1. INTRODUCTION 3 



only after a certain history of observation and experiment has made them 

 appear famiHar and reasonable? Such a development would go even further 

 than did quantitative genetics in reversing the physical pattern of proceeding 

 from macrostructure to microstructure in that the macroscopic principles were 

 not even anticipated in qualitative form before they were predicted by a general 

 theory based upon microscopic or molecular properties. The singular absence 

 of precisely-formulated laws of cellular organization suggests that there simply 

 are no obvious general quantities for measuring cell behaviour which are 

 presented to our senses in the manner that heat, pressure, and volume are in 

 the study of physical phenomena. In this case it will be necessary to discover 

 such system variables in connection with theories developed on the basis of 

 the microstructure of biological systems, assuming that such a development in 

 biology is possible. The present study is an investigation of this possibility, 

 and sets out to derive some general macroscopic or "thermodynamic" func- 

 tions which arise from certain dynamic characteristics of molecular control 

 mechanisms in living cells. The programme is, then, to use the present know- 

 ledge of the molecular organization of cells, so brilliantly exposed by molecular 

 biologists, as the microstructure for a statistical theory from which the general 

 behavioural consequences of this organization can be deduced in terms of 

 functions which bear a complete formal analogy with the classical thermo- 

 dynamic quantities of temperature, free energy, work, etc. 



In cell biology the present situation appears to be that there are no laws of 

 motion governing molecular and macromolecular activities analogous to 

 Newton's laws for molecular motion in physical systems, and no phenomeno- 

 logical relations analogous to the laws of thermodynamics. A programme 

 which sets out to derive macroscopic laws of cell behaviour from microscopic 

 principles would seem, therefore, to be rather a vague one, insofar as there is 

 nothing to start from and nothing to prove. However, there are three considera- 

 tions which suggest that the situation is not quite so unsatisfactory as this. 

 The first is that we now have some quite detailed knowledge about the sequence 

 of molecular events which appears to form the fundamental mechanism for 

 controlling macromolecular synthesis and activity in cells. This mechanism 

 is based upon the principle of negative feedback, long familiar to engineers. Its 

 basic logical or algebraic feature is that the molecular and macromolecular 

 species involved in the control sequence form a closed causal circuit which is 

 essentially self-regulating. According to current theory the molecular species 

 constituting the closed control loop for regulating genetic activities in cells 

 are deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), 

 protein (usually an enzyme), and metabolite; and the activities are synthesis of 

 mRNA by informationally homologous DNA, synthesis of the homologous 

 protein species by mRNA, catalysis of a metabolic transformation by the 

 protein (enzyme), and finally the repression of mRNA synthesis at the DNA 

 locus by the metabolite resulting from the catalytic activity of the enzyme. 

 These are the bare bones of the theory, which will be discussed more fully 

 in Chapters 3 and 4, along with other control loops which regulate macro- 

 molecular activities at different "levels" of cellular organization. 



