THE PROBLEM OF VIRULENCE 9 



tween the two forces, mild and locally limited if the protective pow- 

 ers far outweigh the invasive powers of the micro-organisms, violent 

 if the balance is reversed. This conception is probably a correct one 

 in the case of the large majority of diseases those in which invasion 

 is accompanied by more or less rapid and violent inflammatory and 

 other reactions. In diseases like leprosy, tuberculosis, and a few 

 others of the more chronic infections it is also possible that extensive 

 invasion of the body depends, not so much upon the active invasive 

 powers of the micro-organism, powers which we will attempt to 

 analyze presently, but rather upon the fact that for reasons of in- 

 solubility and lack of irritating properties on the part of the invader 

 no reaction is set up at first, and the invasion, though progressive, 

 elicits no violent symptoms and no energetic opposition. The in- 

 vader therefore progresses unopposed, becoming an incitant of dis- 

 turbed bodily functions to the degree of actual disease only when it 

 has gained a foothold in some organ and begun to proliferate, or 

 has multiplied in such numbers that the cumulative effect of its 

 toxic powers becomes manifest. 



Such a conception would assign the slow and gradual but pro- 

 gressively invasive powers of such diseases as tuberculosis, leprosy, 

 and syphilis in which systemic symptoms are manifest only after 

 the disease has gained an extensive foothold, to the lack of acute 

 physiological reaction resulting from the presence of the invading 

 micro-organism. In the case of such infections as those caused by 

 some of the yeasts or blastomyces we have seen foci of blastomycotic 

 lodgment in the kidney and other organs surrounding which there 

 was neither an accumulation of mobile cells (leukocytes or lympho- 

 cytes) nor any evidence of cloudy swelling or other injury, by 

 poisons, of adjacent parenchyma cells. Here, as in tuberculosis 01 

 leprosy, the reaction induced by the presence of the micro-organisms 

 is slow and gradual expressed in an eventual fixed tissue-cell reac- 

 tion and giant-cell formation similar to that induced by insoluble 

 foreign bodies. And it may well be that the progressive ability to 

 multiply without arousing the invaded body to rapid and powerful 

 reaction may account for the .prolonged period of apparent well- 

 being in the early stages of such infections and permit the invaders 

 to pervade the body so extensively. 



This point of view has been, we believe, most clearly expressed 

 by Theobald Smith. 12 Bacteria may lack invasive or pathogenic 

 properties and be, therefore, immediately destroyed after gaining 

 entrance to the host. They may be powerfully invasive and because 

 of lack of adaptation arouse a violent defensive reaction on the part 

 of the host. "There is another type of parasite," Smith says, "which 

 may dispense largely with both offensive and defensive processes. 

 We can conceive of this type as exerting a metabolic activity approx- 

 12 Theobald Smith. Journ. of A. M. A., May, 1913, Vol. 60. 



