VISUALIZING MEDICAL HISTORY THE PHYSIOLOGY OF RESPIRATION* By HENRY SEWALL, M.D.

DENVER, COLORADO

he President of the Colorado which new interest and new meaning might State Medieal Society, Dr. Boyd, be thrown around important persons and signalized his election to office by events of the past. effecting an addition to the pro­ My task has been frankly pedagogical in Tgram for the annual meeting which design,must and its progress convinced me that give it permanent distinction in the records. the scheme furnishes a method by which He has harbored the lofty ambition to have the student might profitably record the portrayed by means tangible to vision and evolution of his chosen science. to touch, as far as may be, the History of Somewhat similar devices have been Medicine. employed before, but no apology need be To the present writer was assigned the offered for another attempt to lure the task of representing in some way the interest of readers to the treasury of history progress of Physiology. The allotment was from which have been drawn the funds for accepted in the spirit with which we con­ our present buildings. This knowledge is a front the impossible: the whole cannot be key to understanding. Its discipline exer­ done, therefore its smallest fraction assumes cises the finest powers of mind and feeling. a relative importance in the calculus. In trying out the purpose under discus­ On reflection an idea was conceived, and sion my venture was restricted to the grew apace, that real help both in the learn­ history of a single field of animal physiology, ing and teaching of history could be gained that of Respiration. I am indebted to Dr. by coordinating the concepts of time and H. J. Corper for preliminary trials of the space in an objective picture. This would chart idea, and especially to Dr. Sanford provide the study of history with somewhat Withers, who has devoted his skill to the the same sort of aid that chemistry, preparation of the chart itself. physics or biology finds in its practical The calendar of our chart is represented demonstrations. in the column on the left. It will be noted It was determined to construct a chart that of one hundred and five biographical representing historical time on which should names recorded only eleven are included be allocated the names and life tenures of within the first twenty centuries; therefore the makers of a certain branch of science. but small space is allotted to each of these It seemed obvious that such visual localiza­ periods. But from the sixteenth to the tion of men must not only greatly assist the nineteenth century, inclusive, ample space memory in recalling their place in history is given to the division of each century but accentuate the relation of man to man into decades. and to the development of knowledge. No The family name of each personage, and argument should be needed for allying any under it the date of his birth and death, are visual device to historical representation. recorded within a rectangle which covers The cinema has amply demonstrated two decades on the chart, and is placed at its popular appeal in the field of portraiture. about the middle of his career. From the My own idea has been to stimulate unused middle of the lower side of each rectangle a association centers in the brain through line is drawn below to a point representing * Read before the San Diego County Medical the date of birth of the individual; similarly, Society, Jan. 5, 1926. from the upper side, above to a point cor- responding to the date of his death. The trust I have not prematurely buried any time of birth determines the order of our of my subjects. biographical index, the names following in A glance at the chart shows who were that relation from left to right and from contemporaries, as well as the temporal below upward. Decedents in the twentieth sequence of individuals. An attempt has

century have their life lines terminated at been made to indciate by heavier lettering the beginning of that epoch, or the brackets one’s estimate of the predominant charac­ round their names impinge directly upon it. ters in the development of science. In five cases it was impossible to learn It was designed at the outset to append a the dates of death in time for this review. I legend to each name, setting forth the accomplishments of the person. This proved all were obliged to undergo purification.” impracticable, and it is advised that bio­ This usually consisted of a cold bath, per­ graphical data be preserved in a card index haps with salt, or they were treated with which, for teaching purposes, should form incense and fumigations, and a rigorous an important adjunct to the chart. It is diet or fasting was imposed. Among the obvious that overcrowding of names in the most impressive surroundings the votary late centuries could be avoided by broaden­ was permitted to approach the statue of ing the diagram. Possibly the chart should the god and offer sacrifice with prayers, and have been given the form of a triangle with even touch his diseased member to the base above. hand of the image. Genealogical tables begin at the top and As evening approached the final prepara­ are read downwards. First-class authority tions were made for the elaborate and final has advised that procedure here. But I pre­ course of treatment by incubation. Dressed fer to typify the development of knowledge in white, the patient was assigned a pallet as upward, like a tree. Again, economy of after placing sacrifices on the altar. The space might have been secured by omitting white-robed priest offered an impressive the blank period of the Dark Ages, but we prayer and the patient was enjoined to sleep should have thus lost the contrast with and fear nothing. In early morning the other times. priests, one of them in the costume of the If this chart awakens any interest, such god, returned bringing ointment to anoint will probably be manifested by attention the sick body, and sacred serpents, which directed to its omissions and derelictions. crept over the sleepers and were supposed Medical history and tradition cover some to whisper the remedy in the ear and some­ five thousand years antedating the Chris­ times to nip it. tian Era. Hippocrates could not have sprung “The experience of the night, acting on fuII-panopIied from chaos. We want to an overheated imagination, the assumed know the soil and the cultivation which appearance of the deity, possibly in the form made him possible. Through timely good of a serpent, and the application of the fortune Dr. W. A. Jayne, of Denver, has hand of the god—all in the dim light while in just given us an account of the religio- a state midway between sleeping and medical lore as culled from