BACTERIA 
AND 
The Germ Theory of Disease. 
EIGHT LECTURES DELIVERED AT THE 
CHICAGO MEDICAL COLLEGE, 
BY 
Dr. H. CRADLE, 
.(i ’ 
PROF. OF PHYSIOLOGY, CHICAGO MEDICAL COLLEGE ; OCULIST TO THE 
MICHAEL REESE HOSPITAL. 
CHICAGO: 
W, T. Keener, 96 Washington Street. 
1883. Copyrighted 1883, by W. T. Keener, in. Wi.fi OJJlcc of the Librarian of 
Congress, at Washington, D. C. CONTENTS. 
LECTURE I. 
The Germ Theory considers many Diseases as a Struggle between the 
Animal System and Microscopic Parasites Invading it.—Parasites 
throughout Nature.—Diseases of Plants—The Silk-worm Disease. 
Bacteria—their Occurrence with Putrefaction.—Definition of Putre- 
faction and Fermentation.—These Processes are the Life-work of 
Living Beings.—Bacteria in the Air.—The False Doctrine of Sponta- 
neous Generation.—Germs not Pre-existent in the Bodies of Living 
Plants and Animals.—Classification of Bacteria, 1 
LECTURE 11. 
The Examination of Bacteria.—Staining Methods.—lllumination with 
Abbe’s Condenser.—Structure of Bacteria.—The Flagellum.—Bac- 
terial Movements.—Reproduction.-—Spores and their Vitality and 
Power of Resistance.—Composition of Bacteria.—Bacterial Food. 
Oxygen.—“ Fermentation is Life without Free Oxygen.”—Aerobes 
and Anaerobes.—The Influence of Temperature upon Bacteria and 
their Spores.—Desiccation.—Germs in the Air, 
22 
LECTURE 111. 
Duration of Life of Bacteria.—Their Destruction 
ducts.—Antiseptic Agents.—The Struggle for Supremacy between 
Different Bacteria, and between Bacteria and Animal Tissues.— 
Predisposition to Parasitic Diseases.—-Are there Different Kinds of 
Bacteria?—The Cultivation of Bacteria.—The Variations in the 
Vital Powers of Bacteria.—Mitigated Disease-germs.—Fermenta- 
tions; Putrefaction.—Decomposition of Urea.—Lactic, Butyric, 
Acetic, Viscous and othei1 Fermentations.—Pigment Bacteria.—Blue 
Pus: Blue Milk.—Bacteria in the Soil of the Earth, 
47 LECTURE IV. 
Bacteria on the Surface of the Animal Body and in the Digestive 
Canal.—Their Work in Digestion.—Germs in the Healthy Tissues. 
—The Research for Pathogenic Bacteria.—Microscopic Detection, 
Cultivation and Inoculation of Germs.—Charbon.—lts Parasites 
and their Mode of Producing and Spreading the Disease.—Pro- 
tective Vaccination with Mitigated Germs.—The Germicide Treat- 
ment.—Chicken-cholera, 75 
LECTURE Y. 
Surgical Infections. - Aseptic Wounds. Suppuration. Abscesses.— 
Furuncles. Osteomyelitis. Pyaemia.— Decomposition of Pus.— 
Traumatic Fever.—Putrid Poisoning.—Septicaemia, 106 
LECTURE YI. 
Surgical Infections (continued).—Erysipelas.—Progressive Gangrene.— 
Progressive Phlegmons. Malignant (Edema. Symptomatic 
Charbon (Quarter Evil).—Immunity from Intravenous Injection.— 
Tuberculosis: The Disease is Infectious.—The Bacillus Tuber- 
culosis.—Inoculation with the Isolated Bacilli,—The Mode of 
Spreading of the Disease.—Methods of Staining the Baccilli.—The 
Significance of their Presence in the Sputum, 141 
LECTURE YII. 
Glanders.—Typhoid Fever.—Relapsing Fever.—Small-Pox.—Cow-Pox.— 
Sheep-Pox.—Measles.—Malaria.— Diphtheria.—Leprosy.—Syphilis, 
—The Milk-Fever Epidemic in Aberdeen, 171 
LECTURE YIII. 
Local Diseases.—Inflammations.—Gonorrhoea and Gonorrhoeal Con- 
junctivitis.^—Trachoma.—Croupous Pneumonia. Endocarditis.— 
Inflammations of Diathetic Origin.—Sympathetic Ophthalmia.— 
Whooping-Cough.—Rhinoscleroma.—Pterygium.—Carious Teeth.— 
The Poison of Rhus Toxicodendron.—The Importance and Future 
of the Germ-Theory. Parasitic Mould-Fungi. Actinomycosis, 
197 THE GERM-THEORY OF DISEASE. 
LECTUEE I. 
The Germ Theory considers many Diseases as a Struggle between the- 
Animal System and Microscopic Parasites Invading it. Parasites 
throughout Nature. Diseases of Plants—The Silk-worm Disease- 
Bacteria—their Occurrence with Putrefaction. Definition of Putre- 
faction and Fermentation.—These Processes are the Life-work of 
Living Beings. Bacteria in the Air.—The False Doctrine of Sponta- 
neous Generation.—Germs not Pre-existent in the Bodies of Living 
Plants and Animals. Classification of Bacteria. 
In no department of medicine is there a greater 
separation between onr present knowledge and the 
views of our ancestors, than in iEtiology. In most 
other branches of medical science we stand upon the 
shoulders of those who preceded us. The therapeutic 
practice of to-day, however superior to that of the 
last century, has been evolved so gradually, has 
passed through such a continuous transition, that it 
would be difficult to point out any one period as the 
beginning of a new epoch. But the knowledge of the 
causes of disease is an acquisition of the most recent 
times, is the work only of the present generation. The 
vague references of former physicians to impurities of 
the blood, chemical dyscrasia, a genius epidemicus, and 2 
THE GERM THEORY OF DISEASE. 
the exaggerated belief in that omnipotent bug-bear— 
cold—we can but regard as speculations without basis. 
Without underrating the earnest work done by medical 
men of a former period, it is evident that the causes of 
diseases, with the exception of some of the more patent 
instances, escaped them. It is only within the last twenty 
years, or less, that evidence is accumulating showing that 
many ailments to which flesh is heir, are due to the 
invasion of the organism by microscopic parasites or 
their germs. Daily, almost, new facts are discovered, 
which substantiate more and more this germ theory of 
disease. In the light of the germ theory, diseases are 
to be considered as a struggle between the organism and 
the parasites invading it. As far as the germ theory is 
applicable, it eliminates the factor “accident” from the 
consideration of disease, and assigns disease a place in 
the Darwinian programme of nature. 
In the modern conception disease is a disturbance of 
the normal play of some one, or different parts of the 
organism, the reaction to .an unaccustomed influence. 
According to the germ theory, the foreign influence pro- 
ducing this disturbance, is in very many instances the 
existence of foreign microscopic beings in the interior 
of the animal body, and the number of diseases of which 
the germ theory reveals the origin, is constantly aug- 
menting. 
Yet the germ theory meets still with much opposition 
and, what is worse, indifference, and nowhere more than 
in this country. Much of this opposition is due to— 
ignorance. I would account for this in the following 
way; There is but little original work published on this 
topic in the English language, especially in this country. 
Although foreign discoveries soon find their way into 
our journals, they appear, as a rule, in the form of an MICEOSCOPIC PAEASITES. 
3 
abstract, without much description of the methods 
used in obtaining the results. But the fruits of 
experimental sciences can only be well appreciated by 
him who knows how they were obtained. If we can- 
not critically examine the methods, we are at a loss 
in assigning the proper value to the conclusions, so 
that the most conscientious work may be received 
with distrust, because we are unprepared for its 
results, while the illogical conclusions of another 
author are sometimes implicitly accepted, because 
they agree with prior notions. Certainly no other 
experimental science can offer greater contrasts than 
research on the germ theory between thorough 
investigation on the one hand, and almost valueless 
work on the other. With some familiarity, however, 
with the literature, one learns to distinguish readily 
between some slipshod observations, and hasty conclu- 
sions therefrom, and the more reliable results obtained 
by methods which equal in accuracy those employed 
in physical sciences. 
If we were to drop our acquired medical notions, 
and were to approach the study of disease from the 
standpoint of the modern naturalist, the germ theory 
would present itself in a more attractive light. 
Throughout nature every species of living beings 
struggles for its existence with all other beings with 
which it comes in immediate contact. In numerous 
instances this struggle amounts to the preying of a 
smaller species upon the body of larger creatures, the 
former deriving from the organism of their host their 
means of subsistence. 
Throughout the animal and the vegetable kingdoms, 
parasitism is of common occurrence. Often the host 
carries but a single invader, but as the discrepancy 4 
THE GERM THEORY OF DISEASE. 
between the size of the parasite and the organism 
harboring it, increases, the number of the intruders is. 
also apt to enlarge. The greater the difference in the 
dimensions of the contending beings, and the wider 
they are apart in the botanical or zoological scale, the 
more desperate does the struggle become. If the host 
cannot oppose a resistance to the attack of the 
invaders, cannot dislodge them in time, he is doomed 
to succumb. No botanist would be at a loss to illus- 
trate this occurrence by reference to numerous 
instances in the vegetable kingdom, the most frequent 
examples being a struggle between the higher plants 
and fungi. Indeed it is claimed that all diseases of 
plants are of parasitic origin. The role of the lower 
organism is too plain in such cases to admit of a 
doubt, while its size renders the investigation compar- 
atively simple. 
The parasitic existence of lower animals in the 
bodies of higher beings is also a common observation. 
But unless these parasites are present in large num- 
bers they do not usually compromise the health of 
their host to any great extent, as an instance of which 
I might mention intestinal worms. It is only when 
we observe beings of such microscopic dimensions and 
consequent multitude in numbers as the trichina 
spiralis, or the filaria, found in the blood of chyluria, 
that we see health and life seriously menaced by the 
invasion of animal parasites. Much more numerous, 
however, are diseases traceable to the development of 
lower plants in the interior of animal bodies. In- 
stances of this occurrence can be found in all animals 
down to insects and worms. In proof of this state- 
ment I cannot do better than dwell at some length 
upon one of the best studied examples of a parasitic 5 
SILK-WOEM DISEASE. 
disease in lower animals—viz: the pebrine of the silk- 
worm. 
This disease occurs in epidemics in silk-raising dis- 
tricts, sometimes to such an extent as almost to anni- 
hilate that industry. The caterpillars attacked by it 
show black spots on their skin, lose their appetite and 
die. In the blood and all the tissues of the worm 
small oval granules were observed by various investi- 
gators. Although these granules were recognized as a 
species of the lowest fungi, their relation to the dis- 
ease was not established until Pasteur proved them to 
be the cause. In simple but conclusive experiments 
he showed that the disease could be produced in 
healthy specimens by feeding them on material con- 
taining these granules, or by inoculating them from a 
wound. On the basis of positive observations he 
■explained thus the spreading of the epidemic. He 
further showed that the butterfly transmits the disease 
to its offspring, in case it survives up to the act of 
copulation. For the parasitic growth can be found in 
the e££, if either male or female be tainted with the 
o o' 
disease. Although Pasteur did not succeed in finding 
anv means of arresting the disease in the individual 
animal, he taught the silk raisers how to check the 
■epidemic. The copulating insects which at this stage 
of their existence are doomed to die any way, are 
•examined microscopically, and the eggs of all diseased 
butterflies are destroyed. The healthy eggs raised in 
a disinfected locality reproduce a healthy stock. No 
more eloquent proof can be given of the importance 
■of Pasteur’s work than a statistical report of the silk 
industry of France. While the silk crop of 1853 
amounted to 26,000,000 kilograms, it had fallen grad- 
ually in consequence of the disease to 4,000,000 kilo- 6 
THE GERM THEORY OF DISEASE. 
grams in 1865. Since the application of the scientific 
triumphs achieved by Pasteur, the disease has been 
practically exterminated and the crops have risen 
again to their former standard. So much for the 
practical application of the germ theory to a disease 
of lower animals! Of course it might be said, and it 
has been said, that research on lower animals can 
throw no light on human pathology, but do such 
gratuitous assertions, bred of ignorance and prejudice, 
deserve serious consideration? 
As an instance of vegetable parasites found in dis- 
eases of the higher animals and man, I need but 
refer to certain affections of the skin. It is now 
generally admitted that various skin diseases are due 
to the growth of different fungi on the affected spot. 
But as regards such parasites living only on the sur- 
face of the body, you will find ample information in 
any of the text-books on skin diseases. Hence I can 
pass at once to the description of those parasites 
which enter into the interior of the system, and 
which have of late attracted most attention, as the 
presumptive cause of most general diseases, viz.; 
bacteria. 
This species of microscopic beings consists of uni- 
cellular organisms, the smallest representatives of ani- 
mated nature. Certain peculiarities in the nutrition 
and mode of reproduction, upon which we shall dwell 
later, characterize them as plants. They are commonly 
classed as the lowest forms of fungi. In fact, the 
Germans call them “ Spaltpilze,” dividing fungi (also 
Schizomycetee or Schistomycetse). If we include among 
the fungi all plants which lack chlorophyll, or some 
equivalent pigment, the bacteria belong to this class. 
But morphologically they differ from the true fungi BACTERIA THEIR MODE OF LIFE. 
7 
in consisting of single short cells, not ramifying into 
a mycelium. In their form, on the other hand, they 
resemble the algrn, but differ again from them in not 
containing chlorophyll. However, leaving to botanists 
the mooted question whether the bacteria are to rank 
with one or the other group of plants, or whether 
they constitute a genus by themselves, we will proceed 
to study their mode of life. It will be the better 
plan to describe in the first place the bacteria which 
we encounter outside of the animal body. 
The earliest use of the microscope in the hands 
of Leeuwenhoek showed that these minute organisms 
abound wherever processes of decomposition or putre- 
faction occur. A drop of water from a stagnant pool, 
a fragment of an animal cadaver, or of vegetable 
refuse, all teem with microscopic life. We need not 
concern ourselves at present with the infusorial animals 
or the algae likely to be encountered there as well; 
for while these forms frequently inhabit the same soil 
in common with bacteria, they are irrelevant to our 
topic. Appearing in the form of minute granules and 
variously shaped rods, the bacteria tax the power of 
the microscope for their sharp definition. The larger 
rods, especially when closely grouped, can be seen 
with a power of 100 to 200 diameters, while the finer 
granules require an amplification of 400 times or more 
for- their mere detection. Wherever dead animal or 
vegetable material is left in a moist state, bacteria 
make their appearance. No putrefaction or rotting 
occurs in which their presence cannot be shown. In 
the words of the French dramatist Dumas: “They are 
the agents of corruption in nature.” 
That these apparently structureless rods and gran- 
ules are living beings is proven by their power of 8 
THE GERM THEORY OF DISEASE. 
multiplication. Tlie best, and sometimes the only 
criterion of life in the case of the lowest organisms 
is the of reproducing their kind under 
proper conditions. With sufficient patience we can 
watch a bacterium growing in size and ultimately 
dividing into two or more fragments similar in form, 
but of course smaller, than the parent. We can 
demonstrate their multiplication even in a more simple 
manner, without such painstaking observations; for if 
•a single one of these organisms, or at least the 
smallest practical number, be introduced into a fluid, 
like meat infusion, in which they find nourishment, 
they will speedily multiply. Though this fluid may 
have been clear as crystal originally, it becomes turbid 
from the presence of myriads of bacteria. 
Before inquiring as to the relation of bacteria to 
putrefaction, it will be well to give a precise defini- 
tion of the latter term. Every day experience shows 
us that, while inorganic substances are chemically 
stable, dead organic material left to itself will gradu- 
ally change in appearance,—in other words, it decom- 
poses. As a rule it loses its consistency, becomes 
softer, and ultimately liquefies. The decomposition 
is furthermore indicated by a disagreeable odor. In 
fact, popularly the nose is the judge of decompo- 
sition, and we seldom think of rottenness without 
smell. But the smell varies with the nature •of 
the material. The chemical substances to which it 
is due are ammonia, sulphuretted hydrogen, sometimes 
phosphoretted hydrogen, various volatile fatty acids, 
like butyric, valerianic, caprylic, and other acids, 
besides traces of many other organic compounds. 
Further examination shows that putrefaction consists 
of a very complicated series of chemical changes. 9 
DEFINITION OP FERMENTATION. 
