Biological Aspects of Circadian Rhythms

329 Pages·1973·16.716 MB·English

by  Franz Halberg (auth.), J. N. Mills (eds.)

Biological Aspects of Circadian Rhythms
Biological Aspects
of
Circadian Rhythms
Edited by
J. N. Mills
Department of Physiology
University of Manchester
Manchester M13 9PT
England
<:P PLENUM PRESS· London and New York . 1973
Plenum Publishing Company Ltd.
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Copyright © 1973 by Plenum Publishing Company Ltd.
Softcover reprint of the hardcover 1st edition 1973
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No part of this book may be reproduced, stored in a retrieval
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ISBN-13: 978-1-4613-4567 -1 e-ISBN-13: 978-1-4613-4565-7
DOl: 10.1007/978-1-4613-4565-7
Library of Congress Catalog Number: 72-77044
The Whitefriars Press Ltd., London and Tonbridge
Contributors
]. G. Bohlen Research Assistant, University of Minnesota,
Minneapolis, Minnesota 55455, U.S A.
F. Halberg Department of Pathology, Medical School, Univer
sity of Minnesota, Minneapolis, Minnesota 55455,
U.S.A.
]. E. Harker Girton College, Cambridge CB3 OjG, England.
F. Hawking Medical Research Council, National Institute for
Medical Research, Mill Hill, London N. W. 7 ,
England.
G. V. T. Matthews The Wildfowl Trust, Slimbridge, Gloucester
GL2 7BT, England.
]. N. Mills Department of Physiology, Manchester University,
Oxford Road, Manchester M13 9PL, England.
A. Reinberg Laboratoire de Physiologie, Fondation Adolphe de
Rothschild, 29 rue Manin 75, Paris 19, France.
H. W. Simpson Department of Pathology, University of Glasgow,
Glasgow C4, Scotland.
M. B. Wilkins Department of Botany, University of Glasgow,
Glasgow W2, Scotland.
v
Preface
A "biological clock" has now been inferred in so many and such diverse
organisms and tissues that even a summary of the more interesting and
important observations would be a tedious and encyclopaedic compila
tion, whose bibliography would assume a daunting size. It would also be
obsolescent on the day of publication. The new titles appearing in the
monthly lists are scattered through many journals, but a new journal
devoted exclusively to rhythm research published its first issue in May,
1970-the Journal of Interdisciplinary Cycle Research-and another,
Chronobiology, appears in 1973.
In this volume several authors have been asked to review separate
aspects within their own fields of study, in the hope that thereby the
reader might gain an idea of the many directions of active progress and
be better placed to interrelate them than would be possible after a more
exhaustive study of a limited part of the field. The outcome is a series of
essays in which each contributor has exercised his individuality in ideas,
style and presentation, and, at some points, in vocabulary, although the
glossary includes a number of terms which have been fairly generally
used.
All biological study, indeed all scientific endeavour, must begin with
observation and in the study of rhythms there is still plenty of scope for
such, whether of the feeding habits of insects (Ch. 6), the migratory
behaviour of birds (Ch. 8), or the complex adaptive rhythms of a great
range of parasites (Ch. 5). Halberg (Ch. 1) devotes some attention to
means of amassing useful observations upon human subjects, and
Reinberg, writing about pharmacological rhythms (Ch. 4), considers that
we are not yet in a position to pass beyond observation towards a
coherent explanation. There are, however, scattered observations of, for
example, circadian variations in concentration of an enzyme responsible
for inactivation of a drug, which point the way to further exploration;
and in Ch. 2 an attempt is made to work out causal sequences between a
single controlling clock and the various observable manifestations of
rhythmicity. This inevitably raises the problem of whether there is such a
single clock or whether the rhythms in different organs and tissues are
controlled by a multiplicity of clocks, a problem which is mentioned in
several chapters. Studies on plants provide the best evidence that an
internal clock is a widespread property of cells, and experiments on
vii
Vill PREFACE
unicellular plants (Ch. 7) offer the best hope of understanding the
intimate mechanism of the clock, since both microanatomical and
biochemical dissection is more practicable than with more complex
organisms. Almost nothing is known of transmission processes between a
clock and observable rhythmic processes in plants whereby, for example,
the movements of different leaves could be coordinated; but in animals,
where both nervous and hormonal means are available, such study is
easier and it has been attempted in insects (Ch. 6) and in mammals
(Ch. 2). In mammals difficulties arise because so many variables oscillate
circadianly and since they can influence one another, often mutually, it
is very difficult to exclude all external factors, rhythmic or random, that
can affect any of them. There is therefore need for statistical procedures,
often of some complexity, for defining rhythms, and some of these are
described by Halberg (Ch. 1).
