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Popular Science Monthly/Volume 80/June 1912/Research in Medicine II

RESEARCH IN MEDICINE[1]
By Professor RICHARD M. PEARCE

UNIVERSITY OF PENNSYLVANIA

II. The Development of Laboratories for the Medical Sciences

IT would be interesting to trace in the events and activities of the later years of the eighteenth and early years of the nineteenth centuries that development of general thought which exerted indirectly an influence on modern medicine; but, under the circumstances, I can outline only a few; it was the period of the struggle for American Independence, of the French Revolution and of England's abolition of the slave trade. The world was becoming wiser and more humane; men and women were no longer hanged for witchcraft; the principle of education for all was being recognized; and it was also at this time that the insane were treated as persons ill of disease and not as prisoners, to be chained together and crowded into filthy pens until death should end their misery.

Captain Cook was enlarging the boundaries of the known world, Daguerre was establishing the art of photography, Murdoch was developing the use of coal gas as an illuminant. Watts was improving the steam engine, Fulton was concerned with the steamboat and Stephenson somewhat later with the steam locomotive. Machinery was being invented to replace hand labor, and advances in technical and industrial procedures were rapidly following one another.

It was likewise a period marked by the rise of great chemists and physicists, as Lavoisier, Scheele, Priestley, Avogadro, Dalton, Gay-Lussac, Davy, Volta, Franklin and Galvani; great naturalists as Cuvier, Humboldt and Lamarck; and great astronomers and mathematicians as Herschel and Laplace. At the time, the activities of these men were not seen to be directly contributory to the science and practise of medicine, but as the years went on and it became more and more evident—largely as the result of their work—that knowledge was to be gained not by establishing all-embracing systems of philosophy, but by the accumulation of facts through exact observation and experiment, their methods became the property of all branches of science and so, naturally, of medicine. In addition to method, moreover, these men offered, in the fruits of their labors, a not inconsiderable amount of data of direct value to medicine, in the establishing of sound principles of physiology.

In the meantime, however, the practise of medicine labored under great difficulties and was largely a matter of empiricism. Without a knowledge of etiology, without pathological anatomy, that firm foundation for diagnosis, and without a rational therapy it could be nothing else. Mercury, cinchona, cathartics and bleeding were the general methods of treatment. Great and noble men filled the universities-and hospitals; they labored conscientiously, and elaborated systems, and did what they could to relieve human misery, but to the advance of the science of medicine they contributed little or nothing.

Anatomy as a descriptive science dealing with adult structures and their gross appearance had been well established; l)ut it waited for its fullest development upon the methods destined to establish histology and embryology. Experimental physiology, except as Haller and Hunter had influenced it, was an unknown field, soon, however, to be widely explored as the result of the introduction of instruments of precision and analytical methods. Pathology, dependent upon the methods of histology and physiology was marking time, and, in turn, internal medicine awaited the development of pathological anatomy. Surgery, slowly improving technical procedures, likewise marked time until anesthesia and asepsis opened new worlds to it.

The advance in these general subjects it is my intention to follow along the lines of physics, chemistry and biology, as they developed in France, England and Germany. And, if in the course of this presentation I have much to say about the work shops of these sciences, it is because universities, laboratories and hospitals, as. well as societies and journals, represent the visible machinery of nineteenth century research in medicine, and whether we regard them as the cause or the effect of the awakening of 70 years ago, they to-day constitute our hope for the future of medical research.

It is difficult to select a starting point for a systematic survey. Chemistry, however, appears to promise the most direct course, for it was toward the end of the eighteenth century that Lavoisier introduced the modern scientific spirit of exact measurement as applied to chemical phenomena and through it established the great reform responsible for modern chemical knowledge and research. Carbonic acid had already been discovered by Black, hydrogen by Cavendish, nitrogen by Rutherford and ammonia by Priestley; oxygen had been studied by Priestley, Scheele and Lavoisier, so that with Dalton's atomic theorv, Cavendish's analysis of the air and Lavoisier's study of oxidation, definite knowledge of the chemistry of air and water, and of combustion and respiration was at hand for the use of the physiologist and physiological chemist. At about the same time the science of crystallography was established and somewhat later Davy's use of the electric current in the study of the alkaline earths.