From the fact that fresh animal and vegetable tis- 
sues are mixtures of complex substances to start 
with, it can be inferred that the study of putrefac- 
tive changes is not a simple matter. On the whole, 
putrefaction can be characterized as a splitting up of 
complex organic molecules into more simple combina- 
tions. In some cases this will proceed far enough to 
result at last in the appearance of inorganic com- 
pounds like carbonic acid, sulphuretted hydrogen, am- 
monium salts, and free nitrogen. To get a fuller 
insight, however, into the chemistry of putrefaction, it 
would be necessary to follow the changes of every indi- 
vidual chemical substance of which the complex organic 
matter consists. Such a detailed study is at present 
foreign to our purpose. But to complete the defi- 
nition, it must be added that the putrefactive 
changes are not due to any chemical or physical 
influences, other than the life-work of the micro- 
scopic beings present. 
Confusion is apt to arise in the choice of the words 
putrefaction and fermentation. The latter term is not 
limited to the conversion of sugar into alcohol, though 
employed most commonly in that connection. Origin- 
ally fermentation signifies a change started in a 
medium by the introduction of a minute quantity of 
some other substance, the change being often indi- 
cated by the formation of gas bubbles. The classical 
instance of a fermentation is of course the conversion 
of sugar inby alcohol, and carbonic ' acid, the agent 
starting the process, the so-called ferment, being yeast. 
But we speak also of the acetic acid fermentation of 
alcohol, the lactic acid fermentation of sugars, and 
others. It will be shown later on that these fermen- 
tations are processes comparable to the putrefactive 10 
THE GERM THEORY OF DISEASE. 
changes. Hence no sharp line of distinction can be 
drawn. Common usage perhaps prefers the word 
fermentation when the resulting products are not 
obnoxious to the nose, or are at least useful to man, 
while closely allied changes, accompanied by a disa- 
greeable smell, are termed rotting. 
The invariable presence of bacteria in all putrefying 
material suggests their close relation to that process, 
but whether cause or result—can only be decided by 
experiment, not by observation alone. The experi- 
mental proof, however, is so conclusive that it must be 
accepted as an axiom, that no putrefaction can occur 
without the presence of bacteria, and that bacteria are 
the sole and only cause of such decomposition. 
In order to demonstrate this truth, it has been 
found most convenient to make use of clear solutions 
of organic substances, for instance infusions of animal 
or vegetable tissues. All that has been learned in 
this manner applies equally to the decomposition of 
the original solid substances, but it is not so con- 
venient to demonstrate it. For in transparent solutions 
bacteria can be detected more readily than on the 
surface of solids. Moreover the occurrence, or absence, 
of a turbidity in the previously clear fluid, is so sug- 
gestive of the presence of, or freedom from, bacteria, 
that the microscope need not be appealed to in every 
case. The first and most demonstrative result of such 
observations has been that putrefaction is arrested by 
any and all means, which arrest the development of 
bacteria. For the present let us merely consider the 
employment of heat for that purpose. Like all other 
living beings bacteria are killed by a sufficient heat. 
The boiling point of water is sufficient to kill all 
bacteria (though, as we will learn later, the germs, or HEAT ARRESTS DEVELOPMENT, 
11 
seeds of some species resist even that temperature, 
and can thus cause errors on the part of observers). 
If hence an infusion of meat, or turnip, or cucumber, 
or beet, be boiled thoroughly and the vessel containing 
it be closed, so as to prevent the subsequent entrance 
of bacteria,, the solution will keep fresh indefinitely. 
No matter how long a time we allow to elapse, we 
will find no evidence of putrefaction on opening the 
vessel. Neither odor nor turbidity are observed, the 
microscope detects no bacteria and chemical analysis 
reveals no change. Another portion of the same 
infusion kept without being boiled, speedily decom- 
poses. In some days at the latest, it will be found 
muddy, malodorous and teeming with bacterial life. 
The agent, therefore, which destroys the few bacteria 
pre-existing in the solution, has prevented that solution 
from spoiling. But the infusion thus preserved has- 
not lost its aptitude for putrescence. For no matter 
how long it has been kept sweet, it will begin to 
undergo decomposition at once, as soon as we reintro- 
duce bacteria into it. We can introduce a drop of 
another putrefying solution, or merely dip into it a 
needle previously in contact with rotten material. The 
transfer into it of the smallest practicable quantity of 
bacteria will start putrescence immediately. It is not 
even necessary to bring bacteria intentionally into the 
fluid; they are distributed throughout nature to such 
an extent that it is difficult to avoid introducing them 
unintentionally by contact with fingers, instruments or 
dust. On account of the analogy of this phenomenon 
to the communication of contagious diseases by contact 
with patients affected, we may also call the introduc- 
tion of bacteria into a soil free of them an infection. 
But success in these simple and conclusive experiments. 12 
THE GERM THEORY OF DISEASE. 
has only been attained after patient research on the 
part of many observers. 
The first condition for success in these experiments 
is the thorough purification of the glass vessels: i. e., 
the destruction of all bacteria adherent to the walls. 
If we resort to heat as the readiest agent .of destruc- 
tion, we require an exposure of the whole vessel to a 
temperature of at least 150° C. for over an hour. 
On a small scale we can. succeed by heating a test 
tube momentarily to a higher degree with sufficient 
care in a large flame. The solution having been 
transferred into the prepared vessel, it is then boiled. 
Ordinarily a momentary boiling will suffice. But care 
must be taken that the fluid does not wet the sides of 
the glass and dry there in a thin layer. For any 
bacteria pre-existing in the fluid would now be subjected 
to the boiling heat in the dry state, in which state 
they are not killed with any certainty by that temper- 
ature. With sufficient attention to such details we 
can succeed in destroying all living organisms in the 
interior of the glass. This is technically called steril- 
izing the solution, and is the preparatory step in all 
such research. But such a solution will keep sterilized 
and sweet only under certain precautions; for instance, 
on sealing the flask. For experience has shown that 
all terrestrial objects have dried bacteria, or their 
germs, adhering to them, that bacteria constitute a 
part of all dust. Even avoiding all contact with 
objects impure in the sense of our experiments, we 
will find that no solution, however well sterilized, will 
keep long when exposed to the air. It is not difficult 
to show that the agent starting putrefaction in steril- 
ized solutions is not gaseous, but consists of solid 
particles floating in the air. For as was first shown BACTERIA IN THE AIR. 
13 
by Schroeder and Dusch (1854), air can be deprived 
of its power of starting decomposition by filtration 
through densely packed cotton. A sterilized solution 
can be kept forever unchanged by plugging the mouth 
of the bottle tightly with dry cotton. Pasteur, to 
whom we owe the most demonstrative experiments on 
this topic, has succeeded likewise in keeping solutions, 
fresh by drawing out the neck of the flask into a long, 
thin and tortuous tube. The putrescible substances 
are thus fully exposed to the gases of the atmosphere,, 
but any solid particles suspended in the air are caught 
in the meshes of the cotton, or deposited along the 
sides of Pasteur’s narrow bent tubes. If we have once 
succeeded in destroying all germs in the flask and in 
the solution, neither bacteria nor any other living 
beings will ever be found in material thus preserved. 
Yet the most energetic decomposition, accompanied by 
the corresponding development of bacteria, will soon 
ensue upon removing the protecting plug of cotton, or 
snipping off the drawn-out neck of the flask. To put 
it in common parlance, wherever we sow bacteria in a 
proper soil we will reap a crop of bacteria. Prior to 
the researches just mentioned, it had been shown by 
Schwann * that the air could be rendered incapable of 
starting putrefaction by passing it through a highly 
heated tube. This indeed was the first proof that 
putrefaction can be started by a “something” in the 
air different from the gases. The solid particles which 
we now know to be the agents concerned, were simply 
burned in Schwann’s experiments. Helmholtz, who has 
also worked on this subject, found, on the other hand, 
that pure oxygen obtained by electrolysis, could not' 
provoke decomposition of sterilized fluids. 
*Poggendorf’s Annalen, 1837. 14 
THE GERM THEORY OE DISEASE. 
The floating matter in tire air lias been rendered 
visible by Tyndall* in an ingenious manner. 
Who has not watched the motes dancing in the sun- 
beam, the track of which is revealed by their presence? 
The path of a ray of light is by itself not visible. 
We perceive the light only when it enters the eye. 
We see the bright spot on the wall where the sun- 
beam impinges, because it reflects some of the light 
into our eye. For the same reason a mote in the 
path of the light appears to us an illuminated speck. 
When the atmospheric dust consists of particles too 
fine to be seen separately, it causes the appearance of 
a cloudiness when struck by the beam of light. 
Tyndall made use of this principle and heightened its 
effect by causing a beam of strong light to pass 
through a chamber otherwise completely darkened. 
Under these circumstances the track of the ray ap- 
pears luminous only if the air contains any floating 
particles. In many localities, at least in those where 
Tyndall experimented, the dust consists entirely of 
organic matter, and can be burned completely. A 
spirit lamp held under the luminous track of a light- 
beam produces a gap in its continuity. The draught 
ascending from it contains no more solid particles, can 
reflect no more light and appears therefore intensely 
black, when compared with the light streak. If the 
air remains undisturbed in a case hermetically closed, 
all its dust will be found deposited on the sides of 
box, after the lapse of a few days. By smearing 
the walls with glycerine Tyndall prevented the depos- 
ited particles from rising again. Through suitably 
arranged glass windows he could examine the path 
of a beam of sunlight or electric light traversing the 
Matter of the Air, 1882. SPONTANEOUS GENERATION. 
15 
box. This track became fainter and fainter, nntil at 
last the absolute purity of the enclosed air was indi- 
cated by its perfect transparency. No light was inter- 
cepted and scattered, for no floating particles existed 
there, and the path of the ray could no longer be seen. 
The same result could also be obtained in the course 
of a few minutes by burning the dust of the enclosed 
air by means of a wire heated with an electric current. 
In the most elegant manner did Tyndall show that 
this optically pure air, identical with the surrounding 
air, but deprived of its dust, could not produce 
decomposition. Test tubes had been let into the 
bottom of such cases air-tight. They could be filled 
through a movable pipette perforating a rubber 
diaphragm in the top of the case, the entrance of the 
pipette being protected by a packing of cotton. After 
filling the glasses with various putrescible substances 
and plugging the pipette, they were sterilized by five 
minutes’ boiling. Though exposed to the air in the 
box these organic solutions kept sweet indefinitely, 
while a second set of test tubes similarly filled and 
similarly treated were teeming with life and most 
offensive in smell after a few days’ exposure to the 
impure air of the laboratory. Are not these various 
experiments complete proof of the role of atmospheric 
dust as a cause of putrefaction? Is there a link 
wanting in the chain of evidence that the air cannot 
by itself start decomposition, but that it contains 
floating particles, living dust, which on reaching the 
proper soil develop into the organisms whose life- 
work reveals itself in putrefaction. 
Yet this well-sustained doctrine of the origin of the 
agents of putrefaction from germs suspended in the 
air, has encountered much opposition at different times 16 
THE GERM THEORY OF DISEASE. 
in the past. It would be a waste of time to follow 
in detail all the objections raised against it, to nar- 
rate the numerous experiments apparently opposed to 
it. For in every instance has later research by others 
shown that such contradictory experiments were as 
defective in their execution, as the conclusions drawn 
from them were premature. No one now doubts the 
relation of bacteria to putrefaction; no one claims that 
decomposition ever occurs without lower organisms 
living on dead material. But now and then a voice 
is yet heard, maintaining that these organisms are 
not necessarily introduced from without; that they can 
arise without ancestors, can occur by new formation, 
or spontaneous generation. 
A historical survey shows us that the theory of 
spontaneous generation was formerly applied to most 
all lower animals, until their eggs were discovered by 
advancing research. As the methods of observation 
became more perfect, the field in which spontaneous 
generation was supposed to prevail, was gradually 
narrowed down, and now no one would dare to speak 
of it except in connection with bacteria, the very 
beings which tax the powers of the present micro- 
scopes to the utmost. For a refutation of the older 
champions of spontaneous generation I can refer you 
to Cheyne’s “Antiseptic Surgery,” adding only that 
former arguments have more recently been reproduced 
and multiplied by Bastian.* 
The strong point of these arguments is the appear- 
ance of bacteria in organic material presumably 
sterilized, while apparently none have been introduced 
from without. Hence it is claimed they must have 
arisen from the dead organic substances, organic mole- 
*Beginnings of Life, 1872. SPONTANEOUS GENERATION. 
17 
cules have been revivified and have turned into 
bacteria. Such a bold assertion, so opposed to all our 
knowledge of life, requires unimpeachable proof, 
which its promulgators are far from producing. The 
chances of error in such research are numerous. In 
the first place not one of the adherents of spontaneous 
generation can or does claim to have purified his 
flasks sufficiently in all instances. Usually the only 
attempt at this indispensable precaution was the boil- 
ing of the contents after the glasses were filled. 
This destroyed indeed all developed bacteria pre-exist- 
ing in the fluid. But any dried germs adhering to 
the walls of the flasks were not necessarily killed by 
the heat of dry steam. We can heat desiccated germs 
above 100° C. without depriving them of vitality. 
Furthermore there is no guarantee that a brief boil- 
ing of the fluid will kill the germs suspended in the 
air of the vessel. If a small amount of fluid is put 
into a large flask there remains a large bulk of air 
which it is not easy to purify. This seems to have 
been the cause of the uncertainty of result obtained 
by Wyman,* an impartial observer who did not deduce 
unwarranted conclusions from his failure to maintain 
his solutions free from germs and decomposition. All 
experimenters who have been successful in proving the 
stability of organic material when protected against 
the germs in the air, agree, that their success became 
constant only after learning the methods. Experience 
taught them gradually what errors to avoid. 
Bastian, the latest champion of spontaneous gener- 
ation, or, as he calls it, “ Archebiosis,” claims that 
the introduction of bits of cheese into the solutions 
will invariably lead to the appearance of organisms in 
spite of prolonged boiling. This fact as such has been 
*Silliman’s Journal, 1862 and 1867. 18 
THE GERM THEORY OF DISEASE. 
confirmed by Colin,* who showed, however, that the 
organism appearing under these circumstances is 
invariably one and the same (viz; Bacillus subtilis), 
and that this bacterium will form spores or seeds 
which can withstand boiling for some time. The pre- 
existence of these spores in the cheese, where they 
have been actually demonstrated, is the clue to this 
alleged instance of spontaneous generation. 
Tyndall has encountered similar instances of the 
resistance of spores to the heat of boiling water, 
but he has also shown how to destroy these spores, f 
For, when the fluid after boiling cools down to 
a proper temperature, i. e. about 30° to 40° C., 
these spores will germinate. In the developed state 
the resulting bacteria are easily killed by heat, even 
less than that of boiling water. Hence a brief boil- 
ing repeated at intervals of several hours, never fails 
to sterilize a solution. And thus all arguments to the 
effect that bacteria can appear in the interior of 
closed flasks after boiling can be overthrown by 
Tyndall’s methods of repeated boiling. 
It has been urged that the existence of spontaneous 
generation cannot be disproven by the permanent 
sterility of boiled fluids, for we do not know in what 
way heat may interfere with the new formation of 
living beings, an argument which must be respected 
until disproven by experiment. Observations, however, 
on the part of Yan der Broeck, of Heberts and others 
have shown, that substances as putreseible as grape 
juice, and the tissues of various vegetables, will not 
putrefy at all if received in glass tubes previously 
heated. In these experiments these substances them- 
selves were neither heated nor in any other way acted 
*Beitraege z. Biologie d. Pfianzen, Bd. 1., Heft 3, p. 188. 
"{■Floating Matter, etc., p. 210. CLASSIFICATION OF BACTERIA. 
19 
upon, but simply removed and kept with precautions 
preventing the access of germs. For no bacteria can* 
be found in the interior of living plants and animals. 
It will be shown later on that also the animal fluids, 
blood and urine, so readily alterable when exposed 
to the air, can be preserved fresh indefinitely, if only 
protected against sources of external infection. Hence 
there remains really no proof whatever, that spon- 
taneous generation can ever occur under any circum- 
stances with which we are acquainted. 
It is necessary to have some system under which 
to classify the various forms of bacteria met with. 
Different systems have been proposed, of which the 
best one is that of Cohn.* It is based only on the 
forms of these beings, and according to their shape 
it recognizes them as, 
I. (round grannies). 
11. Microsacteria (short rods). 
111. Desmobacteria (straight filaments). 
IY. Spirobacteria (spiral filaments). 
