Although Napoleon Bonaparte, First Consul, was not lacking in self-appreciation, he probably did not realize that in selecting a physician for his own needs he was markedly influencing the progress of medical science as a whole. Yet so strangely are cause and effect adjusted in human affairs that this simple act of the First Consul had that very unexpected effect. For the man chosen was the envoy of a new method in medical practice, and the fame which came to him through being physician to the First Consul, and subsequently to the Emperor, enabled him to promulgate the method in a way otherwise impracticable. Hence the indirect but telling value to medical science of Napoleon's selection.

The physician in question was Jean Nicolas de Corvisart. His novel method was nothing more startling than the now-familiar procedure of tapping the chest of a patient to elicit sounds indicative of diseased tissues within. Every one has seen this done commonly enough in our day, but at the beginning of the century Corvisart, and perhaps some of his pupils, were probably the only physicians in the world who resorted to this simple and useful procedure. Hence Napoleon's surprise when, on calling in Corvisart, after becoming somewhat dissatisfied with his other physicians Pinel and Portal, his physical condition was interrogated in this strange manner. With characteristic shrewdness Bonaparte saw the utility of the method, and the physician who thus attempted to substitute scientific method for guess-work in the diagnosis of disease at once found favor in his eyes and was installed as his regular medical adviser.

For fifteen years before this Corvisart had practised percussion, as the chest-tapping method is called, without succeeding in convincing the profession of its value. The method itself, it should be added, had not originated with Corvisart, nor did the French physician for a moment claim it as his own. The true originator of the practice was the German physician Avenbrugger, who published a book about it as early as 1761. This book had even been translated into French, then the language of international communication everywhere, by Roziere de la Chassagne, of Montpellier, in 1770; but no one other than Corvisart appears to have paid any attention to either original or translation. It was far otherwise, however, when Corvisart translated Avenbrugger's work anew, with important additions of his own, in 1808.

"I know very well how little reputation is allotted to translator and commentators," writes Corvisart, "and I might easily have elevated myself to the rank of an author if I had elaborated anew the doctrine of Avenbrugger and published an independent work on percussion. In this way, however, I should have sacrificed the name of Avenbrugger to my own vanity, a thing which I am unwilling to do. It is he, and the beautiful invention which of right belongs to him, that I desire to recall to life."[1]

By this time a reaction had set in against the metaphysical methods in medicine that had previously been so alluring; the scientific spirit of the time was making itself felt in medical practice; and this, combined with Corvisart's fame, brought the method of percussion into immediate and well-deserved popularity. Thus was laid the foundation for the method of so-called physical diagnosis, which is one of the corner-stones of modern medicine.

The method of physical diagnosis as practised in our day was by no means completed, however, with the work of Corvisart. Percussion alone tells much less than half the story that may be elicited from the organs of the chest by proper interrogation. The remainder of the story can only be learned by applying the ear itself to the chest, directly or indirectly. Simple as this seems, no one thought of practising it for some years after Corvisart had shown the value of percussion.

Then, in 1815, another Paris physician, Rene Theophile Hyacinthe Laennec, discovered, almost by accident, that the sound of the heart-beat could be heard surprisingly through a cylinder of paper held to the ear and against the patient's chest. Acting on the hint thus received, Laennec substituted a hollow cylinder of wood for the paper, and found himself provided with an instrument through which not merely heart sounds but murmurs of the lungs in respiration could be heard with almost startling distinctness.

The possibility of associating the varying chest sounds with diseased conditions of the organs within appealed to the fertile mind of Laennec as opening new vistas in therapeutics, which he determined to enter to the fullest extent practicable. His connection with the hospitals of Paris gave him full opportunity in this direction, and his labors of the next few years served not merely to establish the value of the new method as an aid to diagnosis, but laid the foundation also for the science of morbid anatomy. In 1819 Laennec published the results of his labors in a work called Traite d'Auscultation Mediate,[2] a work which forms one of the landmarks of scientific medicine. By mediate auscultation is meant, of course, the interrogation of the chest with the aid of the little instrument already referred to, an instrument which its originator thought hardly worth naming until various barbarous appellations were applied to it by others, after which Laennec decided to call it the stethoscope, a name which it has ever since retained.

In subsequent years the form of the stethoscope, as usually employed, was modified and its value augmented by a binauricular attachment, and in very recent years a further improvement has been made through application of the principle of the telephone; but the essentials of auscultation with the stethoscope were established in much detail by Laennec, and the honor must always be his of thus taking one of the longest single steps by which practical medicine has in our century acquired the right to be considered a rational science. Laennec's efforts cost him his life, for he died in 1826 of a lung disease acquired in the course of his hospital practice; but even before this his fame was universal, and the value of his method had been recognized all over the world. Not long after, in 1828, yet another French physician, Piorry, perfected the method of percussion by introducing the custom of tapping, not the chest directly, but the finger or a small metal or hard-rubber plate held against the chest-mediate percussion, in short. This perfected the methods of physical diagnosis of diseases of the chest in all essentials; and from that day till this percussion and auscultation have held an unquestioned place in the regular armamentarium of the physician.

Coupled with the new method of physical diagnosis in the effort to substitute knowledge for guess-work came the studies of the experimental physiologists—in particular, Marshall Hall in England and Francois Magendie in France; and the joint efforts of these various workers led presently to the abandonment of those severe and often irrational depletive methods—blood-letting and the like—that had previously dominated medical practice. To this end also the "statistical method," introduced by Louis and his followers, largely contributed; and by the close of the first third of our century the idea was gaining ground that the province of therapeutics is to aid nature in combating disease, and that this may often be accomplished better by simple means than by the heroic measures hitherto thought necessary. In a word, scientific empiricism was beginning to gain a hearing in medicine as against the metaphysical preconceptions of the earlier generations.


I have just adverted to the fact that Napoleon Bonaparte, as First Consul and as Emperor, was the victim of a malady which caused him to seek the advice of the most distinguished physicians of Paris. It is a little shocking to modern sensibilities to read that these physicians, except Corvisart, diagnosed the distinguished patient's malady as "gale repercutee"—that is to say, in idiomatic English, the itch "struck in." It is hardly necessary to say that no physician of today would make so inconsiderate a diagnosis in the case of a royal patient. If by any chance a distinguished patient were afflicted with the itch, the sagacious physician would carefully hide the fact behind circumlocutions and proceed to eradicate the disease with all despatch. That the physicians of Napoleon did otherwise is evidence that at the beginning of the century the disease in question enjoyed a very different status. At that time itch, instead of being a most plebeian malady, was, so to say, a court disease. It enjoyed a circulation, in high circles and in low, that modern therapeutics has quite denied it; and the physicians of the time gave it a fictitious added importance by ascribing to its influence the existence of almost any obscure malady that came under their observation. Long after Napoleon's time gale continued to hold this proud distinction. For example, the imaginative Dr. Hahnemann did not hesitate to affirm, as a positive maxim, that three-fourths of all the ills that flesh is heir to were in reality nothing but various forms of "gale repercutee."