In a word, activity in chemistry was evident everywhere, and theory and methods were being rapidly developed, but nowhere was chemistry a part of university study. Berzelius, Gay-Lussac and others had organized laboratories for the training of chemists, but it remained for the University of Giessen to establish the first chemical laboratory under the control of a university. Here, Liebig in 1836, when only 21 years of age, opened his laboratory and began his labors in organic chemistry.

The event is of importance, not only for chemistry, bnt for medical research in general, for the admission of chemistry to the university was the first step towards the overthrow of the "natur-philosopher" and hence to the development of that modern science which has made German universities so justly famous. It is also important from another point of view; in France science had been the work of the academicians, in England of workers in private laboratories or in those supported by commercial companies; by the new departure at Giessen, the precedent for university laboratories was established, and the world has since followed Germany's lead.

This laboratory of Liebig at Giessen was a success immediately and became the training school for most of the eminent chemists outside of Paris. The training offered at Giessen was systematic and methodical in qualitative, quantitative and organic analysis. In his autobiography, Liebig speaks of the difficulty "as the numbers increased, of the practical teaching itself" but "a progressive way of working" was thought out and tried, I can not refrain from quoting his own words concerning the development of the work in organic chemistry.

The first years of my residence at Giessen were almost exclusively devoted to the improvement of organic analysis, and with the first successes there began at the small university an activity such as the world had not yet seen. . . . Every one was obliged to find his own way for himself. . . . We worked from dawn to the fall of night, there were no recreations and pleasures at Giessen. The only complaints were those of the attendant, who in the evenings, when he had to clean, could not get the workers to leave the laboratory.

In another place he says:

I have found among all who frequent this laboratory (Giessen) for technical purposes a prominent inclination to occupy themselves with applied chemistry. They usually follow hesitatingly and with some suspicion my advice to leave alone all this time-absorbing drudgery, and simply to become acquainted with the necessary ways and means of solving purely scientific questions.

Such were the habits, the methods of work and the ideals of the man who in four years established that simple and accurate method of organic analysis known by his name. From his labors and those of Wohler, who in 1828 announced the first synthesis of an organic substance (urea) dates our modern organic chemistry. Liebig representing the school of Gay-Lussac and Wöhler that of Berzelius, one at Giessen and the other at Göttingen, serve as an interesting example of scientific cooperation to develop a new science.

Liebig's work led directly to those activities which we now group under the term physiological or biological chemistry, but physiology was at this time making rapid strides along another line of attack—the application of the principles of mechanics and physics. The part of physics in medicine from Galileo to Roentgen is one of the most fascinating phases of the history of medicine; in principle and practise, in theory and science, its influence has been one of fundamental importance and in its application to methods of clinical diagnosis it shares equally with pathological anatomy in the awakening of modern clinical medicine. The first widely reaching application was in Harvey's interpretation of the circulation of the blood and the action of the heart, but it was not until organized physiological laboratories had been instituted that the application of the principle of physics bore abundant fruit. To recall the state of physics at that time it is only necessary to state that the work of Galvani and Volta was completed and that Ampere and Ohm, Faraday and Wheatstone, were still active. Charles Bell had already (1811) given to England the second of two great discoveries in physiology, the differentiation of sensory and motor nerves. Haller, as we have seen, had in the preceding century presented and discussed the irritability of muscle. The time was at hand for the study of the general physics of muscle and nerve and the special senses. Ernst Weber announced the principles of his psycho-physics in 1825 and Johannes Müller those of his physical chemistry in 1826; Purkinjé had already established the first university laboratory of physiology in 1824 at Breslau; in 1838 the celebrated physiological institute at Berlin was formed under the direction of Müller and in 1840 Ernst Weber was made professor of physiology at Leipzig. From these two centers, Berlin and Leipzig, from Johannes Müller and Ernst PL Weber, came a great volume of minute investigations based on exact methods of inquiry. Both schools were largely busied with studies of the mechanism of the perceptions of the senses, that of Weber tending to include mental phenomena, thus anticipating the modern school of psychologists, that of Müller including not only the methods of physics, but also those of general biology. Müller (1801-1858) was indeed the last of a school which attempted to embrace all of the territory of biology in its broad sense; a territory which now has its separate and distinct fields of morphology, physiology and chemistry. He may, however, be regarded as responsible for some of the divisions into which the older biology has been split, and for the impulse to new lines of study, for he was the teacher of the masters who came in time to occupy high places in biology, of Schwann and Henle in anatomy, of Du Bois-Reymond and Helmholtz in physiology and of Virchow in pathological anatomy. It is not surprising therefore that it was the proud boast of this school that not only had it dispelled the vague notions of the old metaphysical school and established in its stead the true scientific spirit, but that it had filled so many of the chairs of medicine, physiology and anatomy in the German universities that the scientific spirit has been applied to "every branch of medical science, which it has in consequence drawn into the circle of the exact or mechanical sciences." (Merz.)

