59-' 



NA TURE 



[October 13, 1904 



viz. the functional activity ol muscle and nerve centre on the 

 one hand, that of gland on the other? The obvious 

 contrasts which exist between secretion, muscular contrac- 

 tion, and reflex innervation need not be dwelt upon ; the 

 one thing with which we have to do is the nature of the 

 chemical processes which are associated with these three 

 forms of activity. If analogies are to be sought for it is 

 here they will be found. 



I submit to the section, and particularly to those members 

 of it who are engaged in experimental researches on the 

 subject, that the most important contrast between the con- 

 comitant chemical processes of gland function and muscle 

 function consists in this, that whereas the former is not in 

 any marked degree katabolic, the dominant process in the 

 oxidation which is inseparably associated with the perform- 

 ance of muscular function is katabolic. We can readily 

 account for this by reference to the fact that whereas the 

 processes in muscle and in refle.x centre are excitatory, those 

 in glands are for the most part determined by stimuli of a 

 very different kind from those that evoke nervous or muscular 

 action, which last act e.xclusively as liberators of katabolic 

 processes which are waiting to be discharged. 



We have long been accustomed to regard the process by 

 which, in muscle, chemical is translated into mechanical 

 energy as explosive and instantaneous, and to take the end- 

 result — the discharge of carbon dioxide — as the necessary 

 concomitant of the production of heat and work ; but as I 

 remarked before. Dr. Fletcher recently published ex- 

 periments which seem to show that for the attainment of 

 this ultimate result it is essential that the muscle should 

 be abundantly supplied with oxygen, in failure of which 

 the oxidation process may stop short before its completion. 

 I trust that we shall have the advantage of hearing to-day 

 the further results of his researches, and particularly that 

 he will give us information as to the relation between 

 efificiency of contraction and the degree of completeness of 

 the oxidation process. 



In conclusion, the questions which present themselves 

 are : — 



(i) Whether it may be generally stated that the oxygen 

 which is conveyed to the living matter of the tissues by 

 the blood is stored as " intramolecular oxygen " until it is 

 required for the performance of katabolic functions, and, if 

 so, what is the chemical relation between the stored oxygen 

 and the living molecules by which it is held? In submitting 

 this question, I must again ask that the use of the term 

 " living molecule " may be condoned. 



(2) Whether it may be assumed that every disintegrative 

 process conditionates a subsequent integrative process by 

 which the status quo is restored in the same living molecule ; 

 if so, does the anabolic effect which in muscle follows the 

 change of form constitute as much a part of the response 

 to stimulation as the catabolic effect which precedes the 

 change of form? Can this be said of the chemical process 

 which is associated with functional activity in gland? 



Continuing the discussion. Dr. W. M. Fletcher pointed out 

 that in the muscle cell only the katabolic processes had 

 been effectively studied, and that these are characteristic of 

 the special material giving energy for contraction — a 

 material probably without analogue in the gland cell. The 

 classical conceptions, due to Pfliiger and to Hermann, of 

 this material as a highly oxygenated substance breaking 

 down, whether rapidly as in contraction or slowly as in 

 survival periods, by inevitable stages to the ultimate stages 

 of carbonic acid and water, irrespective of a contemporary 

 supply of oxygen, were discussed and compared with the 

 views of Verworn. It was urged that while a preliminary 

 oxygenation of the living molecule may be admitted on wide 

 grounds as the condition of irritability, such a conception 

 by no means precludes the idea of additional oxidative pro- 

 cesses occurring at some stage or stages of the katabolic 

 disintegration. Disintegration effected under anaerobic 

 conditions might, on this view, stop short of its normal 

 end-products, these being replaced by representatives of 

 earlier stages in the breakdown. Evidence in this direction 

 has been got from three main classes of experiment. In 

 the case of excised muscle. Dr. Fletcher's observations of 

 the relation of oxygen supply to the yield of carbonic acid 

 in rest and in activity, and to the onset of fatigue and of 

 rigour, were described and held to be incompatible with the 

 view that the entrance of oxygen conditioned the lability 



NO. 1824, VOL. 70] 



