THE CENTURY'S PROGRESS IN SCIENTIFIC
MEDICINE.

BY HENRY SMITH WILLIAMS, M.D.

I.

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 Rozière 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. 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, René Théophile Hyacinthe Laënnec, 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, Laënnec 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.

WILLIAM J. MORTON.

The possibility of associating the vary-
ing chest sounds with diseased conditions
of the organs within appealed to the fer-
tile mind of Laënnec as opening new
vistas in therapeutics, which he deter-
mined to enter to the fullest extent prac-
ticable. His connection with the hos-
pitals of Paris gave him full opportunity
in this direction, and his labors of the
next few years served not merely to es-
tablish the value of the new method as
an aid to diagnosis, but laid the founda-
tion also for the science of morbid anat-
omy. In 1819 Laënnec published the
results of his labors in a work called
*Traité d'Auscultation Médiate*, a work
which forms one of the landmarks of
scientific medicine. By mediate auscul-
tation is meant of course the interroga-
tion of the chest with the aid of the little
instrument already referred to, an instru-

ment which its originator thought hardly
worth naming until various barbarous
appellations were applied to it by others,
after which Laënnec 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 essen-
tials of auscultation with the stethoscope
were established in much detail by Laën-
nec, 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 con-
sidered a rational science. Laënnec's ef-
forts cost him his life, for he died in 1826

41

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, Pi-
orry, perfected the method of percus-
sion by introducing the custom of tap-
ping, not the chest directly, but the fin-
ger 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 auscul-
tation have held an unquestioned place
in the regular armamentarium of the
physician.

Coupled with the new method of phys-
ical diagnosis in the effort to substitute
knowledge for guess-work came the
studies of the experimental physiologists
—in particular, Marshall Hall in England.
and François Magendie in France; and
the joint efforts of these
various workers led
presently to the aban-
donment of those se-
vere and often irra-
tional depletive meth-
ods—blood-letting and
the like—that had pre-
viously dominated med-
ical practice. To this
end also the "statis-
tical method," intro-
duced by Louis and his
followers, largely con-
tributed; 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 better ac-
complished by simple
means than by the he-
roic measures hitherto
thought necessary. In
a word, scientific em-
piricism was begin-
ning to gain a hear-
ing in medicine, as
against the metaphys-
ical preconceptions of
the earlier genera-
tions.

II.

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 distin-
guished patient's malady as " gale réper-
cutée "—that is to say, in idiomatic Eng-
lish, the itch "struck in." It is hardly
necessary to say that no physician of to-
day would make so inconsiderate a diag-
nosis 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 oth-
erwise is evidence that at the beginning
of the century the disease in question en-
joyed a very different status. At that

RUDOLF VIRCHOW.

42

HARPER'S NEW MONTHLY MAGAZINE.

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 répercutée."

All of which goes to show how easy it may be for a masked pretender to impose

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

LOUIS PASTEUR.

on credulous humanity; for nothing is more clearly established in modern knowledge than the fact that "gale répercutée" 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

44

phoid 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 Kölliker 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.

### III.

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 toward it even vaguely. Davy, in England, had indeed originated the method

of medication by inhalation, and carried 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. Moreover, there had been nothing in Davy's experiments to lead any one to suspect the possibility that a surgical operation might be rendered painless in this way; and, indeed, the surgeons of Europe had acknowledged with one accord that all hope of finding a means to secure this most desirable end 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. Charles W. Wells, of Hartford, Connecticut. The drug with which he experimented was nitrous oxide: the operation which 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 mat-

47

painless operations were said to be per-
formed through practice of hypnotism,
and Dr. Long feared that his own suc-
cess might be due to an incidental hyp-
notic influence rather than to the drug.
Hence he delayed announcing his appar-
ent discovery until he should have op-
portunity for further tests—and oppor-
tunities did not come every day to the
country practitioner. And while he wait-
ed, Morton anticipated him, and the dis-
covery 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 that science has ever conferred
upon humanity.

