INFECTIOUS DISEASES.--THE HISTORICAL IMPORTANCE OF EPIDEMICS OF
DISEASE.--THE LOSSES IN BATTLE CONTRASTED WITH THE LOSSES IN ARMIES
PRODUCED BY--INFECTIOUS DISEASES.--THE DEVELOPMENT OF KNOWLEDGE OF
EPIDEMICS.--THE VIEWS OF HIPPOCRATES AND ARISTOTLE.--SPORADIC AND
EPIDEMIC DISEASES.--THE THEORY OF THE EPIDEMIC CONSTITUTION.--THEORY
THAT THE CONTAGIOUS MATERIAL IS LIVING.--THE DISCOVERY OF BACTERIA BY
LOEWENHOECK IN 1675.--THE RELATION OF CONTAGION TO THE THEORY OF
SPONTANEOUS GENERATION.--NEEDHAM AND SPALLANZANI.--THE DISCOVERY OF
THE COMPOUND MICROSCOPE IN 1605.--THE PROOF THAT A LIVING ORGANISM IS
THE CAUSE OF A DISEASE.--ANTHRAX.--THE DISCOVERY OF THE ANTHRAX
BACILLUS IN 1851.--THE CULTIVATION OF THE BACILLUS BY KOCH.--THE MODE
OF INFECTION.--THE WORK OF PASTEUR ON ANTHRAX.--THE IMPORTANCE OF THE
DISEASE.
These are diseases which are caused by living things which enter the
tissues of the body and, living at the expense of the body, produce
injury. Such diseases play an important part in the life of man; the
majority of deaths are caused directly or indirectly by infection. No
other diseases have been so much studied, and in no other department
of science has knowledge been capable of such direct application in
promoting the health, the efficiency and the happiness of man. This
knowledge has added years to the average length of life, it has
rendered possible such great engineering works as the Panama Canal,
and has contributed to the food supply by making habitation possible
over large and productive regions of the earth, formerly uninhabitable
owing to the prevalence of disease. It is not too much to say that our
modern civilization is dependent upon this knowledge. The massing of
the people in large cities, the factory life, the much greater social
life, which are all prominent features of modern civilization, would
be difficult or impossible without control of the infectious diseases.
The rapidity of communication and the increased general movement of
people, which have developed in equal ratio with the massing, would
serve to extend widely every local outbreak of infection. The
principles underlying fermentation and putrefaction which have been
applied with great economic advantage to the preservation of food were
many of them developed in the course of the study of the infectious
diseases. Whether the development of the present civilization is for
the ultimate advantage of man may perhaps be disputed, but medicine
has made it possible.
The infectious diseases appearing in the form of great epidemics have
been important factors in determining historical events, for they have
led to the defeat of armies, the fall of cities and of nations. War is
properly regarded as one of the greatest evils that can afflict a
nation, since it destroys men in the bloom of youth, at the age of
greatest service, and brings sorrow and care and poverty to many. But
the most potent factor in the losses of war is not the deaths in
battle but the deaths from disease. If we designate the lives lost in
battle, the killed and the wounded who die, as 1, the loss of the
German army from disease in 1870-71 was 1.5, that of the Russians in
1877-78 was 2.7, that of the French in Mexico was 2.8, that of the
French in the Crimea 3.7, that of the English in Egypt 4.2. The total
loss of the German army in 1870-71 from wounds and disease was 43,182
officers and men, and this seems a small number compared with the
129,128 deaths from smallpox in the same period in Prussia alone. In
the Spanish American war there were 20,178 cases of typhoid fever with
1,580 deaths. In the South African war there were in the British
troops 31,118 cases of typhoid with 5,877 deaths, and 5,149 deaths
from other diseases while the loss in battle was 7,582. The Athenian
plague which prevailed during the Peloponnesian war, 431-405 B.C., not
only caused the death of Pericles, but according to Thucydides a loss
of 4,800 Athenian soldiers, and brought about the downfall of the
Athenian hegemony in Greece. In the Crimean war between 1853-56,
16,000 English, 80,000 French and 800,000 Russians died of typhus
fever. The plague contributed as much as did the arms of the Turks to
the downfall of Constantinople and the Eastern Empire in 1453. It was
the plague which in 1348 overthrew Siena from her proud position as
one of the first of the Italian cities and the rival of Florence, and
broke the city forever, leaving it as a phantom of its former glory
and prosperity. The work on the great cathedral which had progressed
for ten years was suspended, and when it was resumed it was upon a
scale adjusted to the diminished wealth of the city, and the plan
restricted to the present dimensions. As a little relief to the
darkness the same plague saw the birth of the novel in the tales of
Boccaccio, which were related to a delighted audience of the women who
had fled from the plague in Florence to a rural retreat.
