PERIODICITY IN HUMAN BEINGS AND MICE 851 



background of earlier work (e.g., Snell et ai, 1944; Bykow, 1953; 

 Aschoff, 1958), we can conclude for the functions, conditions, and 

 species so far rigorously studied that the failure to shift by manipula- 

 tion of the lighting regimen the timing of 24-hr rhythms can result 

 from (1) the institution of certain unusual circumstances (e.g., 

 starvation), under which otherwise secondary sync signals (latent or 

 modulating synchronizers, e.g., feeding time) may gain dominance 

 over the phase of rhythm (Halberg, Visscher, and Bittner, 1953), or 

 from (2) a failure to allow for the necessary shift time. To illustrate 

 the latter point, the results of an outstanding investigator of mitotic 

 rhythm may be cited since they may have led to the view that in 

 mammals (Blumenfeld, 1944) by contrast to birds (Riley, 1937) the 

 phase of mitotic rhythm is independent of the lighting schedule. 

 Blumenfeld, in 1944, had not noted an inversion of epidermal mitotic 

 rhythm 2 days after inversion of lighting, and in our laboratory we 

 have confirmed this finding at the 3 -day time point after lighting 

 inversion. Under Blumenf eld's (1944) conditions as well as ours 

 (Halberg, Bittner, and Smith, 1957), a 2- or 3 -day period of inversed 

 lighting did not suffice to reverse the rhythm in cell division of the 

 mammal studied, even though the identical period may suffice for a 

 similar purpose in lower forms of life. 



In viewing these results, we must remember that several rhythms 

 are known to persist in continuous darkness in various animal forms 

 (for reviews see Calhoun, 1945; Halberg, in press; Kleitman, 1949). 

 As regards the mouse, earlier work has dealt mostly with the 24-hr 

 rhythm in body activity (Calhoun, 1945; Johnson, 1939), while more 

 recently it was found in our laboratory and elsewhere that the 

 rhythms in body temperature and in tail blood eosinophils (Halberg, 

 Visscher, and Bittner, 1953; Panzenhagen and Speirs, 1953) also 

 persist after the institution of a regimen of continuous darkness as 

 well as after removal of the eye (for over 1 month postoperative, the 

 effects of the latter procedure are roughly comparable to those of the 

 maintenance in darkness). Results obtained recently in our labora- 

 tory further suggest that the same applies to rhythms such as those in 

 mitotic activity. It seems fair to generalize that 24-hr rhythms in the 

 mammal are not necessarily "brought about" by lighting. The effects 



