PART I EXPERIMENTS IN PHYSIOLOGY |
EXPERIMENTS ON ANIMALS I
THE BLOOD I.—Before Harvey Galen, born at Pergamos, 131 A.D., proved by experiments on animals that the brain is as warm as the heart, against the Aristotelian doctrine that the office of the brain is to keep the heart cool. He also proved that the arteries during life contain blood, not p?e?a (Greek: pneuma), or the breath of life:— "Ourselves, having tied the exposed arteries above and below, opened them between the ligatures, and showed that they were indeed full of blood." Though all vessels bleed when they are wounded, yet this experiment was necessary to refute the fanciful teaching of Erasistratus and his followers, of whom Galen says:— "Erasistratus is pleased to believe that an artery is a vessel containing the breath of life, and a vein is a vessel containing blood; and that the vessels, dividing again and again, come at last to be so small that they can close their ultimate pores, and keep the blood controlled within them; yea, though the pores of the vein and of the artery lie side by side, yet the blood remains within its proper bounds, nowhere passing into the vessels of the breath of life. But when the blood is driven with violence from the veins into the arteries, forthwith there is disease; and the blood is poured the wrong way into the arteries, and there withstands and dashes itself against the breath of life coming from the heart, and turns the course of it—and this forsooth is fever." For many centuries after Galen, men were content to worship his name and his doctrines, and forsook his method. They did not follow the way of experiment, and invented theories that were no help either in science or in practice. Here, in Galen's observation of living arteries, was a great opportunity for physiology; but the example that he set to those who came after him was forgotten by them, and, from the time of Galen to the time of the Renaissance, physiology remained almost where he had left it. Of the men of the Renaissance, Servetus, CÆsalpinus, Ruinius, and others, Harvey's near predecessors, this much only need be said here, that they did not discover the circulation of the blood; and that the claim made a few years ago to this discovery, on behalf of CÆsalpinus, by his countrymen, was not successful. But it is probable that Realdus (1516-1557) did understand the passage of blood through the lungs, but not the general circulation. He says:— "The blood is carried through the pulmonary artery to the lung, and there is attenuated; thence, mixed with air, it is carried through the pulmonary vein to the left ventricle of the heart: which thing no man hitherto has noted or left on record, though it is most worthy of the observation of all men.... And this is as true as truth itself; for if you will look, not only in the dead body but also in the living animal, you will always find this pulmonary vein full of blood, which assuredly it would not be if it were designed only for air and vapours.... Verily, I pray you, O candid reader, studious of authority, but more studious of truth, to make experiment on animals. You will find the pulmonary vein full of blood, not air or fuligo, as these men call it, God help them. Only there is no pulsation in the vein." (De Re AnatomicÂ, Venice, 1559.) Fabricius ab Aquapendente, Harvey's master at Padua, published his work on the valves of the veins—De Venarum Ostiolis—in 1603. He did not discover them. Sylvius speaks of them in his Isagoge (Venice, 1555), and they were known to Amatus (1552), and even to Theodoretus, Bishop of Syria, who lived, as John Hunter said of Sennertus, "the Lord knows how long ago." But Fabricius studied them most carefully; and in anatomy he left nothing more to be said about them. In physiology, his work was of little value; for he held that they were designed "to retard the blood in some measure, lest it should run pell-mell into the feet, hands, and fingers, there to be impacted": they were to prevent distension of the veins, and to ensure the due nourishment of all parts of the body. It is true that he compared them to the locks or weirs of a river, but he understood neither the course nor the force of the blood: as Harvey said of him, "The man who discovered these valves did not understand their right use; neither did they who came after him"—Harum valvularum usum rectum inventor non est assecutus, nec alii addiderunt; non est enim ne pondere deorsum sanguis in inferiora totus ruat; sunt namque in jugularibus deorsum spectantes, et sanguinem sursum ferri prohibentes. Men had no idea of the rapidity and volume of the circulation; they thought of a sort of Stygian tide, oozing this way or that way in the vessels—CÆsalpinus was of opinion that it went one way in the daytime and another at night—nor did they see that the pulmonary circulation and the general circulation are one system, the same blood covering the whole course. The work that they did in anatomy was magnificent; Vesalius, and the other great anatomists of his time, are unsurpassed. But physiology had been hindered for ages by fantastic imaginings, and the facts of the circulation of the blood were almost as far from their interpretation in the sixteenth century as they had been in the time of Galen. II.—Harvey (1578-1657) The De Motu Cordis et Sanguinis in Animalibus was published at Frankfurt in 1628. And it begins with these words: Cum multis vivorum dissectionibus, uti ad manum dabantur:— "When by many dissections of living animals, as they came to hand, I first gave myself to observing how I might discover with my own eyes, and not from books and the writings of other men, the use and purpose of the movement of the heart in animals, forthwith I found the matter hard indeed, and full of difficulty: so that I began to think, with Frascatorius, that the movement of the heart was known to God alone. For I could not distinguish aright either the nature of its systole and diastole, or when or where dilatation and contraction took place; and this because of the swiftness of the movement, which in many animals in the twinkling of an eye, like a flash of lightning, revealed itself to sight and then was gone; so that I came to believe that I saw systole and diastole now this way now the other, and movements now apart and now together. Wherefore my mind wavered; I had nothing assured to me, whether decided by me or taken from other men: and I did not wonder that Andreas Laurentius had written that the movement of the heart was what the ebb and flow of the Euripus had been to Aristotle. "At last, having daily used greater disquisition and diligence, by frequent examination of many and various living animals—multa frequenter et varia animalia viva introspiciendo—and many observations put together, I came to believe that I had succeeded, and had escaped and got out of this labyrinth, and therewith had discovered what I desired, the movement and use of the heart and the arteries. And from that time, not only to my friends, but also in public in my anatomical lectures, after the manner of the Academy, I did not fear to set forth my opinion in this matter." It is plain, from Harvey's own words, that he gives to experiments on animals a foremost place among his methods of work. Take only the headings of his first four chapters:— i. CausÆ, quibus ad scribendum auctor permotus fuerit.
ii. Ex vivorum dissectione, qualis fit cordis motus.
iii. Arteriarum motus qualis, ex vivorum dissectione.
iv. Motus cordis et auricularum qualis, ex vivorum dissectione. He thrusts it on us, he puts it in the foreground. Read the end of his Preface:— "Therefore, from these and many more things of the kind, it is plain (since what has been said by men before me, of the movement and use of the heart and arteries, appears inconsistent or obscure or impossible when one carefully considers it) that we shall do well to look deeper into the matter; to observe the movements of the arteries and the heart, not only in man, but in all animals that have hearts; and by frequent dissection of living animals, and much use of our own eyes, to discern and investigate the truth—vivorum dissectione frequenti, multÂque autopsiÂ, veritatem discernere et investigare." Finally, take the famous passage in the eighth chapter, De copi sanguinis transeuntis per cor e venis in arterias, et de circulari motu sanguinis:— "And now, as for the great quantity and forward movement of this blood on its way, when I shall have said what things remain to be said—though they are well worth considering, yet they are so new and strange that I not only fear harm from the envy of certain men, but am afraid lest I make all men my enemies; so does custom, or a doctrine once imbibed and fixed down by deep roots, like second nature, hold good among all men, and reverence for antiquity constrains them. Be that as it may, the die is cast now: my hope is in the love of truth, and the candour of learned minds. I bethought me how great was the quantity of this blood. Both from the dissection of living animals for the sake of experiment, with opening of the arteries, with observations manifold; and from the symmetry of the size of the ventricles, and of the vessels entering and leaving the heart—because Nature, doing nothing in vain, cannot in vain have given such size to these vessels above the rest—and from the harmonious and happy device of the valves and fibres, and all other fabric of the heart; and from many other things—when I had again and again carefully considered it all, and had turned it over in my mind many times—I mean the great quantity of the blood passing through, and the swiftness of its passage—and I did not see how the juices of the food in the stomach could help the veins from being emptied and drained dry, and the arteries contrariwise from being ruptured by the excessive flow of blood into them, unless blood were always getting round from the arteries into the veins, and so back to the right ventricle—I began to think to myself whether the blood had a certain movement, as in a circle—coepi egomet mecum cogitare, an motionem quandam quasi in circulo haberet—which afterward I found was true." This vehement passage, which goes with a rush like that of the blood itself, is a good example of the width and depth of Harvey's work—how he used all methods that were open to him. He lived to fourscore years; "an old man," he says, "far advanced in years, and occupied with other cares": and, near the end of his life, he told the Hon. Robert Boyle that the arrangement of the valves of the veins had given him his first idea of the circulation of the blood:— "I remember that when I asked our famous Harvey, in the only discourse I had with him, which was but a while before he died, what were the things which induced him to think of the circulation of the blood, he answered me that when he took notice that the valves in the veins of so many parts of the body were so placed that they gave free passage of the blood towards the heart, but opposed the passage of the venal blood the contrary way, he was invited to imagine that so provident a cause as Nature had not so placed so many valves without design; and no design seemed more probable than that, since the blood could not well, because of the interposing valves, be sent by the veins to the limbs, it should be sent by the arteries, and return through the veins, whose valves did not oppose its course that way." But between this observation, which "invited him to imagine" a theory, and his final proofs of the circulation, lay a host of difficulties; and it is certain, from his own account of his work, that experiments on animals were of the utmost help to him in leading him "out of the labyrinth." III.—After Harvey 1. The Capillaries The capillary vessels were not known in Harvey's time: the capillamenta of CÆsalpinus were not the capillaries, but the ?e?^?a (Greek: neura) of Aristotle. It was believed that the blood, between the smallest arteries and the smallest veins, made its way through "blind porosities" in the tissues, as water percolates through earth or through a sponge. The first account of the capillaries is in two letters (De Pulmonibus, 1661) from Malpighi, professor of medicine at Bologna, to Borelli, professor of mathematics at Pisa. In his first letter, Malpighi writes that he has tried in vain, by injecting the dead body, to discover how the blood passes from the arteries into the veins:— "This enigma hitherto distracts my mind, though for its solution I have made many and many attempts, all in vain, with air and various coloured fluids. Having injected ink with a syringe into the pulmonary artery, I have again and again seen it escape (become extravasated into the tissues) at several points. The same thing happens with an injection of mercury. These experiments do not give us the natural pathway of the blood." But, in his second letter, he describes how he has examined, with a microscope of two lenses, the lung and the mesentery of a frog, and has seen the capillaries, and the blood in them:— "Such is the divarication of these little vessels, coming off from the vein and the artery, that the order in which the vessel ramifies is no longer preserved, but it looks like a network woven from the offshoots of both vessels." He was able, in a dead frog, to see the capillaries; and then, in a living frog, to see the blood moving in them. But, in spite of this work, it took nearly half a century before Harvey's teaching was believed by all men—Tantum consuetudo apud omnes valet. 