This is not the place to go into detail concerning the investigations of Müller and his school of physiology. His law of "specific energies," Du Bois Reymond's electro-physiology and Helmholtz's work on musical acoustics and physiological optics indicate the character and scope of the work. The keynote of it all Müller himself has expressed in his "Elements of Physiology" as follows:

Though there appears to be something in the phenomena of living beings which can not be explained by ordinary mechanical, physical or chemical laws, much may be explained, and we may without fear push these explanations as far as we can, so long as we keep to the solid ground of observation and experiment.

These principles and the labors of this school were advanced wonderfully, in 1847, by Ludwig's invention of the kymograph and the elaboration of methods of graphic registration, factors which established this phase of physiology on a sound basis and exerted an influence which medicine feels to this day. This, however, was not the only influence of Müller. As a biologist with general interests he stimulated general biological research and it was undoubtedly this influence exerted through Schwann that led the latter to grasp the importance of Schleiden's work on vegetable cells and to apply the observations of the latter to the cells of the animal body.

But although the cell doctrine, in its modern conception, is the result of the work of these two men, Schleiden and Schwann, it is not to be supposed that they were the first to study cells, for before Schleiden considerable attention had been given to the structure of vegetable tissues. Robert Hooke in 1665 had given to the spaces in cork and similar structure the names of "cells"; Malpighi (1674) and Grew (1683) had, as far as their low power lenses would allow, described plant tissue as made up in part of cell-like cavities provided with firm walls and filled with fluid, and in part of long tube-like vessels. Treviranus, in 1806, demonstrated that these tubes arose as the result of cells becoming attached end to end, the intervening ends eventually disappearing. The nucleus of the cell had been discovered in 1831 by Brown, who, however, failed to realize its importance. Not so Schleiden. He attached great importance to the nucleus and by the numerous observations (1839-1843) which he brought forward was able to formulate a definite cell theory for plants; later when this theory was applied to animal tissues and developed by Schwann and Virchow it became an influence as great as that of the theory of evolution, in the development of modern biology.

Schwann, who was at the time an assistant of Müller, received directly from Schleiden the impulse to compare animal and vegetable cells. While carrying out for Müller the experimental study of nerve and muscle, necessary for the proper preparation of his chief's great book on physiology, he became interested in the histological study of these structures and it was at this time that he described the nerve fiber sheath which now bears his name. Once, when he was dining with Schleiden in 1837, the conversation turned to the nuclei of vegetable cells, Schleiden's description of these recalled to Schwann similar structures which he had seen in animal tissues. The resemblance between the animal and plant cells was, without loss of time, confirmed by both observers and the result was Schwann's famous paper (1839) on the accordance in structure of animal and plant tissues.

It is difficult for the student of to-day, thoroughly drilled concerning the details of cell structure in his courses in normal and pathological histology, to realize that only a little over 70 years ago the essential feature of the animal cell, the nucleus, was not recognized, and that it was a botanist who first brought the subject to the attention of a physiologist. Medicine in all its phases has advanced rapidly along the path thus opened up by Schleiden and Schwann. To-day we are interested above all other things in the chemistry of the cell, but from the time of Schwann to the time of Pasteur the study of the morphology of the cell in health and in disease was one of the chief interests of scientific medicine.

It is not to be supposed, however, that Schwann had the conception of the cell which we have to-day. He, as Schleiden before him, made faulty observations and drew faulty conclusions. The important features of Schwann's work were the recognition of the nucleus, not the cell wall, as the important part of the cell, the demonstration of the union or grouping of the cells to form tissues,[2] and the demonstration that the distinctive cells of the tissues of the adult develop from the undifferentiated cells of the early embryo. The misconceptions of the early histologists were natural when we recall the great technical difficulties with which they had to contend. The microtome, the microscope, and differential staining methods, in their present-day perfection did not exist for them. It was the day of the razor and hand sectioning. The first microtome appears to have been that used by Professor His in 1866; the improvements leading to the perfection of the present-day microtome did not begin until 1875. The development of the objective of the compound microscope was just beginning in Schwann's time (1830). Although iodine was early used, it was not until about 1857 that Geleach called attention to carmine, the first nuclear stain to be introduced into histological technic. At first, tissues were examined only in the fresh state and even later when hardened they were not imbedded as now in celloidin or paraffin, but placed between vegetable pith or blocks of amyloid organs during the process of cutting.

