Introduction xv 



phages. A concise statement of this theory can be found in Adams' book ( 1 ) , 

 and a more generahzed formulation is presented in two later analyses of this 

 problem (137,29). 



An important clue to the nature of the elementary recombinational event 

 in phage was uncovered by Hershey and Chase (74), described in their second 

 paper of this collection. They noted that among the progeny of mixed infec- 

 tions about 2% of the particles are heterozygous, in that these individuals 

 carry homologous loci, or alleles, from both parents of the cross. The heterozy- 

 gosity is only partial, however, in that in any one heterozygote virus only a 

 very limited segment of the genome is actually of biparental provenance, most 

 of its loci being homozygous, or derived from only one or the other of the 

 parents. The structure and behavior of these heterozygotes suggested to 

 Hershey and Chase that the formation of heterozygotes and the formation of 

 recombinants might be related processes. The nature of heterozygotes was 

 considered further by Levin thai (100), who demonstrated that such viruses 

 are recombinant for genetic loci on opposite sides of the limited region of 

 heterozygosity. Levinthal then inferred that recombinant phages, in fact, arise 

 through the formation of heterozygotes in the course of phage reproduction by 

 the partial replica, or copy-choice, recombination mechanism. This inference 

 found further support from Levinthal's calculation that the observed frequency 

 of heterozygotes is great enough to explain the observed frequency of recom- 

 binational events. 



Once the viral DNA had been identified as the germinal substance, it 

 became possible to consider in actual chemical terms how the hereditary 

 information is stored in the resting phage and how it is replicated in the 

 vegetative phage. After deoxyribonucleic acid was discovered by Miescher 

 in 1871, some 60 years of chemical study of this substance revealed that its 

 building block is the nucleotide, composed of one molecule each of phosphoric 

 acid, deoxyribose, and either adenine, guanine, thymine, or cytosine. More 

 recently, it was established that DNA molecules are, in fact, polymers of very 

 high molecular weight, each molecule containing more than 10* nucleotide 

 units joined through phosphate diester bonds linking successive deoxyribose 

 molecules (cf. 36). The actual molecular architecture of DNA was worked 

 out finally by Watson and Crick (151), whose paper is presented here. Wat- 

 son and Crick showed that the DNA molecule consists of two helically inter- 

 twined polynucleotide chains laterally held together by a pair of hydrogen 

 bonds between a complementary pair of purine and pyrimidine residues on 

 opposite chains. The nature of the DNA molecule suggests that the only 

 specific aspect which could distinguish one DNA macromolecule from another 

 is the precise sequence of the four possible purine-pyrimidine base pairs along 

 the complementary nucleotide chains, i.e. that the hereditary information is a 

 message written into the DNA macromolecule in an alphabet containing four 

 letters. This structure also suggested to Watson and Crick a mechanism by 

 which the DNA molecule could replicate itself; for if the two complementary 



