PERIODICITY IN HUMAN BEINGS AND MICE 843 



1956) and on epidermal mitoses (Halberg, in press) in this species, 

 represent serially independent spotchecks at only two times of day. 

 These were the times of the usual high and low of rhythm in the intact 

 animal, and at these times no significant differences in mean values 

 were found in states of adrenal cortical insufficiency. Such findings 

 may be interpreted inter alia as lack of rhythm or as a change in period 

 or phase, since the latter effect also may account for the lack of a 

 significant difference at the clock hours of the usual "high" and "low" 

 of rhythm. 



In discussing the degree and the nature of the dependence upon 

 corticoid of basic cellular functions (e.g., mitosis) we must also 

 remember that circadian periods have been recorded under controlled 

 conditions, in the absence of conventional nerves and hormones, in 

 lower forms of life (Hastings and Sweeney, 1957b; references in 

 Bruce and Pittendrigh, 1957; Pittendrigh and Bruce, 1957). In these 

 cases the "generator" of rhythm obviously is in the cell. Moreover, a 

 mammalian tissue has recently been shown to undergo periodic 

 mitoses in culture under controlled conditions (Hupe and Gropp, 

 1957). Most likely, none of the integrative mammalian functions can 

 be regarded as independent "generators" of metabolic rhythms, even 

 when a secretion such as that of the adrenal is necessary for "mainte- 

 nance"; instead, the sequential changes of cellular metabolism may 

 constitute the more basic characteristic underlying periodicity in the 

 mammal as well as in the unicellular. 



Rather than restricting ourselves to test indirectly hypotheses in- 

 volving metabolic "clocks" or "generators," it seems desirable to 

 speak of the leads and lags in phase of metabolic events defined in 

 time, when illustrative examples are known and their effects demon- 

 strated (Fig. 15). In adopting this biochemical viewpoint, the different 

 "maintenance" factors, superimposed upon cellular cycles such as 

 specific endocrines, can be regarded as subserving specialized tasks of 

 organismic synchronization. (To the degree to which the cellular 

 cycles can then be regarded as the beneficiaries of synchronization in 

 mechanisms of transport, they are likely to be victims as well as syn- 

 chronization failure!). Several superficially divergent aspects of the 

 problem of physiologic "synchronization" have already been discussed 

 or documented by Kalmus (1957) and Bunning (1957), or by Ball 



