250 IMMUNITY 



organism may be attenuated by growing at a temperature 

 above the optimum. This is the method used in preparing 

 anthrax vaccine as done by Pasteur originally. (4) Instead 

 of growing at a higher temperature the culture may be 

 heated in such a w^ay that it is not killed but merely weak- 

 ened. Black-leg vaccines are made by this method. (5) 

 Chemicals are sometimes added to attenuate the organisms, 

 as was formerly done in the preparation of black-leg vaccine 

 by Kruse's method in Germany. The use of toxin-anti- 

 toxin mixtures in immunizing against diphtheria and in the 

 preparation of diphtheria antitoxin from horses is an appli- 

 cation of the same principle, though here it is the jjroduct 

 of the organism and not the organism whose action is weak- 

 ened. (6) Within the past few years the workers in "the 

 Pasteur Institute in Paris have been experimenting with 

 vaccines prepared by treating living virulent bacteria with 

 antisera ("sensitizing them"), so that they are no longer 

 capable of causing the disease when introduced, but do 

 cause the production of an active immunity. The method 

 has been used with typhoid fever bacilli in man and seems 

 to be successful. It remains to be tried out further before 

 its worth is demonstrated (the procedure is more compli- 

 cated and the chance for infection apparently much greater 

 than by the use of killed cultures) . The term sero-hacterins 

 is used by manufacturers in this country to designate such 

 bacterial vaccines. (7) Growing on artificial culture media 

 reduces the virulence of most organisms after a longer or 

 shorter time. This method has been tried with many 

 organisms in the laborator}\ The difficulties are that the 

 attenuation is very uncertain and that the organisms tend to 

 regain their virulence w^hen introduced into the body. 



B. C. G. (Bacillus of Calmette-Guerin) a culture of the 

 tubercle bacillus grown by Calmette and Guerin on a special 

 bile medium for thirteen years to reduce its virulence is now 

 being tried out extensively in France and other countries of 

 Europe as a preventive of tuberculosis. It is given new-born 

 babies by mouth. Repetition of the vaccination after four 

 or five years is recommended by Calmette. The efficacy of 

 the method remains to be demonstrated. 



In producing active immunity against many bacterial 



