The preceding lectures have shown, not merely the difficulty, but the impossibility, of interpreting life as a physico-chemical process on the general conception of physics and chemistry as formulated on the lines of Galileo and Newton. They have also shown that the attempt to eke out the physico-chemical interpretation by assuming the interference in vital processes of an agency which, since it is neither visible nor tangible, we can properly call a supernatural agency, is equally unsatisfactory in enabling us to comprehend life. To overcome these difficulties it is necessary to deal radically with our hypotheses, and the necessity for this was indicated in general terms in the first lecture.

Hippocrates treated the unconscious activities of life as natural processes. He claimed the right to interpret them in accordance with actual observation, regardless of superstition and of the intrusion of philosophical opinions not based on observation of them. In observing Nature just as she appears in the phenomena of life, and basing his interpretations directly on the observations, he founded scientific medicine, and with it, as it seems to me, scientific biology. The co-ordinated activity manifested in the phenomena of life was regarded by Hippocrates as nothing more than a visible and tangible manifestation of Nature. He found co-ordination and its maintenance in the aspect of Nature which he was studying, and refused to be moved by the philosophical atomism of his time. His influence, through Aristotle and later Greek thinkers and observers, appears to have been a very great one, though Aristotle unfortunately put his teaching into a form essentially similar to that of vitalism.

It seems to me that the attitude of Hippocrates was, and is, the only attitude possible in scientific biology. What we may call the Galilean or Newtonian conception of the visible and tangible universe assumes that the visible and tangible world consists of self-existent bodies, each of which is capable of acting on other self-existent bodies, and being acted on by them, but this mutual action being a mere accident in the self-existence of the bodies. The gradual development of this general conception in the eighteenth and nineteenth centuries seemed to show that the universe must be regarded as consisting of self-existent and eternally-existent atoms, and that the sum of their actions and reactions upon one another when expressed as energy is just as eternally self-existent and constant as the atoms themselves. Until the middle of the nineteenth century, however, the phenomena of heat and temperature were not brought under this conception. Scientific men, including, for instance, Lord Kelvin when he first came as Professor to Glasgow, still believed that heat is a substance. It was another great Scottish physicist, John James Waterston, who, as the late Lord Rayleigh, discovered through an unpublished paper in the Archives of the Royal Society, was the first to formulate clearly the modern conception of heat, gases, and temperature. On that conception a perfect gas is an absolutely chaotic assemblage of perfectly elastic molecules in very rapid motion, and clashing with one another in every possible way. Heat is just the chaotic kinetic energy or, as it was then called, vis viva of the molecules; and temperature varies with the mean vis viva of the molecules, absolute zero of temperature corresponding to a state in which the molecules would be at rest in relation to one another. Heat energy is thus chaotic energy. In liquids and solids the chaotic movements are restrained by blindly acting forces of attraction between the molecules, so that their energy is constantly passing from the kinetic into the potential form and back, in accordance with Mayer's conception; but the energy is still chaotic.

It is easy to see that not only heat energy, but ultimately speaking all visible and tangible activity of every kind, is chaotic on the Newtonian conception, unless this activity is in some way guided. It is also easy to see that since heat is constantly being produced by the mutual action on one another of larger masses, and this process is only incompletely reversible, the energy of the universe must be running down, on the Newtonian conception, towards a dead level of temperature. As actually the universe has not yet done this, we can argue, if we like, that it must have been created in time, just as we can argue, with Paley, that since living organisms are wonderful pieces of machinery which could not have arisen by chance, they must have been created—by an outside God who left the machinery to go to pieces in a chaotic world as all other machinery goes to pieces. Evidently, however, the implications of such an argument are essentially irreligious.

Waterston's writings, published or still unpublished, are so interesting and important that I have collected them together, and they are in course of publication.1 Among them is an essay on “The Mental Functions.” His early studies were mainly in the direction of physiology and psychology, and in this essay he discusses, as Descartes had done two centuries earlier, to what extent a living organism or conscious person can be interpreted on physico-chemical principles. He goes as far as it seems possible to go in this direction; but, unlike Descartes, he realizes the actual nature of his task and sees that the co-ordination which manifests itself in both physiological and psychological phenomena cannot be interpreted physically, unless, indeed, the physical world is something different from what, on the Newtonian interpretation, it appears to be.

