The History of the Study of Respiration

By
J. Murray Kinsman M.D.
Dean of University of Louisville
College of Medicine 1927
Presented to the Innominate Society

 

Respiration under natural conditions

The beginning of accurate knowledge concerning the physiology of breathing dates back to the 17th century. Before that time, the ideas if vogue about why and how we breathe were as mystical and strange as the conception of the circulation were paradoxical. As a matter of course, the latter directly influenced the former, as we shall see. Hippocrates “counted air as an instrument of the body,” just as food eaten was. Galen, whose influence on medical thought and progress was so tremendous and devastating for many centuries, enunciated the doctrine, which held away until observation began to replace speculation. In the Galenic Doctrine, the movements of respiration served a triple purpose:

                        First:      The air introduced by breathing served to cool and to regulate the innate
                                      heat of the heart; that fire which placed there at the beginning continued there all life long,
                                      and was the one source of the warmth of the body.

Second:  The pumping action of the chest served to introduce into the blood the air, which was necessary
                          for the generation in the left side of the heart of the vital spirits, which were thence distributed over
                          the body by the arteries.

Third:    The same action served to get rid of the friligimous, the products of the innate fire burning in the heart. Both
                         the pure air engendering the vital spirits and the foul vapors, the effect of the hearts labors, were supposed to
                         pass by the vein-like artery, the pulmonary vein, the one, one way, the other the other; while blood was
                         supposed to pass trough minute pores in the septum of the heart from the right to the left side, while the vital
                         spirits passed through the same channels in the contrary direction.

For 1500 years, this was the status of knowledge concerning the physiology of respiration. Nor did the next step materially aid knowledge; for Van Helmont rather added confusion when he elaborated his principles of the five “digestion,” the fourth of which says that the darker and thicker blood of the vena cava undergoes a “fermentation” in the heart and arteries whereby it becomes lighter in color and more volatile.

However, Borelli gave a clear idea of the mechanics of respiration, apply the new principles that had been arrived at of muscular contradiction on the other. But on the chemical side of the question, he made no contribution, except to reject the old idea that the movements of respiration were for the purpose of cooling the heart, and for getting rid of the heart’s smoky vapors. He considered respiration much more essential to life that the circulation he recognized that air was taken into the circulation, but being a physicist, insisted that the interaction was not chemical but a physical entrance of particles of air into the blood stream. It is probably that Borelli’s ideas were influenced to a large extent by the work of his contemporaries, of whom I am about to speak.

But now, real knowledge concerning breathing began to take form in a consecutive progressive manner. In this advancement, the English school of scientists played almost the entire part. It began with Robert Boyle, who was primarily a physicist, and especially interested in the weight and pressure of the air. In 1660, he showed that air was essential to both life and combustion by placing a candle and a small animal in a vessel, and evacuation the air. He was the first to intimate that the change, whatever it might be, that was effected by breathing, was identical with that going on in the burning of the candle.

Next, Robert Hooke showed that after the thorax of a dog had been widely opened, life could be prolonged indefinitely by artificial respiration. This proved that the whole of the essential business of respiration takes place in the lungs, and that the movements of the chest are of only value in so far as they mechanically, by alternately collapsing and expanding the lungs, bring air to them.  He went even further; by keeping the lungs motionless but full-distended by maintaining a powerful blast with the bellows, the air escaping through minute holes pricked in the lung surface, he demonstrated that mere movement of the lungs is not essential, but that what does matter is continuous supply of fresh air.

Using the lead given him by Hooke’s experiments with artificial respiration, Richard Lower ups4t the old ideas that the change in color of the blood took place in the heart rather than in the lungs. He noticed that the blood as it entered the lungs was dark in color, but as it left them, it became bright red, so long as artificial respiration was kept up. When this was stopped, the blood pulmonary veins and left heart became dark and venous. When he injected dark venous blood into the insufflated lungs, he saw that it became a bright red in color. This was clear evidence to him that the change in color of the blood in tits passage through the lungs was due simple to its contact with the air there, moreover to its taking up something from the air. He then demonstrated for the first time the necessity of fresh air for the maintenance of life. “Were if not for this,” he says, “we should breathe as well in the most filthy prison as among the most delightful pastures.” The same fresh air is needed for our breathing as for the burning of a flame; “in fact, where a fire burns readily, there can we easily breathe.”

