8o RESPIRATION 



will produce such a large effect that not only will a large amount 

 of oxygen go into combination, but also an increased proportion 

 of CO. The thick lines show the curve for CO-haemoglobin as 

 calculated on this hypothesis, and the dots show the actual ob- 

 servations. There is in reality perfect agreement with the theory 

 that oxygen and CO combine with haemoglobin in exact propor- 

 tion to their relative affinities for haemoglobin and their partial 

 pressures, just as in the upper curve of Figure 23. The great sig- 

 nificance of this in connection with the explanation of CO poison- 

 ing will be referred to later. 



It remains to discuss the explanation of the various dissocia- 

 tion curves to which reference has been made. We have seen above 

 that Barcroft and his pupils found that when a solution of oxy- 

 haemoglobin is freed, or approximately freed, from salts it gives 

 a dissociation curve which is a simple rectangular hyperbola, in 

 accordance with the simple reaction 



Hb + O 2 ^HbO 2 . 



A. V. Hill pointed out in 1910 that the varying values obtained 

 for the osmotic pressure of haemoglobin solutions in presence of 

 salts indicates that the molecules are more or less aggregated to- 

 gether owing to the influence of the salts ; and he showed that this 

 fact was capable of explaining the deviation from a rectangular 

 hyperbola of the dissociation curve. Thus if, in consequence of 

 the aggregation, the reaction were 



Hb 2 + 2O 2 ^Hb 2 O 4 , 



the curve would no longer be a rectangular hyperbola but would 

 approximate to that given for oxyhaemoglobin in presence of a 

 certain proportion of salts. By assuming a suitable proportion of 

 aggregation of the haemoglobin molecules as Hb 2 , Hb 3 , etc., we 

 can therefore construct equations which will give the actual dis- 

 sociation curves. He also gave a general form of equation to meet 

 the varying cases. In this equation there are two constants, which 

 must be suitably chosen. 



The subject was also taken up by Douglas, J. B. S. Haldane, 

 and myself. We adopted Hill's aggregation theory, but in a dif- 

 ferent form. It seemed to us that the aggregation in protein solu- 

 tions is a phenomenon of the same general nature as precipitation, 

 the precipitate being, however, only formed in very small parti- 

 cles consisting of only two, three, or at any rate a few molecules. 