The knowledge which has come from the study of infectious disease has
served also to broaden our conception of disease and has created
preventive medicine; it has linked more closely to medicine such
sciences as zoölogy and botany; it has given birth to the sciences of
bacteriology and protozoölogy and in a way has brought all sciences
more closely together. Above all it has made medicine scientific, and
never has knowledge obtained been more quickening and stimulating to
its pursuit.
Although the dimensions of this book forbid much reference to the
historical development of a subject, some mention must still be made
of the development of knowledge of the infectious diseases. It was
early recognized that there were diseases which differed in character
from those generally prevalent; large numbers of people were affected
in the same way; the disease beginning with a few cases gradually
increased in intensity until an acme was reached which prevailed for a
time and the disease gradually disappeared. Such diseases were
attributed to changes in the air, to the influence of planets or to
the action of offended gods. The priests and charlatans who sought to
excuse their inability to treat epidemics successfully were quick to
affirm supernatural causes. Hippocrates (400 B.C.), with whom medicine
may be said to begin, thought such diseases, even then called
epidemics, were caused by the air; he says, "When many individuals are
attacked by a disease at the same time, the cause must be sought in
some agent which is common to all, something which everyone uses, and
that is the air which must contain at this time something injurious."
Aristotle recognized that disease was often conveyed by contact, and
Varro (116-27 B.C.) advanced the idea that disease might be caused by
minute organisms. He says, "Certain minute organisms develop which the
eye cannot see, and which being disseminated in the air enter into the
body by means of the mouth and nostrils and give rise to serious
ailments." In spite of this hypothesis, which has proved to be
correct, the belief became general that epidemics were due to
putrefaction of the air brought about by decaying animal bodies, (this
explaining the frequent association of epidemics and wars,) by
emanations from swamps, by periods of unusual heat, etc.
With the continued study of epidemics the importance of contagion was
recognized; it was found that epidemics differed in character and in
the modes of extension. Some seemed to extend by contact with the
sick, and in others this seemed to play no part; it was further found
impossible in many cases to show evidence of air contamination, and
contamination of the air by putrefactive material did not always
produce disease. Most important was the recognition that single cases
of diseases which often occurred in epidemic form might be present and
no further extension follow; this led to the assumption in epidemics
of the existence of some condition in addition to the cause, and which
made the cause operative. In this way arose the theory of the epidemic
constitution, a supposed peculiar condition of the body due to changes
in the character of the air, or to the climate, or to changes in the
interior of the earth as shown by earthquakes, or to the movements of
planets; in consequence of this peculiar constitution there was a
greater susceptibility to disease, but the direct cause might arise in
the interior of the body or enter the body from without. The character
of the disease which appeared in epidemic form, the "Genius
epidemicus," was determined not by differences in the intrinsic cause,
but by the type of constitution which prevailed at that time. The
first epidemic of cholera which visited Europe in 1830-37 was for the
most part referred to the existence of a peculiar epidemic
constitution for which various causes were assigned. It was only when
the second epidemic of this disease appeared in 1840 that the
existence of some special virus or poison which entered the body was
assumed.
Meanwhile, by the study of the material of disease knowledge was being
slowly acquired which had much bearing on the causes. The first
observations which tended to show that the causes were living were
made by a learned Jesuit, Athanasius, in 1659. He found in milk,
cheese, vinegar, decayed vegetables, and in the blood and secretions
of cases of plague bodies, which he described as tiny worms and which
he thought were due to putrefaction. He studied these objects with the
simple lenses in use at that time, and there is little doubt that he
did see certain of the larger organisms which are present in vinegar,
cheese and decaying vegetables, and it is not impossible that he may
have seen the animal and vegetable cells.
The first description of bacteria with illustrations showing their
forms was given by Loewenhoeck, a linen dealer in Amsterdam in 1675.
