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SCIENCE 



[N. S. Vol. XXIX. No. 745 



As we descend the scale it is still found in the 

 lamprey, but missing in the arthropoda — the 

 lobster and horseshoe crab, for example (Mel- 

 lanby, '08; Lyman). This is only one of the 

 chemical differences between vertebrate and 

 invertebrate muscle and at once raises the 

 question whether it is at all likely that creatin 

 is functionally associated with contraction of 

 muscle. Creatin apparently occurs in the non- 

 striated variety of vertebrate muscle which is 

 so frequently (and I believe without experi- 

 mental justification) compared directly with 

 the muscles of invertebrates (Saiki). Un- 

 fortunately, most of our information is still 

 based upon the outcome of color tests rather 

 than actual isolation experiments. Generally 

 speaking the quantity of creatin seems to be 

 larger in the muscles of warm-blooded ani- 

 mals, the hedgehog furnishing an unexplained 

 exception in this series (Mellanby, '08). 



Creatin is present in the embryonic tissues 

 in mammals and in the developing chick, in 

 which latter case it must be directly synthe- 

 sized from the food-supply. Creatinin has 

 not been found at any time (Mendel and 

 Leavenworth; Mellanby, '08). In the chick 

 the formation of creatin is apparently syn- 

 chronous with, but independent of, the growth 

 cf the muscle. Mellanby has attempted to 

 correlate the rapid increase in creatin during 

 the later embryonic period with correspond- 

 ingly rapid development of some organ, and 

 naturally refers to the liver. He argues that 

 since the cross-striated muscles of the inver- 

 tebrates are identical with those of vertebrates 

 — a contention which we are not inclined to 

 admit as conclusive — and are creatin-free, 

 muscle can not account for the phylogeny of 

 oreatin. Mellanby adds as a further biological 

 speculation that since the " gland of the mid- 

 gut" of invertebrates has no morphological 

 or physiological connection with the liver of 

 vertebrates, this newly introduced organ might 

 account for the origin of creatin in vertebrate 

 metabolism. 



How constant is the creatin content of adult 

 muscles; and is it altered during activity? 

 In the light of the meager and conflicting data 

 available to-day, a satisfactory answer can not 

 be given to these questions. Yet they are of 



fundamental importance for any adequate dis- 

 cussion of the role of creatin. Mellanby's 

 convincing experiments on isolated muscles 

 showed that muscular work leaves creatin un- 

 affected, as does the survival of muscle. The 

 stability of muscle creatin is the keynote of 

 his contentions. On the other hand, Graham- 

 Brown and Catheart reported an increase in 

 the so-called total creatinin in stimulated 

 frogs' legs when the organs were isolated, and 

 a decrease when the circulation remained in- 

 tact. Weber and Howell and Duke have ob- 

 served that the vigorously beating isolated 

 heart gives more of these compounds to the 

 fluid perfusing it, than does the quiescent 

 organ. In this connection it is of interest 

 that, according to Uiano, the creatin of the 

 muscle appears to be held in some non-dif- 

 fusible form in the contractile tissue and is 

 only released when the integrity of the muscle 

 bundles is impaired. This observation may 

 help to explain the unique property of muscle 

 tissue to contain such conspicuous quantities 

 of the compound. 



We must bear in mind that all experiments 

 such as those just reported are conducted 

 under artificial conditions different from what 

 pertains in normal muscular activity. The 

 isolated or perfused muscles are working both 

 without adequate repair of the contractile 

 substance and under impoverished nutritive 

 conditions. A disintegration of the tissues 

 with possible liberation of creatin under such 

 circumstances may be an incident in this 

 abnormal situation rather than a customary 

 expression of muscular contraction; just as 

 we know that certain features of metabolism 

 in starvation are the evidence of extraordinary 

 katabolic changes rather than normal se- 

 quences. At any rate, we need to know more 

 about the actual creatin content of muscle 

 under a variety of both normal and unusual 

 conditions, such as rest, activity, starvation 

 and muscular disease, before the final word 

 can be spoken. 



The study of the metabolism of creatin and 

 creatinin has lately received a new trend 

 through the work of Gottlieb and his collab- 

 orators (Gottlieb, Stangassinger, Eothmann). 

 An elaborate investigation of the behavior of 



