THE CENTRAL PROBLEMS OF THE BIOCHEMISTRY OF CELL DIVISION 493 



in these interactions the mitotic apparatus conditions are governed by 

 the fluctuating of thioldisulphide systems such as the protein of the 

 Sakai-Dan cycle, and that the success of the dithiodiglycol method 

 depends on a mimicking, and no more, of such a svstem in the hving 

 celL 



Perhaps we mav speculate a step further. If the mitotic apparatus is 

 such a dynamic thiol-disulphide svstem, is it not possible that the protein- 

 to-protein interaction includes not only S S bonds and SH groups in a 

 state of dynamic interchange, but also sites where pairs of SH groups are 

 only half-oxidized ? It is likely, from the Michaelis principle of two-step 

 oxidation that such intermediates have at least a transitory existence. Is it 

 conceivable, in a structure composed of so many interacting molecules, 

 that there is an appreciable number of such sites at anv given time, and 

 that they are a factor in the stability of the mitotic apparatus in vivo. This 

 speculation would view the apparatus as having some of the properties of 

 a gigantic free radical, and this is something that we hope to test. For the 

 time being, one speculates in this way because everyday experience with 

 the apparatus shows : that it is high in protein SH, at least after fixation [36], 

 that it behaves in isolation procedures as a structure that depends on 

 sulphur-to-sulphur links, and yet it certainly does not fit our image of a 

 stable S — S bonded structure. This proposal cannot be defended in any 

 rigorous way, but I wished to mention it here because it is in fact the 

 predictive basis for our current work on the mitotic apparatus. 



These problems of stability are not confined to the mitotic apparatus, 

 but to other structures of the cell whose existence is inferred for good 

 reasons but which do not assert themselves either after biochemical 

 isolations or common electron-microscopic fixation. Examples are the gel 

 states of the cytoplasm studied by the late L. V. Heilbrunn and his school 

 and the structure involved in intracellular streaming, discussed in this 

 symposium by Robert Allen. It will not be surprising if the structure of the 

 cell does, after all, include a level of intermolecular organization so 

 dynamic and so sensitive that it has escaped our rather violent direct 

 attacks so far. Such ideas of a "protoplasmic" organization, popular in an 

 earlier era of cell biology but often rejected as being bevond experimental 

 consideration, may yet become accessible to test. 



II. Concluding comments 



The first step in building a bridge is to span a chasm with a simple 

 cable, and this is what is called for if Molecular Biology is to come to grips 

 with the uncomfortably complex problems of the whole cell such as cell 

 division. An individual experimenter can ignore such problems of the 

 higher levels of cellular organization for the benefits of working with clean 



