176 Colchicine 



were not standardized. Recent Avork re^ icwed in otlicr chapters indi- 

 cates the complexity of the alkaloidal content of Caleb innu and the 

 great differences in loxicitx of substances cheniicalh \er\ close to 

 colchicine. 



Forensic medicine cjuite natmally was often interested in the prob- 

 lem of htmian poisoning, accidental or criminal. A vast amount of 

 literature on this subject exists. ])ut it has not been found necessary to 

 include it in this book. HowcAcr, one most imjjortant fact made clear 

 in this field is the long jjersistence of the alkaloid in the body after 

 death.-' The jiroblcms of the metalDolism of colchicine will be taken 

 up further in this chajner. 



.\11 ^vork on colchicine before 1934, excepting onh iliat on blood- 

 forming tissues and Ijlood cells, which will l)e discussed later, was 

 confined to pharmacological methods and chemical testing. No study 

 of the morj)h()logical changes was made, and these remained unsus- 

 pected for a long time. 1 he aim of this chapter is not to give a detailed 

 study of the j^harmacology of colchicine, but to place it in a new per- 

 spective, that of spindle-poisoning. The significance of this in a field 

 apparently so distant from cytology can be illustrated b\ modern 

 descriptions of death from colchicine poisoning. These will sho^v some 

 of the comj)lexities of the jjharmacology of that ver\ ancient drug, 

 Colcliuinn. 



7.2: Colchicine Poisoning in Man 



The junior author happened to make the first detailed post-mortem 

 study after the disco\ery of the action of colchicine on cell division. ^^ 

 In 1941, a woman of 42, attempting suicide, swallowed 60 1-mg. 

 pills of colchicine "f4oude." She lived eight days after this very 

 high dose; delayed letliality is nearly always found in colchicine poi- 

 soning. Vomiting and diarrhea were |jrominent, the I)lood mea in- 

 creased to \.5 gm. per thousand, and there were nervous troubles which 

 were considered to be e\ idence of polynetuitis. An important decrease 

 in the number of white blood cells and of platelets was noticeable. 

 A bone-marrow study was performed only two hours before death, that 

 is to say, eight days after colchicine had started to act. The abnormal 

 percentage of metaphases, mainly of the star type, illustrated that 

 sjjindle activity had not yet entirely recovered (Fig. 7.1) . 



Microscopic evidence of this was found at the post-mortem exami- 

 nation.-- Arrested metajjhases coidcl be seen in lymph glands, in the 

 spleen, and in the Lieberkiihn glands of the intestine. 1 he histological 

 changes in the liver were remarkable. Here, 4 per cent of all li\er cells 

 were in a condition of arrested metaphase. .\bout 15 per cent of these 

 mitoses were ball metaj^hases, while the others showed scattered 

 chromosomes. Other findings interesting from the ]:)oint of \ icAV ol the 



