306 TRANSACTIONS OF SECTION I. 



Creatin Investigations Old and New. 



It is extraordinary how, in spite of the enormous amount of work which 

 has been done upon the subject, our knowledge of the significance of creatin 

 "has advanced so little since Meissner's really wonderful investigations in 1868, 

 now so entirely ignored. In spite of the unsatisfactory methods then available, 

 he concluded that in the bird creatin and not creatinin occurs in the urine, that 

 its amount is increased by giving meat or injecting creatin, that it is higher on 

 a protein rich diet such as liver than on a protein poor diet such as grain, and 

 that it is increased in fasting. 



From his observations on mammals he concluded that urea and creatinin 

 have different origins, thus anticipating Folin's theory of endogenous and 

 exogenous metabolism, and that, in the study of creatin metabolism, feeding 

 with meat must be avoided. He found that creatinin was excreted in the 

 smallest amounts in animals gaining weight on a protein poor diet. 



The work upon creatin metabolism which has been carried on in many 

 laboratories during the past few years has been somewhat fragmentary and 

 difficult to combine into an organic whole, but I believe that it can be so 

 combined and that a more or less reasonable explanation can be given by the 

 recognition of the fact that its significant part is the guanidin nucleus, and 

 that it is in connection with this that its real meaning is to be found, that free 

 guanidin is detoxicated and rendered available for synthesis into muscle sub- 

 stance by the formation of creatin. 



Folin's method has made the investigation of creatin a very simple matter, 

 but so far no reliable and rapid method has been devised for the determination 

 of guanidin or methyl-guanidin. Hence our knowledge of the metabolism of 

 these substances is still very defective. Probably it will not be possible greatly 

 to enlarge it until better methods of analyses have been devised. 



III. Conclusion. 



To look back upon the progrese of knowledge of any branch of science, even 

 upon one so limited in range as that of protein metabolism, is like looking 

 back upon the records of ancient voyages of discovery. There are the same 

 dreams of enchanted islands far to the West — the islands of the Hesperides : 

 the same imaginary accounts of their position and of their characters, too often 

 accepted as all sufficing; the same spirit of scepticism driving some bolder 

 spirit to embark in his cockle-shell boat and sail forth on the ocean of 

 discovery, to find if these imaginings have any reality; the same picking up of 

 some small fragments of flotsam and jetsam, hinting that somewhere out there 

 the land is really to be found ; the same failure to advance due to the badly 

 equipped ships or to imperfect seamanship; and again the imagination playing 

 round the few observations and reconstructing images as unreal as those which 

 they displace. Again, as the ships' compasses and means of navigation improved, 

 another attempt pressed further and ending in the discovery of land indeed-- 

 but of some barren reef simply telling that not there lie the islands sought 

 for, and warning the next explorer that some other course must be laid. 

 Again the study of the records of past failures and the attempt to decide whnt 

 must be the next line of advance. Then the next voyage is started, the 

 course set south-west instead of north-west, till some fine morning another 

 barren rock is sighted. But now the mariner starboards his helm and off 

 goes the ship on another tack till haplv the promised island lies ahead — not one 

 island but an archipelago, the exploration of which is to be the work of many 

 followers of the original discoverer. 



In the discovery of the true position and ojeneral features nf the metabolism 

 of the proteins in nutrition Liebig, Voit, Pfliiger, Zuntz, and Rubner have 

 been the great pioneers. To us is left the smaller task of exploring and chartino; 

 the archipelago thev discovered, of investigating each separate island and of so 

 making complete the great work of our predecessors. And althouch the 

 voyages before us may be less arduous than theirs, it is still well before em- 

 barking to let our imagination play forward along our course, to consider the 

 difficulties and dangers of the voyage, and to see that our boat i« adequately 

 equipped. Much of what I have said to-day must be considered as of this nature. 



