The Bacteriophage Principle. 



223 



a typhoid convalescent. The fact that the lytic agent could be 

 transmitted apparently indefinitely in series and that it was only 

 active against vigorously growing bacteria, suggested that the 

 lytic agent might be derived from the bacterial cell itself. * My 

 next step was to try to produce a lytic principle from the typhoid 

 bacilli without any interaction with the living animal body. 



I proceeded on a theory first suggested by d'Herelle, but dis- 

 carded by him, namely, that the so-called phenomenon of d'Herelle 

 might be due either to an activation of the natural autolysin 

 present in all bacteria, or to the removal of autolysin-inhibiting 

 substance. Once this natural autolysin was liberated, it could 

 in turn liberate an active autolysin from the next generation of 

 bacteria and so on indefinitely. 



It seemed possible from the work of Twort and other observers, 

 such as Cantacuzene and Marie, and from the more recent papers 

 of Turro, that tissue extracts might play a part in starting the 

 activities of the autolysin. 



I want to report briefly on some preliminary results I have 

 obtained by the action of tissue extracts on typhoid bacilli. Up 

 to the present time, I have obtained lysis of typhoid bacilli, 

 transmittable in series by the action of extracts of two different 

 tissues, namely: small intestine and liver. Both tissues were 

 derived from guinea pigs. In the case of the small intestine, 

 three small intestines from normal guinea pigs were pooled, 

 washed and minced. Without drying the tissue was divided and 

 extracted in different strengths of glycerine. After 11 days ex- 

 traction in 50 per cent, glycerine at 37 0 C. some of the supernatant 

 fluid was centrifuged and filtered through a Berkfeld. The ad- 

 dition of a small amount of this filtrate to a young turbid typhoid 

 culture produced a slight amount of clearing as compared with the 

 control. A loop from this tube was plated and then heated at 

 55 0 C. The plate showed regular and irregular colonies. The 

 broth fishings of the irregular colonies carry the lytic principle 

 and typhoid bacilli can be dissolved in series starting with a broth 

 fishing of one of these irregular colonies. It has also been possible 

 to transmit the lytic principle from the first tube after heating to 

 kill the resistant typhoid bacilli, and I have obtained lysis of 

 typhoid bacilli in seventh generation removed from the tissue 



