CHAPTER XL 



THE BACTERIOPHAGE: PRESENT STATUS OF THE QUESTION 

 OF ITS NATURE AND MODE OF ACTION' 



J. BRONFENBRENNER 



Laboratories of the Rockefeller Institute for Medical Research, New York City 



THE PARTICULATE NATURE OF BACTERIOPHAGE 



According to D'Herelle, transmissible lysis is the result of an acute infectious dis- 

 ease of bacteria. The etiological factor of this disease is an "autonomous ultra-mi- 

 croscopic corpuscle" — Bacteriopha'ium intcstinale." The corpuscular nature of the ac- 

 tive agent'^ of transmissible lysis is claimed by D'Herelle on the basis of the following 

 observations. 



If filtrates of cultures subjected to the action of bacteriophage are examined un- 

 der an ultra-microscope, they show the presence of minute granules. Some of these 

 granules can be seen entering the bacterial cells and multiplying within them.4 The 

 identification of these particles with the active agent is supported by the observation 

 that on prolonged standing, or as the result of intensive centrifugation of active fil- 

 trates, the particles tend to settle to the bottom of the container, and coincident with 

 this settling, the active agent collects in the lower strata of the solution.^ When ac- 

 tive filtrate is spread over the surface of agar seeded with susceptible bacteria, it 

 causes the appearance of discrete foci of lysis, and the number of such foci (plaques) 

 is proportional to the concentration of active agent in the solution.'' 



That the active agent is present in the filtrates in the form of indivisible units 

 follows also from the fact that it exhibits no gradual diminution of its activity on 

 serial dilution (such as exhibited by antiseptics, for instance), but becomes at once 

 totally ineffective as soon as dilution is carried beyond the point at which a certain 

 quantum of the agent is present. This quantum (about iXio-'° cc.) cannot be sub- 

 divided on further dilution.'' The question arises as to the nature of these quanta of 

 the active agent. 



' Editors' note. — It is regretted that a chapter by Dr. d'Herelle which had been promised 

 has not been received. 



^d'Herelle, F. : The Bacteriophage and Its Behavior, pp. 354-55. Williams & Wilkins, 1926. 



^Throughout this discussion the terms "bacteriophage," "phage," and "active agent" (of trans- 

 missible lysis) are used interchangeably to designate the agent without commitment as to its nature. 

 In referring to the hypothetical living virus of D'Herelle, the terms Bactcriophagiim intcstinale or 

 Protobios bactcriophagus are used. 



4 d'Herelle, P.: Immunity in Natural Infectious Disease, p. 255. Williams & Wilkins, 1Q24; The 

 Bacteriophage and Its Behavior, p. 273. Williams & Wilkins, 1Q26; ibid., p. 370. Williams & Wilkins, 

 ig26. 



5 d'Herelle, F. : The Bacteriophage and Its Behavior, p. 2S0. Williams & Wilkins, 1926. 

 'd'Herelle, F.: Compt. rend. Acad, de Sc, 165, 373. 191 7. 



7 The effect of dilution on the distribution of the a"ctive agent is therefore analogous to that of 

 bacterial suspensions, for instance. See Bronfcnbrenner, J., and Korb, C: J. E.xper. Med., 42, 4S3. 

 1925- 



52s 



