The first five lectures of the previous course were devoted to showing that Biology must be regarded as a science which is differentiated from the physical sciences owing to its fundamental axioms being different from those of the physical sciences. This matter is so important that a full discussion was required of the attempts which have been made to harmonize biological observation with the axioms of the physical sciences. As, however, was emphasized in the last lecture of the previous course, we cannot, in the perception and description of biological phenomena, dispense with preliminary physical interpretation, the result being that the co-ordination which is characteristic of biological phenomena seems to be only discovered by contrast, as if it were imposed from without on physical phenomena, and as if it were only through the progressive discovery of this imposition that biological interpretation makes progress.
In the history of physiology nothing is more striking than the fact that advance in distinctively biological interpretation depends upon the application of accurate physical and chemical methods and measurements. Apart from such methods and measurements when they are put together, we should know nothing definite of biological co-ordination as contrasted with mechanism. The widespread assertion that the application of accurate physical and chemical investigation to life has been leading towards a physico-chemical conception of life is a ridiculous travesty of scientific history.
What I wish now to discuss is the intimate connexion which exists between biological and physical interpretation. We cannot rest satisfied with the idea that molecules or atoms, though they still continue to be molecules or atoms essentially independent of one another, yet behave within living organisms as if they had there and then lost their independence and become possessed by a foreign influence. Such an idea amounts to the same thing as vitalism, and is thus subject to the fatal objections which were pointed out in the fourth lecture of the previous course.
As a sort of friendly practical compromise with the Newtonian or mechanical ideas under the influence of which they have been brought up, biologists are constantly being driven into vitalistic or animistic modes of expression; while representatives of the physical sciences are perhaps even more willing to accept this compromise in so far as they come into contact with biological phenomena. Yet the great majority of biologists, at any rate, have realized that the attempted compromise is impossible, and on this point I am in full agreement with them.
From a philosophical standpoint it is of the utmost importance to face and thoroughly discuss the difficulty; for similar difficulties appear again in connexion with the psychological branches of knowledge. On the one hand, we seem to have a world of essentially independent Newtonian molecules, atoms, electrons, and other “bodies” acting on one another. On the other hand, in connexion with biological phenomena, we seem to have a world in which the “bodies” do not behave as such, but as the expression of an actively and specifically co-ordinated whole. It seems to me that there is only one solution of the apparent contradiction. This solution is that the appearance of a world of independent bodies is only appearance, while the biologically interpreted world is at any rate something nearer to reality itself.
With our upbringing in the tradition of the Newtonian interpretation of visible and tangible reality it is very hard for us to accept such a solution, or even realize its meaning. The practical utility of the Newtonian interpretation is enormous. In every direction it has opened to us new possibilities of prediction and consequently of controlling our environment; and it is steadily continuing to open further possibilities. We cannot possibly dispense with it. Nevertheless, as will be pointed out more fully in the succeeding lectures, it is constantly threatening to obscure completely our vision of reality as a whole. The time is more than ripe for coming to an understanding with it.
The only understanding which seems to me possible is that the Newtonian interpretation represents only a provisional working hypothesis. This can be no mere spatial or temporal limitation, but must apply everywhere as soon as we examine our visible and tangible world more thoroughly and from a point of wider view than that of ordinary physical investigation. We constantly fail to perceive things correctly because we are only seeing them partially, and this is very strikingly the case when we attempt to apply physical interpretations to biological phenomena. From a point of narrower view the physical interpretation may give promise of being satisfactory, but from a point of wider view the biological interpretation is alone possible.
