CHEMICAL INTERFERENCE WITH PHAGE GROWTH 275 



hibition by leucine can be reversed by isoleucine, valine, or 

 norleucine (Fowler and Cohen, 1948). Cysteine has been 

 found toxic for phage development and causes an abortive loss 

 of the adsorbed phage (Fowler and Cohen, 1948; Mutsaars, 

 1950; Tanami and Kawashima, 1953). The inhibition by 

 cysteine has been related to its ability to bind metals (Spizizen, 

 Kenney, and Hampil, 1951), but also to a more specific dis- 

 organisation of amino acid metabolism, particularly that of 

 threonine (Gots and Hunt, 1953). A lysogenic strain of £". coli 

 K12, which is known to be inhibited by valine, will not produce 

 lambda phage in the presence of valine unless isoleucine is 

 added (Gots and Hunt, 1953). An inhibition of T2 growth by 

 methionine has also been reported (Czekalowski, 1952). 



c. Prevention of DNA Synthesis as a Consequence of Protein Deficiency 



Cohen (1948) showed that 5-methyItryptophan inhibits both 

 protein and DNA synthesis in bacteria infected with T2. This 

 suggested that protein formation is an essential prerequisite for 

 DNA synthesis. Further analysis by Burton (1955) showed that 

 if deprivation of amino acids is delayed for 7 minutes after infec- 

 tion with T2, phage and subsequent protein synthesis is still pre- 

 vented, but DNA of the hydroxymethylcytosine type is formed. 

 Similar results have been obtained independently with another 

 inhibitor of protein synthesis, chloramphenicol (Melechen, 1955; 

 Tomizawa and Sunakawa, 1956, Hershey and Melechen, 

 1957). This antibiotic had been shown previously to prevent 

 phage formation at some stage (Edlinger, 1951; Bozeman, 

 Wisseman, Hopps, and Danawskas, 1954). The essentials of 

 these findings may be summarized by saying that the synthesis of 

 phage DNA requires an initial synthesis of protein which may be 

 inhibited by 5-methyl tryptophan or chloramphenicol. If syn- 

 thesis of the initial protein is first allowed, continued synthesis of 

 protein is not required for DNA synthesis. Thus, the delayed 

 addition of the inhibitors will permit DNA synthesis but will 

 prevent the formation of further protein which is necessary for 

 phage growth. Hershey and Melechen (1957) employed this 