Each of these groups is then further subdivided 
into separate species. Usage, however, amongst the 
most reliable authors has further simplified this 
classification, so that now the word bacteria is used 
commonly in a generic sense, while three subdivi- 
sions are recognized, termed, according to the form, 
(1) Micrococcus, (2) Bacillus and (8) Spirillum. 
Micrococci, or, simply cocci, identical with Cohn’s 
Sphserobacteria, are granules either round or elliptical, 
of about one half to two micromillimeters in diameter, 
or even smaller. According to a rather cumber- 
some nomenclature introduced by Billroth,-j* we speak 
of diplo-coccus when two granules adhere together in 
fUntersuchungen ueber d. Yegetations-formen von Coccobacteria 
septica, 1874. 
*Beitraege zur Biologie der Pflanzen, Bd. L, Zweites Heft, p. 146. 20 
THE GERM THEORY OF DISEASE. 
dumb-bell form, and of streptococcus when a series' 
of them are joined, forming a chain. Quite com- 
monly micrococci collect in groups, sometimes pretty 
large, held together by a matrix of mucous-like or 
gelatinous consistency. This is called the Zoogloea 
form (Billroth’s Gliacoccus). 
Bacilli are, as the name indicates, rods. The dis- 
tinction between the short rods constituting Cohn’s 
Microbacteria and the longer threads—really chains 
of rods—which he terms I)esrnobacteria, has not 
been maintained by usage, because impracticable. 
Bacilli have a length of from one to six micromil- 
limeters, or even beyond. Their diameter may be- 
as much as one, or even two micromillimeters, but is 
sometimes so small as to be unmeasurable. The 
French use the word vibrio for bacillus, though this 
term is often employed indiscriminately. Bacilli 
may take the zoogloea form but are oftener found 
in dense “ swarms ” without the gelatinous basis. 
Some varieties do not segment or separate, or sepa- 
rate only imperfectly in segments, as they grow,, 
and thus form thread-like chains. When the sea:- 
o 
mentation of the chains is distinct they are some- 
times termed Leptothrix. 
Spirilla is the common term for the Spirobacteria of 
Cohn, though he distinguishes between spirochsete, a 
screw-shaped thread with flexible and narrow coil, 
and the spirillum, a more rigid and wider screw. 
Spirilla represent threads twisted in the form of a 
screw, with from one to four or five turns; their 
length may be four to fifteen micromillimeters, with 
a diameter of the convolutions from two to three 
micromillimeters. Some giant forms, however, are 
met with of nearly three times the largest of these 
dimensions. Spirilla occur only singly, or in densely SPIRILLA. 
21 
matted clusters. It seems very questionable to me 
whether spirilla really belong to the bacteria. For, as 
regards their mode of reproduction nothing certain is 
known, while both in their shape, as well as in their 
behavior to staining agents they differ radically from 
other bacteria. Since we will have but little occa- 
sion to refer again to the order of spirilla, except 
with reference to two kinds found only in the human 
body, it may be well to state here, that different 
representatives of this family are encountered in 
many stagnant waters. It is not known that they 
exert any action upon the soil in which they vege- 
tate comparable to putrefaction or fermentation. THE GERM THEORY OF DISEASE. 
LECTURE 11. 
The Examination of Bacteria.—Staining Methods.—lllumination with 
Abbe’s Condenser.—Structure of Bacteria.—The Flagellum.—Bac- 
terial Movements.—Reproduction.—Spores and their Vitality and 
Power of Resistance.—Composition of Bacteria.-—Bacterial Food. 
Oxygen.—“ Fermentation is Life without Free Oxygen.”—Aerobes 
and Anaerobes.—The Influence of Temperature upon Bacteria and 
their Spores.—Desiccation.—Germs in the Air. 
The examination of living bacteria is often unsatis- 
factory, on account of their minuteness and transparency. 
In many cases also their motion interferes with close 
observation. Save a few striking forms it is scarcely 
possible to identify different bacteria examined fresh. 
It was hence no slight merit on the part of Koch to 
perfect a method facilitating bacteria] examinations.. 
Instead of viewing them suspended in fluids, Koch 
spreads the fluid containing them in the thinnest layer 
possible on an ordinary cover glass, and dries it.* 
The bacteria are not distorted and do not shrink by 
drying, but retain their natural appearance, and indeed 
appear more striking in air than in fluids of about 
the same index of refraction as the bacterial body 
itself. In order to prevent this dried spot from redis- 
solving on the application of staining, agents it must 
*Beitraege zur Biologic der Pflanzen, Bd. 11., Heft 111., p. 399. STAINING METHODS. 
23 
be rendered insoluble by the action of absolute alcohol. 
Still more convenient, as Koch has since shown, is the 
hardening influence of heat by drawing the specimen 
a few times through a gas or spirit flame. The best 
staining of bacteria can be accomplished with aniline 
colors, in moderately concentrated aqueous solution, for 
instance, methyl violet (blue ink), methyl green, 
magenta, and many others. Aniline brown in glycer- 
ine solution (half glycerine, half water) is also useful, 
especially in the case of bacteria in albuminous fluids, 
or for photographic purposes. A drop of the aniline 
solution is placed upon the dried spot on the cover 
glass and left there some minutes. The time of 
exposure varies with the concentration of the dye, and 
the kind of bacteria. The solution is now washed off 
with a jet of water and the glass is dried, if desirable 
with the aid of gentle heat. The specimen can be 
examined in water, or mounted permanently in Canada 
balsam. In successful mountings the bacteria alone 
should be stained. In order to perceive well the color 
of such minute objects, no diaphragm with narrow 
aperture can be used beneath the stage of the micro- 
scope; on the contrary, the more diffuse the illumina- 
tion, the more striking does the color appear. 
In the midst of animal tissues the detection of 
bacteria is a more difficult matter than in fluids. 
Formerly sections of tissues were treated with acetic 
acid, or solution of potassic hydrate, whereby any 
colonies of bacteria were indeed rendered more appar- 
ent, on account of the greater transparency of the 
other tissues. But in the case of single bacteria 
scattered throughout the tissue, this method is of 
little use. The staining of bacteria, especially with 
aniline colors, as introduced by Weigert, was therefore 
quite an improvement. Certain manipulations, however, THE GEEM THEORY OF DISEASE. 
are necessary to produce good staining. Tissues must 
be hardened in alcohol preparatory to cutting into thin 
sections. The sections are then put into strong watery 
solutions of aniline colors, methyl-violet, magenta, 
brown, or others. In his most recent publication* 
Weigert recommends especially gentian-violet in one 
per cent, solution as the most reliable staining agent. 
Methyl-blue has also been lauded highly by Ehrlich. 
Experience must show how long the individual section 
is to remain in the dye—some minutes, or many hours. 
After sufficient staining, the sections are washed in 
water and decolorized in dilute acetic acid, or as 
"Weigert now prefers it in neutral absolute alcohol, 
which extracts the color out of all parts but the 
nuclei and the micro-organisms present. They are then 
mounted in the usual manner in Canada balsam. In 
such specimens only bacteria and cell nuclei are 
stained, and therefore attract the eye. But in the 
case of very small bacteria, when scattered throughout 
the tissue, the amount of color is too slight to be 
recognized, except with a special mode of illumination 
introduced by Koch.j- 
It is only by the aid of this method that the syste- 
matic detection of bacteria in animal tissues is possible. 
The principle of this method is the following: The 
microscopic image of uncolored objects depends for 
its formation upon differences in the refractive indices 
of the component parts of the object. If the differ- 
ent fibres and cells of a colorless section had the same 
common index of refraction—that is, produced the same 
deviation throughout of the rays of light passing 
*Yirchow’s Archiv, Bd. 84, p. 275. 
"(Investigations into the Etiology of Traumatic Infective Diseases. 
Translated by W. Watson Cheyne. Sydenham Society: 1880. p. 24. 
(The German original appeared in 1878.) ILLUMINATION STRUCTURE. 
25 
through them, no structure could be seen. It is only 
because the different rays are refracted differently by 
the different parts of the object, that an image is 
formed of light and shadow. This image is most 
pronounced when the rays of light which illuminate 
the object from below are parallel, while the more 
diffuse the illumination the more effaced is the dis- 
tinction between light and shadow in the image. But 
all this does not apply to the image of colored objects. 
In this case the brighter the light the more striking 
is the color. The image of stained microscopic objects 
is thus made up of the structure-image and the color- 
image. If the former is well developed by illumina- 
tion through only a narrow diaphragm beneath the 
microscopic stage it can hide feebler details in the 
■color-image, for instance, isolated bacteria moderately 
stained. Hence, in order to bring out best the pure 
color-image, the structure-image should be effaced by 
the most diffuse illumination possible. This can be 
best accomplished by means of an Abbe’s condenser, 
a combination of lenses below the stage, having a 
■short focal range and wide aperture. The object is 
thus flooded with light to such an extent that the 
structure and contours almost disappear, while any 
stained particles, no matter how small, stand forth 
prominently. 
It is only since the introduction of Koch’s methods 
of examination, that we can identify individual bacteria 
■with certainty. Prior to this, the most confusing 
errors had been committed in the description of 
bacteria. Since the distinction between different 
species depends often upon minute differences in the 
dimensions, and upon peculiarities in the form, which 
seem so insignificant as to scarcely attract the eye, 
it is evident that the most conscientious drawings 26 
THE GERM THEORY OF DISEASE. 
of such minute objects are unreliable for identifica- 
tion. It is only the photograph which can be 
accepted as unimpeachable evidence in a comparison 
of the forms observed by different authors. Again 
we are under the greatest obligations to Dr. Koch 
for perfections in the photographic reproduction of 
bacteria. 
The examination of bacteria*, either living or 
stained, reveals no further structure. No cell wall can 
be recognized with certainty. No nucleus is ever 
seen. The body appears to be homogenous proto- 
plasm. In some instances, however, a whip-like cord, 
the flagellum, is found as a prolongation of the body 
of certain rod-shaped bacteria at either end. In the 
larger spirilla this structure is distinct enough to be 
recognized tolerably easily, especially when it is not 
in too violent motion. For the flagellum is the organ 
of motion comparable to the cilia of the lower animals. 
The flagella of bacilli, however, are so delicate as to 
be scarcely recognizable, though with good lenses and 
very oblique illumination they have been seen in even 
the smaller forms (Bacterium termo) by Dollinger and 
Drysdale.* Koch has shoAvn that the flagellum 
becomes more distinct in the dried specimen. He 
obtained the best result, however, by staining the 
specimen on the cover glass with concentrated aqueous 
extract of logwood. It is rendered more striking by 
subsequent treatment with chromic acid solution. Ani- 
line colors will not stain the flagellum. No flagella 
have ever been seen in any specimen of micrococcus. 
Many forms of bacteria are in a state of continual 
motion during life which interferes, of course, with 
close observation. It is necessary to distinguish 
between purely passive movements and the locomotion 
-'‘Monthly Microscopical Journal, Sept. 1875 BACTERIAL MOVEMENTS. 
27 
due to the vital contractions of the bacterial body. 
The passive motion is identical in nature with the 
molecular or Brownian movements observable in all 
sufficiently small particles suspended in a limpid fluid.. 
When an alcoholic solution of shellac is precipitated 
by the addition of water, the minutely divided parti- 
cles of shellac are seen under the microscope to be in a 
state of constant trembling and dancing movement, 
being carried - hither and thither by faint currents in 
the fluid in which they are suspended. The molecular 
agitation is intensified by radiant heat. This Brownian 
movement explains why very fine precipitates settle 
with such slowness, especially when not protected 
against light and heat. This passive movement can 
involve dead bacteria as well as living ones. It is 
hence not stopped by the action of poisons. The 
Brownian movement is observed in all micrococci not 
united in chains or groups. Indeed, in most cases 
micrococci possess only this passive movement, though 
in inaccurate descriptions they have often been spoken 
of as actively moving. Yet some varieties, for instance 
the micrococcus found by Ogston in pus, present a 
motion, which must be recognized as of the active 
order. The Brownian movement involves also the 
smaller forms of rod-shaped bacteria. In very viscid 
fluids these movements are checked. 
Quite different from this passive agitation is the 
active locomotion by which bacilli and spirilla and 
some forms of micrococci shoot to and fro in the field. 
With eel-like flexions these organisms propel them- 
selves, now slowly, then rapidly, and suddenly change 
direction, often with a precision comparable to the 
voluntary motion of animals. At the same time rota- 
tion around the axis of the body is often seen, espe- 
cially when this axis forms an acute angle with the THE GEKM THEORY OE DISEASE. 
axis of the microscope. These movements are accom- 
plished mainly by aid of the flagella, though the 
sinuous twisting of the body must also play some 
part. The active movements are of course stopped by 
any poison or agent killing the bacteria. Yet arrest 
of this motion is not necessarily indicative of death, 
for the bacteria may be benumbed and still recover, 
for instance, by extreme cold or heat. Moreover many 
forms of bacilli never show these movements, while 
other species possess motion only during a part of 
their life-time. 
The only absolute criterion of the life of bacteria 
is their power of multiplication. Under proper condi- 
tions of nourishment and temperature each granule 
or rod elongates and then divides into two. When 
the young organisms thus formed remain attached to 
each other partially or wholly, chains and threads are 
produced. If the division occurs in more than 
one direction groups are formed. The substance 
constituting the basis of zoogloea masses is probably 
derived by transformation of the outer part of the 
bacterial body. The multiplication by fission con- 
tinues until the soil is exhausted, or until the waste 
products of the bacterial tissue-change accumulate to 
a poisonous extent. The terrific rate of reproduction 
of these micro-organisms can be better appreciated by 
quoting some figures from Cohn. Observation has 
shown that a bacterial generation can arise in the 
course of about one. hour. At this rate a single 
bacterium would produce two in one hour; these by 
doubling would increase to four in the second hour, 
and so on—until after the lapse of three days the 
scarcely conceivable figure of 4772 billions would be 
attained. A single bacterium termo is a rod about 
■one micromillimeter thick, and twice as long. Assum- REPRODUCTION. 
ing the specific gravity of the bacterial body to be 
equal to that of water it would require 636000 mil- 
lions of bacteria for the weight of one milligram.. 
But a single bacterium could raise a progeny within 
twenty-four hours equalling in weight milligram, 
while the bacterial family with a pedigree reaching 
back three days, would balance the scales at 7-1- 
million kilograms (7500 tons). In reality this scarcely 
credible rate of reproduction is not maintained long 
from want of nourishment. Yet a growth not far 
behind these marvellous figures can be observed when 
bacteria invade a solid soil—for instance, a cooked 
potato. The merest speck with which the soil is 
infected, will grow at the proper temperature at such 
a rate, that within a day the whole potato is trans- 
formed into a bacterial mass. 
Fission is not the only mode of reproduction of 
bacteria. Propagation by spores can be observed in 
all the larger forms of bacilli, but has not yet been 
seen in some of the smaller species of rods, nor in 
micrococci. The formation of spores is a criterion by 
which we can assign bacteria to the vegetable king- 
dom, for in animals we never observe the appearance 
of germs coincident with the death of the parent, 
which mode of reproduction is quite common amongst 
plants. Sporification always alternates with fission. 
As far as observation goes, young bacilli invariably 
grow and multiply by division for some time before 
they produce spores. Continued vegetation without 
change of soil is usually terminated by the formation 
of spores, and these spores will not as a rule germi- 
nate in the unchanged soil where they were produced. 
The conditions, however, governing sporification are 
not fully understood. The process has been best 
studied in the bacillus anthracis (the parasite of THE GERM THEORY OF DISEASE. 
splenic fever), and in a similar organism, encountered 
on the surface of hay, the bacillus subtilis. At a 
certain stage in the life of these bacilli there appear 
faint granules in the interior of the rods which 
change gradually into brilliant oval spots nearly as 
wide as the original rod. Of these there may be 
from one to five in a row in each bacillus. During 
this time the bacterial body becomes fainter and 
disintegrates, until finally the spores separate, each 
being surrounded by a fine halo, probably of proto- 
plasm. In some instances the spores are held 
together by this mass, like a string of beads. In 
other species of bacilli the spores are not always so 
highly refractive and brilliant as in the instances 
described. They may also appear at the ends of the 
rod instead of in its interior, but these forms have 
not been so well studied. Ordinarily spores are 
immovable. But I have seen some spores, probably 
of the bacillus, which causes buytric acid fermenta- 
tion, shoot to and fro in a manner which could only 
have been produced by a powerful flagellum, though 
I could not recognize the latter. On account of the 
similarity in form and size, individual spores cannot 
be distinguished with certainty from single micrococci. 
