TOXINS, IMMUNITY, ETC. 499 



plague pneumonia is of great infectivity in producing other 

 cases of plague pneumonia. If we except infection through the 

 respiratory passages in such cases, it may be said that direct 

 infection from patient to patient is relatively uncommon. This 

 is in accordance with the fact that in bubonic plague the bacilli 

 are not discharged from the unbroken surface of the body, and 

 are only present in the secretions in severe cases. 



Toxins, Immunity, etc. As is the case with most organisms 

 which extensively invade the tissues, the toxins in plague 

 cultures are chiefly contained in the bodies of the bacteria. 

 Injection of dead cultures in animals produces distinctly toxic 

 effects ; post mortem, haemorrhage in the mucous membrane of 

 the stomach, areas of necrosis in the liver and at the site of in- 

 oculation, may be present. The toxic substances are compara- 

 tively resistant to heat, being unaffected by an exposure to 65 C. 

 for an hour. By the injection of dead cultures in suitable doses, 

 a certain degree of immunity against the living virulent bacilli 

 is obtained, and, as first shown by Yersin, Calmette, and 

 Borrel, the serum of such immunised animals confers a degree 

 of protection on small animals such as mice. On these facts the 

 principles of preventive inoculation and serum treatment, pre- 

 sently to be described, depend. It may also be mentioned that 

 the filtrate of a plague culture possesses a very slight toxic action, 

 and the Indian Plague Commission found that such a filtrate has 

 practically no effect in the direction of conferring immunity. 



1. Preventive Inoculation HaffkinJs Method. To prepare 

 the preventive fluid, cultures are made in flasks of bouillon with 

 drops of oil on the surface (in India Haffkine employed a 

 medium prepared by digesting goat's flesh with hydrochloric 

 acid at 140 C. and afterwards neutralising with caustic soda). 

 In such cultures stalactite growths (vide supra) form, and the 

 flasks are shaken every few days so as to break up the stalactites 

 and induce fresh crops. The flasks are kept at a temperature 

 of about 25 C., and growth is allowed to proceed for about 

 six weeks. At the end of this time sterilisation is effected by 

 exposing the contents of the flasks to 65 C. for an hour; 

 thereafter carbolic acid is added in the proportion of '5 per cent. 

 The contents are well shaken to diffuse thoroughly the sediment 

 in the fluid, and are then distributed in small sterilised bottles 

 for use. The preventive fluid thus contains both the dead 

 bodies of the bacilli and any toxins which may be in solution. 

 It is administered by subcutaneous injection, the dose, which 

 varies according to the " strength," being on an average about 

 7*5 c.c. Usually only one injection is made, sometimes two, 



