Spindle and Cytoplasm 67 



Wide ranges of concentration induce a wide variety ot reactions. 

 These ransje from extremely minute chanoes inxolviny tlie spindle 

 orientation, the tropokinesis,^^ to the full c-mitosis, slatlniiokine- 

 sis, obtained by strong doses.^^. ss, 73, 25 These two reactions repre- 

 sent the extremes, between Avhich there can occin- many intermediate 

 changes. 



Before proceeding further, we should recall the old argument about 

 spindle liber reality as opposed to "artefact." If we are dealing with a 

 specific molecular problem, the possibility that spindle fibers are arte- 

 facts woidd seriously influence oin- proposition. Perhaps the whole 

 concept would be annulled. Rut excellent results, obtained from 

 treated and untreated cells and Irom living and fixed materials, have 

 opened up new approaches. Hence, the argument that spindle fibeis 

 are not real is almost extinct. An entirely new series of studies with 

 phase contrast microscopes, polarization microscopes, cinematography, 

 and other techniques has shown that fixed and stained fibers are 

 similar to the living functional linear structures. ^'' Colchicine has 

 been employed most eff^ectively in these studies. 



A high specificity can be demonstrated between colchicine and 

 spindle fibers.i^- ^o. ». ss. 54 Moreover, this specificity can be cjuickly 

 destroyed if the chemical structure of the drug is changed only slightly. 

 Pharmacobiologists have known for a long time that certain deriva- 

 tives such as colchiccine are less active pharmacologically than colchi- 

 cine. Numerous chemical deri\atives of colchicine are accurately 

 kno^\•n by chemists and these have become available to biologists.^*' 

 For example, isocolchicine is a transformed molecule of colchicine, 

 that involves a shift in the position of keto and methoxyl groups on 

 ring C. By this change the specificity between spindle fiber and colchi- 

 cine is reduced. '^^ Isocolchicine is one hiuidred times less active in 

 producing a c-mitosis than colchicine. 



The specificity between colchicine and spindle appears to be on the 

 order of the enzyme and substrate specificity. 



Admittedly, the spindle fiber mechanism is complex, highly orga- 

 nized, and delicately coordinated. But much is understood of this 

 mechanism in animals and plants. Cytologists agiee that two sets of 

 fibers are formed at each regular mitosis: the continuous and the 

 chromosomal. 



The reaction between colchicine and the several components of 

 the spindle appears, then, to have a quantitative basis. Some portions 

 of the sj)indlc can be inactivated leaving other jiortions activated. 

 Such fractionating possibilities have been demonstrated,^"' and this 

 fact merits attention. 



