Organism and Environment as Illustrated by the Physiology of Breathing

In this connection we may recall the facts relating to the effects of practice in the carrying out of any operation, such as writing, riding a bicycle, or playing a musical instrument. Here frequent repetition of what was at first a difficult and very imperfectly per- formed operation leads to its being performed with ease and certainty, without there being any conscious- ness of the innumerable details of nervous and muscu- lar adjustment which are involved.

Of all other analogous facts the most remarkable, in the higher organisms, are those relating to reproduc- tion of the whole organism. None of the innumerable structures special to the adult organism are present in the developing ovum ; but as if guided by stimuli which awaken memories of its parents and ancestors, it builds up the adult structures and activities by degrees, often reproducing even the finest nuances in the character of either parent. In a living organism the past lives on in the present, and the stored adaptations of the race live on from generation to generation, wak- ing up into response when the appropriate stimulus comes, just as conscious memory is awakened.

Looking at all these facts we are inevitably forced to the conclusion that the life of an organism, includ- ing its relations to internal and external environment, is something of prime reality, since it persists actively and as a whole, and moreover tends to do so in more and more detail with enlarging experience, so that life is a true development. What persists is neither a mere definitely bounded physical structure nor the activity of such a structure. There is no sharp line of demar- cation between a living organism and its environment. The persistence of the internal environment and its activities is, in fact, as evident as that of the more central parts of an organism ; and a similar persistence, becoming less and less detailed, extends outwards into

the external environment. An organism and its en- vironment are one, just as the parts and activities of the organism are one, in the sense that though we can distinguish them we cannot separate them unaltered, and consequently cannot understand or investigate one apart from the rest. It is literally true of life, and no mere metaphor, that the whole is in each of the parts, and each moment of the past in each moment of the present. Organic wholeness covers both space and time, and in the light of biological fact absolute space and time, and self-existent matter and energy, are but abstractions from, or partial aspects of, reality.

We are thus brought face to face with a conclusion which to the biologist is just as significant and funda- mental, and just as true to the facts observed, as the conclusion that mass persists is to the physicist. We saw previously that the structure of a living organism has no real resemblance in its behaviour to that of a machine, since the parts of a machine can be separated without alteration of their properties. All of these properties are also independent of whether the machine is in action or at rest. In the living organism, on the other hand, no such separation can be made, and the "structure" is only the appearance given by what seems at first to be a constant flow of specific material, beginning and ending in the environment. We have now seen that the apparent flow has a persistence and power of development of its own, which we cannot account for by mere constancy in the physical and chemical environment. What persists is not mere matter or energy: for the matter and energy which

seem to pass through an organism are constantly being replaced. Nor is it mere form : for the flowing mate- rial is intensely specific. Structure, composition and activity are inseparably blended together in life, and no phenomenon in the inorganic world seems to us to be similar to the phenomenon of life. The funda- mental facts with regard to life do not fit into the conceptions by means of w^hich we at present interpret inorganic phenomena. Life is something which the biologist as such must treat as a primary reality, and no mere artifact. It is with life, and not merely with physics or chemistry, or bio-physics or bio-chemistry, that these lectures have dealt. From the outset of my own scientific work I have been guided by the concep- tion that it is with life, and not with what physics and chemistry are at present capable of interpreting, that physiology deals ; and this conception has grown clearer in my mind as a scientific working hypothesis with advancing experience as a physiological worker. What aims does this conception carry with it for physiological investigation? The ground hypothesis or conception is that each detail of organic structure, composition, and activity is a manifestation or expres- sion of the life of the organism regarded as a separate and persistent whole. We have therefore to make use of this hypothesis as a tool for investigation, just as the physicist uses the conceptions of mass and energy, or the chemist the atomic theory. We assume, therefore, that it will be found on sufficient investiga- tion that the scattered observations of living organisms with which preliminary sensory observations supply

us are capable of unification under our guiding hypothesis ; and we proceed to investigate them further with this faith present to us. We notice, for instance, that animals breathe. The breathing is a manifesta- tion of the animal's life, for any hindrance to breath- ing is violently resisted with the animal's whole available power. Further investigation shows us more definitely what breathing is, the essential element in breathing being the due supply of oxygen to the body, and removal of carbon dioxide. By more detailed investigations, such as I have endeavoured to describe in these lectures, we reach a further knowledge of how the phenomena of breathing are integral manifesta- tions of the whole life of the organism, including its past history ; and the aim remains before us of reach- ing similar knowledge of how the development, main- tenance and functional efficiency of each structural element are regulated.

