ACQUIRED IMMUNITY 67 



fully virulent rabic virus, beginning with a dilution of 1 to 10,000 

 and rapidly working up to a dilution of 1 to 10. In tuberculosis 

 immunization with fully virulent cultures in small amounts has been 

 attempted by Webb, Williams, and Barber, 24 using the Barber method 

 of isolation, and giving a single micro-organism at the first injec- 

 tion. That such a method is feasible, if carried out with sufficient 

 care, even with the most virulent germs, was demonstrated by the 

 same workers. They succeeded in immunizing animals against 

 anthrax (with cultures kept 12 hours on agar) 25 by injecting a 

 single thread (3 to 6 bacilli) as the first dose, and then gradually 

 increasing the amount. 



In the general laboratory immunization of animals treatment 

 with virulent bacteria in sublethal doses is of considerable value and 

 frequently employed. 



It would seem that possibly this method or some modification of 

 it will be found to have very definite advantages over methods in 

 which either attenuated or dead bacteria are employed. Bail's work 

 upon the ag;gressins and upon anti-aggressin immunity (see chapter 

 I, page 21) has opened the possibility that virulent bacteria pro- 

 vide, within the living body, specific aggressive substances which are 

 not produced in the test tube. If this proves to be true, and the 

 question is by no means settled, it may be necessary in such cases 

 to immunize with organisms which are in a condition capable of 

 producing these aggressins. Sublethal doses of fully virulent or- 

 ganisms would furnish these conditions more perfectly than at- 

 tenuated avirulent strains, in which the invasive (aggressive) power 

 is considerably diminished. 



The methods of active immunization so far described differ from 

 those which are to follow in that the preceding were all based upon 

 the use of living bacteria or virus, whereas the methods to be de- 

 scribed below depend upon the treatment of animals with dead bac- 

 teria or bacterial products. It is well to call attention in this place 

 to the fact that a number of recent investigations seem to point to 

 the greater efficiency of immunization with living germs. This 

 method has recently given hopeful results in the case of plague in 

 the hands of Strong; 26 and Metchnikoff and Besredka, 27 in their 

 attempt to vaccinate chimpanzees against typhoid fever, make the 

 statement that vaccination with dead typhoid bacilli or autolysates 

 does not confer adequate protection, but that this can be attained by 

 treatment with small doses of the living bacilli. 



24 Webb, Williams, and Barber. Jour, of Med. Res., Vol. 15, 1909. 



25 This was not possible where the organisms were taken directly from 

 the blood of a dead mouse. In such cases even a single thread caused fatal 

 disease. 



26 Strong. Jour, of Med. Res., May, 1908. 



27 Metchnikoff and Besredka. Ann. Past., Vol. 25, 1911. 