Surely the technical difficulties were great and we are not surprised that both Schleiden and Schwann believed new cells to be formed through a process of "crystallization" from a "mother liquor" or cytoblastema and that the cell was a vesicle with a solid wall. This question of minute structure and that of mitosis yielded eventually to improvements in tecnnique and Schleiden's theory of the formation of cells de novo was discarded, and we know from Virchow's famous aphorism "omnis cellula e cellula" that in his time it was established that cells arose only by the division of preexisting cells. This general law was the result largely of the work of botanists, as Hugo von Mohl and Nägeli, and was applied by Virchow (1858) to animal tissues only after much work had been done on such tissues by Kölliker, Reichert and Remak. It was not until 1873 (Anton Schneider) that an insight into the details of cell division was gained and it was 1882 when the part of the nucleus in karyokinesis was satisfactorily demonstrated and Flemming could supplement Virchow's aphorism with another "omnis nucleus e nucleo."

Thus did Schleiden, a botanist of the University of Jena, and Schwann, assistant (1824r-1838) to Müller, establish one of the most brilliant and most important generalizations of the century, which became at once the basis of all morphological studies, and, as applied by Virchow, placed pathology on a scientific basis, and has continued as a result of its general biological applications—to development, inheritance and immunity—to influence medicine profoundly. As Verworn has said:

It is to the cell that the study of every bodily function sooner or later drives us. In the muscle lies the problem of the heart beat and that of muscular contraction; in the gland cell resides the cause of secretion; in the epithelial cell, in the white blood corpuscle, lies the problem of the absorption of the food, and the secrets of the mind are hidden in the ganglion cell.

It will be necessary to return to the cell theory again in discussing the development of pathology, but we may leave it for the moment to trace one other line of advance made by the physiologist; an advance in that phase of the subject which Du Bois Reymond characterized, in 1880, as "vivisection and zoochemistry" in contrast to the electrophysiology of nerve and muscle with which his own name is so closely linked, and in contrast also to the phase of physiology in which histology, following the lead of Schwann, was playing so large a part. This third field in physiology necessitates a shift of scene to France and Claude Bernard and his school and the study of the functions of organs and their secretions.

Claude Bernard (1813-1878) was the pupil and successor of Magendie. Magendie did many things, but best of all he made "the experimental method the corner stone of normal and pathological physiology and pharmacology." (Welch.) By this method he demonstrated, as Charles Bell had divined, the essentially different functions of the anterior and posterior roots of spinal nerves. Also he founded a journal of experimental physiology.

Bernard, departing widely from Magendie's work, followed in his researches one main idea, the action of the nervous system on the chemical changes which constitute the basis of nutrition and this problem he attempted to solve by either direct experimental investigation of nerves, or by chemical researches or by a combination of both methods. His most important discoveries were the demonstration (1) of the significance of the pancreatic juice in digestion; (2) the glycogenic function of the liver and (3) the vasomotor system. These investigations (1850-1860) with those of Ludwig (1851) on the mechanism of the secretion of the glands, with the earlier observation on gastric digestion made by our own countryman, William Beaumont (1833), and the discovery of pepsin by Schwann (1835) represent the principles out of which our present conception of the physiology of digestion has developed. Not only did Bernard make discoveries and work out the lines of progress for the study of the outward or external secretions of glands, but as a result of his study of the influence of the liver on carbohydrate metabolism, he formulated the theory of "internal secretions," which represents a field of physiology cultivated in the past few years with the greatest success and still full of promise for the future.

Bernard has the distinction of being the first man of science to whom France accorded a public funeral, a recognition not alone of personal worth, but also of the nation's debt to science and to research in the field of medicine.