All of which goes to show how easy it may be for a masked pretender to impose on credulous humanity, for nothing is more clearly established in modern knowledge than the fact that "gale repercutee" was simply a name to hide a profound ignorance; no such disease exists or ever did exist. Gale itself is a sufficiently tangible reality, to be sure, but it is a purely local disease of the skin, due to a perfectly definite cause, and the dire internal conditions formerly ascribed to it have really no causal connection with it whatever. This definite cause, as every one nowadays knows, is nothing more or less than a microscopic insect which has found lodgment on the skin, and has burrowed and made itself at home there. Kill that insect and the disease is no more; hence it has come to be an axiom with the modern physician that the itch is one of the three or four diseases that he positively is able to cure, and that very speedily. But it was far otherwise with the physicians of the first third of our century, because to them the cause of the disease was an absolute mystery.

It is true that here and there a physician had claimed to find an insect lodged in the skin of a sufferer from itch, and two or three times the claim had been made that this was the cause of the malady, but such views were quite ignored by the general profession, and in 1833 it was stated in an authoritative medical treatise that the "cause of gale is absolutely unknown." But even at this time, as it curiously happened, there were certain ignorant laymen who had attained to a bit of medical knowledge that was withheld from the inner circles of the profession. As the peasantry of England before Jenner had known of the curative value of cow-pox over small-pox, so the peasant women of Poland had learned that the annoying skin disease from which they suffered was caused by an almost invisible insect, and, furthermore, had acquired the trick of dislodging the pestiferous little creature with the point of a needle. From them a youth of the country, F. Renucci by name, learned the open secret. He conveyed it to Paris when he went there to study medicine, and in 1834 demonstrated it to his master Alibert. This physician, at first sceptical, soon was convinced, and gave out the discovery to the medical world with an authority that led to early acceptance.

Now the importance of all this, in the present connection, is not at all that it gave the clew to the method of cure of a single disease. What makes the discovery epochal is the fact that it dropped a brand-new idea into the medical ranks—an idea destined, in the long-run, to prove itself a veritable bomb—the idea, namely, that a minute and quite unsuspected animal parasite may be the cause of a well-known, widely prevalent, and important human disease. Of course the full force of this idea could only be appreciated in the light of later knowledge; but even at the time of its coming it sufficed to give a great impetus to that new medical knowledge, based on microscopical studies, which had but recently been made accessible by the inventions of the lens-makers. The new knowledge clarified one very turbid medical pool and pointed the way to the clarification of many others.

Almost at the same time that the Polish medical student was demonstrating the itch mite in Paris, it chanced, curiously enough, that another medical student, this time an Englishman, made an analogous discovery of perhaps even greater importance. Indeed, this English discovery in its initial stages slightly antedated the other, for it was in 1833 that the student in question, James Paget, interne in St. Bartholomew's Hospital, London, while dissecting the muscular tissues of a human subject, found little specks of extraneous matter, which, when taken to the professor of comparative anatomy, Richard Owen, were ascertained, with the aid of the microscope, to be the cocoon of a minute and hitherto unknown insect. Owen named the insect Trichina spiralis. After the discovery was published it transpired that similar specks had been observed by several earlier investigators, but no one had previously suspected or, at any rate, demonstrated their nature. Nor was the full story of the trichina made out for a long time after Owen's discovery. It was not till 1847 that the American anatomist Dr. Joseph Leidy found the cysts of trichina in the tissues of pork; and another decade or so elapsed after that before German workers, chief among whom were Leuckart, Virchow, and Zenker, proved that the parasite gets into the human system through ingestion of infected pork, and that it causes a definite set of symptoms of disease which hitherto had been mistaken for rheumatism, typhoid fever, and other maladies. Then the medical world was agog for a time over the subject of trichinosis; government inspection of pork was established in some parts of Germany; American pork was excluded altogether from France; and the whole subject thus came prominently to public attention. But important as the trichina parasite proved on its own account in the end, its greatest importance, after all, was in the share it played in directing attention at the time of its discovery in 1833 to the subject of microscopic parasites in general.

The decade that followed that discovery was a time of great activity in the study of microscopic organisms and microscopic tissues, and such men as Ehrenberg and Henle and Bory Saint-Vincent and Kolliker and Rokitansky and Remak and Dujardin were widening the bounds of knowledge of this new subject with details that cannot be more than referred to here. But the crowning achievement of the period in this direction was the discovery made by the German, J. L. Schoenlein, in 1839, that a very common and most distressing disease of the scalp, known as favus, is really due to the presence and growth on the scalp of a vegetable organism of microscopic size. Thus it was made clear that not merely animal but also vegetable organisms of obscure, microscopic species have causal relations to the diseases with which mankind is afflicted. This knowledge of the parasites was another long step in the direction of scientific medical knowledge; but the heights to which this knowledge led were not to be scaled, or even recognized, until another generation of workers had entered the field.


Meantime, in quite another field of medicine, events were developing which led presently to a revelation of greater immediate importance to humanity than any other discovery that had come in the century, perhaps in any field of science whatever. This was the discovery of the pain-dispelling power of the vapor of sulphuric ether inhaled by a patient undergoing a surgical operation. This discovery came solely out of America, and it stands curiously isolated, since apparently no minds in any other country were trending towards it even vaguely. Davy, in England, had indeed originated the method of medication by inhalation, and earned out some most interesting experiments fifty years earlier, and it was doubtless his experiments with nitrous oxide gas that gave the clew to one of the American investigators; but this was the sole contribution of preceding generations to the subject, and since the beginning of the century, when Davy turned his attention to other matters, no one had made the slightest advance along the same line until an American dentist renewed the investigation.

In view of the sequel, Davy's experiments merit full attention. Here is his own account of them, as written in 1799:

"Immediately after a journey of one hundred and twenty-six miles, in which I had no sleep the preceding night, being much exhausted, I respired seven quarts of nitrous oxide gas for near three minutes. It produced the usual pleasurable effects and slight muscular motion. I continued exhilarated for some minutes afterwards, but in half an hour found myself neither more nor less exhausted than before the experiment. I had a great propensity to sleep.

"To ascertain with certainty whether the more extensive action of nitrous oxide compatible with life was capable of producing debility, I resolved to breathe the gas for such a time, and in such quantities, as to produce excitement equal in duration and superior in intensity to that occasioned by high intoxication from opium or alcohol.

"To habituate myself to the excitement, and to carry it on gradually, on December 26th I was enclosed in an air-tight breathing-box, of the capacity of about nine and one-half cubic feet, in the presence of Dr. Kinglake. After I had taken a situation in which I could by means of a curved thermometer inserted under the arm, and a stop-watch, ascertain the alterations in my pulse and animal heat, twenty quarts of nitrous oxide were thrown into the box.

"For three minutes I experienced no alteration in my sensations, though immediately after the introduction of the nitrous oxide the smell and taste of it were very evident. In four minutes I began to feel a slight glow in the cheeks and a generally diffused warmth over the chest, though the temperature of the box was not quite 50 degrees. . . . In twenty-five minutes the animal heat was 100 degrees, pulse 124. In thirty minutes twenty quarts more of gas were introduced.