Much effort has been devoted to demonstrating that rhythms are
indeed endogenous, rather than responses to rhythmic external
influences. An endogenous origin is now fairly generally accepted for a
wide range of rhythms, although many more are clearly simple responses
to outside influences; the alternation of light and darkness for example,
accounts for some of the more obvious plant rhythms, such as opening
and closing of flowers. These wholly external rhythms are often
neglected by students of rhythms as of little interest, although to the
physiologist their functional value indicates a great diversity of evolu·
tionary adaptions. The rhythms of parasites (Ch. 5), though largely
exogenous, are of special interest for their adaptive value. When the
vector, such as a night-flying mosquito, is itself periodic in its habits, it is
essential that the parasite be accessible at the correct time of day. For
this purpose an endogenous clock within the parasite, which would be
unlikely to keep perfect time indefinitely, is less satisfactory than an
appropriate response to a rhythmically varying factor within the host;
the periodicity of host, parasite and vector must somehow be coordi
nated if the parasite is to be perpetuated. Other aspects of parasite
development, such as the maturation of the sporozoites of the malarial
plasmodia, need however a sufficiently accurate internal clock.
The alternation of light and darkness is the most consistent oscillation
resulting from the passage of day and night. It is therefore not surprising
that in most species light exerts a dominant influence upon the clock and
that it operates through a great variety of light-sensitive organs and
pigments, suggesting that such mechanisms have appeared m(!.ny times in
the course of evolution. Such mechanisms have, presumably, a genetic
basis; and individual differences in rhythmic behaviour have been shown,
alike in plants (Ch. 7) and in insects (Ch. 6), to be due to minor genetic
differences. The alternation of light and darkness follows a very different
course in different parts of the globe, from the tropics, where there is a
PREFACE
IX
constant LD 12: 12. with little annual vanatlOn, to the poles where
conditions are always LL or DD, and the annual cycle of climatic
variation is dominant. The consequences of this are considered in Ch. 3.
The Arctic, in particular, has been the scene of much recent investiga
tion, some of it as yet unpublished. Responses to varying day length are
prominent in species of temperate latitudes, but would be valueless in
the tropics. Man has modified many of his habits far too rapidly to
permit evolutionary adaption, so that the persistence of his endogenous
rhythms is often disadvantageous. This is most notable in night or shift
workers, or in those who fly rapidly across many time zones. Their
disadvantages may be relieved when we gain a better understanding of
these rhythms.
The most widespread use made of an internal clock by plants and
animals alike is to time and trigger off rhythmic processes appropriate to
the external meteorological oscillation. A further use, described in birds
in Ch 8 but known to exist also in insects, is for navigation. Navigators
who depend upon solar or sidereal observation have always needed an
accurate chronometer; the same need is present for all animals navigating
by the sun, and is apparently supplied by an internal circadian clock.
Rhythms with a period longer than a day are hardly mentioned here;
many are known to exist, such as the monthly rhythms of intertidal
animals and annual rhythms in many species. They present greater
difficulties of investigation, since the student of rhythms always hopes to
be able to observe several successive cycles under comparable conditions,
whereas a bird over several years is likely to show changes referable to
aging; and comparable conditions are more difficult to maintain for years
than for days. In Ch.8 evidence is however adduced to suggest that
many birds have a timing device responsible for their annual cycles of
behaviour. Whether this is ascribable to a circadian clock combined with
a "demultiplication process", or whether the timing process is entirely
distinct, is a matter for future study. Every chapter indeed reveals areas
of ignorance wide open for further investigation.
As with any developing discipline, new technical terms have been
found necessary and some former terms have needed precise definition.
