Organism and Environment as Illustrated by the Physiology of Breathing

ELECTRICITY AND MATTER. By Joseph John Thomson, d.sc, ll.d., PH.D., F.R.S., Fellow of Trinity College and Cavendish Professor of Experimental Physics, Cambridge University . THE INTEGRATIVE ACTION OF THE NERVOUS SYSTEM. By Charles S. Sherrington, d.sc, m.d., hon. ll.d. tor., f.r.s., Holt Pro- fessor of Physiology, University of Liverpool. RADIOACTIVE TRANSFORMATIONS. By Ernest Rutherford, d.sc, LL.D., F.R.S., MacdonaldProfessor of Physics, McCrill University.

MODYNAMICS TO CHEMISTRY. By Dr. Walther Nernst, Pro- fessor and Director of the Institute of Physical Chemistry in the University of Berlin. PROBLEMS OF GENETICS, ^t/ William Bateson, m.a., f.r.s.. Director of the John Innes Horticultural Institution, Merton Park, Surrey, England. STELLAR MOTIONS. With Special Reference to Motions Determined by Means of the Spectrograph. By William Wallace Campbell, scd., LL.D., Director of the Lick Observatory, University of California.

THEORIES OF SOLUTIONS. By Svante Arrhenius, ph.d., scd., m.d.. Director of the Physico-Chemical Department of the Nobel Institute, Stockholm, Sweden. IRRITABILITY. A Physiological Analysis of the General Effect of Stimuli in Living Substances. By Max Verworn, m.d., ph.d.. Pro- fessor at Bonn Physiological Institute. PROBLEMS OF AMERICAN GEOLOGY. By William North Rice, Frank D. Adams, Arthur P. Coleman, Charles D. Walcott, Waldemar LiNDGREN, Frederick Leslie Ransome, and William D. Matthew.

{Second printing.) Price $5.00 net. THE PROBLEM OF VOLCANISM. By Joseph Paxson Iddinos, ph.b., PHYSIOLOGY OF BREATHING. By John Scott Haldane, m.d., LL.D., F. R. s., Fellow of New College, Oxford University. In the year 1883 a legacy of eighty thousand dollars was left to the President and Fellows of Yale College in the city of New Haven, to be held in trust, as a gift from her children, in memory of their beloved and honored mother, Mrs. Hepsa Ely Silliman.

On this foundation Yale College was requested and directed to establish an annual course of lectures de- signed to illustrate the presence and providence, the wisdom and goodness of God, as manifested in the natural and moral world. These were to be designated as the Mrs. Hepsa Ely Silliman Memorial Lectures. It was the belief of the testator that any orderly presentation of the facts of nature or history con-, tributed to the end of this foundation more effectively than any attempt to emphasize the elements of doctrine or of creed; and he therefore provided that lectures on dogmatic or polemical theology should be excluded from the scope of this foundation, and that the sub- jects should be selected rather from the domains of natural science and history, giving special prominence to astronomy, chemistry, geology, and anatomy.

It was further directed that each annual course should be made the basis of a volume to form part of a series constituting a memorial to Mrs. SiUiman. The memorial fund came into the possession of the Cor- poration of Yale University in the year 1901 ; and the present volume constitutes the thirteenth of the series of memorial lectures. Yale University did me the great honour of inviting me to deliver the Silliman Lectures for 1915. Owing to the war I was unable to give the lectures in the ap- pointed year ; and I must first of all thank the Univer- sity for permitting me to postpone them till the present time.

The subject of the full lectures, as they will, I hope, before long appear in book form under the imprint of the Yale University Press, is the Physiology of Breath- ing. Much of the material contained in them is, how- ever, of a technical character, hardly suited for public lectures. With the approval of the President, I have therefore delivered the following four public lectures confined to points of more general interest, the nature of which is indicated by the title.

The problem presented by the co-ordinated main- tenance of reactions between organism and environ- ment— Vitalistic and Mechanistic attempts at explana- tion. Alveolar air and the exact regulation of its CO^ percentage. Effects of breathing compressed air in diving and tunnelling. Co-ordination of the responses to central and periph- eral nervous stimuli, so that the respiratory apparatus acts as a whole. The combinations of COg in the blood and their dissociation.

Effects of oxygenation of haemoglobin on the disso- ciation of COg. ^^* -^■- i^ Extreme delicacy of the physiological regulation of the blood reaction. Regulation of the blood-reaction by the lungs, liver, and kidneys. Acclimatisation to oxygen want: — the Anglo-Ameri- can Expedition to Pike's Peak in 1911. Acclimatisation effects on the haemoglobin percent- age and blood-volume. Acclimatisation effects on active secretion inwards of oxygen by the lungs.

