Organism and Environment as Illustrated by the Physiology of Breathing

If we look, not merely at the internal, but also at the external activities of an organism Claude Bernard's generalisation seems still to hold. The co-ordinated activities of the senses and muscular system are mainly directed to the end of providing for nutrition. Behind and controlling these activities are the instinctive ex- citatory or inhibitory impulses which we know as hunger, thirst, satiety, discomfort and comfort. These impulses may be regarded as expressions of the many- sided activities which are all directed towards keeping the internal and external environment constant.

On examining the forms which vitalism has taken we find that the vital principle has been commonly regarded as an influence which resists the tendencies of physical and chemical influences to produce disin- tegration of the body structure. The great chemist Liebig, for example, looked at the oxidation processes in the body from this point of view, and regarded the vital force as something protecting the structure of the body from becoming the prey of oxidation.

But let us examine the whole matter more closely. It is quite evident that the activities of the various parts of the body are not merely in the direction of maintaining the internal environment constant, but also in the direction of disturbing it. The muscles by their activity may be engaged in obtaining nutriment for the body, but they are also consuming this nutri- ment wholesale. The kidneys are not merely remov- ing superfluous or harmful material from the blood, but they, too, are consuming oxygen and other sub- stances, and producing CO2 and other metabolic products. This is also true even of the lungs and the respiratory centre, for the respiratory centre is vio- lently excited by the products of its own oxidation if its blood supply is checked. Now when we examine those activities which tend to disturb the internal

environment we find that they are no less persistent than the activities which maintain its constancy. The muscles still continue to consume oxygen and form heat, even though they are for the time at rest, and though all loss of heat from them is prevented. The kidneys still absorb oxygen when they are not secret- ing. In a sense, too, they are still secreting, even when there is no external sign of secretion, for the absence of external secretion is only the expression of an equal balance between constant intake and constant output of material. When the muscles and sense-organs are not at work on the getting of food, or in other con- servative processes, they seem to employ themselves otherwise — for instance in what we know as play.

No physiological facts are more significant than those relating to the persistence of the fundamental metabolic phenomena. In Liebig's time it was observed that the excretion of urea rises and falls with the amount of nitrogenous food consumed, although dur- ing starvation there is still a certain minimum excre- tion of urea. This was interpreted as signifying that all superfluous nitrogenous food simply falls a prey to oxygen, and is wasted. When, however, the facts were further investigated it was found that within wide limits the oxidation in the body does not increase or diminish with increase or diminution of the nitrog- enous food consumed. Even after long starvation the oxygen consumption per unit of body weight is practically undiminished during rest. When more nitrogenous food is consumed in the body and oxidised to urea, less fat or carbohydrate is consumed.

Rubner showed that nitrogenous food, fat, and car- bohydrate are substituted for one another as material for oxidation in exact proportion to the energy which they yield in the body. The sum of this energy per unit of body weight remains constant during rest, whether food is given or withheld. Even when loss of heat is prevented as far as possible, the oxidation pro- cesses in the body remain sensibly constant in spite of prolonged deprivation of food. The diminished oxida- tion of nitrogenous material during starvation depends simply on the fact that the body stores its energy- forming material mainly as fat, and consequently uses up mainly fat during starvation. When all the fat is exhausted there is again, before death from starva- tion, a great increase in the oxidation of nitrogenous material. This latter fact adds new emphasis to the persistence of the oxidation processes.

The internal environment which is maintained so constant is in reality the expression of a balance be- tween activities which disturb and activities which restore it. When we speak of "the function" of an organ and regard this function as what it does to restore the internal environment we are thinking in terms of an imperfect and misleading conception of what that organ is, and what an organism is : for we are thinking of only one side of its activities to the exclusion of others which are just as important. To put this into philosophical language we are thinking abstractly, or regarding only a part of the reality we are dealing with. We can speak more correctly of

the function of a part of a machine: for this part does nothing else than fulfil its function, provided the machine is assumed to be perfect and stable. In a living organ however we are dealing with something of which the functions, if we speak of functions, are endless, since the activities are endless, constantly seeming to grow in number as we investigate further. Its true function, to the eye of a physiologist, is to maintain these endless activities in balance with the endless activities of other organs, and not merely to perform one specified action.

