542 THE BACTERIOPHAGE 



ing culture of susceptible bacteria, the regeneration of the agent takes place during 

 the phase of active growth, and precedes the lysis of bacteria (when the latter takes 

 place at all). Thus, the possibility that the active agent is liberated as a result of 

 lysis of bacteria seems to be excluded. 



As to the actual nature of the active substance and the mechanism of its produc- 

 tion by bacteria, there exists great divergence of opinion.' So far there has been no 

 definite evidence offered to substantiate any of the opinions expressed. However, 

 since the active agent is comparatively stable under ordinary conditions, there is 

 hope that it may be isolated in pure state and its nature may then be determined.' 



As to the nature of the effect of this hypothetical substance on normal bacteria, 

 resulting on the one hand in its own regeneration and on the other in the disappear- 

 ance of visible bacterial growth, there exist two views. The majority of workers 

 think that this effect consists in the vitiation of bacterial metabolism accompanied 

 by the accumulation of products which under normal conditions either are not formed 

 at all, or appear only temporarily as intermediary links in the chain of metabolic 

 reactions. The accumulation of these products in turn causes disfunction of new gen- 

 erations of bacteria, and thus perpetuates the disease leading finally to autolysis of 

 the bacteria.^ Thus far, however, no proof has been brought forward to identify the 



' Nicolle, C: loc. cil.; Otto, R., and Winkler, W. F.: loc. cit.; Bordet, J., and Ciuca, M.: Com pi. 

 rend. Soc. de biol., 83, 1293. 1920; Kabeshima, T.: ibid., p. 219. 1920; Doerr, R.: Klin. Wchnschr., i, 

 1489, 1537. 1922; Bail, O.: Wien. klin. Wchnschr., 35, 765. 1922; Eastwood, A.: /. Hyg., 23, 317. 

 1924; Hadley, P.: /. Infect. Dis., 40, i. 1927; Rosenthal, L.: Conipt. rend. Soc. de biol., 95, 612. 

 1926. 



^ Some of the experiments now in progress in the writer's laboratory indicate that purification 

 of this agent can be carried to a point where it no longer gives any of the protein tests, though its 

 activity or antigenic properties remain unimpaired. 



3 According to some investigators, the products of this vitiated metabolism of bacteria possess 

 enzymatic properties (Kuttner, A. G.: loc. cit.; Pico, C. E. : loc. cit.; Prausnitz, C: loc. cit.; Hajos, 

 K.: loc. cit.; Saldanha, A.: loc. cit.; Otto, R., and Winkler, W. F. : loc. cit.) or are capable of acting as 

 catalysts activating the normal intracellular proferments of the bacteria (Kabeshima, T.: loc. cit.; 

 Burnet, F. M.: /. Path. &" Bad., 28, 407. 1925). The relative specificity of phage action is ex- 

 plained by them on the basis of Salkowsky's findings that ferments in general (and proteolytic fer- 

 ments in particular) are often most active against the constituents of such cells which originally 

 produced them (Salkowsky, E., quoted from von Preisz, H.: Die Bakteriophagie, p. 90. Fischer, 1925). 



According to others, these products resemble growth hormones (Doerr, R. : loc. cit.) or exhibit 

 cytotoxic properties (Meuli, H.: loc. cit.), and increase the rate of metabolic activities of bacteria 

 to such an extent that lysis occurs as a terminal stage of this trophic disease. 



It has also been suggested that with the abnormally rapid rate of growth, the amount of pro- 

 teolytic enzyme set free by the bacteria is so great that the supply of protein is exhausted and the 

 ferments attack the bacteria themselves (Seiffert, W.: Seuchenbekampfung, 2, 234. 1925). 



According to Bail (Bail, O.: Deutsche med. Wchnschr., 51, 13. 1925), autolysis of bacteria is 

 due to the loss by the bacterial chromosomes of their anabolic function. The cells with imperfect 

 chromosomes, possessing only the function of katabolism, undergo dissolution. The imperfect chro- 

 mosomes are thereby set free, and are capable of initiating similar vitiation in other bacteria. 



Other workers suggest that the abnormality in bacterial development leading to autolysis is 

 transmitted from generation to generation by heredity (WoUman, E.: A^m. de VInst. Pasteur, 39, 

 789. 1925; Bordet, J., and Ciuca, M.: Conipt. rend. Soc. de biol., 83, 1293. 1920), or is perpetuated 

 through a continuous effect of bacterial dissociation which results in the tendency of the culture 

 to give off increasing numbers of non-viable, autolyzing variants (Eastwood, A.: loc. o7.; Arkwright, 

 J. A.: Brit. J. Exper. Path., 5, 23. 1924; Hoder, F.: Ztschr. f. Inwmnitatsforsch. u. exper. Therap., 

 42. 197. 1925). 



I 



