384 B. MAGASANIK 



that either extensive depolymerization occurred when the nucleoprotein 

 was spht, or that each particle of nucleoprotein contains as many as 10 

 molecules of PNA. 



IV. The Isolation of Pentose Nucleic Acids 

 1. General 



It is the aim of biochemical research to relate the chemical properties of 

 natural substances to their function in the living organism. An important 

 early step in work of this kind is, therefore, the isolation of pure compounds 

 which are characterized by possessing specific biological activity. In most 

 cases the activity is first observed in the intact organism. An organ or 

 group of cells rich in this activity is chosen as starting material for the 

 isolation of the compound responsible for the activity. The components of 

 the cells are fractionated by physical and chemical methods, using the 

 quantitative measurement of the biological activity as a guide. The mild- 

 ness or harshness of the isolation procedure depends on the nature of the 

 carrier of the activity; the disappearance of the activity at any step gives 

 immediate notice that this step must be avoided. Finally, the molecular 

 homogeneity of the material thought to be the smallest carrier of the 

 biological activity is investigated by physical methods. 



The success of this approach in the isolation of pure proteins is, in large 

 measure, due to the striking and easily measurable biological activity so 

 many proteins such as enzymes, antibodies, and hormones possess. The 

 lessons learned concerning the conditions under which their biological 

 properties are lost, such as the action of heat, strong acids and bases, etc., 

 could be applied to proteins with less striking biological activities. The 

 biological importance of proteins encouraged the development of physical 

 methods such as ultracentrifugation, electrophoresis, and the measurement 

 of diffusion by which their homogeneity could be investigated. 



The situation is quite different with regard to nucleic acids, and particu- 

 larly pentose nucleic acids. At present, in spite of much work and greatly 

 more speculation, the function of PNA is not known and its biological 

 activity can, therefore, not be measured. One must be content to aim at 

 the recovery of material characterized in the cell only by the chemical 

 properties of its constituents, the purine and pyrimidine bases, pentose, 

 and phosphate; all that can be achieved is the separation of this material 

 from all compounds of different chemical composition. It is not known 

 whether a particular manipulation used in the course of the isolation 

 procedure will cause a change in the properties of the PNA which are 

 responsible for its function in the cell. Furthermore, the homogeneity of 

 the isolated material cannot as yet be deduced with any degree of certainty 

 from physical measurements. The difficulty of relating the results of diffu- 



