ness. Having arrived at this point he begins to correlate the known structure of the retina with what is required of it, and finds that the number of objects which he can discriminate in the field of vision is as numerous as, but not more numerous than, the parts of the retina, i. e., the cones which are concerned in discriminating them. So far he has no difficulty; but the method of correlation fails him from the moment that he considers that each object point in the field of vision is colored, and that he is able to discriminate not merely the number and relations of all the object points to each other, but the color of each separately. He then sees at once that each cone must possess a plurality of endowments for which its structure affords no explanation. In other words, in the minute structure of the human retina we have a mechanism which would completely explain the picture of which I am conscious, were the objects composing it colorless, i. e., possessed of one objective quality only, but it leaves us without explanation of the dif ferentiation of color.

Similarly, if we are called upon to explain the function of a secreting gland, such, e. g., as the liver, there is no difficulty in understanding that inasmuch as the whole gland consists of lobules which resemble each other exactly, and each lobule is likewise made up of cells which are all alike, each individual cell must be capable of performing all the functions of the whole organ. But when by exact experiment we learn that the liver possesses not one function but many, when we know that it is a storehouse for animal starch, and that each cell possesses the power of separating waste coloring matter from the blood, and of manufacturing several kinds of crystallizable products, some of which it sends in one direction and others in the opposite, we find again that the correlation method fails us, and that all that our knowledge of the minute structure has done for us is to set before us a question which though elementary, we are quite unable to answer.

By multiplying examples of the same kind, we should in each case come to the same issue, namely, plurality of function with unity of structure, the unity being represented by a simple structural elementbe it retinal cone or cell-possessed of numerous endowments. Whenever this point is arrived at in any investigation, structure must for the moment cease to be our guide, and in general two courses or alternatives are open to us. One is to fall back on that worn-out Deus ex machina-protoplasm, as if it afforded a sufficient explanation of everything which cannot be explained otherwise, and accordingly to defer the consideration of the functions which have no demonstrable connection with structure as for the present beyond the scope of investigation; the other is, retaining our hold of the fundamental principle of correlation, to take the problem in reverse, i. e., to use analysis of function as a guide to the ultra-microscopical analysis of structure.

I need scarcely say that of these two courses the first is wrong, the second right, for in following it we still hold to the fundamental prin

ciple that living material acts by virtue of its structure, provided that we allow the term structure to be used in a sense which carries it beyond the limits of anatomical investigation, i. e., beyond the knowledge which can be attained either by the scalpel or the microscope. We thus (as I have said) proceed from function to structure, instead of the other way.

At present the fundamental questions in physiology,-the problems which most urgently demand solution, are those which relate to the endowments of apparently structureless living matter, and the problem of the 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 purpose 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 Professor Foster has given the very acceptable substitute metabolism. Metabolism is only another word for "change," but in using it we understand 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 cyclosis 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 structural plan which was once latent in a form of living material of great apparent simplicity. From the phys iological side this apparently simple material is seen to be capable of the discharge 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 endeavor to show you, the exist ing 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 absorp tion 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 concomitants. As regards electricity, we have no proof of the dependence of the electrical properties of plants and animals on chemical action. But all the other activities which have been mentioned are fundamentally chemical.

Let us first consider the relation of oxygen to living matter and vital process. For three quarters of a century after the fundamental discov. eries of Lavoisier and Priestley (1772-'76) the accepted doctrine was that the effete matter of the body was brought to the lungs by the cir culation 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.

Between 1872 and 1876, as the result of an elaborate series of investigations of the respiratory process, the proof was given by Pflüger* 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, absorbing it with such avidity, that although its own substance retains its integrity, no free oxygen can exist in its neighborhood. 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 constantly 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 re-action between them, i. e., the oxidation, is intrinsic, i. e., takes place within the living molecular frame-work.

* Pflüger's Archir, 1872, vol. VI, p. 43; and 1975, vol. x, p. 251. "Ueber die physiologische Verbrennung in den lebendigen Organismen."