Let me illustrate this statement by an example from a part of physiology with which I am specially familiar, namely, the physiology of breathing. In the act of breathing, air passes into and out of the lungs, and this is rendered intelligible to us mechanically by the dynamical theory of gases on the one hand, and on the other by the action of the respiratory muscles on the structures forming the lung-walls. To continue the mechanical interpretation, within the lungs a process of gaseous interchange occurs between the air in the alveoli or ultimate air-sacs of the lungs and the blood circulating through the capillaries on the outer surface of these air-sacs. In this exchange oxygen is taken up by the blood and carbon dioxide given off to the air. When we investigate this process more closely, we find that during rest under normal conditions the partial pressures of oxygen and carbon dioxide, or the pressures with which they diffuse out of the gas and out of the blood, come into complete equilibrium as the blood passes through, the blood taking up oxygen and losing carbon dioxide, while the air loses oxygen and takes up carbon dioxide, till, when the blood has become “arterialized,” equilibrium is established. This is perfectly intelligible mechanically on the theory of diffusion, considering the enormous capillary surface presented in the lungs. When conditions giving rise to shortage of oxygen exist, as during muscular exertion or life at high altitudes, there is what seems to be quite clear evidence that oxygen is actively driven or secreted through the capillary walls into the blood; but we may leave this out of account for the present.
Now let us consider more closely what is happening in the blood. From the mechanical standpoint it is being pumped round the body and through the lungs by the action of the heart, and on chemical examination of it we find that its corpuscles contain a coloured substance, haemoglobin, which has the property of taking up oxygen to form a loose molecular combination, oxy-haemoglobin. The oxygen diffuses off from this substance when the surrounding diffusion pressure of oxygen is low, as in the capillaries of the systemic circulation, and is taken up again when the oxygen diffusion pressure is relatively high, as in the lungs. It thus acts mechanically as a carrier of oxygen to the tissues. Similarly we find in the blood compounds of carbon dioxide and alkali. Owing to the action upon them of haemoglobin and other proteins which act as acids in an alkaline medium, they are decomposed in the lung capillaries when the diffusion pressure of carbon dioxide is relatively low, the alkali combining with the substances just mentioned, and the carbon dioxide being liberated into the alveolar air. In the systemic capillaries, on the other hand, with the diffusion pressure of carbon dioxide relatively high, the alkali recombines with carbon dioxide, the double process of gaseous exchange which occurs in both the systemic and the lung capillaries being specially favoured by the facts that in proportion as haemoglobin is deprived of its oxygen it acts less strongly as an acid, while in proportion as it absorbs carbon dioxide it holds on less tightly to oxygen.
So far the process of respiration can be interpreted as a purely mechanical one, assuming that the required structures and chemical compounds are present, and that the respiratory muscles and heart play their mechanical part in the process. When, however, we put all the observations together, we find that the whole process is regulated in the most delicate manner at every point, and the whole of the structures concerned are being constantly maintained with corresponding delicacy.
In the first place, the pumping action of the respiratory muscles is so regulated as to keep the partial pressure of carbon dioxide in the alveolar air very exactly constant from minute to minute under ordinary conditions. This has the effect of keeping the reaction or hydrogen ion pressure of the arterial blood extremely constant, since the arterial blood becomes more alkaline, or less, according as the partial pressure of carbon dioxide falls or rises in the alveolar air. In fact, the breathing is regulating in the most delicate manner the reaction of the blood—so delicately in fact that no existing method of determining the reaction is sufficiently delicate to follow the slighter variations which are sufficient to produce a marked effect on the breathing. Were it not that the kidneys also are engaged in regulating the balance of alkalies and acids in the blood, so that when the pressure of carbon dioxide in the alveolar air is kept constant the reaction of the arterial blood is also normally almost exactly constant, the pressure of carbon dioxide in the alveolar air would never be steady; and since in man much more acid than alkali is constantly being formed in the body, the blood would soon become acid.
When the reaction of the arterial blood tends to become less alkaline, it excites a nerve-centre or centres in the brain in such a manner as to evoke increase in the respiratory movements, or corresponding diminution or complete cessation if the blood becomes more alkaline, provided that the altered alkalinity of the blood is communicated through cell-walls to the nerve-centres. We can see at once that in this way the respiratory movements are made to harmonize with the varying production of carbon dioxide by the body. This production, for instance, is often ten times as great during muscular exertion as during rest; but the respiratory movements are correspondingly increased, so that the reaction of the arterial blood, or at any rate the liquid in contact with the protoplasm of nerve-centres, is kept almost steady. As, moreover, the production of carbon dioxide runs parallel with consumption of oxygen, an adequate oxygenation of the arterial blood is at the same time automatically secured except under exceptional conditions which are dealt with in the manner described in the discussion of acclimatization in Lecture V of the previous course.
