THE middle of the seventeenth century saw the profession thus far on
its way--certain objective features of disease were known, the art of
careful observation had been cultivated, many empirical remedies had
been discovered, the coarser structure of man's body had been well
worked out, and a good beginning had been made in the knowledge of how
the machinery worked--nothing more. What disease really was, where
it was, how it was caused, had not even begun to be discussed
intelligently.
An empirical discovery of the first importance marks the middle of the
century. The story of cinchona is of special interest, as it was the
first great specific in disease to be discovered. In 1638, the wife
of the Viceroy of Peru, the Countess of Chinchon, lay sick of an
intermittent fever in the Palace of Lima. A friend of her husband's,
who had become acquainted with the virtues, in fever, of the bark of
a certain tree, sent a parcel of it to the Viceroy, and the remedy
administered by her physician, Don Juan del Vego, rapidly effected
a cure. In 1640, the Countess returned to Spain, bringing with her
a supply of quina bark, which thus became known in Europe as "the
Countess's Powder" (pulvis Comitissae). A little later, her doctor
followed, bringing additional quantities. Later in the century,
the Jesuit Fathers sent parcels of the bark to Rome, whence it was
distributed to the priests of the community and used for the cure of
ague; hence the name of "Jesuits' bark." Its value was early recognized
by Sydenham and by Locke. At first there was a great deal of opposition,
and the Protestants did not like it because of its introduction by the
Jesuits. The famous quack, Robert Talbor, sold the secret of preparing
quinquina to Louis XIV in 1679 for two thousand louis d'or, a pension
and a title. That the profession was divided in opinion on the subject
was probably due to sophistication, or to the importation of other and
inert barks. It was well into the eighteenth century before its virtues
were universally acknowledged. The tree itself was not described until
1738, and Linnaeus established the genus "Chinchona" in honor of the
Countess.(1)
(1) Clements R. Markham: Peruvian Bark, John Murray, London,
1880; Memoir of the Lady Anna di Osoria, Countess of Chinchona
and Vice-Queen of Peru, 1874.
A step in advance followed the objective study of the changes wrought in
the body by disease. To a few of these the anatomists had already called
attention. Vesalius, always keen in his description of aberrations from
the normal, was one of the first to describe internal aneurysm. The
truth is, even the best of men had little or no appreciation of the
importance of the study of these changes. Sydenham scoffs at the value
of post-mortems.
Again we have to go back to Italy for the beginning of these studies,
this time to Florence, in the glorious days of Lorenzo the Magnificent.
The pioneer now is not a professor but a general practitioner, Antonio
Benivieni, of whom we know very little save that he was a friend of
Marsilio Ficino and of Angelo Poliziano, and that he practiced in
Florence during the last third of the fifteenth century, dying in 1502.
Through associations with the scholars of the day, he had become a
student of Greek medicine and he was not only a shrewd and accurate
observer of nature but a bold and successful practitioner. He had formed
the good habit of making brief notes of his more important cases, and
after his death these were found by his brother Jerome and published in
1507.(2) This book has a rare value as the record of the experience of
an unusually intelligent practitioner of the period. There are in all
111 observations, most of them commendably brief. The only one of any
length deals with the new "Morbus Gallicus," of which, in the short
period between its appearance and Benivieni's death, he had seen enough
to leave a very accurate description; and it is interesting to note that
even in those early days mercury was employed for its cure. The surgical
cases are of exceptional interest, and No. 38 refers to a case of angina
for which he performed a successful operation. This is supposed to have
been a tracheotomy, and if so, it is the first in the fourteen centuries
that had elapsed since the days of Antyllus.(3) There are other
important cases which show that he was a dexterous and fearless surgeon.
But the special interest of the work for us is that, for the first time
in modern literature, we have reports of post-mortem examinations made
specifically with a view to finding out the exact cause of death. Among
the 111 cases, there are post-mortem records of cases of gallstones,
abscess of the mesentery, thrombosis of the mesenteric veins, several
cases of heart disease, senile gangrene and one of cor villosum. From no
other book do we get so good an idea of a practitioner's experience at
this period; the notes are plain and straightforward, and singularly
free from all theoretical and therapeutic vagaries. He gives several
remarkable instances of faith healing.
(2) De abditis nonnullis ac mirandis morborum et sanationum
causis. 8th, Florence, Gandhi, 1507.
(3) Possibly it was only a case of angina Ludovici, or
retro-pharyngeal abscess.