III. Regulation of the Environment, Inter- nal AND External 61 Evidence that this control depends upon the metabo- lism of the tissues. Evidence that the heart's action in pumping blood depends on the same conditions. In reality the constancy of the internal or external environment is a balance between disturbing and re- storing influences, each of which persists. The ordinary idea of "function" in an organ is mis- leading. "Causes" and "stimuli." Physiology as an endless maze of causes.

IV. Organic Regulation as the Essence of Life. Inadequacy of Mechanistic Examination of mechanistic interpretation of regula- tion of the environment. In life the whole is in the parts and the past is in the present. Organism, environment, and life-history can- not be separated. Relation of physiological to physical and chemical investigation of organisms. The limitations of existing physical and chemical conceptions. Vitalism the inevitable accompaniment of attempted mechanistic interpretations of life.

Animal physiology deals with the activities ob- served in living animals, including men; but under certain limitations. It deals in the first place with all the activities which are unconscious, such as diges- tion, circulation of the blood, secretion, or the growth and maintenance of the tissues. It deals, also, with the unconscious element in conscious action. I may, for instance, breathe consciously, or move my pen in writing, or hear the noise which it makes ; but of the details involved in any of these acts I have no direct consciousness. They are only revealed by experi- mental physiology. Physiology deals, also, with the sensations, impulses, and instincts of all kinds which appear in consciousness ; but does not deal with the meaning and conscious control which are attached to them. It does not deal with this meaning and con- scious control for the very good reason that the facts relating to them cannot be combined with the other material of physiology into a homogeneous sys- tem of scientific knowledge. If, however, the mean- ing and conscious control attached to sensation and instinct are disregarded, the latter can be treated as a part of physiology, and are so treated by physiologists.

regarded as a whole, it is evident that in the case of any given organism they are co-ordinated in such a way that the Hfe of the organism tends to maintain itself as a whole, or at any rate to fulfil its character- istic life-history. This applies not less to the reactions between the organism and its environment than to those between the parts of the organism. In the inorganic world as ordinarily observed and inter- preted we find no such co-ordinated maintenance. How are we to understand its presence in the organic world? This is of course a very old question; but I wish to reconsider it in these lectures in the light, more particularly, of the very rapid advances which have been made during the last few years in the physiology of breathing.

We are familiar with two opposing theories as to the nature of the co-ordination. One of these is that known as vitalism, which assumes that within the living body there is constantly at work a special influ- ence, the so-called "vital principle," which guides the blind physical and chemical reactions which would otherwise play havoc with the organism. The other is that the body is a very complex and delicate mechanism, so arranged as to bring about the co- ordination. According to one school this mechanism is the result of natural selection, though according to another its origin must be sought in special creation. I hope to be able to convince you that neither the vitalistic nor the mechanistic theory of the relation between organism and environment is tenable, and

that we must look to a more thorough and direct interpretation.^ Breathing is a form of physiological activity which goes on whether we are conscious of it or not. Only by a great effort can we suspend it for 30 or 40 sec- onds, and any hindrance to breathing is violently resisted. Although in the seventeenth century Mayow came very near to discovering the chemical changes in air during breathing, it was not till the latter half of the eighteenth century that these changes were understood. Black found that what we now call carbon dioxide is given off in breathing, and Priestley found that what we now call oxygen disappears as such. Lavoisier put these and many other facts together, and showed that just as in ordinary com- bustion of carbonaceous material, so in connection with respiration, oxygen combines with carbon and hydrogen to form carbon dioxide and water, and to liberate heat. Hence breathing is a process in which the essential factors are the conveyance of oxygen into the body, and the removal from it of carbon dioxide. Breathing can thus be compared to the supply of air to a fire and the carrying off by the air of the products of combustion.

'^ It has been suggested to me that if a convenient label is needed for the doctrine upheld in these lectures the word "organicism" might be employed. This word was formerly used in connection with the somewhat similar teaching of such men as Bichat, von Baer, and Claude Bernard. Cf. G. Delage, L'Heredite, Paris, 1903, p. 435. process does not occur to any appreciable extent in the lungs, but in the living tissues of the body gener- ally. Oxygen is taken up by the blood in the lungs, and thence carried by the circulation to every part of the body, the blood yielding its oxygen to the tissues in passing. Similarly the carbon dioxide formed is carried by the blood from the tissues to the lungs, where it is given off to the air breathed.

