THE MANUFACTURE OF VACCINES. 469 



ATTENUATED VIRUSES. There are several methods which may be 

 employed in attenuating or modifying viruses. The processes involve 

 the treatment of viruses in such ways that they may be injected into the 

 normal animal body without danger of producing serious disease lesions, 

 while at the same time sufficient specific infectious qualities must be 

 present to produce mild reactions. The successful vaccine should 

 be attenuated or modified to the point which represents a happy medium 

 and which clearly indicates both safety and activity. The following 

 are the more important methods used to modify viruses: 



Attenuation by growth at a temperature above the optimum, illustrated 

 by Pasteur's method of preparing anthrax vaccine. 



Attenuation by passage of the virus through some species other than the 

 animal for which the virus is specific. Smallpox vaccine may be regarded 

 as the result of the modification of the virus by passage through the heifer. 



Attenuation of the virus by drying at constant temperature. The 

 Pasteur method of prophylactic treatment for rabies is based upon this 

 method. 



Attenuation by chemicals. The growth of certain pathogenic bacteria 

 in the presence of weak antiseptics weakens their disease-producing 

 activities. 



Other methods of immunization: 



The simultaneous method or hypodermatic application of the virus 

 together with protective serum, as in hog cholera vaccination. 



The association or combination of the specific pathogenic bacteria 

 with those of other species as illustrated by the apparent restraining 

 action of yeasts upon pyogenic bacteria and the antagonism which Ps. 

 pyocyanea exerts toward Bact. anthracis. 



The filtration of liquid cultures of pathogenic organisms, such as 

 Bact. diphtheria or B. tetani, and the consequent separation of the 

 organisms from the toxin. The toxin is used to immunize animals in 

 the production of antitoxin. 



The destruction of young living cultures of specific bacteria by 

 moist heat at a temperature slightly above their thermal death-point. 

 Heated cultures of B. typhosus and Bact. pestis are sometimes used 

 as prophylactics against typhoid fever and bubonic plague. 



There are many vaccines in practical and experimental use at the 

 present time. Among those which are of recognized value as shown by 

 extensive practical use and reliable clinical statistics, the following are 



