MUTATION AND PHENOTYPIC VARIATION IN PHAGES 297 



unknown cofactors. The host-induced modification., as we 

 have seen, also show a dependence on bacterial physiology that 

 might be interpreted in nutritional terms. 



Both heated and host-modified phages might well be investi- 

 gated to look for cofactor deficiencies (Luria and Human, 1952), 

 and above all to settle the question of penetration. The promis- 

 ing test of penetration is cross-reactivation between phage pairs 

 differing both in genetic markers and phenotypic modifications 

 (Streisinger and Franklin, 1956; Garen and Zinder, 1955). 



Another special case of phenotypic modification was described 

 by Sagik (1954). He found that lysates of T2 often contain 

 phage particles that are noninfective because of failure to adsorb. 

 He demonstrated the noninfective particles by reactivating them 

 in various ways, for example by gentle heating. A similar effect 

 was demonstrated in another line of T2, not subject to heat 

 activation, in another way (Hershey and Melechen, 1957). 

 Sagik showed that at least part of the effect could be ascribed to 

 interactions between free phage particles and other products, 

 presumably related to receptor substances, released at the time of 

 lysis. Adams (1955) found that even the active particles in 

 such lysates fail to adsorb at °, whereas phage produced in salt- 

 free broth, where it presumably cannot combine with the in- 

 hibitor, adsorbs equally well at and 37 ° C. Y. T. Lanni and 

 F. Lanni, in unpublished experiments, obtained evidence that 

 the defective phage particles can be produced intracellularly, 

 which throws doubt on the adequacy of Sagik's interpretation 

 of the phenomenon. 



3. Hereditary Variation (Mutation) 



If one examines the properties of related phages such as T2, 

 T4, T6, and CI 6, one finds both qualitative and quantitative 

 differences in numerous properties. A catalogue of such differ- 

 ences would furnish a good idea of the capacity of the phages in 

 the group to vary by mutation. For practical reasons, it m.ay 

 not be possible to observe all the potential mutations directly. 

 However, by appropriate crossing one can transfer mutant 



