PERIODICITY IN HUMAN BEINGS AND MICE 859 



Generally speaking, in the case of a system open to the environment, 

 such as the organism, we shall bias our model whether we attribute 

 its basic phenomena entirely to factors from without or entirely to 

 mechanisms from within — and 24-hr rhythms are a case in point. As 

 has been done in the past, we could classify without further qualifica- 

 tion 24-hr changes in physiologic state among conditioned reflexes or 

 among stress reactions, and we may also continue to relate them to 

 known or as yet unknown (cosmic) factors from without; but in so 

 doing we may adopt a biased approach. The demonstration of shifts 

 in phase of rhythm following changes in schedule of known environ- 

 mental factors, in human beings as well as in mice, may be used, on 

 the one hand, to suggest that the periodic operation of unknown 

 cosmic factors does not have to be invoked (as sometimes is done) in 

 accounting for physiologic rhythms. On the other hand, any factor, 

 terrestrial or cosmic, will be more rigorously studied if effects upon 

 rhythmic variables are evaluated as deviations from the normal period, 

 amplitude, or phase of rhythm, rather than as deviations from an 

 imaginary straight base line. Along similar lines of thought, the 

 complex 24-hr periodic changes of the body as a whole may, perhaps, 

 fruitfully be regarded as physiologic entities in their own right, rather 

 than solely as conditioned reflexes or stress reactions. The importance 

 of dealing with such entities can be demonstrated in studies of the 

 outcome of exposure to noxious agents in defined phases of rhythm. 



Phase of Rhythm, a Determinant of Response, Particularly to Noxious Agents 



If factors such as genetics, age, sex, and physical environment are 

 kept comparable, the phase of the 24-hour periodic changes in physio- 

 logic state can critically determine survival from noxious agents. Cases 

 in point are death, from bacterial toxins (Halberg and Stephens, 1958 ) 

 or noise-induced convulsions (Halberg, Bittner, Gully, Albrecht, and 

 Brackney, 1955; Halberg, Jacobsen, Bittner, and Wadsworth, 1958; 

 for underlying factors see Halberg, Engel, Halberg, and Gully, 1952, 

 and Harner and Halberg, 1958). 



Recent work in this department, with Doctor E. Haus, also shows 

 hours of different resistance to toxic doses of alcohol or ouabain. The 

 factors underlying such periodic changes in susceptibility are not the 

 same from one agent to the next. Tests done at the same time, on 