A glossary has thus been included, though some new terms, such as
Chronobiology and Chronopharmacology, are omitted since they are
self-explanatory; and where the sense is clear without their use, an
attempt has been made to eschew needless technical terms.
The reader wishing access to a more general bibliography may consult
a recent book, Human Circadian Rhythms, by R. T. W. L. Conroy and
J N. Mills [Churchill, 1970], whose Introduction lists other books and
published proceedings of conferences.
J.N.M.
Glossary
(N .B.-A glossary of terms used only in Chapter 5 appears at
the end of that chapter)
Acrophase The time of the peak value of the sine curve fitted to a
rhythmically oscillating variable. This may be
expressed as clock time, or time in relation to some
other variable, or in degrees of arc.
Amplitude One half of the total regular excursion of a wave; best
restricted to mathematically fitted sine waves. Abbrevi
ated C or A. Range is used in a less precise sense to
describe the usual difference between maximum and
minimum if no analysis has been performed.
Circadian (of a rhythm). With a period of approximately 24 h,
strictly 20 to 28 h. Dian is sometimes used for a more
precise period of 23.9-24.1 h.
Clock A hypothetical mechanism in the brain, or other organ,
which records the passage of approximately 24 hours
and transmits this information to otIter systems.
Clock hours Are given according to international nomenclature in
hours and minutes for 24 h (i.e., 6 a.m. = 0600; 6 p.m.
and 37 min = 1837; midday = 1200; midnight = 2400
or 0000).
DD In continuous darkness. LL-In continuous light.
LD-In alternating light and darkness. LD followed by
two numerals: the hours of light and darkness e.g.
LD 1: 1, alternating one hour each of light and dark
ness; LD 4:20, alternate periods of 4 h light and 20 h
darkness. When it is desirable to specify the clock
hours, the form L 0600-1800 D 1800-0600 is used.
Diurnal Pertaining to the day rather than night. Contrast
nocturnal.
Endogenous (Of a rhythm.) Maintained from within the organism,
independently of rhythmic external stimuli.
Exogenous (Of a rhythm.) Dependent upon rhythmic stimuli from
without the organism. (Loosely, of a stimulus): giving
rise to a rhythm.
xi
xu GLOSSARY
Free-running (Of a rhythm.) Observed under conditions when
exogenous stimuli are lacking, and endogenous
rhythms are unmasked. The period usually differs
slightly from 24 h.
LD.LL See DD.
Mesor The mean of the sine curve fitted to a rhythmic
variable. This is equal to the mean of the determined
values if these have been sampled at regular intervals
for an integral number of cycles. The term "level" has
been also used. Abbreviated Co or M.
Nocturnal Pertaining to the night rather than day. Contrast
diurnal.
Nychthemeral (Of a rhythm.) Oscillating in time with the alternation
of day and night. (Of hahits, circumstances, etc.)
Conforming to the influences imparted by the alterna
tion of day and night.
Nychthemeron A night and a day.
Period The time interval occupied by a wave, q.v.
Range See Amplitude.
Synchronizer See Zeitgeber.
Wave The complete pattern of a periodic variation which is
repeated at regular intervals.
Zeitgeber (Lit. "time-giver"). Some authors prefer to use
synchronizer, or entraining agent. A stimulus which
gives rise to an exogenous rhythm, or determines the
phase or period of an endogenous rhythm. The
common Zeitgeber are nychthemeral. In deference to
its German origin, the plural is identical with the
singular.
Contents
Contributors · v
Preface
• VII
Glossary
• IX
Chapter 1 Laboratory Techniques and Rhythmometry
F. Halberg ............ . 1
Chapter 2 Transmission Processes Between Clock and
Manifestations
J. N. Mills . . . . . . . . . . . . 27
Chapter 3 Latitude and the Human Circadian System
H. W. Simpson and]. G. Bohlen . . . . 85
Chapter 4 Chronopharmacology
A. Reinberg 121
Chapter 5 Circadian Rhythms of Parasites
F. Hawking . ..... . 153
Chapter 6 Circadian Rhythms in Insects
J. E. Harker. . . . . . . 189
Chapter 7 Circadian Rhythms in Plants
M. B. Wilkins . . . . . . 235
Chapter 8 Biological Clocks and Bird Migration
G. V. T. Matthews 281
Index . . 313