"My sensations were now pleasant; I had a generally diffused warmth without the slightest moisture of the skin, a sense of exhilaration similar to that produced by a small dose of wine, and a disposition to muscular motion and to merriment.

"In three-quarters of an hour the pulse was 104 and the animal heat not 99.5 degrees, the temperature of the chamber 64 degrees. The pleasurable feelings continued to increase, the pulse became fuller and slower, till in about an hour it was 88, when the animal heat was 99 degrees. Twenty quarts more of air were admitted. I had now a great disposition to laugh, luminous points seemed frequently to pass before my eyes, my hearing was certainly more acute, and I felt a pleasant lightness and power of exertion in my muscles. In a short time the symptoms became stationary; breathing was rather oppressed, and on account of the great desire for action rest was painful.

"I now came out of the box, having been in precisely an hour and a quarter. The moment after I began to respire twenty quarts of unmingled nitrous oxide. A thrilling extending from the chest to the extremities was almost immediately produced. I felt a sense of tangible extension highly pleasurable in every limb; my visible impressions were dazzling and apparently magnified, I heard distinctly every sound in the room, and was perfectly aware of my situation. By degrees, as the pleasurable sensations increased, I lost all connection with external things; trains of vivid visible images rapidly passed through my mind and were connected with words in such a manner as to produce perceptions perfectly novel.

"I existed in a world of newly connected and newly modified ideas. I theorized; I imagined that I made discoveries. When I was awakened from this semi-delirious trance by Dr. Kinglake, who took the bag from my mouth, indignation and pride were the first feelings produced by the sight of persons about me. My emotions were enthusiastic and sublime; and for a minute I walked about the room perfectly regardless of what was said to me. As I recovered my former state of mind, I felt an inclination to communicate the discoveries I had made during the experiment. I endeavored to recall the ideas—they were feeble and indistinct; one collection of terms, however, presented itself, and, with most intense belief and prophetic manner, I exclaimed to Dr. Kinglake, 'Nothing exists but thoughts!—the universe is composed of impressions, ideas, pleasures, and pains.' "[3]

From this account we see that Davy has anaesthetized himself to a point where consciousness of surroundings was lost, but not past the stage of exhilaration. Had Dr. Kinglake allowed the inhaling-bag to remain in Davy's mouth for a few moments longer complete insensibility would have followed. As it was, Davy appears to have realized that sensibility was dulled, for he adds this illuminative suggestion: "As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place."[4]

Unfortunately no one took advantage of this suggestion at the time, and Davy himself became interested in other fields of science and never returned to his physiological studies, thus barely missing one of the greatest discoveries in the entire field of science. In the generation that followed no one seems to have thought of putting Davy's suggestion to the test, and the surgeons of Europe had acknowledged with one accord that all hope of finding a means to render operations painless must be utterly abandoned—that the surgeon's knife must ever remain a synonym for slow and indescribable torture. By an odd coincidence it chanced that Sir Benjamin Brodie, the acknowledged leader of English surgeons, had publicly expressed this as his deliberate though regretted opinion at a time when the quest which he considered futile had already led to the most brilliant success in America, and while the announcement of the discovery, which then had no transatlantic cable to convey it, was actually on its way to the Old World.

The American dentist just referred to, who was, with one exception to be noted presently, the first man in the world to conceive that the administration of a definite drug might render a surgical operation painless and to give the belief application was Dr. Horace Wells, of Hartford, Connecticut. The drug with which he experimented was nitrous oxide—the same that Davy had used; the operation that he rendered painless was no more important than the extraction of a tooth—yet it sufficed to mark a principle; the year of the experiment was 1844.

The experiments of Dr. Wells, however, though important, were not sufficiently demonstrative to bring the matter prominently to the attention of the medical world. The drug with which he experimented proved not always reliable, and he himself seems ultimately to have given the matter up, or at least to have relaxed his efforts. But meantime a friend, to whom he had communicated his belief and expectations, took the matter up, and with unremitting zeal carried forward experiments that were destined to lead to more tangible results. This friend was another dentist, Dr. W. T. G. Morton, of Boston, then a young man full of youthful energy and enthusiasm. He seems to have felt that the drug with which Wells had experimented was not the most practicable one for the purpose, and so for several months he experimented with other allied drugs, until finally he hit upon sulphuric ether, and with this was able to make experiments upon animals, and then upon patients in the dental chair, that seemed to him absolutely demonstrative.

Full of eager enthusiasm, and absolutely confident of his results, he at once went to Dr. J. C. Warren, one of the foremost surgeons of Boston, and asked permission to test his discovery decisively on one of the patients at the Boston Hospital during a severe operation. The request was granted; the test was made on October 16, 1846, in the presence of several of the foremost surgeons of the city and of a body of medical students. The patient slept quietly while the surgeon's knife was plied, and awoke to astonished comprehension that the ordeal was over. The impossible, the miraculous, had been accomplished.[5]

Swiftly as steam could carry it—slowly enough we should think it to-day—the news was heralded to all the world. It was received in Europe with incredulity, which vanished before repeated experiments. Surgeons were loath to believe that ether, a drug that had long held a place in the subordinate armamentarium of the physician, could accomplish such a miracle. But scepticism vanished before the tests which any surgeon might make, and which surgeons all over the world did make within the next few weeks. Then there came a lingering outcry from a few surgeons, notably some of the Parisians, that the shock of pain was beneficial to the patient, hence that anaesthesia—as Dr. Oliver Wendell Holmes had christened the new method—was a procedure not to be advised. Then, too, there came a hue-and-cry from many a pulpit that pain was God-given, and hence, on moral grounds, to be clung to rather than renounced. But the outcry of the antediluvians of both hospital and pulpit quickly received its quietus; for soon it was clear that the patient who did not suffer the shock of pain during an operation rallied better than the one who did so suffer, while all humanity outside the pulpit cried shame to the spirit that would doom mankind to suffer needless agony. And so within a few months after that initial operation at the Boston Hospital in 1846, ether had made good its conquest of pain throughout the civilized world. Only by the most active use of the imagination can we of this present day realize the full meaning of that victory.

It remains to be added that in the subsequent bickerings over the discovery—such bickerings as follow every great advance—two other names came into prominent notice as sharers in the glory of the new method. Both these were Americans—the one, Dr. Charles T. Jackson, of Boston; the other, Dr. Crawford W. Long, of Alabama. As to Dr. Jackson, it is sufficient to say that he seems to have had some vague inkling of the peculiar properties of ether before Morton's discovery. He even suggested the use of this drug to Morton, not knowing that Morton had already tried it; but this is the full measure of his association with the discovery. Hence it is clear that Jackson's claim to equal share with Morton in the discovery was unwarranted, not to say absurd.

