VARIATIONS IN TYPHOID BACILLI 299 



upon proteotoxin, but without their finding anything in the nature of 

 a capsule which could explain the phenomenon. Ransom and Kita- 

 shima, Mtiller (1911), Hamburger, Walker (1904) and several other 

 workers have also produced inagglutinability by cultivating on sera 

 containing agglutinin. Forges and Prantschoff (1906) used this method, 

 obtaining irregular results, and attribute this to individual variations 

 in the strains used. 



Moon (1911) produced two substrains of a single typhoid bacillus 

 culture by the Barber method, one of which agglutinated with anti- 

 typhoid serum and the other did not. A few generations later both 

 bacilli showed equal agglutinability. 



In Zinsser's book (1918) Infection and Resistance, he states: 



''This lessened susceptibility to antibodies is noticeable not only in 

 strains cultivated from the body in disease, but can be produced arti- 

 ficially by cultivating the bacteria on inactivated, homologous immune 

 serum. Such strains may not only increase in virulence, but lose in 

 both agglutinability and susceptibility to bactericidal effects." 



Sacquepee (1901) obtained similar variations by keeping the organ- 

 isms in collodion sacs in the peritoneal cavity. Sawyer (1912) iso- 

 lated a strain from a typhoid carrier's stool which did not agglutinate 

 with a serum dilution of 1 to 50, but after 11 transplants within two 

 weeks the culture became agglutinable. The same phenomenon has 

 been observed by Scheller (1908). 



Recently Gay and Claypole (1913) studying the typhoid bacillus, 

 found that when they produced the carrier state in rabbits the organ- 

 isms isolated from such rabbits (culturally true typhoid bacilli) failed 

 completely to agglutinate in serum produced with a stock culture and 

 which agglutinated such stock cultures in dilutions as high as 1 : 20,000. 

 The blood and bile cultures which were inagglutinable by means of the 

 ordinary antiserum, were readily clumped by means of a serum pro- 

 duced by immunizing rabbits with cultures grown on a blood agar 

 medium. If confirmed, these observations, like those of Bordet and 

 Sleeswyk, would indicate a complete alteration of antigenic properties 

 by means of cultivation on blood media, and prolonged residence in the 

 animal body; for the serum produced with the cultures upon blood, not 

 only agglutinated these cultures, but also the plain agar growths, and 

 if the cultures on blood were carried along for some generations on plain 

 agar, they again became agglutinable by the serum produced with the 

 plain agar culture. Gay (1914-15) uses this observation to explain the 

 occasional inagglutinability in ordinary sera, of typhoid bacilli recently 



