THE CHEMICAL BASIS OF HEREDITY 17 



essential tool in the investigation of the physical chemistry of genetic 

 material. On the other hand, the physical chemical studies are providing 

 the biologist with an understanding of the molecular basis of the biological 

 specificity and information-carrying capacity of the nucleic acids. 



The experiments of classical genetics have provided evidence that 

 hereditary information is carried in unit packets which have been called 

 genes. The transformation experiments have provided evidence that 

 genetic information is carried in nucleic acid molecules. What is the 

 relation between the biological unit, the gene, and the chemical unit, the 

 molecule? To answer this question, let us first consider evidence which 

 identifies the biological unit by means of transformation experiments. 



Unit factor transmission 



The use of drug-resistant strains in transformation experiments pro- 

 vides a means for better quantification than has been possible with type 

 specificity. Drug-resistant strains are found as rare variants in drug- 

 sensitive populations. For example, when 10^ penicillin-sensitive pneu- 

 mococci are placed in contact with a killing concentration of penicillin on 

 a solid medium, an occasional cell survives and forms a colony. If such 

 a colony is then allowed to grow for many generations in the absence of 

 penicillin, and its progeny are tested for resistance, each daughter cell 

 will grow and form a colony on penicillin-agar, as shown in Figure 1.6. 

 Thus the colony isolated from the first penicillin plate consisted of cells 

 which differed from all the rest of the population in being penicillin- 

 resistant. All of its progeny are resistant, and DNA extracts from such 

 strains will transform sensitive cells into resistant ones. Similarly, DNA 

 extracts from strains resistant to other drugs, such as streptomycin, 

 cathemycin, and sulfanilamide, will transform sensitive cells into the 

 corresponding resistant type. Doubly and triply resistant strains can be 

 produced by serial steps of transformation, and one can test the ability 

 of their DNA extracts to transform cells into each resistant type. Since 



TABLE 1.3 

 Double Transformation with Unlinked Markers 



(After Hotchkiss, 1954, Symposium on Genetic Recombination, 

 /. Cell. Comp. Physiol., 45:1) 



„ „-,. _ ^ ,, Transformants 



Donor DNA Receptor Ceils tt. — i f: — n 



Smgie Double 



pen-r str-r pens str-s pen-r str-s 0. 01 



pen-r str-r 0.0001 

 pen-s str-r 0.01 