In claiming that the mechanical interpretation of visible reality is a “philosophical” interpretation, Newton practically claimed that the mechanical interpretation represents that reality. The real ground for this claim is that with the help of the mechanical interpretation we can predict phenomena with, on the whole, wonderful success in the inorganic world. But we cannot do so in the organic world; and even in the inorganic world the success is only a limited one, as was pointed out in the first lecture.2

In the organic world of life we find that structure and activity cannot be separated from one another. The structure is alive, and in destroying life we also destroy the molecular structure in which it manifests itself. Moreover, we cannot separate living structure from its encircling environment or prevent the living structure from reproducing that environment if we partially remove it without destroying life. Between living structure and its environment we can draw no distinct line such as we seem to be able to draw between an inorganic body and its environment. The parts, including environment involved in life, and the activities which manifest themselves in the parts, are evidently so related that for each the others are pre-supposed. We can only regard them as organized manifestations of a persistent whole; and in particular we cannot, even in thought, separate the structure from the activity or from the environment and its influence, unless we entirely neglect what actual observation shows us to be their real characters. With lifeless structure, or the lifeless body of an organism, it is different. From the hieroglyphics written in the lifeless structure we can, it is true, infer much about the life which was manifested in the living structure; but this is only indirect inference. We cannot possibly examine separately the parts involved in life as we examine separately the parts of a machine. In particular we cannot separate the influence of the environment, since environment belongs to the unity which we perceive as life.

It is thus not sufficient to regard life from the mere abstract standpoint of mass and energy. This abstract standpoint takes no account of the fact that in life mass is maintained in the specific form of structure by corresponding specific activity. It is the recognition of this fact which distinguishes biology from the mechanical sciences of the Newtonian philosophy; and in biology the conceptions of inertial mass and energy are replaced by that of active organic maintenance.

Since living structure and environment cannot be separated, different centres of life must, and do, run into one another, as in the case of the lives of individual cells in different tissues of a higher animal or plant. But the resulting life is no mere sum of individual lives. Each local centre of life is necessarily modified in accordance with the altered environment due to the presence of other centres, and the resulting complex life is no less an organized unity than each centre would be by itself. In communities of separate animals, plants, or unicellular organisms, we see the same thing, though on a less striking scale. The result of the fusion of many lives is still only one life, though in this one life there is full representation of each of its constituent lives.

Within, or surrounded by, living structure we find what we can only interpret as deposits of liquid, solid, or gaseous material, though these deposits are organically determined as regards their composition and amount, and sometimes very exactly, as in the case of supporting material, or the blood, or the alveolar air in the lungs. In so far as they are organically determined, but no further, we can treat them as part of the living structure or its physiological environment.

Outside the living structure and its immediate environment is what we interpret on Newtonian principles as the physical and chemical environment. In so far as this is indifferent to life, it does not concern biology; but in so far as it enters into life, its action upon organisms and their action upon it are organically determined, just like other life-processes. The influence of environment through sense-organs and in other ways is evidently co-ordinated organically. In the case of light, for instance, brightness and colour are evidently under complete organic control; and the physiology of vision deals with this control, which is not intelligible physically, as Locke saw clearly when he discussed “secondary qualities.” Whether or not, or how, an organism responds to what, from the physical standpoint, is a physical action upon it, depends on organic control. The action, regarded as mere physical action, may prove to be a positive or negative specific stimulus, or may evoke no response at all; but whatever the result, the physiological reaction is normally under organic coordination, and only intelligible as part of an organized activity. It is this organic co-ordination which biology deals with. Quite evidently, biology does not claim to be a general philosophy of Nature, and only deals with life.

Living organized structure and activity are just as visible and tangible to us as mechanical structure and action. In biological observation, and in arts such as medicine, dependent on biological observation, it is visible and tangible organized structure and activity that we are dealing with, and our interpretations must be in terms of that structure and activity. As biologists, and realizing the nature of our observations, and their essential difference from observations which can be described and interpreted in mechanical terms, we must, following Hippocrates, insist firmly on biological interpretation, without which our observations would become a veritable chaos.

