98 BIOLOGY OF PNEUMOCOCCUS 



for eighteen hours or longer, extensive areas of pneumonia were 

 found. As a control, the authors made intratracheal injections of 

 living, virulent pneumococci which were followed by a transient, 

 slight lesion and recovery, or later by death from septicemia with- 

 out pneumonic lesions. The addition, however, of a sublethal dose 

 of toxic autolysate to the living pneumococci altered the reaction 

 of the animal so that an extensive pneumonia developed associated 

 with unrestrained multiplication of the organism. This synergistic 

 property was far more pronounced than that of the virulin of 

 Pittman and Falk and was more like that of an aggressin. 



Yamamoto (1929) 1557 listed unheated pneumococcal filtrate, 

 heated filtrate, and "standard pneumococcus vaccine" (?) accord- 

 ing to toxicity in a ratio of 1 to 2 to 6, but none of the three was 

 notably toxic, not less than 6.0 cubic centimeters of the last-named 

 preparation being required to kill a rabbit. 



In 1929, Parker 1060 returned to a study of the necrotizing sub- 

 stance of Pneumococcus in comparison with the lung-toxic princi- 

 ples in autolysates. She found both substances to be sensitive to 

 heat and to oxidation, and both were neutralized by the same anti- 

 autolysate serums. The lung-toxic principle, however, was ab- 

 sorbed or inactivated by red blood cells, whereas the necrotizing 

 principle was not. In the discussion, Parker wrote: 



Since pneumococcus hemotoxin is present in the anaerobic autolysate 

 and is also absorbed by red cells, it seemed possible that it was this 

 substance in the autolysates which caused the diffuse lung lesions and 

 death of guinea pigs. However, it was found that the intratracheal in- 

 jection of pneumococcus hemotoxin prepared by the method of Avery 

 and Neill only occasionally produced the characteristic reaction caused 

 by the intratracheal injection of the anaerobic autolysates. From these 

 experiments we believe, therefore, that the necrotizing and lung-toxic 

 principles, and probably the pneumococcus hemotoxin also, are all sepa- 

 rate entities in the anaerobically produced autolysates described. 



Pittman and Southwick 1093 were also attracted by this problem. 

 In their experiments, the injection into mice of extracts produced 