But unlike micrococci they are not stained, as a rule, 
by aniline colors. 
Spores are characterized by a much greater resistance 
to damaging influences than the adult bacteria. They 
can withstand higher temperatures, and are killed only 
by very few poisons. As long as the spores do not 
germinate they are practically immortal as far as time 
is concerned, which is true also of many other vege- 
table seeds. The transformation of the vulnerable 
bacteria into the almost indestructible permanent form 
-of spores explains the persistence of the species under BACTERIAL FOOD. 
31 
unfavorable circumstances. When placed into the 
proper soil and kept at favorable temperature the 
spores germinate within a few hours. The oval 
granule elongates in one direction, loses its brilliancy, 
and is thus converted into a young bacillus which 
keeps on growing and dividing. As soon as the 
germination is complete, the remarkable resisting power 
of the spore is lost. If thus the spores are difficult 
to kill by continuous boiling, heating at intervals 
according to the method of Tyndall will effectually 
sterilize any soil by giving the spores time to germi- 
nate and attacking the bacteria in their least resisting 
form. 
Like all living beings bacteria can grow only at the 
expense of the food which they consume. In any soil 
in which they do not find sufficient nourishment they 
cease to grow. What substances they require can be 
inferred from the composition of their bodies. The 
only analysis published of bacterial protoplasm is by 
Kencki and Schaffer.* The bacteria (evidently the 
common forms of putrefaction) growing in gelatine 
solution were isolated by boiling with 2 to 3 per cent, 
of hydrochloric acid, after which procedure they could 
be filtered off. The bacterial mass contained 85 per 
cent, of water. Of the solids 85 per cent, were 
albuminoids; the fats amounted to 6 to 7 per cent., 
and the ashes to 3or 4 per cent. About two per cent, 
of the solids was not definitely recognized, probably 
cellulose. The albumen of bacteria, which the authors 
propose to call myko-protin, differs slightly in its 
properties from animal and vegetable albuminoids. As 
a matter of special interest Nencki points out that it 
contains less nitrogen than other albuminoid sub- 
stances, only 13.65 per cent, (instead of 15 to 16 per 
*Jcarnal f. pract. Chemie. Yol. 20, 1879, p. 443. 32 
THE GERM THEORY OF DISEASE. 
cent). In bacterial colonies in the form of zoogloea. 
masses the authors found no chemical differences. 
They hence consider the zoogloea the transformed 
bacterial bodies and not a separate substance. 
A solution intended for the growth of bacteria must 
contain the necessary salts, viz.; phosphates and 
sulphates of potassium and magnesium (perhaps also 
calcium). They can be either chemically free or 
combined • with some of the organic principles. The 
albumen need not pre-exist as such in the solution. 
Like all plants bacteria (at least some species of 
them) can build up their albumen from simpler nitro- 
genous compounds. Indeed, this faculty of forming 
albumen synthetically is one of the criteria by means 
of which bacteria are assigned to the vegetable king- 
dom. The simplest chemical substances from which 
bacteria can elaborate their nitrogenous principles are 
the salts of ammonia with vegetable acids. Although 
fats and hydrocarbons form part of the bacterial 
protoplasm, they need not be furnished as such; they 
can be formed at the expense of the albumen or its 
elements. Hence bacteria can thrive actively in fluids 
of very simple composition, which contain only a 
compound of ammonia with a vegetable acid, besides 
the necessary salts. Such a fluid is usually termed a 
cultivating solution. The first one devised by Pasteur, 
which yet bears his name, consists of 10 parts of 
crystallized sugar, and 1 part of tartrate of ammonium, 
and the ashes of 1 part of yeast (about 0.075 parts 
per weight) in 100 parts of distilled water. The 
sugar was added because the mixture was intended 
originally for the nutrition of yeast, but it is not 
necessary for the growth of bacteria. Cohn’s solution, 
also much used, has the following formula: Distilled 
water, 20.; Tartrate of Ammonium, 0.2; Phosphate of RELATION TO OXYGEN. 
33 
Potassium, 0.1; Sulphate of Magnesium, 0.1; Basic 
Phosphate of Calcium, 0.01. 
While these proportions need not be accurately 
maintained, experience has shown, that they are the 
most favorable on the wdiole. But it must not be 
supposed that such mineral solutions, since they 
permit the growth of bacteria, are necessarily the best 
soil for them. Although bacteria can build up their 
organic principles from simpler molecules, they thrive 
much better, when a more elaborate food is offered 
them. An infusion of almost any vegetable or animal 
tissue is by far a better soil for them than these 
mineral solutions. This is quite apparent from the 
fact that such infusions become turbid speedily when 
exposed to the air, while Pasteur’s or Cohn’s solutions 
are not readily infected by the germs of atmospheric 
dust. It is only when bacteria already developed are 
sown in these solutions, that they will multiply. 
Probably the acid reaction of these mineral solutions 
is by itself unfavorable to bacteria, wdiich thrive best 
in alkaline soil. But even this hindrance removed, 
such mineral solutions cannot nourish those species of 
bacteria accustomed to living in the animal body. 
Adapted as these forms are to a parasitic mode of 
life, they are not able to build their organic principles 
by synthesis. Many of them will not grow in any soil 
wdiich does not closely resemble in composition the 
animal juices. Many authors have committed the 
most confusing errors by attempting to cultivate dis- 
ease germs in mineral solutions, in which they could 
find no nourishment. Under these circumstances the 
occurrence of a turbidity. could have been due only to 
the accidental introduction of other germs. 
The relation of bacteria to oxygen is as yet 
involved in much uncertainty. Some of the forms 34 
THE GEEM THEORY OE DISEASE. 
occurring in the common putrefactive processes con- 
sume oxygen and exhale carbonic acid like other 
living beings. This fact can be demonstrated by 
gasometric analysis in any closed vessel in which they 
vegetate. The influence of oxygen on the life of such 
bacteria, as manifested in their movements, has been 
studied experimentally by Grossmann and Mayerhausen.* 
A cover-glass, on the lower side of which there was a 
drop of fluid containing bacteria, was used as the cover 
of a microscopic gas chamber. Bacteria were thus 
observed while different gases were passed through 
the chamber. The movements were most energetic 
when the bacteria were exposed to pure oxygen, and 
ceased after a while, whenever this agent was replaced 
by any other gas. Lately the influence of oxygen 
upon bacterial movement has even been suggested by 
Engelrnann as the most delicate test for free oxygen. 
On placing on the same slide putrefactive bacteria 
together with vegetable cells containing chlorophyll, 
and varying the intensity of the illumination, the 
bacteria indicated by their active motion, whenever the 
green plant cells liberated oxygen under the influence 
of light. 
While the want of active movement during the 
absence of oxygen does not necessarily signify the 
death of the bacteria, it has been shown that the 
prolonged deprivation of oxygen does kill certain 
bacteria as well as higher species of living beings. 
In the case of the organism concerned in the fermen- 
tation of urine, as well as the bacterial parasite of 
splenic fever, reproduction ceases after deprivation of 
oxygen. 
While thus some bacteria require oxygen like other 
*Pflueger’s Archiv f. d. ges. Physiologic, Yol. 15, p. 245. 35 
AEROBES AND ANAEROBES. 
forms of life, there are other species differing entirely 
in this respect. Pasteur was the first to show that 
under some circumstances life can continue without 
free oxygen. He demonstrated this in the case of the 
yeast plant, which is commonly classed amongst the 
fungi. This being can live with, or without, free 
oxygen. It grows most energetically when exposed to 
oxygen, though its development does not cease com- 
pletely when deprived of it. Its chemical activity, 
however, as manifested by the conversion of the 
sugary soil in which it lives into alcohol, is most 
marked in the absence of oxygen. This statement 
once disputed by Brefeld and by Traube, has subse- 
quently been confirmed by them upon further research. 
Pasteur, indeed, denies even that the yeast cell causes 
fermentation at all, when it can get free oxygen, 
claiming that in a fermenting solution exposed to the 
air, the oxygen is consumed in the lower strata before 
the fermentation begins. He formulates his views in 
the famous statement that “ fermentation is life with- 
out free oxygen.” He explains in fact the fermenta- 
tive action of the yeast cell by its avidity for oxygen. 
For when the latter element is not present in the free 
state, the yeast cell procures the oxygen it needs at 
the expense of the substances which it can split up. 
Although it would seem that no oxygen could be 
seized by the yeast when it splits up sugar into 
alcohol and carbonic acid, still this is not strictly true. 
For Pasteur showed that really a part of the sugar is 
transformed into other products, viz: glycerine, succinic 
acid, etc., and thereby yields oxygen to the yeast. 
Pasteur proved, furthermore, that also some other 
beings, for instance the mould-fungi known as. Mucor, 
can ferment sugar when deprived of oxygen, but have 
not that property when exposed to air. However, it 36 
THE GERM THEORY OF DISEASE. 
would be foreign to our topic to discuss all of 
Pasteur’s ingenious observations on yeast, and tlieir 
conclusiveness. For further details I must refer you 
to his instructive “ Studies on Fermentation.”* 
On extending his observations to bacteria, Pasteur 
found that some of these as well can exist without 
free oxygen. He claimed this originally for the 
bacillus concerned in butyric acid fermentation, but 
subsequently showed it to be true of certain other 
species. Not only are the fermentative changes due 
to these organisms impossible in the presence of oxygen, 
but the very movements of such bacteria are checked 
by that gas, and their development hindered. 
Pasteur hence recognizes amongst bacteria two 
classes, the Aerobes and the Ancerohes. The former 
require free oxygen, the latter cannot live in its pres- 
sure. According to the views of Pasteur only 
aneerobic bacteria, or at least such forms as can 
temporarily exist without free oxygen, produce the 
changes of putrefaction and fermentation. The facts, 
however, which Pasteur adduces are neither numerous 
enough nor sufficiently convincing to prove the theory 
that fermentation is always life without free oxygen,. 
The principal fact, however, upon which Pasteur bases 
his theory, viz; that at least certain bacteria can live,, 
multiply, and produce fermentative changes, without 
the presence of free oxygen, has been fully substan- 
tiated by others, Huefnerf showed that putrefaction 
can occur in a vacuum by inclosing putrescible sub- 
stances in a flask, the narrow neck of which was bent 
horizontally and closed hermetically after all air had 
been expelled by boiling the fluid. A drop of 
bacterial fluid had previously been placed in a hollow 
Translation by Faulkner and Robb, 1879. 
fJournal f. pract. Chemie. Vol. 13, (1876) p. 475. LIFE WITHOUT OXYGEN. 
•depression in the bent neck of the flask, so that the 
organisms could not be killed by the steam. On 
inverting the flask the bacteria were brought into the 
boiled contents. On opening the flask after some 
days, the contents were rotten and teeming with 
bacteria. But no description is given of their form. 
Subsequently Jeanneret and Nencki* repeated similar 
experiments with the same result. The putrefaction 
proceeded about six times as slowly as it did in the 
presence of oxygen, but the chemical products of the 
decomposition of gelatine or albumen were the same, 
whether oxygen was present or not. The validity of 
these observations was contested by Gunningf on the 
.ground that the last traces of oxygen cannot be 
removed from a fluid by either boiling or the action 
of an air pump. For even under these circumstances 
a delicate reaction for oxygen can still be obtained, 
by means of the bluing of a mixture of ferrous 
sulphate with yellow prussiate of potassium in solution, 
with the addition of a drop of a solution of hypo- 
sulphite of sodium. That such a minute trace of 
oxygen must be taken into consideration with refer- 
ence to bacterial tissue change, he tries to render 
evident by the following figures. If we assume the 
weight of a single large bacterium to be o oqoq 
milligram, and if from analogy with higher beings we 
admit that bacteria consume about 1 per cent, of 
their weight of oxygen in 24 hours, one million 
bacteria would require at the most ytto'w milligram, 
i- e., approximately cubic centimeters of 
oxygen. But Gunning overlooks the enormous num- 
bers of bacteria existing in putrid solutions. Any one 
familiar with the microscopic appearance of blood, 
f. pract. Ohemie. Vol. 15, p. 353. 
fJournal f, pract. Chemie. Vol. 16, p. 314, and Vol. 17, p. 266. 38 
THE GERM THEORY OF DISEASE. 
must admit that in any rotting solution bacteria are 
many times more numerous than are the red corpus- 
cles in the blood. Since of the latter there are five 
millions in every cubic millimeter of blood, thirty 
millions bacteria per cubic millimeter of a putrid fluid 
is certainly a low estimate. At this rate, and on the 
basis of Gunning’s figures, the putrid solution would 
consume its equal bulk of oxygen in twenty-four hours. 
The possibility of putrefaction without free oxygen 
has indeed been shown by Nencki* in later and more 
elaborate experiments in which the absence of oxygen 
was guaranteed by the presence of an alkaline solu- 
tion of pyrogallic acid in a separate portion of the set 
of bent tubes employed. This fluid would have 
absorbed any traces of oxygen, and indicated this 
occurrence by turning brown. The putrefaction ivas 
brought to a stand-still after a time if the volatile 
products of decomposition were prevented from 
escaping. But when these substances were allowed to 
escape through a tube dipped into a solution of 
pyrogallic acid in order to prevent the entrance of 
oxygen, the process continued without air. Under 
these circumstances, however, other forms of bacteria 
were found than in a soil exposed to the atmosphere.. 
Nencki saw principally a form of micrococcus, and, to 
less extent, long bacilli. This agrees with the obser- 
vation that in ordinary rotting fluids the shorter rods 
abound on the surface where they can procure' 
oxygen, while in the deeper strata not reached by 
that gas, micrococci vegetate mainly. 
The behavior of bacteria towards oxygen varies also- 
with reference to its allotropic form, viz; ozone.. 
While this gas kills certain bacteria of putrefaction 
at once, as was shown by their disintegration in the- 
f. pract. Chemie. Vol. 19, p. 337. INFLUENCE OF TEMPERATURE. 
39 
experiments of Grossmann and Mayerhausen, it does 
not seem to harm the bacilli of splenic fever blood. 
Of further observations with this gas I can find no 
account. Common oxygen, however, when compressed 
to a tension of five atmospheres is fatal to all living 
beings, as Paul Bert has shown in his fascinating 
experiments on compressed air. Bacteria are not 
exceptions to this universal reaction; they are killed 
at once by this agent in its compressed condition. 
But the spores of bacteria can resist this poisonous 
influence; of all living matter they are the most diffi- 
cult to destroy. Hence, Bert could not realize the 
hope of distinguishing between the processes due to 
bacterial life, and the changes produced by chemical 
ferments, by means of oxygen at a high pressure. For 
although the soluble ferments are not hindered in 
their action by compressed oxygen, the spores will 
likewise resist, and can afterwards germinate under 
proper conditions. 
When bacteria are sown in proper soil, their rate 
of development and their chemical energy depend 
upon the temperature. At low temperatures bacteria 
are benumbed; as soon as warmth is applied they 
re-awake, and their vital energy is then commensurate 
to the temperature up to a certain limit, beyond 
which they are again benumbed and ultimately killed. 
Extreme cold does not seem able to destroy all 
bacteria, for in the experiments of Frisch, exposure 
to 110° C. below zero did not kill the bacillus of 
splenic fever blood. According to Eidam* the bacteria 
of putrefaction (B. termo) begin their movements and 
multiplication at 5-|° C. The vital energy then pro- 
ceeds proportionate to the temperature up to 35° C.; 
beyond this it again flags and at 40° C. the 
*Cohn’s Beitraege z. Biologie d. Pfianzen, Bd. I, Heft 111, p. 208. 40 
THE GERM THEORY OF DISEASE. 
condition of heat torpor ensues. These limits of 
temperature are not the same for all bacteria. The 
bacilli found on the surface of hay can yet grow 
between 47° and 50° C. according to Cohn, but 
their development is arrested above this point. In 
fact the larger spore-producing bacilli seem more 
resistant than the smaller organisms. The formation 
of spores cannot take place below 15° to 18° C. 
(Koch), and is checked again by a temperature 
probably variable with the different species. Pasteur 
claims that 43° C. prevents sporification in the 
case of the bacilli of splenic fever. This limit prob- 
ably varies with the nature of the medium in which 
they grow, since Koch has seen spores form at this 
temperature. The hay-bacillus ceased to produce 
spores only at 50° C. when cultivated in an infu- 
sion of hay by Cohn*. 
