CHEMOTHERAPY 519 



serum. Search has failed to reveal any record of further trials of 

 this combined form of treatment in pneumococcal infections. 



In this connection a comparison of the protective power of cin- 

 chona derivatives and of antipneumococcic serum may not be out 

 of place. Felton 404 reported that the specific protective globulin of 

 immune horse serum was one million times more effective against 

 Pneumococcus than was quinine sulfate and one hundred thousand 

 times more powerful than optochin. 



EFFECT ON VIRULENCE OF PNEUMOCOCCUS 



Drug-fastness. In Chapter V, the effect of optochin in inducing 

 variation in pneumococci was described. In that biological change 

 the bacterial cell acquires a tolerance for the drug. Morgenroth 

 and Kaufmann 922 " 5 showed that the passage of a pneumococcal 

 strain four times through animals treated with optochin caused 

 the organisms to lose their sensitivity to the action of the drug. 

 The observation was confirmed by Tugendreich and Russo, 1429 and 

 by Koehne, 738 who discovered that pneumococci suffered an enor- 

 mous loss of susceptibility after cultivation in the presence of op- 

 tochin in vitro. Schnabel and Jungeblut* likewise demonstrated the 

 acquisition by the bacterial cell of a high-grade resistance follow- 

 ing cultivation in broth containing optochin. Koch, by growing 

 pneumococci in artificial media, could decrease optochin sensitivity 

 without destroying the virulence of the organisms. After a few ani- 

 mal passages the strains regained their normal sensitivity. 



During this process of biological adaptation, according to 

 Jungeblut, 697 the bacterial cell may lose virulence but, on the other 

 hand, Lewy 807 was able to maintain the full virulence of strains of 

 pneumococci by alternate passage through untreated mice and 

 through culture media containing optochin, although the strain 

 had become eighty to one hundred twenty times more resistant to 



* Quoted from Neufeld and Schnitzer,iooo from whose account and that of 

 Browning* 59 much of the above information is taken. 



