392 Colchicine 



a demonstration of the singularity of colchicine. The action of nar- 

 cotics on divisions of sea-urchin eggs was studied by Hertwig in 

 1887,^* two years before the discovery of c-mitosis by Pernice;^^ in- 

 activation of the spindle was conspicuous. Phenylurethane in "nar- 

 cotic" doses was later used in experimental work to study the in- 

 fluence of mitosis on the respiration;'--^ the latter was not modified 

 when the spindle was inactivated. In plants, Nemec''*' studied another 

 narcotic, chloral hydrate. Figure 17.1, which is from a later paper,9s 

 demonstrates how similar the arrested mitoses after chloral hydrate 

 are to c-mitosis. The induction of polyploid plants was, however, 

 never recorded, probably because of the too great toxicity of this 

 narcotic. This points to one of the principal qualities of colchicine 

 and explains most of its success in practical botanical work: its low 

 toxicity and high efficiency.^^ 



A classical monograph dealing with animal ceils was written by 

 Politzer,'"' who had done important work in the years 1920-1930. 

 Several basic dyes appear to influence the spindle, but Politzer's work 

 is mainly concerned with chromosome poisons, which act somewhat 

 similarly to the ionizing radiations (so-called "radiomimetic" drugs) , 

 and he mentions only occasionally metaphase poisoning and spindle 

 destruction. 



In 1929, in A. P. Dustin's laboratory, Piton"« demonstrated the 

 action of various arsenical derivatives on mitoses in mice. These ex- 

 periments were later extended to grafted tumors.-^ However, the 

 concept of t-mitosis did not yet exist, and observing the gradual in- 

 crease in the numbers of mitoses, it was thought that a mitotic 

 stimulation was taking place. Actually, it was only after the study 

 of colchicine that it was clearly realized that arsenicals were also 

 spindle poisons, and much later, that they also influenced jilant 

 mitosis. Another curious observation is that of Rosenfeld,"'* who 

 noted arrested metaphases in cells treated with ammonia. 



On the other hand, it was demonstrated by Lewis'^^ that heat alone 

 could inactivate the spindle. Sax observed a similar behavior of plant 

 mitoses in Tradescatilia^*'^ This research opened a way for the suc- 

 cessful production of polyploid plants (cf. Chapter 11) and poly- 

 ploid vertebrates (cf. Chapter 16A) , but it was not linked to the 

 other observations of what came to be called c-mitosis.^" After the 

 discovery of colchicine, and mainly after the observation of its action 

 on plant cells, a host of new spindle poisons was described, and other 

 chemical and physical means of arresting metaphases were found. 

 None Avas more efficient than colchicine, with the exception of some 

 derivatives closely related to colchicine. 



77.7-2 .- Colchicine and tlie spindle. Before discussing further 

 other mitotic poisons, it is imj^ortant to stress the peculiar properties 



