NINETEENTH-CENTURY MEDICINE
PHYSICAL DIAGNOSIS
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.
PARASITIC DISEASES
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.
PAINLESS SURGERY
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.
PASTEUR AND THE GERM THEORY OF DISEASE
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.
EXPERIMENTS WITH GRAPE SUGAR
"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."
FOREIGN ORGANISMS AND THE WORT OF BEER
"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.
LISTER AND ANTISEPTIC SURGERY
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.
PREVENTIVE INOCULATION
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.
SERUM-THERAPY
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.