Cottle, Chicago, Illinois, a mentor ofmedical research and education. He is indebted to Mrs. Inga Platou and Mr. Al Shemesh, Department ofMedical Illustration, University ofMinnesota, for most ofthe illustrations and to Mrs. Ruth Loewenson for much valuable help with the statistical aspects ofthe work. 49I However, individual biologists and clinicians, now as before, remain fascinated by periodicity. There is a Society for Study of Biologic Rhythms, with Professor A.Jores as mentor. By 1938,Joreshad stimulated much interest with a review ofthe already then voluminous literature on the physiology and pathology of 24-hour rhythms (1). One of his concluding references was to Hufeland, whose remarks on the subject of"our natural chronology" with 24 hourly units are reproduced fully in Figure 1. CHRISTOPHER WILLIAM HUFELAND, M. D. FJDMC IECTUBER ON MKDlClKE AT Ititi. ART PROLONGING LIFE. LOKDON: miKTEO FOB J. EEIL. KO. 1+8, OXFCBD-STIlEr G. N.DCC ,XtVlIThat period of twenty-four hours formed by the régulai revolution of our earth, in which all its inhabitants -partake, is particularly dirUnguiflied in the phyfical œconomy of man. This regular period isapparent ¡n ail difeafes ; and all the other frnall periods, fo wonderful in our phyfical hlftory, are by it in reality determined . It is, as it were, the unity of our natural chronology.— Fig. I.—Reproductions from a book by Hufeland, second English translation, published 1797: left, title page; right, part ofpage 201 (2). Hufeland's statement was made in 1797 without data yet with foresight (2). Today, as some twenty years ago, one must start almost where Hufeland left off. However, one must be cautious about generalizing from data, lest inspiration desynchronize from evidence, as it has in the past. This essay deals with some of the evidence for a physiological functional organization in time, along the 24-hour scale. The particular data discussed herein, and in an earlier review (3), were chosen because of familiarity. (For reviews ofimportant other work, see refs. 4-12.) II. Circadian Periods Many body functions undergo variations recurring at roughly 24-hour intervals, in the presence or absence of known environmental changes with similar periods. This applies to continuous but rhythmic phenomena 492 Franz Halberg · 24-Hour Periodicity Perspectives in Biology and Medicine · Summer i960 with a peak and trough recurring roughly every 24 hours as well as to discrete events, noted about once a day. The intervals separating these consecutive periodic events are similar but usually not identical. Over many days, the period may average out to exactly 24 hours long (13). (See Figs. 2 and 3.) Alternatively, it may be consistently and significantly different from 24 hours by a...


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