144 TEMPORAL ORGANIZATION IN CELLS 



condition (within limits), and then turned off again if induction does not occur, 

 requires a much more specific timing mechanism than is usually proposed for 

 the development of competence. The competent state is usually regarded as 

 some general metabolic condition which does not inhibit or prevent the action 

 of a specific inducer. And it is the exogenous inducer that is generally regarded 

 as the agent which turns on the gene, in analogy with substrate induction in 

 bacteria, not an internal mechanism within the cell. Fhckinger does not make 

 any suggestion about the possible biochemical mechanism which might 

 underlie a sequential initiation of gene action. However, it is difficult to avoid 

 connecting his theory with the clock mechanisms which are known to operate 

 in cells, and to seek an explanation of both sets of phenomena in terms of the 

 same fundamental activity: oscillations generated by feed-back control 

 mechanisms in single cells. We might visualize the development of a particular 

 competence in analogy with the setting of an alarm clock. At particular 

 developmental stages in the differentiation of a cell, biochemical clocks might 

 be started which go off" at some later time. The process of going off" would 

 be the occurrence of high levels of genetic activity at certain loci, in the same 

 way that in a circadian clock high levels of activity at particular genetic loci 

 occur at a certain time of day. The high level of activity lasts for some time, and 

 then drops off again. The dynamic basis for such behaviour would again 

 be found in the interactions of non-linear oscillators, where subharmonic 

 phenomena can generate clocks with a great variety of periods and oscillatory 

 amphtudes. 



Flickinger's theory suggests all-or-none behaviour in gene activity, a 

 phenomenon which has not yet been discussed in the present study. However, 

 we will soon see how such discontinuous oscillations can occur in feedback 

 control systems of the class we are considering, so that we may have a dynamic 

 basis for the occurrence of discontinuities in genetic activity as demanded by 

 an on-off theory of competence. The suggestion made here, then, is that the 

 timing mechanisms which appear to operate in developing cells, may be com- 

 prehended in terms of non-linear biochemical oscillations of the type we are 

 considering, and the higher-order phenomena which arise from their inter- 

 action. The theory proposed by Flickinger is possibly an overstatement of the 

 case for the autonomy of the cellular activities controlling the gain and loss of 

 cell competence, but it certainly emphasizes this aspect of the developmental 

 process and the role of the genes in it. Waddington (1940) has for many years 

 emphasized the importance of genetic control over developmental events in 

 cells, and he explicitly implicates specific gene activities in the generation of 

 competence (Waddington, 1956). However, there remains in this more general 

 statement of the phenomenon the question of causality in the initiation of 

 gene activities. Undoubtedly the specific causal agent will often be an exo- 

 genous inducer; but it is necessary to have another mechanism as well in order 

 to explain the embryological facts, and an internal cellular timing mechanism 

 seems to be a very real possibility. 



We must be careful to realize, however, that there is one fundamental dif- 

 ference between the time-structure of embryonic cells and that of circadian or 



