Sept. 26, 1889] 



NATURE 



523 



facts arrived at in the first instance by anatomical methods of 

 research, Histol 'gy, once the guide of Physiology, has now 

 become her handmaid. 



During the last ten or fifteen years Histology has carried her 

 methods of research to such a degree of perfection that further 

 improvement scarcely seems possible. As compared with these 

 subtle refinements, the " minute anatomy" of thirty years ago 

 appears coarse — the skill for which we onca took credit seems 

 but clumsiness. Notwithstanding, the problems of the future 

 from their very nature lie as completely out of reach of the one 

 as of the other. It is by different methods of investigation that 

 our better equipped successors must gain insight of those vital 

 processes of which even the ultimate results of microscopical 

 analysis will ever be, as they are now, only the outward and 

 visible sign. 



In what has preceded, I have endeavoured to show that at 

 present the fundamental questions in physiology, the pro- 

 blems which most urgently demand solution, are those 

 which relate to the endov/ments of apparently structureless 

 living matter, and that the most important part of the 

 work of the immediate future will be the analysis of these 

 endowments. With this view, what we have to do is, first, to 

 select those cases in which the vital process offers itself in 

 its simplest form, and is consequently best understood ; and, 

 secondly, to inquire How far in these particular instances we 

 may, taking as our guide the principle I have so often mentioned 

 as fundamental, viz. the correlation of structure with function, 

 of mechanism with action, proceed in drawing inferences as to 

 the mechanism by which these vital processes are in . these 

 simplest cases actually carried out. 



The most distinctive peculiarity of living matter as compared 

 with non-living is that it is ever changing while ever the same, 

 i.e. that life is a state of ceaseless change. For our present pur- 

 pose I must ask you, first, to distinguish between two kinds of 

 change which are equally characteristic of living organisms — • 

 namely, those of growth and decay on the one hand, and those 

 of nutrition on the other. Growth the biologist calls evolution. 

 Growth means the unfolding, i.e. development, of the latent 

 potentialities of form and structure which exist in the germ, and 

 which it has derived by inheritance. A growing organism is 

 not the same to-day as it was yesterday, and consequently not 

 quite the same now as it was a minute ago, and never again 

 will be. This kind of change I am going to ask you to exclude 

 from consideration altogether at this moment, for in truth it 

 does not belong to Physiology, but rather to Morphology, and 

 to limit your attention to the other kind which includes all 

 other vital phenomena. I designated it just now as nutrition, 

 but this word expresses my meaning very inadequately. The 

 term which has been used for half a century to designate the 

 sum or complex of the non-developmental activities of an 

 organism is "exchange of material," for which Prof. Foster has 

 given the very acceptable substitute Metaboli-m. Metabolism 

 is only another word for " change," but in using it we under- 

 stand it to mean that, although an organism in respect of its 

 development may never be what it has been, the phases of 

 alternate activity and repose which mark the flow of its life- 

 stream are recurrent. Life is a Cytlosis in which the organism 

 returns after every cycle to the same point of departure, ever 

 changing yet ever the same. 



It is this antithesis which constitutes the essential distinction 

 between the two great branches of biology, the two opposite 

 aspects in which the world of life presents itself to the inquiring 

 mind of man. Seen from the morphological side, the whole 

 plant and animal kingdom constitutes the unfolding of a struc- 

 tural plan which was once latent in a form of living material of 

 great apparent simplicity. From the physiological side this 

 apparently simple material is seen to be capable of the dis- 

 charge of functions of great complexity, and therefore must 

 possess corresponding complexity of mechanism. It is the 

 nature of this invisible mechanism that physiology thirsts to 

 know. Although little progress has as yet been made, and 

 little may as yet be possible, in satisfying this desire, yet, as I 

 shall endeavour to show you, the existing knowledge of the 

 subject has so far taken consistent form in the minds of the 

 leaders of physiological thought that it is now possible to 

 distinguish the direction in which the soberest speculation is 

 tending. 



The non-developmental vital functions of protoplasm are the 

 absorption of oxygen, the discharge of carbon dioxide and water 



and ammonia, the doing of mechanical work, the production of 

 heat, light, and electricity. All these, excepting the last, are 

 known to have chemical actions as their inseparable concomit- 

 ants. As rega'-ds electricity, we have no proof of the depend- 

 ence of the electrical properties of plants and animals on 

 chemical action. But all the other ac.ivities which have been 

 mentioned are fundamentally chemical. 