2. The Blood-pressure Harvey had seen the facts of blood-pressure—the great quantity of blood passing through, and the swiftness of its passage—but he had not measured it. Keill's experiments on the blood-pressure (1718) were inexact, and of no value; and the first exact measurements were made by Stephen Hales, who was rector of Farringdon, Hampshire, and minister of Teddington, Middlesex; a Doctor of Divinity, and a Fellow of the Royal Society. His experiments, in their width and diversity, were not surpassed even by those of John Hunter, and were extended far over physiology, vegetable physiology, organic and inorganic chemistry, and physics; they ranged from the invention of a sea-gauge to the study of solvents for the stone, and he seems to have experimented on every force in Nature. The titles of his two volumes of Statical Essays (1726-1733) show the great extent of his non-clerical work:— Volume I. Statical Essays, containing Vegetable Statics, or an Account of some Statical Experiments on the Sap in Vegetables, being an Essay towards a Natural History of Vegetation; also, a Specimen of an Attempt to Analyse the Air, by a great Variety of Chymio-Statical Experiments. Volume II. Statical Essays, containing HÆmostatics, or an Account of some Hydraulic and Hydrostatical Experiments made on the Blood and Blood-vessels of Animals; also, an Account of some Experiments on Stones in the Kidneys and Bladder, with an Enquiry into the Nature of those anomalous Concretions. "We can never want matter for new experiments," he says in his preface. "We are as yet got little further than to the surface of things: we must be content, in this our infant state of knowledge, while we know in part only, to imitate children, who, for want of better skill and abilities, and of more proper materials, amuse themselves with slight buildings. The farther advances we make in the knowledge of Nature, the more probable and the nearer to truth will our conjectures approach: so that succeeding generations, who shall have the benefit and advantage both of their own observations and those of preceding generations, may then make considerable advances, when many shall run to and fro, and knowledge shall be increased." His account of his plan of measuring the blood-pressure, and of one of many experiments that he made on it, is as follows:— "Finding but little satisfaction in what had been attempted on this subject by Borellus and others, I endeavoured, about twenty-five years since, by proper experiments, to find what was the real force of the blood in the crural arteries of dogs, and about six years afterwards I repeated the like experiments on two horses, and a fallow doe; but did not then pursue the matter any further, being discouraged by the disagreeableness of anatomical dissections. But having of late years found by experience the advantage of making use of the statical way of investigation, not only in our researches into the nature of vegetables, but also in the chymical analysis of the air, I was induced to hope for some success, if the same method of enquiry were applied to animal bodies.... "Having laid open the left crural artery (of a mare), I inserted into it a brass pipe whose bore was 1/6 of an inch in diameter; and to that, by means of another brass pipe which was fitly adapted to it, I fixed a glass tube of nearly the same diameter, which was 9 feet in length; then, untying the ligature on the artery, the blood rose in the tube 8 feet 3 inches perpendicular above the level of the left ventricle of the heart, but it did not attain to its full height at once: it rushed up gradually at each pulse 12, 8, 6, 4, 2, and sometimes 1 inch. When it was at its full height, it would rise and fall at and after each pulse 2, 3, or 4 inches, and sometimes it would fall 12 or 14 inches, and have there for a time the same vibrations up and down, at and after each pulse, as it had when it was at its full height, to which it would rise again, after forty or fifty pulses." 3. The Collateral Circulation After Hales, came John Hunter, who was five years old when the Statical Essays were published. His experiments on the blood were mostly concerned with its properties, not with its course; but one great experiment must be noted here that puts him in line with Harvey, Malpighi, and Hales. He got from it his knowledge of the collateral circulation; he learned how the obstruction of an artery is followed by enlargement of the vessels in its neighbourhood, so that the parts beyond the obstruction do not suffer from want of blood: and the facts of collateral circulation were fresh in his mind when, a few months later, he conceived and performed his operation for aneurysm (December 1785). The "old operation" gave him no help here; and "Anel's operation" was but a single instance, and no sure guide for Hunter, because Anel's patient had a different sort of aneurysm. Hunter knew that the collateral circulation could be trusted to nourish the limb, if the femoral artery were ligatured in "Hunter's canal" for the cure of popliteal aneurysm; and he got this knowledge from the experiment that he had made on one of the deer in Richmond Park, to see the influence of ligature of the carotid artery on the growth of the antler. The following account of this experiment was given by Sir Richard Owen, who had it from Mr. Clift, Hunter's devoted pupil and friend:— "In the month of July, when the bucks' antlers were half-grown, he caused one of them to be caught and thrown; and, knowing the arterial supply to the hot 'velvet,' as the keepers call it, Hunter cut down upon and tied the external carotid; upon which, laying his hand upon the antler, he found that the pulsations of the arterial channels stopped, and the surface soon grew cold. The buck was released, and Hunter speculated on the result—whether the antler, arrested at mid-growth, would be shed like the full-grown one, or be longer retained. A week or so afterward he drove down again to the park, and caused the buck to be caught and thrown. The wound was healed about the ligature; but on laying his hand on the antler, he found to his surprise that the warmth had returned, and the channels of supply to the velvety formative covering were again pulsating. His first impression was that his operation had been defective. To test this, he had the buck killed and sent to Leicester Square. The arterial system was injected. Hunter found that the external carotid had been duly tied. But certain small branches, coming off on the proximal or heart's side of the ligature, had enlarged; and, tracing-on these, he found that they had anastomosed with other small branches from the distal continuation of the carotid, and these new channels had restored the supply to the growing antler.... Here was a consequence of his experiment he had not at all foreseen or expected. A new property of the living arteries was unfolded to him." All the anatomists had overlooked this physiological change in the living body, brought about by disease. And the surgeons, since anatomy could not help them, had been driven by the mortality of the "old operation" to the practice of amputation. 4. The Mercurial Manometer Hale's experiments on the blood-pressure were admirable in their time; but neither he nor his successors could take into account all the physiological and mathematical facts of the case. But a great advance was made in 1828, when Poiseuille published his thesis, Sur la Force du Coeur Aortique, with a description of the mercurial manometer. Poiseuille had begun with the received idea that the blood-pressure in the arteries would vary according to the distance from the heart, but he found by experiment that this doctrine was wrong:— "At my first experiments, wishing to make sure whether the opinions, given À priori, were true, I observed to my great astonishment that two tubes, applied at the same time to two arteries at different distances from the heart, gave columns of exactly the same height, and not, as I had expected, of different heights. This made the work very much simpler, because, to whatever artery I applied the instrument, I obtained the same results that I should have got by placing it on the ascending aorta itself." He found also, by experiments, that the coagulation of the blood in the tube could be prevented by filling one part of the tube with a saturated solution of sodium carbonate. The tube, thus prepared, was connected with the artery by a fine cannula, exactly fitting the artery. With this instrument, Poiseuille was able to obtain results far more accurate than those of Hales, and to observe the diverse influences of the respiratory movements on the blood-pressure. He sums up his results in these words:— "I come to this irrevocable conclusion, that the force with which a molecule of blood moves, whether in the carotid, or in the aorta, etc., is exactly equal to the force which moves a molecule in the smallest arterial branch; or, in other words, that a molecule of blood moves with the same force over the whole course of the arterial system—which, À priori, with all the physiologists, I was far from thinking." And he adds, in a footnote:— "When I say that this force is the same over the whole course of the arterial system, I do not mean to deny that it must needs be modified at certain points of this system, which present a special arrangement, such as the anastomosing arches of the mesentery, the arterial circle of Willis, etc." Later, in 1835, he published a very valuable memoir on the movement of the blood in the capillaries under different conditions of heat, cold, and atmospheric pressure. 5. The Registration of the Blood-pressure Poiseuille's work, in its turn, was left behind as physiology went forward: especially, the discovery of the vaso-motor nerves compelled physiologists to reconsider the whole subject of the blood-pressure. If Poiseuille's thesis (1828) be compared with Marey's book (1863), Physiologie MÉdicale de la Circulation du Sang, it will be evident at once how much wider and deeper the problem had become. Poiseuille's thesis is chiefly concerned with mathematics and hydrostatics; it suggests no method of immediate permanent registration of the pulse, and is of no great value to practical medicine: Marey's book, by its very title, shows what a long advance had been made between 1828 and 1863—Physiologie MÉdicale de la Circulation du Sang, basÉe sur l'Étude graphique des mouvements du coeur et du pouls artÉriel, avec application aux maladies de l'appareil circulatoire. Though the contrast is great between Hales' may-pole and Poiseuille's manometer, there is even a greater contrast between Poiseuille's mathematical calculations and Marey's practical use of the sphygmograph for the study of the blood-pressure in health and disease. Marey had the happiness of seeing medicine, physiology, and physics, all three of them working to one end:— "La circulation du sang est un des sujets pour lesquels la mÉdecine a le plus besoin de s'Éclairer de la physiologie, et oÙ celle-ci À son tour tire le plus de lumiÈre des sciences physiques. Ces derniÈres annÉes sont marquÉes par deux grands progrÈs qui ouvrent aux recherches À venir des horizons nouveaux: en Allemagne, l'introduction des procÉdÉs graphiques dans l'Étude du mouvement du sang; en France, la dÉmonstration de l'influence du systÈme nerveux sur la circulation pÉriphÉrique. Cette derniÈre dÉcouverte, que nous devons À M. Cl. Bernard, et qui depuis dix ans a donnÉ tant d'impulsion À la science, montre mieux que toute autre combien la physiologie est indispensable À la mÉdecine, tandis que les travaux allemands ont bien fait ressortir l'importance des connaissances physiques dans les Études mÉdicales." Marey's sphygmograph was not the first instrument of its kind. There had been, before it, HÉrisson's sphygmometer, Ludwig's kymographion, and the sphygmographs of Volckmann, King, and Vierordt. But, if one compares a Vierordt tracing with a Marey tracing, it will be plain that Marey's results were far advanced beyond the useless "oscillations isochrones" recorded by Vierordt's instrument. Beside this improved sphygmograph, Chauveau and Marey also invented the cardiograph, for the observation of the blood-pressure within the cavities of the heart. Their cardiograph was a set of very delicate elastic tambours, resting on the heart, or passed through fine tubes into the cavities of the heart,[1] and communicating impulses to levers with writing-points. These writing-points, touching a revolving cylinder, recorded the variations of the endocardial pressure, and the duration of the auricular and ventricular contractions.
