PRESIDENTIAL ADDRESS. 303 



Crcatin and Total Nitrogen in Muxcle. Thick and Thin of Salmon. 



5 Salmon ^feeding). 



Total NitroL'cn. Creatiii. 

 Thin. " Thick. Thin. Thick. 



3-57 3-61 0-241 0-224 



Crcatin T.N. 6-7 6-2 



5 Kelts (prolonged fast). 

 3-13 31S 0-241 0-279 



8- 



IMyers and Fine's conclusions have been severely criticised by Stanley 

 Benedict and Osterberg.^^ 



These investigators maintain that creatin is a material which is being 

 constantly formed during the course of a fast, that only that part which is not 

 metabolised is excreted and that the amount excreted is no index of the amount 

 of muscle tissue catabolised. They base their conclusions upon experiments upon 

 dogs rendered completely diabetic by phloridzin. Having shown that during 

 fasting such dogs excrete large amounts of creatin — as had been already demon- 

 strated by Cathcart and Taylor — they gave washed fibrin or washed flesh, both 

 creatin free, in sufficient quantity to nearly cover the loss of nitrogen, and 

 because the creatin excretion under these conditions was still maintained they 

 conclude that it is not the result of the breakdown of muscle tissue. Certainly 

 when these proteins are given an abundant source of the guanidin required for 

 creatin formation has been furnished, and it appears to me to be no proof what- 

 ever that in fasting the creatin in the urine is not the result of the catabolism 

 of muscle setting free a proportionate amount of creatin. 



But it raises another and very interesting question : granting that the 

 creatin is liberated by muscle breakdown why does it appear in the urine in 

 the absence of carbohydrates and in conditions of imperfect oxygenation of the 

 blood ? This question will be dealt with later. 



In 1910 I looked upon creatin as part of the muscle molecule — if one may 

 be allowed to use such a term — and considered that the amount of creatin 

 excreted was a measure of muscular disintegration. 



This view that creatin is an integral part of the muscle molecule and that it 

 is liberated only upon death has now been adopted by Folin."° 



The evidence is by no means conclusive. The only experimental work 

 recorded is that of Urano which cannot be considered as in any way satisfactory. 



Some recent experiments as yet unpublished by Wishart tend to show that 

 the creatin exists as such in the muscles, and not as an integral part of its 

 substance. In these experiments a frog was killed by a blow on the head and 

 instantly one hind leg still in situ was frozen hard in a mixture of ice and 

 salt and the whole of the extraction process carried out near the freezing point 

 up to the hydrolysis of the filtrate. The difference in favour of the unfrozen 

 muscle was comparatively small. Further experiments on the subject are in 

 progress 



Unfrozen. 

 •076 

 •072 



Frozen. 

 •070 

 -063 

 -058 



•071 



Folin's demonstration of the accumulation of injected creatin in muscle 

 also seems to me to indicate that in part at least it may exist in a free state. 



Tt may well be that in fasting, when the muscle proteins are used as a 

 source of energy or are carried to more essential organs, the free creatin may 

 be liberated proportionately to the break-down and excreted without the reduced 

 muscle tissue showing any percentage decrease. 



In 1910 I argued against the possibility of there being an increased pro- 

 duction of creatin in fasting and I still think the argument is valid. Since the 

 creatin nitrogen must come from somewhere, any increase in the excretion of 

 creatin should be accompanied by a decrease in the excretion of nitrogen in 