But another still more important point, often entirely missed in popular accounts of physiology, has appeared clearly. Within wide limits the oxidation process is practically independent of the abundance in supply of either oxygen or food material to the body. The amount of oxygen in the air breathed, or carried by the blood to the tissues, may be increased greatly without increasing the rate of oxidation; and even after long starvation the consumption of oxygen per unit of body weight remains about the same. The oxidation process is thus evidently very closely regu- lated, in the burning of a fire there is no such regu- lation unless it is artificially brought about. Although increase in the breathing does not cause increase in the rate of oxidation, yet it is evident that increase in breathing and in the rate of circulation accompanies increase in the rate of oxidation, as for instance during muscular exertion. Here again we have regulation coming in, but this time it is regulation of the air supply.

To account for the regulation the vitalistic theory presupposes the activity of the "vital principle" as a regulating agent which controls the consumption of oxygen and regulates the air-supply, thus playing the part of a stoker who regulates the supply of both fuel and air to a furnace. On the mechanistic theory the regulation is automatic, and due to the working of a mechanism connected with the fire. The latter theory is of course the orthodox one at present. It is not, however, these theories which I wish to discuss in these lectures, but the character of the facts which each of the two theories is an attempt to explain. When the true character of these facts is realised it seems to me that the old and ever recurring contro- versy between mechanists and vitalists disappears.

It has been known for more than a century that breathing is dependent on the integrity of a very small area of the brain in the medulla oblongata. When this area, known as the respiratory centre, is destroyed all signs of co-ordinated breathing efforts disappear. Severance of the nervous connections between this centre and the various respiratory muscles paralyses these muscles ; but so long as any connections are left respiratory efforts continue, and do so after severance of the connections between the centre and the higher parts of the brain. The action of this centre came to be regarded as automatic, inspiratory and expiratory impulses being alternately discharged from the centre down the motor or efferent nerves leading to the inspiratory or expiratory muscles, but no afferent impulses being required to liberate these rhythmic dis- charges. It was also found about the same time that any interference with the supply of properly aerated blood to the centre causes greatly increased activity

of the centre. A further very significant fact, ob- served originally by Hook in the seventeenth century, but forgotten and rediscovered by Rosenthal in 1875, is that if the blood in the lungs is over-aerated by artificial ventilation, the breathing stops for a time, the condition known as apnoea being established. It seemed, therefore, that just as increased breathing, or hyperpnoea, is due to defective aeration of the blood, so apnoea is due to excessive aeration. This interpre- tation of apnoea was soon challenged, as we shall see, but was firmly established by an ingenious experiment of Fredericq. He crossed the circulation of two animals, so that the blood coming from the lungs of the first animal passed to the respiratory centre of the second, and vice versa. It was then found that when excessive artificial ventilation was applied to the lungs of the first animal the second became apnoeic, or vice versa ; while great hyperpnoea in the first animal was produced by the stoppage of the breathing in the second.

When aeration of the blood is defective in the lungs two changes in the arterial blood occur. On the one hand its content in oxygen becomes less, and on the other hand it becomes more highly charged with carbon dioxide. Blood which is not aerated with oxygen has a dark purple tint, contrasting with the bright scarlet of fully aerated blood. This dif- ference in colour is due to the fact that haemoglobin, the substance which gives blood its colour and is contained in the red blood corpuscles, is the substance which carries nearly the whole of the oxygen, and

changes colour from a dark purple to bright scarlet when it takes up oxygen. The oxygen is taken up in the form of a weak chemical combination, the com- pound having the property of being stable only in presence of a certain concentration of free oxygen, and dissociating rapidly as the concentration of oxygen falls. The function fulfilled by haemoglobin as a car- rier of oxygen from the lungs to the tissues is thus readily intelligible, as well as the difference in colour between arterial and venous blood. Substances in the blood combine to form similar readily dissociable com- pounds with carbon dioxide, but no change in colour is associated with this process.

Both deficiency of oxygen and excess of carbon dioxide in the air were found to produce increase in the breathing, and till recently the respective parts played by oxygen and carbon dioxide in regulating the breathing were by no means clear, and opinions on the subject were divided. I was myself led to investigate the whole subject through observations on the effects of air vitiated by respiration or by the gases met with in coal-mines and other confined spaces.