One of the earliest steps in this voyage of discovery is to find any detail of structure or activity that can be regarded as a "normal." We look for normal structure, normal chemical composition, and normal standards of activity. And we do so because we know that life maintains itself: that this maintenance ex- presses itself in normals for everything connected with life. In the inorganic world there appear to be no normals in this sense ; and chance, not order, seems, to the present very limited vision of physical science, to reign supreme.

When we have found what appears to be a normal, such, for instance, as a normal concentration of carbon dioxide in the alveolar air, we first test it under vary- ing conditions so as to make sure of its relative stability, and then proceed to investigate its connection with and subordination to other normals. Thus we find that the normal concentration of carbon dioxide in the alveolar air is connected with or subordinate to the normal composition of the blood, the normal activity of the respiratory centre, heart, kidneys, and other organs, the normal composition and amount of the food and the normal concentration of oxygen in the air. Our general working hypothesis would have told in a general way that connections of this kind must exist; but special investigation could alone tell us how they exist and how one is directly subordinate to another. It is this kind of investigation that is experimental physiology. The normals of anatomy are not mere physical structure, nor are the normals of physiology mere averages : they are manifestations of the life of an organism regarded as a whole. We have seen, for instance, in the case of the alveolar carbon dioxide pressure, in the percentage of haemo- globin in the blood, in the structure of bone-marrow, how a subordinate normal alters as the organism adapts itself so as to preserve its more fundamental normals under new conditions. In pathological condi- tions we find remarkable alterations in subordinate normals, and these alterations are undoubtedly the expression, to a large extent, of adaptations to the altered conditions. Pathological phenomena are not mere chance effects of the environment on the organ-

ism. Pathology is a real science, and part of the science of biology. Anatomy and physiology, but more particularly anatomy, have become hide-bound in the conception that living structure is simply physical structure; and in consequence of this anatomy has for the present the aspect of almost a dead science, in spite of the new life impulse from experimental embryology. The time has come for biology to liberate herself and step forth as a free and living experimental science, with a world before her to conquer by the help of clearer ideas of what life is, and how it can be investigated.

Biology is no inexact science, contented with rough pictorial approximations. The bane of physiology in the past has been inexact measurement and imperfect observation. The new physiology will be different. Its* measurements and observations will be more exact, and, as has been shown in the previous lectures from actual instances, of a delicacy often far exceeding that of existing physical and chemical methods. But the observations and measurements will not be of phe- nomena which if isolated are mere illusions. The new physiology will not be content with causes, but will seek out the organisation of which "causes" are only the outward appearance.

For the reasons already given, organism and en- vironment cannot be separated in considering life. But we seem to be able to reach a satisfactory inter- pretation of the physics and chemistry of the external, and even of the internal environment, when these states are looked at apart from their relations to organic activity. The oxygen which passes into the lungs is just ordinary oxygen, driven inwards to the alveoH by an ordinary atmospheric pressure difference. The process is organically regulated, but the regulation appears to be something external to the oxygen, which still retains its usual properties. We can then trace its diffusion into the blood, its combination with haemo- globin, its carriage onwards by the pumping action of the heart, and its dissociation from the haemoglobin in the systemic capillaries. It has come under more intimate organic control in the blood, but we can still trace it as molecules of ordinary oxygen. When it reaches and is absorbed by the tissues in cell metabol- ism the organic control becomes far more intimate. It is caught up in a whirl in which its behaviour is from the physical and chemical standpoint utterly mys- terious. We can imagine no form of chemical com- bination which will now explain the behaviour of the oxygen. The mental picture of oxygen atoms or mole- cules seems to fade away, and to be replaced by an- other picture in which organisation is not something external to organised material, but is absolutely iden- tical with the material, so that both the material and its movements are nothing but manifestations of the organisation. It is life and not matter which we have before us.