Dr. Long's association with the matter was far different and altogether honorable. By one of those coincidences so common in the history of discovery, he was experimenting with ether as a pain-destroyer simultaneously with Morton, though neither so much as knew of the existence of the other. While a medical student he had once inhaled ether for the intoxicant effects, as other medical students were wont to do, and when partially under influence of the drug he had noticed that a chance blow to his shins was painless. This gave him the idea that ether might be used in surgical operations; and in subsequent years, in the course of his practice in a small Georgia town, he put the idea into successful execution. There appears to be no doubt whatever that he performed successful minor operations under ether some two or three years before Morton's final demonstration; hence that the merit of first using the drug, or indeed any drug, in this way belongs to him. But, unfortunately, Dr. Long did not quite trust the evidence of his own experiments. Just at that time the medical journals were full of accounts of experiments in which painless operations were said to be performed through practice of hypnotism, and Dr. Long feared that his own success might be due to an incidental hypnotic influence rather than to the drug. Hence he delayed announcing his apparent discovery until he should have opportunity for further tests—and opportunities did not come every day to the country practitioner. And while he waited, Morton anticipated him, and the discovery was made known to the world without his aid. It was a true scientific caution that actuated Dr. Long to this delay, but the caution cost him the credit, which might otherwise have been his, of giving to the world one of the greatest blessings—dare we not, perhaps, say the very greatest?—that science has ever conferred upon humanity.

A few months after the use of ether became general, the Scotch surgeon Sir J. Y. Simpson[6] discovered that another drug, chloroform, could be administered with similar effects; that it would, indeed, in many cases produce anaesthesia more advantageously even than ether. From that day till this surgeons have been more or less divided in opinion as to the relative merits of the two drugs; but this fact, of course, has no bearing whatever upon the merit of the first discovery of the method of anaesthesia. Even had some other drug subsequently quite banished ether, the honor of the discovery of the beneficent method of anaesthesia would have been in no wise invalidated. And despite all cavillings, it is unequivocally established that the man who gave that method to the world was William T. G. Morton.


The discovery of the anaesthetic power of drugs was destined presently, in addition to its direct beneficences, to aid greatly in the progress of scientific medicine, by facilitating those experimental studies of animals from which, before the day of anaesthesia, many humane physicians were withheld, and which in recent years have led to discoveries of such inestimable value to humanity. But for the moment this possibility was quite overshadowed by the direct benefits of anaesthesia, and the long strides that were taken in scientific medicine during the first fifteen years after Morton's discovery were mainly independent of such aid. These steps were taken, indeed, in a field that at first glance might seem to have a very slight connection with medicine. Moreover, the chief worker in the field was not himself a physician. He was a chemist, and the work in which he was now engaged was the study of alcoholic fermentation in vinous liquors. Yet these studies paved the way for the most important advances that medicine has made in any century towards the plane of true science; and to this man more than to any other single individual—it might almost be said more than to all other individuals—was due this wonderful advance. It is almost superfluous to add that the name of this marvellous chemist was Louis Pasteur.

The studies of fermentation which Pasteur entered upon in 1854 were aimed at the solution of a controversy that had been waging in the scientific world with varying degrees of activity for a quarter of a century. Back in the thirties, in the day of the early enthusiasm over the perfected microscope, there had arisen a new interest in the minute forms of life which Leeuwenhoek and some of the other early workers with the lens had first described, and which now were shown to be of almost universal prevalence. These minute organisms had been studied more or less by a host of observers, but in particular by the Frenchman Cagniard Latour and the German of cell-theory fame, Theodor Schwann. These men, working independently, had reached the conclusion, about 1837, that the micro-organisms play a vastly more important role in the economy of nature than any one previously had supposed. They held, for example, that the minute specks which largely make up the substance of yeast are living vegetable organisms, and that the growth of these organisms is the cause of the important and familiar process of fermentation. They even came to hold, at least tentatively, the opinion that the somewhat similar micro-organisms to be found in all putrefying matter, animal or vegetable, had a causal relation to the process of putrefaction.

This view, particularly as to the nature of putrefaction, was expressed even more outspokenly a little later by the French botanist Turpin. Views so supported naturally gained a following; it was equally natural that so radical an innovation should be antagonized. In this case it chanced that one of the most dominating scientific minds of the time, that of Liebig, took a firm and aggressive stand against the new doctrine. In 1839 he promulgated his famous doctrine of fermentation, in which he stood out firmly against any "vitalistic" explanation of the phenomena, alleging that the presence of micro-organisms in fermenting and putrefying substances was merely incidental, and in no sense causal. This opinion of the great German chemist was in a measure substantiated by experiments of his compatriot Helmholtz, whose earlier experiments confirmed, but later ones contradicted, the observations of Schwann, and this combined authority gave the vitalistic conception a blow from which it had not rallied at the time when Pasteur entered the field. Indeed, it was currently regarded as settled that the early students of the subject had vastly over-estimated the importance of micro-organisms.

And so it came as a new revelation to the generality of scientists of the time, when, in 1857 and the succeeding half-decade, Pasteur published the results of his researches, in which the question had been put to a series of altogether new tests, and brought to unequivocal demonstration.

He proved that the micro-organisms do all that his most imaginative predecessors had suspected, and more. Without them, he proved, there would be no fermentation, no putrefaction—no decay of any tissues, except by the slow process of oxidation. It is the microscopic yeast-plant which, by seizing on certain atoms of the molecule, liberates the remaining atoms in the form of carbonic-acid and alcohol, thus effecting fermentation; it is another microscopic plant—a bacterium, as Devaine had christened it—which in a similar way effects the destruction of organic molecules, producing the condition which we call putrefaction. Pasteur showed, to the amazement of biologists, that there are certain forms of these bacteria which secure the oxygen which all organic life requires, not from the air, but by breaking up unstable molecules in which oxygen is combined; that putrefaction, in short, has its foundation in the activities of these so-called anaerobic bacteria.

In a word, Pasteur showed that all the many familiar processes of the decay of organic tissues are, in effect, forms of fermentation, and would not take place at all except for the presence of the living micro-organisms. A piece of meat, for example, suspended in an atmosphere free from germs, will dry up gradually, without the slightest sign of putrefaction, regardless of the temperature or other conditions to which it may have been subjected. Let us witness one or two series of these experiments as presented by Pasteur himself in one of his numerous papers before the Academy of Sciences.


"In the course of the discussion which took place before the Academy upon the subject of the generation of ferments properly so-called, there was a good deal said about that of wine, the oldest fermentation known. On this account I decided to disprove the theory of M. Fremy by a decisive experiment bearing solely upon the juice of grapes.

"I prepared forty flasks of a capacity of from two hundred and fifty to three hundred cubic centimetres and filled them half full with filtered grape-must, perfectly clear, and which, as is the case of all acidulated liquids that have been boiled for a few seconds, remains uncontaminated although the curved neck of the flask containing them remain constantly open during several months or years.

