LET us return to Padua about the year 1600. Vesalius, who made the school the most famous anatomical centre in Europe, was succeeded by Fallopius, one of the best-known names in anatomy, at whose death an unsuccessful attempt was made to get Vesalius back. He was succeeded in 1565 by a remarkable man, Fabricius (who usually bears the added name of Aquapendente, from the town of his birth), a worthy follower of Vesalius. In 1594, in the thirtieth year of his professoriate, he built at his own expense a new anatomical amphitheatre, which still exists in the university buildings. It is a small, high-pitched room with six standing-rows for auditors rising abruptly one above the other. The arena is not much more than large enough for the dissecting table which, by a lift, could be brought up from a preparing room below. The study of anatomy at Padua must have declined since the days of Vesalius if this tiny amphitheatre held all its students; none the less, it is probably the oldest existing anatomical lecture room, and for us it has a very special significance.

Early in his anatomical studies Fabricius had demonstrated the valves in the veins. I show you here two figures, the first, as far as I know, in which these structures are depicted. It does not concern us who first discovered them; they had doubtless been seen before, but Fabricius first recognized them as general structures in the venous system, and he called them little doors—"ostiola."

The quadrangle of the university building at Padua is surrounded by beautiful arcades, the walls and ceilings of which are everywhere covered with the stemmata, or shields, of former students, many of them brilliantly painted. Standing in the arcade on the side of the "quad" opposite the entrance, if one looks on the ceiling immediately above the capital of the second column to the left there is seen the stemma which appears as tailpiece to this chapter, put up by a young Englishman, William Harvey, who had been a student at Padua for four years. He belonged to the "Natio Anglica," of which he was Conciliarius, and took his degree in 1602. Doubtless he had repeatedly seen Fabricius demonstrate the valves of the veins, and he may indeed, as a senior student, have helped in making the very dissections from which the drawings were taken for Fabricius' work, "De Venarum Osteolis," 1603. If one may judge from the character of the teacher's work the sort of instruction the student receives, Harvey must have had splendid training in anatomy. While he was at Padua, the great work of Fabricius, "De Visione, Voce et Auditu" (1600) was published, then the "Tractatus de Oculo Visusque Organo" (1601), and in the last year of his residence Fabricius must have been busy with his studies on the valves of the veins and with his embryology, which appeared in 1604. Late in life, Harvey told Boyle that it was the position of the valves of the veins that induced him to think of a circulation.

Harvey returned to England trained by the best anatomist of his day. In London, he became attached to the College of Physicans, and taking his degree at Cambridge, he began the practice of medicine. He was elected a fellow of the college in 1607 and physician to St. Bartholomew's Hospital in 1609. In 1615 he was appointed Lumleian lecturer to the College of Physicians, and his duties were to hold certain "public anatomies," as they were called, or lectures. We know little or nothing of what Harvey had been doing other than his routine work in the care of the patients at St. Bartholomew's. It was not until April, 1616, that his lectures began. Chance has preserved to us the notes of this first course; the MS. is now in the British Museum and was published in facsimile by the college in 1886.(26)

The second day lecture, April 17, was concerned with a description of the organs of the thorax, and after a discussion on the structure and action of the heart come the lines:

