26 



THE HISTORY OF TROPICAL MEDICINE 



quinine from cinchona-bark. For further particulars see Chapter 

 XL. on Malaria. 



Arsenic and Antimony.- — Thanks to Morgan's work it is possible 

 to give a brief history of these two metalloids, which belong to the 

 nitrogen group of the fifth vertical series of the periodic classifica- 

 tion, and are related to the non-metals phosphorus and nitrogen 

 and to the metal bismuth. 



Arsenic occurs in nature in combination with cobalt, as smaltite and 

 cobaltite, both of which are included under the term cobolt, which was found 

 by a German artist to be capable of making sympathetic ink when acted upon 

 by aqua fortis, the action of which was studied in 1737 by Hellot and in 1760 

 by Cadet de Gassicourt, who produced a highly inflammable stinking fluid 

 therefrom, and this Then6rd concluded was a complex acetate containing 

 arsenic. 



D aring the years 1 837-1 843 Bunsen isolated this complex, to which Berze- 

 lius gave the name cacodyl, and in 1858 Baeyer, having first made primary 

 methyl arsenicals, produced methylarsenic acid, the soluble salts of which are 

 employed medicinally as new cacodyl and arrpenal. In 1 860-1 863 Bechamp 

 made the first aromatic arsenical, and in the seventies Michaelis, in collabora- 

 tion with other workers, not merely extended this knowledge, but prepared 

 the first aromatic antimony compounds. In 1902 Bechamp's compound was 

 first tried in medicine by Thomas and Breinl for sleeping sickness, being called 

 atoxyl because of its comparatively non-toxic action, and it is the drug which 

 has been used with such success in sleeping sickness in the Sudan. Atoxyl 

 was shown in 1907 by Ehrlich and Bertheim to be the sodium salt of ^-arsenitic 

 acid, being a derivative of quinquevalent arsenic. 



/ONa, 



Atoxyl, NH.,C6H4AsO<( contains from 25-95 to 20*78 per cent, of 



arsenic, according to the amount of water of crystallization. Mono-acetylated 



/ONa. 



atoxyl is CHgCONHCgHs AsO<^ 



According to Mesnil and NicoUe's experiments, and the observations of 

 Nierenstein. it is not the arsenic in these compounds which is to be looked upon 

 as the effective agent, but the amido-group, which may possibly be the effec- 

 tive agent in trypan red, afridol blue, afridol violet, and parafuchsin, which 

 do not contain arsenic, but possess amido-groups, and affect trypanosomes in 

 a similar manner to atoxyl. According to Ehrlich, Levaditi, and Yama- 

 nouchi, atoxyl undergoes a reduction in the animal tissues. Ehrlich has 

 prepared two derivatives of atoxyl, one of which, already mentioned (arseno- 

 phenylglycin) , is very effective in mice on atoxyl-resistant trypanosomes. 

 Levaditi and Yamanouchi have also prepared an active derivative of atoxyl, 

 which they call trypanotox^/l. Nierenstein thinks that atoxyl is oxydized 

 in the tissues, and it is only in the nascent state that it becomes efficacious. 



Owing to the fact that large doses of atoxyl lead to such unpleasant results 

 as optic atrophy, gastro-intestinal inflammation, and peripheral neuritis, 

 other arsenical preparations have been recommended ; and the firm Burroughs 

 and Wellcome has introduced, under the trade name of soamin, a prepara- 

 tion somewhat similar to atoxyl. but said to be less poisonous. It is given 

 in the same doses as atoxyl, but the therapeutic results do not appear to 

 have been very successful. Soamin, according to the published formula, is 

 C2H4NH2AsO(OH) (ONa) 5H2O. 



Atoxyiate of mercury was introduced by Uhlenluth, but is less satisfactory 

 than atoxyl. 



Combinations of Mesnil's afridol and atoxyl, Ehrlich's parafuchsin and 

 atoxyl, picric acid, safranin, trypaflavin, and other dyes and atoxyl, have been 



