Apbil 9, 1909] 



SCIENCE 



585 



in the living muscles of tlie body itself. It 

 was a further short step to associate muscular 

 contraction with alterations in the creatin 

 content of the contractile tissues; and to look 

 for variations in creatinin output in relation 

 to the muscular work done by the individual. 

 In addition to this the creatin of the muscles 

 has, because of its structural relationship, been 

 ■discussed in the past as an important pre- 

 <;ursor of urea, on the assumption that the 

 guanidin rest can be readily converted to 

 urea in metabolism: 



HN=C 

 NH, 





Ten years ago Dr. F. G. Hopkins wrote : 



The variations in the urinary creatinin gen- 

 erally follow very closely those of urea, but there 

 can be no doubt that its quantity depends largely 

 on the amount of creatin taken with the food. 



At that time the story was as simple as it 

 was brief. The creatin of the muscle was in 

 some way derived from the proteins of the 

 body; the creatinin of the urine was referable 

 to the creatin ingested or furnished by the 

 muscles of the body. Feeding experiments 

 with meat and its products seemed to bear out 

 this view and analogies lent further support. 

 From the outset the study of these prob- 

 lems was hampered by the lack of a suitable 

 process for the estimation of these compounds. 

 The Neubauer method, in which creatinin is 

 isolated as a double salt with zinc chloride, 

 was practically the only one available. Older 

 testimony and more recent critical investiga- 

 tions leave no doubt that this method is utterly 

 unreliable as a quantitative procedure for the 

 estimation of creatinin. All of the earlier 

 work based upon it must therefore be attended 

 with a probability of error which has necessi- 

 tated a revision of the entire subject. Here, 

 as in so many other instances in scientific re- 

 search, a good experimental method has opened 

 up entirely new fields of observation; and to 

 Professor Folin is due the credit for a satis- 

 factory quantitative procedure for estimating 

 creatin and creatinin based on Jaffe's color 

 test with picric acid and an alkali. It has 



given the impetus to numerous investigations 

 since its publication in 1904; in truth, this 

 method, the simplicity of which makes it 

 available in every clinic, has been responsible 

 for a revolution in some of our ideas of metab- 

 olism. I propose to present some of these 

 newer aspects of the physiology of creatin 

 and creatinin, and to view them in the light 

 of recent investigation; to inquire to what 

 extent certain current hypotheses are justified. 

 Bear in mind that a brief review within the 

 limits of a symposium can neither be exhaust- 

 ive nor do full justice to the newly accumu- 

 lated mass of evidence; it is intended to be 

 suggestive rather than critical — ^to propound 

 problems rather than solve them. 



Let us first consider the significance of 

 creatin and creatinin in the muscle. The evi- 

 dence now seems conclusive that creatinin is 

 not present preformed in the muscular tissues 

 (Grindley and Woods; MeUanby, '08; Mendel 

 and Leavenworth). The fact that chemical 

 manipulations of the extracts of muscle are 

 quite likely to convert creatin into creatinin 

 explains the constant occurrence of both of 

 these compounds in commercial extracts of 

 meat; and it warns against aU conclusions re- 

 garding the physiological conversion of one 

 compound into the other whenever appropriate 

 conditions of analysis have not been rigor- 

 ously maintained. When it is remembered 

 that mere evaporation on a water-bath, under 

 the acid reaction which arises post mortem, 

 is sufficient to induce the conversion of creatin 

 into creatinin, the liability of analj^tical error 

 is emphasized. The difficulties are further 

 increased by the fact that quantitative con- 

 version of creatin into creatinin for analytical 

 purposes is likewise attended with undeniable 

 uncertainty (Folin, '06). These features are 

 mentioned at the outset because they have 

 served to complicate the experimental results 

 to a degree where nothing short of experience 

 seems to furnish adequate critique of the 

 claims of investigators. 



Creatin has been found in the muscles of all 

 vertebrates which have been examined for it. 

 From the phylogenetic point of view it is in- 

 teresting, on the other hand, to note the ab- 

 sence of creatin from invertebrate muscle. 