The illustration will give one an idea of the extraordinarily crabbed hand in which the notes are written, but it is worth while to see the original, for here is the first occasion upon which is laid down in clear and unequivocal words that the blood CIRCULATES. The lecture gave evidence of a skilled anatomist, well versed in the literature from Aristotle to Fabricius. In the MS. of the thorax, or, as he calls it, the "parlour" lecture, there are about a hundred references to some twenty authors. The remarkable thing is that although those lectures were repeated year by year, we have no evidence that they made any impression upon Harvey's contemporaries, so far, at least, as to excite discussions that led to publication. It was not until twelve years later, 1628, that Harvey published in Frankfurt a small quarto volume of seventy-four pages,(27) "De Motu Cordis." In comparison with the sumptuous "Fabrica" of Vesalius this is a trifling booklet; but if not its equal in bulk or typographical beauty (it is in fact very poorly printed), it is its counterpart in physiology, and did for that science what Vesalius had done for anatomy, though not in the same way. The experimental spirit was abroad in the land, and as a student at Padua, Harvey must have had many opportunities of learning the technique of vivisection; but no one before his day had attempted an elaborate piece of experimental work deliberately planned to solve a problem relating to the most important single function of the body. Herein lies the special merit of his work, from every page of which there breathes the modern spirit. To him, as to Vesalius before him, the current views of the movements of the blood were unsatisfactory, more particularly the movements of the heart and arteries, which were regarded as an active expansion by which they were filled with blood, like bellows with air. The question of the transmission of blood through the thick septum and the transference of air and blood from the lungs to the heart were secrets which he was desirous of searching out by means of experiment.

One or two special points in the work may be referred to as illustrating his method. He undertook first the movements of the heart, a task so truly arduous and so full of difficulties that he was almost tempted to think with Fracastorius that "the movement of the heart was only to be comprehended by God." But after many difficulties he made the following statements: first, that the heart is erected and raises itself up into an apex, and at this time strikes against the breast and the pulse is felt externally; secondly, that it is contracted every-way, but more so at the sides; and thirdly, that grasped in the hand it was felt to become harder at the time of its motion; from all of which actions Harvey drew the very natural conclusion that the activity of the heart consisted in a contraction of its fibres by which it expelled the blood from the ventricles. These were the first four fundamental facts which really opened the way for the discovery of the circulation, as it did away with the belief that the heart in its motion attracts blood into the ventricles, stating on the contrary that by its contraction it expelled the blood and only received it during its period of repose or relaxation. Then he proceeded to study the action of the arteries and showed that their period of diastole, or expansion, corresponded with the systole, or contraction, of the heart, and that the arterial pulse follows the force, frequency and rhythm of the ventricle and is, in fact, dependent upon it. Here was another new fact: that the pulsation in the arteries was nothing else than the impulse of the blood within them. Chapter IV, in which he describes the movements of the auricles and ventricles, is a model of accurate description, to which little has since been added. It is interesting to note that he mentions what is probably auricular fibrillation. He says: "After the heart had ceased pulsating an undulation or palpitation remained in the blood itself which was contained in the right auricle, this being observed so long as it was imbued with heat and spirit." He recognized too the importance of the auricles as the first to move and the last to die. The accuracy and vividness of Harvey's description of the motion of the heart have been appreciated by generations of physiologists. Having grasped this first essential fact, that the heart was an organ for the propulsion of blood, he takes up in Chapters VI and VII the question of the conveyance of the blood from the right side of the heart to the left. Galen had already insisted that some blood passed from the right ventricle to the lungs—enough for their nutrition; but Harvey points out, with Colombo, that from the arrangement of the valves there could be no other view than that with each impulse of the heart blood passes from the right ventricle to the lungs and so to the left side of the heart. How it passed through the lungs was a problem: probably by a continuous transudation. In Chapters VIII and IX he deals with the amount of blood passing through the heart from the veins to the arteries. Let me quote here what he says, as it is of cardinal import:

"But what remains to be said upon the quantity and source of the blood which thus passes, is of a character so novel and unheard of that I not only fear injury to myself from the envy of a few, but I tremble lest I have mankind at large for my enemies, so much doth wont and custom become a second nature. Doctrine once sown strikes deeply its root, and respect for antiquity influences all men. Still the die is cast, and my trust is in my love of truth, and the candour of cultivated minds."(28) Then he goes on to say:

"I began to think whether there might not be A MOVEMENT, AS IT WERE, IN A CIRCLE. Now this I afterwards found to be true; and I finally saw that the blood, forced by the action of the left ventricle into the arteries, was distributed to the body at large, and its several parts, in the same manner as it is sent through the lungs, impelled by the right ventricle into the pulmonary artery, and that it then passed through the veins and along the vena cava, and so round to the left ventricle in the manner already indicated."(29)

The experiments dealing with the transmission of blood in the veins are very accurate, and he uses the old experiment that Fabricius had employed to show the valves, to demonstrate that the blood in the veins flows towards the heart. For the first time a proper explanation of the action of the valves is given. Harvey had no appreciation of how the arteries and veins communicated with each other. Galen, you may remember, recognized that there were anastomoses, but Harvey preferred the idea of filtration.