Biology, whether on its physiological or morphological side, is nothing but the progressive discovery and elucidation of the maintenance of visible and tangible organized activity in living organisms. We can trace this progressive discovery and elucidation in the history of the two main branches and various subordinate branches of biological science. What we cannot trace, however, is any progress towards a comprehensive physico-chemical interpretation of biological observation. The attempts at this, such as the attempts of Descartes or of Schwann, have been gross and palpable failures. We can, it is true, make great use of physico-chemical interpretations where we are dealing with phenomena artificially isolated from their biological context. The driving of blood through the blood-vessels, of air into and out of the lungs, or the solution of food-material in the alimentary canal, can be, for instance, when they are considered in isolation from the conditions which determine them, interpreted as simply physical and chemical processes; but in such processes the general organic determination is not only evident, but is every year becoming more and more evident as regards detail. In so far as we neglect this organic determination we are neither biologists nor physiologists, but simply physicists or chemists.

It seems to me very important for biologists and for all those engaged in arts which are concerned with life, whether animal or vegetable, to realize that they are dealing with what can only be interpreted generally as the specifically co-ordinated and persistent phenomenon which we call life.

Let me illustrate this from investigations in which I have myself been concerned. Twenty-five years ago the physiology of breathing was in a very confused position. On the one hand, it was known that both deficiency in the oxygen concentration and excess in the carbon dioxide concentration of the air within the lungs lead to an increase of the breathing, and that excessive voluntary or artificially produced breathing leads to the cessation of spontaneous breathing known as apnoea. Thus we could apparently understand why it is that when more oxygen is used up in the body, and more carbon dioxide produced, as in muscular exertion, the breathing is increased.

On the other hand, however, it had been concluded, on apparently good experimental evidence, that breathing is also regulated independently by nervous impulses passing up the vagus nerves which supply the lungs, impulses which stop the breathing being liberated by distention of the lungs with air, and impulses which produce inspiratory effort, or cessation of impulses which stop it, being caused by collapse of the lungs. It was found also that apnoea could be produced, even with air containing a very low oxygen percentage. The apnoea produced in this way, or by simple distension of the lungs, was known as “vagus apnoea.” It had also been found in some experiments that during, and for long after, muscular exertion the breathing was increased, though less carbon dioxide and quite as much oxygen were present in the blood and the expired air.

There thus seemed to be at least two sets of influences, essentially independent of one another, affecting the breathing, and apparently tending to conflict with one another, since the increased breathing produced by muscular exertion or in other ways would tend, apparently, to produce vagus apnoea, and the influence of the vagus nerves would in general appear to be restricting the depth of breathing. In any case, the influence of the vagus nerves seemed not to be co-ordinated in any way with the supply of oxygen to, and removal of carbon dioxide from, the body.

What struck me was that this is not the way of a living organism, and from my student days I had rejected the mechanistic standpoint in physiology. The experimental evidence seemed not really satisfactory, so I set about, along with scientific friends, to clear it up, and it took many years to do this at all completely. In the first place, we showed that in ordinary breathing the depth and frequency, or either separately, are so regulated as to maintain an extremely constant pressure of carbon dioxide in the air of the lung alveoli, a method for the direct investigation of which I had devised. The arterial blood which leaves the lungs is evidently saturated with carbon dioxide to a diffusion pressure corresponding to the concentration of carbon dioxide in the alveolar air, and this diffusion pressure, acting through the circulating blood on the nervous centres in the brain, determines the nervous respiratory impulses. As already mentioned, we can go further still: it is the “reaction,” or hydrogen ion diffusion pressure, as affected by the diffusion pressure of carbon dioxide, which determines the nervous impulses; and this enables us to understand how it is that the breathing is sometimes increased though the pressure of carbon dioxide in the arterial blood is low. The cause of the true apnoea which follows over-ventilation of the lungs is simply the washing-out of too much carbon dioxide from the arterial blood, and there is no other cause. It requires only an extremely slight extra washing-out to produce complete apnoea; and even when the oxygen percentage of the alveolar air is very low the apnoea is easily produced, though not so easily as with a normal oxygen percentage.

