The Antitoxins 127 



they are present. In some cases, however, animals that have 

 been long subjected to the immunization treatment, and whose blood 

 contains large quantities of free antitoxin, unexpectedly become 

 abnormally sensitive (hypersensitivity) to the toxin, and may die 

 after receiving a very small dose. This may be attributed to a 

 difference in the combining activity of the receptors attached to the 

 cells, and those separated and free in the serum. If the former 

 developed a greater affinity for the toxin than the latter, it would 

 unite with them by preference and intoxication ensue. If the treat- 

 ment by which the antitoxins are produced is interrupted, they im- 

 mediately begin to lessen in quantity, and eventually disappear. 

 Their occurrence in the blood determines that they shall be found 

 in all the body juices, though in varying quantity. 



Their chemical composition, which experiment shows to be of 

 protein nature, determines that when practical use is to be made 

 of them, they must not be administered by the stomach, as diges- 

 tion is usually followed by their destruction. In infants, the protein 

 digestion being feeble, antitoxins pass from the mother's milk to 

 the blood of the sucking offspring without digestion, but the ad- 

 ministration of antitoxins by this method at later periods of life is 

 followed by effects too uncertain to be depended upon. For practical 

 therapeutic purposes, therefore, the administration must always be 

 made hypodermically or intravenously. 



Diphtheria Antitoxin. — This was first utilized for practical 

 therapeutic purposes by Behring.* As usually prepared by the 

 administration of the toxin, it is essentially an antitoxin and has 

 no destructive action upon the diphtheria bacilli. In therapeutics 

 it is employed to neutralize or "fix" the toxin circulating in the 

 blood, not to destroy the bacilli, or to effect the regeneration of the 

 tissues injuriously acted upon by the toxin. Martin is of the 

 opinion that such purely antitoxic serums are inferior to those con- 

 taining other immunity products, such as bacteriolysins, and recom- 

 mends that the whole culture instead of the filtered culture be used 

 in the immunization of the animal. If this is done, the bacteriolytic 

 effect is added to the antitoxic effects of the serum. 



The serum may be used to prevent or to cure diphtheria. 



The antitoxin is commercially manufactured at present by im- 

 munizing horses against increasing quantities of diphtheria toxin 

 until the proper degree of immunity has been attained, then with- 

 drawing the antitoxic blood. The details are as follows: 



I. The Preparation of the Toxin. — The toxic metabolic products of tha 

 Bacillus diphtheriee are for the most part freely soluble, and are therefore best 

 prepared in cultures grown in fluid media. The medium best adapted to the 

 purpose is that lecommended by Theobald Smith. f 



To make it, the usual meat infusion receives the addition of a culture of 



* "Deutsche med. Wochenschrift," 1890, Nos. 49 and 50; "Zeitschrift fiir 

 Hygiene," etc., 1892, xii, p. i; "Die Blutserumtherapie," Berlin, 1902. 

 t "Journal of Experimental Medicine," May and July, 1899, p. 373. 