Thus far I have presented the beginnings of those branches of medicine which deal with normal structure and function. Next in order of development comes that science which is concerned with the study of disease, pathology and upon which are based sound diagnosis and rational therapy and for this reason the science of most interest in medicine. Pathology owes its position as a recognized science to the genius of Virchow, but, in its development, it also owes much to the period I have just discussed, as I will show in due time. To present this development properly it is necessary to turn back to 1761 and Morgagni. I must again remind you that in Morgagni's time medical science can hardly be said to have existed. It was the period of a vague philosophy which attempted to systematize diseases according to symptoms, with no reference to the anatomical conditions causing the symptoms. It was Morgagni who first insisted that the clinical history should be set side by side with the results of the autopsy and who by his publication "De Sedibus et Causis Morborum" threw the first gleam of light on the causes and nature of diseased processes, and thus gave a stimulus to the study of pathological anatomy. Before Morgagni's time, and for some time after, pathological anatomy was mainly concerned with the recording of the rare and curious, with malformations and obvious departures from the normal type; observations oftentimes interesting, but not systematized or harmonized. Morgagni is responsible for the maxim that observations should be "weighed not counted," and it was undoubtedly this point of view which influenced his observations and led eventually to the doctrine that most diseases were to be explained by changes in the organs of the body.

Another step in advance was taken when Bichat, about a quarter of a century later, referred disease to the tissues of the organs. In the meantime John Hunter (1738-1793) had applied to the problems of clinical medicine methods which we now recognize as those of experimental pathology. Still pathology was not a science; it was not systematized and it had no underlying principle. The systematization of pathological anatomy came through Rokitansky[3] (1804-1878) and the underlying principle of pathology from Virchow in 1858.

Rokitansky, the father of pathological anatomy, was an assistant to Johann Wagner, later succeeding him in 1834 as prosector and finally in 1844 as professor of pathological anatomy at Vienna. Wagner had encouraged the application to pathology of the methods of anatomy, and the publication of Rokitansky's "Handbuch der pathologischen Anatomie," completed in 1846 (one year before Virchow's "Archiv" was founded), presented to the profession the results of a most thorough study of the details of pathological anatomy. It is said that Rokitansky performed, as the basis for his classifications, more than thirty thousand autopsies. His position in pathology has been likened to that of Linnæus in botany. "Even to-day nothing can equal the accuracy of Rokitansky's observations. There are few things he did not see. When some lesion or combination of lesions seems entirely new, it is often only necessary to go back to the work of Rokitansky to find that he had observed and accurately described it." (Councilman.) Although he encouraged the development of pathological histology, pathological chemistry and experimental pathology, he took no active part in these subdivisions of pathology and used the microscope but little. He seems to have been content with the establishment of pathological anatomy as a descriptive science.

Between Rokitansky's work and Virchow's cell theory there is no obvious connection. Between Morgagni, Bichat and Virchow we have an interesting link, that formed by the successive theories which placed disease in the organs, the tissues and the cell, respectively. Rokitansky worked with the organs and tissue and had no influence in carrying the quest on to the cell. The influences which led Virchow to the latter are wholly those we have discussed in the story of physiology and its beginnings, the personal influence of Johannes Müller, Schwann's writings and the results of the application to medicine of the methods of physics and chemistry. That he appreciated the importance of the relations of pathology, on the one hand, to physiology, and on the other to clinical medicine is shown in the title of his Archives established in 1847. It is not surprising, therefore, that he was not satisfied with the pathology as merely the descriptive and classifying science of Rokitansky and that he was the first to recognize that pathology was the study of life under abnormal circumstances, and that chemistry, physiology and embryology had a direct bearing on pathology and that the methods of all the other natural sciences should be applied to the elucidation of the problems of pathology and thus to those of medicine.

Virchow's "cellular pathology," as announced in its final form in 1858, must be considered as a general biological principle as important in the field of its application as Darwin's "Origin of Species" published one year later.

It is said that Virchow first began the observations which culminated in his doctrine of cellular pathology in his student days, while serving as an assistant in the eye clinic of the Berlin Hospital. Here he became interested in the fact that in keratitis and wounds of the cornea healing took place without the appearance of plastic exudate. This led to an investigation which indicated the occurrence of repair by the multiplication of preexisting cells. These studies led eventually to his theory, which Lord Lister has described as the "true and fertile doctrine that every morbid structure consists of cells which have been derived from preexisting cells as a progeny." In this theory he brought pathological processes into relation with normal growth, hence his axiom "omnis cellula e cellula." This was the underlying principle, which, following Rokitansky's work in classification, gave pathology a place among the biological sciences. With his cell doctrine as a guide he made many important contributions to histology both normal and pathological, and outlined a classification of new growths which is the basis of all present-day knowledge of tumors.