It is impossible here to describe the subsequent study of those more abstruse problems that the older physiologists had not so much as thought of: the minutest variations of the blood-pressure, the multiple influences of the nervous system on the heart and blood-vessels, the relations between blood-pressure and secretion, the automatism of the heart-beat, the influence of gravitation, and other finer and more complex issues of physiology. But, even if one stops at Marey's book, now more than forty years old, there is an abundant record of good work, from the discovery of the circulation to the invention of the sphygmograph. II
THE LACTEALS Asellius, in his account of his discovery of the lacteal vessels (1622), is of opinion that certain of "the ancients" had seen these vessels, but had not recognised them. He has a great reverence for authority: Hippocrates, Plato, Aristotle, the Stoics, Herophilus, Galen, Pollux, Rhases, and a host of other names, he quotes them all, and all with profound respect; and comes to this conclusion: "It did not escape the ancients, that certain vessels must needs be concerned with containing and carrying the chyle, and certain other vessels with the blood: but the true and very vessels of the chyle, that is, my 'veins,' though they were seen by some of the ancients, yet they were recognised by none of them." He can forgive them all, except Galen, qui videtur nosse omnino debuisse—"but, as for Galen, I know not at all what I am to think. For he, who made more than six hundred sections of living animals, as he boasts himself, and so often opened many animals when they were lately fed, are we to think it possible that these veins never showed themselves to him, that he never had them under his eyes, that he never investigated them—he to whom Erasistratus had given so great cause for searching out the whole matter?" Probably, the milk-white threads had been taken for nerves by those who had seen them: and those who had never seen them, but believed in their existence, rested their belief on a general idea that the chyle must, somehow, have vessels of its own apart from the blood-vessels. What Galen and Erasistratus must have seen, Asellius and Pecquet discovered: and Harvey gives a careful review of the discovery in his letters to Nardi (May 1652) and to Morison (November 1653). He does not accept it; but the point is that he recognises it as a new thing altogether. A year or two after he had made the discovery, Asellius died; and his work was published in 1627 by two Milanese physicians, and was dedicated by them to the senate of the Academy of Milan, where Asellius had been professor of anatomy. The full title of his book is, De Lactibus sive Lacteis Venis, quarto Vasorum Mesaraicorum genere novo invento, Gasparis Asellii Cremonensis, Anatomici Ticinensis, Dissertatio. Qu sententiÆ anatomicÆ multÆ vel perperam receptÆ convelluntur vel partim perceptÆ illustrantur. He gives the following account of the discovery, in the chapter entitled Historia primÆ vasorum istorum inventionis cum fide narrata. On 23rd July 1622, demonstrating the movement of the diaphragm in a dog, he observed suddenly, "as it were, many threads, very thin and very white, dispersed through the whole mesentery and through the intestines, with ramifications almost endless"—plurimos, eosque tenuissimos candido-sissimosque ceu funiculos per omne mesenterium et per intestina infinitis propemodum propaginibus dispersos:— "Thinking at first sight that they were nerves, I did not greatly heed them. But soon I saw that I was wrong, for I bethought me that the nerves, which belong to the intestines, are distinct from these threads, and very different from them, and have a separate course. Wherefore, struck by the newness of the matter, I stopped for a time silent, while one way and another there came to my mind the controversies that occupy anatomists, as to the mesenteric veins and their use; which controversies are as full of quarrels as of words. When I had pulled myself together, to make experiment, taking a very sharp scalpel, I pierce one of the larger threads. Scarcely had I hit it off, when I see a white fluid running out, like milk or cream. At which sight, when I could not hold my joy, turning to those who were there, first to Alexander Tadinus and Senator Septalius, both of them members of the most honourable College of Physicians, and, at the time of this writing, officers of the public health, 'I have found it,' I say like Archimedes; and therewith invite them to the so pleasant sight of a thing so unwonted; they being agitated, like myself, by the newness of it." He then describes the collapse and disappearance of the vessels at death, and the many experiments which he made for further study of them; and the failure, when he tried to find them in animals not lately fed. He did not trace them beyond the mesentery, and believed that they emptied themselves into the liver. The discovery of their connection with the receptaculum chyli and the thoracic duct was made by Jehan Pecquet of Dieppe, Madame de SÉvignÉ's doctor, her "good little Pecquet." The full title of his book (2nd ed., 1654) is, ExpÉrimenta Nova Anatomica, quibus incognitum hactenus Receptaculum, et ab eo per Thoracem in ramos usque subclavios Vasa Lactea deteguntur. He has not the academical learning of Asellius, nor his obsequious regard for the ancients; and the discovery of the thoracic duct came, as it were by chance, out of an experiment that was of itself wholly useless. He had killed an animal by removing its heart, and then saw a small quantity of milky fluid coming from the cut end of the vena cava—Albicantem subinde Lactei liquoris, nec certe parum fluidi scaturiginem, intra VenÆ CavÆ fistulam, circ[=a] dextri sedem Ventriculi, miror effluere—and found that this fluid was identical with the chyle in the lacteals. In another experiment, he succeeded in finding the thoracic duct—"At last, by careful examination deep down along the sides of the dorsal vertebrÆ, a sort of whiteness, as of a lacteal vessel, catches my eyes. It lay in a sinuous course, close up against the spine. I was in doubt, for all my scrutiny, whether I had to do with a nerve or with a vessel. Therefore, I put a ligature a little below the clavicular veins; and then the flaccidity above the ligature, and the swelling of the distended duct below the ligature, broke down my doubt—Ergo subducto paulo infra Claviculas vinculo, cum a ligatur sursum flaccesceret, superstite deorsum turgentis alveoli tumore, dubium meum penitus enervavit.... Laxatis vinculis, lacteus utrinque rivulus in Cavam affatim Chylum profudit." It is to be noted that Asellius and Pecquet, both of them, made their discoveries as it were by chance. Unless digestion were going on, the lacteals would be empty and invisible; and, on the dead body, lacteals, receptaculum, and thoracic duct would all be empty. For these reasons, it cost a vast number of experiments to prove the existence, and to discover the course, of these vessels. Once found in living animals, they could be injected and dissected in the dead body; but they had been overlooked by Vesalius and the men of his time. From the discovery of the lacteals came the discovery of the whole lymphatic system. Daremberg, in his Histoire des Sciences MÉdicales (Paris, 1870), after an account of Pecquet's work, says:— "Up to this point, we have seen English, Italians, and French working together, with more or less success and genius, to trace the true ways of blood and chyle: there is yet one field of work to open up, the lymphatics of the body. The chief honour here belongs, without doubt, to the Swede Rudbeck, though the Dane Bartholin has disputed it with him, with equal acrimony and injustice." Rudbeck's work (1651-54) coincides exactly, in point of time, with the first and second editions, 1651 and 1654, of Pecquet's De Lactibus. It may be said, therefore, that the whole doctrine of the lymphatic system was roughed out half-way through the seventeenth century. III
THE GASTRIC JUICE From many causes, the experimental study of the digestive processes came later than the study of the circulation. As an object of speculative thought, digestion was a lower phase of life, the work of crass spirits, less noble than the blood; from the point of view of science, it could not be studied ahead of organic chemistry, and got no help from any other sort of knowledge; and, from the medical point of view, it was the final result of many unknown internal forces that could not be observed or estimated either in life or after death. It did not, like the circulation, centre itself round one problem; it could not be focussed by the work of one man. For these reasons, and especially because of its absolute dependence on chemistry for the interpretation of its facts, it had to bide its time; and RÉaumur's experiments are separated from the publication of Harvey's De Motu Cordis et Sanguinis by a hundred and thirty years. The following account of the first experiments on digestion is taken from Claude Bernard's Physiologie OpÉratoire, 1879:— "The true experimental study of digestion is of comparatively recent date; the ancients were content to find comparisons, more or less happy, with common facts. Thus, for Hippocrates, digestion was a 'coction': for Galen, a 'fermentation,' as of wine in a vat. In later times, van Helmont started this comparison again: for him, digestion was a fermentation like that of bread: as the baker, having kneaded the bread, keeps a little of the dough to leaven the next lot kneaded, so, said van Helmont, the intestinal canal never completely empties itself, and the residue that it keeps after each digestion becomes the leaven that shall serve for the next digestion. "The first experimental studies on the digestion date from the end of the seventeenth century, when the Academy of Florence was the scene of a famous and long controversy between Borelli and Valisnieri. The former saw nothing more in digestion than a purely mechanical act, a work of attrition whereby the ingesta were finely divided and as it were pulverised: and in support of this opinion Borelli invoked the facts that he had observed relating to the gizzard of birds. We know that this sac, with its very thick muscular walls, can exercise on its contents pressure enough to break the hardest bodies. Identifying the human stomach with the bird's gizzard, Borelli was led to attribute to the walls of the stomach an enormous force, estimated at more than a thousand pounds; whose action, he said, was the very essence of digestion. Valisnieri, on the contrary, having had occasion to open the stomach of an ostrich, had found there a fluid which seemed to act on bodies immersed in it; this fluid, he said, was the active agent of digestion, a kind of aqua fortis that dissolved food. "These two opposed views, resulting rather from observations than from regularly instituted experiments, were the starting-point of the experimental researches undertaken by RÉaumur in 1752. To resolve the problem set by Borelli and Valisnieri, RÉaumur made birds swallow food enclosed in fenestrated tubes, so that the food, protected from the mechanical action of the walls of the stomach, was yet exposed to the action of the gastric fluid. The first tubes used (glass, tin, etc.) were crushed, bent, or flattened by the action of the walls of the gizzard; and RÉaumur failed to oppose to this force a sufficient resistance, till he employed leaden tubes thick enough not to be flattened by a pressure of 484 pounds: which was, in fact, the force exercised by the contractile walls of the gizzard in turkeys, ducks, and fowls under observation. These leaden tubes—filled with ordinary grain, and closed only by a netting that let pass the gastric juices—these tubes, after a long stay in the stomach, still enclosed grain wholly intact, unless it had been crushed before the experiment. When they were filled with meat, it was found changed, but not digested. RÉaumur was thus led at first to consider digestion, in the gallinaceÆ, as pure and simple trituration. But, repeating these experiments on birds of prey, he observed that digestion in them consists essentially in dissolution, without any especial mechanical action, and that it is the same with the digestion of meat in all animals with membranous stomachs. To procure this dissolving fluid, RÉaumur made the birds swallow sponges with threads attached: withdrawing these sponges after a definite period, he squeezed the fluid into a glass, and tested its action on meat. That was the first attempt at artificial digestion in vitro. He did not carry these last investigations very far, and did not obtain very decisive results; nevertheless he must be considered as the discoverer of artificial digestion." After RÉaumur, the AbbÉ Spallanzani (1783) made similar observations on many other animals, including carnivora. He showed that even in the gallinaceÆ there was dissolution of food, not mere trituration: and observed how after death the gastric fluid may under certain conditions act on the walls of the stomach itself. "Henceforth the experimental method had cut the knot of the question raised by the theories of Borelli and Valisnieri: digestion could no longer be accounted anything but a dissolution of food by the fluid of the stomach, the gastric juice. But men had still to understand this gastric juice, and to determine its nature and mode of action. Nothing could be more contradictory than the views on this matter. Chaussier and Dumas, of Montpellier, regarded the gastric juice as of very variable composition, one time alkaline, another acid, according to the food ingested. Side by side with these wholly theoretical opinions, certain results of experiments had led to ideas just as erroneous, for want of rigorous criticism of methods; it was thus that MontÈgre denied the existence of the gastric juice as a special fluid; what men took for gastric juice, he said, was nothing but the saliva turned acid in the stomach. To prove his point, he made the following experiment:—He masticated a bit of bread, then put it out on a plate; it was at first alkaline, then at the end of some time it became acid. In those days (1813) this experiment was a real embarrassment to