We can endeavour to hold on to the physical and chemical picture, and to seek for substances in the living structure which combine with, or enter into other physical or chemical relations with the oxygen. But a little consideration shows that even if we find such instances, their presence and formation is organic- ally determined by something beyond ; and of this something we can form no physical or chemical pic- ture. We also realise more clearly that in following the physical and chemical picture of the oxygen from the outset we have only done so by ignoring the organic control which, though present, seems less intimate. We have ignored, or put aside for the time, the regu- lated maintenance of breathing, the maintenance of the delicate normal structure of the lungs and of other parts connected with breathing, the regulation of the circulation and of the composition of the blood, and the maintenance of endless other things in which organic regulation manifests itself. But when we reach the living tissues we can ignore the organic regu- lation no longer : for we can see nothing clearly except an evident manifestation of the most intimate organic regulation. The physical and chemical picture is entirely obliterated by the picture of organism.

We may reflect that although we cannot at present trace the combinations into which oxygen enters in the living tissues, yet the oxygen atoms are there in some form. We can demonstrate their presence by ele- mentary analysis, and we can separate chemical com- pounds, such as proteins, which contain oxygen. It can therefore be only a matter of further investigation to discover how the oxygen and other atoms combine in the living tissues and how these compounds react with one another to bring about the phenomena of life. This reflection brings us very close to a fundamental question. Physics and chemistry have brought us not

one step nearer to a physico-chemical conception of the characteristic phenomena of Hfe, though they have been indispensable in elucidating these phenomena — in enabling us to formulate with increasing sharpness and detail the preponderant and omnipresent role of organisation in connection with biological phenomena. The more clearly we consider the matter the more clearly does it appear that this failure is not merely due to lack of ordinary physical and chemical data of the kind already familiar to us. No such data that we can remotely conceive would help us : no advance, for instance, in our knowledge of the chemical consti- tution and physical properties of protein compounds. We can reach no other conclusion than that it is the very conceptions of matter and energy, of physical and chemical structure and its changes, that are at fault, and that we are in the presence of phenomena where these conceptions, so successfully applied in our interpretation of the inorganic world, fail us.

What reasons have we for assuming, as we are apt to assume, that our physical and chemical conceptions or mental pictures of the surrounding universe corre- spond with reality ? The reason is that they do actually enable us to predict much of our experience of the inorganic world, and up to a certain point have proved eminently reliable. Nevertheless they leave an enor- mous blank in our knowledge : for they assume a world of various kinds of matter and various forms of energy, variously distributed ; but as to why this vari- ety and distribution exist they leave us in ignorance. From the very nature of the ordinary conceptions of

matter and energy as independent entities this igno- rance is unavoidable. Clear enough indications exist, however, that the progress of pure physical and chemi- cal investigation is pointing towards truer and more adequate conceptions. The discoveries of the periodic law and of the transmutations of chemical elements in connection with radio-activity indicate an underlying connection between different forms of matter. With Faraday's discovery that in electrolytic dissociation the ions have each a definite electrical charge, and the more recent discoveries of the energy locked up in atoms, and liberated as radio-activity in their decompo- sition, an underlying connection between matter and the energy associated with it has become no less ap- parent. Thus even if we look only at the evidence afforded by the investigation of the inorganic world it seems clear enough that our present conceptions are only working hypotheses: — ^the pictures which our own generation has formed of it; but only imperfect pictures not adequately representing reality.