The "De Motu Cordis" constitutes a unique piece of work in the history of medicine. Nothing of the same type had appeared before. It is a thoroughly sensible, scientific study of a definite problem, the solution of which was arrived at through the combination of accurate observation and ingenious experiment. Much misunderstanding has arisen in connection with Harvey's discovery of the circulation of the blood. He did not discover that the blood moved,—that was known to Aristotle and to Galen, from both of whom I have given quotations which indicate clearly that they knew of its movement,—but at the time of Harvey not a single anatomist had escaped from the domination of Galen's views. Both Servetus and Colombo knew of the pulmonary circulation, which was described by the former in very accurate terms. Cesalpinus, a great name in anatomy and botany, for whom is claimed the discovery of the circulation, only expressed the accepted doctrines in the following oft-quoted phrase:

"We will now consider how the attraction of aliment and the process of nutrition takes place in plants; for in animals we see the aliment brought through the veins to the heart, as to a laboratory of innate heat, and, after receiving there its final perfection, distributed through the arteries to the body at large, by the agency of the spirits produced from this same aliment in the heart."(30) There is nothing in this but Galen's view, and Cesalpinus believed, as did all his contemporaries, that the blood was distributed through the body by the vena cava and its branches for the nourishment of all its parts.(*) To those who have any doubts as to Harvey's position in this matter I would recommend the reading of the "De Motu Cordis" itself, then the various passages relating to the circulation from Aristotle to Vesalius. Many of these can be found in the admirable works of Dalton, Flourens, Richet and Curtis.(31) In my Harveian Oration for 1906(32) I have dealt specially with the reception of the new views, and have shown how long it was before the reverence for Galen allowed of their acceptance. The University of Paris opposed the circulation of the blood for more than half a century after the appearance of the "De Motu Cordis."

To summarize—until the seventeenth century there were believed to be two closed systems in the circulation, (1) the natural, containing venous blood, had its origin in the liver from which, as from a fountain, the blood continually ebbed and flowed for the nourishment of the body; (2) the vital, containing another blood and the spirits, ebbed and flowed from the heart, distributing heat and life to all parts. Like a bellows the lungs fanned and cooled this vital blood. Here and there we find glimmering conceptions of a communication between these systems, but practically all teachers believed that the only one of importance was through small pores in the wall separating the two sides of the heart. Observation—merely looking at and thinking about things—had done all that was possible, and further progress had to await the introduction of a new method, viz., experiment. Galen, it is true, had used this means to show that the arteries of the body contained blood and not air. The day had come when men were no longer content with accurate description and with finely spun theories and dreams. It was reserved for the immortal Harvey to put into practice the experimental method by which he demonstrated conclusively that the blood moved in a circle. The "De Motu Cordis" marks the final break of the modern spirit with the old traditions. It took long for men to realize the value of this "inventum mirabile" used so effectively by the Alexandrians—by Galen—indeed, its full value has only been appreciated within the past century. Let me quote a paragraph from my Harveian Oration.(33) "To the age of the hearer, in which men had heard and heard only, had succeeded the age of the eye in which men had seen and had been content only to see. But at last came the age of the hand—the thinking, devising, planning hand, the hand as an instrument of the mind, now re-introduced into the world in a modest little monograph from which we may date the beginning of experimental medicine."