the men who believed in the existence of a special gastric juice: we have now no need to refute it. "These few instances suffice to show how the physiologists were unsettled as to the nature and properties of the gastric juice. Then (1823) the Academy had the happy idea of proposing digestion as a subject for a prize. Tiedemann and Gmelin in Germany, Leuret and Lassaigne in France, submitted works of equal merit, and the Academy divided the prize between them. The work of Tiedemann and Gmelin is of especial interest to us on account of the great number of their experiments, from which came not only the absolute proof of the existence of the gastric juice, but also the study of the transformation of starch into glucose. Thus the theory of digestion entered a new phase: it was finally recognised, at least for certain substances, that digestion is not simply dissolution, but a true chemical transformation." (Cl. Bernard, loc. cit.) In 1825 Dr. William Beaumont, a surgeon in the United States Army, began his famous experiments on Alexis St. Martin, a young Canadian travelling for the American Fur Company, who was shot in the abdomen on 6th June 1822, and recovered, but was left with a permanent opening in his stomach. Since the surgery of those days did not favour an operation to close this fistula, Dr. Beaumont took St. Martin into his service, and between 1825 and 1833 made a vast number of experiments on him. These he published,[2] and they were of great value. But it is to be noted that the ground had been cleared already, fifty years before, by RÉaumur and Spallanzani:— "I make no claim to originality in my opinions, as it respects the existence and operation of the gastric juice. My experiments confirm the doctrines (with some modifications) taught by Spallanzani, and many of the most enlightened physiological writers." (Preface to Dr. Beaumont's book.) Further, it is to be noted that Alexis St. Martin's case proves that a gastric fistula is not painful. Scores of experiments were made on him, off and on, for nine years:— "During the whole of these periods, from the spring of 1824 to the present time (1833), he has enjoyed general good health, and perhaps suffered much less predisposition to disease than is common to men of his age and circumstances in life. He has been active, athletic, and vigorous; exercising, eating, and drinking like other healthy and active people. For the last four months he has been unusually plethoric and robust, though constantly subjected to a continuous series of experiments on the interior of the stomach; allowing to be introduced or taken out at the aperture different kinds of food, drinks, elastic catheters, thermometer tubes, gastric juice, chyme, etc., almost daily, and sometimes hourly. "Such have been this man's condition and circumstances for several years past; and he now enjoys the most perfect health and constitutional soundness, with every function of the system in full force and vigour." (Dr. Beaumont, loc. cit. p. 20.) In 1834 EberlÉ published a series of observations on the extraction of gastric juice from the mucous membrane of the stomach after death; in 1842 Blondlot of Nancy studied the gastric juice of animals by the method of a fistula, such as Alexis St. Martin had offered for Dr. Beaumont's observation. After Blondlot, came experiments on the movements of the stomach, and on the manifold influences of the nervous system on digestion. It has been said, times past number, that an animal with a fistula is in pain. It is not true. The case of St. Martin is but one out of a multitude of these cases: an artificial orifice of this kind is not painful. IV
GLYCOGEN Claude Bernard's discovery of glycogen in the liver had a profound influence both on physiology and on pathology. Take first its influence on pathology. Diabetes was known to Celsus, AretÆus, and Galen; Willis, in 1674, and Morton, in 1675, noted the distinctive sweetness of the urine; and their successors proved the presence of sugar in it. Rollo, in 1787, observed that vegetable food was bad for diabetic patients, and introduced the strict use of a meat diet. But Galen had believed that diabetes was a disease of the kidneys, and most men still followed him: nor did Rollo greatly advance pathology by following not Galen, but AretÆus. Later, with the development of organic chemistry, came the work of Chevreuil (1815), Tiedemann and Gmelin (1823), and other illustrious chemists: and the pathology of diabetes grew more and more difficult:— "These observations gave rise to two theories: the one, that sugar is formed with abnormal rapidity in the intestine, absorbed into the blood, and excreted in the urine; the other, that diabetes is due to imperfect destruction of the sugar, either in the intestine or in the blood. Some held that it underwent conversion into lactic acid as it was passing through the intestinal walls, while others believed it to be destroyed in the blood by means of the alkali therein contained."[3] Thus, before Claude Bernard (1813-1878), the pathology of diabetes was almost worthless. And, in physiology, his work was hardly less important than the work of Harvey. A full account of it, in all its bearings, is given in Sir Michael Foster's Life of Claude Bernard (Fisher Unwin, 1899). In Bernard's LeÇons sur le DiabÈte et la GlycogenÈse Animale (Paris, 1877), there is a sentence that has been misquoted many times:— Sans doute, nos mains sont vides aujourd'hui, mais notre bouche peut Être pleine de lÉgitimes promesses pour l'avenir. This sentence has been worked so hard that some of the words have got rubbed off it: and the statement generally made is of this kind:— Claude Bernard himself confessed that his hands were empty, but his mouth was full of promises. Of course, he did not mean that he was wrong in his facts. But, in this particular lecture, he is speaking of the want of more science in practice, looking forward to a time when treatment should be based on science, not on tradition. Medicine, he says, is neither science nor art. Not science—Trouverait-on aujourd'hui un seul mÉdecin raisonnable et instruit osant dire qu'il prÉvoit d'une maniÈre certaine la marche et l'issue d'une maladie ou l'effet d'une remÈde? Not art, because art has always something to show for its trouble: a statue, a picture, a poem—Le mÉdecin artiste ne crÉe rien, et ne laisse aucune oeuvre d'art, À moins d'appliquer ce titre À la guÉrison du malade. Mais quand le malade meurt, est-ce Également son oeuvre? Et quand il guÉrit, peut-il distinguer sa part de celle de la nature? To Claude Bernard, experiments on animals for the direct advancement of medicine seemed a new thing: new, at all events, in comparison with the methods of some men of his time. He was only saying what Sir John Burdon Sanderson said in 1875 to the Royal Commission:— It is my profound conviction that a future will come, it may be a somewhat distant future, in which the treatment of disease will be really guided by science. Just as completely as mechanical science has come to be the guide of the mechanical arts, do I believe, and I feel confident, that physiological science will eventually come to be the guide of medicine and surgery. Anyhow, lecturing a quarter of a century ago on diabetes, his special subject, Claude Bernard spoke out his longing to compel men into the ways of science, to give them some immediate sign which they could not refuse to see:— "At this present time, medicine is passing from one period to another. The old traditions are losing ground, and scientific medicine (la mÉdecine expÉrimentale) has got hold of all our younger men: every day it gains ground, and will establish itself against all its critics, and in spite of the excesses of those who are over-zealous for its honour.... And when men ask us what are the results of scientific medicine, we are driven to answer that it is scarcely born, that it is still in the making. Those who care for nothing but an immediate practical application must remember Franklin's words, What is the use of a new-born child, but to become a man? If you deliberately reject scientific medicine, you fail to see the natural development of man's mind in all the sciences. Without doubt, our hands are empty to-day, but our mouth may well be filled with legitimate promises for the future." He died in 1878. The following account of the discovery of glycogen is taken from his Nouvelle Fonction du Foie (Paris, 1853):— "My first researches into the assimilation and destruction of sugar in the living organism were made in 1843: and in my inaugural thesis (Dec. 1843) I published my first experiments on the subject. I succeeded in demonstrating a fact hitherto unknown, that cane-sugar cannot be directly destroyed in the blood. If you inject even a very small quantity of cane-sugar, dissolved in water, into the blood or under the skin of a rabbit, you find it again in the urine unchanged, with all its chemical properties the same.... I had soon to give up my first point of view, because this question of the existence of a sugar-producing organ, that I had thought such a hard problem of physiology, was really the first thing revealed to me, as it were of itself, at once." He kept two dogs on different diets, one with sugar, the other without it; then killed them during digestion, and tested the blood in the hepatic veins:— "What was my surprise, when I found a considerable quantity of sugar in the hepatic veins of the dog that had been fed on meat only, and had been kept for eight days without sugar: just as I found it in the other dog that had been fed for the same time on food rich in sugar.... "Finally, after many attempts—aprÈs beaucoup d'essais et plusieurs illusions que je fus obligÉ de rectifier par des tÂtonnements—I succeeded in showing, that in dogs fed on meat the blood passing through the portal vein does not contain sugar before it reaches the liver; but when it leaves the liver, and comes by the hepatic veins into the inferior vena cava, this same blood contains a considerable quantity of a sugary substance (glucose)." His further discovery, that this formation of sugar is increased by puncture of the floor of the fourth ventricle, was published in 1849. It is impossible to exaggerate the importance of Claude Bernard's single-handed work in this field of physiology and pathology:— "As a mere contribution to the history of sugar within the animal body, as a link in the chain of special problems connected with digestion and nutrition, its value was very great. Even greater, perhaps, was its effect as a contribution to general views. The view that the animal body, in contrast to the plant, could not construct, could only destroy, was, as we have seen, already being shaken. But evidence, however strong, offered in the form of numerical comparisons between income and output, failed to produce anything like the conviction which was brought home to every one by the demonstration that a substance was actually formed within the animal body, and by the exhibition of the substance so formed. "No less revolutionary was the demonstration that the liver had other things to do in the animal economy besides secreting bile. This, at one blow, destroyed the then dominant conception that the animal body was to be regarded as a bundle of organs, each with its appropriate function, a conception which did much to narrow inquiry, since when a suitable function had once been assigned to an organ there seemed no need for further investigations.... "No less pregnant of future discoveries was the idea suggested by this newly-found-out action of the hepatic tissue, the idea happily formulated by Bernard as 'internal secretion.' No part of physiology is at the present day being more fruitfully studied than that which deals with the changes which the blood undergoes as it sweeps through the several tissues, changes by the careful adaptation of which what we call the health of the body is secured, changes the failure or discordance of which entails disease. The study of these internal secretions constitutes a path of inquiry which has already been trod with conspicuous success, and which promises to lead to untold discoveries of the greatest moment; the gate to this path was opened by Bernard's work." (Sir M. Foster, loc. cit.) But the work to be done, before all the clinical facts of the disease can be stated in terms of physiology, is not yet finished. In England, especial honour is due to Dr. Pavy for his life-long study of this most complex problem. V
