110 BENZER ET AL. 



The even numbered phages represent the group of widest distribu- 

 tion. Many of the coU phages studied by earher workers belong to 

 this group. 



lo. Cof actor Activation. — (T. F. Anderson, 1945, 1948b; Hershey 

 and Delbriick, unpubHshed; Wolhnan and Stent, unpubhshed.) 



It has been found that T4 and T6 exist in two states, "active" and 

 "inactive," depending on the presence of certain amino acids, called 

 cofactors. If suspended in cofactor-free synthetic medium, such phages 

 will be in the inactive state and will not be adsorbed to their host 

 bacteria. When cof actor of sufficient concentration is added, the phages 

 become active and are then able to adsorb on, and later lyse, the host 

 cells. 



L-tryptophan is the most active cofactor found thus far, and its 

 action has been studied in the greatest detail. Other aromatic amino 

 acids, such as phenylalanine, show less activity. Only the L-isomers 

 appear to be effective. Indole is an inhibitor to the activation by L-tryp- 

 tophan (Delbriick, 1948 and unpublished), and it is assumed that com- 

 petition occurs between cofactor and inhibitor at specific sites on the 

 phage. 



It has been estimated that the number of cofactor molecules associ- 

 ated with each phage particle is of the order of two hundred. 



The process of activation is reversible, and the reaction velocities 

 with which gain or loss of activity occurs upon addition or removal of 

 cofactor can be studied. The following results were found: 



( 1 ) Activation and deactivation appear to follow first order kinet- 

 ics and to be "one-hit" processes. 



(2) The rate of activation varies approximately with the fifth 

 power of the cofactor concentration at low concentrations of cofactor 

 and is independent of the cofactor concentration at high cofactor con- 

 centration. 



(3) The rate of deactivation is greatly retarded by concentrations 

 of cofactor which cause only very little activation if mixed with in- 

 active phage. 



A model of the activation mechanism has been formulated which 

 ties together these findings. The phage is thought to contain key places 

 which can be in either an active or an inactive state. Each phage has 

 either just one or a large number of such key places. The key places 

 become active by a reaction involving the simultaneous presence of 