The apparent apnoea produced through the vagus nerves on distension of the lungs is not apnoea at all, but only suspension of inspiratory action, while expiratory action is not only present, but constantly increasing. We do not record this expiratory action if we only record the action of an inspiratory muscle such as the diaphragm; and this led to a mistaken interpretation. There is, in fact, no such thing as vagus apnoea. We found, moreover, that the action of the vagus nerve in arresting or “inhibiting” inspiratory effort is completely under the control of the action of carbon dioxide on the nerve-centres in the brain. The action of the vagus nerves is, in actual fact, such as to regulate the depth and frequency of the breathing in accordance with the strength of the chemical respiratory stimuli, so that the action of the vagus nerves is in complete coordination with that of the chemical stimuli; and these bring the breathing into co-ordination with the activities of every part of the body.

We thus seem to have what could be described in the language which is at present customary as a “beautifully co-ordinated mechanism” for keeping the composition of the arterial blood constant as regards its diffusion pressure of carbon dioxide, and consequently also of oxygen. We might call it the “mechanism of breathing.” Although, however, it is beautifully coordinated, it is not mechanism. The reasons for this conclusion are as follows. In the first place, there is no definite chain of physico-chemical causation between a certain definite hydrogen ion pressure or deficient oxygen pressure and the activity of the nerve-centre in the brain. If we ask why the centre should act more vigorously or become quiescent according as the hydrogen ion pressure rises or falls to an extent so minute that it can hardly be detected by physical or chemical means, there is no physical or chemical answer. In the second place, the reaction, and with it the structure of all the tissues concerned in giving effect to the reaction, and in exciting it in a normal manner, remain constant day after day and year after year, in spite of the extreme lability of the living structures concerned. They are evidently maintained actively, and they have developed actively with the organism itself. It is the old story: we have discovered highly co-ordinated activity; but if we attribute the co-ordination to complexity of structure, then we are at once faced by the question how this complex structure is maintained, and by what mechanism it has been developed from a germ in which it was not present.

The co-ordinated behaviour and co-ordinated structure cannot be expressed in terms of an essentially chaotic physico-chemical world: they are just a part of Nature, as Hippocrates taught. Though inorganic Nature may appear to us through Newtonian spectacles as if she were chaotic, these spectacles blur our vision when we study biological phenomena, so that we do not see what are otherwise evident facts.

Let me take another instance—that of the process of acclimatization—from the physiology of respiration. At a low barometric pressure, such as exists at high altitudes, the concentration of oxygen molecules, and consequently the pressure which they exercise, is diminished. Other things being equal, the partial pressure of oxygen in the lung alveoli, and consequently in the arterial blood, tends to fall to a still greater relative extent. The natural response is excitation of the respiratory nerve-centres and increase of the breathing; but, as was pointed out in the third lecture, anything like a full response in this direction is for some time prevented, owing to the fact that if the breathing, or the rate of circulation, is increased, the pressure of carbon dioxide becomes lowered, which tends to diminish the breathing and circulation by lowering the hydrogen ion concentration of the blood. To this lowering, however, the kidneys respond in the normal manner by gradually excreting alkali, so that, as the man becomes acclimatized, a nearly full respiratory response to the lowered oxygen pressure becomes possible, and the breathing can become considerably increased.

At the same time there is another gradual response, discovered many years ago. The percentage of haemoglobin in the blood is increased, and this tends to diminish the fall in oxygen pressure which would otherwise occur in the systematic capillaries. As has quite recently been shown very clearly by Argyll Campbell,3 the percentage of haemoglobin in the blood goes up and down in inverse proportion to the oxygen pressure in the arterial blood. Both this reaction, and the change in blood composition owing to excretion of alkali, show how closely the composition of the blood and the formation or elimination of its constituents are co-ordinated with the breathing.

Another and very interesting physiological reaction occurs during acclimatization. Between the air of the lung alveoli and the blood passing through the lungs there is a very delicate layer of living cells; and the question arose whether, in acclimatization to high altitudes, or under other conditions, this delicate layer takes any active part in driving oxygen inwards into the blood, or simply acts mechanically, like a non-living moist membrane, so that the oxygen passes in by simple diffusion. I had discovered a method of investigating this difficult question quantitatively; and one answer which our experiments gave was that during rest under normal conditions at anywhere near normal barometric pressure the mean oxygen pressure is exactly the same in the blood leaving the alveoli as in the alveolar air. There is thus no evidence of active secretion under normal resting conditions, and the intake of oxygen is apparently by simple diffusion. We can thus interpret the process as a mere mechanical one, though of course there is no mechanical explanation of how the amazingly delicate and highly co-ordinated structure of the lungs is maintained and developed.