The fineness of the linen being determined by the number of threads in
a given area, it is necessary to examine it with a magnifying lens,
and he succeeded in perfecting a simple lens with which objects
smaller than had been seen up to that time became visible. It must be
added that he was probably endowed with very unusual acuteness of
vision. He found in a drop of water, in the fluid in the intestines of
frogs and birds, and in his evacuations, objects of great minuteness
which differed from each other in form and size and in the peculiar
motion which some of them possessed. In the year 1683 he presented to
the Royal Society of London a paper describing a certain minute
organism which he found in the tartar of his teeth. After these
observations of Loewenhoeck became known to the world they quickly
found application in disease, although the author had expressed
himself very cautiously in this regard. The strongest exponent of the
view of a living contagion was Plenciz, 1762, a physician of Vienna,
basing his belief not only on the demonstration of minute organisms by
Loewenhoeck which he was able to verify, but on certain shrewdly
conceived theoretical considerations. He was the first to recognize
the specificity of the epidemic diseases, and argued from this that
each disease must have a specific cause. "Just as a certain plant
comes from the seed of the same plant and not from any plant at will,
so each contagious disease must be propagated from a similar disease
and cannot be the result of any other disease." Further he says, "It
is necessary to assume that during the prevalence of an epidemic the
contagious material undergoes an enormous increase, and this is
compatible only with the assumption that it is a living substance."
But as is so often the case, speculation ran far ahead of the
observations on which it is based. There was a long gap between the
observations of Loewenhoeck and the theories of Plenciz, justified as
these have been by present knowledge. In the spirit of speculation
which was dominant in Europe and particularly in Germany in the latter
half of the eighteenth and the first half of the nineteenth centuries,
hypotheses did not stimulate research, but led to further
speculations. As late as 1820 Ozanam expressed himself as follows:
"Many authors have written concerning the animal nature of the
contagion of disease; many have assumed it to be developed from animal
substance, and that it is itself animal and possesses the property of
life. I shall not waste time in refuting these absurd hypotheses." The
theory of a living contagion was too simple, and not sufficiently
related to the problems of the universe to serve the medical
philosophers.
Knowledge of the minute organisms was slowly accumulating. The first
questions to be determined were as to their nature and origin. How
were they produced? Did they come from bodies of the same sort
according to the general laws governing the production of living
things, or did they arise spontaneously? a question which could not be
solved by speculation but by experiment. The first experiments, by
Needham, 1745, pointed to the spontaneous origin of the organisms. He
enclosed various substances in carefully sealed watch crystals from
which the air was excluded, and found that animalculi appeared in the
substance, and argued from this that they developed spontaneously. In
1769, Spallanzani, a skilled experimental physiologist, in a brilliant
series of experiments showed the imperfect character of Needham's work
and the fallacy of his conclusions. Spallanzani placed fluids, which
easily became putrid, in glass tubes, which he then hermetically
sealed and boiled. He found that the fluid remained clear and
unchanged; if, however, he broke the sealed point of such a tube and
allowed the air to enter, putrefaction, or in some cases fermentation,
of the contents took place. He concluded that boiling the substances
destroyed the living germs which they contained, the sealed tubes
prevented the air from entering, and when putrefaction or fermentation
of the contents took place the organisms to which this was due, being
contained in the air, entered from without. Objection was made to the
conclusions of Spallanzani that heating the air in the closed tubes so
changed its character as to prevent development of organisms in the
contents. This objection was finally set aside by Pasteur, who showed
that it was not necessary to seal the end of the tube before boiling,
but it could be closed by a plug of cotton wool, which mechanically
removed the organisms from the air which entered the tube, or if the
tube were bent in the shape of a _U_ and the end left open,
organisms from the air could not pass into the tube against gravity
when air movement within the tube was prevented by bending. The
possibility of spontaneous generation cannot be denied, but that it
takes place is against all human experience.
It was not possible to attain any considerable knowledge of the
bacteria discovered by Loewenhoeck until more perfect instruments for
studying them were devised. Lenses for studying objects were used in
remote antiquity, but the compound microscope in which the image made
by the lens is further magnified was not discovered until 1605, and
when first made was so imperfect that the best simple lenses gave
clearer definition. With the betterment of the microscope, increasing
the magnifying power and the sharpness of the image of the object
seen, it became possible to classify the minute organisms according to
size and form and to study the separate species. The microscope has
now reached such a degree of perfection that objects smaller than one
one hundred thousandth of an inch in diameter can be clearly seen and
photographed.