To know accurately the anatomical changes that take place in disease is
of importance both for diagnosis and for treatment. The man who created
the science, who taught us to think anatomically of disease,
was Morgagni, whose "De sedibus et causis morborum per anatomen
indagatis"(4) is one of the great books in our literature. During the
seventeenth century, the practice of making post-mortem examinations
had extended greatly, and in the "Sepulchretum anatomicum" of Bonetus
(1679), these scattered fragments are collected.(5) But the work
of Morgagni is of a different type, for in it are the clinical and
anatomical observations of an able physician during a long and active
life. The work had an interesting origin. A young friend interested in
science and in medicine was fond of discoursing with Morgagni about his
preceptors, particularly Valsalva and Albertini, and sometimes the young
man inquired about Morgagni's own observations and thoughts. Yielding
to a strong wish, Morgagni consented to write his young friend familiar
letters describing his experiences. I am sorry that Morgagni does not
mention the name of the man to whom we are so much indebted, and who,
he states, was so pleased with the letters that he continually solicited
him to send more and more "till he drew me on so far as the seventieth;
. . . when I begged them of him in order to revise their contents; he
did not return them, till he had made me solemnly promise, that I would
not abridge any part thereof" (Preface).
(4) Venice, 1761.
(5) Boerhaave remarked that if a man wished to deserve or get a
medical degree from ONE medical author let it be this. (James
Atkinson: Medical Bibliography, 1834, 268.)
Born in 1682, Morgagni studied at Bologna under Valsalva and Albertini.
In 1711, he was elected professor of medicine at Padua. He published
numerous anatomical observations and several smaller works of less
importance. The great work which has made his name immortal in
the profession, appeared in his eightieth year, and represents the
accumulated experience of a long life. Though written in the form
of letters, the work is arranged systematically and has an index of
exceptional value. From no section does one get a better idea of the
character and scope of the work than from that relating to the heart
and arteries--affections of the pericardium, diseases of the valves,
ulceration, rupture, dilation and hypertrophy and affections of the
aorta are very fully described. The section on aneurysm of the
aorta remains one of the best ever written. It is not the anatomical
observations alone that make the work of unusual value, but the
combination of clinical with anatomical records. What could be more
correct than this account of angina pectoris--probably the first in the
literature? "A lady forty-two years of age, who for a long time, had
been a valetudinarian, and within the same period, on using pretty quick
exercise of body, she was subject to attacks of violent anguish in the
upper part of the chest on the left side, accompanied with a difficulty
of breathing, and numbness of the left arm; but these paroxysms soon
subsided when she ceased from exertion. In these circumstances, but with
cheerfulness of mind, she undertook a journey from Venice, purposing
to travel along the continent, when she was seized with a paroxysm, and
died on the spot. I examined the body on the following day.... The aorta
was considerably dilated at its curvature; and, in places, through
its whole tract, the inner surface was unequal and ossified. These
appearances were propagated into the arteria innominata. The aortic
valves were indurated...." He remarks, "The delay of blood in the aorta,
in the heart, in the pulmonary vessels, and in the vena cave, would
occasion the symptoms of which the woman complained during life; namely,
the violent uneasiness, the difficulty of breathing, and the numbness of
the arm."(6)
(6) Cooke's Morgagni, Vol. 1, pp. 417-418. I cannot too warmly
commend to young clinicians the reading of Morgagni. English
editions are available--Alexander's three-volume translation of
1769 and Cooke's Abridgement (London, 1822), of which there was
an American edition published in Boston in 1824.
Morgagni's life had as much influence as his work. In close
correspondence with the leading men of the day, with the young and
rising teachers and workers, his methods must have been a great
inspiration; and he came just at the right time. The profession was
literally ravaged by theories, schools and systems--iatromechanics,
iatrochemistry, humoralism, the animism of Stahl, the vitalistic
doctrines of Van Helmont and his followers--and into this metaphysical
confusion Morgagni came like an old Greek with his clear observation,
sensible thinking and ripe scholarship. Sprengel well remarks that "it
is hard to say whether one should admire most his rare dexterity and
quickness in dissection, his unimpeachable love of truth and justice in
his estimation of the work of others, his extensive scholarship and rich
classical style or his downright common sense and manly speech."
Upon this solid foundation the morbid anatomy of modern clinical
medicine was built. Many of Morgagni's contemporaries did not fully
appreciate the change that was in progress, and the value of the new
method of correlating the clinical symptoms and the morbid appearances.
After all, it was only the extension of the Hippocratic method
of careful observation--the study of facts from which reasonable
conclusions could be drawn. In every generation there had been men of
this type--I dare say many more than we realize--men of the Benivieni
character, thoroughly practical, clear-headed physicians. A model of
this sort arose in England in the middle of the seventeenth century,
Thomas Sydenham (1624-1689), who took men back to Hippocrates, just as
Harvey had led them back to Galen. Sydenham broke with authority
and went to nature. It is extraordinary how he could have been so
emancipated from dogmas and theories of all sorts. He laid down the
fundamental proposition, and acted upon it, that "all disease could be
described as natural history." To do him justice we must remember,
as Dr. John Brown says, "in the midst of what a mass of errors and
prejudices, of theories actively mischievous, he was placed, at a time
when the mania of hypothesis was at its height, and when the practical
part of his art was overrun and stultified by vile and silly nostrums"
("Horae Subsecivae," Vol. I, 4th ed., Edinburgh, 1882, p. 40).
