Factor in the Mechanism of Bacterial Infection. 515 



centrations, together with the detoxicated bacteria of gas gangrene, has also 

 failed to produce gas gangrene, even although an extensive sore was 

 frequently produced as the result of the injection of the lactic acid. 



The negative results have been reported in detail because they demonstrate 

 clearly how difficult it is to elicit the pathogenic action of the bacteria of 

 gas gangrene or their spores. In this respect they resemble the bacterium of 

 tetanus. We are informed by Dr. Tulloch that, in his experience, it is not 

 possible to induce tetanus regularly and with certainty after infection with 

 the spores by any of the means given in the literature and tested by him. 

 As the negative results of the experiments given above accumulated, the 

 conviction grew that in normal animals, in which the experimental 

 conditions can be controlled and kept constant, an adequate explanation 

 of the relation between these bacteria and the specific disease with which 

 they are associated cannot be deduced from the occasional and apparently 

 accidental production of gas gangrene or of tetanus, as the case may be, 

 which sometimes occurs, but must be based on a definite factor, by which 

 these conditions can be elicited from the bacteria or their spores with 

 certainty and at will. Such a factor was eventually found in injections of 

 small doses of a soluble ionisable calcium salt. The severity of the trauma 

 which can be inflicted on animals infected with the detoxicated bacteria or 

 their spores without eliciting from them the specific disease, stands in 

 striking contrast to the phenomenon which will now be described. 



Calcmm Salts as an Accessory Factor in Gas Gangrene and Tetanus. 

 Doses of 2"5 mgrm. of calcium chloride, when injected subcutaneously into 

 mice of 10-15 grm. weight, together with a suspension of a virulent strain 

 of B. Welchii or of Vibrion septique, will produce a violent gas gangrene in 

 every case. The same dose when injected with a suspension of the tetanus 

 bacillus or its spores will produce tetanus. Larger doses up to 5 mgrm. have 

 the same efi"ect. With mice the dose of calcium chloride cannot safely be 

 increased above 10 mgrm., since with doses of such magnitude the toxic 

 action of calcium salts comes into play. Doses of 10 mgrm. are, as a rule, 

 without any ill effect for normal mice of 15-20 grm. weight. Sometimes, 

 however, even with such a dose the animals are ill a few hours after the 

 injection and die within 24 hours. With smaller doses the effect becomes at 

 first irregular, and if the dose is further diminished fails to appear. The 

 smallest dose with which it has been possible to cause gas gangrene with the 

 spores of Vibrion septique has been 0"5 mgrm. of calcium nitrate. For 

 guinea-pigs of 250 grm. weight the minimal dose necessary to produce this 

 effect in every case is larger, namely, 5 mgrm. of calcium chloride. With 