We have every reason to believe that just as respiration is delicately regulated to keep the reaction and oxygen pressure of the arterial blood steady, so the circulation through every part of the body is regulated with similar delicacy to keep the local composition of the blood as steady as possible. Our knowledge on this subject is still, however, very defective, and it is only in man that we can even measure satisfactorily the rate of the general circulation under varying conditions of work, etc., and the gas-pressures of the mixed venous blood returning to the lungs. The ideas, formerly current, of the breathing and circulation going on in a blind mechanical manner are now obsolete, and it was, I think, the exact quantitative study in man of the regulation of respiration that gave them their death-blow. Apart from quantitative study of this kind, in which I have myself been engaged for most of my scientific life, biological co-ordination is entirely obscure.
We can form no mechanical conception of why it is that the respiratory centre responds, and continues to respond, with such amazing delicacy to minute changes in a certain definite hydrogen ion pressure, or why the kidneys show a similar delicacy in response, so that with the very slightest diminution or increase in hydrogen ion pressure of the blood they secrete urine containing either far less or far more acid, thus exerting a most powerful influence in steadying the reaction of the blood. Calculation from our actual experiments on man shows that a deficiency in ionized hydrogen of one part by weight in about one million million parts of arterial blood is sufficient to suspend completely the activity of the respiratory centre, although, owing to cell-walls being only partially permeable to certain substances the reaction of the blood sometimes does not communicate itself fully to the respiratory centre and other parts.
All that we can say from a mechanical or physico-chemical standpoint as to this and other responses of equal delicacy, is that various parts of the body respond, and often with the most amazing delicacy and constancy, to slight changes in their “normal” environment. The kidneys, for instance, respond by immensely increased or diminished excretion of water to a scarcely measurable increase or diminution in the diffusion pressure of water in the blood. This, as I have shown in my book on Gases and Liquids,1 has hitherto been wrongly called a diminution or increase in the osmotic pressure of the blood.
When the chemical nature of substances which evoke responses is unknown, they are now usually called “hormones” if they are produced within the body, or “vitamins” if they come from outside sources; and there is a curious popular idea abroad that the discovery of hormones and vitamines is a great step towards a physico-chemical explanation of life. In actual fact, however, the more we discover as to the physiological necessity for the presence in the blood of various substances in specific amounts, often extremely small, the further are we from any physico-chemical understanding of life, since there is just so much more for the specific maintenance of which we have no physico-chemical explanation. We also must not mistake the invention of a convenient word for the discovery of something new in principle. Practically every substance present in the body, beginning with water, which is the most abundant substance, acts when in solution in the same physically and chemically unintelligible manner as a “hormone” in the narrower sense.
Not only is the influence of hydrogen ion pressure (and oxygen pressure) on respiratory activity physically unintelligible, but the maintenance and development of all the structures and chemical substances essentially concerned in respiration are equally unintelligible physically. Almost as a matter of course we assume that these structures and substances are maintained in their normal state of delicate adjustment; but when we ask how this is brought about there is absolutely no answer from the physico-chemical side. How, for instance, is the living structure so maintained that liquid is prevented from leaking out of the blood into the alveoli? As death approaches, wholesale leakage often begins to occur with dramatic suddenness. The “death-rattle” of pulmonary oedema has been familiar since antiquity. We can investigate one by one the various conditions on which the maintenance or development of normal structure and composition depends, and there seems to be no limit to the complexity of these conditions from the physico-chemical standpoint. But of their specific co-ordination in maintaining and originating normal structure we can find no trace of a physico-chemical explanation, so that each discovery makes the attainment of such explanation seem more remote.
