INTRODUCTION J 



reported and correcdy interpreted many of the significant as- 

 pects of bacteriophage action, and in 1921 published his classic 

 book entitled Le bacteriophage: son role dans rimmiinite. 



D'Herelle, stimulated by the announcement that hog cholera 

 was due to the synergistic action of a bacterium and a virus, was 

 searching for evidence of such a mixed etiology for bacillary 

 dysentery in man. He prepared Chamberland filtrates of stools 

 of dysentery patients and added these filtrates to young cultures 

 of Shiga's bacillus. He incubated the mixtures overnight intend- 

 ing to inject the supposed mixture of bacterium and virus into 

 experimental animals next day. To his surprise some of the 

 culture fluids were clear and sterile. He filtered some of the 

 lysed cultures and inoculated fresh cultures of Shiga's bacillus 

 with the filtrates, keeping other cultures of the bacterium as un- 

 inoculated controls. On incubation overnight he found the con- 

 trol cultures to be turbid as expected while the bacterial cultures 

 inoculated with the filtrates were completely clear. The "lytic 

 principle" could be passed indefinitely from culture to culture 

 using each time for phage inoculum a bacteria-free filtrate of the 

 previous culture. This behavior suggested to him an ultravirus, 

 pathogenic for bacteria, destroying its host cells as it multiplied. 

 During the next few years bacteriophages were found for a 

 variety of pathogenic bacteria such as staphylococci, cholera 

 vibrio, and typhoid bacteria. Because of the susceptibility of 

 pathogenic bacteria to phages, and because of the wide distribu- 

 tion of phages in nature, d'Herelle suspected that they played a 

 role in resistance to and recovery from disease. 



D'Herelle shares with Twort credit for the discovery of phages 

 and did much of the basic research concerning them. In addi- 

 tion his ideas relating phages to immunity to disease attracted 

 the general attention of medical scientists, indirectly yielding 

 both practical and theoretical benefits. The importance of the 

 role of bacteriophages in natural control of infectious disease has 

 not been assessed to this day, however. 



A vast amount of research was devoted to possible therapeutic 

 ^applications of bacteriophages between 1920 and 1940. In 



