DAILY RHYTHMS 479 



3. is temperature-independent, or nearly so, within wide ecological 

 temperature limits. 



4. This endogenous self-sustaining oscillation (ESSO) is an innate 

 feature of cellular organization; it is not learned. [In addition to the 

 discussion given on this point in Pittendrigh and Bruce (1957) and 

 Pittendrioh (1958), see the excellent, more recent study of Hoffman 

 (1957).f 



5. The phase and period of ESSO (the cell's clock) are susceptible, 

 like those of other self-sustaining oscillations, to entrainment by other 

 systems to which it can be coupled. Specifically, the ESSO's of living 

 cells can be coupled to a light cycle (and more indirectly to a 

 temperature cycle) of the environment which establishes the ap- 

 propriate phase of the living clock and corrects the error in its innate 

 natural period. (Other environmental cycles — pressure, cosmic rays, 

 air ionization, etc. — cannot be coupled to ESSO, and in a constant, 

 or aperiodic, regime of light or temperature the oscillator is free- 

 running, thus revealing its natural period.) 



6. As with other self-sustaining oscillators, the phase of ESSO as a 

 free-running system can be shifted by single, nonperiodic signals of 

 light or temperature — the signals to which it can be coupled. 



The working hypothesis of a fundamentally similar ESSO under- 

 lying all living clocks (Pittendrigh and Bruce, 1957) has only a 

 general heuristic value until it is open to possible experimental rejec- 

 tion. In this connection two general points are noted. 



First, fully acceptable tests must await some knowledge of the 

 concrete physical nature of ESSO, and presently we have absolutely 

 none. Moreover, as discussed fully in the writers' papers, there are 

 difficulties in the way of discovering the physical nature of the cell's 

 clock: in spite of increasing and highly interesting information on 

 chemical periodicities in the cell and the organism (e.g., Barnum, 

 Jardetzky, and Halberg, 1957) we still lack the necessary criterion 

 for distinguishing primary (causative) cycles from those they control. 

 Thus, it remains desirable in the present state of the problem to 

 develop the formal oscillator model from physiological data to as ex- 

 plicit and restrictive a form as possible as a lead to its concrete nature. 



Second, we are consequently limited in the meantime to using 

 formal properties in testing the hypothesis of a common mechanism. 



