324 Essays in Biochemistry 



changes into somatic cells of the same heredity (for a review see ref . 4) , 

 the composition and structure of nuclear protein may undergo drastic 

 changes: the change of protamines into histones is but one example. 

 In addition, the study of the quantity of DNA and of protein (per 

 single set of chromosomes) revealed that, although the quantity of 

 DNA remains the same in all cells of a species, 5 the quantity of protein 

 varies a great deal. All these findings can be taken as an indication 

 (though not as an absolute proof) that in higher species also the DNA 

 serves as a determinant of heredity. 



This concept encountered difficulties, however. Workers in the field 

 were still influenced by the authority of "old masters" (especially 

 P. A. Levene 6 ) who, on the basis of erroneous chemical analysis, con- 

 cluded that the DNA from all sources contains equimolar amounts of 

 individual purines and pyrimidines; that these form subunits ("tetra- 

 nucleotides") ; and that, in fact, all deoxyribonucleic acids are identical, 

 being merely composed of identical "tetranucleotides." Lehmann- 

 Echternacht even reported that he had actually isolated this (purely 

 fictitious) substance. Of course, the identical and simple DNA mole- 

 cules could not serve as highly specific heredity determinants. 



These erroneous views about the structure of DNA were slowly 

 corrected, mainly through the work of Chargaff and his collaborators 

 (for a review see ref. 4). It was found that the DNA has a highly 

 complex asymmetrical structure; 7 that the individual purines and 

 pyrimidines, as a rule, are not present in equimolar amounts; that the 

 "tetranucleotide" unit simply does not exist; 8 that the composition of 

 the whole DNA is different for each species but similar for different 

 organs of the same species ; 9 and that the DNA of one type of cell is 

 actually a mixture of different molecules.* 10,:l1 All these features arc 

 necessary if the DNA molecules are to serve as heredity determinants ; 

 but the finding of these features does not, of course, furnish a proof 

 that the DNA molecules actually are heredity determinants. 



The Transforming Phenomenon 



The study of the nature of the transforming principle furnished the 

 most acceptable proof that one heredity determinant is DNA. The 

 transforming phenomenon will be discussed at greater length because 

 it offers unique possibilities for studying the correlation between the 



* Assuming the molecular weight of DNA to be of the order of 5 X 10 6 , the 

 number of possible combinations of sequence of different nucleotides for the 

 DNA molecules of just one composition is of the order of 10 9000 . 