the earliest waking—were readily interpretated as a times. divine visitation, a celestial dream or When in earliest ancient Greece a man vision.” Thus the injunction to faith was greatly distinguished himself in any field he crystallized in a belief so strong that it is no was likely to be, as it were, canonized after wonder that most disorders might be his death and raised to the rank of a demi­ expected to receive amelioration by induc­ god and patron of the particular activities tion of a placid state of mind, and the in which he had been adept. Such was functional troubles be cured by suggestion. Asklepios, first mentioned by Homer in the Such, in general, was the method of applica­ Iliad as a “blameless physician.” tion of priest-medicine in all ancient coun­ So famous became the cures of intractable tries. It would be a grave error to assume diseases effected by his votaries that various that this therapeusis was guided by con­ healing shrines, or Asklepieia, became estab­ scious deceit. It was simply ingeniously lished throughout Greece, which were devised to get results. thronged by patients. It is a far cry from the times of treatment “Only the pure were permitted to of disease by incubation to the operations of approach the god, and on entering the hieron modern cults ofsimilar inspiration, but it may ‘ Jayne, W. A. The Healing Gods of Ancient well be doubted whether the modern methods Civilizations. New Haven, 1925. are as effective as were the ancient ones. In the unproductive centuries following “At his death Miiller’s chair was split Galen it would be interesting to depict into three, Du Bois Reymond took physiol­ how the germ of Greek Medicine was ogy, Virchow took pathological anatomy preserved by the long line of Arabian and and Reichert took morphology.” other scholars who marked time in the Carl Ludwig (1816-1895) must have march of knowledge through the Dark reflected some of the best characteristics of Ages. It would be desirable to apply the his master, Miiller. His was a gentle, serious, graphic method to the influence of the but withal humorous soul. There seemed to Church and of the Universities to be no vanity or selfishness in him. During the development of our knowledge. his years as professor of physiology at Adverse criticism could be fairly opposed Leipzig earnest students of research flocked to my choice of portraits for our gallery of to him from all over the world to the fame. Such comment, based on research, number, it is said, of more than three would itself be high reward. It has been my hundred. When they had no preconceived effort not to pad this catalogue but still task he assigned them a subject of research to escape convention in notation, not only and very often personally performed for or of those who have produced knowledge in with them the experiments which often led our chosen field but of those who have to discoveries of permanent value. The pub­ preserved it or have inseminated other lications detailing such work rarely con­ minds and inspired research. tained Ludwig’s name or, if so, only as joint Thus Johannes Miiller (1801-1858) author. opened the modern epoch in physiology It was my privilege to be admitted to his through the genius of his intellectual chil­ laboratory for the winter of 1879 when he dren. Though we cannot ascribe to Johannes was sixty-three. In the idle moments just Miiller any single discovery of paramount before his evening lecture preceding supper importance, two things conspired to make he would likely come by my table and say, him a salient figure in physiological history. in German, “Now tell us a joke.” One First, he must have been a most attractive evening after the lecture the professor was and inspiring personality; second, his power intently engaged in a dissection of the of imparting information and of arousing carotid region in a dead dog. After a while scientific ideals must have been phenomenal. I ventured to ask what he was about. He His general textbook on physiology was the said that in the morning’s experiment he first great modern treatise on the subject had noted milky chyle in the lymphatic and for years remained its authoritative of the carotid sheath and he was trying to handbook. discover how the chyle from the abdominal No less important than the character of lacteals could have reached the neck. Here the man was the special stage in scientific was the old man patiently plugging away intellectual evolution at which he entered. after the fatigues of a busy day in order to The time was ripe; the minds of men were clear up a new fact which would not wait seething. Not otherwise can we explain that for solution. The young man looked on for from among his pupils there emerged Vir­ many minutes and then went to his supper. chow, the pathologist; Briicke and Wagner, But the old man must have stuck to his physiologists; Helmholtz and Du Bois Rey­ job, for in the morning, when I asked him mond, physiologists, physicists, mathema­ his results, he said: “I found a collateral ticians; and such other masters of biological circulation between the thoracic duct and science as Claparede, Ludwig, Schwann, the cervical lymphatics.” It set me to Volkmann, Reichert, Lachmann, Vierordt, thinking, perhaps it was this sort of thing Trochel, KoIIiker, Remak, Lieberkuhn and that made Ludwig preeminent. Haeckel. Sharpey (1802-1880) preserved the spirit of biological research in England in his of his own day. Galton had found, as I time and taught Michael Foster (1836— remember, that in English history there 1907) and Burdon Sanderson (1828-1905). was a certain small number of men with Foster founded the School of Physiology minds of very first rank per million of at Cambridge and helped breed Martin, population. Looking back to Athens in the Gaskell, Dew-Smith and Lea, to name only palmy days of Greece he found that the ratio of very great men to the population of the dead, including Langley who left us but a Athens was very much higher. He con­ few weeks ago; and, through Martin (1848- cludes that these intellectual mountains 1896) he gave the first great general impulse must have been planted on a high plateau. to physiology in America. Burdon Sander­ He deduces, accordingly, that the intellec­ son fathered physiology at Oxford. tual ability of the average Athenian of that Boerhaave was the Roman Centurion of day was as much higher than that of the his time. Roger Bacon first struck the key­ Englishman of his day as was the ability of note in the march of Experimental Science the English above that of the aboriginal after a thousand years of imitation and African savage. speculation. In the ten centuries following Galen, Even a superficial glance at our chart comprising the