No adult bacteria have as yet been found to 
survive after long exposure to 60° C. when in the 
moist state. Even a lower thermal limit than this has 
been found to destroy some bacteria. Eidam killed 
bacterium termo by 14 hours’ exposure to 45° C., 
or by the action of 50° C. during three hours, 
while Chauveau destroyed the life of the more 
resistant splenic fever bacillus by an exposure to 
50° C. for only 20 minutes. Many contradictory 
results, however, have been recorded oh account of 
inaccuracy of the methods. The submersion of a test 
tube filled with the bacterial cultivating fluid in an 
open water bath heated to the desired degree does 
not guarantee that the bacteria are really exposed to 
the temperature of the water bath. Under such 
circumstances the poor conductivity of the glass tube 
and of the water, the evaporation of fluid from the 
*Beitraege z. Biologie d. Pfianzen, Bd. 11., Heft 11, p. 249. DESTRUCTION BY HEAT. 
41 
surface of tlie bacterial liquid, and the cooling influ- 
ence of currents of air above the surface, these all 
prevent the bacterial soil from reaching the tempera- 
ture of the surrounding bath, at least for an uncer- 
tain length of time. The only reliable method is the 
one followed by Chauveau, viz: to inclose a relatively 
small quantity of the bacterial fluid in a thin-walled 
closed pipette, and to suspend this in the interior of 
the water bath. This observer did thus really find a 
low temperature to suffice for the destruction of the 
micro-organisms, because they were actually heated to 
this point (50° C.). 
The spores of bacteria can undoubtedly resist a 
much higher degree of temperature than suffices for 
the destruction of the developed forms. All observers 
agree that the boiling point of water is the lowest 
limit to be relied upon for their annihilation. Thus 
Fitz* found that the spores of a bacillus producing the 
butyric fermentation of glycerine were killed with 
certainty by 3 to 20 minutes’ boiling, while it required 
2 to 6 hours to destroy them at 95° C. and 7 to 
11 hours at 80° C. According to the last researches 
by Kochf the spores of the splenic fever parasite, as 
Well as of the different bacilli found in the surface 
soil of the earth, are infallibly killed by 100° C. But 
while the former yield after two minutes’ boiling, the 
earth spores resist up to 10 to 15 minutes. Convinced 
by the uniformity of his own results Koch ventures to 
state, that probably all spores die at 100° C., provided 
only that they are really exposed to that temperature. 
For in the numerous contradictory observations by 
other authors a guarantee was not always given, that 
*Berichte d. deutschen chemischen Gesellschaft, Yol. 15, p. 867, 
1882. 
tMittheilungen a. d. Kaiserl. Gesundheitsamte. 1881. p. 322. 42 
THE GERM THEORY OF DISEASE. 
the spores were really heated to the point stated. In 
the case of test tubes immersed in a water bath the 
method most commonly used—the reasons above stated 
why the bacteria did not reach the temperature of the 
water bath hold good, as Koch has shown by thermo- 
metric measurement. He demonstrated likewise that 
even inside of closed boilers, filled flasks exposed to the 
contained steam do not reach the temperature of the 
compressed steam, until after the' lapse of a long time 
proportionate to the size of the flask. Moreover, if 
the fluid containing spores spurts, some of the spores 
may dry on the side of the vessel above the level of 
the fluid, and dry spores are not killed by 100° C. 
Hence Koch regards with suspicion all former statements 
that spores can resist prolonged boiling. Yet Tyndall* 
states that he has boiled hay infusions for hours (in 
one case even 8 hours) without being able to sterilize 
them, apparently with the utmost accuracy of method. 
It is also claimed by Pasteur that, in alkaline fluids, 
spores are not killed with certainty by boiling at the 
atmospheric pressure. Milk, however, which in the 
earlier experiments of Schroeder could not be sterilized 
at 100° C., Pasteur succeeded in keeping pure by 
prolonged boiling. At any rate, wet spores can be 
inevitably killed by a few minutes’ exposure to 110° C. 
(under pressure). 
In the dried state bacteria are less readily destroyed 
by heat. The experience of most observers has shown 
this to be a fact, but I can find no definite statements 
as regfirds the least temperature requisite to kill the 
developed forms. In the experiments of Koch all 
adult bacteria were destroyed by an hour’s sojourn in 
a hot-air chamber in which the temperature rose at 
last to about 120° C. Spores, however, were not 
Matter, etc., p. 199. DESICCATION. 
43 
injured under these circumstances. Their resistance 
was only overcome by three hours’ exposure to 140° C. 
Drying by itself does not immediately destroy the 
life of bacteria. Spores in this condition are practi- 
cally imperishable, but in the case of the developed 
forms the possibility of a return to the living condi- 
tion when moistened again, does not seem to persist 
forever. From statements by various authors it is to 
be inferred that the length of time during which this 
dormant vitality of the dried bacteria can last varies 
in different species. According to the precise state- 
ments of Koch the bacillus of splenic fever lost its 
vitality inside of 12 to 30 hours when well dried in 
thin layers, but in thicker masses, not completely 
desiccated, it survived during some weeks. 
Further studies of the influence of desiccation upon 
the life of bacteria are required, in order to explain 
in what form germs exist in the air. 
Bodies of such minute size as bacteria have such an 
immense surface compared with their bulk, that they 
must speedily dry and shrivel, when floating in an 
air not saturated with aqueous vapor. How long the 
developed forms can survive under these circumstances 
we do not know, though the spores are not injured 
whatsoever, judging from all experiments to the point. 
Microscopic examination of the air is rather unsatisfac- 
tory. The atmospheric dust does, of course, settle upon 
a slide and can be collected in a drop of glycerine, or 
other adhesive fluid, and then examined, but numerous 
observations made thus by different authors have taught 
very little. The shrivelled bacteria cannot be easily 
recognized and certainly not identified; moreover, it 
can not be decided by the microscope, whether the 
dried specimen is dead or yet capable of development, 
A better method to get an insight into the nature of 44 
THE GERM THEORY OF DISEASE. 
the atmospheric dust is to expose to it a nutritive soil 
in which the bacteria deposited by the air can develop. 
Of course, due care must be taken to previously ster- 
ilize thoroughly this soil, and the vessels in which it 
is contained. The speediness with which bacteria 
appear, and the forms observed, indicate their distribu- 
tion in the air, but not the condition in which they 
existed there. In his now classical observations, Pas- 
teur* learned thus, that the tops of uninhabited 
mountains were surrounded by an atmosphere con- 
taining but few germs. Similar has also been the 
experience of Tyndall. In undisturbed vaults Pasteur 
found also a scantiness of aerial germs, the quietude 
and want of ventilation favoring the subsidence of all 
suspended matter. The existence of much dust in the 
air does not necessarily indicate a corresponding abund- 
ance of germs, for on open roads the dust may be 
largely mineral or soot. ’ But in laboratories where 
investigations on germs have long been carried on, the 
air becomes infected finally to an extent compromising 
further research. After Tyndall had handled hay in 
his laboratory for some time, he found it very difficult 
to sterilize his solutions on account of the prevalence 
in the air of bacterial spores always found on the sur- 
face of hay. Prom the researches of both Pasteur and 
Tyndall it seems likely that the germs are not distrib- 
uted uniformly throughout the atmosphere of a locality, 
but form miniature clouds of floating matter separated 
by intervals of pure air. For when a series of similar 
vessels is exposed to the air, the separate fluids do 
not all become infected at one and the same time, nor 
do they all harbor the same organisms. 
The question, how bacteria rise into the air, is one 
*Memoire sur les corpuscles organises qui existent en suspension 
dans I’atmosphere. Comptes rendus. T. 52. GERMS IN THE AIR. 
45 
°f great importance, if we attribute to these beings 
any role in the production of disease. It has been 
shown by Naegeli* that a current of air cannot 
carry off germs from a solution over which it passes. 
The bacteria will not even rise out of their fluid soil, 
when the air bubbles through the fluid, unless 
spurting occurs. On account of these facts great 
stress has been laid by Wernichf on the importance 
°f wetting all substances from which infective germs 
might rise, in order to prevent the detachment of 
the germs. Wernich found also that bacteria dried 
°n the surface of solid bodies, are not carried off by 
currents of air, unless mechanical agitation reduces 
this bacterial coating to dust. Of course any dust 
light enough to remain suspended is taken up by 
Very faint air currents. In the case of dry porous 
Todies, the detachment of adherent bacteria is more 
readily produced by air permeating them with suffi- 
cient force, but is prevented ordinarily by wetting. 
Still Naegeli and Buchner £ have recently demon- 
strated that the porous soil of the earth will yield 
germs existing in it, to ascending currents of air, 
even when wet, which fact has probably quite a 
Tearing upon the significance of the soil in the 
spreading of infectious diseases. In their experiments 
a sandy soil was sterilized by heat, and then impreg- 
nated with cultivating solutions containing well-char- 
acterized forms of bacteria. On top of it were 
placed glasses filled with sterilized nutritive solutions, 
and the whole was covered with an inverted bell jar. 
*Whose researches are fully quoted and corroborated by Buchner in 
a lecture “On the escape of bacteria into the air,” in “Yortraege 
Sehalten in den Sitzungen des Aerztlichen Yereins zu Munchen—Zur 
der Infections-krankheiten. 1880, p. 293.” 
tGmndriss der Desinfectionslehre, 1880, p. 131 et seq. 
fCentralblatt f. d. med. Wissenschaften, No. 29, 1882. 46 
THE GERM THEORY OF DISEASE. 
Ascending currents of air were then started by 
warming the soil. The air in filtering through the 
pores of the sand detached bacteria and carried them 
up into the beakers, where the characteristic forms 
were found on being allowed to develop. As the air 
ascended through the sand a crackling noise was 
heard, indicative of the rupturing of minute bubbles 
of fluid, so that the detachment of bacteria was really 
due to a miniature spurting. A similar crackling 
noise can be observed when the surface-water changes 
its level in the soil of the earth, which occurrence is 
connected, by a large school of pathologists with 
changes in the sanitary condition of the locality. DURATION OF LIFE OF BACTERIA. 
47 
LECTUEE 111. 
Duration of Life of Bacteria.—Their Destruction by their own Pro- 
ducts.—Antiseptic Agents.—The Struggle for Supremacy between 
Different Bacteria, and between Bacteria and Animal Tissues.— 
Predisposition to Parasitic Diseases.—Are there Different Kinds 
of Bacteria?—The Cultivation of Bacteria.—The Variations in the 
Vital Powers of Bacteria.—Mitigated Disease-germs.—Fermenta- 
tions; Putrefaction. Decomposition of Urea. Lactic, Butyric, 
Acetic, Viscous and other Fermentations.—Pigment Bacteria.—Blue 
Pus: Blue Milk.—Bacteria in the Soil of the Earth. 
The growth of bacteria, even in the most suitable 
soil, cannot continue indefinitely. It must be remem- 
bered, that bacteria can only develop as long as they 
are supplied with food, and when the soil is exhausted 
their supply of food is cut off. But in reality their 
growth often ceases before this theoretical limit is 
attained. Almost every nutritive solution containing 
bacteria regains its clearness ultimately, after the 
lapse of a variable length of time. The bacteria are 
deposited gradually at the bottom and all fermentative 
action ceases. Examined at this time the solution may 
yet be found to contain sufficient nourishment, though 
all bacterial development has ceased. In some cases 
Ifie bacteria themselves are even dead, as proven by 
their incapability of growing in a fresh soil. Those 
species, however, which can bear spores usually pro- 48 
THE GEEM THEOEY OE DISEASE. 
duce them under these circumstances, so that the race 
does not die out. In a soil in which bacteria have 
ceased to multiply, it is moreover impossible to raise 
another crop of the same kind on infecting the solu- 
tion again with fresh bacteria or their germs. The 
nutritive fluid seems to possess immunity against a 
second infection. 
The cause of this phenomena has been investigated 
in the hope of throwing some light on the pathology 
of infectious diseases. For many infectious diseases, 
presumably due to the invasion of the body by micro- 
scopic parasites, have a self-limited duration comparable 
to the limited growth of bacteria in a nutritive solu- 
tion. Moreover, one attack of such a disease grants 
the body an immunity against subsequent infection, as 
we have also seen it to be the case in exhausted 
culture-fluids. 
Various chemists have pointed out recently, that in 
the course of putrefaction several substances are 
formed possessing antiseptic properties. There is 
really nothing strange in this occurrence. It is quite 
well known that in the case of higher animals some 
of the products of their own tissue-change are poison- 
ous, if they accumulate to an undue extent. This is 
true also of some species of bacteria. Wernich* espe- 
cially has called attention to the fact, that the bacteria 
of putrefaction produce the very substances which, 
when they accumulate sufficiently, arrest further devel- 
opment, or even kill their producers. Several of these 
products,—for instance, indol, skatol, phenol and some 
others, he subjected to the actual test, and found them 
to check bacterial growth, when present to the extent 
in which they actually occur in old rotten material. 
He hence defends the view, that bacterial development 
Archiv, Vol. 78, p. 51. EXHAUSTION OF SOIL. 
is ultimately arrested by the accumulation of its own 
products. But this is by no means true in every case. 
Pasteur, for instance, cultivated in chicken broth the 
bacteria, which cause chicken-cholera. After a few 
days’ growth, all further development ceased. But in 
this case no poisonous products had accumulated; the 
solution was simply exhausted. 
There is no proof, however, that the limited dura- 
tion of certain infectious diseases depends upon either 
the exhaustion of the animal body with reference to 
some nutritive substance required by the bacteria, or 
upon the accumulation of bacterial products poisonous 
to their producers. Even if either factor were of any 
importance in the limitation of acute infectious dis- 
eases, it could not be supposed that it had any 
connection with the immunity against subsequent 
attacks. For in the animal economy, subject as it is 
to continuous tissue-change, the lack of any one 
ingredient of the body would soon be compensated 
for by its new formation, while any accumulated 
foreign substances would be speedily eliminated. The 
growth of bacteria on a dead soil cannot be compared 
directly with their vegetation in the living animal 
body. In the latter instance the parasites must com- 
pete with the animal cells, and are hence subjected to 
influences absent outside of the body. Any expla- 
nation intended to account for the immunity granted 
by the first attack of an infectious disease, must take 
into consideration the properties of the living animal 
cells and cannot be put exclusively on a chemical 
basis. 
The development of bacteria in a suitable soil can 
be checked by a variety of influences which may be 
classified as physical, chemical, and biological. 
Of the physical influences upon bacterial life none 50 
THE GERM THEORY OF DISEASE. 
are more potent than the temperature. But this topic 
we have previously considered fully. It has been 
stated that bacteria are also sensitive to light, their 
development being checked by exposure to the sun’s 
rays. But the experiments do not seem to be suffi- 
ciently precise to merit further discussion. Electricity 
has no direct effect upon bacteria, its destructive influ- 
ence being due to the acids and alkalies formed by 
electrolysis. Intense motion, however, checks bacterial 
life. Howarth* found that the bacteria of putrefac- 
tion were hindered in development by shaking during 
twenty-four hours the tubes in which they had been 
sown, while forty-eight hours’ agitation killed them. 
Reinked subsequently tried to distinguish between the 
effects of a continuous motion of the fluid, and of the 
sudden shocks to which the bacteria are subjected by 
shaking. In order to produce these shocks at a much 
more rapid rate, than can be done by mechanical 
agitation, he caused waves of sound to pass through 
the cultivating solution, and did thus succeed in 
checking bacterial development, but could not kill 
them. But then the shocks produced by sound waves 
are not as violent as those due to shaking. However 
suggestive these experiments may be, the research has 
not been carried far enough to furnish any important 
results. 
The chemical influences hindering bacterial life may 
relate to either the absence of necessary substances or 
the presence of harmful agents. We have previously 
discussed the necessity of food for bacterial life and 
shown, that there are differences according to the 
species which we observe. While some of the more 
prevalent varieties can assimilate food offered them in 
Archiv f. Physiologic, Yol. 17, p. 125. 
fPflueger’s Archiv, Yol. 23, p. 434. ANTISEPTIC AGENTS. 
51 
the simplest form, others, especially the pathogenic 
kinds require the most elaborate animal fluids for 
their nutrition. Besides the nutritive substances 
proper there are few chemicals, the presence of which 
in unlimited quantity is indifferent to bacterial growth. 
An undue excess of even the inorganic salts, which 
they require normally, checks their development. 
