THE PROBLEM OF NUCLEOTIDE SEQUENCE IN DEOXYRIBONUCLEIC ACIDS 69 



of the links that are disrupted repeatahly during the mild fractionation pro- 

 cedure. In this view, in its extreme form, the nucleus of a given species 

 could conceivably contain only one type of deoxyribonucleic acid. At the 

 other extreme would have to be placed the view that a given nucleic acid 

 preparation may comprise an entire spectrum of differently constituted 

 individuals so that no two nucleic acid molecules within the same nucleus 

 would be entirely identical [lo]. That neither of these opposite extremes can 

 as yet be disavowed entirely demonstrates the deep cleft that still exists 

 between metabiological assertions and scientific facts. 



THE PROBLEM OF MACROMOLECULAR STRUCTURE 



It would, of course, be good if the investigator of the structure of a 

 deoxyribonucleic acid knew whether he was dealing with one chain or 

 with two [11] or even more [12] complementary chains; but at the present, 

 little advanced, state of our knowledge of the nucleic acids this is not 

 essential. The value of anv information on the sequential characteristics 

 of the nucleic acid is not diminished if the complementary chains are 

 considered to be joined at one end or even at both ends, as may well be 

 the case, so as to constitute an uninterrupted sequential progression. I 

 am not aware of the demonstration of distinct end groups in undegraded 

 deoxyribonucleic acid. 



The maintenance of sequence integrity of the preparations to be 

 examined is, on the other hand, a problem of great importance. If — quite 

 apart from the secondary valence forces supporting the architecture of 

 the secondary or tertiary structures of the deoxyribonucleic acids — there 

 really exist weak links in their primary structure [13], it may be essential 

 to avoid the rupture of the latter, since otherwise valuable features of 

 sequential arrangement may be lost. This applies, of course, even more to 

 the avoidance of chemical or enzymic degradation during the isolation. 



It is quite likely that very few of the deoxyribonucleic acid preparations 

 described so far, and none of the models proposed to describe their struc- 

 ture, are representative of the native state. The actual operative entity — • 

 though not necessarily amenable to biological testing /// vitro — possibly is 

 an aggregate of very long polynucleotide chains linked to each other, 

 perhaps by oligopeptide bridges, and bonded to proteins in a spatially 

 unique configuration. If this is so, the problem of heterogeneity, men- 

 tioned in the preceding section, is ostensible rather than actual, having 

 been introduced as a necessary, but strictly non-biological, artifact of 

 purification. By this token, a preferred isolation method for deoxyribonu- 

 cleic acid would be one that avoided, as far as possible, denaturation by 

 chemical or physical means. Nearest to these requirements is perhaps 

 the procedure described on p. 326 of a previous survey [7] and applied 