Dark Ages, my judgment presents elements of interest. Beginning at gives place only to the Persian, Avicenna the bottom we note that for the first seven (980-1036). hundred years of history the outstanding Suddenly the sixteenth century blooms figures of medicine were essentially all with a galaxy of medical investigators or Greek. Even so, following the Golden Age feeders of medical thought. Of eleven per­ of Art, Science and Philosophy there was a sonages listed no less than seven were lapse of some four centuries before the Italians and nearly all were contemporaries. advent of Galen, the prototype of the It is curious to observe that, including modern investigating but imperiously self­ Leonardo, all of our eleven heroes were confident “successful practitioner” of anatomists whose studies of the heart and medicine. blood vessels gave the soundest possible Then followed a barren period of some basis for the subsequent perception of fourteen centuries wherein the truths and function. And I will assume that an intelli­ errors of Galen continued to dominate gent conception of the respiration must thought and in which the data of knowledge begin with a study of the circulation as it were transcribed by Arabian, Persian and ends in that of metabolism. Jewish physicians. Contemplating the medical masters of It may be good for the soul to dwell upon this era it must be a dull student who would the masters of this Golden Age of Greece. not get delight in turning the leaves of They included the incomparable Phidias, Choulant’s reproduction of their drawings.^ sculptor; Hippocrates, sage of medicine; Vesalius, the “Father of Anatomy,” is Euripides, Aeschylus and Aristophanes, said to have been inspired by Leonardo da poets; Socrates and Plato, philosophers; Vinci. At a time when any conflict with Aristotle, the chief and leader in every authority always adumbrated the Stake, branch of contemporary knowledge. Sir Vesalius’ was the first masterful spirit Francis Galton, founder of the science of which dared throw contempt on teachings eugenics, in his “Hereditary Genius,”^ made of Galen that had ruled minds for fourteen interesting comparisons between the intel­ centuries. Leonardo da Vinci was himself so lectual planes of the ordinary Athenians of universal a genius that we are likely to over- those days and of the average Englishmen 3 Choulant, L. History and Bibliography of Ana­ 2 Galton, F. Hereditary Genius, etc. New and tomic Illustration. Trans, by Mortimer Frank, revised ed. with an American preface. N. Y., 1871. Chicago, 1920. look his special contributions to physiology. that the passage of blood from one ventricle He apparently preceded Boyle by a cen­ to the other was by seepage through invis­ tury and a half in the experimental demon­ ible pores in the interventricular septum. stration that pure air was necessary both to A passage in a work by Servetus denies burning flames and to animal life: he says: the patency of the septum and asserts that “Where flame cannot live no animal that the blood passes from the right ventricle breathes can sustain existence.” into the pulmonary artery, whence it trans­ Allbutt^ says of him: “The student of his udes into the pulmonary veins. exquisite drawings cannot but think that Some six years later Columbus (1516- Leonardo, with his prodigious imagination 1559) reached more or less independently and mastery of hydraulics, must have dis­ the same conclusions, realized more com­ covered the circulation of the blood,' but in pletely than Servetus its great importance his manifold and various interests failed to and claimed priority of discovery. But the proclaim it. He suggested that the blood Italians have a stronger claim for the might return from the lungs to the heart in discoverer of the circulation in Andreas expiration.” Caesalpinus (1524-1603) who published a It is inspiring to realize that the human work in 1571, forty-five years before Harvey mind and body can reach the heights scaled began his public lectures and fifty-seven by him. He lives in fame as a painter, an years before he published his discovery, architect, a sculptor, a scientist, an engi­ in which he, Caesalpinus, “assumes a neer, a mechanician, a musician. You know constant and physiological transit of the his painting of the Last Supper; perhaps blood from the arteries to the veins, through you have seen his Mona Lisa. the anastomosis, which he termed the The reader of Luciani’s work on “Human ‘vasa in capillamenta resoluta,’ to every Physiology,”® will find there recorded the part of the body; this perpetual forward evidence on which Italy claims Caesalpinus, movement of the blood from the venae with certain countrymen, as the discoverer cavae to the right heart, thence to the of the circulation of the blood. lungs, from the lungs to the left heart and We shall find that the story of discovery from the left heart to the arteries was of the circulation of the blood leading to termed by him ‘Circulatio.’ Harvey (1578-1657) took a century in the But, as Robert Willis points out, though writing. Beginning with Servetus (1509- Caesalpinus used the right words in his 1553), who was burned at the stake through description, the right ideas were given them the machinations of the bigot, John Calvin, by others a century after him. For he still we find light beginning to shine upon the speaks of the permeation of the ventricular physiological darkness.® Galen himself is septum by the blood; and he still refers to said to have hit upon much of its truth. the flux and reflux of the blood in the veins There was a general conception among the in a tide-like manner. Apparently he did not ancients that the blood somehow got from really grasp the idea of a continuous blood the right to the left ventricle; but their circuit, any more than Fabricius (1537— erroneous ideas as to the function of the 1619), who finding that all veins connecting respiration blinded them to the importance with the venae cavae have valves, grasped of the lungs to the circulation. They thought the main function of these. The credit for guessing that the purpose of the valves is Allbutt, Sir T. C. Greek Medicine in Rome., etc. to keep up a venous current in one direction N. Y., 1921, p. 317, footnote. only is given to Sarpi (1552-1623); some ® Luciani, L. Human Physiology. Trans, by Welby, N. Y., 1911-1921,1, 157. authors even credit Sarpi with discovering ® Osler, Sir W. Michael Servetus. Bull. Johns Hop­ the general circulation. kins Hosp., Balt., 1910, XXI, I. Lucian i, L. Op. cit., i, 163. Robert Willis, in his Life of Harvey We cannot doubt that, even as an under­ prefacing his Works in the Sydenham graduate, Harvey’s mind must have been Library, submitted the Italian claims to saturated with the doctrines of the circula­ searching criticism and declared: “The tion as then conceived. His was the ready world saw nothing of the circulation of the mind to apprehend the truth, and his the blood in Servetus, Columbus, Caesalpinus, genius, as so well exemplified later in or Shakespeare, until William Harvey had Lavoisier and Pasteur, to realize that but taught and written.” A modern physiolo­ one, the experimental, method was capable gist, the late John G. Curtis, in a scholarly monograph, has dissected Harvey’s mental­ of defining the boundary between truth and ity as represented in his experiments and error. dialectic.