Substances which can kill bacteria or arrest their 
growth are usually termed disinfectants or antiseptics. 
But these terms should not be used as loosely as they 
often are. Formerly, before the role of bacteria was 
understood any substance was called a disinfectant, 
provided it destroyed, or • even masked, the smell of 
putrefaction. Subsequently it was at least attempted 
to learn whether a so-called disinfectant destroyed the 
bacteria themselves. But the criterion at first chosen 
was an imperfect one. In the earlier experiments, 
different observers simply added the agent to be 
tested to bacterial fluids, and watched with the micro- 
scope the effect upon the movements. Now there are 
many dangerous kinds of micro-organisms, which never 
possess any movements, while when vital movements 
do exist, their arrest is by no means indicative of 
death. The only trustworthy criterion of the death of 
bacteria is the absence of their power of multipli- 
cation, when transplanted into the proper soil. By the 
Use of appropriate methods based on this principle a 
more precise information as to the value of disinfec- 
tants was furnished by Buchholz*, Wernich,j- and 
Jalan de la Croix. But even these results are yet 
open to objections. First these authors did not dis- 
tinguish between developed bacteria and their more 
*Arch. f. experim. Pathologie, Bd. IV., p. 7. 
fVirchow’s Archiv, Yol. 78, p. 51. 
jArch. f. exp. Path., B. 13, H. 3 and 4. 52 
THE GERM THEORY OF DISEASE. 
resistant spores, while on the other hand they did not 
extend their researches to any but the common forms 
of putrefaction. Koch* with his usual thoroughness 
has drawn up the following program for the study of 
disinfectants. It is to be learned first of all, which 
is the least concentration of the substance to be 
tested, requisite to check bacterial development by its 
presence, without killing the bacteria. Secondly, how 
much of the agent must be added in order to deprive 
the developed forms permanently of their power of 
reproduction, and how long must the disinfectant con- 
tinue to act in order to accomplish this? Thirdly, can 
the substance destroy the more resistant spores and in 
what concentration? It is to be borne in mind finally 
that the results thus found apply strictly only to that 
kind of bacteria upon which they were obtained. 
Practically, however, great differences have so far not 
been found between different species, provided they are 
examined at the same period of their development. 
The researches of Koch have overthrown many of 
our customary, but incorrect notions of disinfection. 
They have shown, that it is not an easy task to kill 
even the developed bacteria, while the spores defy 
most so-called antiseptics. The most powerful of all 
disinfectants he found in corrosive sublimate. No 
other agent can as readily destroy the spores (of 
bacillus anthracis and other varieties) as bichloride 
of mercury, its action being instantaneous even in a 
dilution of one part in five thousand, provided, of 
course, there are no chemicals present, which unite 
with and thus render inert the disinfectant. If not 
antagonized by the presence of such interfering 
substances it can permanently check bacterial growth, 
as long as one part in 330,000 is present in the 
aus dem Gesundheitsamt, p. 234. ANTISEPTIC AGENTS. 
53 
Next to corrosive sublimate, Kocli places 
bromine, iodine and chlorine. Carbolic acid, the most 
common antiseptic agent, is by no means as reliable 
as is usually supposed. Nothing less than a 8 per 
cent, solution of it can destroy spores, requiring for 
this purpose at least seven days, while a 5 per cent, 
solution suffices only in from 24 to 48 hours. The 
developed forms, however, it can kill quite readily 
(inside of two minutes) in the strength of half of one 
per cent. Its power of completely arresting bacterial 
development is not manifested in any dilution of less 
than lin 850, which suffices to check the splenic 
fever bacilli, while for the common forms of putrefac- 
tion-bacteria one part in 400 to 500 is required. A 
most interesting fact observed by Koch is the inert- 
ness of carbolic acid when dissolved in oil. In this 
form it is perfectly harmless to both spores and devel- 
oped bacteria, when immersed in it in the dried state. 
It can lienee not be used for the disinfection of instru- 
ments, or the hands, in an oily solution. But in the 
interior of wounds the carbolated oil is not so inert, 
for under these circumstances some of the carbolic 
acid is gradually yielded by the oil to the water 
of the moist surface, in which it dissolves to form an 
active solution. Dissolved in alcohol carbolic acid is 
likewise wholly inert. Of other agents Koch found 
very few capable of destroying spores. The only ones 
fhat could be relied upon to accomplish this within 
less than twenty-four hours were permanganate of 
potassium (5 per cent.) and osmic acid (1 per cent. 
S°l). A 5 per cent, solution of chloride of iron de- 
stroyed them within six days, which neither sulphate 
■°f copper nor chloride of zinc were competent to do. 
The latter agent, indeed, has been much overrated by 
surgeons, according to Koch, for its presence to the 54 
THE GERM THEORY OE DISEASE, 
extent of half of one per cent, did not even hinder the 
development of the bacillus anthracis. Hydrochloric 
acid (2 per cent.), sulphuric acid (1 per cent.), chromic 
acid (1 per cent,), boracic acid (5 per cent.), tannic 
acid (5 per cent.), benzoic acid (concentrated) dis- 
solved in water, as well as a host of other substances, 
were found inert with reference to spores. It was 
learned, on the other hand, by Koch, that certain 
substances, while not very destructive to bacteria can 
prevent their growth by their presence in minute 
quantities; for instance, allyl alcohol, one part in 
167,000, mustard oil 1 in 33,000, arsenite of potas- 
sium lin 10,000. Researches similar to those of 
Koch, and on the whole confirmatory of them, have 
been conducted by Arloing and Thomas on the bacillus 
of symptomatic charbon. Since I could not obtain 
the original in the “Lyon Medical” I could not learn 
whether they distinguished strictly between the spores 
and the developed forms. They assign to nitrate of 
silver a disinfectant value, second only to corrosive 
sublimate. Sulphurous acid, an agent still much used 
for disinfection on a large scale, was found by Koch 
quite unreliable. Its action on spores is very feeble. 
While it can kill the developed forms, if present in 
the air to the extent of 1 per cent, (by volume) 
within some twenty minutes or less, it fails to pene- 
trate into the interior of thicker masses, and its effect 
is therefore uncertain. 
Besides the evident physical and chemical conditions 
which affect bacterial life, an influence is exerted also 
upon the growth of any bacterial variety by the co-ex- 
istence of other species of micro-organisms or, in fact, 
any other living beings in the same soil. This influence 
we might term biological. Of course it should be ulti- 
mately analyzed into its physical and chemical factors, THE STRUGGLE FOR SUPREMACY. 
55 
but these we are not yet conversant with. Bacteria 
like all living beings must struggle for their existence, 
when forced to compete with other species. Within 
certain limits different varieties can co-exist in the same 
soil. Thus most rotten material contains several kinds 
of bacteria. But when any one species is better 
adapted to the soil than another it will soon extermi- 
nate the latter. This can be observed especially in 
“ pure cultures ” when only one variety vegetates in 
a protected soil. As soon as a different kind, of 
greater reproductive power (at least under the existing 
circumstances) is introduced, it will crowd the original 
population out of existence. The more prevalent kinds 
of bacteria found in all decomposing material are 
evidently those best fitted for the struggle, as their 
very prevalence shows. If hence it is desired to 
cultivate in closed flasks some special kind of bacteria, 
Lot so hardy, so to speak, as the more common species, 
the least carelessness in manipulation may frustrate 
the object, for if a single bacterium of a different 
kind gets in by accident, it will multiply so fast as to 
exterminate the others. By overlooking this fact 
grave errors have been committed in the study of 
alleged pure cultivations. The struggle for supremacy 
between different species of bacteria explains also why 
it is, that the blood of certain infectious diseases loses 
its virulence, i. e. its power of producing the same 
disease in other individuals on inoculation, when it is 
allowed to putrefy. Thus in splenic fever and in 
septicaemia the agent causing the disease has been 
recognized in certain bacteria existing in the living 
blood. The same blood, when rotten, is found deprived 
of its special virulent properties. Its disease-breeding 
bacteria have been replaced by the common micro- 
organisms of putrefaction. In the case of splenic 56 
THE GERM THEORY OE DISEASE. 
fever blood it has been learned by Koch and by 
Toussaint that the destruction of the parasites is really 
caused by a deprivation of oxygen which the putrefac- 
tion-bacteria appropriate eagerly at the expense of the 
pathogenic variety. For the latter are killed by the 
deprivation of oxygen, no matter how produced, but 
can continue their life in the presence of other 
bacteria, within certain limits, if freely supplied with 
that gas. In other cases it has not been learned how 
one variety can crowd another out of existence, 
whether it be by abstraction of the food, or oxygen, 
or by the formation of products poisonous to the other 
kind, or by other influences yet unknown. 
When bacteria vegetate in the interior of the ani- 
mal body there occurs likewise a struggle for existence 
between the bacteria and the animal cells. We are 
again ignorant as to the weapons of the contending 
armies, we do not know yet how the warfare is carried 
on between the hostile vegetable and animal cells, but 
that the struggle exists is evident, and it must ter- 
minate in the victory of one or the other side. The 
battle won by the tissues means recovery from the 
disease, while the supremacy of the invading parasites 
amounts to death of the animal, or—in the more pro- 
tracted cases—to perpetuation of the local disorder. 
We must never lose sight of the fact that the living 
animal body is not a mere “culture-flask” in which 
bacteria can multiply without hindrance. If the para- 
sites can grow at all inside of the animal system, they 
can only do so by overcoming the opposition on the 
part of the animal cells. But the resistance of the 
animal body to the parasitic invasion varies with the 
kind of bacteria and the species of animal. To illus- 
trate this I might anticipate future remarks by point- 
ing out that the merest trace of splenic fever bacilli VARIATIONS IN THE POWER OF RESISTANCE. 
57 
introduced into the body of a rabbit will inevitably 
multiply and kill the animal, while much larger num- 
bers of the parasites can be successfully resisted by 
the dog. Again, while a certain kind of bacteria can 
readily grow in the system of the common mouse, and 
produce thereby the symptoms of septicaemia, they 
cannot be made to invade the body of a field-mouse. 
Such instances could easily be multiplied. But besides 
the differing resisting powers of different species of 
animals, we must recognize also variations between 
different individuals of the same species. Indeed, in 
human pathology this has always been admitted under 
the name “•predisposition to a disease.” We are all 
aware that apart from the influence of race and age 
there are individual peculiarities which render the 
bearer more or less likely to contract an infectious 
disease. The nature of this predisposition is as yet 
wholly unknown. Very little light has been thrown 
upon it by experiments on animals, mainly for the 
reason that the infecting material is usually employed 
in such massive doses, as to obliterate minor differences 
in the susceptibility of the victim. There is all reason 
to believe that in most cases the amount of infectious 
material producing the “ natural ” disease, is a mere 
trace, compared with the quantity employed for experi- 
mental purposes. Moreover it is not known whether 
the individual susceptibility varies as much in other 
species of animals as it does amongst mankind. Many 
°f the shallowest arguments against the validity of 
the germ theory would not have been brought forth 
had their authors but remembered, that the pathogenic 
bacteria vegetating in the tissues are resisted by the 
animal cells, and that this resistance is variable in 
different cases. Our ignorance of the nature of this 
Resistance does not justify us in overlooking it. 58 
THE GERM THEORY OE DISEASE. 
Throughout these lectures we have referred to dif- 
ferent varieties of bacteria; it is now time to examine* 
whether the various forms met with constitute separate 
and distinct species, or whether all bacteria no matter 
what their shape are but different stages of one and 
the same micro-organism. There is as yet a diversity 
of opinion upon this subject. A certain school headed 
by Naegeli claims that all bacteria constitute but one 
species, and that the different forms are mutually 
convertible. On the other hand Cohn defends the 
view, so ably supported by Koch, that bacteria should 
be the generic name of a class of plants with nu- 
merous species as sharply characterized as could be 
expected of beings of such simple structure. But 
mere opinion should be of no great weight, we want 
facts. 
It can be readily seen, that it is difficult to adduce 
the facts. For the proof of the correctness of one or 
the other view rests upon the possibility (or impossi- 
bility) of transforming one variety into another under 
the eyes of the observer. On account of the übiquity 
of bacteria such an observation is much more difficult 
to make in a reliable manner than might be supposed. 
In order .to learn whether a certain form of bacteria 
represents a distinct species we must cultivate it, as we 
would any higher plant, in different soils and under 
different circumstances. But every time the flask is 
opened in which this is done and every time we 
transfer a drop to a new flask we run the risk of the 
accidental introduction of other germs from the air 
even if -we purify our instruments and vessels scrupu- 
lously. The crop therefore which we raise may not be 
at all derived from the stock we have sown. Hence it 
is very difficult to maintain the purity of a successive 
series of cultures in flasks. This difficulty is not CULTIVATION OF BACTERIA. 
diminished, though the occurrence of an impurity can 
he more readily detected, if we take such a small 
quantity of the cultivating solution, that the whole 
culture can be surveyed under the microscope. This 
can be done by placing a single drop on the under 
surface of a cover-glass resting upon a hollow glass 
slide, or supported by a ring of parafine upon an 
ordinary slide. By means of this method the growth 
of bacteria can be watched continuously, or at inter- 
vals, and the entrance of any foreign species detected 
speedily. This method, however, is applicable only 
to those forms presenting a characteristic appearance 
easily recognized. A decided improvement for the 
maintenance of a culture in a state of purity, has 
lately been introduced by Koch. This consists in the 
use of a solid soil. A solution of gelatine, about 
3 per cent, in strength, is allowed to congeal in watch 
glasses, or in the form of flat drops simply on a slide. 
It must contain an addition of meat extract, blood 
serum, vegetable infusions, or some other nutritive 
substances. It is to be sterilized previously by 
repeated heating according to the method of Tyndall. 
A temperature of 58° C. cannot be surpassed if serum 
is used, Avithout coagulating the latter. Moreover this 
suffices if repeated for about an hour at a time. The 
bacteria are planted on this solid soil by scratching it 
with a needle dipped into the material from which 
the bacteria are to be derived. The great advantage 
of this method is the absence of currents in the soil. 
The progeny of each single bacterium cannot be 
carried hither and thither as Avould be the case in 
fluids, but remains collected around the centre, where 
the parent cell Avas implanted. This is true of the 
bacteria we soav as Avell as of the germs which get in 
accidentally. The entrance of foreign bacteria coming 60 
THE GERM THEORY OF DISEASE. 
from the air we cannot prevent altogether, but the 
crop which they engender does not get mixed with 
the bacteria under observation. It extends more or 
less rapidly from the spot where the foreign germs 
settled, but does not invade the whole soil. Experi- 
ence has shown, that different bacteria growing on 
such a solid soil can be distinguished by the different 
forms of colonies which they produce, and by the 
manner in which the growth extends. According to 
the kind under observation the growth appears in the 
form of larger or smaller globules, arborescent pro- 
jections, flat scums, or simply diffused masses radiating 
from the furrow of implantation, with or without, lique- 
faction of the soil. Hence with a low power of the 
microscope, or even with the naked eye any impurity 
of the culture due to foreign germs can be 
detected in time, and the desired purity be main- 
tained by transferring a trace from the intact portion 
to a fresh sterilized soil. Impregnated gelatine is not 
the only available solid soil, though it possesses the 
special advantage of transparency. Many of the more 
prevalent forms can grow on the surface of a slice of 
a boiled potato. In fact observations on this sub- 
stratum suggested to Koch the advantage of a solid 
soil. A drawback to the gelatine soil is its low 
melting point, viz: 28° C. In my own experience 
most of the grades to be had in commerce here 
became fluid at even a lower temperature in spite of 
accurate neutralization of any trace of acidity present. 
In order to obviate this difficulty Koch has lately 
used solidified blood serum. The blood is allowed to 
clot in a purified vessel, and after standing twenty- 
four hours in a cool place the serum is drained off. 
This is then heated to 58° C. an hour at a time 
during several successive days in order to sterilize it, MUTABILITY OR STABILITY. 
61 
hereupon it is transferred into suitable vessels and 
converted into an amber-like gelatinous solid mass by 
beating it up to 65° C. This transparent soil offers 
the best possible nutrition to pathogenic bacteria, and 
unlike gelatine does not melt on warming. 
On taking a historical review of the evidence 
brought forth in favor of either the mutability, or 
stability, of bacterial species, we will find that the 
former view has been steadily losing ground. As the 
methods of cultivation became more reliable and their 
sources of error were better understood, it had to be 
admitted that in most cases the alleged transformation 
of one kind into another was simply the substitution 
of accidentally admitted germs for the original stock. 