Let us first consider the re'ation of oxygen to living matter 

 and vital process. For three-quarters of a century after the 

 fundamental di-^coveries of Lavoisier and Priestley (1772-76), the 

 accepted doctrine was that the effete matter of the body was brought 

 to the lungs by the circulation and burnt there, of which fact the 

 carbon dioxide expired seemed an obvious proof. Then came 

 the discovery that arterial blood contained more oxygen than 

 venous blood, and consequently that oxygen must be conveyed 

 as such by the blood-stream to do its purifying work in all parts 

 of the body, this advance in the understanding of the process 

 being crowned a few years later by the discovery of the oxygen- 

 carrying properties of the colouring-matter of the blood, in which 

 the present President of the Royal Society took so prominent a 

 part. Finally, between 1872 and 1876, as the result of an ela- 

 borate series of investigations of the respiratory process, the 

 proof was given by Pfliiger^ that the function of oxygen in the 

 living organism is not to destroy effete matter either here or 

 there, but rather to serve as a food for protoplasm, which, so 

 long as it lives, is capable of charging itself with this gas, ab- 

 sorbing it with such avidity, that, although its own substance 

 retains its integrity, no free oxygen can exist in its neighbour- 

 hood. This discovery, of which the importance is comparable 

 with that of Lavoisier, can best be judged of by considering its 

 influence on other fundamental conceptions of the vital process. 

 The generally accepted notion of effete matter waiting to be 

 oxidized was associated with a more general one, viz. that the 

 elaborate structure of the body was not permanent, but con- 

 stantly undergoing decay and renewal. What we have now 

 learnt is, that the material to be oxidized comes as much from 

 the outside as the oxygen which burns it, though the reaction 

 between them, i.e. the oxidation, is intrinsic, i.e. takes place 

 within the living molecular framework. 



Piotoplasm, therefore, understanding by the term the visible 

 and tangible presentation to our senses of living material, comes 

 to consist of two things — namely, of framework and of content — 

 of channel and of stream — of acting part which lives and is 

 stable, and of actedon part which has never lived and is labile, 

 that is, in a state of metabolism, or chemical transformation. 



If such be the relation between the living framework and the 

 stream which bathes it, we must attribute to this living, stable, 

 acting part, a property which is characteristic of the bodies 

 called in physiological language ferments, or enzymes, the 

 property which, following Berzelius, we have for the last half- 

 century expressed by the word catalytic ; and use, without 

 thereby claiming to understand it, to indicate a mode of action 

 in which the agent which produces the change does not itself 

 take part in the decompositions which it produces. 



I have brought you to this point as the outcome of what we 

 know as to the essential nature of the all-important relation 

 between oxygen and life. In botanical physiology the general 

 notion of a stable catalyzing framework, and of an interstitial 

 labile material, which might be called catalyte, has been arrived 

 at on quite other grounds. This notion is represented in plant 

 physiology by two words, both of which correspond in meaning 

 — Micellae, the word devised by Niigeli, and the better word 

 Tagmata, substituted for it by Pfeffer. Niigeli's word has been 

 adopted by Prof. Sachs as the expression of his own thought in 

 relation to the ultra-microscopical structure of the protoplasm of 

 the plant cell. His view is that certain well-known properties of 

 organized bodies require for their explanation the admission that 

 the simplest visible structure is itself made up of an arrangement 

 of units of a far inferior order of minuteness. It is these 

 hypothetical units that Nageli has called micellae. 



Now, Nageli in the first instance confounded the micellae with 

 molecules, conceiving that the molecule of living matter must be 

 of enormous size.'- But, inasmuch as we have no reason for be- 

 lieving that any form of living material is chemically homo- 

 geneous, it was soon recognized, perhaps first by Pfeffer, but 

 eventually also by Nageli himself, that a micella, the ultimate 



' Pjhiget's .Archiv, vol. vi., 1872, p. 43. and vol. x., 1875, p. 251, " Ueber 

 die phy^iologische Verbrennung in den lebendigen Organismen " 



^ Nageli, "Theorie der G.nhrung ; Bei rjg iur Molecular Physiologic," 

 p. 121 (1879). 