In the organic world we meet with something in the face of which these working hypotheses are far more definitely inadequate; and the very existence of biology is a direct challenge to them. We can never- theless see how they can, up to a certain point, be used successfully in interpreting biological phenomena. For we can take the structure of the living body, not as living structure, but as something given and independ- ent of its environment; and having once made this fundamentally false assumption we can proceed with the investigation of the supposed physical structure

in the same way as the physicist or chemist would pro- ceed. This method yields much provisional informa- tion for further investigation and more correct inter- pretation, through which real physiology advances ; and the mere possession of the provisional informa- tion is itself of great value. By showing that the living body could in certain respects be regarded as a heat- producing machine Lavoisier made a great step for- wards, though he did not realise that the heat-produc- tion is organically regulated. For an animal in normal environment the hypothesis that there is a constant relation between intake of energy in the form of free oxygen and food-material, and output of energy as heat and in other forms, has stood the test of the most rigorous experiments. The fundamental observations of Regnault and Reiset, Pfliiger, Rubner, and others have, however, shown that both intake and output of energy are strictly regulated, like other physiological activities ; and what is implied in this organic regula- tion has already been discussed. The preliminary comparison of the organism to an energy-transforming machine has been of great value in certain directions, but has misled, and still continues to mislead, physiolo- gists in others. The real source of the misunder- standing has been the assumption that physical and chemical working hypotheses are more than working hypotheses of limited profitable application, and accu- rately correspond to reality itself.

This assumption has given rise to the mechanistic theory of life as a necessary corollary, as well as to all that is vaguely designated as "materialism." But though the assumption is false it must be borne in mind that working hypotheses applicable to the available sense data are indispensable to the advance of knowl- edge and practice. With limited data crude and simple working hypotheses, sufficient to cover the data with- out further complication, are alone of practical use; and both knowledge and practice, in dealing with iso- lated and imperfect data, naturally proceed on crude hypotheses. Where we can as yet see no organic determination in isolated observations relating to life the best available description of them is in mechanis- tic terms such as we apply to the inorganic world. Such descriptions supply an indispensable basis for more adequate description and interpretation ; but to give a general application to the crude working hypothe- ses on which these descriptions are based implies a disregard of the wider biological observations which indicate that further investigation would reveal organic determination. This disregard is a very marked fea- ture in current text-books of physiology. Each part of physiology, and even each subdivision of a part, is apt to be treated in isolation from the rest, with the necessary consequence that not only is no place left for the facts relating to organic determination, but the isolated details are very imperfectly described, as has been illustrated again and again in the course of these lectures.

The real reason of this defect is that physiologists have been endeavouring to fit their descriptions to the imperfect current working hypotheses of physics and chemistry — an attempt which, in view of the facts of physiology can only end in certain failure. They assume as self-evident, for instance, that what they are dealing with is "living matter." In reality these two words contradict one another. What we interpret as being in the sense ordinarily current, "matter," cannot be also interpreted as living.

Why has physiology failed to free herself from this misunderstanding? The fact of organic regulation has been evident enough from early times, and, except in more or less recent text-books, has received promi- nent attention from physiological writers. Various causes have, I think, contributed, and I should like now to refer to one which is specially prominent. The physiologists who laid most stress on organic regulation adopted the theory known as Vitalism — a theory which, though unorthodox, is still very much alive, and of which the eminent experimental embryol- ogist, Hans Driesch, is probably the best-known living representative. The vitalistic theory is that although matter and energy are, whether outside or inside of the body, just what current physical and chemical con- ceptions describe them as, yet in the living body they are guided by what older physiologists called the "vital spirit," "vital force," or "vital principle," and what Driesch^ calls "entelechy." As is well known, Driesch discovered the fact that if the constituent cells of an embryo in its earliest stages of development are dis-

1 The clearest and shortest exposition of Driesch's argu- ment is, I think, contained in his recent book, The Problem of Individuality, London, 1914. arranged, or separated entirely from one another, a complete embryo may still develop, even from a single cell. He argues from this and other facts of analogous character, (1) that any mechanistic explanation of life is unthinkable, and ( 2 ) that we must assume the inter- ference of a guiding influence, "entelechy," which directs the material present, so that it develops in the right way.

Driesch's destructive criticism of the mechanistic theory is particularly searching and cogent, and it seems to me that both he and the older vitalists have been justified up to the hilt in refusing to accept this theory. In the previous part of this lecture I have endeavoured to express the vitalistic criticism in a still more general form than it has assumed in the writings of the vitalists. To me the mechanistic theory of life appears impossible, not merely in connection with the facts of heredity and embryology, but at every point in biology.

