215 



Comment on papers 18—23 



The first application of an artificial radioactive isotope as a tracer in life sciences 

 aimed to determine if and to what extent the mineral constituents of the skeleton 

 of the fully grow-n rat are renewed. ^-P was used in this investigation (paper 18), 

 which demonstrated the renewal of an appreciable part of the mineral constituents 

 of the skeleton of the rat. The replaceable fraction of the bone phosphate was 

 found to constitute about 30 per cent, a result which was confirmed by later inves- 

 tigations. This study was carried out and its result published simultaneously- 

 (1935) with ScHOENHEiMER and Rittenberg's first classical investigation on th(^ 

 dynamic nature of fat deposits, followed by numerous others of a similai- type. 

 The result that the formation of the bone is a dynamic process, involving conti- 

 nuous loss and replacement was for many an unexpected and puzzling one. This 

 is shown by a remark of the Editor of Nature. In those days, each issue of Nature 

 contained a short survey of the contents of the "Letters to the Editor". In this 

 survey it is stated: ". . . . The authors (Chiewitz and Hevesy) further believe (!) 

 that the formation of the bone is a dynamic process involving continuous loss 

 and replacement." A larger fraction of the epiphysial apatite molecules than 

 of the diaphysial ones was found to be renewed, which is partly due to the fact 

 that mineral molecules of the epiphysial tissue come more easily in contact with 

 plasma and lymph containing the active phosphate than those of the more per- 

 fectly mineralized diaphysial tissue. The first animals investigated included also 

 rachitic rats (paper 19). At first the puzzling result that the fiaction of bone 

 phosphate renewed in the rachitic rat was found to be larger than in the healthy 

 animal, was at least partly due to the less well mineralized and thus more epiphysial 

 nature of the rachitic skeleton. The uptake of minute amounts of ^^P by the enamel 

 was found to take place even when preventing contact between enamel and sali\'a 

 (paper 20). 



Since the specific activity of plasma phosphate diminishes with time, the 

 sensitivity of the radioactive indicator correspondingly decreases (the same acti- 

 vity indicates a larger amount of phosphorus). To arrive at an exact figure for the 

 renewed fraction of the apatite phosphate, we must know the specific activity 

 of the plasma inorganic phosphate throughout the experiment. An alternative 

 method is to keep the plasma inorganic phosphate activity at a constant level 



apatite ^^p spec, activity 



throughout the experiment. The ratio — — X 100 determined 



plasma inorganic ^^P 



at the end of the experiment indicates then the percentage apatite renewal. By 

 following the last mentioned procedure (paper 21), after the lapse of 50 days 

 30 per cent of the femur epiphysis phosphorus, but only 7 per cent of the diaphysis 

 phosphorus of the rabbit, was found to be renewed. A 44 per cent renewal of the 

 scapula phosphate took place, and a full renewal of the apical and medial incisor 

 phosphate occurred. At least two-thirds of the last mentioned renewals was due 

 to incisor growth. The constancy of the serum-calcium and serum-phosphorus 

 content of the plasma is maintained by homeostatic; mechanism, for which 

 the skeleton is primarily responsible. The regulation is achieved mostly by a 

 slight change in the amount of dissolved and newly formed bone apatite. 



While in the above mentioned investigations the dynamic nature of a substan- 

 tial part of the skeleton apatite was demonstrated and the fraction of the latter 