Up to this time, no one, apparently, thought of anything except the whole air as concerned in breathing. Lower must have had a vague idea that it was not the whole air, but only a part of it, - “the lungs take up “something” form the air,” – but he could go no further. He did stimulate further inquiry, however, and now began what Sir Clifford Allbritt calls “the pathetic quest for oxygen.” This quest was destined to be zigzag in its course, with many turnings back and retracing of the same path. Many times were these investigations confronted with the truth, only to turn away from it because of preconceived and deeply imbedded ideas of which they could not rid themselves? The greatest obstacle to recognition of the truth was the false phlogiston theory, introduced by Stahl, the essence of which was the view that when a combustible body, a phlogisticated body, underwent combustion, it lost a principle called phlogiston, and became dephlogisticated. In dong so it suffered a loss. So strongly did this theory take hold of the scientific mind that it was not until 100 years later that it was finally overthrown by the researchers and clear thinking of Lavoisier. And yet Mayow, of whom I am about to speak, showed conclusively, before Stahl enunciated his phlogiston theory that a body in combustion gained weight rather than lost it. So prone are men’s minds, even the most acute, to accept fanciful theories.

John Mayow, an English chemist, demonstrated that a candil will blow out, and a mouse of sparrow die after a time, if placed in a ar to which access of fresh air is prevented. He showed further, that when a candle is burned in a closed vessel over water, the water rises after the primary depression due to expansion from heating, has passed off. The same thing takes place in breathing. He found that under these circumstances, experimenting with various animals, the air is reduced in volume by about 1/14th.

Mayow explained the combustible matter, to be burned, requires what he calls ingeo-aereal particles, which we call oxygen today; and that these particles, which we call oxygen today; and that these particles either come from the air, preexist in the matter itself, or may be added to it by mixing with it other matter containing them. He also recognized that in combustion, the igneo-aereal particles enter into combination with the substance burned, and so increase the weight of the latter. It is remarkable that in spite of this observation, supported by experiment, years later Stahl should have formulated his phlogiston theory, in which he says that a substance in being burned loses weight; in other words, fives off phlogiston. It makes one wonder whether the same thing may not be going on today- that we simply have eyes that see not, and so overlook facts that are perhaps staring us in the face.

He recognized the essential similarity between respiration and combustion, and in discussing the former says:

“ The reason why the animal can live some time after the candle has gone out, seem to be as follows: The flame of the candle needs for its maintenance a continuous and at the same time a sufficiently full and rapid stream of igneo-acreal particles. Whence it comes about that if the succession if igneoaereal particles be interrupted, ever for a moment, or if these are not supplied in adequate quantity, the flame presently sinks and goes out. Hence, so soon as the igneoaereal particles begin to reach the flames scantily and slowly, it is soon extinguished. For animals, on the other hand, a lesser store of the aereal-food is sufficient, and is supplied at intervals, so that the animal can be sustained by the aereal particles remaining after the candle has gone out. Here it may be remarked that the movements (expansions of the aereal particles which may remain in the said flask, and towards transferring them into the blood of the breathing animal. Whence it comes about that the animal does not perish until just b3efore the aereal particles are wholly exhausted; and whence it is that air in which an animal is suffocated is diminished in volume more than twice as much as that in which a candle goes out.”

He proceeded to elucidate the mechanism of respiration. He said that air entered the lungs during inspiration simply and solely because that pressure or elastic force of the atmosphere drove it in to fill up the increased space afforded by the enlarged and dilated thorax. He made a model of the lungs with bladder and bellows to illustrate this point. He believed that the igneo-aereus particles entered the blood, but assumed the existence for this purpose, of minute pores, invisible to the naked eye. He ridiculed the old idea that air cools the heart, and that blood passes through the septum of the heart.