THE PANCREAS Here again Claude Bernard's name must be put first. Before him, the diverse actions of the pancreatic juice had hardly been studied. Vesalius, greatest of all anatomists, makes no mention of the duct of the pancreas, and speaks of the gland itself as though its purpose were just to support the parts in its neighbourhood—ut ventriculo instar substerniculi ac pulvinaris subjiciatur. The duct was discovered by Wirsung, in 1642: but anatomy could not see the things that belong to physiology. Lindanus (1653) said, I cannot doubt that the pancreas expurgates, in the ordinary course of Nature, those impurities of the blood that are too crass and inept to be tamed by the spleen: and, in the extraordinary course, all black bile, begotten of disease or intemperate living. Wharton (1656) said, It ministers to the nerves, taking up certain of their superfluities, and remitting them through its duct into the intestines. And Tommaso Bartholini (1666) called it the biliary vesicle of the spleen. This chaos of ideas was brought into some sort of order by Regnier de Graaf, pupil of FranÇois de Bois (Sylvius). De Bois had guessed that the pancreas must be considered not according to its position in the body, but according to its structure: that it was analogous to the salivary glands. He urged his pupil to make experiments on it: and de Graaf says:— "I put my hand to the work: and though many times I despaired of success, yet at last, by the blessing of God on my work and prayers, in the year 1660 I discovered a way of collecting the pancreatic juice." And, by further experiment, he refuted Bartholini's theory that the pancreas was dependent on the spleen. Sylvius had supposed that the pancreatic juice was slightly acid, and de Graaf failed to note this mistake; but it was corrected by Bohn's experiments in 1710. Nearly two hundred years come between Regnier de Graaf and Claude Bernard: it is no wonder that Sir Michael Foster says that de Graaf's work was "very imperfect and fruitless." So late as 1840, there was yet no clear understanding of the action of the pancreas. Physiology could not advance without organic chemistry; de Graaf could no more discover the amylolytic action of the pancreatic juice than Galvani could invent wireless telegraphy. The physiologists had to wait till chemistry was ready to help them:— "Of course, while physical and chemical laws were still lost in a chaos of undetermined facts, it was impossible that men should analyse the phenomena of life: first, because these phenomena go back to the laws of chemistry and physics; and next, because they cannot be studied without the apparatus, instruments, and all other methods of analysis that we owe to the laboratories of the chemists and the physicists." (Cl. Bernard, Phys. OpÉr., p. 61.) Therefore de Graaf failed, because he got no help from other sciences. But it cannot be called failure; he must be contrasted with the men of his time, Lindanus and Bartholini, facts against theories, not with men of this century. And Claude Bernard went back to de Graaf's method of the fistula, having to guide him the facts of chemistry observed by Valentin, Tiedemann and Gmelin, and EberlÉ. His work began in 1846, and the AcadÉmie des Sciences awarded a prize to it in 1850:— "Let this vague conception (the account of the pancreas given in Johannes MÜller's Text-book of Physiology) be compared with the knowledge which we at present have of the several distinct actions of the pancreatic juice, and of the predominant importance of this fluid not only in intestinal digestion but in digestion as a whole, and it will be at once seen what a great advance has taken place in this matter since the early forties. That advance we owe in the main to Bernard. Valentin, it is true, had in 1844 not only inferred that the pancreatic juice had an action on starch, but confirmed his view by actual experiment with the juice expressed from the gland; and EberlÉ had suggested that the juice had some action on fat; but Bernard at one stroke made clear its threefold action. He showed that it on the one hand emulsified, and on the other hand split up, into fatty acids and glycerine, the neutral fats; he clearly proved that it had a powerful action on starch, converting it into sugar; and lastly, he laid bare its remarkable action on proteid matters." (Sir Michael Foster, loc. cit.) Finally came the discovery that the pancreas—apart from its influences on digestion—contributes its share, like the ductless glands, to the general chemistry of the body:— "It was discovered, a few years ago, by von Mering and Minkowski, that if, instead of merely diverting its secretion, the pancreas is bodily removed, the metabolic processes of the organism, and especially the metabolism of carbo-hydrates, are entirely deranged, the result being the production of permanent diabetes. But if even a very small part of the gland is left within the body, the carbo-hydrate metabolism remains unaltered, and there is no diabetes. The small portion of the organ which has been allowed to remain (and which need not even be left in its proper place, but may be transplanted under the skin or elsewhere) is sufficient, by the exchanges which go on between it and the blood generally, to prevent those serious consequences to the composition of the blood, and the general constitution of the body, which result from the complete removal of this organ." (Prof. SchÄfer, 1894.) Here, in this present study of "pancreatic diabetes," by Dr. Vaughan Harley and others, are facts as important as any that Bernard made out: in no way contradicting his work, but adding to it. The pancreas is no longer taken to be only a sort of salivary gland out of place: over and above the secretion that it pours into the intestines, it has an "internal secretion," a constituent of the blood: it belongs not only to the digestive system, but also, like the thyroid gland and the suprarenal capsules, to the whole chemistry of the blood and the tissues. So far has physiology come, unaided by anatomy, from the fantastic notions of Lindanus and the men of his time: and has come every inch of the way by the help of experiments on animals. Professor Starling's observations, on the chemical influence of the duodenal mucous membrane on the flow of pancreatic fluid, have advanced the subject still further. VI
THE GROWTH OF BONE The work of du Hamel proved that the periosteum is one chief agent in the growth of bone. Before him, this great fact of physiology was unknown; for the experiments made by Anthony de Heide (1684), who studied the production of callus in the bones of frogs, were wholly useless, and serve only to show that men in his time had no clear understanding of the natural growth of bone. De Heide says of his experiments:— "From these experiments it appears—forsan probatur—that callus is generated by extravasated blood, whose fluid particles being slowly exhaled, the residue takes the form of the bone: which process may be further advanced by deciduous halitus from the ends of the broken bone." And Clopton Havers, in his Osteologia Nova (London, 1691), goes so far the wrong way that he attributes to the periosteum not the production of bone, but the prevention of over-production; the periosteum, he says, is put round the shaft of a bone to compress it, lest it grow too large. Du Hamel's discovery (1739-1743) came out of a chance observation, made by John Belchier,[4] that the bones of animals fed near dye-works were stained with the dye. Belchier therefore put a bird on food mixed with madder, and found that its bones had taken up the stain. Then du Hamel studied the whole subject by a series of experiments. To estimate the advance that he gave to physiology, contrast de Heide's fanciful language with the title of one of du Hamel's papers—QuatriÈme MÉmoire sur les Os, dans lequel on se propose de rapporter de nouvelles preuves qui Établissent que les os croissent en grosseur par l'addition de couches osseuses qui tirent leur origine du pÉrioste, comme le corps ligneux des Arbres augmente en grosseur par l'addition de couches ligneuses qui se forment dans l'Écorce. Or take an example of du Hamel's method:— "Three pigs were destined to clear up my doubts. The first, six weeks old, was fed for a month on ordinary food, with an ounce daily of madder-juice—garance grappe—put in it. At the end of the month, we stopped the juice, and fed the pig in the ordinary way for six weeks, and then killed it. The marrow of the bones was surrounded by a fairly thick layer of white bone: this was the formation of bone during the first six weeks of life, without madder. This ring of white bone was surrounded by another zone of red bone: this was the formation of bone during the administration of the madder. Finally, this red zone was covered with a fairly thick layer of white bone: this was the layer formed after the madder had been left off.... We shall have no further difficulty in understanding whence transudes the osseous juice that was thought necessary for the formation of callus and the filling-up of the wounds of the bones, now we see that it is the periosteum that fills up the wounds, or is made thick round the fractures, and afterward becomes of the consistence of cartilage, and at last acquires the hardness of bones." These results, confirmed by Bazan (1746) and Boehmer (1751), were far beyond anything that had yet been known about the periosteum. But the growth of bone is a very complex process: the naked eye sees only the grosser changes that come with it; and du Hamel's ingenious comparison between the periosteum and the bark of trees was too simple to be exact. Therefore his work was opposed by Haller, and by Dethleef, Haller's pupil: and the great authority of Haller's name, and the difficulties lying beyond du Hamel's plain facts, brought about a long period of uncertainty. Bordenave (1756) found reasons for supporting Haller; and Fougeroux (1760) supported du Hamel. Thus men came to study the whole subject with more accuracy—the growth in length, as well as the growth in thickness; the medullary cavity, the development of bone, the nutrition and absorption of bone. Among those who took up the work were Bichat, Hunter, Troja, and Cruveilhier; and they recognised the surgical aspect of these researches in physiology. After them, the periosteal growth of bone became, as it were, a part of the principles of surgery. From this point of view of practice, issued the experiments made by Syme (1837) and Stanley (1849): which proved the importance of the epiphysial cartilages for the growth of the bones in length, and the risk of interfering with these cartilages in operations on the joints of children. Finally, with the rise of anÆsthetics and of the antiseptic method, came the work of Ollier, of Lyon, whose good influence on the treatment of these cases can hardly be over-estimated. VII
THE NERVOUS SYSTEM As with the circulatory system, so with the nervous system, the work of Galen was centuries ahead of its time. Before him, Aristotle, who twice refers to experiments on animals, had observed the brain during life: for he says, "In no animal has the blood any feeling when it is touched, any more than the excretions; nor has the brain, or the marrow, any feeling, when it is touched": but there is reason for believing that he neither recognised the purpose of the brain, nor understood the distribution of the nerves. Galen, by the help of the experimental method, founded the physiology of the nervous system:— "Galen's method of procedure was totally different to that of an anatomist alone. He first reviewed the anatomical position, and by dissection showed the continuity of the nervous system, both central and peripheral, and also that some bundles of nerve fibres were distributed to the skin, others to the muscles. Later, by process of the physiological experiment of dividing such bundles of fibres, he showed that the former were sensory fibres and the latter motor fibres. He further traced the nerves to their origins in the spinal cord, and their terminations as aforesaid. From these observations and experiments he was able to deduce the all-important fact that different nerve-roots supplied different groups of muscles and different areas of the skin.... An excellent illustration of his method, and of the fact that we ought not to treat symptoms, but the causes of symptoms, is shown very clearly in one of the cases which Galen records as having come under his care. He tells us that he was consulted by a certain sophist called Pausanias, who had a severe degree of anÆsthesia of the little and ring fingers. For this loss of sensation, etc., the medical men who attended him applied ointments of various kinds to the affected fingers; but Galen, considering that that was a wrong principle, inquired into the history, and found that while the patient was driving in his chariot he had accidentally fallen out and struck his spine at the junction of the cervical and dorsal regions. Galen recognised that he had to do with a traumatism affecting the eighth cervical and first dorsal nerve; therefore, he says, he ordered that the ointments should be taken off the hand and placed over the spinal column, so as to treat the really affected part, and not apply remedies to merely the referred seat of pain."[5] Galen, by this sort of work, laid the foundations of physiology; but the men who came after him let his facts be overwhelmed by fantastic doctrines: all through the ages, from Galen to the Renaissance, no great advance was made toward the interpretation of the nervous system. Long after the Renaissance, his authority still held good; his ghost was not laid even by Paracelsus and Vesalius, it haunted the medical profession so late as the middle of the seventeenth century; but the men who worshipped his name missed the whole meaning of his work. This long neglect of the experimental method left such a gap in the history of physiology, that Sir Charles Bell seems to take up the experimental study of the nervous system at the point where Galen had stopped short; we go from the time of Commodus to the time of George the Third, and there is Bell, as it were, putting the finishing touch to Galen's facts. It is true that experiments had been made on the nervous system by many men; but a dead weight of theories kept down the whole subject. For a good instance, how imagination hindered science, there is the following list, made by Dr. Risien Russell, of theories about the cerebellum:— "Galen was of opinion that the cerebellum must be the originator of a large amount of vital force. After him, and up to the time of Willis, the prevalent idea seems to have been that it was the seat of memory; while Bourillon considered it the seat of instinct and intelligence. Willis supposed that it presided over involuntary movements and organic functions; and this view, though refuted by Haller, continued in the ascendency for some time. Some believed strongly in its influence on the functions of organic life; and according to some, diseases of the cerebellum appeared to tell on the movements of the heart.... Haller believed it to be the seat of sensations, as well as the source of voluntary power; and there were many supporters of the theory that the cerebellum was the seat of the sensory centres. Renzi considered this organ the nervous centre by which we perceive the reality of the external world, and direct and fix our senses on the things round us. Gall, and later Broussais, and others, held that this organ presided over the instinct of reproduction, or the propensity to love; while Carus regarded it as the seat of the will also. Rolando looked on it as the source of origin of all movements. Jessen adduced arguments in favour of its being the central organ of feeling, or of the soul, and the principal seat of the sensations." It is plain, from this list, that physiology had become obscured by fanciful notions of no practical value. If a better understanding of the nervous system could have been got without experiments on animals, why had men to wait so long for it? The Italian anatomists had long ago given them all the anatomy that was needed to make a beginning; the hospitals, and practice, had given them many hundred years of clinical facts; nervous diseases and head injuries were common enough in the Middle Ages; and by the time of Ambroise ParÉ, if not before, post-mortem examinations were allowed. The one thing wanted was the experimental method; and, for want of it, the science of the nervous system stood still. Experiments had been made; but the steady, general, unbiassed use of this method had been lost sight of, and men were more occupied with logic and with philosophy. Then, in 1811, came Sir Charles Bell's work. If any one would see how great was the need of experiments on animals for the interpretation of the nervous system, let him contrast the physiology of the eighteenth century with that one experiment by Bell which enabled him to say, "I now saw the meaning of the double connection of the nerves with the spinal marrow." It is true that this method is but a part of the science of medicine; that experiment and experience ought to go together like the convexity and the concavity of a curve. But it is true also that men owe their deliverance from ignorance about the nervous system more to experiments on animals than to any other method of observing facts. 