November 20, 1919] 



NATURE 



323 



a 



I 



the first twelve days of incubation up to the time of 

 the appearance of creatin. That the cholin of the 

 lecithin of the yolk is the precursor is rendered probable 

 by the evidence adduced by Reisser and by Baumann 

 Hines and Marker that creatin is formed from cholin. 

 That free methyl-guanidin is a normal constituent 

 of muscle has been shown by the work of various in- 

 vestigators, and these results have been confirmed re- 

 cently by Henderson. It is a normal constituent of 

 the urine, even of such animals as the horse, which 

 lives upon a creatin-free diet. 



Guanidin and methyl-guanidin have marked physio- 

 logical actions. They stimulate the efferent neurons 

 of the spinal cord, causing tremors, jerkings, and 

 extensor tonus. In large doses applied to the spinal 

 cord, they paralyse. On the nerve-endings in muscle 

 they have first a stimulating effect, so that the elec- 

 trical excitability is increased, but later and in large 

 doses they have a curare-like action. The svmptoms 

 are similar to those following ablation of the para- 

 thyreoids and to those of idiopathic tetany in children. 

 In the blood and in the urine of parathvreoid ectomised 

 dogs and in the urine of children with tetany. Burns 

 and Sharpe demonstrated an enormous increase in the 

 amount of guanidin present, an increase to which 

 Koch had previously directed attention. 



The conclusion seems to be that, under normal con- 

 ditions, free methyl-guanidin maintains a tonic action 

 on the efferent neurons and so on the muscles, and 

 that the amount of guanidin is controlled by the 

 parathyreoids. 



The few observations so far made point to the ex- 

 cretion unchanged of only a part of injected guanidin. 

 A possible explanation of this seems to be that part 

 is linked with acetic acid and so converted to creatin. 

 and then rendered inert. 



Previous work on the formation of creatin from 

 glycocyamin, guanidin acetic acid, renders this prob- 

 iaWe. Recently in my laboratory- Wishart has found a 

 istinct increase in the creatin content of the muscles 

 after the injection of guanidin sulphate, thus proving 

 the conversion. 



The nature of the combination of creatin in muscle 

 is not yet known. Folin maintains that creatin is an 

 integral part of the muscle substance, and that it is 

 liberated as muscle dies and disintegrates. Evidence 

 of this is lacking, and some recent experiments bv 

 Wishart show that in muscle frozen during life and 

 extracted near the freezing-point the creatin content 

 is the same as in muscle treated in the usual wav. 

 Folin 's own work on the concentration of creatin in 

 muscle does not seem to support his theory. 



In the light of these results and of this view of the 

 mode of formation of creatin from guanidin, what is 

 the significance of the creatin which appears in the 

 urine? This problem may best be investigated in 

 animals in which the question of the relationship of 

 creatin to creatinin need not be considered. Meissner 

 in 1868 maintained that this is the case in birds, and 

 his conclusion I verified in 1910. It has since been 

 further substantiated by the work of Thompson. In 

 birds during fasting the excretion of creatin is in- 

 creased, just as in mammals the excretion of the com- 

 bined creatin and creatinin is generally increased. 

 Myers and Fine claim that the creatin excreted is 

 derived from the creatin present in muscle at the be- 

 ginning of the fast, while Stanley Benedict and Oster- 

 berg maintain that there is a constant fresh formation 

 of creatin. The experimental basis of the latter con- 

 clusion seems to be unsubstantial, since thev adminis- 

 tered protein containing arginin and therefore guani- 

 din, from which the creatin might have been formed. 

 In 1910 I maintained that, from the amount of 

 NO. 2612, VOL. 104] 



creatin excreted by the bird during a fast, the amount 

 of muscle disintegrated might be calculated. Whether 

 the liberated creatin is simply excreted, or whether its 

 resynthesis into muscles is prevented, the amount in 

 the urine indicates the breakdown and non-regenera- 

 tion of muscle, i.e. the actual disintegration. Hence 

 a study of the relationship of the creatin nitrogen to 

 the total nitrogen excreted enables a conclusion to be 

 drawn as to whether the loss is falling chiefly upon 

 muscle or upon other organs of the body. A study of 

 the metabolism of the bird in fasting shows that such 

 conclusions may be drawn, and, accepting Folin 's most 

 recent view of the significance of urinary creatin and 

 creatinin, the excretion of the nitrogen in these sub- 

 stances, taken along with the total excretion of 

 nitrogen, affords a means of elucidating further the 

 progress of protein metabolism in fasting. 



The work of Cathcart and others seems to show that 

 creatin, in the presence of carbohydrates, may be re- 

 synthesised into the muscle substance. This in no way 

 invalidates the view that it is formed to detoxicate 

 guanidin. Lecithin, which is undoubtedly used in the 

 construction of the tissues, plays a like part in de- 

 toxicating cholin. 



As regards the relationship of creatin to creatinin, 

 in spite of the very considerable literature which has 

 appeared upon the subject, our knowledge has advanced 

 little since the time of Meissner. The mass of evi- 

 dence seems to favour the view that the creatinin daily 

 excreted is derived from the creatin of muscle, but 

 that the power of conversion is very limited, and that 

 it varies in different individuals and in different species 

 of animal. 



The considerations here adduced seem to point to 

 the conclusions : — ^(i) That creatin is formed from excess 

 guanidin or methyl-guanidin in order to limit the toxic 

 action of these; (2) that it is to a limited extent stored 

 in muscle, any excess being excreted in the urine, 

 either unchanged as in the bird, or in the form of 

 creatinin in the mammal ; (3) that during fasting 

 and in the absence of carbohydrates it is liberated as 

 the muscle disintegrates; and (4) that it mav be re- 

 combined into the muscle molecule if the supply of 

 carbohydrate., is adequate. 



RADIOTELEGRAPHY DURING THE SOLAR 

 ECLIPSE OF M/IF 29.1 



T N connection with the solar eclipse of May 29 the 

 A committee arranged for the carrying out of ex- 

 periments on the effect of the eclipse on signals trans- 

 mitted across the central line. The British Admiralty 

 stations ,at Ascension and the -Azores transmitted con- 

 tinuously during the transit of the umbra across the 

 .Atlantic Ocean. Observing stations north of the 

 equator were for the most part asked to listen to 

 Ascension for at least an hour round about the time 

 when the umbra passed between themselves and 

 -■Vscension ; observers south of the equator were asked 

 for the most part to listen to the Azores. Certain 

 selected stations north of the equator were also asked 

 to listen to the .Azores, so as to afford check observa- 

 tions upon the variations which might be observed in 

 signals passing across the central line of the eclipse, 

 and, similarly, selected stations south of the central 

 line were asked to listen to .Ascension. The .American 

 station at Sayville also transmitted a programme 

 during a portion of the period of the eclipse, and 

 arrangements were made for special experiments 

 between Darien and the Falklands, and between an 

 Egyptian station and a South African station. 



' Report of a Committee of the Kritish Association presented to .Section A 

 at tlie Bournemouth meeting, September 1919. 