With his activities as anthropologist-archeologist we are not especially concerned except as they indicate the wide range of his interests. He was one of the founders of the German Anthropological Society, and later its president, and made expeditions with Schliemann to Troy, Egypt, Nubia and the Peloponnese.

Of vast importance to medicine, however, was his establishment of the first pathological laboratory, at the time he returned (in 1855) to Berlin from Würzburg after a political exile of eight years; an exile due to his sympathy with the revolutionary tendencies of 1848. This laboratory was the forerunner of the many which have been founded in the past fifty-five years in all parts of the world, and which have been found essential not only for the purpose of teaching and research, but also in the modern hospital. And again of importance is that influence exerted through his famous pupils such as Leyden, v. Recklinghausen, Cohnheim, Waldeyer, Kühne and Rindfleisch, to mention only the more prominent, who carried his views to other fields and continued his methods. Other great influences were to extend the territory of pathology, as, for examples, Cohnheim's conception of experimental pathology, Weigert's tinctorial methods for the differentiation of cells and tissues, Ehrlich's application of these methods to the study of the blood, Metchnikoff's studies in comparative pathology, and finally the science of bacteriology; but with Virchow remains the credit of having established pathology as a science of university rank.

The third of a century beginning in 1838 with the founding of Liebig's laboratory and ending in 1858 with the publication of Virchow's doctrine of cellular pathology, represents a greater advance in the science of medicine than the combined activities of all the preceding centuries. What was the influence of these advances on the art and practise of medicine? Medicine at the beginning of the century was still influenced by the metaphysical treatment of scientific subjects. The previous century had been one of schools and systems, those of Cullen and Brown in England, Broussais in France and Hoffman and Stahl in Germany. It was also the time of Hahnemann (1753-1844) and the rise of homeopathy. The prevailing tendency was to base disease on the study of symptoms, without regard to the underlying pathological changes causing the symptoms. A few quotations may bring this period of change from the old to the new prominently before you.

Helmholtz writes of the period of his student life:

My education fell within a period of the development of modern medicine when among thinking and conscientious minds there reigned perfect despair. It was not difficult to understand that the older and mostly theorizing methods of treating medical subjects had become absolutely useless. . . . We can not wonder if many honest, serious thinking men turned away in dissatisfaction from medicine, or if they from principle embraced an extreme empiricism.
And again he says:
At that time there were many among the younger doctors who, in despair about their science, gave up all therapeutics, and took to empiricism.

This was from a scientific man, who had much to do with the changes about to come, and perhaps somewhat biased; but we have the view of Stieglitz, an "old and learned practitioner," expressed in 1840:

German medicine was sunk so low and is so emasculated as to require any sort of shaking up. Whatever gives it a new direction will be wholesome, though new errors or possibilities may result therefrom.

But, to continue Helmholtz's remarks:

The right kind of work brought forth its fruits much sooner than many had hoped. The introduction of mechanical notions into the theories of circulation and respiration, a better insight into the phenomena of heat, the more minutely elaborated physiology of the nerves, speedily produced practical results of the greatest importance; the microscopical examination of parasitic tissues, the stupendous development of pathological anatomy, led irresistibly from nebulous theories to real facts.

As Helmholtz was born in 1821 his point of view is that of one who saw both the old and the new; the old in his student days, the new as one of those who labored to bring about the change. His view is largely that of the scientist, but we have fortunately the reminiscences of another, a practitioner of medicine, who labored as a student of medicine in those days of rapid change. I refer to Abraham Jacobi, our own Jacobi, "the father of pediatrics," who studied, as he tells us in his McGill address, "in three universities from 1847 to 1851, in Griefswald, Göttingen and Bonn." Referring to this period, he says:

I have lived under the eyes of and contemporaneously with great men and during the development of modern medicine. . . not as a cooperator, it is true, but as an interested looker-on, when great things happened.

Aside from Vienna, where Rokitansky taught, there were

only two places in all Germany in which pathological anatomy could be learned. One of them was Würzburg, there was Virchow, the other was Göttingen, there was Frerichs. So to Göttingen I went in search of pathological anatomy. . . . At the same time I looked for the advantages of chemical laboratory work under Wiggers and Wohler.