Thus, it is evident that Mayow had in reality discovered oxygen, although he did not isolate it. He failed to realize, however, that something passed in the reverse direction from the blood into the lungs. He had, nevertheless, achieved a great deal, and yet it was almost in vain, for it was not until 100 years later that the facts he had uncovered were rediscovered, while in the meantime, the knowledge of the physiology of breathing stood at a standstill, beset with strange theories and speculations. Leading the way in the latter was Holler, who went back to the old physical hypothesis of respiration; but instead of accepting the idea that the air cools the blood, states the exact opposite, that animal heat is produced by the mechanical friction of the blood through the lungs, and so increase heat production. He admitted that possibly some air entered the blood, but considered this a negligible factor.

Meanwhile, Stephen Kales laid down an English rector, who devoted much of his life to science the basis for further investigation. He formulated the general principle that gases exist in two states; one as free gas; the other fixed gas, in combination with other substances. This principle had a great deal of influence in subsequent investigation.

Joseph Black, in Glasgow, rediscovered CO2, which he called “fixed air.” (Van Helmont had first discovered it 100 years before, calling it “gas sylvstre). Black recognized it as being present in ordinary air, though he thought at first that it constituted all of the air that was not respirable; later, however, he recognized that there was some other part still, that was not respirable, when Rutherford discovered nitrogen.

To Joseph Priestley, and English minister, who had to flee to America because of his political views, is usually given the credit for the discovery of oxygen, although as we have seen, Mayow had first recognized it as “ igneo-aereal particles.” Priestly came to recognize its presence during the course of experiments to render vitiated air respirble once more. This he did by growing plants and vegetable matter in large vessels containing vitiated air, where, after some months he found that a flame would burn again and an animal live in it. He also obtained oxygen by the heating of mercuric and other oxides. But so obsessed was he with the old phlogiston idea, that he tempted to explain his results on this basis, and instead of arriving at the truth of the chemistry of respiration, got further from it. He denied that CO2 came from the lungs, as Black had shown, but insisted that the phlogiston is respired air decomposed the latter into CO2.

It remained for Lavoisier to clarify the situation. He showed that “air vitiated by breathing, contains 1/16th part of an seriform acid (CO2) like that which is obtained by chalk. When this was removed, the remaining air still failed to support life or a flame, and he called it “azotic air” (N2). With amazing clearness, he brought our knowledge of the chemistry of respiration almost to its present status, when he said; “We may therefore regard as proved:-

“1. Respiration affects only the air eminently respirable; the rest of the atmosphere, the mephitic part (N2) remains
                 unchanged.

“2. Animals shut up in a confined atmosphere succumb, so soon as they have absorbed or converted into aeriform
                 calcic acid the greater part of the respirable portion of the atmosphere, leaving a remainder.

“3. The calcinations of metals in atmosphere goes on until the air eminently respirable contained in the atmosphere is
                  exhausted and combined with the metal, but will not go on afterwards.

“4. This remainder is the same in calcinations and in respiration, provided that in the latter case the aeriform calcic
                  acid be removed; and in any case is reconverted into ordinary atmospheric air by adding to it air eminently
                  respirable.

“ 5. If we augment or diminish the quantity of metal which can be calcied in it, and to a certain extent, the time during
                  which the animal can live in it.”

He went one step further: he concluded that “besides the part converted into carbonic acid, a portion of the inspired vital air does not issue as it enters. The results, there for, one of the two things; this part either unites with the blood or combines (in the lungs) with a portion of hydrogen to form water.” (Cavendish had discovered Hydrogen in 1781.) He was really the first man to isolate oxygen, and many prefer to give him the credit usually given to Priestly.

Lavoisier made only one mistake: he thought that the oxidation of carbon and hydrogen supplied by the food, takes place in the bronchi into which they are secreted as “ a humor secreted from the blood and which is principally composed of Carbon and Hydrogen.” Had he stopped before this, he would have brought the knowledge of the chemistry of respiration essentially to the point where it is today; but by putting forth this hypothesis, he created still other obstacles which required more years to overcome.

It was Lagrnge who presented the idea that oxidation takes place in all parts of the body to which blood circulates, excepting that he thought it occurred in the blood itself, and not in the tissues, as we know today, and which Apallanzalli demonstrated. In spite of that, however, Lavoisier’s ideas held away, and it was not until Gaston Magnus, by use of a mercuric air pump, showed that both arterial and venous blood contain both O2 and CO2, though in different proportions, that this problem was finally solved.

