204 INFECTION AND IMMUNITY 



presence of the antitoxin, and again set free after destruction of the 

 antitoxin by heat. A similar observation, made soon after by Wasser- 

 mann ^ in the case of pyocyaneus toxin and antitoxin, fully supported 

 the results of Calmette. 



An ingenious proof of the direct action of antitoxin upon toxin 

 was obtained by Martin and Cherry.^ It was found by them that veiy 

 dense filters, the pores of which had been filled with gelatin, permitted 

 toxin to pass through under high pressure, while the presumably larger 

 antitoxin molecule was held back. Through such filters they forced 

 toxin-antitoxin mixtures, under a pressure of fifty atmospheres, at vary- 

 ing intervals after mixing. They found that, if filtered immediately, 

 all the toxin in the mixtures came through, but that, as the interval 

 elapsing between mixing and filtration was prolonged, less and less toxin 

 appeared in the filtrate, until, finally, two hours after mixing, no toxin 

 whatever passed through the filter. Besides demonstrating the direct 

 action of antitoxin upon toxin, this work of Martin and Cherry showed 

 that the element of time entered into the toxin-antitoxin reaction, just 

 as it enters into reactions of known chemical nature. The absolute non- 

 participation of the living tissue cells in these reactions was demonstrated 

 by Ehrlich himself. Kobert and Stillmarck ^ had shown that ricin pos- 

 sessed the power of causing the red blood cells of defibrinated blood to 

 agglutinate in solid clumps, a reaction which could easily be observed 

 in vitro. Ehrhch,* who had obtained antiricin in 1891 by injecting 

 rabbits with increasing doses of ricin, found that this antibody pos- 

 sessed the power of preventing the hemagglutinating action of ricin 

 in the test tube. By a series of quantitatively graded mixtures of ricin 

 and antiricin, with red blood cells as the indicator for the reaction, he 

 succeeded in proving not only that the toxin-antitoxin neutralization 

 was in no way dependent upon the living animal body, but that definite 

 quantitative relations existed between the two substances entirely 

 analogous to those which, according to the law of multiple proportions, 

 govern reactions between different substances of known chemical 

 nature. Similar quantitative results were subsequently obtained by 

 Stephens and Myers ^ for cobra poison and its antitoxin, by Kossel ° 



• Wassermann, Zeit. f. Hyg., xxii, 1896. 



' Martin and Cherry, Proc. Royal Soc, London, Ixiii, 1898. 

 3 Kobert und Stillmarck, Arb. d. phar. Inst. Dorpat, 1889. 



* Ehrlich, Fort. d. Med., 1897. 



» Stephens and Myers, Jour, of Path, and Bact., 1898. 

 « Kossel, Berl. klin. Woch., 1898. 