"In a small quantity of water I washed a part of a bunch of grapes, the grapes and the stalks together, and the stalks separately. This washing was easily done by means of a small badger's-hair brush. The washing-water collected the dust upon the surface of the grapes and the stalks, and it was easily shown under the microscope that this water held in suspension a multitude of minute organisms closely resembling either fungoid spores, or those of alcoholic Yeast, or those of Mycoderma vini, etc. This being done, ten of the forty flasks were preserved for reference; in ten of the remainder, through the straight tube attached to each, some drops of the washing-water were introduced; in a third series of ten flasks a few drops of the same liquid were placed after it had been boiled; and, finally, in the ten remaining flasks were placed some drops of grape-juice taken from the inside of a perfect fruit. In order to carry out this experiment, the straight tube of each flask was drawn out into a fine and firm point in the lamp, and then curved. This fine and closed point was filed round near the end and inserted into the grape while resting upon some hard substance. When the point was felt to touch the support of the grape it was by a slight pressure broken off at the point file mark. Then, if care had been taken to create a slight vacuum in the flask, a drop of the juice of the grape got into it, the filed point was withdrawn, and the aperture immediately closed in the alcohol lamp. This decreased pressure of the atmosphere in the flask was obtained by the following means: After warming the sides of the flask either in the hands or in the lamp-flame, thus causing a small quantity of air to be driven out of the end of the curved neck, this end was closed in the lamp. After the flask was cooled, there was a tendency to suck in the drop of grape-juice in the manner just described.

"The drop of grape-juice which enters into the flask by this suction ordinarily remains in the curved part of the tube, so that to mix it with the must it was necessary to incline the flask so as to bring the must into contact with the juice and then replace the flask in its normal position. The four series of comparative experiments produced the following results:

"The first ten flasks containing the grape-must boiled in pure air did not show the production of any organism. The grape-must could possibly remain in them for an indefinite number of years. Those in the second series, containing the water in which the grapes had been washed separately and together, showed without exception an alcoholic fermentation which in several cases began to appear at the end of forty-eight hours when the experiment took place at ordinary summer temperature. At the same time that the yeast appeared, in the form of white traces, which little by little united themselves in the form of a deposit on the sides of all the flasks, there were seen to form little flakes of Mycellium, often as a single fungoid growth or in combination, these fungoid growths being quite independent of the must or of any alcoholic yeast. Often, also, the Mycoderma vini appeared after some days upon the surface of the liquid. The Vibria and the lactic ferments properly so called did not appear on account of the nature of the liquid.

"The third series of flasks, the washing-water in which had been previously boiled, remained unchanged, as in the first series. Those of the fourth series, in which was the juice of the interior of the grapes, remained equally free from change, although I was not always able, on account of the delicacy of the experiment, to eliminate every chance of error. These experiments cannot leave the least doubt in the mind as to the following facts:

Grape-must, after heating, never ferments on contact with the air, when the air has been deprived of the germs which it ordinarily holds in a state of suspension.

"The boiled grape-must ferments when there is introduced into it a very small quantity of water in which the surface of the grapes or their stalks have been washed.

"The grape-must does not ferment when this washing-water has been boiled and afterwards cooled.

"The grape-must does not ferment when there is added to it a small quantity of the juice of the inside of the grape.

"The yeast, therefore, which causes the fermentation of the grapes in the vintage-tub comes from the outside and not from the inside of the grapes. Thus is destroyed the hypothesis of MM. Trecol and Fremy, who surmised that the albuminous matter transformed itself into yeast on account of the vital germs which were natural to it. With greater reason, therefore, there is no longer any question of the theory of Liebig of the transformation of albuminoid matter into ferments on account of the oxidation."


"The method which I have just followed," Pasteur continues, "in order to show that there exists a correlation between the diseases of beer and certain microscopic organisms leaves no room for doubt, it seems to me, in regard to the principles I am expounding.

"Every time that the microscope reveals in the leaven, and especially in the active yeast, the production of organisms foreign to the alcoholic yeast properly so called, the flavor of the beer leaves something to be desired, much or little, according to the abundance and the character of these little germs. Moreover, when a finished beer of good quality loses after a time its agreeable flavor and becomes sour, it can be easily shown that the alcoholic yeast deposited in the bottles or the casks, although originally pure, at least in appearance, is found to be contaminated gradually with these filiform or other ferments. All this can be deduced from the facts already given, but some critics may perhaps declare that these foreign ferments are the consequences of the diseased condition, itself produced by unknown causes.

"Although this gratuitous hypothesis may be difficult to uphold, I will endeavor to corroborate the preceding observations by a clearer method of investigation. This consists in showing that the beer never has any unpleasant taste in all cases when the alcoholic ferment properly so called is not mixed with foreign ferments; that it is the same in the case of wort, and that wort, liable to changes as it is, can be preserved unaltered if it is kept from those microscopic parasites which find in it a suitable nourishment and a field for growth.

"The employment of this second method has, moreover, the advantage of proving with certainty the proposition that I advanced at first—namely, that the germs of these organisms are derived from the dust of the atmosphere, carried about and deposited upon all objects, or scattered over the utensils and the materials used in a brewery-materials naturally charged with microscopic germs, and which the various operations in the store-rooms and the malt-house may multiply indefinitely.

"Let us take a glass flask with a long neck of from two hundred and fifty to three hundred cubic centimetres capacity, and place in it some wort, with or without hops, and then in the flame of a lamp draw out the neck of the flask to a fine point, afterwards heating the liquid until the steam comes out of the end of the neck. It can then be allowed to cool without any other precautions; but for additional safety there can be introduced into the little point a small wad of asbestos at the moment that the flame is withdrawn from beneath the flask. Before thus placing the asbestos it also can be passed through the flame, as well as after it has been put into the end of the tube. The air which then first re-enters the flask will thus come into contact with the heated glass and the heated liquid, so as to destroy the vitality of any dust germs that may exist in the air. The air itself will re-enter very gradually, and slowly enough to enable any dust to be taken up by the drop of water which the air forces up the curvature of the tube. Ultimately the tube will be dry, but the re-entering of the air will be so slow that the particles of dust will fall upon the sides of the tube. The experiments show that with this kind of vessel, allowing free communication with the air, and the dust not being allowed to enter, the dust will not enter at all events for a period of ten or twelve years, which has been the longest period devoted to these trials; and the liquid, if it were naturally limpid, will not be in the least polluted neither on its surface nor in its mass, although the outside of the flask may become thickly coated with dust. This is a most irrefutable proof of the impossibility of dust getting inside the flask.

"The wort thus prepared remains uncontaminated indefinitely, in spite of its susceptibility to change when exposed to the air under conditions which allow it to gather the dusty particles which float in the atmosphere. It is the same in the case of urine, beef-tea, and grape-must, and generally with all those putrefactable and fermentable liquids which have the property when heated to boiling-point of destroying the vitality of dust germs."[7]

There was nothing in these studies bearing directly upon the question of animal diseases, yet before they were finished they had stimulated progress in more than one field of pathology. At the very outset they sufficed to start afresh the inquiry as to the role played by micro-organisms in disease. In particular they led the French physician Devaine to return to some interrupted studies which he had made ten years before in reference to the animal disease called anthrax, or splenic fever, a disease that cost the farmers of Europe millions of francs annually through loss of sheep and cattle. In 1850 Devaine had seen multitudes of bacteria in the blood of animals who had died of anthrax, but he did not at that time think of them as having a causal relation to the disease. Now, however, in 1863, stimulated by Pasteur's new revelations regarding the power of bacteria, he returned to the subject, and soon became convinced, through experiments by means of inoculation, that the microscopic organisms he had discovered were the veritable and the sole cause of the infectious disease anthrax.