It is evident that the balancing of molecular activi- ties on which the maintenance of the internal environ- ment depends is centred in the bodies of the cells which make up the living tissues. The composition and volume of the blood are the outcome of their joint active or passive influences. We are thus brought back to the problems of cell-secretion, cell-respiration, cell-nutrition, cell-movement, cell-heat-production — problems which, as we have already seen, are only different aspects of one problem — that of what may be called cell-metabolism. Living cells are the nodal points of the molecular and ionic streams of which one outcome is the constant internal environment. The living cells are the seat of the molecular or ionic accelerations or retardations which manifest them- selves in secretion, and of the main chemical changes which express themselves as metabolism in its varied outward forms. When we concentrate attention ex- clusively on some one detail of cell-metabolism we

necessarily lose sight of the co-ordination which ex- presses itself in the persistence or constancy of cell- structure and of the internal environment. But the co-ordination is plain when we look at the phenomena as a whole, and becomes more and more detailed the more we penetrate towards the living tissue elements. The phenomena of breathing have turned out to be the outward expression of one side of the co-ordinated activities which we lump together under the name of metabolism. Our conception of breathing depends, therefore, on the ideas we can form of this metabolism.

At the conclusion of this lecture let us glance at what may be called physiological causation. All physi- ological activities seem to be in response to external or internal causes or "stimuli." Physiologists speak of a "stimulus" rather than a "cause," since the word "stimulus" expresses the fact that other external con- ditions determine the response besides the stimulus itself. The response depends, not merely on the strength of the stimulus, but on the "excitability" of the responding tissue. In other words the response may be partially or wholly inhibited or greatly in- creased by varying conditions in the environment of the tissue. The character or direction of the response may also depend on these conditions, or even on the strength of the stimulus itself.

As has been already shown, the respiratory centre normally responds with rhythmic inspiratory and ex- piratory responses to the stimulus of a very minute diminution in the alkalinity of the blood. But the duration of the responses is modified by stimuli de- pendent on inflation or deflation of the lungs, while the extent of inflation or deflation which is effective in this direction depends on the strength of the primary chemical stimulus. The effect of this primary stimulus is also dependent on the supply of oxygen to the centre, and is increased if the oxygen supply is defective. If we prefer to put the matter in another way, deficiency of oxygen is itself a stimulus to the centre, but is dependent for its effect on the reaction of the blood, and is quite ineffective if the alkalinity increases slightly. Other substances, such as morphia, chloral, or chloroform, diminish the responses of the centre to a given diminution in blood alkalinity ; and from the analogy of other tissues we may be quite sure that slight changes in the concentration of the salts and other substances in the blood, or changes in its temperature, must similarly affect the response of the centre in one direction or another. We can even imagine the respiratory centre responding, not, as normally, to changes in alkalinity, but to changes in the concentration of, say, calcium salts.

When we seek for the "cause" of a physiological reaction we are thus landed in a maze of contributory causes. We can wander in this maze for as long as we like, but there is no end to it. So far as it is possible to judge, those who seek in physiological phenomena for the same kind of causal explanations as can usually be assigned in connection with inorganic phe- nomena have no prospect but to remain seeking indefi- nitely, unless they cut the knot by relapsing into vital- ism.

But is there no scientific clue through this apparent maze? Does not the element of regulation which, as we have seen throughout, is the outstanding feature of biological phenomena, furnish the clue? In the next lecture this question will be discussed. In the previous lecture we saw that the internal environment is kept constant as the result of a con- tinuous and extraordinarily delicate regulation of the balance between opposing activities. What general conception can we form of this balancing process?

An obvious possible interpretation is that each of the various organs concerned in the balancing process has such a physical and chemical structure that it reacts to a given small deviation in the internal en- vironment so as to prevent further deviation in this direction. As the combined result of the reactions of all the organs the internal environment as a whole remains constant. It is evident, for Instance, that the respiratory centre reacts to very small differences In the hydrogen Ion concentration In the blood, In such a way as to prevent larger differences from occurring. The temperature-regulating centre reacts to small dif- ferences in the blood-temperature. The kidneys react in a similar way to very small differences In the con- centrations of water, urea, and numerous other inor-

ganic or organic substances. The organs, such as the liver, or fat-containing tissues, in which material is stored, appear to behave similarly; and we have now every reason to believe that we should find the same regulating activity in every organ or part of the body if our methods of investigation were sufficiently deli- cate, and we knew the small differences to be detected. In every direction the progress of physiology and pathology is revealing the astounding delicacy and complication of the regulating processes.

