November 3, 1916] 



SCIENCE 



625 



that both the kidneys and the liver play a 

 part in this regulation; but of the marvel- 

 lous accuracy of the regulation physiol- 

 ogists had, till the recent work on the 

 physiology of breathing, no clear concep- 

 tion. 



It is not merely the hydrogen ion con- 

 centration of the blood that is accurately 

 regulated, but also its capacity for taking 

 up a constant amount of C0 2 in presence 

 of a constant partial pressure of this gas. 

 This capacity depends on the concentra- 

 tion of and balance between alkaline salts 

 and albuminous substances in the blood. 

 Recent investigations by Christiansen, 

 Douglas and myself have shown that this 

 concentration and balance are so accu- 

 rately maintained day by day, and month 

 by month that under normal conditions no 

 deviations can be detected by the most 

 delicate existing method of blood gas anal- 

 ysis. The balance can be temporarily up- 

 set by what may be called violent means; 

 but within an hour it is back again to 

 normal. It is, of course, evident that if the 

 carrying-power of blood for C0 2 did not 

 remain normal the breathing and eircula- 

 lation would not, without special adjust- 

 ment, remain normal. 



Now let us look back for a moment, and 

 see where we now stand. The experimental 

 study of the physiology of breathing has 

 led us to the discovery of four normals, 

 the maintenance of which furnishes the 

 interpretation of a mass of what would 

 otherwise be isolated and unintelligible ob- 

 servations. We have first of all the normal 

 alveolar C0 2 pressure. This turns out to 

 be directly subordinate to the normal regu- 

 lation of the hydrogen ion concentration 

 of the blood, the normal reaction of the 

 respiratory center to hydrogen ion con- 

 centration, and the normal regulation of 

 the capacity of the blood for carrying C0 2 . 

 With tie discovery of each of these normals 



we have obtained deeper and deeper in- 

 sight into the physiology of breathing. We 

 have done this, not by merely seeking for 

 causes in the physical sense, but by seeking 

 for interconnected normals and their 

 organization with reference to one another 

 and to other organic normals. These nor- 

 mals represent, not structure in the ordi- 

 nary physical sense, but the active mainte- 

 nance of composition. We may fitly call 

 this living structure, since so far as we 

 know all living structure is actively main- 

 tained composition, the atoms and molec- 

 ules entering into which are never the same 

 from moment to moment according to the 

 ordinary physical and chemical interpre- 

 tation. Our method has thus been essen- 

 tially the same as that of the anatomist who 

 seeks for the normal — the type — which 

 runs through and dominates the variety of 

 detail which he meets with, and who 

 reaches more and more fundamental types. 



I wish, now, to point out that the same 

 method has been applied, and is being ap- 

 plied, to other departments of physiology, 

 even though the physiologists applying it 

 may have failed to realize the far-reaching 

 significance of their results. 



I will refer first to the general physiol- 

 ogy of the blood. The facts that the hydro- 

 gen ion concentration and capacity for 

 carrying C0 2 are very accurately regu- 

 lated in the blood are no isolated facts in 

 physiology, although the accuracy of our 

 physiological means of measurement ren- 

 ders them peculiarly striking. Claude 

 Bernard, in his Legons sur les phenomenes 

 de la vie, was, I think, the first to point 

 out clearly that the composition of the 

 blood, as well as its temperature, is physi- 

 ologically regulated. He was led to this 

 conclusion more particularly by his ob- 

 servations that in prolonged starvation 

 there is still sugar in the blood, and that 

 even when great excess of sugar is intro- 