What we do discover, however, and in ever-increasing detail, is that when we look at the phenomena of the life of any organism in their relation to one another, they are the expression of actively maintained specific and co-ordinated unity. The structure is an expression of specific co-ordinated activity; and the activity is specifically co-ordinated in such a manner that the structure is maintained. It is true that when we isolate from one another the phenomena of life we see nothing more than the essential chaos of self-existent units of matter and energy acting on one another in a manner which though here intelligible is there quite unintelligible. But this appearance of chaos and unintelligibility vanishes when we regard the phenomena as a whole and interpret them biologically. We then see clearly the active maintenance and reproduction of specific structure which we call life. We also realize that the assumption of this maintenance furnishes us with a working hypothesis which gives us a clue through the apparent unintelligibility, and enables us to predict what will happen and see backwards into what has happened. This working hypothesis is the working hypothesis of biology, and differentiates biology completely from the physical sciences. In so far as we do not yet see how to apply this hypothesis we have to content ourselves with provisional physical interpretation, so far as it goes; but it is mere futility to shut our eyes to the co-ordination in so far as it is already known and embodied in the very nomenclature of biology, or to cease to search for it where we have not yet traced it. Such is the futility of attempted mechanistic interpretation.
Let us imagine the physical picture of what is occurring in a lung alveolus. The alveolus seems to contain a swarm of myriads of perfectly elastic molecules moving with enormous velocity and colliding at all angles with one another and with the alveolar walls. The scene is apparently one of absolutely chaotic interaction of minute “bodies.” Molecules of oxygen are also constantly shooting into and through the molecular interstices of the alveolar and capillary walls and so disappearing, but are replaced by means of an intermittent stream of pure air passing up and down the bronchial tubes. In a similar manner molecules of carbon dioxide are appearing and being carried away. It is because the walls are sufficiently leaky and of sufficient surface, and since the partial pressure of oxygen (though not of nitrogen) molecules is greater on the inner than on the outer surface of the walls, that, by the law of probability, on the whole more oxygen molecules pass inwards than outwards, and similarly for the passage of carbon dioxide outwards. It is also because when the alveolus alternately expands and becomes smaller there is alternately a less and greater concentration of molecules within it that, by the law of probability, air passes out of and into it, more oxygen and less carbon dioxide being present in the incoming than in the outgoing air, so that, on the whole, oxygen passes into the alveolus from the outside air, and carbon dioxide passes out.
If we confine our attention to the gas in the alveolus, this mechanical picture seems to represent what is occurring within it, and according to the Newtonian “philosophy” represents reality. But the activity which ultimately maintains the flow of gas molecules, the structure of the alveolar walls, and all the other structures involved in breathing, determines all the phenomena, and we perceive the specific character of this determination in perceiving the life as a specifically co-ordinated whole, just as it is as a whole, in which self-existent letters, or daubs of paint, or notes, disappear, that we perceive a word, or a sentence, or a picture, or a piece of music. As participating in the life of the organism, the activity in the lung alveoli and other responding structures has taken on an interpretation quite different from the physical interpretation. It is not mere mechanical chaos, but organic co-ordination that we perceive; and to a biologist the organic co-ordination is the essential feature.
If we insist that the organic co-ordination which we find in the activities of a living organism is only something imposed from without on the physical reality, we are involved in all the difficulties of vitalism or animism. The only possible course, therefore, is to conclude that, in spite of appearances, when we regard part of the phenomena in isolation, the organic co-ordination is part of their very nature, so that the biological interpretation of the phenomena is the truer interpretation. In other words, the phenomenon we are dealing with is no mere chaos of self-existent bodies acting on one another, but is the expression of life.
This involves a radical change in our interpretation of the phenomena, since it is now only in superficial appearance that the mechanical interpretation holds good. We can hardly help glossing over the change in interpretation by means of the assumption that the co-ordination is only a form of artificial restraint by an outside influence in the form of a “vital force” or by whatever other name we designate this influence. This course is not open to us, however, as has already been pointed out. We cannot escape the conclusion that the physical interpretation must in ultimate analysis give place to a biological interpretation.
