F. J. W. ROUGHTON, J. W. LEGGE and P. NICOLSON 



of man and dog) and this provides further evidence in favour of our 

 present contentions. 



Roughton investigated 6 the importance of factor 3 by itself, by 

 calculating the rate at which 2 or CO would penetrate into a layer of 

 haemoglobin solution of the same haemoglobin concentration and 

 average thickness as pertain to the red blood corpuscle, but without 

 any bounding membrane to the layer. His approximate calculations 

 indicated that factor 3 would be expected to cut down the rate of the 

 reaction 2 + Hb-> 2 Hb to about one quarter of its rate in homo- 

 geneous solution, whereas the slower reaction CO + Hb -> COHb 

 should only be cut down to about two-thirds of its solution rate. 

 Factor 3 should thus be responsible for a significant part, but by no 

 means the whole, of the discrepancy between the rates in the corpuscle 

 and in solution. The remainder was attributed to factor 2, i.e. the 

 limiting effect of diffusion through the membrane surrounding the red 

 blood corpuscle, but the mathematical technique available at the time 

 was insufficient for factors 2 and 3 to be tackled jointly. 



During the past two years newer methods of calculation based on 

 the calculus of finite differences 16 , 17 have been applied by one of us 

 (P. N.) to the problem. Sufficiently exact numerical solutions have 

 been obtained both for the particular conditions under which the 

 experimental data have so far been obtained, and also for more general 

 cases. The success of this theoretical investigation has encouraged two 

 of us (J. W. L. and F. J. W. R.) to secure new and more accurate 

 comparisons on the rate of combination of CO with sheep haemo- 

 globin in homogeneous solutions and in corpuscle suspensions, pre- 

 pared from the same blood. No new data have as yet been obtained on 

 the more physiologically interesting reaction of 2 with haemoglobin, 

 since the latter proved, both on technical and on theoretical grounds, 

 to be less suitable for exact work than the CO + Hb reactions. We 

 have also obtained new experimental and theoretical data on the 

 comparative rates of dissociation of 2 Hb in the corpuscle and in 

 solution. As a result it has become possible to put forward tentative 

 calculations as to the actual permeability of the corpuscle membrane 

 to CO and 2 , the latter of which is of course the most important 

 substance that passes through the corpuscle membrane in vivo. 



Our recent experimental data have been obtained essentially by the 

 method of Hartridge and Roughton 4 but with the use of the Millikan 

 photo-colorimeter 8 , 9 for measuring the proportions of the various 

 haemoglobin compounds in place of the Hartridge reversion spectro- 

 scope. The details of the theoretical assumptions, the mathematical 

 equations and their numerical solutions are given in full in a current 

 paper by Nicolson and Roughton 18 to which reference should be made 



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