Up to a certain point we can rest satisfied in the idea that the regulation of the internal medium de- pends upon the specific structures and corresponding reactions of the organs which bring about the regula- tion. But the more we learn about the delicacy and complexity of the regulating processes, the more defi- nitely does a difficulty appear. It is not for nothing that the body regulates its internal environment so exactly. The investigations which reveal the exacti- tude of the regulation reveal equally its fundamental importance to the nutrition and normal working of every part of the body. The organs and tissues which regulate the internal environment are themselves centres of nutritional activity, dependent from moment to moment on their environment. They are constantly taking up and giving off material of many sorts, and their "structure" is nothing but the appearance taken by this flow of material through them. The fact has already been referred to that when the supply of oxygen to the tissues is seriously restricted the result is not merely a slowing down of activity, but actual

structural change. Similar structural change is known to result from many other slight alterations in the composition of the blood; and so far as the evidence goes, it points to the conclusion that the specific struc- ture of every part of the body depends upon the spe- cific composition of the blood, as well as on the influ- ence of the adjacent tissues or external environment. The regulation by the tissues and organs of the inter- nal environment is thus only their regulation of their own structure and activity.

A living organism has, in truth, but little resemblance to an ordinary machine. The individual parts of the latter are stable, within very wide limits of immediate environment, and in no way dependent on whether the machine is in action or at rest. This stability does not exist in the living organism. We find, it is true, that the living organism may react in a constant man- ner to a given change, just as a machine might do ; but on investigation this turns out to be because the inter- nal environment is at the time constant or "normal," Were it otherwise not even the superficial resemblance would hold. As we have seen, for example, in the case of the respiratory centre, this reasoning applies to nervous reactions just as much as to other physi- ological reactions.

It seems clear, therefore, that we cannot base our explanation of the constancy of the internal environ- ment on the structure of the organs which regulate it, since closer examination shows that the "structure" of these organs is itself dependent on the constancy of the internal environment. We are only reasoning in a circle when we attempt to explain the constancy of the internal environment by the specific characters of bodily structure. The fact is that both the internal environment and the "structure" of the body remain approximately constant; but of this fact no explana- tion has been reached.

The explanation cannot lie in the external environ- ment, since this is far less constant than the internal environment, which it constantly tends to disturb. It is nevertheless the case that the external environ- ment, in so far as it is in relation with the organism, exhibits constancy. The composition and amount of the food and drink in the alimentary canal approxi- mate to a certain average; the partial pressures of oxygen and carbon dioxide in the air which is in contact with the body, in the lungs, remain also nearly constant under most conditions ; the impressions trans- mitted inwards from without are similarly more or less constant on an average ; and excesses of heat or cold are generally avoided. Just as the internal en- vironment seems, at first sight, to be regulated by the organism, so also does the external environment, but to a far less intimate extent. In both external and internal environment, the regulation is the expression of a balancing of opposing processes of loss or gain of material or energy ; and the processes involving loss are no less persistent on the whole than those involving gain.

It is mainly through the nervous system that the body is, in the higher organisms, in relation with the external environment. When we look broadly at the activities of the nervous system, they are evidently of such a character that the external environment, is regulated just as is the internal environment. It is in virtue of these nervous activities that the stream of material and energy which is constantly entering and leaving the body is kept so nearly constant. Appetite and satiety, muscular activity and fatigue, external temperature and heat loss, external light or sound or other sensory stimuli and the responses to them, are balanced against one another through the nervous system. We cannot draw any complete line of separation between the regulation of the internal and that of the external environment; for evidently the one is complementary to, and indispensable to, the other. Regulation of the external environment is in fact only the outward extension of regulation of the internal environment, and the ultimate de- pendence on the external environment of the organs which regulate it is as evident as their more immediate dependence on the internal environment. Deficiency or excess in normal stimuli, normal nutrition, normal temperature and respiratory exchange, are as impor- tant to the nervous system as to other organs. The environment determines the nervous reactions, and the nervous reactions the environment, but the constancy or regulation which emerges is still unexplained. The conception of an organism as a mere labile structure which determines, and is at the same time determined by, its environment is unsatisfactory, for the reason that the specific persistence of life is left unaccounted for. The facts must be examined more closely.

