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ical about these assumptions that you can prevent yourself from doing the ex- 

 periment. That is not what is intended. It is merely that when we evaluate 

 these experiments we must do so in a context of certain limitations that I think 

 are obvious. 



When we talk about a precursor entering a high molecular weight com-- 

 ponent, we envision many intermediate steps, but as a simplification we can say 

 that the precursor enters a pool; i.e. , a labeled precursor enters an unlabeled 

 pool with which it mixes. The assumption is made that it mixes homogeneously 

 in that pool and it is extracted from that pool into an essentially homogenous 

 high molecular weight compound. 



Certain modifying factors have to be introduced here. This pool may 

 have subcompartments. The assumption is usually made that the precursor 

 equilibrates rapidly through all of these compartments, so that an essentially 

 homogeneous pool is established, and from this pool it is then extracted to make 

 a high molecular weight nucleic acid. 



Certain modifying factors can be introduced into the size of the pool 

 and into the equilibration between the compartments that will radically modify 

 the specific activity of this precursor. For instance, if the pool is small in 

 size (the samie amount of activity goes into a pool that contains much less of the 

 precursor), then the specific activity is going to be higher. 



Another modifying factor is that the precursor may enter this pool but 

 it may not equilibrate in all the compartments. 



The other problem that we meet is that the precursor may enter a pool 

 that is much greater in size, then the specific activity of the precursor will 

 drop. 



How homogeneous is the composition of the high molecular weight 

 nucleic acid? If labeled glucose is injected into an animal and the glycogen is 

 isolated from liver at various times, there are areas of the glycogen molecules 

 that are labeled heavily and some that contain little or no radioactivity. This 

 modifies to a certain extent our interpretation of nucleic acids. We don't know 

 with certainty, although here again we have some pretty good evidence that is 

 beginning to accumulate, whether a precursor assimilated into a nucleic acid is 

 distributed homogeneously throughout that high molecular weight material. 



With respect to phosphorus, we have some good data from Heidel- 

 berger's laboratory that shows that there are subgroups within the nucleic acid 

 molecule with different rates of incorporation of radiophosphorus. 



COHN: Would it be fair to point out that in the case of glycogen you 

 have essentially a spherically expanded molecule, whereas in the case of the 

 nucleic acid you have a linearly expanded molecule. 



CARTER: This is perhaps one of the first times that Dr. Cohn has 

 gone on record as giving up the branched chain hypothesis of ribose nucleic 

 acid structure. 



CHARGAFF: Not necessarily. He has not gone that far. 



CARTER: Well, we have introduced quite a few reservations into the 

 interpretation of these data. I think it is apparent that the experiments that will 

 tell us most about the influence of radiation upon the metabolism of labeled nu- 



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