It still remains the case, nevertheless, that it is only ultimately that the biological interpretation holds good. The transition to biological interpretation has the character of an act of faith. There is far more in the phenomena than we can see how to interpret biologically, just as there is far more in an actual picture than we can see how to interpret artistically. Though the apparent mechanical chaos is not really a chaos, yet it is only imperfectly and by contrast that we can interpret it as being actually organic co-ordination and unity. The process of normal respiration may, for instance, be interfered with by some apparent mechanical cause, and from the biological standpoint this failure of organic control is unintelligible. Thus in order to fill in to the best of our ability the gaps in biological interpretation, we must have recourse to physico-chemical interpretation, and this interpretation, in its proper subsidiary place, is indispensable. Without clear mechanical theories of gases and liquids, of solution and diffusion, of partially permeable membranes and osmosis, and of chemical combination and dissociation, we could not piece together a coherent account of physiology, however true it is that the mere application to physiology of mechanical conceptions leads to only a confused medley of isolated observations, which are of little use for practical purposes.
Apart from the biological conception of active organic co-ordination, the physiology of respiration, or of excretion or circulation, is not only quite unsatisfactory, but is also apt to be very misleading. It tends to become, in fact, a futile travesty of scientific knowledge. On the other hand, unless we have clear conceptions as to what can be interpreted in physical and chemical terms within and around living organisms, we can form no clear ideas as to organic co-ordination. Looking back at the attempted mechanistic physiology of the latter part of last century, what is very striking is the absence of clearly applied physical and chemical conceptions from the minds of the leaders of the movement, although they were constantly speaking of physico-chemical explanations. Their attempted physico-chemical explanations of physiological activities were woolly to an extreme extent.
For purposes of illustration I have considered the case of alveolar air. A similar process of reasoning would apply to the contents of the alimentary canal or to the composition of the blood at any part of the body. Within what we are accustomed to regard as the substance of the body itself, organic co-ordination seems, however, to manifest itself in a much more directly effective and striking manner. Specific composition and activity are evident at once, without our having to seek for them by careful and accurate analysis and measurement. The more, also, we succeed in applying analysis and measurement to the substance, form, and activities of living protoplasm, the more clearly does organic coordination manifest itself. The days are long past when “protoplasm” was regarded as merely a solution and suspension of simple though somewhat indefinite composition. Not only the structure, but also the composition, of any variety of cell is specific and complex, while the activities of the cell are such that this specific structure and composition are being constantly maintained and reproduced. Each individual cell, moreover, plays its specific part in maintaining the specific structure and composition characteristic of the life of a specific organism.
This part is never a mere mechanical part. We must regard each cell as behaving in a specific manner in presence of neighbouring cells, so that their nutrition and growth are “normal.” At the same time the nutrition and development of cells at a distance are organically co-ordinated. The behaviour at a distance in this way of so-called ductless glands and other organs is now well known. Perhaps, however, it is apt to be forgotten that the mere fact that the body develops and maintains itself as an organic whole shows quite clearly the coordinated mutual behaviour of all the different parts in the promoting or restraining of development. This influence is exerted in part direct from cell to cell, but largely through the bloodstream.
Owing to the artificial separation of anatomy from physiology it was for long imagined that different parts of the body develop and grow independently of their influence on one another, and that, for example, developing germ-cells develop independently of the influence on them of the rest of the parent organism. These ideals are devoid of any real foundation, and are inconsistent with the conception of organic coordination and unity. There can be no real separation between anatomy and physiology, although, under the baneful influence of attempted mechanistic or vitalistic conceptions of life, anatomy almost abdicated its position as an experimental science.
The alveolar air, or the contents of the alimentary canal, or the blood, may be regarded as the more or less immediate environment of the body-cells. The relation of the external environment to the conception of organic unity will be discussed in the next lecture.
Gases and Liquids, Oliver & Boyd, 1928.