We have seen that it is characteristic of an organ- ism to react towards disturbing influences in such a way as to maintain approximate constancy in its struc- ture, internal environment, and even external environ- ment. If the disturbance is merely slight, temporary, and of normal occurrence, a simple and normal com- pensating reaction occurs, and everything seems after- wards to return again to its former state. But if the disturbance is abnormal, or continued, a significant fact emerges more and more clearly : for new and apparently original compensatory reactions arise, or an ordinary compensatory reaction is greatly strength- ened, or supplemented. The new reaction is accom- panied by corresponding structural change, which re- mains to a greater or less extent after the cause of distuibance has disappeared.

We are now in contact with facts of a sort which tend to lie in the background in connection with the customary laboratory physiology of the present time, but which spring into such prominence in common everyday observation, and particularly in connection with clinical medicine and surgery, as to make the physiology of ordinary text-books appear somewhat unreal. In the course of these lectures various facts of the class here referred to have been described. The Anglo-American expedition to Pike's Peak was undertaken with the express object of ascertaining to what extent, and in what manner, the body adapts itself to a continued diminished concentration of oxy- gen in the air breathed. The results showed that new adaptations, apart from those demonstrable during

short exposures, come into play during prolonged ex- posure to a diminished oxygen concentration. Another striking instance of the same class of fact is in con- nection with the effects, referred to in the previous lecture, of repeated bleeding or transfusion of blood, as observed by Boycott and Douglas. After repeated bleedings the animal replaces the lost blood with increasing rapidity. After repeated transfusions it gets rid of the excess with corresponding readiness. Presumably in the one case there is an increase in the amount or activity of the blood-forming tissues, and in the other an increase of the blood-destroying tissues.

We have only to look round, outside the limits of the present conventional physiology, in order to find innumerable instances of similar facts. Striking ex- amples are afforded by the phenomena of immunity to attacks by micro-organisms, and to the action of poisons. Still more remarkable instances are those connected with the recovery of function or reproduc- tion of tissue after injury or disease, or even complete loss of parts of the body. In the higher organisms reproduction of lost parts is a less prominent feature than in lower organisms, but indirect restoration of function is a fact of common observation, and is in some ways more significant and remarkable.

It thus appears that with disturbance of external or internal environment, or living structure, the reactions which occur are, whether immediate or gradual, of such a character that the organism adapts itself so as to maintain, not merely its existence as a structure, but also its characteristic activities and relations to exter- nal environment. The life of the organism may be modified, it is true ; but in the modification it retains all its essential characteristics, so that its identity is un- mistakable. It persists actively, and not merely pas- sively. Without active adaptation everything would tend to go from bad to worse, as in the case of an untended machine.

If the internal environment is interfered with, as by loss of material or the introduction of foreign or super- fluous material, the occurrence of adaptive changes is evident. If the structural elements of the body are interfered with, as in local injuries or infective attacks, processes of repair soon manifest themselves at the damaged point: the leaky and paralysed blood-vessels become functionally competent again : exuded material is absorbed ; and the altered and functionally abnormal tissue elements and nerve-endings return to a normal condition. We are gradually coming to realise how intensely delicate is the adjustment of immediate internal environment and organised structure involved in the existence of normal conditions, and the more we realise this the more significant appears the process of recovery or adaptation. Another point with regard to this process is that if injury has not gone too far the restored tissues have become more resistant. It is, for instance, a well-known fact that the blisters and other signs of local injury produced by unaccustomed hard use of the hands or feet are no longer produced after "hardening" by practice. The tissues have become adapted to the new conditions, and the adaptation is

no mere "functional" change, but is also "structural," as shown, for instance, by thickening of the epithelium. When structural elements are destroyed or actually removed, the process of reproduction is limited in the higher organisms. We then observe the phenomenon of other parts with similar function taking on the special functions of the lost part. Gradual recovery owing to other parts performing missing functions is a matter of everyday experience in Medicine and Sur- gery ; and though the evidence is to a large extent still indirect, we cannot doubt that in all such cases struc- tural changes are associated with the functional adap- tation. The phenomena of vicarious function are also quite clearly adaptive changes, i.e., changes of such a nature that the life of the organism maintains as a whole its identity.

When one regards the facts of memory from the purely physiological standpoint it is evident that memory is a phenomenon of the same nature as adap- tation. An experience or effort which has been gone through leaves its mark in the body as increased power of reaction to a similar experience or performance of a similar effort, just as an attack of an infectious disease, or vaccination, leaves its mark in a power of quickly repelling a similar infection. Were it not so memory would be a useless incumbrance.