When air highly vitiated by respiration or combus- tion of carbonaceous material is breathed the amount of air inspired or expired is increased. The increase is due to the carbon dioxide in the air ; for when this is removed there is no increase unless the deficiency of oxygen is extreme. The effect produced on the breath- ing by carbon dioxide in the inspired air increases out of proportion to increase in the percentage of the car- bon dioxide. This fact suggested that in ordinary

breathing the ventilation of the lungs is such as to keep the percentage of carbon dioxide approximately constant in the air which is in close contact with the blood in the small airspaces or alveoli inside the lungs. If this is so, it is clear that the nearer the percentage of carbon dioxide (CO2) in the inspired air approaches that in the lung alveoli the greater will be the quantity of air which must be breathed in order to keep the lung air normal in composition.

The matter was investigated a few years ago by Mr. Priestley and myself. We found that a sample of the alveolar air could easily be obtained by catch- ing the last parts of a deep breath expired through a tube, and that for any individual under normal condi- tions, the percentage of CO2 in this air remains prac- tically constant during rest. On the other hand the percentage of oxygen in the inspired and alveolar air could be varied within wide limits without affecting either the amount of air breathed or the percentage of CO2 in the alveolar air. It was only when the oxygen percentage fell very low that the breathing was increased. The percentage of CO2 in the alveolar air is not quite the same in different individuals, but the average is 5.6 per cent for adult men.

When air containing different percentages of CO2 was breathed it was found that the volume of air breathed was increased to such an extent as to keep the percentage of CO, in the alveolar air as nearly nor- mal as possible. Nevertheless there was always a very slight increase in the alveolar CO2 percentage with each increase in the breathing. For an increase of 100 per cent in the ventilation of the lungs over the normal resting ventilation there was an increase of about 0.2 per cent in the CO2 percentage in the alveolar air. Very accurate methods of sampling and gas analysis were of course needed in order to detect these differences. When the percentage of CO2 in the inspired air reaches about the normal percentage in the alveolar air there is extreme panting. With higher percentages a point is soon reached where the CO2 begins to produce abnormal effects, culminating in loss of consciousness. The breathing then quiets down to a large extent, and this quieting down of the breath- ing, as observed in animals, led formerly to a misinter- pretation of the effects of COg on the breathing.

If the breathing is by voluntary effort forced for a time, so as to reduce the percentage of CO2 in the alveolar air, a period of apnoea results. This effect depends entirely on the reduction of the percentage of CO2 in the alveolar air, for if the inspired air con- tains about 5 per cent of CO2 it is impossible to pro- duce apnoea by forced breathing, since under these conditions it is impossible to reduce the alveolar CO2 percentage below normal. Careful observations by Douglas and myself showed that it is only necessary to reduce the alveolar CO2 percentage by 0.2 per cent in order to produce apnoea. It thus appears that a rise of about 0.2 per cent in the alveolar CO2 percentage is sufficient to double the breathing, while a fall of 0.2 per cent produces cessation of breathing.

We are now in a position to understand, up to a certain point, how the breathing is regulated. The quantity of CO2 brought to the lungs by the blood is constantly varying in accordance with varying states of bodily activity. For instance during the exertion of walking at a moderate rate the quantity of CO2 brought to the lungs is three or four times what it is during rest. If the breathing did not increase correspondingly, the percentage of CO2 in the alveolar air would rise, and loss of consciousness would result. But with the slightest rise in the alveo- lar CO2 percentage the breathing begins to increase, and thus keeps down the alveolar CO2. When, there- fore, the production of CO2 is three times what it is during rest, the breathing is also increased to nearly three times what it is during rest. The alveolar CO2 percentage rises, it is true; but only by 0.4 per cent. This slight rise produces, as we have seen, an increase of 200 per cent in the breathing, so that the increase in breathing is almost proportional to the increase in the production of COo. Analysis of the alveolar air, and determination of the CO2 produced and volume of air breathed during rest and work show that this explanation works out in practice, provided that no disturbing causes come in.

As the oxygen percentage in the alveolar air runs parallel with the CO2 percentage, it is evident that regulation of the oxygen percentage is involved in regulation of the CO2 percentage. The net result is that both the percentage of oxygen and that of COo in the alveolar air are very constant, in spite of great changes in the amount of oxygen consumed and CO2 given off by the body. There is no doubt that it is through the blood that sHght changes in the CO2 percentage of the alveolar air affect the respiratory centre. The effects of these changes are equally rapid and marked when all the nervous connections between the lungs and the respir- atory centre are severed.