Great impetus was given to the biological investigation of disease by
the discoveries which led to the formulation of the cell theory in
1840 and the brilliant work of Pasteur on fermentation,[1] but it was
not until 1878 that it was definitely proved that a disease of cattle
called anthrax was due to a species of bacteria. What should be
regarded as such proof had been formulated by Henle in 1840. To prove
that a certain sort of organism when found associated with a disease
is the cause of the disease, three things are necessary:
1. The organism must always be found in the diseased animal and
associated with the changes produced by the disease.
2. The organism so found must be grown outside of the body in what is
termed pure cultures, that is, not associated with any other
organisms, and for so long a time with constant transfers or new
seedings that there can be no admixture of other products of the
disease in the material in which it is grown.
3. The disease must be produced by inoculating a susceptible animal
with a small portion of such a culture, and the organism shown in
relation to the lesions so produced.
It is worth while to devote some attention to the disease anthrax.
This occupies a unique position, in that it was the first of the
infectious diseases to be scientifically investigated. In this
investigation one fact after another was discovered and confirmed;
some of these facts seemed to give clearer conceptions of the disease,
others served to make it more obscure; new questions arose with each
extension of knowledge; in the course of the work new methods of
investigation were discovered; the sides of the arch were slowly and
painfully erected by the work of many men, and finally one man placed
the keystone and anthrax was for a long time the best known of
diseases. Men whose reputation is now worldwide first became known by
their work in this disease. It was a favorable disease for
investigation, being a disease primarily of cattle, but occasionally
appearing in man, and the susceptibility of laboratory animals made
possible experimental study.
Anthrax is a disease of domestic cattle affecting particularly bovine
cattle, horses and sheep, swine more rarely. The disease exists in
practically all countries and has caused great economic losses. There
are no characteristic symptoms of the disease; the affected cattle
have high fever, refuse to eat, their pulse and respiration are rapid,
they become progressively weaker, unable to walk and finally fall. The
disease lasts a variable time; in the most acute cases animals may die
in less than twenty-four hours, or the disease may last ten or
fourteen days; recovery from the disease is rare and treatment has no
effect. It does not appear in the form of epidemics, but single cases
appear frequently or rarely, and there is seemingly no extension from
case to case, animals in adjoining stalls to the sick are not more
prone to infection than others of the herd. On examination after death
the blood is dark and fluid, the spleen is greatly enlarged (one of
the names of the disease "splenic fever" indicates the relation to the
spleen) and there is often bloody fluid in the tissues.
Where the disease is prevalent there are numbers of human cases. Only
those become infected who come into close relations with cattle, the
infection most commonly taking place from small wounds or scratches
made in skinning dead cattle or in handling hides. The wool of sheep
who die of the disease finds its way into commerce, and those employed
in handling the wool have a form of anthrax known as wool-sorters'
disease in which lesions are found in the lungs, the organisms being
mingled with the wool dust and inspired. In Boston occasional cases of
anthrax appear in teamsters who are employed in handling and carrying
hides. The disease in man is not so fatal as in cattle, for it remains
local for a time at the site of infection, and this local disease can
be successfully treated.
The beginning of our knowledge of the cause dates from 1851, when
small rod-shaped bodies (Fig. 17) were found in the blood of the
affected cattle, and by the work of a number of observers it was
established that these bodies were constantly present. Nothing was
known of their nature; some held that they were living organisms,
others that they were formed in the body as a result of the disease.
