THE PROBLEM OF VIRULENCE 21 



invade. As a matter of fact we have learned, since that time, that 

 staphylococci may secrete soluble substances, "leukocidins," which 

 injure white blood cells, and that many bacteria produce similar 

 poisons, "hsemotoxins," which specifically injure red blood cells 

 thereby causing anaemia and reducing the resistance of the host. 

 However, the correlation and further elaboration of these thoughts 

 of Salmon and Smith, of Bouchard and of Krnse was left to Bail, 39 

 in what is known as his "aggressin theory." Bail maintains on the 

 basis of careful experimentation that virulent bacteria can produce 

 within the animal body substances which he calls "aggressins," upon 

 which depend their invasive powers or virulence. These substances 

 are secreted only under stress of the struggle against the unusual 

 defences, are not demonstrable in test-tube cultures, and are in 

 themselves, according to Bail, entirely non-toxic. 



He obtains these aggressins by injecting virulent bacteria into the 

 peritoneal cavity of a guinea pig and immediately after death re- 

 moving the exudate. This he centrifugalizes, removes the bacteria 

 and cells, and sterilizes the supernatant liquid by the addition of 

 small quantities of chloroform. The action of the exudates in which 

 aggressins have been produced by the bacteria is the following: 

 (We take this tabulation from Bail's own paper on typhoid and 

 cholera aggressins in the Archiv fur Hygiene, Vol. 52, p. 342.) 



1. Sublethal doses of typhoid bacilli or cholera spirilla become 

 lethal when the aggressin is injected with them. 



2. Lethal doses of bacilli which ordinarily would cause a slow 

 infection only cause a rapid and severe infection when aggressins 

 are added. 



3. The addition of aggressin neutralizes the bacteria-destroy- 

 ing power of immune serum in the peritoneal cavity of a guinea pig. 



4. The injection of aggressin alone produces subsequent im- 

 munity. 



It is impossible to discuss with completeness the arguments ad- 

 vanced for and against the correctness of Bail's views until we have 

 described in detail the mechanism of protection at the disposal of 

 animals. But the main objection brought against this theory is that 

 of Wassermann and Citron, 40 who claim that all these properties of 

 the aggressive exudates can be explained by the fact that they con- 

 tain extracts of the bacteria (endotoxins), which, injected with 

 a sublethal dose of bacteria, merely enhance their action in the same 

 way that this would have been accomplished by the injection of 

 additional dead bacterial bodies. It will require much further work 

 before this point is settled, and the problem is peculiarly involved and 



39 Ball. Archiv f. Hijg., Vols. 52 and 53, 1905 ; Folio serologica, Vol. 7, 

 1911. 



40 Wassermann and Citron. Deutsche med. Woch.,, Vol. 31, 28, 1905. 



