SALVARSAN AND NEOSALVARSAN IN TREATMENT OF SYPHILIS 793 



strength of Schaudinn's statement regarding the close biologic relation- 

 ship of the spirochetes of syphilis to trypanosomes, Uhlenhuth was led 

 to employ atoxyl in the treatment of experimental spirillosis in fowls. 

 These experiments, in addition to those of Weisser and Metchnikoff, 

 demonstrated beyond doubt the curative and prophylactic properties of 

 atoxyl in spirillar infections. The drug was, therefore, administered 

 in cases of syphilis in the human subject. It was found to exert a very 

 beneficial effect, especially in malignant forms of the disease. Further 

 experience, however, demonstrated that atoxyl was too toxic for use in 

 the human subject, for digestive disturbances, nephritis, and especially 

 optic atrophy could be traced to its use, even in small doses. As a 

 therapeutic agent, therefore, it has gradually come into disfavor. 



Ehrlich and Bertheim then made the valuable discovery that the 

 chemical constitution of atoxyl was not, as had been supposed, that of a 

 metarsenate, but that it was in reality that of a para-amidophenyl- 

 arsenate. Working on this basis, these observers prepared the substance 

 known as arsacetin (the sodium salt of acetylpara-amidophenylarsenic 

 acid), which, although less toxic than atoxyl, did not fulfil the require- 

 ments of a remedy, and its use was discontinued because of its toxic 

 effects on human tissues. To lessen the relatively great toxicity of these 

 compounds for human tissues was a problem that Ehrlich set out to 

 solve. A most important advance in this direction was made when it 

 was discovered that the unsaturated trivalent arsenic in arsenobenzol 

 and arsenophenylglycin has a greater parasiticidal power relative to its 

 toxic action on the tissues of the host than the pentavalent arsenic 

 compounds, such as atoxyl and arsacetin. 



Finally, after testing hundreds of these arsenical compounds, it was 

 found that in dioxydiamidoarsenobenzol we had a substance that ap- 

 proached the ideal in chemotherapy, since it is a drug that possesses a 

 maximum degree of parasitotropism and a minimum degree of organo- 

 tropism. Ehrlich and Hata designated this light yellow, readily oxidiz- 

 able powder as No. 592. Its hydrochloric acid salt was designated No. 

 606, and constitutes the well-known salvarsan. 



In the published account of their researches Ehrlich and Hata 1 

 describe an extensive series of investigations in experimental relapsing 

 fever, spirillosis of fowls, and syphilis of rabbits. These go to prove the 

 high curative value of salvarsan, its relatively feeble toxicity for the 



1H pie experimentelle Therapie der Spirillosen," Berlin, 1910; Zeitschr. f. 

 Immunitatsf., Ref. 1910, 1123. Numerous publications from the Institute of Exper- 

 imental Therapy, Frankfort. 