® It was not until 1616, in his thirty-eighth The reader of the evidence cannot but year, that he began those public lectures in grant that for a hundred years before which he unfolded his theory of the circula­ Harvey the darkness had been lighted now tion of the blood. “It was in 1628, the year and then by flashes of inspiration. The of his fiftieth birthday that Harvey pub­ image of the truth stood out plainly enough lished, at Frankfort on the Main, his but its meaning was not perceived. Its famous Latin treatise entitled ‘An Anatom­ conception was not grasped, and conse­ ical Exercise on the Motion of the Heart and quently was not pursued. Not until Harvey Blood in Animals.’”® Thus, not until fourteen applied the inductive method with the tool years after graduating in medicine did he of experimentation was the truth grasped, begin to teach in public and not until twelve and even then more than a generation years after this and twenty-six years after elapsed before Malpighi (1628-1694) com­ graduation did he publish his doctrine. But pleted the proof of the blood circuit by this by no means completed his work. It is discovery of the capillary circulation. interesting, indeed, that after clearing the Harvey graduated in Arts after three way for a full comprehension of the physiol­ years at Cambridge. He then, at the age of ogy of respiration, Harvey still remained nineteen, chose the great University at subject to the Aristotelian doctrine that the Padua for his medical course, where he main purpose of respiration was to cool the studied five years and obtained his licen­ innate heat of the body. But in later life his tiate. Among several able instructors at clear mind lost confidence in this belief, but Padua, Harvey appears to have been offered no substitute; as to respiration he especially indebted to the famous anato­ concludes: “Surely a more knotty subject mist, Fabricius ab Aquapendente. The latter could hardly be found.”® studied intensively the valves in the veins. Harvey’s failure to advance a theory of He believed their function to be to prevent respiration on insufficient evidence was a undue congestions of blood in the periphery, worthy and hardly inferior counterpart of to strengthen the veins and to prevent their his positive exploits. overdistention; all fundamental properties, A good deal of sociologic interest attaches but he failed to see their relation to the to the fact that Harvey won distinguished afferent blood current of which his great success as a practicing physician during the pupil was to make such trenchant use. years of his experimental work and his Harvey returned to England the year of public exposition of its results in lectures. his graduation (1602) and within two years He was appointed personal physician and began the practice of his profession in attendant upon the King, Charles i, and London. probably drew his clientele from the highest 8 Curtis, J. G. Harvey’s Views on the Use of the and most remunerative social circles. Circulation of the Blood, etc. N. Y., 1915. ® Curtis, J. G. Op. cit. But upon the publication of his work on Jean Baptiste Van Helmont was the noblest the circulation in 1628, at the age of fifty, of the experimental alchemists, precursor of there seems to have been a sudden falling off Priestley and Lavoisier, the founders of modern in his practice, so jolting and so immediate chemistry. He found that on burning coal and that the two events would appear to bear in the fermentation of wine, a gas which he the relation of cause and effect. This may called gas sylvestre escaped, which was incapable of maintaining a flame and produced asphyxia start disquieting reflections in the minds of and death in mammals. This gas may develop younger workers today; but they may in the heart of the earth, as in the Grotto del confidently entertain the assurance that, in Cane near Naples; it bubbles up in certain our times, early publication of the right kind mineral waters, and could be evolved from the of stuff is the most certain and efficient and calcareous concrements found in the crab’s ethical instrument with which to open that stomach by dissolving them in vinegar.^® oyster, the world. Indeed, the provisions for the endowment of research have been so It is interesting to note that Van Helmont generous within the past decade or more coined the word “gas,” from what ety­ that that great truthteller, T. H. Huxley, mology is not clear. if alive today, would not venture to repeat The seventeenth century is marked by the his declaration of the early seventies, when activities of a collection of astounding in advising students as to the choice of a intellects. Fortunately research took the road career, he said in effect: “ It would be better of the physical sciences. We have seen that for the material welfare of a young man the impulse to chemical study on modern without affluence that he should be a lines was given by Van Helmont. drunkard than that he should become a With Galileo (1564-1642), and following victim to the divine dipsomania of original him, mathematics and physics were devel­ research.” oped to a high plane. Galileo strongly We now enter an era in which the funda­ influenced the intellects of his contempo­ mental chemical facts underlying respira­ raries. Fascinated and enthused with their tion, which Harvey had lacked, began to observations and experiments in inorganic be unfolded. nature, the thinkers of those days were fain At the time when Harvey had probably to explain the phenomena of life itself as the essentially completed his theory of the expression of the laws of physics and chemis­ circulation, one of his contemporaries made try operating within a peculiar environ­ the first distinct contribution to the chem­ ment, the organized body, thus anticipating istry of the respiration. This was a curious our most modern doctrine. After the manner medical genius, the Belgian, Van Helmont of the ancients, the viewpoints of students (1577“ 1644). He was founder of the so-called were represented by different schools of latrochemical School, which, with