The publication of this belief in 1863 aroused a furor of controversy. That a microscopic vegetable could cause a virulent systemic disease was an idea altogether too startling to be accepted in a day, and the generality of biologists and physicians demanded more convincing proofs than Devaine as yet was able to offer.

Naturally a host of other investigators all over the world entered the field. Foremost among these was the German Dr. Robert Koch, who soon corroborated all that Devaine had observed, and carried the experiments further in the direction of the cultivation of successive generations of the bacteria in artificial media, inoculations being made from such pure cultures of the eighth generation, with the astonishing result that animals thus inoculated succumbed to the disease.

Such experiments seem demonstrative, yet the world was unconvinced, and in 1876, while the controversy was still at its height, Pasteur was prevailed upon to take the matter in hand. The great chemist was becoming more and more exclusively a biologist as the years passed, and in recent years his famous studies of the silk-worm diseases, which he proved due to bacterial infection, and of the question of spontaneous generation, had given him unequalled resources in microscopical technique. And so when, with the aid of his laboratory associates Duclaux and Chamberland and Roux, he took up the mooted anthrax question the scientific world awaited the issue with bated breath. And when, in 1877, Pasteur was ready to report on his studies of anthrax, he came forward with such a wealth of demonstrative experiments—experiments the rigid accuracy of which no one would for a moment think of questioning—going to prove the bacterial origin of anthrax, that scepticism was at last quieted for all time to come.

Henceforth no one could doubt that the contagious disease anthrax is due exclusively to the introduction into an animal's system of a specific germ—a microscopic plant—which develops there. And no logical mind could have a reasonable doubt that what is proved true of one infectious disease would some day be proved true also of other, perhaps of all, forms of infectious maladies.

Hitherto the cause of contagion, by which certain maladies spread from individual to individual, had been a total mystery, quite unillumined by the vague terms "miasm," "humor," "virus," and the like cloaks of ignorance. Here and there a prophet of science, as Schwann and Henle, had guessed the secret; but guessing, in science, is far enough from knowing. Now, for the first time, the world KNEW, and medicine had taken another gigantic stride towards the heights of exact science.


Meantime, in a different though allied field of medicine there had been a complementary growth that led to immediate results of even more practical importance. I mean the theory and practice of antisepsis in surgery. This advance, like the other, came as a direct outgrowth of Pasteur's fermentation studies of alcoholic beverages, though not at the hands of Pasteur himself. Struck by the boundless implications of Pasteur's revelations regarding the bacteria, Dr. Joseph Lister (the present Lord Lister), then of Glasgow, set about as early as 1860 to make a wonderful application of these ideas. If putrefaction is always due to bacterial development, he argued, this must apply as well to living as to dead tissues; hence the putrefactive changes which occur in wounds and after operations on the human subject, from which blood-poisoning so often follows, might be absolutely prevented if the injured surfaces could be kept free from access of the germs of decay.

In the hope of accomplishing this result, Lister began experimenting with drugs that might kill the bacteria without injury to the patient, and with means to prevent further access of germs once a wound was freed from them. How well he succeeded all the world knows; how bitterly he was antagonized for about a score of years, most of the world has already forgotten. As early as 1867 Lister was able to publish results pointing towards success in his great project; yet so incredulous were surgeons in general that even some years later the leading surgeons on the Continent had not so much as heard of his efforts. In 1870 the soldiers of Paris died, as of old, of hospital gangrene; and when, in 1871, the French surgeon Alphonse Guerin, stimulated by Pasteur's studies, conceived the idea of dressing wounds with cotton in the hope of keeping germs from entering them, he was quite unaware that a British contemporary had preceded him by a full decade in this effort at prevention and had made long strides towards complete success. Lister's priority, however, and the superiority of his method, were freely admitted by the French Academy of Sciences, which in 1881 officially crowned his achievement, as the Royal Society of London had done the year before.

By this time, to be sure, as everybody knows, Lister's new methods had made their way everywhere, revolutionizing the practice of surgery and practically banishing from the earth maladies that hitherto had been the terror of the surgeon and the opprobrium of his art. And these bedside studies, conducted in the end by thousands of men who had no knowledge of microscopy, had a large share in establishing the general belief in the causal relation that micro-organisms bear to disease, which by about the year 1880 had taken possession of the medical world. But they did more; they brought into equal prominence the idea that, the cause of a diseased condition being known, it maybe possible as never before to grapple with and eradicate that condition.


The controversy over spontaneous generation, which, thanks to Pasteur and Tyndall, had just been brought to a termination, made it clear that no bacterium need be feared where an antecedent bacterium had not found lodgment; Listerism in surgery had now shown how much might be accomplished towards preventing the access of germs to abraded surfaces of the body and destroying those that already had found lodgment there. As yet, however, there was no inkling of a way in which a corresponding onslaught might be made upon those other germs which find their way into the animal organism by way of the mouth and the nostrils, and which, as was now clear, are the cause of those contagious diseases which, first and last, claim so large a proportion of mankind for their victims. How such means might be found now became the anxious thought of every imaginative physician, of every working microbiologist.

As it happened, the world was not kept long in suspense. Almost before the proposition had taken shape in the minds of the other leaders, Pasteur had found a solution. Guided by the empirical success of Jenner, he, like many others, had long practised inoculation experiments, and on February 9, 1880, he announced to the French Academy of Sciences that he had found a method of so reducing the virulence of a disease germ that when introduced into the system of a susceptible animal it produced only a mild form of the disease, which, however, sufficed to protect against the usual virulent form exactly as vaccinia protects against small-pox. The particular disease experimented with was that infectious malady of poultry known familiarly as "chicken cholera." In October of the same year Pasteur announced the method by which this "attenuation of the virus," as he termed it, had been brought about—by cultivation of the disease germs in artificial media, exposed to the air, and he did not hesitate to assert his belief that the method would prove "susceptible of generalization"—that is to say, of application to other diseases than the particular one in question.

Within a few months he made good this prophecy, for in February, 1881, he announced to the Academy that with the aid, as before, of his associates MM. Chamberland and Roux, he had produced an attenuated virus of the anthrax microbe by the use of which, as he affirmed with great confidence, he could protect sheep, and presumably cattle, against that fatal malady. "In some recent publications," said Pasteur, "I announced the first case of the attenuation of a virus by experimental methods only. Formed of a special microbe of an extreme minuteness, this virus may be multiplied by artificial culture outside the animal body. These cultures, left alone without any possible external contamination, undergo, in the course of time, modifications of their virulency to a greater or less extent. The oxygen of the atmosphere is said to be the chief cause of these attenuations—that is, this lessening of the facilities of multiplication of the microbe; for it is evident that the difference of virulence is in some way associated with differences of development in the parasitic economy.