Listen to what he says upon the method of the study of medicine: "In
writing therefore, such a natural history of diseases, every merely
philosophical hypothesis should be set aside, and the manifest and
natural phenomena, however minute, should be noted with the utmost
exactness. The usefulness of this procedure cannot be easily overrated,
as compared with the subtle inquiries and trifling notions of modern
writers, for can there be a shorter, or indeed any other way of coming
at the morbific causes, or discovering the curative indications than by
a certain perception of the peculiar symptoms? By these steps and helps
it was that the father of physic, the great Hippocrates, came to excel,
his theory being no more than an exact description or view of nature. He
found that nature alone often terminates diseases, and works a cure with
a few simple medicines, and often enough with no medicines at all."
Towards the end of the century many great clinical teachers arose, of
whom perhaps the most famous was Boerhaave, often spoken of as the Dutch
Hippocrates, who inspired a group of distinguished students. I have
already referred to the fact that Franciscus Sylvius at Leyden was the
first among the moderns to organize systematic clinical teaching. Under
Boerhaave, this was so developed that to this Dutch university students
flocked from all parts of Europe. After teaching botany and chemistry,
Boerhaave succeeded to the chair of physic in 1714. With an unusually
wide general training, a profound knowledge of the chemistry of the
day and an accurate acquaintance with all aspects of the history of
the profession, he had a strongly objective attitude of mind towards
disease, following closely the methods of Hippocrates and Sydenham. He
adopted no special system, but studied disease as one of the phenomena
of nature. His clinical lectures, held bi-weekly, became exceedingly
popular and were made attractive not less by the accuracy and care with
which the cases were studied than by the freedom from fanciful doctrines
and the frank honesty of the man. He was much greater than his published
work would indicate, and, as is the case with many teachers of the first
rank, his greatest contributions were his pupils. No other teacher of
modern times has had such a following. Among his favorite pupils may
be mentioned Haller, the physiologist, and van Swieten and de Haen, the
founders of the Vienna school.
In Italy, too, there were men who caught the new spirit, and appreciated
the value of combining morbid anatomy with clinical medicine. Lancisi,
one of the early students of disease of the heart, left an excellent
monograph on the subject, and was the first to call special attention
to the association of syphilis with cardio-vascular disease. A younger
contemporary of his at Rome, Baglivi, was unceasing in his call to
the profession to return to Hippocratic methods, to stop reading
philosophical theories and to give up what he calls the "fatal itch" to
make systems.
The Leyden methods of instruction were carried far and wide throughout
Europe; into Edinburgh by John Rutherford, who began to teach at the
Royal Infirmary in 1747, and was followed by Whytt and by Cullen; into
England by William Saunders of Guy's Hospital. Unfortunately the
great majority of clinicians could not get away from the theoretical
conceptions of disease, and Cullen's theory of spasm and atony exercised
a profound influence on practice, particularly in this country, where it
had the warm advocacy of Benjamin Rush. Even more widespread became the
theories of a pupil of Cullen's, John Brown, who regarded excitability
as the fundamental property of all living creatures: too much of this
excitability produced what were known as sthenic maladies, too little,
asthenic; on which principles practice was plain enough. Few systems of
medicine have ever stirred such bitter controversy, particularly on the
Continent, and in Charles Creighton's account of Brown(7) we read
that as late as 1802 the University of Gottingen was so convulsed by
controversies as to the merits of the Brunonian system that contending
factions of students in enormous numbers, not unaided by the professors,
met in combat in the streets on two consecutive days and had to be
dispersed by a troop of Hanoverian horse.
(7) Dictionary of National Biography, London, 1886, VII, 14-17.
But the man who combined the qualities of Vesalius, Harvey and Morgagni
in an extraordinary personality was John Hunter. He was, in the first
place, a naturalist to whom pathological processes were only a small
part of a stupendous whole, governed by law, which, however, could
never be understood until the facts had been accumulated, tabulated and
systematized. By his example, by his prodigious industry, and by his
suggestive experiments he led men again into the old paths of Aristotle,
Galen and Harvey. He made all thinking physicians naturalists, and he
lent a dignity to the study of organic life, and re-established a close
union between medicine and the natural sciences. Both in Britain and
Greater Britain, he laid the foundation of the great collections and
museums, particularly those connected with the medical schools. The
Wistar-Horner and the Warren Museums in this country originated with men
greatly influenced by Hunter. He was, moreover, the intellectual father
of that interesting group of men on this side of the Atlantic who, while
practising as physicians, devoted much time and labor to the study of
natural history; such men as Benjamin Smith Barton, David Hossack, Jacob
Bigelow, Richard Harlan, John D. Godman, Samuel George Morton, John
Collins Warren, Samuel L. Mitchill and J. Ailken Meigs. He gave an
immense impetus in Great Britain to the study of morbid anatomy, and
his nephew, Matthew Baillie, published the first important book on the
subject in the English language.