So we see that the development of the physiology of respiration from Borelli to Wagnus was almost exclusively the work of three mathematicians, two physicists, and five chemists.

The story of the remaining investigations in regard to this subject can be briefly told. Legallois first showed that lesion of small circumscribed areas of the medulla inhibits breathing, while Florence discovered the location of this “ vital mode.”

Chiefly Pfluges, who invented many physiological instruments of respiration, did the study of the gaseous exchange between the blood and the tissues. He showed that nitrogen is in a state of simple solution in the blood.

Henry Head demonstrated the function of the vague in respiratory movements.

And so, about half a century ago, knowledge concerning breathing under normal conditions reached almost its full completion, in the sense that we understand it today. Later investigations have been directed towards a knowledge of what happens when we breathe in a rarefied atmosphere, as on mountains; in a compressed atmosphere, as in deep sea diving or in tunneling; or in atmospheres polluted with foreign gases; and in disease. Advantage too has been taken of our knowledge of the chemical and physical exchange of gases in the lungs, in attempting to measure the output of blood from the heart. Our knowledge concerning these things is still rather slight and there is a fertile field for investigation along these lines.

Respiration Under Abnormal Conditions

 (a)    Respiration under diminished atmosphere pressure.

This phase of the subject id full of so many interesting observations and experiences that there is no time to take it up in detail; hence I will attempt simply to outline the general principles that have been involved in the study of breathing in a diminished atmospheric pressure. This study has been undertaken under varying conditions, and the methods used have been chiefly as follows: (1) investigation on mountains; (2) investigations in steel chambers, where the pressure can be changed at will; (3) observations in balloons and (4) observations in airplanes.

To Paul Bert belongs the honor of pioneering in this work. He did certain experiments in steel chambers, showing that animals would die when the pressure was reduced sufficiently. He attributed their death to either an increased pressure of CO2 or to a diminished pressure of oxygen. He also showed how death in Balloon ascents etc., could be prevented by breathing pure oxygen, thus increasing its partial pressure in the lungs. He noticed certain mental changes that takes place in diminished atmospheric pressure when pure oxygen is suddenly breathed (pg.360; Haldane.) thought Paul Bert has shown conclusively that the physiological effects of low atmospheric pressure, depend on lowering oxygen pressure, yet the theory was advanced by mosso twenty years later that these effects are due primarily to excessive loss of CO2 from the body, a condition he called acapnia. This theory held sway for a long time. It is now known that acapnia is a secondary result of low oxygen pressure. In the early study of respiration under these conditions, observations were frequently carried out in balloons; a great deal of interesting information was obtained by this method. A pretty good idea of what happens under these conditions can be gained from the reading of two balloon flights that took place, one in 1862, and the other in 1875(page 375-376 Haldane). Observations in airplanes have not been so extensive, because of the inherent difficulties involved, but certain observations have been added to our knowledge.

Major Schroeder of the American Army Air Service reached a height in an airplane as great as had ever been previously reached in a balloon. He, however, became unconscious and had a very narrow escape. Something had happened and had a very narrow escape. Something had happened to his oxygen supply.

Recently another aviator went to an altitude, which was a record for airplanes as shown by his barometer. At this level, his airplane suddenly caught fire, and the oxygen tube some how became dislodged. He had presence enough of mind to replace this first and begin breathing the oxygen. This undoubtedly saved his life. Most of the way down to earth, he kept his airplane in a side slip to keep the flames away. At one time he thought he had the fire out, but it blazed up again, so almost the entire descent was made as a slide slip, he landed safely and rather remarkably because of his skill, and the flames were immediately put out. In spite of all his efforts and precautions to save the recording barometer, the flames had gotten it. Therefore, only his unsupported word substantiates his claim, but there seems to be no reason to doubt that he was telling the truth. Many people observed the skill of his manipulation of the plane.

I have brought this case up to indicate his presence of mind when he breathed an adequate supply of oxygen even under extreme difficulties, for this undoubtedly saved his life.

