636 Dr. H. H. Dale [May 12, 



by the trypan-red in vitro. It seems obvious that the organism of 

 the mouse did not play a purely passive and indifferent part in the 

 curative process. A related and more effective dye, trypan-blue, was 

 introduced by Mesnil and Nicolle, and has found practical application 

 in the treatment of piroplasmosis. 



Though substances of this series were originally investigated on 

 account of their properties as dyes, it has become evident that their 

 dveing action had no essential connection with their curative effects. 

 The latest and most important development of this line of enquiry 

 has been the introduction of the substance known, as yet, only by a 

 number, as "Bayer 205." This is known to have resulted from in- 

 vestigations suggested by the action of trypan-blue, and of a further 

 member of the same series, afridol-violet. But " 205 " is itself a 

 colourless substance, extremely soluble in water, and having none of 

 the properties of a dye. Its composition is still a secret, but it has 

 already proved to have remarkable curative properties, not only on 

 experimental trypanosome infections in small animals, but on the 

 naturally acquired trypanosomiasis of man, the deadly and previously 

 incurable African sleeping-sickness. 



The properties and mode of action of " 205 " are very different 

 from those contemplated at the initiation of the search along these 

 lines. There is no evidence that it has a specific affinity for the para- 

 sites. When treated with it directly they are not visibly harmed, 

 though they lose the power of infection. Most remarkable is the 

 persistence of its effect in the body, the animal which has received an 

 injection being resistant to infection with trypanosomes for weeks or 

 even months. 



Another line of investigation which has been fruitful in result is 

 the search for curative compounds containing arsenic, antimony and 

 bismuth. Thomas and Breinl found that the organic compound of 

 arsenic, known as atoxyl, was much more effective in the treatment of 

 experimental trypanosomiasis than arsenic in organic form. The 

 discovery of the true structure of atoxyl by Ehrlich and Bertheim 

 provided the starting point for the production of a long series of 

 derivatives, with the ultimate discovery, in " salvarsan," of a substance 

 which has found application of immense importance in the treatment 

 of spirochetal infections, including syphilis. Here again, with sal- 

 varsan and other arsenical derivatives, we find that the parasite is not 

 killed by the direct application of the remedy outside the body. There 

 is, however, a clue to the nature of their action afforded by the 

 observation that the arsenious oxides, formed by reduction of sub- 

 stances like atoxyl, or partial oxidation of those like salvarsan, are 

 immensely more toxic to the parasites, and incidentally to the patient, 

 than the parent substances. It is probable that the slow liberation in 

 the body of these oxides, which are too immediately toxic for direct 

 administration, gives the compounds of this series their curative 

 power. 