Before the eighteenth century closed practical medicine had made great
advance. Smallpox, though not one of the great scourges like plague
or cholera, was a prevalent and much dreaded disease, and in civilized
countries few reached adult life without an attack. Edward Jenner, a
practitioner in Gloucestershire, and the pupil to whom John Hunter gave
the famous advice: "Don't think, try!" had noticed that milkmaids
who had been infected with cowpox from the udder of the cow were
insusceptible to smallpox. I show you here the hand of Sarah Nelmes with
cowpox, 1796. A vague notion had prevailed among the dairies from time
immemorial that this disease was a preventive of the smallpox. Jenner
put the matter to the test of experiment. Let me quote here his own
words: "The first experiment was made upon a lad of the name of Phipps,
in whose arm a little vaccine virus was inserted, taken from the hand
of a young woman who had been accidentally infected by a cow.
Notwithstanding the resemblance which the pustule, thus excited on
the boy's arm, bore to variolous inoculation, yet as the indisposition
attending it was barely perceptible, I could scarcely persuade myself
the patient was secure from the Small Pox. However, on his being
inoculated some months afterwards, it proved that he was secure."(8)
The results of his experiments were published in a famous small quarto
volume in 1798.(*) From this date, smallpox has been under control.
Thanks to Jenner, not a single person in this audience is pockmarked!
A hundred and twenty-five years ago, the faces of more than half of you
would have been scarred. We now know the principle upon which protection
is secured: an active acquired immunity follows upon an attack of a
disease of a similar nature. Smallpox and cowpox are closely allied and
the substances formed in the blood by the one are resistant to the
virus of the other. I do not see how any reasonable person can oppose
vaccination or decry its benefits. I show you the mortality figures(9)
of the Prussian Army and of the German Empire. A comparison with
the statistics of the armies of other European countries in which
revaccination is not so thoroughly carried out is most convincing of its
efficacy.
(8) Edward Jenner: The Origin of the Vaccine Inoculation,
London, 1801.
(*) Reprinted by Camac: Epoch-making Contributions to Medicine,
etc., 1909.--Ed.
(9) Jockmann: Pocken und Vaccinationlehre, 1913.
The early years of the century saw the rise of modern clinical medicine
in Paris. In the art of observation men had come to a standstill.
I doubt very much whether Corvisart in 1800 was any more skilful in
recognizing a case of pneumonia than was Aretaeus in the second century
A. D. But disease had come to be more systematically studied; special
clinics were organized, and teaching became much more thorough. Anyone
who wishes to have a picture of the medical schools in Europe in the
first few years of the century, should read the account of the travels
of Joseph Frank of Vienna.(10) The description of Corvisart is of a
pioneer in clinical teaching whose method remains in vogue today
in France--the ward visit, followed by a systematic lecture in the
amphitheatre. There were still lectures on Hippocrates three times a
week, and bleeding was the principal plan of treatment: one morning
Frank saw thirty patients, out of one hundred and twelve, bled!
Corvisart was the strong clinician of his generation, and his accurate
studies on the heart were among the first that had concentrated
attention upon a special organ. To him, too, is due the reintroduction
of the art of percussion in internal disease discovered by Auenbrugger
in 1761.
(10) Joseph Frank: Reise nach Paris (etc.), Wien, 1804-05.
The man who gave the greatest impetus to the study of scientific
medicine at this time was Bichat, who pointed out that the pathological
changes in disease were not so much in organs as in tissues. His
studies laid the foundation of modern histology. He separated the
chief constituent elements of the body into various tissues possessing
definite physical and vital qualities. "Sensibility and contractability
are the fundamental qualities of living matter and of the life of our
tissues. Thus Bichat substituted for vital forces 'vital properties,'
that is to say, a series of vital forces inherent in the different
tissues."(11) His "Anatomic Generale," published in 1802, gave an
extraordinary stimulus to the study of the finer processes of disease,
and his famous "Recherches sur la Vie et sur la Mort" (1800) dealt
a death-blow to old iatromechanical and iatrochemical views. His
celebrated definition may be quoted: "La vie est l'ensemble des
proprietes vitales qui resistent aux proprietes physiques, ou bien la
vie est l'ensemble des fonctions qui resistent a la mort." (Life is the
sum of the vital properties that withstand the physical properties,
or, life is the sum of the functions that withstand death.) Bichat is
another pathetic figure in medical history. His meteoric career ended
in his thirty-first year: he died a victim of a post-mortem wound
infection. At his death, Corvisart wrote Napoleon: "Bichat has just died
at the age of thirty. That battlefield on which he fell is one which
demands courage and claims many victims. He has advanced the science of
medicine. No one at his age has done so much so well."