Most of the recent observations have been planned for the purpose. The effect of altitude has been studied in various parts of the world, depending naturally upon the geography at the place involved. I might mention here some of these places. There are many mountain peaks in the world whose altitudes is high enough to study its effects upon the human body, but few of these are accessible enough to render scientific work possible.

The earliest work along these lines was done by Mosso, who studied the effects of high altitudes at Monta Rose in Italy at an elevation of 15,000 feet; Fujyama in Japan has also been used, but its height is only 12,500 feet. Tenerife, one of the Canary Islands, has been used much; its elevation is 122,000 feet. Many expeditions have been made to Pikes Peek in Colorado, and a great deal of work has been done there. The elevation of this peak is 15,000 feet. Haldane in particular has done a good deal of investigation at this place. The most important, the easiest, and the most reliable information probably have been obtained at Cerro DePasco in Peru. Mountains here in this neighborhood are from 15,000 to 16,000 feet in height. There is a railway, which goes all the way up to the height, so that passengers and scientists can remain quiet during the ascent. This enables the symptoms of mountain sickness to be investigated much more fully. I am going to say very little about mountain sickness. The symptoms, as most everyone knows, consist chiefly of lassitude, headache, coldness of the extremities, nausea, vomiting, and cyanosis, deep and frequent respirations. In the extreme stages, there occurs weakness, almost to the point of collapse. The temperature is sometimes elevated. Recovery form these symptoms will take place, while the patient remains at the same altitude, in a few days, if he is put to bed; and almost immediately upon return to sea level.

The most interesting of all the manifestations of height altitudes is the way in which it affects the mind. Incoherence, amnesia, dullness of the higher senses, and the loss of one’s normal cerebral control, are some of the most important symptoms. Many instances of these effects have been recorded. I will quote tone ore two (Bancroft P. 156-157-163). These symptoms are due entirely to anoxemia with insufficient supply of oxygen to the brain. Observations made at these altitudes have revealed very many points of interest about what goes on in the body with the relation to the red count, the hemoglobin, the reaction of the blood, its chemistry, color, the size of the chest, the size of the heart, but a discussion of these would be out of place here.

The leaders of this kind of work have been Haldane, Barcroft, Meakins, Douglas, Redfield, and others. Its practical importance undoubtedly has to do with aviation chiefly, and to a lesser extent commercially, where mining camps are situated in high altitudes.

(b)   Respiration under increased atmospheric pressure.

A great deal of work also has been done on this subject. Its practical importance is evident particularly in deep sea diving, digging of tunnels, and sinking of caissons. Here, too, Haldane has been a pioneer in the work of discovery. He has by means of thorough study developed a technique of decompression for deep sea divers, so that “caisson disease,” as it is called, is now rather uncommon, although when it does occur, the outlines of treatment have been very specifically set down. An instance, concerning this subject, occurs to the mind in relation to the digging of a tunnel under the Hudson Rover between New York and New Jersey recently. Here the tunnellers were forced to work under high atmospheric pressure for many months. As far as I know, no accidents have occurred, and because of this, the men have been most faithful, seldom leaving their jobs. This has all been made possible because Haldane’s extensive investigation concerning decompression for men working in increased atmospheric pressure.

(c)    Respiration in an abnormal atmosphere.

This has been of practical importance chiefly during the world war when poison gasses came to be used. A certain amount of investigation has been done on this subject, but owing to its obvious limitations, not a great deal. Nor more needs to be said at this time.

I have attempted to summarize briefly the story of the search for the hidden factors involved in breathing from ancient times up to the present time. Most of the work was done under normal conditions until the knowledge of normal breathing was well established. The investigation of breathing under abnormal conditions was delayed until more was known about the normal. It has been possible to sketch only briefly the latter subject. Some of the stories one reads in the investigation that have been undertaken makes very interesting reading matter. We are yet still in the dark about a great many problems.

One of these concerned the effect of foreign gases; another of the relation of circulation to respiration. Time will, we hope, solve these problems.

 

           References

 (1)   “Respiration” Haldane: 1922, New Haven Yale University Press.

 (2) “The Respiratory Function of the Blood” Part 1. Barcroft: 1925, London
                   Cambridge University Press.