its con­ thought. Thus we have the latrochemical gener the latromathematicalor latrophysical School, fathered by Van Helmont. Iatros in School, would form a trenchant examina­ Greek means “physician.” The tenets of the tion theme for the undergraduate student school sought to explain vital phenomena of medical history. Van Helmont more or as the expression of purely chemical forces. less vaguely identified carbonic acid, calling The chemical viewpoint outlasted the cult it “gas Sylvestre,” though it was left for in which it arose and was later the source of Black, one hundred and fifty years later, to great contributions from Willis (1621-1675), accurately isolate it and describe its vital Lower (1631-1691), Mayow (1643-1679), relations. Black (1728-1799), Cavendish (1731-1810), It was nearly two hundred years after Van Priestley (1733-1804), Scheele (1742-1786) Helmont that Lavoisier demonstrated the and Lavoisier (1743-1794). essential nature of the respiratory function: ^°Luciani, L. Op. cit., i, 371. On the other hand the mathematicians land. Both Willis and Lower were popular and physicists, whose first experimental and exceedingly successful practicing physi­ exponent was Bo'relli (1608-1679), founded cians. But the former comes under the the latromathematical School and explained trenchant criticism of Michael Foster who vital phenbmena as due to purely physical stigmatizes him as primarily a money­ forces. getter, an imitator and copyist of phrases Thus Borelli discovered the fact that who cared more for fame than for the muscles do their work by becoming thicker truths of Nature. Foster suspects that and shorter; and his observations and the great classic of Willis, his book on the reasoning on the continuous movement of brain, was rather the work of his assistant. the systemic circulation impelled by the Lower, than his own. Says Foster: “Lower periodic heartbeat reads almost like a . . . was a real man of science, with a modern contribution. The word Physiology, clear penetrating mind, with a genuine love which had been rarely employed in earlier of truth for truth’s sake, a worthy mate of times, “was now coming into general use as Boyle, of Hooke and of Mayow.” But it a part of physics, ‘and this he proposes (in remains for us to criticize the critics. Human his book)’ to ornament and enrich by judgments are largely determined by the mathematical demonstrations.” “ psychology, the experience and the inherent Anticipating Borelli, but a contemporary motives of the judge. Michael Foster was a of his, the great thinker Descartes, who was man of science pure and simple. He despised not an experimental physiologist, wrote the foible of vanity and had no patience extensively on the thesis that the animal with mercenary inclinations. Clifford AII- body was a pure mechanism for expressing butt was, too, a scholar of high rank and a the dictates of the in-dwelling soul. humanitarian of pure ideals. But he was also Foster says of him: a practical physician, familiar with the seamy It was part of his philosophy to show that side of life and with a perception that sordid man consisted of an earthly machine inhabited motives tend to mingle with the purest and governed by a rational soul. . . . He human activities. He knew, as we know, wrote a treatise which stands out as the first many admirable intellects, most useful textbook of Physiology, written after the to science and society but tainted with modern fashion, though in a popular way. We despicable characteristics, and it is but the may perhaps speak of him as the Herbert broadest and highest expression of justice Spencer of the age in so far that his treatise on to separate the true metal from the dross. man bore somewhat the same relation to the Thomas Willis had at least that sensitive physiological inquiries of the time as the perception of truth, which we now and then Principles of Biology to the biological researches witness in a clinical confrere, that leads to of the present day. ^2 right action as if by intuition. Moreover, Allbutt^^ gives a high place in the develop­ Willis seems to have had extraordinary ment of physiology to Thomas Willis. He power of influencing others to do their best says: “It was Willis who made the return work and thus multiply his own best powers. to bio-chemistry, and he first, and soon Not to dwell too long on this side issue, it after his pupil Lower, produced the change is worth noting that everywhere and always of color in the blood experimentally, critical judgment is colored by the environ­ admitting and excluding air.” He introduced ment of the critic. Talk of medical education iatrochemistry or biochemistry into Eng- with the man of the laboratory and you will get one point of view; talk with the practical Luciani, L. Op. cit. clinician and you will get another. We must 12 Foster, Sir M. History of Physiology. Cam­ bridge, 1901, p. 58. often fall back in our conclusions on the Allbutt, T. C. Op. cit. abstract fact that truth is one and indivis- ibie. We must realize with the billiard player misunderstood; it played a role to fit the that every slightest impulse given the ball hypothesis of the origin of animal heat. effects its progress and that its final destina­ What a masterly conception was the tion is determined by exact mathematics. pneuma of Galen, modified from his pred­ One of the most significant features of this ecessors’, entering the lungs with the air, richly fruitful period is found in the type and reaching the heart through the pulmonary training of the men who developed its veins, generating animal spirits which, biological science. Garrison writes of it: transported by the blood, vivified the body; “Thus the development of the physiology and the “fuliginous vapors” generated by of respiration, from Borelli to Magnus, combustion could escape in the air of was almost exclusively the work of three expiration! Thus the soul and vitality were mathematicians, two physicians and five given a physical basis, perhaps as com­ chemists.” prehensible to a layman as our ether and We must now turn for a moment to the electron. Indeed, to a man from Mars the physiological conception of the Greeks. ponderable electricity and riotous ether From Aristotle to, but not including, John of today might appear of the same intel­ Mayow we find speculation dominating the lectual order as pneuma.^^ interpretation of natural phenomena. To quote again from Garrison^®: The ancients completely misunderstood the purpose of the respiration. They never “Before Harvey’s time,” says Allbutt, “res­ dreamed that it was the agent of combus­ piration was regarded not as a means of com­ tion in the body but supposed it to be a bustion but of refrigeration. How man became safety, cooling device to prevent overheating such a fiery dragon was the puzzle!’’ Harvey’s demonstrations showed that the blood is of the organism through its inherent fire. changed from venous to arterial in the lungs, This misconception led them into a blind but beyond that point, as even Pepys has alley which received no outer light until the recorded in his Diary, no one could tell how or time of John Mayow and from which why we breathe. The successive steps in what thought did not emerge until led by Lavoi­ Sir Clifford Allbutt calls the “pathetic quest for sier. But this period of history must be oxygen” were as follows: First, the distin­ barren for us unless we can assume the guished chemist Robert Boyle made experi­ viewpoint of the great minds of those days. ments with flames and animals in vacuo (1660), To the early investigators two things demonstrating that air is necessary for life above all must have stigmatized higher as well as for combustion. Next, Robert Hooke living beings: one was animal heat; the other ... in 1667, showed, by blowing a bellows was vitality itself. What more natural, then, briskly over the open thorax of a dog, that than to conceive that fierce combustion was artificial respiration can keep the animal alive without any movement of either chest or lungs. a sign of mammalian life and that the This experiment, which had also been performed turbulent heart was the seat thereof? And by Vesalius, proved that the essential feature of it was altogether reasonable to suppose that respiration is not in its intrinsic movements, but such a furnace should have a damper; and in certain blood changes in the lungs. The next what more obvious than that the cool air step was made by Richard Lower, of Cornwall entering the lungs through the respiratory ... an able physiologist and successful prac­ motion should prevent the fires within the titioner, who was first to perform direct trans­ heart from consuming the body? We find, fusion of blood from one animal to another accordingly, that for twenty centuries, (February, 1665), and who, with Schneider, including at the end even Harvey himself, overthrew the old Galenic idea (even upheld the function of respiration was completely Allbutt, T. C. Op. cit. Chapter on Pneumatism, Garrison, F. H. History of Medicine, Ed. 3, p. 224. Phila., 1921. Garrison, F. H. Op. cit. by Vesalius) that the nasal secretions originate friends, the masters of medicine of Greece in the pituitary body. . . . About 1669 Lower and Rome. I cannot in this brief sketch injected dark venous blood into the insufflated venture to play the expositor or critic of the lungs, and concluded that its consequent phlogiston theory. It seems to me, perhaps bright color was due to the fact that it had erroneously, to foreshadow the modern con­ absorbed some of the air passing through the ception of zymogen, the inactive principle lungs. Finally, John Mayow . . . another Cornish- from which the active ferment of secretory man, demonstrated, in a series of convincing glands is developed. experiments, that the dark venous blood is Thus, Foster quotes the chemist F. Sylvius changed to bright red by taking up a certain (ca. 1660): “Briefly, in the act of composi­ ingredient in the air which, as being a con­ tion, as an instrument there intervenes and stituent of nitre (knos), he termed the igneo- is most potent, fire, flaming, fervid, hot; aerial particles or nitro-aerial spirit of air. but in the very substance of the compound there intervenes, as an ingredient, as it is Under this unfortunate appellation commonly called, as a material principle Mayow clearly distinguished the properties of fire, not fire itself. This I was the first to of oxgyen. call ‘phlogiston.’” It would have been rare A more pertinent illustration of the fruit­ humor to have called it “perspicuity”! fulness of the inductive method in science Foster thus writes could not be found than in this modern Priestley, as I have said, was devoted to the history of respiration. But just as Van phlogiston theory. He thought phlogiston; he Helmont’s “gas sylvestre” had long to wait could not lay hold of any subject save from the before Black rediscovered “fixed air,” car­ phlogiston point of view. Air supported com­ bon dioxide, so Mayow’s conception was bustion because it took up the phlogiston given born too soon. out by the burning body. Common air was to a More than a hundred years elapsed before certain extent free from phlogiston, it was Priestley isolated oxygen and identified its dephlogisticated, and in proportion as it was so properties but, in a most interesting way, dephlogisticated, it could support combustion. failed to comprehend its relations to com­ Common air supported combustion to a bustion and respiration because his imagi­ certain extent only, a part only of it could support combustion because it was only par­ nation was enthralled by the phlogiston tially dephlogisticated. The new air (oxygen) theory of chemistry which had been enun­ which he got from the metallic oxides was ciated by Stahl a hundred years before. wholly dephlogisticated. . With all the speculative ardor but with­ out the genius of the Greeks, it is curious Briefly, according to the phlogiston how Stahl, with a hypothesis borrowed from theory, combustion was a concomitant of the now obscure Beecher, should have so chemical decomposition and not, as we know long influenced the philosophy of physi­ it, of chemical combination. ology and chemistry. It is an interesting illustration of the History, like current society, is often superiority of Science to narrow nationalism ruled by perverted minds of dominating to find the Englishman, Foster, volunteer force. It is hard even today to grasp the this tribute: “Whether Lavoisier got at his viewpoint of the phlogiston theory. If my result wholly of himself or no, he and he little essay here can induce others to read alone, not Priestley in any way, got at the Foster’s satisfying account, it will be well true meaning of the result. He and he alone rewarded; they will then want to browse really discovered Oxygen.” round the well-spring set flowing by Garri­ From his most fortunate association in son, and they may let Allbutt take them research with the great mathematician by the hand and introduce them to his Foster, M. Op. cit., p. 168. Laplace, Lavoisier with him developed the brate and invertebrate. Foster says of following conclusion: him^^: Respiration is therefore a combustion, slow In addition to many valuable observations it is true, but otherwise perfectly similar to as to the effects of circumstances and environ­ the combustion of charcoal. It takes place in ment, such as temperature, hibernation and the interior of the