THE PLAN OF CELLULAR REPRODUCTION 173 



The existence of a specific "trigger" or stimulus is questionable; it re- 

 mains to be proved. Like our university students, the cell may need only 

 to complete the right number and kinds of courses for credit in order to 

 graduate; a final examination may be unnecessary. 



Controls and stimuli 



The time map of mitosis implies that the various preparations for 

 division, reproductive and synthetic, run parallel to one another; it also 

 implies that they may be dissociable. That they are dissociable is a fact. 

 Chromosomes may reproduce if centrioles have not reproduced. Cen- 

 trioles may reproduce independently of chromosomes. The work of 

 Zeuthen and Scherbaum on the synchronization of Tetrahymena shows 

 that preparations for division, not all of which have been specified, are 

 actually set back in time without much eflFect on DNA synthesis or 

 growth. There is no reason to think that the synthesis of the protein 

 molecules which will make up the mitotic apparatus is related to the 

 filling of the mitotic "energy reservoir," although it is possible to sup- 

 pose that the assembled mitotic apparatus is an activated structure and 

 is itself the energy reservoir. This last point is discussed elsewhere 

 ( Mazia, 1960 ) . Obviously the various preparations normally have to be 

 coordinated to some degree, but they are at least experimentally 

 separable. 



This way of looking at cell reproduction leads to an attitude to- 

 ward its suppression, stimulation, and control which is rather obvious, 

 once stated, but is by no means implicit in most of the past expressions 

 on the subject. It is simply this: that every cell may be regarded as 

 being on the way to division, that reproduction is an immanent tend- 

 ency of all cells. Cells which are not reproducing are viewed as being 

 blocked with respect to one or more of the preparations for division. 

 It can be any one of them, since the condition of division is the meeting 

 of all of the prerequisites. In practice, the blockage of chromosome re- 

 production is the most common feature of cells whose division is sup- 

 pressed, but it is by no means the only one. For example, Gelfant 

 ( 1958 ) has shown that the epidermis of the rabbit ear contains a popu- 

 lation of cells which have already completed the doubling of DNA but 

 are thrown into division only by some biochemical consequence of 

 wounding the tissue. This release of the cells into division has been in- 

 terpreted by Bullough (1955) in terms of the energy supply, although 

 Gelfant ( 1960 ) criticizes this particular interpretation. 



Just as the natural inhibition of division could operate on any one 

 of a number of the prerequisites, so there could be any one of a num- 

 ber of targets for action of anti-mitotic agents. Similarly, the "stimula- 

 tion" of division would be viewed as the release of a blocked prepara- 



