PROGRESS OF THE ISOTOPIC METHODOLOGY 999 



of the neutrons emitted transforming some of the ^ag atoms of the car- 

 bondisulfide into radioactive P atoms. By extracting the carbondisulfide 

 with diluted acid or with water a solution of ^sp ^as obtained and first 

 applied in 1935 in the investigation if and to what extent the phosphorus 

 atoms of the mineral constituents of the skeleton are replaced. Within 

 24 days 30% of these were found to be renewed. As about 300 mgm bone 

 phosphorus were involved in the renewal process and the total phosphorus 

 content of the blood of the rat amounts to not move than 10 mgm, most 

 of the phosphorus atoms which entered the mineral constituents of the 

 skeleton must have been previously located in the organs. These experi- 

 ments^^\ in which artificial radioactive tracers found their first applica- 

 tion, thus brought out the dynamic state of the phosphorus com- 

 pounds of the organs as did simultaneously Schoenheimer and 

 Rittenberg's investigations, applying a stable isotopic tracer, the 

 incessant rejuvenation of fatty acids and other molecular body con- 

 stituents. It was soon made clear that isotopic methods offer the only 

 possibility of studying the organism as a whole under practically 

 equilibrium conditions. 



The 32p available in the earliest investigations with artificially pro- 

 duced radioactive indicators, though of very modest activity (less than 

 1 /zC) was found to be useful in numerous investigations. It sufficed 

 even to carry out the first clinical red corpuscle volume determination. 

 For numerous other investigations these minute activities did, however, 

 not suffice, for example to follow, after injecting radiophosphorus to the 

 goat, the incorporation of ^sp into the various phosphorus compounds 

 of the milk. These and many other investigations became only possible 

 after the availability of cyclotron-produced radiophosphorus. While the 

 availability of pile-produced radioactive isotopes alone made possible 

 the exceedingly extended application of radioactive tracers which 

 we witness today, the construction of the cyclotron was one of the 

 greatest events in the history of applications of radioactive indicators. 

 In 1939 already, only four years after the first application of 32p in phy- 

 siological studies, the first paper of John Lawrence and his collaborators 

 appeared^^) in which cyclotron-produced radiophosphorus was applied in 

 clinical studies of leukemia followed by numerous communications on 

 various clinical topics in which radioactive isotopes were applied by them 

 and others as indicators. We shall discuss later some important work 

 carried out by the Berkeley group. In 1939 furthermore a paper was 

 published in Copenhagen on the resorption of phosphate from the human 

 intestine. By comparing the specific activity of the urine and faeces P, 

 it was possible to distinguish between the endogenous and exogenous 

 phosphate present in the faeces^^^ 



It was cyclotron-produced iodine which Hamilton^^^ applied in his 

 pioneer studies of radioiodine uptake by the thyroid. Radioactive 