lung without giving rise to the like on the respiratory process, these sensible light because the matter of the fire memoirs (published in 1803, after the death of (the caloric) as soon as it is set free is forthwith Spallanzani) contain two far reaching con­ absorbed by the humidity of these organs. The clusions. The one is that the tissues, like the heat developed by this combustion is com­ body as a whole, respire, that is to say con­ municated to the blood which is traversing the sume oxygen and produce carbonic acid; the lungs, and from the lungs is distributed over the other is that animals (snails) placed in an whole animal system. atmosphere of hydrogen or nitrogen give out The great Lavoisier, possibly overper­ carbonic acid in the same way that they do in common air. suaded by his physiological associate Sequin, had limited the site of animal combustion But history here repeats itself. Human to the bronchial tubes, the assumed fuel minds could not clearly grasp Spallanzani’s being carbonaceous matter excreted therein. conception, even when W. T. Edwards, as Curiously enough, another great French late as 1823, published his extraordinary mathematician beside Laplace here entered essay, “The Influence of Physical Agents on the physiological quest and diverted it into Life,” setting forth essentially the modern the right path. Lagrange (1736-1813), doctrine. Scientific men continued in the assisted by a skilled chemist, Hassenfratz, belief that the lungs were the main or only reasoned that were the lungs the sole seat seat of oxidations in the body. The theory of the generation of bodily heat, as postu­ of Lagrange assumed the presence in the lated by Lavoisier, not only should the blood both of oxygen and carbonic acid, but lungs be manifestly warmer than the rest of the demonstration of this fact demanded the body but they would likely be consumed far more perfect apparatus than was then by combustion. Lagrange (1791) accord­ available. We have to wait until 1837, after ingly advanced the idea that the blood pass­ the Invention of the mercurial air pump, ing through the lungs absorbed the oxygen when Gustav Magnus (1802-1870), pro­ of the inspired air and in the course of its fessor of physics at Berlin, settled the con­ circulation through the body the dissolved troversy. By the Torricellian vacuum he oxygen combined little by little with the was able to extract both from arterial and carbon and the hydrogen of the blood, venous blood oxygen and carbonic acid, warming the body and forming carbonic though in different proportions, together acid and water to be returned in the venous with a small proportion of nitrogen. He circulation to the lungs and there excreted found that the percentage of oxygen was with the expired air. greater in arterial blood and of carbonic But the great error of Lavoisier and the acid in venous blood. Magnus supposed that lesser one of Lagrange were both exploded gas exchanges in the lungs between the air by Spallanzani’s demonstration of tissue and the blood took place according to the respiration. familiar law of diffusion, the gases being The Abbe Spallanzani (1729-1799), who held in the blood in simple solution. had already spent many years in the most But in 1857 Lothar Meyer (1830-1895) convincing experimental development of showed that the amount of oxygen liberated our knowledge of digestion, devoted much from the blood does not increase propor­ of his latter dife to the study of the physi­ tionately to the diminution of pressure in ology of the respiration in'animals both'verte­ Foster, M. Op. cit., p. 253. the air pump, as it should according to respiration, as commonly understood, ceases Dalton’s law, but that the oxygen does not and metabolism begins. begin to come off in quantity until the pres­ We here reach the boundary of misinter­ sure upon the blood has been reduced to pretations that had endured through the ages. one-fiftieth of an atmosphere. The meaning Thought had ripened in a fruitful field of these facts is, broadly speaking, that of facts and as if by inspiration scientific oxygen diffuses from the air ceffs of the fungs men began to perceive the meaning of into the moist lining epithefium, thence to animal metabolism. the lymph within the tissue spaces, thence Modern pathology teaches that the occur­ through the moist walls of the pulmonary rence of infectious disease postulates indu­ capilfaries; it is there taken up by the bitably the previous inclusion within the circufating blood plasma. Aff this is supposed sick body of a foreign entity which ferments to proceed according to the faw of diffusion. without visible expression for a longer or Now comes into action a vitaf mechanism shorter period of incubation. Like germs, of surpassing importance, the hemogfobin ideas have their waves with troughs of confined within the red corpuscles. dormancy and crests of reproduction; their This substance has an extraordinary periods of incubation and variations in affinity for oxygen. Crudely speaking it virulence. A susceptible mind conceives sucks up the oxygen from the fluid in which and gives birth to a thought which repre­ it swims and packs it away among its sents a truth in Nature. It seems to fall chemical side chains. Hemogfobin can thus stillborn; but no, it has infectivity and after absorb many times its own volume of oxy­ a longer or shorter time it is born again, gen condensed in the chemicaf compound, and at its second birth it finds not single oxyhemogfobin. It can thus reduce the minds only, but hosts of minds prepared to tension of oxygen in the bfood plasma to react to it. about of an atmosphere and stiff under Our little review seems to show that the normal conditions the hemoglobin of the discovery of a general truth needs two red corpuscles in the pulmonary veins is conditions: first, the ready, apprehensive nearly saturated with oxygen. These vehi­ mind; second, a fund of appropriate facts cles hurry on their course throughout the collected through various sources for an body and wherever there is oxygen defi­ indefinite period. Harvey’s was the ready ciency below a partial pressure of about mind adequately furnished with substantial f:5o of an atmosphere a portion of the cargo facts regarding the circulation of the blood is unloaded until, after passage of the capil­ whence he was able to educe the truth, laries, and in proportion to the activities of even though he lacked the final proof the living tissues, the load of oxygen is provided by Malpighi. But he failed to sensibly decreased. The scarlet color of explain the respiration because the funda­ the arterial blood changes in the veins to a mental facts were wanting. No incident of bluish tint, due to admixture of reduced