of the molecule without further inlluence upon the sub- 

 sequent course of katabolism. A second class of evidence 

 was derived from the work of Chauveau and Kauffinan, 

 Ludwig and his pupils, Minot and others, upon the respir- 

 ation of muscles with artificial circulation. An increased 

 yield of carbonic acid due to activity was claimed or denied 

 by these observers strikingly in proportion to the success- 

 with which the artificial circulation had been made to re- 

 produce the normal. A third and large body of evidence 

 is supplied by observers like Araki, Geppert, Meyer, and 

 others, who have studied the results of muscular contraction 

 with normal circulation, but under conditions of deficient 

 oxidation. Anaerobic conditions always appear to diminish 

 the amount of carbonic acid expired, while increasing the 

 amount of acid products in the tissues, the blood, or the 

 excreta. 



Prof. N. Zuntz (Berlin), in a letter addressed to the 

 section, referred to some of the points which it had been 

 suggested should be dealt with in the discussion, in the 

 following terms : — " Is one justified in drawing a hard and 

 fast line between the anabolic and the katabolic processes 

 on theoretical grounds? Would it not be more correct to 

 take Pfliiger's view and regard that process as the normal 

 one in which every katabolicallv decomposed molecule is 

 at the very moment of decomposition anabolically regener- 

 ated by taking up oxygen and oxidisable groups? In this 

 case one would regard the katabolic processes, which render 

 the molecular structure less stable and give rise to free 

 affinities, as the factor which inaugurates and makes 

 possible normal anabolism. In this connection, however, 

 the fact remains that anabolism can also take place later 

 on, if an element such as oxygen, necessary to the building 

 up of the molecule, should be wanting at the time that the 

 katabolic processes occur. It is accordingly a subject for 

 investigation to decide whether subsequent regenerative 

 processes occurring in the above manner take place as easily 

 as normal assimilation occurring at the same time as the 

 breaking down of the molecule, or whether they use up 

 more energy if they occur later. I have already some data 

 which tend to show that anabolism demands more energy 

 if it has to take place at a period after the katabolic pro- 

 cesses, but I dare not yet give any definite verdict on the 

 question. 



In regard to the question as to how far the metabolic 

 processes may be the work of an oxidase, I should like to 

 lay stress on the fact that the fundamental importance of 

 innervation for katabolic processes in muscle is not easy to 

 reconcile with the assumption that these processes are much 

 affected by ferments. Neither does the great influence 

 which the tension of a muscle has on oxidation processes in 

 it harmonise with our knowledge of the action of enzymes. 



Prof. T. G. Brodie described the results obtained in ex- 

 periments, conducted in conjunction with Mr. Barcroft, upon 

 the gaseous exchanges in the kidneys under the different 

 conditions of rest and activity. In all cases they had found 

 that the amount of o.xygen taken in by a kidney which was 

 made to secrete urine actively was greatly in excess of that 

 absorbed by a resting kidney, while on the other hand the 

 quantity of carbonic acid eliminated showed far slighter 

 variations. In the greater number of their experiments 

 they had found that the kidney at rest eliminated a greater 

 volume of carbonic acid than it absorbed of oxygen. Their 

 results thus indicated that the performance of work by the 

 kidney was accompanied by an appro.ximately proportional' 

 increase in the intake of oxygerj, while the output of 

 carbonic acid, although increased, was usually much less 

 in amount. From the fact that the carbonic acid output 

 was often in excess of the oxygen intake, it would seem that 

 the final metabolic changes, as evidenced by the carbonic 

 acid output, was a more gradual process, though the results 

 they had obtained, up to the present, did not warrant the 

 conclusion that the carbonaceous waste products resulting 

 from the activity of the tissue were confined to carbonic 

 acid only. 



Mr. J. Barcroft, in discussing the metabolism of glands 

 generally, pointed out that there were three methods which 

 had been used for the investigation of their gaseous meta- 

 bolism. In the first, an excised organ was kept in an 

 enclosed space, and the surrounding air analysed. Thi* 

 method had been dealt with by Mr. Fletcher, who had 

 pointed out that the method slied light on the katabolic 



