13 



troyed by phagocytosis. Experiments in vitro provide supporting 

 evidence, since virulent pneumococci are not ingested by leucocytes 

 except in the presence of immune serum, and the leucocytes are 

 thought to play an essential part in the mechanism and not to act 

 merely as scavengers. 



Perhaps the above observations on the attenuating action of 

 immune serum may serve to amplify Neufeld's theory, the sugges- 

 tion being that the action of immune serum is not entirely bacterio- 

 tropic. A certain number of pneumococci may not be directly 

 subjected to phagocytosis in the presence of immune serum. 

 These may give rise to new generations in the animal body, but 

 such bacteria would, under the influence of the immune serum, 

 be subjected at the onset of growth to rapidly progressive attenua- 

 tion and would soon be destroyed. 



Summary. 



1. Virulent pneumococci become attenuated by growth in 

 homologous immune serum. 



2. The loss of virulence is associated with an alteration of the 

 immunological characters. 



The attenuated pneumococcus does not stimulate the pro- 

 duction of protective substances in the blood of inoculated 

 rabbits. 



3. There is a morphological distinction between the colonies 

 of the virulent and the attenuated pneumococci. The virulent 

 colonies are smooth and the attenuated rough in character, the 

 distinction being similar to that between the R and S varieties of 

 B. dysenterise, &c. described by Arkwright. 



4. The S pneumococcus produces in young broth cultures a 

 specific soluble substance ; the R pneumococcus does not. 



5. The S form agglutinates with specific serum, producing a 

 firm gelatinous precipitate ; the R form produces loose clumps 

 which are readily shaken up. 



6. An R strain may revert in all respects to the S type, or 

 may remain unchanged after many generations in subculture in 

 plain blood broth. On the other hand, the morphological dis- 

 tinction between the R and the S forms may tend to disappear, 

 while the immunological differences persist. 



7. The attenuation of pneumococci by immune serum in the 

 test-tube indicates that the mode of action of the serum in a 

 protection experiment is a direct one upon the pneumococcus. 



A double action may be suggested : — 



(a) The serum may disorganise the biological functions 

 of the pneumococcus by precipitating the capsule, thus 

 inhibiting the secretion of anti-leucocytic substances and 

 rendering it temporarily harmless. 



(b) When pneumococci divide in the animal body in the 

 presence of immune serum, it is suggested that the influence 

 of the serum may cause progressive attenuation of subse- 

 quent generations. 



November, 1922. 