Among the scientific happenings of Jacobi's first medical year (1847) are the following: Helmholtz's address on the conservation of energy; the use of ether anesthesia in obstetric practise by Hamner and in dentistry by Delabarre (first used by Warren at Boston in 1846); Liebig's researches on meats; the employment of prismatic glasses by Kreke and Bonders; the first use of chloroform by Simpson; the employment of Duchenne of faradization in the treatment of paralysis; the discovery of unstriped muscle fibers by Kölliker and the studies by Semmelweis of the etiology of fever in puerperal women.

Among the events of the next five years, during three of which he was a student and two a political prisoner, Jacobi mentions: Bunsen's quantitative analysis of urea, the founding of spectral analysis, the use of cold for anesthesia, Claude Bernard's puncture of the fourth ventricle and his demonstration of the glycogenic function of the liver and of the vasomotor nerves; the discovery of Trichophyton tonsurans and Balantidium coli by Malmsten, the invention of the spirometer by Hutchinson and of the ophthalmoscope by Helmholtz, and the sphygmograph by Vierordt. Altogether Jacobi tells of a host of observations made in a short period of six years. And the list is not one of laboratory discoveries only. It includes important advances in clinical medicine and surgery, as Meigs's discovery of the importance of thrombosis as a cause of death in puerperal women, Marion Sims's vesico-vaginal operation, Detmold's operation for abscesses of the cranial cavity, Walker's work on the infectious nature of secondary syphilis, Romberg's studies of tabes dorsalis, Pravaz's invention of subcutaneous injection, Kuchenmeister's discovery of the connection between tænia and the scolex found in pork, Bigelow's resection of the femur and Bennet's work on leucocythemia.

More could be quoted from Jacobi's impression of this period, but this is enough to show that medicine was advancing not only in the laboratory, but in the clinic. One may, as Jacobi says, "recognize in my fragmentary enumeration, facts of crucial import."

These advances in clinical medicine and surgery were due to several factors; to the increasing use of the methods of physics, chemistry and biology, to the influence of pathology, to the introduction of new procedures in diagnosis, and in surgery, to the facility of operation offered by anesthesia. What a change in the practise of medicine these observations and applications brought about! How different their influence from that of the earlier schools and systems with which we associate the names of Brown, Cullen, Broussais, Hoffman and Stahl!

Such schools and systems, while of interest to the general historian of medicine, offer no assistance to one seeking the lines of advance dependent on investigation or research in medicine. Fortunately for the history of clinical medicine the systematists did not occupy the field to the exclusion of those guided by objective observation, for we find Sydenham (1624-1689) and Boerhaeve (1668-1738) studying disease unbiased by schools or systems, and applying the methods of close observation which we now recognize as those of modern clinical medicine. But although Sydenham and Boerhaeve and their followers aided progress by the addition of some positive knowledge to clinical medicine, their influence on the development of medicine was not great, for they were before the days of Morgagni, Haller, Hunter, Bichat and Rokitansky and the methods associated with these names.[4] Without pathological anatomy clinical classification was impossible, and without physiology and the methods of the physiologist, clinical interpretation was difficult. The influence of pathological anatomy on clinical medicine was felt first in England through Baillie (1761-1823), a pupil of Hunter; in France, after Bichat, through Louis, Andral and Lænnec; in Germany through Schonlein and Romberg; and in America through the pupils of Louis. The discovery of the diseased conditions with which we associate the names of Bright, Pott, Addison, Graves, Stokes and Hodgkins came at this time, as also Marshall Hall's discrimination of diseases of the spinal cord and Bayle's study of tuberculosis of the lung. It was the period when the best members of the profession endeavored to give to the study of symptoms the same precision as characterized anatomical observation and to combine the results of this method with the revelations of pathological anatomy. It was this method that culminated in Louis's so-called "numerical or statistical method," the method of basing conclusions on large groups of records rather than on isolated observations, and which, in this country, through the work of two of Louis's students, Gerhard and Stillé, led to the differentiation of typhoid fever from typhus fever, with which it had been confounded.

