1. INTRODUCTION 5 



measurements on the behaviour of whole, hving cells in response to certain 

 stimuli. This is the study of biological clocks, and more generally it is the study 

 of timing mechanisms in biological systems. It has become apparent that the 

 complex biochemical activities which underly the structure and function of 

 cells and organisms do not form a homogeneous pattern in time such that all 

 processes occur simultaneously at fixed rates. Rather there is a rhythm to 

 these activities whereby they are ordered relative to one another in time, first 

 one and then another activity rising to a maximum and then falling off again. 

 The most obvious rhythm which occurs in organisms is a daily cycle of acti- 

 vities which is linked to the light-dark cycle of the planet; but there is a whole 

 spectrum of rhythms, having different periods and giving to an organism a very 

 complex but well-defined time structure. 



Two of the most significant developments in this field of study are the 

 demonstration of clock mechanisms in single cells, and the realization that the 

 occurrence of clocks or timing devices is very probably a universal feature of 

 cellular organization. The experimental study of temporal organization in cells 

 therefore offers the observational background against which to test a thermo- 

 dynamic theory of time structure arising from certain dynamic charac- 

 teristics of cellular control mechanisms. It provides the phenomenological 

 element without which a thermodynamic study would fail to be of any real 

 significance. It is true that the phenomenology of the temporal aspects of 

 cellular organization has not by any means reached the point where quantita- 

 tive relations can be defined between such variables as clock period, tempera- 

 ture, and light regime, for example; or between embryological competence, 

 developmental age, and the period of an environmental temperature cycle. 

 However, there has been some progress in this direction, and it seems not too 

 optimistic to believe that the scattered wealth of observational data may one 

 day be comprehended within a general theory of temporal organization in cells. 



There is, of course, the possibility that timing mechanisms are strictly deter- 

 ministic devices and that time structure in cells must be understood not in 

 terms of general macroscopic parameters, which represent the statistical 

 properties of a system made up of many individual oscillators of some kind, 

 but in terms of the operation of one single deterministic timing device. This is 

 a continuing debate. However, the weight of evidence, which shows that it is 

 extremely difficult to tamper with the clock without kilUng the cell, indicates 

 that we are dealing here with a general feature of cell organization. This is 

 the conviction of Harker (1958), Hastings (1959), Pittendrigh (1960), and other 

 prominent workers in the field : it constitutes a basic assumption in the present 

 study. 



The other general assumption which underlies the present analysis, is also 

 shared with Hastings and Sweeney (1959) and Pittendrigh (1961). It is that the 

 fundamental dynamic behaviour which gives rise to time structure in cells is 

 the occurrence of continuing oscillations in macromolecular concentrations, 

 arising in consequence of the operation of negative feed-back devices for the 

 control of molecular and macromolecular activities. The occurrence of oscilla- 

 tions in negative feed-back circuits is famihar to engineers and the phenomenon 