1. Sir Charles Bell (1778-1842) The great authority of Sir Charles Bell has been quoted a thousand times against all experiments on animals:— "Experiments have never been the means of discovery; and a survey of what has been attempted of late years in physiology, will prove that the opening of living animals has done more to perpetuate error than to confirm the just views taken from the study of anatomy and natural motions." He wrote, of course, in the days before bacteriology, before anÆsthetics; he had in his mind neither inoculations, nor any observations made under chloroform or ether, but just "the opening of living animals." He had also in his mind, and always in it, a great dislike against the school of Magendie. Let all that pass; our only concern here is to know whether these words are true of his own work. They occur in a paper, On the Motions of the Eye, in Illustration of the Uses of the Muscles and Nerves of the Orbit; communicated by Sir Humphry Davy to the Royal Society, and read March 20, 1823.[6] This essay was one of a series of papers on the nervous system, presented to the Royal Society during the years 1821-1829. In 1830, having already published four of these papers under the title, The Exposition of the Nervous System, Bell published all six of them, under the title, The Nervous System of the Human Body. In his Preface to this book (1830) he quotes the earliest of all his printed writings on the nervous system, a pamphlet, printed in 1811, under the title, An Idea of a New Anatomy of the Brain, Submitted for the Observation of the Authors Friends. We have therefore two statements of his work, one in 1811, the other in 1823 and 1830. The first of them was written when his work was still new before his eyes. Those who say that experiments did not help Bell in his great discovery—the difference between the anterior and the posterior nerve-roots—appeal to certain passages in the 1830 volume:— "In a foreign review of my former papers, the results have been considered as a further proof in favour of experiments. They are, on the contrary, deductions from anatomy; and I have had recourse to experiments, not to form my own opinions, but to impress them upon others. It must be my apology that my utmost efforts of persuasion were lost, while I urged my statements on the grounds of anatomy alone. I have made few experiments; they have been simple and easily performed, and I hope are decisive.... "My conceptions of this matter arose by inference from the anatomical structure; so that the few experiments which have been made were directed only to the verification of the fundamental principles on which the system is established." If it were not for the 1811 pamphlet, the opponents of all experiments on animals might claim Sir Charles Bell on their side. But while his work was still a new thing, he spoke in another way of it:— "I found that injury done to the anterior portion of the spinal marrow convulsed the animal more certainly than injury to the posterior portion; but I found it difficult to make the experiment without injuring both portions. "Next, considering that the spinal nerves have a double root, and being of opinion that the properties of the nerves are derived from their connections with the parts of the brain, I thought that I had an opportunity of putting my opinion to the test of experiment, and of proving at the same time that nerves of different endowments were in the same cord (nerve-trunk) and held together by the same sheath. "On laying bare the roots of the spinal nerves, I found that I could cut across the posterior fasciculus of nerves, which took its origin from the posterior portion of the spinal marrow, without convulsing the muscles of the back; but that on touching the anterior fasciculus with the point of the knife, the muscles of the back were immediately convulsed. "Such were my reasons for concluding that the cerebrum and cerebellum were parts distinct in function, and that every nerve possessing a double function obtained that by having a double root. I now saw the meaning of the double connection of the nerves with the spinal marrow; and also the cause of that seeming intricacy in the connections of nerves throughout their course, which were not double at their origins." It is impossible to reconcile the 1830 sentences with this vivid personal account of himself; I had an opportunity of putting my opinion to the test of experiment ... an opportunity of proving ... Such were my reasons for concluding ... I now saw.... It is just what all men of science say of their experiments: the very phrase of Archimedes, and Asellius, and de Graaf. If Sir Charles Bell had been working at the facts of chemistry or of botany, who would have doubted the meaning of these words? This same inconsistency of sentences occurs elsewhere in his Nervous System of the Human Body. In one place he says that he has made few experiments: They have been simple, and easily performed, and I hope are decisive. In another he says: "After making several experiments on the cerebrum and cerebellum, I laid the question of their functions entirely aside, and confined myself to the investigation of the spinal marrow and the nerves; a subject which I found more within my power, and which forms the substance of the present volume." Next, take his account of the cranial nerves:— "It was necessary to know, in the first place, whether the phenomena exhibited on injuring the separate roots corresponded with what was suggested by their anatomy.... "Here a difficulty arose. An opinion prevailed that ganglions were intended to cut off sensation; and every one of these nerves, which I supposed were the instruments of sensation, have ganglions on their roots. Some very decided experiment was necessary to overturn this dogma. (Account of the experiment.) By pursuing the inquiry, it was found that a ganglionic nerve is the sole organ of sensation in the head and face: ganglions were therefore no hindrance to sensation; and thus my opinion was confirmed.... It now became obvious why the third, sixth, and ninth nerves of the encephalon were single nerves in their roots.... "Observing that there was a portion of the fifth nerve which did not enter the ganglion of that nerve, and being assured of the fact by the concurring testimony of anatomists, I conceived that the fifth nerve was in fact the uppermost nerve of the spine.... This opinion was confirmed by experiment.... (Account of an experiment on the dead body.) On dividing the root of the nerve in a living animal, the jaw fell relaxed. Thus its functions are no longer matter of doubt: it is at once a muscular nerve and a nerve of sensibility. And thus the opinion is confirmed, that the fifth nerve is to the head what the spinal nerves are to the other parts of the body, in respect to sensation and volition." The value of the experimental method could hardly be stated in more emphatic words. He supposed something, conceived it, had an opinion about it. Anatomy had suggested something to him. He put his opinion to the test of phenomena, that is to say, to the test of visible facts; and then his opinion was confirmed. As with the spinal nerve-roots, so with the fifth cranial nerve—his work was successful, because he followed the way of experiment. He was by nature of a most complex and sensitive temperament, full of contrary forces—one man in 1811, another in 1830. In 1811 he wrote, I now saw the meaning of the double connection of the nerves; in 1830 he had come to hate the stupid sterile materialism of the French school: he beheld anatomy falling behind physiology, and his Windmill Street school perishing to make way for the Hospital schools and for the University of London. He was before everything else a great anatomist: he stood up for the honour of anatomy against the new physiology, and for the honour of the Monroes and the Hunters against Magendie: he hated the notion that any man should proceed to experiments on function till the very last secrets had been got out of structure. He died a few years afterward. The 1830 writings are his last stand for the defence of his country, his school, and his beloved anatomy, against the methods of Magendie; who said of himself, "I am a mere street scavenger, chiffonier, of science. With my hook in my hand and my basket on my back, I go about the streets of science, collecting what I find." This open conflict between Bell's first and last thoughts is a part of his character: he was brilliant, impulsive, changeable, inconsistent; and, what is more important, his honour kept him from trying to evade this trumpery charge of inconsistency; and he reprinted the 1811 Preface in the book that he published in 1830. Doubtless he would have picked his words more carefully if he had foreseen that one of the 1830 sentences would be wrested out of its place in his life's work, and used as false evidence against the very method that he followed. His observations on the cranial nerves brought about an immediate change in the practice of surgery:— "Up to the time that Sir Charles Bell made his experiments on the nerves of the face, it was the common custom of surgeons to divide the facial nerve for the relief of neuralgia, tic douleureux; whereas it exercises, and was proved by Sir Charles Bell to exercise, no influence over sensation, and its division consequently for the relief of pain was a useless operation." (Sir J. Erichsen.) The relation of Magendie's work on the nerve-roots to Bell's work need not be considered here. The exact dates of Bell's observations are given by one of his pupils in the Preface to the 1830 volume. Magendie finally proved the sensory nature of the posterior nerve-roots: "The exact and full proof which he brought forward of the truth which Charles Bell had divined rather than demonstrated, that the anterior and posterior roots of spinal nerves have essentially different functions—a truth which is the very foundation of the physiology of the nervous system—is enough by itself to mark him as a great physiologist." (Sir M. Foster, loc. cit.) 2. Marshall Hall (1790-1857) Reflex action had been studied long before the time of Marshall Hall. The Hon. Robert Boyle (1663) had observed the movements and actions of decapitated vipers, flies, silkworms, and butterflies. Similar observations were made on frogs, eels, and other lower animals, by Redi, Woodward, Stuart, Le Gallois, and Sir Gilbert Blane. According to Richet, it was Willis who first gave the name reflex to these movements. It cannot be said that these first studies of reflex action did much for physiology. But the following translation from Prochaska (1800) shows how they cleared the way for Marshall Hall's work, by the proof that they gave of the liberation of nervous energy in the spinal cord:— "These movements of animals after decapitation must needs be by consent and commerce betwixt the spinal nerves. For a decapitated frog, if it be pricked, not only draws away the part that is pricked, but also creeps and jumps; which cannot happen but by consent betwixt the sensory nerves and the motor nerves. The seat of which consent must needs be in the spinal cord, the only remaining portion of the sensorium. And this reflexion of sensory impressions into motor impressions is not accomplished in obedience to physical laws alone—wherein the angle of reflexion is equal to the angle of incidence, and reaction to action—but it follows special laws as it were written by Nature on the spinal cord, which we can know only by their effects, but cannot fathom with the understanding. But the general law, whereby the sensorium reflects sensory impressions into motor impressions, is the preservation of ourselves." It was not possible, in 1800, to go further, or to put the facts of reflex action more clearly: but this fine sentence gives no hint of the truth that guided Marshall Hall—that the "consent and commerce" of reflex action are to be found at definite points or levels in the spinal cord; that the cord no more "works as a whole" than the brain. The greatness of Marshall Hall's work lies in his recognition of the divisional action of the cord: he proved the existence of definite centres in it, he discovered the facts of spinal localisation, and thus foreshadowed the discovery of cerebral localisation. In his earlier writings (1823-33) he showed how the movements of the trunk and of the limbs are only one sort of reflex action; how the larynx, the pharynx, and the sphincter muscles, all act by the "consent and commerce" of the spinal cord. Later, in 1837, he demonstrated the course of nerve-impulses along the cord from one level to another, the results of direct stimulation of the cord, and other facts of spinal localisation. He noted the different effects of opium and of strychnine on reflex action; and he extended the doctrines of reflex action beyond physiology to the convulsive movements of the body in certain diseases. 