After acclimatization at very high altitudes, however, as well as during muscular exertion and under conditions where symptoms of want of oxygen are produced, as in carbon monoxide poisoning, we found that the mean oxygen pressure of the blood leaving the alveoli is, during rest, very considerably above that in the alveolar air. Thus in the state of acclimatization the oxygen is pushed or secreted inwards actively, just as occurs in the case of the swim-bladder of deep-sea fishes, where the oxygen pressure inside the swim-bladder may be six hundred times that in the sea-water. Many of our experiments were performed after acclimatization on the summit of Pike's Peak in the Rocky Mountains, at a height of 14,100 feet. Apart from the existence of this active secretion along with the other changes already referred to, it seems quite impossible to explain the phenomena of acclimatization.4

The facts relating to acclimatization are very striking, and this has been greatly emphasized by the experiences of the recent Mount Everest expeditions. If a sedentary person living at about sea-level is rapidly transferred in a steel chamber to a barometric pressure corresponding to about 12,000 to 14,000 feet, and left there for a considerable time, nervous symptoms of a most formidable character, known as mountain sickness, show themselves, and may very seriously threaten life. That they are due simply to the diminished oxygen pressure of the air was shown clearly, about fifty years ago, by the French physiologist Paul Bert. But if the transition is gradual, or in not more than moderate steps over a considerable time, no symptoms at all are produced, or any symptoms which show themselves are quickly recovered from. This may hold good, as the Mount Everest experience showed, up to a height of at least 27,000 feet; whereas an unacclimatized person going rapidly to a similarly low barometric pressure in a steel chamber or balloon becomes soon unconscious, and would certainly die if left in the rarefied air.

It is known that during acclimatization the bone-marrow in which the red corpuscles and haemoglobin of the blood are developed becomes hypertrophied. Reasoning from analogy, we may also feel confident that a corresponding change occurs in the nervous and muscular tissues which are concerned in the increased breathing at high altitudes, and in the cells, probably of the lung capillaries, which are concerned in the secretion of oxygen. Thus not merely activity, but also living structure, is concerned in the acclimatization. This is so because life is maintained as a whole which is realized no less in structure than in activity; life is, in fact, just life.

The phenomena of acclimatization to a low oxygen pressure in the air are typical of endless other phenomena met with in the maintenance of life. The development of what is known as a condition of good physical training is another instance, as also is the development of acclimatization to heat—a subject which has interested me greatly. A very striking instance is the development of immunity. Pasteur, who, it seems to me, was a very great biologist though he was not trained as a biologist, rightly read the biological lesson of Jenner's discovery as to vaccination, and of the familiar fact that immunity from an infectious disease follows on recovery from it. This suggested to him the methods by which he was able to produce immunity, first to anthrax infection, and then to hydrophobia. The production of immunity to infection is on all-fours with the production of immunity to mountain sickness.

It is of the essence of our ordinary conception of life that it is an active manifestation of specific structure and activity. An organism therefore gets “acclimatized” or “accustomed” to what seems to stand in its way, and “heals” or reproduces its structure. In all normal physiological activities, including even the twitch of a muscle or the passage of a nerve impulse, there is a recuperative process or stage as well as a process or stage of disturbance, however short or long a time these processes or stages may last. The recuperative process tends to limit or resist the disturbance, and to become more powerful the greater or more frequent the disturbance, so that living structure grows and develops with use.

We can contrast the physiological behaviour of a man at a high altitude with the behaviour of an ordinary petrol engine. Whether we take the engine up very slowly or quickly it becomes more feeble as the height increases, since the mass of oxygen taken in at each stroke becomes less and less. The engine never becomes acclimatized. If we wish to make it work normally in the rarefied air we must so arrange that the air is compressed to about normal atmospheric pressure before it enters the carburettor; but the engine does not arrange this for itself. Neither does it repair itself when it is worn or injured: it is a machine and not a living organism.

