36 Essays in Biochemistry 



Before some of the biochemical objectives in the field of lysogeny 

 can be stated, the biological phenomenon should be described. Fortu- 

 nately, the reader can be referred for the history of the problem and 

 for a summary of the brilliant recent work, mostly by Lwoff and his 

 school, to a masterly review by Dr. Lwoff himself. 1 



We need, therefore, give only a sketchy outline of the biological 

 phenomenon. A wide variety of microorganisms carry, hereditarily, 

 the seeds of their own and of other bacteria's destruction, either within, 

 or closely associated to their genetic material. Under the influence of 

 random metabolic or physical stimuli the metabolism of such organisms 

 can undergo a profound shift, producing seemingly de novo bacterio- 

 phages, which then emerge from the crumbling hulk of the host cell. 

 From this stage on these phages of lysogenic origin apparently differ 

 in no way from other free virulent bacteriophages: their cycle of 

 replication takes place within susceptible host cells which they infect 

 by invasion. 



No chemical investigation of the phenomenon was possible as long 

 as we were limited to the spontaneous rate of occurrence of the lyso- 

 genic phenomenon. Since the frequency of the occurrence of phage 

 development and lysis in a lysogenic culture is low (1%, or less), any 

 chemical study was precluded by the dilution of the object of the 

 study by its stable, colony-mate cells. 



A profound discovery by Lwoff allowed a complete reversal of the 

 above ratio in some lysogenic strains. If cultures of some lysogenic 

 bacteria are exposed to small doses of ultraviolet or X radiation, or 

 to some mutagenic or carcinogenic agent, the fraction of organisms 

 in which the prophage * is induced to proliferate into mature bacterio- 

 phage approaches unity. It should be emphasized that not every strain 

 of lysogenic organism yields to the inducers listed above. 



The Lwoff effect is an almost startling phenomenon. If a milky 

 culture of Bacillus megatherium containing 10 s viable cells per milli- 

 liter is exposed to a small dose of ultraviolet irradiation and then 

 incubated in the dark, the suspension begins to clarify after about 

 60 minutes and within a few minutes the culture becomes water clear. 

 At the same time, it can be demonstrated, by plating for plaques on 

 a sensitive strain of bacteria, that concomitant to the lysis there is a 

 large increase in the free phage titer. 



How can one begin to make a dent in a problem such as this with 

 the tools of the chemist? The great Hopkins'-' gave sound advice on 



* Dr. Lwoff's term for the "form in which lysogenic bacteria perpetuate the 

 power to produce phage." 



