Wounds of Men who received Prophylactic Inoculation. 537 



be reduced by the presence of certain organisms, just as it was enhanced by 

 that of others. This was found actually to be the case. Certain mixed 

 cultures obtained from wounds proved to be non-toxic, although they contained 

 organisms having the morphological characters of B. tetani and which agglu- 

 tinated with the Type sera. That these organisms were not deficient in 

 toxogenic capacity was shown by injecting washed spores obtained from the 

 cultures into animals, along with a tissue debilitant. When this was done, 

 tetanus developed. Further, by growing one of the stock toxic cultures of 

 B. tetani in presence of these mixed growths, the toxogenic capacity of 

 the stock culture was greatly reduced. It has not yet been determined what 

 particular organism or combination of organisms leads to this depression of 

 pathogenicity. Neither can it be stated whether it is the mechanism of 

 infectivity or that of toxogenicity which is thus depressed, although presumably 

 it is the latter. 



Section III. 



Investigation of Serum Prophylaxis in Experimental Animals from the 

 Standpoint of Infection. 



The observations dealt with in Section II indicated a method of procedure 

 whereby research could be applied to investigate immunity to infection which 

 might be conferred by the administration of anti-toxin. 



The inquiry brought out the following facts : — 



(1) In experimental animals — guinea-pigs, rats, and mice — the prophylactic 

 administration of anti-toxin failed to prevent the development of infection if 

 the tissue debilitation at the site of inoculation exceeded a certain degree. This 

 was the case even if the dose of anti-toxin corresponded weight for weight to 

 as much as 40,000 units for a man of 60 kilos. 



(2) Using guinea-pigs, it was found, that by increasing the unitage of anti- 

 toxin administered prophylactically, the incubation period of the infection 

 could be lengthened and the severity of the disease lessened. The quantities 

 of anti-toxin used were 10, 20 and 30 units for animals of 250 grm. weight, 

 giving a weight for weight ratio for man of 2400, 4800, and 7200 units. 

 Saponine was the debilitant used, as it could be easily standardised by physical 

 methods. 



Section IV. 



InqvAry as to whether — 



(a) Monotypical Anti-toxin exhibits Specific Anti-infective Properties. 

 (b) Inoculations of Cultures of B. tetani give rise to Anti-bacterial Bodies 

 Specific to the Type of Organism used. 



{a) From this investigation it appeared that a monotypical anti-toxin was 

 equally active in neutralising the toxin of any or all types of B. tetani. Some 