To the vitalistic theory itself, however, there are insuperable objections. Experience shows us that where an organism reacts in any way it is always in response to some stimulus, whether this stimulus origi- nates from without or within. The stimulus of fertili- sation normally initiates the segmentation of an ovum, and from all analogy we must conclude that the differ- ential stimuli arising from neighbouring cells or other parts determine the subsequent differential behaviour of each cell in the segmented ovum. On separating the cells these differential stimuli are removed, and each cell naturally starts again from the beginning.

Perhaps the case of the respiratory centre or of the kidney illustrates as well as anything else the ob- jections to vitalism. We have seen with what marvel- lous exactitude the respiratory centre regulates the hydrogen ion concentration of the blood, but also that the response of the centre is nevertheless dependent on, and proportional to, an increase, however small, in the hydrogen ion concentration of the blood. If our methods of measurement had been less exact, if, for instance, we had employed rougher methods of gas analysis in investigating the alveolar air, or if we had been compelled to rely simply on the methods, delicate as they seem to a chemist, which are at present avail- able for measuring hydrogen ion concentration, it might have seemed as if the respiratory centre acted without a stimulus, guided by an outside agency, just as a locomotive is guided by the driver, who shuts off or turns on steam according to requirements, and thus keeps his train up to time in spite of various accidental hindrances. Vitalism is a theory of this kind : it ignores the participation of the environment in the regulation, and consequently does not correspond to the observed facts, and is thus of little use as a work- ing hypothesis in actual investigation. Its only real merit is that it serves as a means of expressing facts relating to organic regulation, and the defects of mechanistic theories. These facts are registered by referring them to the vital principle or entelechy.

The further physiology seems to advance in the direction of mechanistic explanations the more ob- viously it is driven into vitalism. For advance in mechanistic explanation implies the assumption of more and more definite and complex physical and chemical structure in the body, and the development and maintenance of this structure has then to be accounted for, with a resulting relapse into vitalism, whether acknowledged or only implied. The help- less struggling in this direction of the mechanistic school which still represents modern orthodox physiol- ogy will be a marvel to future generations. It is in vain that the mechanistic theorists endeavour to exor- cise what du Bois-Reymond called the "spectre of vitalism." This spectre is nothing but the shadow cast by the mechanistic theory itself — a shadow which has only become, and could only become, deeper the longer the mechanistic theory has lasted.

Both the mechanistic and the vitalistic schools have survived up to the present day, but we can under- stand that actual investigators have preferred to avoid vitalism so far as they could, as the vitalistic hypothe- sis seemed to set a limit to experimental investigation, and they rightly and instinctively felt that there is no such limit. So long as vitalism seemed the only alter- native to mechanistic interpretations, they were driven towards the latter. In the din of controversy between vitalists and mechanists there was, however, a com- plete failure to go to the root of the matter, and en- quire into the validity of the assumptions as to physi- cal reality which were accepted by both sides.

In considering the facts of physiology we have hitherto looked at them from the standpoint of the individual organism only. But we know that in all but the lower forms of animal and vegetable life the body is made up of cells and cell-territories, and that each cell is a centre of life. The life of the body as a whole is maintained by co-operation amongst the constituent cells. In the course of the common life the individual cells are constantly perishing and being reproduced, but the continuity or persistence of the common life is as evident throughout these changes as throughout the nutritive processes in which the chemi- cal molecules passing through the body are constantly being replaced.

Not only do the constituent cells reproduce them- selves and perish, but so does the whole organism it- self; and its death is evidently just as much a normal phenomenon as is the death of any of its constituent cells. Death has sometimes been compared to the wearing out of a machine, but such a comparison throws no light on death, since the body is not a machine. Besides death and reproduction, there are many other biological phenomena which show us that life is not merely the life of individual organisms, but the life of a society of organisms. It is the life of a family, and beyond that the life of a species ; or if we endeavour to push the biological analysis still further, the life of the universe itself, though such a life must remain outside the limits of clear mental vision until we can connect biological with physical and chemical conceptions.