"There is no need to insist upon the interesting character of these results and the deductions to be made therefrom. To seek to lessen the virulence by rational means would be to establish, upon an experimental basis, the hope of preparing from an active virus, easily cultivated either in the human or animal body, a vaccine-virus of restrained development capable of preventing the fatal effects of the former. Therefore, we have applied all our energies to investigate the possible generalizing action of atmospheric oxygen in the attenuation of virus.

"The anthrax virus, being one that has been most carefully studied, seemed to be the first that should attract our attention. Every time, however, we encountered a difficulty. Between the microbe of chicken cholera and the microbe of anthrax there exists an essential difference which does not allow the new experiment to be verified by the old. The microbes of chicken cholera do not, in effect, seem to resolve themselves, in their culture, into veritable germs. The latter are merely cells, or articulations always ready to multiply by division, except when the particular conditions in which they become true germs are known.

"The yeast of beer is a striking example of these cellular productions, being able to multiply themselves indefinitely without the apparition of their original spores. There exist many mucedines (Mucedinae?) of tubular mushrooms, which in certain conditions of culture produce a chain of more or less spherical cells called Conidae. The latter, detached from their branches, are able to reproduce themselves in the form of cells, without the appearance, at least with a change in the conditions of culture, of the spores of their respective mucedines. These vegetable organisms can be compared to plants which are cultivated by slipping, and to produce which it is not necessary to have the fruits or the seeds of the mother plant.

The anthrax bacterium, in its artificial cultivation, behaves very differently. Its mycelian filaments, if one may so describe them, have been produced scarcely for twenty-four or forty-eight hours when they are seen to transform themselves, those especially which are in free contact with the air, into very refringent corpuscles, capable of gradually isolating themselves into true germs of slight organization. Moreover, observation shows that these germs, formed so quickly in the culture, do not undergo, after exposure for a time to atmospheric air, any change either in their vitality or their virulence. I was able to present to the Academy a tube containing some spores of anthrax bacteria produced four years ago, on March 21, 1887. Each year the germination of these little corpuscles has been tried, and each year the germination has been accomplished with the same facility and the same rapidity as at first. Each year also the virulence of the new cultures has been tested, and they have not shown any visible falling off. Therefore, how can we experiment with the action of the air upon the anthrax virus with any expectation of making it less virulent?

"The crucial difficulty lies perhaps entirely in this rapid reproduction of the bacteria germs which we have just related. In its form of a filament, and in its multiplication by division, is not this organism at all points comparable with the microbe of the chicken cholera?

"That a germ, properly so called, that a seed, does not suffer any modification on account of the air is easily conceived; but it is conceivable not less easily that if there should be any change it would occur by preference in the case of a mycelian fragment. It is thus that a slip which may have been abandoned in the soil in contact with the air does not take long to lose all vitality, while under similar conditions a seed is preserved in readiness to reproduce the plant. If these views have any foundation, we are led to think that in order to prove the action of the air upon the anthrax bacteria it will be indispensable to submit to this action the mycelian development of the minute organism under conditions where there cannot be the least admixture of corpuscular germs. Hence the problem of submitting the bacteria to the action of oxygen comes back to the question of presenting entirely the formation of spores. The question being put in this way, we are beginning to recognize that it is capable of being solved.

"We can, in fact, prevent the appearance of spores in the artificial cultures of the anthrax parasite by various artifices. At the lowest temperature at which this parasite can be cultivated—that is to say, about +16 degrees Centigrade—the bacterium does not produce germs—at any rate, for a very long time. The shapes of the minute microbe at this lowest limit of its development are irregular, in the form of balls and pears—in a word, they are monstrosities—but they are without spores. In the last regard also it is the same at the highest temperatures at which the parasite can be cultivated, temperatures which vary slightly according to the means employed. In neutral chicken bouillon the bacteria cannot be cultivated above 45 degrees. Culture, however, is easy and abundant at 42 to 43 degrees, but equally without any formation of spores. Consequently a culture of mycelian bacteria can be kept entirely free from germs while in contact with the open air at a temperature of from 42 to 43 degrees Centigrade. Now appear the three remarkable results. After about one month of waiting the culture dies—that is to say, if put into a fresh bouillon it becomes absolutely sterile.

"So much for the life and nutrition of this organism. In respect to its virulence, it is an extraordinary fact that it disappears entirely after eight days' culture at 42 to 43 degrees Centigrade, or, at any rate, the cultures are innocuous for the guinea-pig, the rabbit, and the sheep, the three kinds of animals most apt to contract anthrax. We are thus able to obtain, not only the attenuation of the virulence, but also its complete suppression by a simple method of cultivation. Moreover, we see also the possibility of preserving and cultivating the terrible microbe in an inoffensive state. What is it that happens in these eight days at 43 degrees that suffices to take away the virulence of the bacteria? Let us remember that the microbe of chicken cholera dies in contact with the air, in a period somewhat protracted, it is true, but after successive attenuations. Are we justified in thinking that it ought to be the same in regard to the microbe of anthrax? This hypothesis is confirmed by experiment. Before the disappearance of its virulence the anthrax microbe passes through various degrees of attenuation, and, moreover, as is also the case with the microbe of chicken cholera, each of these attenuated states of virulence can be obtained by cultivation. Moreover, since, according to one of our recent Communications, anthrax is not recurrent, each of our attenuated anthrax microbes is, for the better-developed microbe, a vaccine—that is to say, a virus producing a less-malignant malady. What, therefore, is easier than to find in these a virus that will infect with anthrax sheep, cows, and horses, without killing them, and ultimately capable of warding off the mortal malady? We have practised this experiment with great success upon sheep, and when the season comes for the assembling of the flocks at Beauce we shall try the experiment on a larger scale.

"Already M. Toussaint has announced that sheep can be saved by preventive inoculations; but when this able observer shall have published his results; on the subject of which we have made such exhaustive studies, as yet unpublished, we shall be able to see the whole difference which exists between the two methods—the uncertainty of the one and the certainty of the other. That which we announce has, moreover, the very great advantage of resting upon the existence of a poison vaccine cultivable at will, and which can be increased indefinitely in the space of a few hours without having recourse to infected blood."[8]

This announcement was immediately challenged in a way that brought it to the attention of the entire world. The president of an agricultural society, realizing the enormous importance of the subject, proposed to Pasteur that his alleged discovery should be submitted to a decisive public test. He proposed to furnish a drove of fifty sheep half of which were to be inoculated with the attenuated virus of Pasteur. Subsequently all the sheep were to be inoculated with virulent virus, all being kept together in one pen under precisely the same conditions. The "protected" sheep were to remain healthy; the unprotected ones to die of anthrax; so read the terms of the proposition. Pasteur accepted the challenge; he even permitted a change in the programme by which two goats were substituted for two of the sheep, and ten cattle added, stipulating, however, that since his experiments had not yet been extended to cattle these should not be regarded as falling rigidly within the terms of the test.