Protoplasm therefore (understanding by the term the visible and tangible presentation to our senses of living material) comes to consist of two things, namely, of frame-work and of content,-of channel and of stream,-of acting part which lives and is stable,-of acted-on 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 frame-work 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, which we 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 catalysing frame-work, 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,-Micellæ, the word devised by Nägeli, and the better word, Tagmata, substituted for it by Pfeffer. Nägeli's word has been adopted by Professor 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 Nägeli has called Micellæ.

Now, Nägeli*, in the first instance, confounded the micelle with molecules, conceiving that the molecule of living matter must be of enormous size. But inasmuch as we have no reason for believing that any form of living material is chemically homogeneous, it was soon recognized, perhaps first by Pfeffer, but eventually also by Nägeli himself, that a micellæ, the ultimate element of living material, is not equiva lent to a molecule, however big or complex, but must rather be an arrangement or phalanx of molecules of different kinds. Hence the word Tagma, first used by Pfeffer, has come to be accepted as best expressing the notion. And here it must be noted that each of the physiiologists to whom reference has been made, regards the micellæ, not as a mere aggregate of separate particles, but as connected together so as to form a system;-a conception which is in harmony with the view I gave you just now from the side of animal physiology, of catalysing frame-work and interstitial catalysable material.

Nägeli, "Theorie der Gährung," Beitrag zur Molecular Physiologie, 1879, p. 121. + Pfeffer, Pflanzenphysiologie, Leipsic, 1881, p. 12.

To Professor Sachs, this porous constitution of protoplasm serves to explain the property of vital turgescence, that is, its power of charging itself with aqueous liquid;-a power which Sachs estimates to be so enormous that living protoplasm may, he believes, be able to condense water which it takes into its interstices to less than its normal volume. For the moment it is sufficient for us to understand that to the greatest botanical thinkers, as well as to the greatest animal physiologists, the ultimate mechanism by which life is carried on is not as Professor Sachs* puts it, "slime," but "a very distensible and exceedingly fine net-work."

And now let us try to get a step further by crossing back in thought from plants to animals. At first sight the elementary vital processes of life seem more complicated in the animal than in the plant, but they are on the contrary simpler; for plant protoplasm, though it may be structurally homogeneous, is dynamically polyergic,-it has many endowments-whereas in the animal organism there are cases in which a structure has only one function assigned to it. Of this the best examples are to be found within so-called excitable tissues, viz, those which are differentiated for the purpose of producing (along with heat) mechanical work, light, or electricity. In the life of the plant these endowments, if enjoyed at all, are enjoyed in common with others.

By the study therefore of muscle, of light organ and of electrical organ, the vital mechanism is more accessible than by any other portal. About light orgaus we as yet know little, but the little we do know is of value. Of electrical organs rather more, about muscle a great deal.

To the case of muscle, Engelmann, one of the best observers and thinkers on the elementary questions which we have now before us, has transferred the terminology of Nägeli and Pfeffer as descriptive of the mechanism of its contraction. Muscular protoplasm differs from those kinds of living matter to which I have applied the term "polyergic," in possessing a molecular structure comparable with that of a crystal in this respect that each portion of the apparently homogeneous and transparent material of which it consists resembles every other.

With this ultra-microscopical structure, its structure as investigated by the microscope, may be correlated, the central fact being that, just as a muscular fiber can be divided into cylinders by cross-sections, so each such cylinder is made up of an indefinite number of inconceivably minute cylindrical parts, each of which is an epitome of the whole. These Engelmann, following Pfeffer, calls ino-tagmata. So long as life Jasts each minute phalanx has the power of keeping its axis parallel with those of its neighbors, and of so acting within its own sphere as to produce, whenever it is awakened from the state of rest to that of activity, a fluxion from poles to equator. In other words, muscle, like plant protoplasm, consists of a stable framework of living catalysing

Sachs, Experimental-Physiologie, 1865, p. 443; and Lectures on the Physiology of Plants, English translation, p. 206.