(11) E. Boinet: Les doctrines medicules, leur evolution, Paris,
1907, pp. 85-86.
It was a pupil of Corvisart, Rene Theophile Laennec, who laid the
foundation of modern clinical medicine. The story of his life is well
known. A Breton by birth, he had a hard, up-hill struggle as a young
man--a struggle of which we have only recently been made aware by the
publication of a charming book by Professor Rouxeau of Nantes--"Laennec
avant 1806." Influenced by Corvisart, he began to combine the accurate
study of cases in the wards with anatomical investigations in the
dead-house. Before Laennec, the examination of a patient had been
largely by sense of sight, supplemented by that of touch, as in
estimating the degree of fever, or the character of the pulse.
Auenbrugger's "Inventum novum" of percussion, recognized by Corvisart,
extended the field; but the discovery of auscultation by Laennec, and
the publication of his work--"De l'Auscultation Mediate," 1819,--marked
an era in the study of medicine. The clinical recognition of individual
diseases had made really very little progress; with the stethoscope
begins the day of physical diagnosis. The clinical pathology of the
heart, lungs and abdomen was revolutionized. Laennec's book is in the
category of the eight or ten greatest contributions to the science
of medicine.(*) His description of tuberculosis is perhaps the most
masterly chapter in clinical medicine. This revolution was effected by
a simple extension of the Hippocratic method from the bed to the
dead-house, and by correlating the signs and symptoms of a disease with
its anatomical appearances.
(*) John Forbes's translation of Auenbrugger and part of his
translation of Lacnnec are reprinted in Camac's Epoch-making
Contributions, etc., 1909.--Ed.
The pupils and successors of Corvisart--Bayle, Andral, Bouillaud,
Chomel, Piorry, Bretonneau, Rayer, Cruveilhier and Trousseau--brought a
new spirit into the profession. Everywhere the investigation of disease
by clinical-pathological methods widened enormously the diagnostic
powers of the physician. By this method Richard Bright, in 1836, opened
a new chapter on the relation of disease of the kidney to dropsy, and to
albuminous urine. It had already been shown by Blackwell and by Wells,
the celebrated Charleston (S.C.) physician, in 1811, that the urine
contained albumin in many cases of dropsy, but it was not until
Bright began a careful investigation of the bodies of patients who had
presented these symptoms, that he discovered the association of various
forms of disease of the kidney with anasarca and albuminous urine. In no
direction was the harvest of this combined study more abundant than in
the complicated and confused subject of fever. The work of Louis and of
his pupils, W.W. Gerhard and others, revealed the distinction between
typhus and typhoid fever, and so cleared up one of the most obscure
problems in pathology. By Morgagni's method of "anatomical thinking,"
Skoda in Vienna, Schonlein in Berlin, Graves and Stokes in Dublin,
Marshall Hall, C. J. B. Williams and many others introduced the new and
exact methods of the French and created a new clinical medicine. A
very strong impetus was given by the researches of Virchow on cellular
pathology, which removed the seats of disease from the tissues,
as taught by Bichat, to the individual elements, the cells. The
introduction of the use of the microscope in clinical work widened
greatly our powers of diagnosis, and we obtained thereby a very much
clearer conception of the actual processes of disease. In another way,
too, medicine was greatly helped by the rise of experimental pathology,
which had been introduced by John Hunter, was carried along by Magendie
and others, and reached its culmination in the epoch-making researches
of Claude Bernard. Not only were valuable studies made on the action of
drugs, but also our knowledge of cardiac pathology was revolutionized
by the work of Traube, Cohnheim and others. In no direction did the
experimental method effect such a revolution as in our knowledge of the
functions of the brain. Clinical neurology, which had received a great
impetus by the studies of Todd, Romberg, Lockhart Clarke, Duchenne and
Weir Mitchell, was completely revolutionized by the experimental work
of Hitzig, Fritsch and Ferrier on the localization of functions in
the brain. Under Charcot, the school of French neurologists gave great
accuracy to the diagnosis of obscure affections of the brain and spinal
cord, and the combined results of the new anatomical, physiological and
experimental work have rendered clear and definite what was formerly the
most obscure and complicated section of internal medicine. The end of
the fifth decade of the century is marked by a discovery of supreme
importance. Humphry Davy had noted the effects of nitrous oxide. The
exhilarating influence of sulphuric ether had been casually studied, and
Long of Georgia had made patients inhale the vapor until anaesthetic and
had performed operations upon them when in this state; but it was not
until October 16, 1846, in the Massachusetts General Hospital, that
Morton, in a public operating room, rendered a patient insensible with
ether and demonstrated the utility of surgical anaesthesia. The rival
claims of priority no longer interest us, but the occasion is one of
the most memorable in the history of the race. It is well that our
colleagues celebrate Ether Day in Boston--no more precious boon has ever
been granted to suffering humanity.(*)
(*) Cf. Osler: Proc. Roy. Soc. Med., XI, Sect. Hist. Med., pp.