In endeavouring to interpret living organisms as machines the mechanistic physiology which we have inherited from last century has distorted our ordinary observation and directed attention away from obvious facts. This physiology has thus failed to give to scientific medicine the help which it ought to give, since it has nothing coherent to say about the co-ordination which is the distinguishing feature of life, or about the natural processes of resistance to disturbance and recovery from it. Consequently it throws no light on the manner in which the resistance and recovery are naturally carried out and can be aided by art. These subjects are necessarily ignored, because they are incapable of being stated in terms of the mechanistic interpretation. The body is treated as if it were simply an extremely complex and delicate piece of molecular machinery—so delicate and complex that it seems hopeless for us to interfere when it has gone out of order. Not this interpretation and attitude, but the interpretation and attitude which Hippocrates indicated, has been justified by the progress of scientific medicine.

It is upon what we can actually observe that we must base our conception of life and our scientific treatment of it; and the co-ordination of the structure and activity which we observe in the life of an organism is evidently of its very essence. The whole is alike in the parts and their influence on one another, including the influence of environment; and this is how we perceive and understand living organisms when we perceive and understand them as alive. It seems to me that once for all we must firmly take up the position that for biology the Newtonian “philosophy” is an impossible scientific basis, since it does not correspond with what is visible and tangible in the organic world.

I have maintained this position as consistently as I could for many years. In a presidential address which I delivered before the physiological section of the British Association in 1908 my conclusion was “that in physiology, and biology generally, we are dealing with phenomena which, so far as our present knowledge goes, not only differ in complexity, but differ in kind, from physical and chemical phenomena; and that the fundamental working hypothesis of physiology must differ correspondingly from those of physics and chemistry. That a meeting-point between biology and the physical sciences may at some time be found, there is no reason to doubt. But we may confidently predict that if that meeting-point is found, and one of the two sciences is swallowed up, that one will not be biology.”

When I wrote these words I could see no indication of a meeting-point being actually discovered. The new ideas which have recently been altering the fundamental aspect of the physical world had not yet taken very definite shape. It had not yet become clear that the Newtonian “philosophy” can no longer be regarded from the purely physical standpoint as representing a satisfactory fundamental working hypothesis in its application to inorganic phenomena. The outlook is now very different, as I indicated in the first lecture. The fundamental ideas of physicists seem to be approximating to biological ideas; and at any rate there is no longer any apparent sharp clash between fundamental physical observations and fundamental biological conceptions. The Newtonian conception, enormously useful as it actually is and seems likely to continue, is no longer a “philosophical” conception for physicists.

At the end of his discussion of the physically mysterious co-ordination which shows itself in organic and conscious behaviour, Waterston wrote eighty-five years ago that “we are led to expect that if molecular philosophy is ever destined to advance into the region of organization the phenomena of perceptive consciousness will admit of being applied to illustrate the physical aspect of the elementary powers of matter.”5 There was something prophetic in this remark.

If we ask Nature to reveal the mechanisms of life—for instance the mechanisms of respiration, secretion, circulation, vision, growth, or heredity—we are in reality endeavouring to distort her by the form of the question we are putting. She simply refuses to be distorted, and treats the question as a foolish one, to which there is no answer.

The very nomenclature of biology embodies the conception that life, in whatever form it may occur, occurs as a specific whole, in which the parts and actions are essentially related to one another, and cannot be isolated without destroying their nature. The working hypothesis of biology is that this wholeness exists, and this working hypothesis has carried biology forward just as successfully as the Newtonian conception has carried the physical sciences forward. Biologists are, and always have been, progressively tracing the specific co-ordination which shows itself in the structure, activities, and environment of living organisms. This co-ordination cannot be expressed in terms of ordinary physical and chemical conceptions. For this reason biology must be regarded as a distinct science or group of sciences. A biologist interprets his observations in a different manner from that of a physicist. This, of course, raises a philosophical question, which, however, must be postponed until the second course of lectures is reached.

• 1.

  They are now published under the title The Scientific Papers of John James Waterston, Oliver & Boyd, 1928.

• 2.

  While this book was passing through the press there appeared Professor Eddington's Gifford Lectures at Edinburgh in 1927 on The Nature of the Physical World. In these very striking lectures the ultimate limitations inherent in present conceptions of the inorganic world are very clearly pointed out.

• 3.

  Argyll Campbell, Journ. of Physiol., vol. lxii, p. 211.

• 4.

  Several physiologists have brought forward evidence which they regarded as contradicting these conclusions. My reasons for disagreeing with them are stated in an article which appeared in Physiological Reviews, 1927.

• 5.

  Collected Scientific Papers, 1928, p. 46.