his life better displayed scientific greatness hemoglobin, the color of which is than his self control in renouncing the bluish-black. temptation to build hypotheses out of what Our story has thus led oxygen up to the he recognized as insuflicient data upon the threshold of the tissues. As the avidity of subject of respiration. hemoglobin for oxygen had charged with Much later Priestley with admirable skill it the erythrocytes in the lungs, so the isolated gas which supported combustion hunger of the living tissue cells for the brilliantly and in which animals could live; same vital clement unloads the corpuscles but the meaning of his discovery was with an urgency proportionate to the energy perverted through a premature and errone­ needs of the body. Entering the tissues. ous theory. He visited Lavoisier and probably entity. Perhaps one day some Mendel of the described his production of “completely mind may establish a formula which will dephlogisticated air.” But Lavoisier sensed make education as exact as mechanics. the true explanation and within two years We can now hurry to our goaf. It was not had isolated oxygen and proved that both until after the middle of the nineteenth combustion and respiration represented century that it became established that the essentially the combination of oxygen with solid tissues themselves were the essential combustible matter. sites of oxidation of the body, a conception I may venture to add one incident from already advanced by John Mayow long our own times. Henry Newell Martin, before. Rcgnault and Rciset, Hoppe-Seyler, whom Huxley and Foster had recommended Pllugcr, Ludwig, and their pupils, gave as incumbent of the chair of Biology in the wonderful impulse to physiological research. new Foundation, Johns Hopkins University, Gas analysis of the blood, introduced by set himself immediately to the organization Magnus, formed a special field in this of biological research. Further progress in development and must be looked upon as the physiology of the mammalian heart a direct predecessor of what is now a range seemed to demand that the experimental of biochemistry that is of daily use to conditions be simplified by isolating the practical clinicians. The human body itself organ from the rest of the body. was shown to be a machine which operates The problem was how to effect the return under the law of conservation of energy. of the blood from the aorta directly to the Americans should not forget that it was right auricle without passing through the W. O. Atwater who, as professor of chemis­ complicating systemic circulation. One sleep­ try at Wesleyan University, in the middle less night in i88i the solution of the riddle nineties constructed the first respiration­ flashed through Martin’s mind. He realized calorimeter which approached mechanical that were the main stem of the aorta perfection; and with his colleagues, the late clamped the circuit of the blood might be E. B. Rosa and F. G. Benedict, initiated completed through the walls of the heart researches in animal metabolism which form itself by way of the coronary vessels. a worthy sequel to the earlier work. The next morning he told his assistant of his idea. So, after laboratory hours, a dog Summary of Progress in the Physiology OF Respiration was anesthetized, the heart laid bare, the cavae and aorta were ligated and, under 1. Harvey (1578-1657), after a century of artificial respiration, the heart functioned predecessors beginning, perhaps, with J. normally within a dead body. More than Sylvius (1478-1555) and ending with Sarpi three hundred years after the birth of (1552-1623), cleared the way for the under­ Harvey, but the ready mind appeared. standing of respiration by his demonstration Our story has shown that mere incidents of the circulation of the blood. are abortive without a plot to give them 2. Van Helmont (1577-1644) discovered meaning. One cannot but wonder if such a “gas Sylvestre,” carbonic acid. history does not contain efements which 3. Boyle (1627-1691) proved that air challenge further interpretation. The science is alike necessary to respiration and of genetics is built on the laws of chromo­ combustion. somes and plasms. 4. Hooke (1635—1703) proved by blowing But in a sense, not wholly figurative, air from a bellows over the exposed lungs of mind inseminates mind and Thought has its a dog that respiratory motion was not evolution as truly as Soma. necessary to maintain life. Physicists have declared that matter and 5. Lower (1631-1691) proved that some­ energy are but different phases of the same thing was absorbed from the air in the lungs which turned dark blood bright red. He first and transported by the circulation through­ performed direct transfusion of blood from out the body. animal to animal. 12. Lagrange (1736-1813) advanced the 6. Mayow (1643-1679) proved that it was idea that the principal oxidations of the a definite constituent of air which, taken up body occurred not in the lungs but in the by the blood, turned it from dark red to blood, combining there with carbon and scarlet. He called it the “ nitro-aereal spirit hydrogen; the products returned to the lungs of the air,” and determined its properties— by the venous blood were there expired. a gas known as oxygen. 13. Spallanzani (1729-1799) proved that 7. Black (1728-1799) rediscovered “fixed the tissues themselves respired, i.e., absorbed air,” carbonic acid, and defined its proper­ oxygen and gave off carbonic acid. ties. 14. Gustav Magnus (1802-1870) with the 8. Stahl (1660-1734) obstructed progress mercurial air-pump (Torricellian vacuum) with the phlogiston theory for a hundred extracted both oxygen and carbonic acid, years. with a little nitrogen from the blood. 9. Priestley (1733-1804) discovered 15. Lothar Meyer (1830-1895) showed de-phlogisticated air, or oxygen, but mis­ that the O2 was not held in simple solution understood its function in combustion and in the blood, but came off in quantity only respiration. when the air pressure was reduced to 10. Lavoisier (1743-1794) discovered atmosphere. oxygen and defined its true relation to 16. The law of the conservation of energy combustion and respiration—as a synthesis was applied to the living body; the principal with carbon and hydrogen. seat of oxidations was located in the tissues; 11. Lavoisier and Laplace (1749-1827) metabolism and nutrition were studied by a showed that respiration is a combustion, long fine of investigators, including Regnault only slower than that of ordinary fire. They (1810-1878), Hoppe-Seyler (1825-1895), supposed the oxidation to be limited to the Pfliiger (1829-1910), Bert (1830-1886), lungs, the heat being absorbed therefrom Voit (1831-1908) and Atwater (1844-1907).