65-69, 1918, or, Annals Med. Hist., N.Y., I, 329-332. Cf. also
Morton's publications reprinted in Camac's book cited above.--Ed.
In 1857, a young man, Louis Pasteur, sent to the Lille Scientific
Society a paper on "Lactic Acid Fermentation" and in December of the
same year presented to the Academy of Sciences in Paris a paper on
"Alcoholic Fermentation" in which he concluded that "the deduplication
of sugar into alcohol and carbonic acid is correlative to a phenomenon
of life." A new era in medicine dates from those two publications. The
story of Pasteur's life should be read by every student.(*) It is one of
the glories of human literature, and, as a record of achievement and of
nobility of character, is almost without an equal.
(*) Osler wrote a preface for the 1911 English edition of the
Life by Vallery-Radot.--Ed.
At the middle of the last century we did not know much more of the
actual causes of the great scourges of the race, the plagues, the fevers
and the pestilences, than did the Greeks. Here comes Pasteur's great
work. Before him Egyptian darkness; with his advent a light that
brightens more and more as the years give us ever fuller knowledge. The
facts that fevers were catching, that epidemics spread, that infection
could remain attached to articles of clothing, etc., all gave support to
the view that the actual cause was something alive, a contagium vivum.
It was really a very old view, the germs of which may be found in the
Fathers, but which was first clearly expressed--so far as I know--by
Fracastorius, the Veronese physician, in the sixteenth century, who
spoke of the seeds of contagion passing from one person to another;(12)
and he first drew a parallel between the processes of contagion and
the fermentation of wine. This was more than one hundred years before
Kircher, Leeuwenhoek and others began to use the microscope and to see
animalcula, etc., in water, and so give a basis for the "infinitely
little" view of the nature of disease germs. And it was a study of the
processes of fermentation that led Pasteur to the sure ground on which
we now stand.
(12) Varro, in De Re Rustica, Bk. I, 12 (circa 40 B.C.), speaks
of minute organisms which the eye cannot see and which enter the
body and cause disease.
Out of these researches arose a famous battle which kept Pasteur hard at
work for four or five years--the struggle over spontaneous generation.
It was an old warfare, but the microscope had revealed a new world, and
the experiments on fermentation had lent great weight to the omne vivum
ex ovo doctrine. The famous Italians, Redi and Spallanzani, had led the
way in their experiments, and the latter had reached the conclusion
that there is no vegetable and no animal that has not its own germ. But
heterogenesis became the burning question, and Pouchet in France, and
Bastian in England, led the opposition to Pasteur. The many famous
experiments carried conviction to the minds of scientific men, and
destroyed forever the old belief in spontaneous generation. All along,
the analogy between disease and fermentation must have been in Pasteur's
mind; and then came the suggestion, "What would be most desirable is to
push those studies far enough to prepare the road for a serious
research into the origin of various diseases." If the changes in lactic,
alcoholic and butyric fermentations are due to minute living organisms,
why should not the same tiny creatures make the changes which occur
in the body in the putrid and suppurative diseases? With an accurate
training as a chemist, having been diverted in his studies upon
fermentation into the realm of biology, and nourishing a strong
conviction of the identity between putrefactive changes of the body
and fermentation, Pasteur was well prepared to undertake investigations
which had hitherto been confined to physicians alone.
So impressed was he with the analogy between fermentation and the
infectious diseases that, in 1863, he assured the French Emperor of
his ambition "to arrive at the knowledge of the causes of putrid and
contagious diseases." After a study upon the diseases of wines, which
has had most important practical bearings, an opportunity arose which
changed the whole course of his career, and profoundly influenced the
development of medical science. A disease of the silkworm had, for some
years, ruined one of the most important industries in France, and in
1865 the Government asked Pasteur to give up his laboratory work and
teaching, and to devote his whole energies to the task of investigating
it. The story of the brilliant success which followed years of
application to the problem will be read with deep interest by every
student of science. It was the first of his victories in the application
of the experimental methods of a trained chemist to the problems
of biology, and it placed his name high in the group of the most
illustrious benefactors of practical industries.
In a series of studies on the diseases of beer, and on the mode of
production of vinegar, he became more and more convinced that these
studies on fermentation had given him the key to the nature of the
infectious diseases. It is a remarkable fact that the distinguished
English philosopher of the seventeenth century, the man who more
than anyone else of his century appreciated the importance of the
experimental method, Robert Boyle, had said that he who could discover
the nature of ferments and fermentation, would be more capable than
anyone else of explaining the nature of certain diseases.
