332 Essays in Biochemistry 



cules of one kind are active. If, in addition, every DNA molecule in 

 the cell is assumed to be a potential transforming principle, then the 

 physical and chemical behavior of the bulk of the DNA preparation 

 are representative of the physical and chemical behavior of the active 

 molecules. Obviously, more evidence is needed before such a view 

 can be fully accepted, but even at the present status the "infectivity" 

 of DNA particles is comparable to that of bacterial viruses. 



If one assumes an arbitrary molecular weight of DNA, the above 

 estimates can be expressed in terms of numbers of molecules. For a 

 molecular weight of the order of 5 X 10 6 , the number of DNA molecules 

 of all kinds necessary to transform one cell would be of the order of 

 1000 and the total number of molecules of DNA in one cell of the 

 order of 200. Even if one assumes that all the molecules of DNA in 

 the cell are functional, it still appears that there are too few of them 

 to serve as determinants of all the hereditary characters of the cell. 

 One is tempted to speculate whether the DNA molecules do not 

 determine all the characters or whether one molecule of DNA deter- 

 mines several characters. That the latter may be the case is sug- 

 gested by the discovery of the multiple transformations in H. influ- 

 enzae 23 and in pneumococcus. 24 



In H . influenzae a new strain ab has been obtained by exposing cells 

 b to the transforming principle from cells a (TP a ). The new type 

 produces two capsules (a and b) and yields a new transforming prin- 

 ciple TP 0& capable of producing cells ab from any susceptible receptor 

 cells. These results cannot be obtained by simply mixing TP a with 

 TP 6 in vitro. 



In pneumococcus, the exposure of sensitive cells to the transforming 

 principle from cells bearing two genetic markers, mannitol utilization 

 and streptomycin resistance, produces up to 15 times more cells bearing 

 two markers than would be expected from randomly distributed inde- 

 pendent transformations. Again, this result cannot be obtained by 

 simply mixing the two transforming principles in vitro. 



At present, no evidence exists for the possibility that the two fea- 

 tures reside in separate molecules connected by some link such as 

 protein, since extensive deproteinization and autolytic proteolysis did 

 not abolish the linkage; in addition, no evidence for a double molecular 

 weight of the doubly transforming particles has been obtained. Thus 

 it appears more likely that one molecule of DNA can indeed determine 

 more than one genetical marker. Just how one molecule of DNA can 

 reproduce faultily in the presence of another one (in the same locus?) 

 remains entirely in the domain of speculation. 