Harvey caught the experimental spirit in Italy, with brain, eye and hand as his only aids, but now an era opened in which medicine was to derive an enormous impetus from the discovery of instruments of precision. "The new period in the development of the natural sciences, which reached its height in the work of such men as Galileo, Gilbert and Kepler, is chiefly characterized by the invention of very important instruments for aiding and intensifying the perceptions of the senses, by means of which was gained a much deeper insight into the phenomena than had hitherto been possible. Such instruments as the earlier ages possessed were little more than primitive hand-made tools. Now we find a considerable number of scientifically made instruments deliberately planned for purposes of special research, and as it were, on the threshold of the period stand two of the most important, the compound microscope and the telescope. The former was invented about 1590 and the latter about 1608."(34) It was a fellow professor of the great genius Galileo who attempted to put into practice the experimental science of his friend. With Sanctorius began the studies of temperature, respiration and the physics of the circulation. The memory of this great investigator has not been helped by the English edition of his "De Statica Medicina," not his best work, with a frontispiece showing the author in his dietetic balance. Full justice has been done to him by Dr. Weir Mitchell in an address as president of the Congress of Physicians and Surgeons, 1891.(35) Sanctorius worked with a pulsilogue devised for him by Galileo, with which he made observations on the pulse. He is said to have been the first to put in use the clinical thermometer. His experiments on insensible perspiration mark him as one of the first modern physiologists.

But neither Sanctorius nor Harvey had the immediate influence upon their contemporaries which the novel and stimulating character of their work justified. Harvey's great contemporary, Bacon, although he lost his life in making a cold storage experiment, did not really appreciate the enormous importance of experimental science. He looked very coldly upon Harvey's work. It was a philosopher of another kidney, Rene Descartes, who did more than anyone else to help men to realize the value of the better way which Harvey had pointed out. That the beginning of wisdom was in doubt, not in authority, was a novel doctrine in the world, but Descartes was no armchair philosopher, and his strong advocacy and practice of experimentation had a profound influence in directing men to "la nouvelle methode." He brought the human body, the earthly machine, as he calls it, into the sphere of mechanics and physics, and he wrote the first text-book of physiology, "De l'Homme." Locke, too, became the spokesman of the new questioning spirit, and before the close of the seventeenth century, experimental research became all the mode. Richard Lower, Hooke and Hales were probably more influenced by Descartes than by Harvey, and they made notable contributions to experimental physiology in England. Borelli, author of the famous work on "The Motion of Animals" (Rome, 1680-1681), brought to the study of the action of muscles a profound knowledge of physics and mathematics and really founded the mechanical, or iatromechanical school. The literature and the language of medicine became that of physics and mechanics: wheels and pulleys, wedges, levers, screws, cords, canals, cisterns, sieves and strainers, with angles, cylinders, celerity, percussion and resistance, were among the words that now came into use in medical literature. Withington quotes a good example in a description by Pitcairne, the Scot who was professor of medicine at Leyden at the end of the seventeenth century. "Life is the circulation of the blood. Health is its free and painless circulation. Disease is an abnormal motion of the blood, either general or local. Like the English school generally, he is far more exclusively mechanical than are the Italians, and will hear nothing of ferments or acids, even in digestion. This, he declares, is a purely mechanical process due to heat and pressure, the wonderful effects of which may be seen in Papin's recently invented 'digester.' That the stomach is fully able to comminute the food may be proved by the following calculation. Borelli estimates the power of the flexors of the thumb at 3720 pounds, their average weight being 122 grains. Now, the average weight of the stomach is eight ounces, therefore it can develop a force of 117,088 pounds, and this may be further assisted by the diaphragm and abdominal muscles the power of which, estimated in the same way, equals 461,219 pounds! Well may Pitcairne add that this force is not inferior to that of any millstone."(36) Paracelsus gave an extraordinary stimulus to the study of chemistry and more than anyone else he put the old alchemy on modern lines. I have already quoted his sane remark that its chief service is in seeking remedies. But there is another side to this question. If, as seems fairly certain, the Basil Valentine whose writings were supposed to have inspired Paracelsus was a hoax and his works were made up in great part from the writings of Paracelsus, then to our medical Luther, and not to the mythical Benedictine monk, must be attributed a great revival in the search for the Philosopher's Stone, for the Elixir of Life, for a universal medicine, for the perpetuum mobile and for an aurum potabile.(37) I reproduce, almost at random, a page from the fifth and last part of the last will and testament of Basil Valentine (London, 1657), from which you may judge the chemical spirit of the time.