In 1876 there appeared in Cohn's "Beitrage zur Morphologie der Pflanzen"
(II, 277-310), a paper on the "AEtiology of Anthrax" by a German
district physician in Wollstein, Robert Koch, which is memorable in our
literature as the starting point of a new method of research into
the causation of infectious diseases. Koch demonstrated the constant
presence of germs in the blood of animals dying from the disease. Years
before, those organisms had been seen by Pollender and Davaine, but
the epoch-making advance of Koch was to grow those organisms in a pure
culture outside the body, and to produce the disease artificially
by inoculating animals with the cultures Koch is really our medical
Galileo, who, by means of a new technique,--pure cultures and isolated
staining,--introduced us to a new world. In 1878, followed his study on
the "AEtiology of Wound Infections," in which he was able to demonstrate
conclusively the association of micro-organisms with the disease. Upon
those two memorable researches made by a country doctor rests the modern
science of bacteriology.
The next great advance was the discovery by Pasteur of the possibility
of so attenuating, or weakening, the poison that an animal inoculated
had a slight attack, recovered and was then protected against the
disease. More than eighty years had passed since on May 14, 1796, Jenner
had vaccinated a child with cowpox and proved that a slight attack of
one disease protected the body from a disease of an allied nature. An
occasion equally famous in the history of medicine was a day in 1881,
when Pasteur determined that a flock of sheep vaccinated with the
attenuated virus of anthrax remained well, when every one of the
unvaccinated infected from the same material had died. Meanwhile, from
Pasteur's researches on fermentation and spontaneous generation, a
transformation had been initiated in the practice of surgery, which,
it is not too much to say, has proved one of the greatest boons ever
conferred upon humanity. It had long been recognized that, now and
again, a wound healed without the formation of pus, that is, without
suppuration, but both spontaneous and operative wounds were almost
invariably associated with that process; and, moreover, they frequently
became putrid, as it was then called,--infected, as we should say,--the
general system became involved and the patient died of blood poisoning.
So common was this, particularly in old, ill-equipped hospitals, that
many surgeons feared to operate, and the general mortality in all
surgical cases was very high. Believing that it was from outside that
the germs came which caused the decomposition of wounds, just as
from the atmosphere the sugar solution got the germs which caused the
fermentation, a young surgeon in Glasgow, Joseph Lister, applied the
principles of Pasteur's experiments to their treatment. From Lister's
original paper(*) I quote the following: "Turning now to the question
how the atmosphere produces decomposition of organic substances, we find
that a flood of light has been thrown upon this most important subject
by the philosophic researches of M. Pasteur, who has demonstrated by
thoroughly convincing evidence that it is not to its oxygen or to any of
its gaseous constituents that the air owes this property, but to minute
particles suspended in it, which are the germs of various low forms
of life, long since revealed by the microscope, and regarded as merely
accidental concomitants of putrescence, but now shown by Pasteur to
be its essential cause, resolving the complex organic compounds into
substances of simpler chemical constitution, just as the yeast-plant
converts sugar into alcohol and carbonic acid." From these beginnings
modern surgery took its rise, and the whole subject of wound infection,
not only in relation to surgical diseases, but to child-bed fever, forms
now one of the most brilliant chapters in the history of preventive
medicine.
(*) Lancet, March 16, 1867. (Cf. Camac: Epoch-making
Contributions, etc., 1909, p. 7.--Ed.)
With the new technique and experimental methods, the discovery of the
specific germs of many of the more important acute infections followed
each other with bewildering rapidity: typhoid fever, diphtheria,
cholera, tetanus, plague, pneumonia, gonorrhoea and, most important of
all, tuberculosis. It is not too much to say that the demonstration
by Koch of the "bacillus tuberculosis" (1882) is, in its far-reaching
results, one of the most momentous discoveries ever made.
Of almost equal value have been the researches upon the protozoan forms
of animal life, as causes of disease. As early as 1873, spirilla were
demonstrated in relapsing fever. Laveran proved the association of
haematozoa with malaria in 1880. In the same year, Griffith Evans
discovered trypanosomes in a disease of horses and cattle in India, and
the same type of parasite was found in the sleeping sickness. Amoebae
were demonstrated in one form of dysentery, and in other tropical
diseases protozoa were discovered, so that we were really prepared for
the announcement in 1905, by Schaudinn, of the discovery of a protozoan
parasite in syphilis. Just fifty years had passed since Pasteur had
sent in his paper on "Lactic Acid Fermentation" to the Lille Scientific
Society--half a century in which more had been done to determine the
true nature of disease than in all the time that had passed since
Hippocrates. Celsus makes the oft-quoted remark that to determine
the cause of a disease often leads to the remedy,(*) and it is the
possibility of removing the cause that gives such importance to the new
researches on disease.
(*) "Et causae quoque estimatio saepe morbum solvit," Celsus,
Lib. I, Prefatio.--Ed.