But of equal importance was the second influence which was at work, that of improved methods of diagnosis of diseases of the heart and lungs, the methods of percussion and auscultation. Percussion was first used by Auenbrugger, in 1761, but was treated with contempt and ridicule until 1808 when his pamphlet was translated into French by Corvisart, who proclaimed the value of the method and obtained for it universal recognition. Shortly after, in 1819, came Laennec's work on the use of the stethoscope in auscultation, and Skoda in 1839 did much to extend the use of both percussion and auscultation.

This phase of medicine, the development of instruments and means of studying diseases of the internal organs and the organs of the special senses—the history of the stethoscope, the ophthalmoscope, the laryngoscope, and like instruments—is a most fascinating subject and one worthy of extended treatment, but it must suffice here to state that the new methods of direct exploration brought about a complete revolution in the knowledge of disease and had "more influence on the development of modern medicine than all the 'systems' evolved by the most brilliant intellects of the eighteenth century." (Payne.)

Exact clinical observation, the study of pathological anatomy and the increasing use of instruments and methods tending to accuracy in diagnosis were, therefore, the characteristic features of the early nineteenth century school of medicine. Both medicine and surgery were

developing along lines which ensured accelerated progress under the impetus of the discoveries in bacteriology which were soon to follow, and we could with propriety pass on to the era of bacteriology, if it were not for one great boon, destined to have an enormous influence on the practise of surgery, on the diminution of human suffering and on the general advance of research in medicine. This was the introduction of anesthesia. Surgery had steadily advanced in technic, resourcefulness and daring, but the torments of surgery were such that operations were mainly those of necessity. As Mumford says:

Surgical pain was real enough; there was no disguising it. The terror of operation was a very hell, even in anticipation; the fact itself no man has found words to describe. The shadow of it has lengthened even to our own day. Surgeons as well as patients dreaded the knife.

Robert Liston, two years before the discovery of ether congratulated his students that the "field of operative surgery" was "happily narrowed." Keen writes:

It is a striking commentary on the immediate results of anesthesia to learn that, in the five years before the introduction of ether, only 184 persons were willing to submit themselves to such a dreadful ordeal in the Massachusetts Hospital, an average of 37 operations per annum, or 3 per month. In the five years immediately succeeding its introduction, although the old horror could not be overcome, 487 operations, or almost 100 annually, were performed in the same hospital. During the last year (1898) in the same hospital 3,700 operations were performed.

This change was brought about in 1846, when "W. T. G. Morton, an American dentist, by publicly administering ether, proved to the world that it was a safe and sure anesthetic. The operation was performed by John Collins Warren at the Massachusetts General Hospital and the names anesthesia and anesthetic were suggested by Oliver Wendell Holmes. Anesthesia was therefore essentially a Boston affair as far as its introduction to the world was concerned, but the claims of its discovery made by others (Long, Jackson, Wells, Marcy) leave the question of priority in the knowledge of and use of ether in much confusion. With this phase we are not at present concerned. One year after the demonstration in Boston, Simpson, of Edinburgh, recommended chloroform as an anesthetic of equal value with ether. Not only surgery but obstetrics, dentistry and the various specialties benefited by this great boon of anesthesia and within a year the administration of anesthetics was a universal practise throughout the civilized world. Surgery, freed of its horrors, developed along lines hitherto undreamed of, and made those rapid strides which prepared it for the era of antisepsis in the next generation.

The next lecture will concern itself with the story of Pasteur and the development of bacteriology and the influence of the latter on medicine and surgery.

  1. The Hitchcock lectures, delivered at the University of California, January 23-26, 1912.
  2. This statement does not disregard the work of Bichat (1771-1802), frequently called the "father of histology," to whom is due the credit of first recognizing the fact that the body was made up of distinct and differing tissues. Bichat's results, however, were obtained by the use of chemical reagents. He used the microscope but little, and his work, important as it was, and antedating the cell theory by 40 years, can not be considered as leading to the development of the cell theory.
  3. A worthy predecessor of Rokitansky was Johann Fr. Meckel, whose "Handbuch d. patholog. Anatomie" was published at Halle in 1804, the year of Rokitansky's birth.
  4. Before and about the time of the period so represented, some of the important contributions made to clinical medicine and pathological anatomy were as follows: aneurism and diseases of the heart by Lancisi, Albertini and Senac; an investigation by Fothergill, of the diseases now known as diphtheria and tic-doloreux; of prison and camp fevers by Pringle, of epidemic fevers by Husham; of diseases of the skin by Willan, of angina pectoris by Heberden, and of gastric ulcer by Baillie.