3. Flourens (1794-1867) Beside his work on the nervous system, Flourens studied the periosteal growth of bone, and the action of chloroform;[7] but he is best known by his experiments on the respiratory centre and the cerebellum. The men who interpreted the nervous system followed the anatomical course of that system: first the nerve-roots, then the cord, then the medulla oblongata and the cerebellum, and last the cerebral hemispheres; a steady upward advance, from the observation of decapitated insects to the localisation of centres in the human brain. Flourens, by his work on the medulla oblongata, localised the respiratory centre, the nerve-cells for the reflex movements of respiration:— "M. Flourens a circonscrit ce centre avec une scrupuleuse prÉcision, et lui a donnÉ le nom de noeud vital" (Cl. Bernard.) Afterward came the discovery of cardiac and other centres in the same portion of the nervous system. Flourens also showed that the cerebellum is concerned with the equilibration of the body, and with the coordination of muscular movements; that an animal, a few days old, deprived of sensation and consciousness by removal of the cerebral hemispheres, was yet able to stand and move forward, but, when the cerebellum was removed, its muscles lost all co-ordinate action. (Recherches ExpÉrimentales, Paris, 1842.) And from his work, and the work of those who followed him, on the semicircular canals of the internal ear, came the evidence that these minute structures are the terminal organs of equilibration: that as the special senses have their terminal apparatus and their central apparatus, so the semicircular canals and the cerebellum are the terminal apparatus and the central apparatus of the sense of equilibrium. 4. Claude Bernard (1813-1878) The discovery of the vaso-motor nerves, and of the control of the nervous system over the calibre of the arteries, was made by Claude Bernard at the outset of his work on the influence of the nervous system on the temperature.[8] The evidence of Professor Sharpey before the Royal Commission of 1875 shows how things had been misjudged, before Bernard's time, in the light of "views taken from the Study of Anatomy and Natural Motions":— "I remember that Sir Charles Bell gave the increased size of the vessels in blushing, and their fulness of blood, as an example of the increased action of the arteries in driving on the blood. It turns out to be just the reverse, inasmuch as it is owing to a paralysis of the nerves governing the muscular coats of the arteries." Claude Bernard's first account of his work was communicated to the SociÉtÉ de Biologie in December 1851. The following description is taken from his LeÇons de Physiologie OpÉratoire:— "I will remind you how I was led to the discovery of the vaso-motor nerves. Starting from the clinical observation, made long ago, that in paralysed limbs you find at one time an increase of cold, and at another an increase of heat, I thought this contradiction might be explained by supposing that, side by side with the general action of the nervous system, the sympathetic nerve might have the function of presiding over the production of heat; that is to say, that in the case where the paralysed limb was chilled, I supposed the sympathetic nerve to be paralysed, as well as the motor nerves; while in the paralysed limbs that were not chilled, the sympathetic nerve had retained its function, the systemic nerves alone having been attacked. "This was a theory, that is to say, an idea leading me to make experiments; and for these experiments I must find a sympathetic nerve-trunk of sufficient size, going to some organ that was easy to observe, and must divide this trunk to see what would happen to the heat-supply of the organ. You know that the rabbit's ear, and the cervical sympathetic nerve of this animal, offered us the required conditions. So I divided the nerve; and immediately my experiment gave the lie direct to my theory—Je coupai donc ce filet et aussitÔt l'expÉrience donna À mon hypothÈse le plus Éclatant dÉmenti. I had thought that the section of the nerve would suppress the function of nutrition, of calorification, over which the sympathetic system had been supposed to preside, and would cause the hollow of the ear to become chilled; and here was just the opposite, a very warm ear, with great dilatation of its vessels. "I need not remind you how I made haste to abandon my first theory, and gave myself to the study of this new state of things. And you know that here was the starting-point of all my researches into the vaso-motor and thermic system; and the study of this subject is become one of the richest fields of experimental physiology." Waller, in 1853, studied the vaso-motor centre in the spinal cord; and Schiff, in 1856, found evidence of the existence of two kinds of vaso-motor nerves—those that constrict the vessels, and those that dilate them. This view was finally established in 1858 by Claude Bernard's experiments on the chorda tympani and the submaxillary gland. The LeÇons de Physiologie OpÉratoire were published in 1879. Twenty years later, Sir Michael Foster says of Bernard's work:— "It is almost impossible to exaggerate the importance of these labours of Bernard on the vaso-motor nerves, since it is almost impossible to exaggerate the influence which our knowledge of the vaso-motor system, springing as it does from Bernard's researches as from its fount and origin, has exerted, is exerting, and in widening measure will continue to exert, on all our physiological and pathological conceptions, on medical practice, and on the conduct of human life. There is hardly a physiological discussion of any width in which we do not sooner or later come on vaso-motor questions. Whatever part of physiology we touch, be it the work done by a muscle, be it the various kinds of secretive labour, be it the insurance of the brain's well-being in the midst of the hydrostatic vicissitudes to which the changes of daily life subject it, be it that maintenance of bodily temperature which is a condition of the body's activity; in all these, as in many other things, we find vaso-motor factors intervening. And if, passing the insecure and wavering line which parts health from illness, we find ourselves dealing with inflammation, or with fever, or with any of the disordered physiological processes which constitute disease, we shall find, whatever be the tissue specially affected by the morbid conditions, that vaso-motor influences have to be taken into account. The idea of vaso-motor action is woven as a dominant thread into all the physiological and pathological doctrines of to-day; attempt to draw out that thread, and all that would be left would appear as a tangled heap." 5. Cerebral Localisation Finally, moving upward along the anatomy of the nervous system, physiology came to study the motor-centres and special sense-centres of the cerebral hemispheres. The year 1861 may fairly be said to mark the beginning of the discovery of these centres, when Broca, at a meeting of the Anthropological Society of Paris, heard Aubertin's paper on the connection between the frontal convolutions and the faculty of speech. But, of course, some sort of belief in cerebral localisation had been in the air long before Broca's time. Willis (1621-1675), who was contemporary with Sir Isaac Newton, had written of the brain as though its convolutions, or "cranklings" as he called them, showed that its work was departmental:— "As the animal spirits for the various acts of imagination and memory ought to be moved within certain and distinct limits, or bounded places, and these motions to be often iterated or repeated through the same tracts or paths, for that reason these manifold convolutions and infoldings of the brain are required for these divers manners of ordinations of the animal spirits—to wit, that in these cells or storehouses, severally placed, might be kept the species of sensitive things, and as occasion serves, may be taken from thence."[9] And Gall, a century after Willis, had collected and published, in support of his system of phrenology, many cases and post-mortem examinations showing the differentiation of the work of the brain. Gall is a warning for all time against the dangers of deduction; he had but one idea, and he drove it to death; but the clinical and pathological facts which he amassed, in the hope of establishing a set of doctrines out of all relation to facts, are as true now as ever; and, if he had been content to go the way of induction, and to set himself to the accumulation of facts, he might have become a great physiologist. In his knowledge of the anatomy of the brain, and in the dissection of the brain, he was far ahead of the men of his time; but he followed his own imaginings, and left nothing that could last, except those cases and pathological instances that are buried in the ruins of his system. But there they are, and are still of value. For example, Gall's case of loss of speech, after an injury involving the speech-centres, ought to have commanded the attention of all physiologists: but it came to nothing, because he used it to support his doctrine of organs and bumps, and it shared the fate of that doctrine. Phrenology is gone past recall; it died of that congenital disease, the deductive fallacy; but there was a time when it might have been turned to the service of science. The excitement that Gall aroused by the spread of his ideas shows that some belief in cerebral centres was waiting for development. All men are by nature phrenologists; the commonplace excuses that are offered for lapses of memory, venial offences, and inherited weaknesses, all appeal to the comfortable notion that the offender is not wholly perverted, and that some very small and strictly localised group of cells is at fault. And it is probable that the physiology of the central nervous system, with its present strong tendency toward psychology, will some day be back, at a far higher level, above the point where phrenology went wrong. As Mme. de StaËl said, L'esprit humain fait progrÈs toujours, mais c'est progrÈs en spirale. But the question, whether the general desire for a rational system of psychology will ever commend itself to physiology, belongs to the future. All that is of present concern is the steady, continuous, and successful advance, by the way of induction, and by the help of experiments on animals, toward a clear and accurate statement of the departmental work of the brain. It is one of many instances how science and practice work together, that the modern study of these centres began not in experiment but in experience. The first centres that were thus studied were the speech-centres; and the observation of them arose out of the cases recorded by Bouillard in 1825, and Dax in 1836. Clinical observation, and post-mortem examination, found the speech-centres; physiological experiments had nothing to do with it; and phrenology had, as it were, found them, and then lost them. But at once, so soon as practice gave the word to science, physiology set to work. These clinical facts had been there all the time; loss of speech had gone with disease or injury of "Broca's convolution" ever since man had been on the earth, and nobody had seen the significance of this sequence. Then, after 1861, everything was changed; and in a few years physiology had mapped out a large part of the surface of the brain, and had charted the motor-centres. The story of Broca's convolution is told in Hamilton's Text-Book of Pathology:— "In 1825, Bouillard collected a series of cases to show that the faculty of speech resided in the frontal lobes. In the year 1836 M. Dax, in a paper read to the Medical Congress of Montpellier, stated as a result of his researches that, where speech was lost from cerebral causes, he believed the lesion was invariably found in the left cerebral hemisphere, and that the accompanying paralysis of the right side of the body is consequent upon this. This paper for long lay buried in the annals of medical literature, but was unearthed years afterwards by his son, and presented to the French Academy. Bouillard's views were also disinterred by Aubertin, and in the year 1861 were brought by him before the notice of the Anthropological Society of Paris. Broca, who was present at the meeting, had a patient under his care at the time who had been aphasic (without power of speech) for twenty-one years, and who was in an almost moribund state. The autopsy proved of great interest, as it was found that the lesion was confined to the left side of the brain, and to what we now call the third frontal convolution. Broca was struck with the coincidence; and when a similar case came under his care afterwards, unaware of what had been done by Dax, he postulated the conclusion that the integrity of the third frontal convolution, and perhaps also part of the second, is essential to speech. In a subsequent series of fifteen typical cases examined, it was found that the lesion had destroyed, among other parts, the posterior part of the third frontal in fourteen. In the fifteenth case the destruction had taken place in the island of Reil and the temporal lobe." After 1861, physiology took the lead, and kept it. But, through all the work, science and practice have been held together; the facts of experimental physiology have been and are tested, every inch of the way, by the facts of medicine, surgery, and pathology. The infinite minuteness and complexity of the investigation, and its innumerable side-issues, are past all telling. They who are doing the work, in science and in practice, have always had in their thoughts the fear of fallacies in the interpretation of these highest forms of life. Sir William Gowers, fourteen years ago, wrote as follows of the earlier workers:— "Doubt was formerly entertained as to the existence of differentiation of function in different parts of the cortex, but recent researches have established the existence of a differentiation which has almost revolutionised cerebral physiology, and has vastly extended the range of cerebral diagnosis. The first step of the new discovery was constituted by the clinical and pathological observations of Hughlings Jackson, which