208 BACTERIA PATHOGENIC TO MAN 



2. Various attempts to separate the toxins and antitoxins from 

 neutral mixtures have been failures. Partial successes have, at least 

 in some instances, been shown to depend upon the fact that insufficient 

 time for their complete union was allowed, separation being no longer 

 possible if this were granted. 



3. The accuracy of the titration of toxins and antitoxins to within 

 1 per cent, of error. 



4. Neutralization takes place according to the law of multiple pro- 

 portions, i. e., to save an animal from 1000 fatal doses of diphtheria 

 toxin requires little more than a hundred times as much antitoxin as 

 is required for ten fatal doses, the resistance of the animal itself account- 

 ing for the difference. 



5. The fact that the potency of antitoxin is greatly increased if it is 

 allowed to come in contact with the toxin outside the animal body; 

 and is increased still further if allowed to remain for sufficient time in 

 contact with the toxin at a suitable temperature. The union takes 

 place more quickly at a warm than at a cold temperature. 



The facts now known, therefore, indicate that the antitoxins of 

 tetanus and diphtheria, of snake-poison, of ricin, etc., enter into direct 

 chemical combination with their respective toxins. Many points, 

 however, are still far from clear as to the manner in which both toxins 

 and antitoxins act. 



Testing of Antitoxin. This power, possessed by a definite quan- 

 tity of antitoxin to neutralize a certain amount of toxin, is utilized in 

 testing antitoxin. Guinea-pigs of about 250 grams' weight are sub- 

 cutaneously injected with one hundred or with ten fatal doses of a 

 standardized toxin, which have been previously mixed with an amount 

 of antitoxin believed to be sufficient to protect from the toxin. If the 

 guinea-pig lives four days, but dies soon after, the amount of anti- 

 toxin added to the one hundred fatal doses of toxin was just 1 unit. If 

 the guinea-pig dies earlier, less than 1 unit was added. 



Use of Antitoxin in Treatment and Immunization. The antitoxin 

 in the higher grades is identical with that in the lower grades; there is 

 simply more of it in each drop of the serum. In treatment, however, 

 for the same amount of antitoxin we have to inject less blood serum 

 with the higher grades, and, therefore, have somewhat less danger of 

 rashes and other deleterious results. The amount of antitoxin required 

 for immunization is 300 units for an infant, 500 for an adult, and propor- 

 tionately for those between these extremes. After the observation of 

 the use of antitoxin in the immunization of several thousand cases, I 

 have absolute belief in its power to prevent an outbreak of diphtheria 

 for at least two weeks, and also of its almost complete harmlessness 

 in the small doses required. If it is desired to prolong the immunity 

 the antitoxin injection is repeated every two weeks. For treatment, 

 mild cases should be given 1500 units, moderate cases 2000 to 4000 

 units, and severe cases 5000 units. Where n^LJmprovement follows 

 in twelve hours the dose should be repeated. Intravenous injections give 

 most rapid effect. Antitoxin is not absorbed when given by the mouth. 



