510 ISOTOPIC TRACERS AND NUCLEAR RADIATIONS [Chap. 24 



and nonmetabolic tracing because the labeling isotope for the latter type of 

 experiment often also has a metabolic role. For example, the labeling of 

 erythrocytes with radioiron has been used to study the movement and mixing 

 of blood (Fe20, 21, etc.); however, the iron of labeled hemoglobin has an 

 active role in the metabolic pool, and for long-term experiments the turnover 

 of hemoglobin iron must be considered in any experiment with labeled 

 erythrocytes. Similarly, in studying the movement of labeled bacteria and 

 other foreign cells, the metabolic interchange of the labeling atoms between 

 these cells and their host environment must be considered. 



c. Theory and Techniques of Tracing Physiological Processes. The funda- 

 mental techniques of isotopic tracing in biology are directed toward the 

 answering of two main questions: (1) What path or paths does a labeled 

 material take, qualitatively and quantitatively, in moving and changing 

 within a biological system? (2) At what rate do such processes occur? In 

 addition, isotopes may be used in biochemical analysis by the isotope dilution 

 technique (as already described in Sec. 15.2). 



The first of these questions can in some cases be partly or even entirely 

 answered by other than isotopic techniques. For example, at the metabolic 

 level the tracing of an abnormal substance, or of abnormal amounts of a 

 normal constituent, can be carried out in many cases by microchemical or 

 even macrochemical procedures. Nevertheless, the use of isotopes even in 

 these cases permits of greater accuracy and in many cases much greater 

 simplicity of experimental procedure. For the study of normal metabolism, 

 moreover, nonisotopic techniques offer at best a crude approximation of what 

 isotopic procedures can clearly reveal. Though chemical analysis of parts 

 of a biological system can demonstrate in large outline what the constituents 

 are at any given time, they can tell relatively little as to the exact pattern of 

 movement by which those constituents have become incorporated into the 

 system. With tracers, such processes as the permeability of substances and 

 the transport of microconstituents can be readily revealed. 



The study of rates of biological processes is even less satisfactory if restricted 

 to nonisotopic techniques. In fact only those rates can be conveniently 

 studied nonisotopically which deal either with the production of end products 

 or with changes in the absolute amounts or relative proportions of given 

 constituents in a biological system. In one vital aspect, the functioning of 

 biological systems can be satisfactorily studied only with isotopes; this is 

 the pattern and the rate of change, or turnover rate, of intermediary sub- 

 stances in dynamic equilibrium in a biological system. Even though we 

 might know by other means all the substances that enter a system and all 

 the substances that leave it, we cannot determine merely by chemical means 

 all the intermediate steps and, in particular, the rates at which the trans- 

 formations involved are occurring. However, with isotopes as labeling 



