86 Infection 



upon the invasiveness of the micro-organisms, or the toxicity of their 

 products, or both. 



A few bacteria are almost constant in virulence and can be kept 

 under artificial conditions for years with very little change. Other 

 bacteria begin to diminish in virulence so soon as they are introduced 

 to the artificial conditions of Ufe in the test-tube. Still others, and 

 perhaps the greater number, can be modified, and their virulence 

 increased or diminished according to the experimental manipulations 

 to which they are subjected. 



Variation in virulence is not always a peculiarity of the species, 

 for the greatest differences may be observed among individuals of 

 the same kind. Thus, the streptococcus usually attenuates rapidly 

 when kept in artificial media, so that special precautions have to be 

 taken to maintain it, but Hoist observed a culture whose virulence 

 was unaltered after eight years of continuous cultivation in the 

 laboratory without any particular attention having been devoted 

 to it. What is true of different cultures of the same organisms, is 

 equally true of the individuals in the same culture. To determine 

 such individual differences is quite easy among chromogenic 

 bacteria. If these are plated in the ordinary way it will be found 

 that some colonies are paler and some darker than others. Conn 

 found that by repeating the plating a number of times and always 

 selecting the palest and darkest colonies he was eventually able to 

 produce two cultures, one brilliant yellow, the other colorless, from 

 the same original stock of yellow cocci from milk. 



Decrease of virulence under artificial conditions probably depends 

 upon artificial selection of the organisms in transplantation from 

 culture to culture. When planted upon artificial media, the vege- 

 tative members of the bacterial family proceed to grow actively 

 and soon exceed in number their more pathogenic fellows. Each 

 time the culture is transplanted, more of the vegetative and fewer 

 of the pathogenic forms are carried over, until after the organism 

 is accustomed to its new environment, and grows readily upon the 

 artificial media, it is found that the pathogenic organisms have 

 been largely or entirely eliminated and the vegetative forms alone 

 retained. 



Increase of virulence can be achieved by artificial selection so 

 planned as to preserve the more virulent or pathogenic organisms 

 at the same time that the less virulent and more vegetative organisms 

 are eliminated. In cases in which no virulence remains, the experi- 

 mental manipulation of the culture is directed toward gradual im- 

 munization of the micro-organisms to the defensive mechanisms of 

 the body of the animal for which the organism is to be made virulent. 

 A number of methods are made use of for this purpose. 



Passage Through Animals. — Except in cases where the virulence 

 of the micro-organism is invariable, it is usually observed that the 

 transplantation of the organism from animal to animal without 