Out of the mystic doctrines of Paracelsus arose the famous "Brothers of the Rosy Cross." "The brotherhood was possessed of the deepest knowledge and science, the transmutation of metals, the perpetuum mobile and the universal medicine were among their secrets; they were free from sickness and suffering during their lifetime, though subject finally to death."(38)

A school of a more rational kind followed directly upon the work of Paracelsus, in which the first man of any importance was Van Helmont. The Paracelsian Archeus was the presiding spirit in living creatures, and worked through special local ferments, by which the functions of the organs are controlled. Disease of any part represents a strike on the part of the local Archeus, who refuses to work. Though full of fanciful ideas, Van Helmont had the experimental spirit and was the first chemist to discover the diversity of gases. Like his teacher, he was in revolt against the faculty, and he has bitter things to say of physicians. He got into trouble with the Church about the magnetic cure of wounds, as no fewer than twenty-seven propositions incompatible with the Catholic faith were found in his pamphlet (Ferguson). The Philosophus per ignem, Toparcha in Merode, Royenborch, as he is styled in certain of his writings, is not an easy man to tackle. I show the title-page of the "Ortus Medicinae," the collection of his works by his son. As with the pages of Paracelsus, there are many gems to be dug out. The counterblast against bleeding was a useful protest, and to deny in toto its utility in fever required courage—a quality never lacking in the Father of Modern Chemistry, as he has been called.

A man of a very different type, a learned academic, a professor of European renown, was Daniel Sennert of Wittenberg, the first to introduce the systematic teaching of chemistry into the curriculum, and who tried to harmonize the Galenists and Paracelsians. Franciscus Sylvius, a disciple of Van Helmont, established the first chemical laboratory in Europe at Leyden, and to him is due the introduction of modern clinical teaching. In 1664 he writes: "I have led my pupils by the hand to medical practice, using a method unknown at Leyden, or perhaps elsewhere, i.e., taking them daily to visit the sick at the public hospital. There I have put the symptoms of disease before their eyes; have let them hear the complaints of the patients, and have asked them their opinions as to the causes and rational treatment of each case, and the reasons for those opinions. Then I have given my own judgment on every point. Together with me they have seen the happy results of treatment when God has granted to our cares a restoration of health; or they have assisted in examining the body when the patient has paid the inevitable tribute to death."(39)

Glauber, Willis, Mayow, Lemery, Agricola and Stahl led up to Robert Boyle, with whom modern chemistry may be said to begin. Even as late as 1716, Lady Mary Wortley Montagu in Vienna found that all had transferred their superstitions from religion to chemistry; "scarcely a man of opulence or fashion that has not an alchemist in his service." To one scientific man of the period I must refer as the author of the first scientific book published in England. Dryden sings:

And the verse is true, for by the publication in 1600 of the "De Magnete" the science of electricity was founded. William Gilbert was a fine type of the sixteenth-century physician, a Colchester man, educated at St. John's College, Cambridge. Silvanus Thompson says: "He is beyond question rightfully regarded as the Father of Electric Science. He founded the entire subject of Terrestrial Magnetism. He also made notable contributions to Astronomy, being the earliest English expounder of Copernicus. In an age given over to metaphysical obscurities and dogmatic sophistry, he cultivated the method of experiment and of reasoning from observation, with an insight and success which entitles him to be regarded as the father of the inductive method. That method, so often accredited to Bacon, Gilbert was practicing years before him."(40)