Lederberg: Genetics 



ing RNA fragments together with 

 sources of these components. 

 (7) One molecule of the protein aminoacyl- 

 RNA polymerase. 



In principle, this formidable list might be 

 reduced to a single polynucleotide polymer- 

 ized by a single enzyme. However, any 

 scheme for the enzymatic synthesis of nucleic 

 acid calls for the coincidence of a particular 

 nucleic acid and of a particular protein. This 

 is a far more stringent improbability than the 

 sudden emergence of an isolated DNA such 

 as many authors have suggested, so much more 

 so that we must look for alternative solutions 

 to the problem of the origin of life. These are 

 of two kinds. The primeval organism could 

 still be a nucleic cycle if nucleic replication oc- 

 curs, however imperfectly, without the inter- 

 vention of protein. The polymerase enzyme, 

 and the transfer of information from nucleic 

 acid to protein, would then be evolved refine- 

 ments. Alternatively, DNA has evolved from 

 a simpler, spontaneously condensing polymer. 

 The exquisite perfection of DNA makes the 

 second suggestion all the more plausible. 



The nucleoprotein cycle is the climax of bio- 

 chemical evolution. Its antiquity is shown by 

 its adoption by all phyla. Having persisted for 

 — io 9 years, nucleoprotein may be the most 

 durable feature of the geochemistry of this 

 planet. 



At the present time, no other self-replicat- 

 ing polymers are known or understood. Never- 

 theless, the nucleic system illustrates the basic 

 requirements for such a polymer. It must have 

 a rigid periodic structure in which two or more 

 alternative units can be readily substituted. It 

 must allow for the reversible sorption of spe- 

 cific monomers to the units in its own se- 

 quence. Adjacent, sorbed monomers must 

 then condense to form the replica polymer, 

 which must be able to desorb from the tem- 

 plate. Primitively, the condensation must be 

 spontaneous but reliable. In DNA, the sorp- 

 tion depends on the hydrogen bonding of nu- 

 clein molecules constrained on a rigid helical 

 backbone. This highly specific but subtle de- 

 sign would be difficult to imitate. For the more 

 primitive stages, both of biological evolution 

 and of our own experimental insight, we may- 



prefer to invoke somewhat cruder techniques 

 of complementary attachment. The simplest 

 of these is perhaps the attraction between ionic 

 groups of opposite charge, for example, NH: 

 and COO which are so prevalent in simple 

 organic compounds. If the ingenuity and 

 craftsmanship so successfully directed at the 

 fabrication of organic polymers for the practi- 

 cal needs of mankind were to be concentrated 

 on the problem of constructing a self-replicat- 

 ing assembly along these lines I predict that 

 the construction of an artificial molecule hav- 

 ing the essential function of primitive life 

 would fall within the grasp of our current 

 knowledge of organic chemistry. 



CONCLUSIONS 



The experimental control of cellular geno- 

 type is one of the measures of the scope of 

 genetic science. However, nucleic genes will 

 not be readily approached for experimental 

 manipulation except by reagents that mimic 

 them in periodic structure. Specifically in- 

 duced mutation, if ever accomplished, will 

 then consist of an act of genetic recombination 

 between the target DNA and the controlled 

 information specified by the reagent. Methods 

 for the step-wise analysis and reassembly of 

 nucleic acids are likely to be perfected in the 

 near future in pace with the accessibility of 

 nucleic acid preparations which are homo- 

 geneous enough to make their use worth while. 

 For the immediate future, it is likely that the 

 greatest success will attend the use of biological 

 reagents to furnish the selectivity needed to 

 discriminate one among innumerable classes 

 of polynucleotides. Synthetic chemistry is, 

 however, challenged to produce model poly- 

 mers that can emulate the essential features of 

 genetic systems. 



REFERENCES 



1. Anderson, T. F., "Recombination and Segre- 

 gation in Escherichia coli" Cold Spring Harbor 

 Symposia Quant. Biol., 23:47, 1958. 



2. Arber, W., "Transduction dcs caracteres Gal 

 par le bacteriophage Lambda," Archives des 

 Sciences, Soc. Phys. Hist. Nat. Geneve, 1 1 : 259, 

 1958. 



3. Baron, L. S., Carey, W. F., and Spilman, 

 W. M., "Hybridization of Salmonella Species by 

 Mating with Escherichia coli" Abst. yth Int. 



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