It was a test to try the soul of any man, for all the world looked on askance, prepared to deride the maker of so preposterous a claim as soon as his claim should be proved baseless. Not even the fame of Pasteur could make the public at large, lay or scientific, believe in the possibility of what he proposed to accomplish. There was time for all the world to be informed of the procedure, for the first "preventive" inoculation—or vaccination, as Pasteur termed it—was made on May 5th, the second on May 17th, and another interval of two weeks must elapse before the final inoculations with the unattenuated virus. Twenty-four sheep, one goat, and five cattle were submitted to the preliminary vaccinations. Then, on May 31 st, all sixty of the animals were inoculated, a protected and unprotected one alternately, with an extremely virulent culture of anthrax microbes that had been in Pasteur's laboratory since 1877. This accomplished, the animals were left together in one enclosure to await the issue.

Two days later, June 2d, at the appointed hour of rendezvous, a vast crowd, composed of veterinary surgeons, newspaper correspondents, and farmers from far and near, gathered to witness the closing scenes of this scientific tourney. What they saw was one of the most dramatic scenes in the history of peaceful science—a scene which, as Pasteur declared afterwards, "amazed the assembly." Scattered about the enclosure, dead, dying, or manifestly sick unto death, lay the unprotected animals, one and all, while each and every "protected" animal stalked unconcernedly about with every appearance of perfect health. Twenty of the sheep and the one goat were already dead; two other sheep expired under the eyes of the spectators; the remaining victims lingered but a few hours longer. Thus in a manner theatrical enough, not to say tragic, was proclaimed the unequivocal victory of science. Naturally enough, the unbelievers struck their colors and surrendered without terms; the principle of protective vaccination, with a virus experimentally prepared in the laboratory, was established beyond the reach of controversy.

That memorable scientific battle marked the beginning of a new era in medicine. It was a foregone conclusion that the principle thus established would be still further generalized; that it would be applied to human maladies; that in all probability it would grapple successfully, sooner or later, with many infectious diseases. That expectation has advanced rapidly towards realization. Pasteur himself made the application to the human subject in the disease hydrophobia in 1885, since which time that hitherto most fatal of maladies has largely lost its terrors. Thousands of persons bitten by mad dogs have been snatched from the fatal consequences of that mishap by this method at the Pasteur Institute in Paris, and at the similar institutes, built on the model of this parent one, that have been established all over the world in regions as widely separated as New York and Nha-Trang.


In the production of the rabies vaccine Pasteur and his associates developed a method of attenuation of a virus quite different from that which had been employed in the case of the vaccines of chicken cholera and of anthrax. The rabies virus was inoculated into the system of guinea-pigs or rabbits and, in effect, cultivated in the systems of these animals. The spinal cord of these infected animals was found to be rich in the virus, which rapidly became attenuated when the cord was dried in the air. The preventive virus, of varying strengths, was made by maceration of these cords at varying stages of desiccation. This cultivation of a virus within the animal organism suggested, no doubt, by the familiar Jennerian method of securing small-pox vaccine, was at the same time a step in the direction of a new therapeutic procedure which was destined presently to become of all-absorbing importance—the method, namely, of so-called serum-therapy, or the treatment of a disease with the blood serum of an animal that has been subjected to protective inoculation against that disease.

The possibility of such a method was suggested by the familiar observation, made by Pasteur and numerous other workers, that animals of different species differ widely in their susceptibility to various maladies, and that the virus of a given disease may become more and more virulent when passed through the systems of successive individuals of one species, and, contrariwise, less and less virulent when passed through the systems of successive individuals of another species. These facts suggested the theory that the blood of resistant animals might contain something directly antagonistic to the virus, and the hope that this something might be transferred with curative effect to the blood of an infected susceptible animal. Numerous experimenters all over the world made investigations along the line of this alluring possibility, the leaders perhaps being Drs. Behring and Kitasato, closely followed by Dr. Roux and his associates of the Pasteur Institute of Paris. Definite results were announced by Behring in 1892 regarding two important diseases—tetanus and diphtheria—but the method did not come into general notice until 1894, when Dr. Roux read an epoch-making paper on the subject at the Congress of Hygiene at Buda-Pesth.

In this paper Dr. Roux, after adverting to the labors of Behring, Ehrlich, Boer, Kossel, and Wasserman, described in detail the methods that had been developed at the Pasteur Institute for the development of the curative serum, to which Behring had given the since-familiar name antitoxine. The method consists, first, of the cultivation, for some months, of the diphtheria bacillus (called the Klebs-Loeffler bacillus, in honor of its discoverers) in an artificial bouillon, for the development of a powerful toxine capable of giving the disease in a virulent form.

This toxine, after certain details of mechanical treatment, is injected in small but increasing doses into the system of an animal, care being taken to graduate the amount so that the animal does not succumb to the disease. After a certain course of this treatment it is found that a portion of blood serum of the animal so treated will act in a curative way if injected into the blood of another animal, or a human patient, suffering with diphtheria. In other words, according to theory, an antitoxine has been developed in the system of the animal subjected to the progressive inoculations of the diphtheria toxine. In Dr. Roux's experience the animal best suited for the purpose is the horse, though almost any of the domesticated animals will serve the purpose.

But Dr. Roux's paper did not stop with the description of laboratory methods. It told also of the practical application of the serum to the treatment of numerous cases of diphtheria in the hospitals of Paris—applications that had met with a gratifying measure of success. He made it clear that a means had been found of coping successfully with what had been one of the most virulent and intractable of the diseases of childhood. Hence it was not strange that his paper made a sensation in all circles, medical and lay alike.

Physicians from all over the world flocked to Paris to learn the details of the open secret, and within a few months the new serum-therapy had an acknowledged standing with the medical profession everywhere. What it had accomplished was regarded as but an earnest of what the new method might accomplish presently when applied to the other infectious diseases.

Efforts at such applications were immediately begun in numberless directions—had, indeed, been under way in many a laboratory for some years before. It is too early yet to speak of the results in detail. But enough has been done to show that this method also is susceptible of the widest generalization. It is not easy at the present stage to sift that which is tentative from that which will be permanent; but so great an authority as Behring does not hesitate to affirm that today we possess, in addition to the diphtheria antitoxine, equally specific antitoxines of tetanus, cholera, typhus fever, pneumonia, and tuberculosis—a set of diseases which in the aggregate account for a startling proportion of the general death-rate. Then it is known that Dr. Yersin, with the collaboration of his former colleagues of the Pasteur Institute, has developed, and has used with success, an antitoxine from the microbe of the plague which recently ravaged China.

Dr. Calmette, another graduate of the Pasteur Institute, has extended the range of the serum-therapy to include the prevention and treatment of poisoning by venoms, and has developed an antitoxine that has already given immunity from the lethal effects of snake bites to thousands of persons in India and Australia.

Just how much of present promise is tentative, just what are the limits of the methods—these are questions for the future to decide. But, in any event, there seems little question that the serum treatment will stand as the culminating achievement in therapeutics of our century. It is the logical outgrowth of those experimental studies with the microscope begun by our predecessors of the thirties, and it represents the present culmination of the rigidly experimental method which has brought medicine from a level of fanciful empiricism to the plane of a rational experimental science.