vi Obituary Notices of Fellows deceased. 



parasiticidal action, one of the most striking effects being found in the case 

 of trypan red, a single dose of which might cure a mouse otherwise fatally 

 infected with the trypanosome of mal de caderas. In certain cases, after 

 treatment with a drug, a relapse occurred, and he found that the parasites 

 which had survived its action were no longer susceptible ; in other words, 

 they had acquired drug-fastness. That this had a chemical basis was shown 

 by the fact that the fastness usually applied to substances of the same 

 chemical group, but not to those of other groups, one of which included the 

 arsenic compounds. 



Amongst these last, atoxyl, which had been introdiiced as a trypanocidal 

 substance by Breinl and Thomas, came to be studied, and what proved to be 

 an important discovery was made, when Ehrlich, along with Bertheim, 

 showed that this substance had not the constitution of an acetanilide, as was 

 supposed, but was para-amino-phenylarsenic acid, a substance from which a 

 great number of derivatives with different actions could be formed. For 

 example, by introducing an acetic acid group, a substance, arsacetin, was 

 obtained, which had a much greater effect on trypanosome infections, but 

 was much less toxic to the tissues than atoxyl. Ehrlich thus came to 

 formulate the view that the different atom groups, existing as side-chains in 

 such substances, functioned in different ways ; some were concerned in fixing 

 the substance to the parasite or body-cell — were parasitotropic or organotropic 

 — whilst others produced the toxic effect ; but in every case combination or 

 fixation was essential. 



The problem thus came to be how to vary the structure of the chemical 

 compound so as to produce maximum affinity for the parasite and minimum 

 affinity for the cells of the body, along with the necessary toxic action on the 

 former. Ehrlich further showed that the pentavalent arsenic, in which form 

 it exists in the atoxyl series, has little direct parasiticidal effect until it is 

 reduced to the trivalent form. He thus directed his attention to compounds 

 containing trivalent arsenic, and found that their toxic action on the tissues 

 was reduced when two molecules were combined by means of the arsenic group. 



After the preparation and testing of a large number of substances, as 

 indicated by the numbers, the goal of a satisfactory spirochasticidal substance 

 was reached in dioxydiamidoarsenobenzol (No. 592), the hydrochloride of 

 which is salvarsan (No. 606). In this substance the hydroxyl, aided by the 

 amido groups, bring about the maximum affinity for the spirocheetes, while, of 

 course, the arsenic group leads to the parisiticidal effect. Although Ehrlich 

 did not directly concern himself with practical medicine, no one appreciated 

 more fully than he the precautions necessary for therapeutic success, and the 

 importance of detail as regards administration. Was the drug really without 

 harmful action on the tissues ? Might not a drug-fast strain of spirochsetes 

 be developed ? These and many other questions had to be answered, and a 

 vast amount of experimental work was entailed. Ehrlich gave salvarsan to 

 the medical word in 1910, and experience of the drug during the years since 

 then has pronounced as to its value. 



