Led er berg: Genetics 



in nutritional patterns. This syllogism, so evi- 

 dent once told, has been amplified by Beadle 

 and Tatum from this podium. Its implications 

 for experimental biology and medicine are 

 well known: among these, the methodology 

 of bacterial genetics. Tatum has related how 

 his early experience with bacterial nutrition 

 reinforced the foundations of the biochemical 

 genetics of Neurospora. Then, disregarding 

 the common knowledge that bacteria were too 

 simple to have genes, Tatum took courage to 

 look for the genes that would indeed control 

 bacterial nutrition. This conjunction marked 

 the start of my own happy association with 

 him, and with the fascinating challenges of 

 bacterial genetics. 



Contemporary genetic research is predicated 

 on the role of DNA as the genetic material, of 

 enzyme proteins as the cell's working tools, 

 and of RNA as the communication channel 

 between them (63). Three lines of evidence 

 substantiate the genetic function of DNA. 

 Two are related to bacterial genetics; the third 

 and most general is the cytochemical observa- 

 tion of DNA in the chromosomes, which are 

 undeniably strings of genes. But chromo- 

 somes also contain other constituents besides 

 DNA: we want a technique to isolate a chro- 

 mosome or a fragment of one, to analyze it, 

 and to retransplant it to verify its functional 

 capacity. The impressive achievements of nu- 

 clear transplantation (29) should encourage 

 the audacity needed to try such experiments. 

 The constructive equivalent to chromosome 

 transplantation was discovered by a bacteriolo- 

 gist thirty years ago (20). The genetic impli- 

 cations of the "pneumococcus transformation" 

 in the minds of some of Griffith's successors 

 were clouded by its involvement with the 

 gummy outer capsule of the bacteria. How- 

 ever, by 1943, Avery and his colleagues had 

 shown that this inherited trait was transmitted 

 from one pneumococcal strain to another by 

 DNA. The general transmission of other 

 traits by the same mechanism (25) can only 

 mean that DNA comprises the genes (b). 



To reinforce this conclusion, Hershey and 

 Chase (23) proved that the genetic element of 

 a bacterial virus is also DNA. Infection of a 

 host cell requires the injection of just the DNA 

 content of the adsorbed particle. This DNA 



controls not only its own replication in the 

 production of new phage but also the speci- 

 ficity of the protein coat, which governs the 

 serological and host range specificity of the 

 intact phage. 



At least in some small viruses, RNA also 

 displays genetic functions. However, the he- 

 reditary autonomy of gene-initiated RNA of 

 the cytoplasm is now very doubtful — at least 

 some of the plasmagenes that have been pro- 

 posed as fulfilling this function are now better 

 understood as feedback-regulated systems of 

 substrate-transport (81, 65, 72). 



The work of the past decade thus strongly 

 supports the simple doctrine that genetic infor- 

 mation is nucleic, i.e., is coded in a linear se- 

 quence of nucleotides. This simplification of 

 life may appear too facile, and has/urnished a 

 tempting target for agnostic criticism (37, 41, 

 44, 74). But, while no scientific theory would 

 decry continual refinement and amplification, 

 such criticism has little value if it detracts from 

 the evident fruitfulness of the doctrine in ex- 

 perimental design. 



The cell may, of course, carry information 

 other than nucleic either in the cytoplasm or, 

 accessory to the polynucleotide sequence, in 

 the chromosomes. Epinucleic information has 

 been invoked, without being more precisely 

 defined, in many recent speculations on cyto- 

 differentiation and on such models of this as^ 

 antigenic phase variation in Salmonella (ji, 

 52, 56, 47). Alternative schemes have so much 

 less information capacity than the nucleic cycle 

 that they are more likely to concern the regula- 

 tion of genie functions than to mimic their 

 specificities. 



DNA AS A SUBSTANCE 



The chemistry of DNA deserves to be ex- 

 posed by apter craftsmen (86, 31, 13) and I 

 shall merely recapitulate before addressing its 

 biological implications. A segment of DNA is 

 illustrated in Fig. i. This shows a linear poly- 

 mer whose backbone contains the repeating 

 unit: 



— O — PO,-— O — CH, 



diester phosphate C.-/ 



CH 

 C/ 



CH- 



The carbon atoms are conventionally num- 

 bered according to their position in the furan- 



s-66 