Some fifteen years ago Hallier, one of the pioneers in 
bacterial morphology claimed that mould-fungi, yeast 
cells, and bacteria were but different stages of one 
and the same plant. But it was soon shown by 
competent botanists, that his methods were untrust- 
worthy. 
At the present time no one claims that bacteria can 
ever change into any other form of plants. That 
superstition has been settled long ago and in a very 
positive manner. But Naegeli and his adherents still 
think that a given form of bacteria can change its 
appearance and physiological properties, in fact be 
converted into another variety, when placed under 
altered circumstances. With the exception, however, of 
one doubtful observation by Buchner there remains 
no proof in favor of that view. So far as all trust- 
worthy observation goes, every bacterial species retains 
all its morphological characteristics, no matter in what 
soil it grows, if it grows at all. A bacillus never 
changes into a micrococcus, nor the latter into a 
spirillum. Even minor points of shape remain constant*. 62 
THE GERM THEORY OF DISEASE. 
Rod-shaped bacteria possessing a square end do not 
round off their extremity on growing in another 
medium, and vice versa. Likewise the peculiar form 
in which the growth extends on solid soil, remains 
the same, no matter how often the species is trans- 
planted. The chemical and vital properties likewise 
are peculiar to each bacterial variety. The » micro- 
organism which causes lactic acid fermentation cannot 
start the putrefaction of albumen, or ferment glycerine. 
The bacillus producing splenic fever is not the cause 
of any other disease and the bacteria of septicaemia do 
not produce tuberculosis or other affections. 
This question of the mutability or stability of 
bacterial forms is evidently one of great importance. 
Were it possible, for instance, to change harmless 
bacteria of putrefaction into potent disease germs, 
through influences which occur in nature, there would 
be little hope of ever eradicating any infectious disease. 
But, I must repeat, all evidence, when carefully 
weighed, points towards the permanency of the sepa- 
rate bacterial species. Of course the question cannot 
be decided any other way but by experiment; it would 
be unscientific to assume on theoretical grounds that 
the conversion of one form into another can never be 
realized. But the fact is, that this has not been 
accomplished as yet under any conditions tested, and 
we must therefore recognize a large number of 
separate and distinct species of bacteria as permanent 
varieties in the present state of our science. The 
validity of certain experiments to the contrary we 
shall discuss under the head of splenic fever. 
Pasteur, whose stronghold is evidently not micro- 
scopical morphology, suggested some time since that 
the classification of bacteria should be physiological 
rather than anatomical. He pointed out that different ATTENUATION OF VIRULENCE. 
63 
species, which lie could not distinguish from each 
other with the microscope, still possessed different 
vital properties. Of micro-organisms, apparently alike 
in form, some produce different fermentations; others 
can cause various diseases. His criterion of a species 
therefore was not merely the form, but rather the 
chemical or vital test. But his own later researches 
have shown that this system of classification is not 
tenable. For he himself has made the important 
discovery that the properties of a given species may 
vary in degree with different circumstances, and that 
this altered vital power is then transmitted to the 
succeeding generations. The first instance in which 
fie showed this variability of the vital power of a 
species was in the case of the parasites producing 
chicken-cholera. These micrococci after once entering 
the body of a fowl multiply there to an unlimited 
extent, and with rare exceptions destroy their host’s 
life. The parasites could be cultivated in chicken- 
firoth, in which their further growth ceased after 
some four or five days. They retained their original 
virulence,—i. e. their power of struggling victoriously 
with the tissues of the fowl—indefinitely, if they were 
transferred to a fresh soil from time to time. But 
when they were allowed to remain for months in the 
same flask, their vital power was gradually reduced. 
Samples taken from the flask at successive intervals 
Were found less and less poisonous to the animal. 
The older the crop of parasites the less vigorous was 
their growth in the animal body, and the milder the 
disease to which they gave rise. About nine months’ 
sojourn in the unchanged medium deprived these 
fiacteria of their ability to multiply at all in the 
animal body, though they could still grow in a fresh 
cultivating solution. A still longer sojourn in the 64 
THE GERM THEORY OF DISEASE. 
same flask without change of soil, killed them. 
Pasteur attributes the enfeebling of the bacterial 
vitality to the influence of the oxygen. Por when 
the flasks were hermetically closed the lapse of time 
alone did not reduce the bacterial power of repro- 
duction or their virulence to animals. A further 
point of capital importance discovered by Pasteur is 
the fact, that the altered degree of virulence is trans- 
mitted unchanged through the successive generations, 
when the bacteria thus enfeebled are cultivated in 
a fresh soil. He succeeded thus in transforming one 
variety of bacteria into another, if we take the physi- 
ological properties as the criterion of a variety. If 
on the other hand we take the more correct stand- 
point of characterizing a species by its morphology, 
these researches teach us that the vital power of a 
bacterial variety, i. e. the ability to struggle for its 
existence against the opposition of other living cells, 
can be permanently altered. Pasteur has since shown 
the same to be true of the splenic fever bacilli, and, 
he claims, also of other pathogenic bacteria. 
Whether the power of bacteria to start certain 
fermentations can be permanently altered by the 
mode of cultivation has not been much investigated. 
I can find but a single statement by Pitz, who 
claims that a certain bacillus producing the butyric 
fermentation of glycerine loses this property by 
successive cultivation at 45° C., or by raising several 
generations in a solution of meat extract having a 
large surface exposed to the air. In the case of 
some disease germs it has been further shown by 
some French observers (Toussaint, Chauveau), that 
any temporary influences which, if persistent, would 
destroy the bacteria, reduce permanently their powTer 
of multiplying in and harming the animal body. VARIETIES OF BACTERIA. 
65 
The evidence of clinical medicine, which, it must 
be admitted, can only be suggestive, and never as 
positive as experimental proof, supports the views 
here presented. The study of contagious diseases 
leads to the inference that disease germs are distinct 
and separate species, but that their virulence can 
vary. The infection from a small-pox patient, or a 
case of scarlet fever, or measles, produces only the 
original infection and never any other disease, but 
the severity of an epidemic varies a great deal in 
different years. 
A satisfactory study of the role of bacteria can 
only be undertaken from the standpoint thus pre- 
sented, viz; that there are numerous species differing 
from each other by their structure, shape, mode of 
growth and properties. If we do not admit—at least 
provisionally—the stability of each species, we will 
have no guiding thread to follow through the con- 
fusion of observations. Even should further research 
show, that different varieties of bacteria can be trans- 
formed into each other under conditions with which 
we are not yet acquainted, it would not invalidate our 
knowledge regarding any one species. From this 
point of view the balance of our studies ought 
logically to be devoted to the natural history of each 
separate species of bacteria. But our information is 
as yet too incomplete to permit of such a systematic 
arrangement. It will be more convenient to discuss 
the various occurrences in which bacteria are known 
to be concerned, beginning with fermentations, and 
then passing in review the various diseases, the para- 
sitic origin of which is either proven or suspected. 
Fermentation and putrefaction have been defined 
above as processes of decomposition, in which complex 
molecules are split up into simpler ones. It should 66 
THE GERM THEORY OF DISEASE. 
now be added that these chemical changes are due to 
the life-work of micro-organisms. It is characteristic 
of them, that the mass of living cells accomplishing 
the change may be very small, when compared with 
the amount of material transformed. In what manner 
the micro-organisms affect the chemical changes is but 
imperfectly known. It has been shown in some 
instances, that they form soluble substances termed 
ferments, which produce the chemical changes by 
themselves, independent of the bacteria, which gener- 
ated the ferment. These ferments can also act when 
present in remarkably small quantities, even after the 
living cells producing them have been removed. But 
a non-living soluble ferment can never multiply or 
reproduce itself. That faculty is the exclusive privi- 
lege of living beings. In many fermentations, however, 
no soluble ferments have ever been detected and the 
chemical changes in these cases can only occur in 
the interior of the living cells. The energy of a 
fermentative process, is greatest at the temperature 
most favorable to the life of the species of micro- 
organisms concerned. 
The most common fermentative process in nature is 
the decomposition, or rotting, of complex nitrogenous 
material, like albuminoids, gelatine and the allied veg- 
etable substances. It occurs invariably, when such 
substances are exposed to the air under proper condi- 
tions of moisture and temperature, and in the absence 
of antiseptic agents. Hence ordinarily all animal and 
vegetable refuse rots. The successive chemical stages 
of the putrefactive change have as yet been incom- 
pletely traced. The changes 'which albumen undergoes 
resemble at first the process of digestion. It is con- 
verted into soluble forms partly peptone, and then split 
up into leucin and tyrosin. Subsequently numerous FERMENTATIONS. 
67 
volatile fatty acids, and various polyatomic alcohols 
(phenol, skatol, indol) appear as well as a host of 
other substances in traces. Amongst them are a 
variety of poisonous agents, especially some alkaloids 
(ptomaines). At last the bulk of these derivatives is 
converted into the simplest chemical forms (partly by 
oxydation), viz.; ammonia, carbonic acid, water, sulphu- 
retted hydrogen (and phosphoretted hydrogen). The 
most constant bacterial form met with in putrefaction 
is the bacterium termo. It consists of rods two to 
three micromillimeters in length, one-fifth to one-half 
as thick, often in pairs, sometimes in zoogloea masses. 
It is freely mobile, possessing a most delicate flagellum 
at either end. It is not known to form spores. It is 
distinctly aerobic, requiring oxygen for its growth and 
movements. Pasteur, who does not admit that aerobic 
bacteria can cause fermentation, claims that the bac- 
terium termo, living at the surface of rotting material, 
merely oxydizes the derivatives, but does not produce 
the original decomposition. Nencki, who also defends 
this view? seeks the cause of the original decomposi- 
tion principally in different micrococci living in the 
depth of the material. The latter can continue their 
Work in the absence of oxygen when the bacterium 
termo disappears. Usually there are also different 
forms of larger bacilli present, amongst them often 
the kind known as the hay bacillus, or the bacillus 
subtilis. This micro-organism, one of the most com- 
mon in nature, is found dried on the surface of hay 
aml many grains. It consists of delicate rods with 
dagella either in separate segments some two to six 
micromillimeters in length, or—especially when not 
shaken—in the form of very long threads. 
On account of the resisting power of its spores it is 
Very apt to appear or rather to persist in fluids which THE GERM THEORY OE DISEASE. 
have been boiled. Its presence lias therefore been a. 
stumbling-block to many a champion of spontaneous 
generation. It cannot live without oxygen, and forms, 
hence a membrane-like scum on the surface of the 
fluids in which it grows, without rendering them tur- 
bid in the depth. It cannot cause rotting by itself. 
But other bacilli of different forms and different prop- 
erties are almost always met with in rotting material, 
besides the micrococci above mentioned. Putrid refuse 
presents really an extensive flora of microscopic beings. 
Hence, besides the putrefaction bacteria proper, it may 
harbor disease germs, though they are not always 
present. 
A second form of fermentation of nitrogenous 
material of special medical interest is the transforma- 
tion of urea into carbonate of ammonia. Urine when 
exposed to the air, especially in the vicinity of barns 
and closets, is apt to become ammoniacal. This change 
is due to the presence of the micrococcus urese. If 
this micrococcus be excluded the urine does not turn 
alkaline, although other bacteria may cause rotting. 
Eecent researches by Jaksch* have shown that this 
bacterium appears at first in the form of rods two to 
three micromillimeters in length by one half a micro- 
millimeter in width, which speedily segment and in 
the course of forty-eight hours form micrococci-like 
granules —in chains. Gradually these micrococci 
assume' the zoogloea form, sink to the bottom, and after 
the lapse of some four or six weeks die, unless trans- 
ferred to a fresh soil. Their life and activity requires 
the presence of oxygen. They thrive best at a 
temperature of 30° to 83° C., and are killed by 60° C. 
Jaksch presents some interesting observations on their 
nutrition. Any artificial solution intended to nourish 
*Zeitschrift f. physiologische Chexnie. Bd. V., p. 395. 69 
FERMENTATIONS. 
them, must contain of inorganic salts potassium and 
magnesium in the form of phosphate and sulphate. 
They cannot develop in the absence of any one of 
these elements. They require besides some source of 
nitrogen and carbon, which latter element they cannot 
obtain from urea alone. Urea is transformed by them 
into bicarbonate of ammonium by union with two 
molecules of water. This chemical change is effected 
by means of a soluble ferment secreted by these 
bacteria, which latter can be isolated by precipitation 
with alcohol. In some diseases of the bladder, and 
especially in paralysis of that organ from spinal 
disease, the urine is ammoniacal when freshly voided. 
In such instances the micrococcus ureae is always 
present in the bladder, and has always been intro- 
duced from without. The most common way of 
introduction is evidently the use of impure catheters 
or sounds. In reply to doubts of the truth of this 
statement, Pasteur challenged the French Academy of 
Medicine in 1877 to produce a case of ammoniacal 
urine in which he could not show the presence of 
these bacteria, but this was never done. Possibly the 
bacteria may creep into the bladder by growth 
through the urethra, when this channel is kept filled 
with the dribbling urine, but this is not yet certain. 
In the healthy bladder the micrococcus ureae cannot 
find the conditions requisite for its continued vegeta- 
tion. As was shown by Feltz and Ritter, the. injection 
of these bacteria into the healthy bladders of dogs is 
soon followed by their elimination. 
The hydrocarbons can undergo a variety of fermen- 
tations. Starch can be attacked by bacterium termo, 
Tut, as Wortmann* has shown, only when there is no 
other source of carbon available. In that case a fer- 
*Zeitechrift f. physiologische Chemie. Bd. VI., p. 287. 70 
THE GERM THEORY OF DISEASE. 
ment-like diastase is secreted, which transforms the 
starch into sugar. The sugar is consumed by the 
bacteria as fast as it is formed. 
The fermentation of sugar into alcohol is not due 
to bacteria, but is ordinarily the work of the yeast 
plant. The same change can also be accomplished by 
various mould fungi, even the common penicillium,, 
when submerged in the saccharine solution, so as to- 
be deprived of oxygen. As far as we know, no 
bacteria can produce this fermentation. 
The lactic acid fermentation of sugars is produced 
by a certain species of bacteria, in the form of 
micrococci in chains or pairs. (Lister* and Meyer.-j-) 
The size seems to be somewhat variable. This micro- 
organism gets into the milk, when freshly drawn, 
either from the teats or from the utensils used. It 
seems very difficult to exclude this micro-organism 
on collecting milk. Moreover it is not readily killed 
by heat, as it can certainly withstand the boiling 
temperature for a short time, according to Pasteur and 
others. Yet it is not known whether it exists in the 
form of spores; indeed its morphology has been but 
imperfectly investigated. It changes milk sugar, grape 
sugar and allied varieties into lactic acid, but this 
transformation does not continue long unless alkalies 
are present to neutralize the acid as fast as it is 
formed. For these bacteria are very sensitive to any 
excess of acid. It is claimed that they are anaerobic. 
Their presence is the cause of the souring of milk. 
Of course the higher the temperature of the season 
the quicker this change occurs. In what manner the 
occurrence of a thunder shower can affect the rapidity 
of this process—if it really does so—has never been 
investigated. 
of the London Pathological Society, 1878. 
fMaly’s Jahresbericht f. Thierchemie, 1881. p. 468. FERMENTATIONS. 
71 
The fermentation of lactic acid into butyric acid is 
also due to the life-work of bacteria. This species 
consists of large rods, often in the form of lengthy 
chains, endowed with slow serpentine movements, and 
capable of growing and acting only in the absence of 
free oxygen (Pasteur). 
There occurs, furthermore, a viscous or ropy fermen- 
tation of sugars found at times both in wines and 
milk. The sugar is thereby transformed into a gum- 
like substance, giving the solution a ropy consistency. 
The cause of this change is a large micrococcus, usu- 
ally in the form of chains.* 
The acetic acid fermentation of alcohol is usually 
produced by a species of large micrococci (one to three 
micromillimeters in diameter) which form a dense scum 
on the surface of the alcoholic liquid. The oxydation 
of alcohol into acetic acid can be accomplished also 
by some other varieties, while a different species, not yet 
closely studied, can oxydize the alcohol completely into 
carbonic acid and water. All these forms require the 
presence of oxygen and are checked in their action by 
too great a concentration of the alcohol. Unlike other 
bacterial species, they can thrive in an acid medium. 
Some interesting fermentations involving glycerine 
have been studied by Fitz in several communications 
made to the German Chemical Society (since 1876). 