INTERNAL SECRETIONS
ONE of the greatest contributions of the nineteenth century to
scientific medicine was the discovery of the internal secretions of
organs. The basic work on the subject was done by Claude Bernard, a
pupil of the great Magendie, whose saying it is well to remember--"When
entering a laboratory one should leave theories in the cloakroom." More
than any other man of his generation, Claude Bernard appreciated the
importance of experiment in practical medicine. For him the experimental
physician was the physician of the future--a view well borne out by the
influence his epoch-making work has had on the treatment of disease. His
studies on the glycogenic functions of the liver opened the way for the
modern fruitful researches on the internal secretions of the various
glands. About the same time that Bernard was developing the laboratory
side of the problem, Addison, a physician to Guy's Hospital, in 1855,
pointed out the relation of a remarkable group of symptoms to disease
of the suprarenal glands, small bodies situated above the kidneys, the
importance of which had not been previously recognized. With the loss
of the function of these glands by disease, the body was deprived of
something formed by them which was essential to its proper working.
Then, in the last third of the century, came in rapid succession the
demonstration of the relations of the pancreas to diabetes, of the vital
importance of the thyroid gland and of the pituitary body. Perhaps no
more striking illustration of the value of experimental medicine has
ever been given than that afforded by the studies upon those glands.
The thyroid body, situated in the neck and the enlargement of which is
called goitre, secretes substances which pass into the blood, and
which are necessary for the growth of the body in childhood, for the
development of the mind and for the nutrition of the tissues of the
skin. If, following an infectious disease, a child has wasting of this
gland, or if, living in a certain district, it has a large goitre,
normal development does not take place, and the child does not grow in
mind or body and becomes what is called a cretin. More than this--if in
adult life the gland is completely removed, or if it wastes, a somewhat
similar condition is produced, and the patient in time loses his mental
powers and becomes fat and flabby--myxedematous. It has been shown
experimentally in various ways that the necessary elements of the
secretion can be furnished by feeding with the gland or its extracts,
and that the cretinoid or myxedematous conditions could thus be cured or
prevented.
Experimental work has also demonstrated the functions of the suprarenal
glands and explained the symptoms of Addison's disease, and chemists
have even succeeded in making synthetically the active principle
adrenalin.
There is perhaps no more fascinating story in the history of science
than that of the discovery of these so-called ductless glands. Part
of its special interest is due to the fact that clinicians, surgeons,
experimental physiologists, pathologists and chemists have all combined
in splendid teamwork to win the victory. No such miracles have ever
before been wrought by physicians as those which we see in connection
with the internal secretion of the thyroid gland. The myth of bringing
the dead back to life has been associated with the names of many great
healers since the incident of Empedocles and Pantheia, but nowadays the
dead in mind and the deformed in body may be restored by the touch
of the magic wand of science. The study of the interaction of these
internal secretions, their influence upon development, upon mental
process and upon disorders of metabolism is likely to prove in the
future of a benefit scarcely less remarkable than that which we have
traced in the infectious diseases.
CHEMISTRY
IT is not making too strong a statement to say that the chemistry and
chemical physics of the nineteenth century have revolutionized
the world. It is difficult to realize that Liebig's famous Giessen
laboratory, the first to be opened to students for practical study, was
founded in the year 1825. Boyle, Cavendish, Priestley, Lavoisier, Black,
Dalton and others had laid a broad foundation, and Young, Frauenhofer,
Rumford, Davy, Joule, Faraday, Clerk-Maxwell, Helmholtz and others
built upon that and gave us the new physics and made possible our age
of electricity. New technique and new methods have given a powerful
stimulus to the study of the chemical changes that take place in the
body, which, only a few years ago, were matters largely of speculation.
"Now," in the words of Professor Lee, "we recognize that, with its
living and its non-living substances inextricably intermingled, the
body constitutes an intensive chemical laboratory in which there is ever
occurring a vast congeries of chemical reactions; both constructive and
destructive processes go on; new protoplasm takes the place of old. We
can analyze the income of the body and we can analyze its output, and
from these data we can learn much concerning the body's chemistry. A
great improvement in the method of such work has recently been secured
by the device of inclosing the person who is the subject of the
experiment in a respiration calorimeter. This is an air-tight chamber,
artificially supplied with a constant stream of pure air, and from which
the expired air, laden with the products of respiration, is withdrawn
for purposes of analysis. The subject may remain in the chamber for
days, the composition of all food and all excrete being determined, and
all heat that is given off being measured. Favorable conditions are
thus established for an exact study of many problems of nutrition. The
difficulties increase when we attempt to trace the successive steps in
the corporeal pathway of molecule and atom. Yet these secrets of the
vital process are also gradually being revealed. When we remember that
it is in this very field of nutrition that there exist great popular
ignorance and a special proneness to fad and prejudice, we realize how
practically helpful are such exact studies of metabolism."(13)
(13) Frederick S. Lee, Ph.D.: Scientific Features of Modern
Medicine, New York, 1911. I would like to call attention to this
work of Professor Lee's as presenting all the scientific features
of modern medicine in a way admirably adapted for anyone, lay or
medical, who wishes to get a clear sketch of them.