Next the causal relation of these bodies with the disease was shown
and in several ways. The disease could be caused in other cattle by
injecting blood containing the rods beneath the skin, certainly no
proof, for the blood might have contained in addition to the rods
something which was the real cause of the disease. Next it was shown
that the blood of the unborn calf of a cow who died of the disease did
not contain the rods, and the disease could not be produced by
inoculating with the calf's blood although the blood of the mother was
infectious. This was a very strong indication that the rods were the
cause; the maternal and foetal blood are separated by a membrane
through which fluids and substances in solution pass; but insoluble
substances, even when very minutely subdivided, do not pass the
membrane. If the cause were a poison in solution, the foetal blood
would have been as toxic as the maternal. The blood of infected cattle
was filtered through filters made of unbaked porcelain and having very
fine pores which allowed only the blood fluid to pass, holding back
both the blood corpuscles and the rods, and such filtered blood was
found to be innocuous. It was further shown that the rods increased
enormously in number in the infected animal, for the blood contained
them in great numbers when but a fraction of a drop was used for
inoculation. Attempts were also made with a greater or less degree of
success to grow the rod shaped organisms or bacilli in various fluids,
and the characteristic disease was produced by inoculating animals
with these cultures; but it remained for Koch, 1878, who was at that
time an obscure young country physician, to show the life history of
the organism and to clear up the obscurity of the disease. Up to that
time, although it had been shown that the rods or bacilli contained in
the blood were living organisms and the cause of the disease, this did
not explain the mode of infection; how the organisms contained in the
blood passed to another animal, why the disease occurred on certain
farms and the adjoining farms, particularly if they lay higher, were
free. Koch showed that in the cultures the organisms grew out into
long interlacing threads, and that in these threads spores which were
very difficult to destroy developed at intervals; that the organisms
grew easily in bouillon, in milk, in blood, and even in an infusion of
hay made by soaking this in water. This explained, what had been an
enigma before, how the fields became sources of infection. The
infection did not spread from animal to animal by contact, but
infection took place from eating grass or hay which contained either
the bacilli or their spores. When a dead animal was skinned on the
field, the bacilli contained in the blood escaped and became mingled
with the various fluids which flowed from the body and in which they
grew and developed spores. It was shown by Pasteur that even when a
carcass was buried the earthworms brought spores developed in the body
to the surface and deposited them in their casts, and in this way also
the fields became infected. From such a spot of infected earth the
spores could be washed by the rains over greater areas and would find
opportunity to develop further and form new spores in puddles of water
left on the fields, which became a culture medium by the soaking of
the dead grass. The contamination of the fields was also brought about
by spreading over them the accumulations of stable manure which
contained the discharges of the sick cattle. The tendency of the
disease to extend to lower-lying adjacent fields was due to the spores
being washed from the upper fields to the lower by the spring
freshets. Meanwhile Pasteur had discovered that by growing the
organisms at higher temperatures than the animal body, it was possible
to attenuate the virulence of the bacilli so that inoculations with
these produced a mild form of the disease which rendered the
inoculated animals immune to the fatal disease. The description of
Pasteur's work on the disease as given in the account of his life by
his son-in-law is fascinating.
Hides and wool taken from dead animals invariably contained the spores
which could pass unharmed through some of the curing processes, and
were responsible for some of the cases in man. Owing to the
introduction of regulations which were based on the knowledge of the
cause of the disease and the life history of the organism, together
with the prophylactic inoculation devised by Pasteur, the incidence of
the disease has been very greatly lessened. Looking at the matter from
the lowest point of view, the money which has been saved by the
control of the disease, as shown in its decline, has been many times
the cost of all the work of the investigations which made the control
possible. It is a greater satisfaction to know that many human lives
have been saved, and that small farmers and shepherds have been the
chief sharers in the economic benefits. The indirect benefits,
however, which have resulted from the application of the knowledge of
this disease, and the methods of investigation developed here, to the
study of the infections more peculiar to man, are very much greater.
FOOTNOTE:
[1] The interesting analogy between fermentation and infectious
disease did not escape attention. A clear fluid containing in solution
sugar and other constituents necessary for the life of the yeast cells
will remain clear provided all living things within it have been
destroyed and those in the air prevented from entering. If it be
inoculated with a minute fragment of yeast culture containing a few
yeast cells, for a time no change takes place; but gradually the fluid
becomes cloudy, bubbles of gas appear in it and its taste changes.
Finally it again becomes clear, a sediment forms at the bottom, and on
re-inoculating it with yeast culture no fermentation takes place. The
analogy is obvious, the fluid in the first instance corresponds with
an individual susceptible to the disease, the inoculated yeast to the
contagion from a case of transmissible disease, the fermentation to
the illness with fever, etc., which constitutes the disease, the
returning clearness of the fluid to the recovery, and like the
fermenting fluid the individual is not susceptible to a new attack of
the disease. It will be observed that during the process both the
yeast and the material which produced the disease have enormously
increased. Fermentation of immense quantities of fluid could be
produced by the sediment of yeast cells at the bottom of the vessel
and a single case of smallpox would be capable of infecting
multitudes.