suggested the existence, on each side of the fissure of Rolando, of special centres for the movements of the leg, arm, and face. These observations led to the experiments of Ferner, which resulted in the demonstration of the existence in the cortex of the lower animals of well-defined regions, stimulation of which caused separate movements, or evidence of special sense excitation, while the destruction of the same parts caused indications of a loss of the corresponding function. Hence he came to the conclusion that these regions constitute actual motor and sensory centres. Ferrier had, however, been anticipated in many of these results by two German experimenters, Fritsch and Hitzig, whose results, differing a little in detail, correspond closely in their general significance. Many other investigations of the same character have since been made, of which those of Munk are especially important. The original observations of Hughlings Jackson left little doubt that the general facts, learned from experiments on animals, are true of man; and this conclusion has been to a large extent confirmed by pathological and clinical observations directed to the verification on man of the pathological results. To this verification the labours of Charcot and his coadjutors have largely contributed. But the verification has already made it probable that some differences exist between the brain of man and that of higher animals (even of monkeys), and that the conclusions from the latter cannot be simply transferred to the former." Many and great difficulties, beyond this danger of the fallacy of "simple transference," beset every step of the work: it required the right use of the most delicate and susceptible instruments and tests, and the right understanding of anatomy, microscopic anatomy, comparative anatomy, organic chemistry, electricity, and physics: every moment of advance must be guarded, every word must be weighed. Among the earlier difficulties, was the failure of almost all the physiologists, before Hitzig, to produce muscular action by excitation of the cerebral cortex. Longet, Magendie, Flourens, Matteuci, Van Deen, Weber, Budge, and Schiff, had all failed. Hitzig (Untersuchungen Über das Gehirn, Berlin, 1874) had observed, in man, that it was easy to produce movements of the eyes by the passage of the constant current through the occipital region.[10] Taking this fact for a starting-point, he used a very low current, and thereby succeeded in producing certain definite muscular movements by stimulation of the cortex in animals. Of Hitzig's work, Sir Victor Horsley says:— "It was not till 1870 that the next absolute proof (after Bell's work in 1813) was obtained of the localisation of function, so far as the highest centres of the nervous system were concerned. In that year Fritsch and Hitzig discovered that electrical excitation, with minimal stimuli, of various points of the cortex, caused those storehouses, of which Willis spoke, to discharge, and to reveal their function by the precise limitation of the groups of muscles which they were able to throw into action. These researches were abundantly confirmed and greatly extended by Professor Ferrier, and thus has been constructed in the history of this subject the most recent great platform or stage of permanent advance."[11] The thirty years since Hitzig's work cannot be put here, for they would take a volume to themselves. There have been differences of interpretation of this or that fact, diversities of results, and problems too hard to solve, and other difficulties, such as befall all the natural sciences; but these imperfections amount to very little, when the whole result comes to be reckoned. The marvel is that the work is so nearly perfect, seeing its immeasurable complexity. Let any man, who has but touched the study of physiology, consider what is involved in even the most superficial observation of the simplest facts of the nervous system: for instance, the ordinary nerve-muscle preparation that is taught to every medical student, or the microscopic structure of the spinal cord, or the Wallerian method. Or let him consider how the physiology of the nervous system has been founded on the lower forms of life: the work of Romanes and others on the Medusa and the Echinodermata, and Huxley's work in biology, and the endless chain of forces that are alike in man and in jelly-fishes. Then let him try to estimate the output of hard thinking, for the advance from lower to higher structures, and up to man; the vigilant criticism of all theories and foregone conclusions, the incessant self-judgment and wearisome doubts and disputes all the way, elusiveness of facts, and vagueness of words. And the results thus wrung out of science had still to be stated in terms of practice, and tested by the facts of medicine, surgery, and pathology, and used in every hospital in the civilised world, not only for the saving of life, but also for the diagnosis and medical or surgical treatment of innumerable varieties of disease or injury of the brain, the cord, or the nerves. Sir Michael Foster, in a short summary of the problems of physiology, puts clearly these consummate difficulties of the physiology of the nervous system:— "In the first place there are what may be called general problems, such as, How the food, after its preparation and elaboration into blood, is built up into the living substance of the several tissues? How the living substance breaks down into the dead waste? How the building up and breaking down differ in the different tissues in such a way that energy is set free in different modes, the muscular tissue contracting, the nervous tissue thrilling with a nervous impulse, the secreting tissue doing chemical work, and the like? To these general questions the answers which we can at present give can hardly be called answers at all. "In the second place there are what may be called special problems, such as, What are the various steps by which the blood is kept replenished with food and oxygen, and kept free from an accumulation of water; and how is the activity of the digestive, respiratory, and excretory organs, which effect this, regulated and adapted to the stress of circumstances? What are the details of the vascular mechanism by which each and every tissue is for ever bathed with fresh blood, and how is that working delicately adapted to all the varied changes of the body? And, compared with which all other problems are insignificant and preparatory only, how do nervous impulses so flit to and fro within the nervous system as to issue in the movements which make up what we sometimes call the life of man?" The physiology of the nervous system is wrought to finer issues now than in the time of Bell and Magendie; and this generation of students may live to see the present facts and methods of cerebral localisation as the mere rudiments or elements of science. Happily for mankind, science has already so far elucidated them that they have done good service for the diagnosis and treatment of disease, and for the saving of lives.
Some examples have been given, in the foregoing chapters, of the value of physiological experiments on animals. It would be easy to lengthen the list, for there is no general subject in all physiology that does not owe something to this method: as Mr. Darwin said, in his evidence before the Royal Commission of 1875, "I am fully convinced that physiology can progress only by the aid of experiments on living animals. I cannot think of any one step which has been made in physiology without that aid." Many examples have been left out altogether—the work of Boyle, Hunter, Lavoisier, Haldane, Despretz, and Regnault, on animal heat and on respiration; of Petit, Dupuy, Breschet, and Reid, on the sympathetic system; of Galvani, Volta, Haller, du Bois-Reymond, and PflÜger, on muscular contractility: nothing has been said of the work lately done on the suprarenal glands and "adrenalin," and on the blood-pressure in its relation to secretion. For the most part, only those examples have been taken that occur far back in the history of physiology: more has been said about the past than about the present. First, because it was necessary to put an end to the false statements that are made, by those who are opposed to all experiments on animals, about the work done in the past. Next, because the abstruse details of physiology, in the present, are not intelligible for general reading. Next, because it is impossible now to isolate physiology, or to say what belongs to physiology alone, to have back the simpler problems of the past, to discover the circulation of the blood twice. But the experimental method, alike in the past and in the present, has been the chief way of advance. And if a forecast may be made without offence, it is certain that the work of physiology, as in the past and the present, so in the near future, will exercise a profound influence for good on medical and surgical treatment. Among the subjects that especially occupy physiologists now are, the more exact localisation and interpretation of the special sense-centres, and the better knowledge of the internal secretions and chemical influences of the glands and tissues of the body. It would be hard to find two fields of work more sure to favour the growth of the arbor vitÆ side by side with the arbor scientiÆ. But the last word here must be said by a physiologist of the very highest authority, Professor Starling. He has kindly given me, for this edition, the following note:— "Among the researches of the last thirty years, those bearing on the Circulation of the Blood must take an important place, both for their physiological interest and for the weighty influence they have exerted on our knowledge and treatment of disorders of the vascular system, such as heart disease. We have learned to measure accurately the work done by the great heart-pump; and by studying the manner in which this work is affected by different conditions, we are enabled to increase or diminish it, according to the needs of the organ. Experiments in what is often regarded as the most transcendental department of physiology—i.e. that which treats of muscle and nerve—have thrown light on the wonderful process of 'compensation,' by which a diseased heart is able to keep up a normal circulation. "Vaso-motor System.—Largely by the labours of British physiologists, the exquisite control exercised by the nervous system over every blood-vessel in the body has been brought to light, the paths tracked out, and the mechanisms elucidated, by means of which the circulation through each part of the body is subordinated to the needs of the whole. Since the chief vaso-motor nerves take their course through the sympathetic system, the researches on their distribution have led to the mapping out of the whole of this system, and to an accurate knowledge of its functions. We are now acquainted with the course, to all parts of the body, of the nerves which not only determine the changes in the calibre of the blood-vessels, but affect also the secretion of sweat and the erection of the hairs. Incidentally, the mapping out of these nerves, in the hands of Mackenzie, Head, and others, has led to more power of localising the seat of visceral disease. "Digestion.—Our knowledge of the processes of digestion has of late years received a great accession by the work of Professor Pawlow, of St. Petersburg. His success is largely due to his recognition of the importance of keeping his experimental animals under the most normal conditions possible, and of studying the different parts of the alimentary tract in animals which were not anÆsthetised, but which were free from any pain or even discomfort, either of which conditions materially interferes with the activity of the digestive glands. He therefore established in dogs fistulÆ in chosen portions of the alimentary canal, analogous to the fistula which accident rendered so valuable in the case of Alexis St. Martin. Not only has the knowledge thus gained enabled the physician to understand the sequel of events in disordered digestion, but the success of the operative measures undertaken by physiologists for the elucidation of their science has emboldened surgeons to attack disease in the most various parts of the alimentary canal. "Renewed study of the secretion of pancreatic juice evoked by the passage of the acid digestive products from the stomach into the small intestine, which had been described by Pawlow, has resulted in the discovery of a new class of chemical agents, which act as special messengers from one part of the body to another, and exercise an important function in determining the action of all parts to one common end. "Respiration.—The investigation of the chemical properties of the colouring matter of blood, and of its compound with carbon monoxide, has resulted, in the hands of Dr. Haldane, in the laying down of measures for the prevention of accidents from choke-damp or after-damp in mines. The same investigation has resulted in the discovery of a method of determining the total amount of blood circulating in the body of a living man. The application of this method has already added largely to our knowledge of the pathology of different forms of anÆmia, as well as of the conditions obtaining in heart disease. Experiments by Hill and others on the physiological effects of compressed air have shown the precautions which should be observed in all diving operations. A proper appreciation of these results by diving-engineers would not only entirely obviate the cases of 'caisson disease,' but would enable diving to be carried on safely to a greater depth than has hitherto been attempted. "It is impossible, however, to enumerate all the physiological gains of the last twenty or thirty years, or to point out their manifold applications in the cure and prevention of disease. The full control of the processes of disease, which is the goal of the physician and the surgeon, can only be attained through an accurate knowledge of the conditions governing the functions of the healthy body. The foundation of medicine and surgery is physiology: and it is only on living animals that the processes of life can be investigated."
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