18 TEMPORAL ORGANIZATION IN CELLS 



environmental changes (e.g. substrate induction in bacteria, surface antigen 

 changes in Paramecium in response to temperature variation (Beale, 1954)) 

 or in embryonic cells during development, is to be understood in terms of 

 epigenetic control mechanisms. The study of such discontinuities in biological 

 systems is clearly of very great importance, since one of the most obvious and 

 challenging facts about biological process is that it leads to a finite set of discrete 

 "points of organic stability" (Bateson, 1894), all of which arise from initially 

 undifferentiated or much less differentiated systems. Thus different cells and 

 tissues emerge during embryonic development, different behaviour patterns 

 arise in the learning process in higher organisms, different species in evolution, 

 and different cultures in anthropological development. The importance of 

 some kind of competitive interaction between the components of these systems 

 has been recognized for some time and, in fact, in each field the essential features 

 of a Darwinian or evolutionary process with competition and selection as the 

 major forces operating has been explicitly recognized and delineated. In 

 embryology this idea appears to have started with Wilhelm Roux, and it was 

 developed in some detail at the intracellular level by Spiegelman (1948), whose 

 analysis of the developmental process was epigenetic in the sense that he empha- 

 sized control of enzyme synthesis rather than of enzyme activity in differen- 

 tiating cells. Coming before the current knowledge of molecular control 

 mechanisms, Spiegelman's work was necessarily couched in terms of "weak" 

 interactions between macromolecular synthetic units, and it emphasized the 

 cytoplasmic or non-nuclear aspects of this interaction. Thus the biosynthetic 

 units responsible for enzyme synthesis were regarded as being in competition 

 for precursors, and selection of different enzymic patterns in developing cells 

 depended on the success or failure of the biosynthetic units to survive in the 

 competitive environment. A contemporary description of differentiation by 

 Waddington (1948) tended to place more emphasis upon the importance of 

 the genes as controlling parameters in the epigenetic process, a point of view 

 more in line with current theory, and one which has largely inspired the present 

 work. But it was difficult to produce anything more than a qualitative descrip- 

 tion by means of models depending largely upon weak competitive interaction, 

 although these earlier studies focused attention upon certain very significant 

 features of epigenetic phenomena. 



Strong and Weak Coupling 



The discovery of specific control mechanisms for macromolecular synthesis 

 in cells does not, however, permit one to ignore the fact that all biochemical 

 processes in cells are in some way coupled together. It is this coupling which 

 gives to the living cell its organic unity. The present analysis attempts to dis- 

 tinguish between two classes of coupling between variables: those which form 

 part of the specific control circuits that are responsible for regulating epigenetic 

 states; and those which are non-specific in the sense that they occur in a variety 

 of biochemical processes between which there is no discrimination. For example, 

 there is clearly some kind of coupling between the energy-generating activity 



