236 



FA had not propagated as such but 

 rather was associated with the neces- 

 sary stimulus for further production, 

 the phage. 



DISCUSSION 



Genetic exchange in 5. typhimurium 

 is mediated by a bacterial product 

 which we have called FA (filtrable 

 agent). An individual active filtrate 

 can transfer (transduce) many heredi- 

 tary traits from one strain to another. 

 Although the total activity of this fil- 

 trate encompasses the genotype of its 

 parental culture, each transduction 

 transmits only a single trait per bac- 

 terium. This contrasts with genetic ex- 

 change in E. coli, strain K-12, where 

 there is unrestricted recombination of 

 the several markers that differentiate 

 two parental lines. 



FA may be considered as genetic 

 material which enters the fixed hered- 

 ity of the transduced cell. We may ask 

 whether this transfer is a simple super- 

 addition or a substitutive exchange and 

 replacement of the resident genetic 

 factors. If streptomycin resistance is a 

 recessive mutation, as inferred from 

 studies of heterozygous diploids in E. 

 coli (Lederberg, 1951/?), the transduc- 

 tion of resistance disqualifies the sim- 

 ple addition mechanism. 



Two aspects of FA must be care- 

 fully distinguished: the biological na- 

 ture of the particles themselves and 

 their genetic function. There is good 

 reason to identify the particle with 

 bacteriophage. Nevertheless, the phage 

 particle would function as a passive 

 carrier of the genetic material trans- 

 duced from one bacterium to another. 

 This material corresponds only to a 

 fragment of the bacterial genotype. 

 For example, when FA from a marked 

 prototroph is plated with an auxotroph 

 on minimal agar, the genotype of the 

 presumed "donor nucleus" is not ob- 

 served among the transduced proto- 



ZINDER AND LEDERBERG 



trophs. The hypothesis of FA as a 

 genetic complex rather than a unit 

 might be maintained if the singular ef- 

 fects produced depended on a small 

 chance of release of any particular ac- 

 tivity from a complex particle or on 

 some localized nonheritable happen- 

 stance in the cell that ordinarily left 

 only one function sensitive to trans- 

 duction. Still the originally singly 

 transduced cell develops as an isolated 

 clone. Since the clone is composed of 

 some 10^ bacteria, one might expect 

 that a complex residuum of an FA par- 

 ticle, if viable, would transduce some 

 one of the daughter cells for another 

 character during the growth of the 

 clone. However, each FA particle pro- 

 duces only a single transduced clone. 

 This speaks for the simplicity of its 

 constitution as well as of its genetic 

 effect. 



When LA-22 is transduced from 

 auxotrophy (phenylalanineless and ty- 

 rosineless; tryptophanless) to proto- 

 trophy, we have an apparent dual 

 change. If this mutant is plated on 

 minimal agar supplemented with 

 phenylalanine and tyrosine, it occa- 

 sionally^ reverts to the first step auxo- 

 trophic condition. However, when 

 LA-22 is transduced on this medium, 

 no more first step auxotrophs are 

 found than can be explained by spon- 

 taneous reversion. The majority of the 

 selected colonies are prototrophs. We 

 have not been able to affect more than 

 one trait in any other inter- or intra- 

 strain transductions. It seems likely 

 that the nutrition of LA-22 was deter- 

 mined by two successive mutations at 

 the same genetic site. Davis' (1951) 

 scheme for aromatic biosynthesis cor- 

 roborates this notion. Although the 

 mutant LA-22 can revert spontane- 

 ously to an intermediate allele, trans- 

 duction brings about a substitution of 

 the wild type gene for full synthesis. 



The most plausible hypothesis for 