A few months after the use of ether
became general, the Scotch surgeon Sir
J. Y. Simpson 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 ban-
ished 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 Jen-
nings Morton.

IV.

This discovery of the anaesthetic power
of drugs was destined presently, in addi-
tion to its direct beneficences, to aid great-
ly 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 scien-
tific medicine during the first fifteen years
after Morton's discovery were mainly in-
dependent of such aid. These steps were
taken, indeed, in a field that at first glance

might seem to have a very slight connec-
tion 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
toward 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 super-
fluous to add that the name of this mar-
vellous 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 oth-
er 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 par-
ticular by the Frenchman Cagniard La-
tour and the German, of cell-theory fame,
Theodor Schwann. These men, working
independently, had reached the conclu-
sion, about 1837, that the micro-organ-
isms play a vastly more important rôle
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 pro-
cess 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 inno-
vation should be antagonized. In this
case it chanced that one of the most
dominating scientific minds of the time,

VOL. XCIX.—No. 589.—7

48

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 overestimated the importance of microorganisms.

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.

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 rôle 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 at once succumbed to the disease.

49

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 microscopic 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 toward the heights of exact science.

V.

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 alco-

holic 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 toward success in his great project; yet so credulous were surgeons in general that even some years later the leading surgeons across the Channel 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 Guérin, 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 toward complete success. Lister's priority, however, and the superiority of his method, were freely admitted by the French Academy of Science, 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

50

share in establishing the general belief
in the causal relation that micro-organ-
isms 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 be-
ing known, it may be possible as never
before to grapple with and eradicate that
condition.

The controversy over spontaneous gen-
eration, which, thanks to Pasteur and
Tyndall, had just been brought to a termi-
nation, made it clear that no bacterium
need be feared where an antecedent bac-
terium had not found lodgement; Lister-
ism in surgery had now shown how much
might be accomplished toward prevent-
ing the access of germs to abraded sur-
faces of the body, and destroying those
that already had found lodgement 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 im-
aginative physician, of every working
micro-biologist.

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 empir-
ical success of Jenner, he, like many oth-
ers, had long practised inoculation exper-
iments, and on the 9th of February, 1880,
he announced to the French Academy of
Science that he had found a method of
so reducing the virulence of a disease
germ that, when introduced into the sys-
tem 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 particu-
lar disease experimented with was that
infectious malady of poultry known fa-
miliarly as "chicken cholera." In Octo-
ber 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 dis-
ease 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 mi-
crobe, by the use of which he could pro-
tect sheep, and presumably cattle, against
that fatal malady.

This announcement was immediately
challenged in a way that brought it to
the attention of the entire world. The
president of an agricultural society, real-
izing the enormous importance of the sub-
ject, proposed to Pasteur that his alleged
discovery should be submitted to a deci-
sive public test. He proposed to furnish
a drove of fifty sheep, half of which were
to be inoculated with the attenuated vi-
rus by Pasteur. Subsequently all the
sheep were to be inoculated with viru-
lent 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 propo-
sition. Pasteur accepted the challenge;
he even permitted a change in the pro-
gramme by which two goats were substi-
tuted for two of the sheep, and ten cattle
added; stipulating, however, that since
his experiments had not yet been extend-
ed 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, pre-
pared to deride the maker of so preposter-
ous 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 "prevent-
ive" inoculation, or vaccination, as Pas-
teur termed it, was made on the 5th of
May, the second on the 17th; and another
interval of two weeks must elapse before
the final inoculations with the unattenu-
ated virus. Twenty-four sheep, one goat,
and five cattle were submitted to the pre-
liminary vaccinations. Then, on the 31st
of May, all sixty of the animals were in-

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oculated, a protected and an 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, the 2d of June, 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 afterward, "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 toward 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 dangers. 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.

VI.

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-marking paper on the subject at the Congress of Hygiene at Buda-Pesth.

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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 ev-

erywhere. 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 to-day 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.