THE RELATIOX OF BACTERIA TO DISEASE 147 



may to a large extent be increased or diminished in virulence. The 

 septicaemic class of bacteria when grown in the body fluids gradually 

 produce cells with less substance with affinity for the bactericidal sub- 

 stances of the blood and thus become less vulnerable. The variation 

 in the amount of specific poisons produced by bacteria can be best 

 studied in diphtheria and tetanus. We note, first, that different 

 cultures of diphtheria and tetanus bacilli have wide variations in 

 the amount of toxin which they produce i. e., a diphtheria bacillus 

 obtained from a case of diphtheria will produce in suitable nutrient 

 broth a poison of such strength that 1 c.c. will kill an average-sized 

 guinea-pig, while the poison from another bacillus will kill with a 

 much less quantity, or 0.005 c.c. Further, the bacilli obtained from 

 some sources retain their power of producing poison, when grown on 

 artificial media, for years unaltered, while others lose much of this in 

 a few months. This is equally true of the tetanus bacilli. 



The power to produce toxin can be taken from bacilli by growing 

 them under adverse circumstances, such as cultivation at the maxi- 

 mum temperature at which they are capable of development. Some 

 bacilli are easily attenuated; others are robbed of their virulence only 

 with great difficulty. Increase of toxin-production is more difficult, 

 and it is only possible to obtain it to a certain extent. The means 

 usually employed are the frequent replanting of cultures But with 

 all our efforts we are usually only able to restore approximately the 

 degree of toxin-formation which the cultures originally possessed. The 

 adaptation of bacteria to any nutritive substance, living or dead, so 

 that they will grow more readily, is more easily brought about, pro- 

 vided they will grow at all. The streptococcus from erysipelas and the 

 pneumococcus from pneumonia are typical of this class of bacteria. 

 Inoculate a rabbit with a few streptococci obtained from a case of 

 human sepsis, and, as a rule, no result follows; inject a few million, 

 and usually a local induration or abscess appears; but if one hundred 

 million are administered septicaemia develops. From this rabbit now 

 inoculate another, and we find that a dose slightly smaller suffices to 

 produce the same effect; in the next animal inoculated from this still 

 less is required, and so on, until in time, with some cultures, a very 

 minute number will surely develop and produce death. The same 

 increase in virulence can be noted when septic infection is carried in 

 surgery or obstetrics from one human case to another. By allowing 

 bacteria to continue to develop under certain fixed conditions they 

 become accustomed to them, and less adapted for all that differ. 



Somewhat distinct, again, from that class of bacteria which multiply 

 rapidly are those which, like the tubercle and leprosy bacilli, because 

 of not developing in the blood increase more slowly. Here increase of 

 virulence is shown, as before, by the production of disease through 

 the introduction of very small numbers into the body, but increase 

 in rapidity of development cannot progress except to within certain 

 limits. A single streptococcus may, through its rapid multiplication, 

 produce death in eighteen hours; a single tubercle bacillus, on the 



