DIFFERENTIAL DEVELOPMENTAL MODIFICATION. I 195 



Differences in effect of the various external agents on head frequency 

 depend on their relative effect on the two factors. These which inhibit 

 directly the activation of the head-forming cells decrease head frequency 

 even in long pieces in which the heads are not physiologically inhibited. 

 Those which inhibit nervous activity are effective in increasing head fre- 

 quency in short and posterior pieces in which it is physiologically in- 

 hibited, but they may also inhibit the head-forming cells directly and so 

 decrease head frequency in long and anterior pieces in which it is not 

 physiologically inhibited. Cyanide, for example, inhibits both factors and 

 may decrease or increase head frequency according to length of piece, 

 level of body, period of exposure, and concentration; but results can be 

 controlled and, with sufficient experimental background, predicted. Since 

 the physiological factor inhibiting head development is effective only tem- 

 porarily following section, temporary exposure to cyanide for a day or 

 two after section is most effective in increasing head frequency because, 

 after return to water, the head-forming cells recover more or less com- 

 pletely and are not longer inhibited by the nervous stimulation resulting 

 from posterior section. Exposure to cyanide during the whole period of 

 reconstitution is most effective in decreasing head frequency, because 

 under these conditions its direct action on the head-forming cells is con- 

 tinuous. The anesthetics used in controlling head frequency act more or 

 less like cyanide but are more effective in increasing frequency by in- 

 hibiting the nervous stimulation than in decreasing it by direct action on 

 the head-forming cells. Carbon dioxide, hydrogen ion, organic acids, and 

 strychnine inhibit the nervous factor but have relatively little effect, in 

 the concentrations used, on the head-forming cells; consequently, they 

 are much more effective in increasing head frequency in short and pos- 

 terior pieces than in decreasing it in long and anterior pieces. Tempera- 

 ture, on the other hand, apparently affects chiefly the head-forming cells: 

 a rise in temperature increases, a fall decreases, head frequency. Caffein 

 apparently may serve as an accelerating or a depressing agent according 

 to concentration and exposure period; consequently, it may either increase 

 or decrease head frequency in pieces of the same sort. 



Differential conditioning to low concentrations of external agents and 

 differential recovery may also alter head frequency secondarily : terato- 

 morphic heads may become normal, except for the original median eye, 

 and anophthalmic forms may become teratomorphic. Also, a series of 

 differentially modified head forms, with overdevelopment instead of inhi- 

 bition of the median region, occurs. These modifications are, of course, 