In a cultivating solution containing three per cent, of 
glycerine he observed transformation of the latter into 
ethyl alcohol (at least in part) from the action of a 
rod-shaped bacterium, which he obtained by washing 
the surface of hay. (Buchner has lately denied, how- 
ever, that this is the common bacillus subtilis.) This 
fermentation is a very slow one. A quicker fermenta- 
*Pasteur, also Schmidt-Muhlheim. Pflueger’s Archiv. f. d. ges. Phy- 
siologic. Bd. 27, p. 490. 72 
THE GERM THEORY OF DISEASE. 
tion of glycerine resulting in the formation of butyric 
acid, butyl-alcohol, and other products was obtained 
by the agency of another bacillus larger than the 
former, but derived like it from the surface of hay. 
Certain fermentations result in the appearance of 
colored products. The best known instance of this 
kind is the life-work of the micrococcus prodigiosus. 
This bacterium grows readily on the surface of certain 
solid soils, like potato slices, bread, and other victuals, 
and gives rise to a nearly blood-red scum. This sin- 
gular growth of blood-like patches, which may infest 
a locality like an epidemic, has often attracted popular 
attention, and has formerly started many a superstition. 
The phenomenon, however, is simply due to the vege- 
tation of a micrococcus, colorless by itself, but producing 
a red pigment insoluble in water and having some chem- 
ical resemblance to aniline colors. Usually this micro- 
coccus is crowded out after a few days’ vegetation by an 
invasion of the same soil by other bacteria of putrefac- 
tion, which also destroy the pigment formed. It was 
observed in Cohn’s laboratory that continued experimen- 
tation with this micro-organism caused such a diffusion 
of the germs (dried cocci or spores?) throughout the 
air, that any suitable soil became invariably affected, 
when exposed to the atmospheric dust. Various other 
pigment bacteria have been studied by Schroeter* and 
Cohn.f Quite a variety of pigments could thus be 
obtained by the action of different micro-organisms. 
In these instances the stability of the bacterial species 
can be readily demonstrated even without the micro- 
scope. Tor each species produces only its own peculiar 
pigment, if the soil permits the formation of the latter, 
and never any other. 
*Cohn’s Beitraege z. Biologic d. Pflanzen, Bd. 1., H.-11, p. 109. 
fldem, p. 151. FERMENTATIONS. 
The blue coloration of pus sometimes observed on 
surgical dressings is also the product of bacterial action. 
This form consists of very thin elliptic rods about 1 
to 1.8 micromillimeters in length, partly united in pairs. 
The pigment was found by Fitz to resemble litmus in 
its chemical behavior. It is originally colorless, but 
under the influence of the atmospheric oxygen it turns 
blue. Under some circumstances the presence of this 
same species stains the pus yellow. According to sur- 
gical experience the presence of these parasites in 
wounds is of no special importance. 
Very singular observations have been made by 
Neelsen* on the bacteria which cause the epidemics of 
“blue milk” in dairies. This fermentation, resulting 
in the production of a soluble blue pigment is the 
work of short mobile bacilli vegetating in the milk. 
They are not known to render the milk injurious. 
After a few days’ growth (by fission) they change their 
shape and form chains of shorter segments, which do 
not undergo further change until transferred into a 
fresh soil. Since these short, biscuit-shaped segments 
do not possess any great resisting power to damaging 
influences, Neelsen does not consider them true spores, 
but compares them to the “gonidia” of higher fungi. 
But true spores were observed, when these bacteria (or 
their gonidia) were sown in Cohn’s cultivating solution. 
The growth of the bacteria in this soil was not attended 
by the formation of any pigments. But when an 
addition of lactate of ammonia was made to Cohn’s 
solution the blue pigment was produced. The shape, 
however, of the plant was entirely altered in this solu- 
tion, in which it assumed the appearance of micrococci 
iu zooglcea masses. Neelsen claims that this strange 
Metamorphosis is normal to this species when planted in 
*Beitr. z. Biologie d. Pflanzen, Bd. 111. Heft 11., p. 187. THE GERM THEORY OF DISEASE. 
different soils, for lie could always produce the original 
form of the bacterium by transplanting it back to milk. 
These interesting observations, however, need confir- 
mation. 
The life-work of certain bacteria reveals itself by a 
phosphorescence of the vegetation. Sometimes animal 
refuse, especially salt-water fish, is covered with a slimy 
coat emitting a feeble glow in the dark. In a speci- 
men of meat of this kind Lassar found the cause to 
be the growth of a micrococcus on the surface. 
The above list includes the fermentations best known, 
but by no means all the instances of chemical changes, 
owing to the presence of bacteria. It shows, however, 
the important role played by these minute beings in 
the household of nature. Their significance is the 
more apparent, when we take into consideration that 
they are not only concerned in so many chemical pro- 
cesses on the surface of the globe, but also in a 
continuous series of changes occurring in the soil of 
the earth. The form in which the nitrogen exists in 
the soil undergoes changes, and with it the value of 
the soil for agricultural purposes. Schloesing and 
Muntz showed some time ago that the oxydation of 
ammonia salts and other nitrogenous compounds into 
the form of nitrates is the work of living bacteria. 
Within the last year various communications have been 
made to the French Academy by other observers to 
prove that there occurs likewise a change in the other 
direction, viz.: the reduction of nitrates to a less oxy- 
dized form. This process is also due to the life-work 
of bacteria. BACTERIA ON THE SURFACES OF ANIMALS. 
75 
lecture’iy. 
Bacteria on the Surface of the Animal Body and in the Digestive 
Canal.—Their Work in Digestion.—Germs in the Healthy Tissues. 
—The Research for Pathogenic Bacteria.—Microscopic Detection, 
Cultivation and Inoculation of Germs.—Charbon.—lts Parasites 
and their Mode of Producing and Spreading the Disease.—Pro- 
tective Vaccination -with Mitigated Germs.—The Germicide Treat- 
ment.—Chicken-cholera. 
Tlie prevalence of bacteria, in the vegetating condi- 
tion and dried in suspension in the air, evidently 
brings them into contact with the animal body. They 
exist, usually in a dried state, on the surface of the 
skin and hair, and cannot be removed entirely by 
washing. If secretions occur in which they can vege- 
tate, bacterial life and activity are soon manifested. 
Thus—as Thin has shown—bacteria cause the foul 
odor of bad-smelling feet by their decomposition of 
the sweat, and the persistence of this annoyance is 
due to their vegetation in the ducts of the cutaneous 
glands. With every breath we take, bacteria are depos- 
ited upon the respiratory surfaces. The expired air 
seems to be filtered mainly in the narrow pulmonary 
spaces, and thereby loses the most of the particles it 
contained in suspension, Tyndall has shown that the 
last portion of the exhaled breath does not scatter 
light and is hence optically pure. Gunning has lately 76 
THE GERM THEORY OF DISEASE. 
attempted to prove the purity of the expired air in 
another manner. On allowing it to bubble through a 
sterilized cultivating solution he obtained no infection 
of the fluid. But from the negative results in similar 
experiments by others with common air, I am inclined 
to doubt the reliability of this method. Air in bub- 
bling through fluids does not probably yield its dust 
readily to them. With every morsel of food we con- 
sume, bacteria are carried into the digestive canal, 
where they find the conditions present required for 
their growth, viz.: food, moisture and the proper heat. 
In the mouth some forms or other are always met 
with, the most common one being the Leptothrix buc- 
calis, a chain of short thick segments. Frequently 
also a delicate spirillum with many convolutions occurs 
on the surface of the teeth. Sternberg has found a 
micrococcus in the saliva of some healthy people which 
can produce septicaemia in rabbits. 
In the stomach bacterial activity is normally checked 
by the acid of the gastric juice, although this is 
hardly of sufficient strength to kill all forms. When 
the secretion of the acid ceases during a disease, lactic 
and butyric acid fermentations and perhaps other bac- 
terial processes do occur. In the intestines, however, 
where the reaction is either alkaline or only faintly 
acid, bacteria thrive luxuriously. Their vegetation is 
so rank, that the normal faeces, if not augmented in 
bulk by undigested remnants of food, may consist 
almost entirely of bacteria. Nothnagel,* who has lately 
re-examined this question, finds in the stools quite a 
variety of forms of both micrococci and bacilli. Their 
existence in the intestines is not a morbid occurrence; 
it is normal and—in my opinion—explains one of the 
puzzles in the physiology of digestion. Busch and 
*Zeitschrift f. klinische Medicin, Bd. 3, p. 275. BACTERIA IN THE DIGESTIVE CANAL. 
77 
others who have had the chance to investigate cases 
of intestinal fistula in man or in animals have found, 
that many solid food substances are absorbed in the 
intestines without the aid of gastric or pancreatic juice. 
On the other hand examination of the intestinal juice 
proper shows that it has but feeble digestive properties. 
It is likely that the discrepancies between the different 
observers, who studied intestinal digestion in and out- 
side of the intestines, are due to overlooking the 
putrefactive processes which normally occur in the 
intestines. Certainly the changes which are observed 
in artificial digestion in flasks do not comprise all 
those found in the intestinal canal. Normal digestion 
is evidently complicated by putrefaction. The presence 
of these bacterial parasites in the intestinal canal is 
not at all a damage, but it seems a benefit to the 
animal, for they evidently supplement the action of 
the digestive juices. In the case of one substance at 
least cellulose the digestion in the intestinal tract 
of herbivora is entirely the work of bacteria. 
In the instances so far considered the bacteria exist 
only on the surface—be it external or internal—of the 
body. But a different question, and one of capital 
importance with relation to the germ theory is: do 
bacteria, or their germs exist in the interior of a 
healthy organism, in the blood or in the tissues 
themselves ? 
The microscope cannot detect them in the healthy 
blood and tissues even with the aid of the most deli- 
cate staining methods, but this would be insufficient 
evidence, if their number is very limited. The ques- 
tion can be only decided by the cultivation of any 
pre-existing germs with the exclusion of any coming 
from the outside. Numerous such experiments have 
been made. Van der Brock, Pasteur, Lister and others 78 
THE GERM THEORY OF DISEASE. 
all agree that living blood received in purified vessels 
with antiseptic precautions will not putrefy. Putrefac- 
tive bacteria do not pre-exist in the living blood 
vessels. Recently Zweifel* has denied the accuracy of 
this statement and claimed that the germs which do 
pre-exist are prevented from developing by the oxygen 
of the arterial blood. For, when he removed the 
oxygen, putrefaction set in, and he claims even to 
have seen micrococci (though without putrefaction) in 
the arterial blood on standing in closed vessels. But 
his work does not bear such a stamp of accuracy as 
to entitle it to much faith. To start with, he over- 
looks the fact that the oxygen of the shed blood dis- 
appears pretty soon, under any circumstances, while 
in his attempts to pump out the gases of the blood 
he undoubtedly infected it with germs from without. 
Moreover, he did not prove, that the granules which 
he saw in the blood were really micrococci and not 
the detritus of white blood-corpuscles. 
That the normal urine does not decompose, when 
protected against outside germs has been found by all 
observers. In the case of the milk it has been 
learned by Lister, Cheyne, and Meissner that it 
contains originally no germs, but that it is difficult to 
collect it without introducing lactic acid bacteria from 
the teats. 
Whether bacteria pre-exist in the solid tissues, Bill- 
roth attempted to decide by cutting pieces out of the 
body and throwing them into melted parafiue, which 
was intended to exclude foreign germs. In all his 
experiments putrefaction occurred. These observations 
have since been repeated by many others, but with 
variable results. Although various careful observers, 
for instance, Nencki and Giacosa, j- who worked appar- 
*Zeitschrift f. phys. Chemie. Yol. VI., p, 386. 
f. pract. Chemie, Vol. 20, p. 34. 1879. NO GERMS IN LIVING TISSUES. 
79 
ently with all the precautions of antiseptic surgery, 
have found that they could not preserve tissues in 
their fresh state without decomposition, still it must 
now be admitted that the germs of putrefaction do 
not pre-exist in the healthy living body. For other 
experimenters have succeeded in preserving the fresh 
tissues unaltered, by the exclusion of germs from 
without. Chiene and Ewarts placed various extirpated 
organs partly into carbolated gauze, partly into flasks 
previously purified by heat, and found them pure 
after the lapse of many days, and without the pres- 
ence of bacteria. But the most extensive research on 
this topic seems to have been conducted by Meissner, 
as reported by Eosenbach.* Since his object was to 
learn whether germs existed in living tissues, he 
avoided the use of any antiseptic agents which could 
destroy them, but observed the greatest care in trans- 
ferring his pieces from the animal just killed to 
flasks previously heated. By working in a clean 
room, using only instruments just heated, manipu- 
lating with the utmost quickness and delicacy, he 
succeeded in keeping his specimens free from putre- 
faction in the majority of instances. A most 
important lesson which his experiments taught, and 
which serves to explain the contrary results of other 
observers, is the fact that with increasing practice the 
number of failures became less, and he could at last 
preserve almost every specimen. The weight of 
Evidence is pretty conclusive, therefore, that the living 
healthy animal does not harbor bacteria in its 
tissues. 
Moreover, it has been shown that the bacteria of 
putrefaction are soon destroyed or eliminated if 
purposely introduced into the animal system. If they 
f. Chirurgie, Vol. XIII, p. 344. 80 
THE GERM THEORY OF DISEASE. 
be injected into the blood, and the animal does not 
die from the poisonous effects of some of the products 
of putrefaction, the blood rids itself speedily of these 
micro-organisms. If drawn, after the lapse of a few 
hours, and received in purified vessels it remains free 
from putrefaction, showing that no germs are left in 
it (Oheyne). In the struggle with the animal cells 
the common bacteria of putrefaction are overcome. 
But this is not true of all bacterial varieties. There 
are numerous micro-organisms, which find the condi- 
tions met* with in the animal system suitable to their 
existence, and can lead a parasitic life in the midst 
of the tissues. But this vegetation of parasites in 
the interior of the animal body is not a normal 
occurrence as far as the latter is concerned; some 
disturbance or other is always created thereby, and 
such parasitic bacteria constitute true disease germs. 
The bacterial origin of a disease can only be 
proven by the following observations. First, a char- 
acteristic bacterial species must always be found asso- 
ciated with the disease, and to an extent corres- 
ponding to the nature and degree of the disease. 
Secondly, it must be shown that the same disease can 
be reproduced in susceptible beings by means of the 
isolated parasites, freed from all animal matter 'or 
poisons. It is not an easy matter to furnish these 
proofs in the case of any disease; it requires 
thorough familiarity with the methods, and a critical 
spirit. In order to demonstrate the bacteria in the 
tissues, staining methods must be resorted to. It is 
only when the parasites form large colonies, especially 
in the interior of the vessels, that they can be seen 
by simply clearing the section with acetic acid or 
alkalies. For staining purposes the different aniline 
colors must be tested, since different bacteria react PATHOGENIC BACTERIA. 
81 
differently to such colors. Special complications in 
the staining process have been found necessary in the 
case of the bacilli of leprosy and of tuberculosis. 
Probably there exist yet many pathogenic varieties 
which we have not seen on account of the inability 
to stain them with present means. In the examina- 
tion of stained sections diffuse illumination by means 
of an appropriate condenser, is absolutely indispen- 
sable. Not all the colored particles seen are bacteria. 
Careless manipulation may give rise to precipitates. 
The granules found in many cells, in white blood-cor- 
puscles, and especially in the plasma cells of Ehrlich, 
resemble micrococci. The distinction between micro- 
cocci and other colored granules is absolute only, 
when by reason of their growth they are found in 
regularly arranged colonies. Of course the specimens 
should be taken either from the living subject or 
very soon after death, in order not to be misled by 
die bacteria of putrefaction invading the cadaver. 
Finally the absence of bacteria must not be inferred, 
when they are sought for and not found in an 
improper place, for instance the blood in some local 
disease, or some organ affected only indirectly. 
The only mode of isolating parasitic bacteria from 
die animal tissues is by means of cultivation of the 
former in a proper soil. The animal cells which we 
fransfer with them to the soil die at once, while any 
chemical poisons associated with them cannot multiply 
fike the living bacteria themselves. The implantation 
°f a trace of the first crop in a fresh soil, and a few 
Repetitions of this procedure, dilute any foreign 
matter adhering to the bacteria to such an extent as 
f° practically eliminate it. It is evidently of vital 
importance, that the bacteria sown should be the real 
parasites, and not merely accidental associates. It is, 82 
THE GERM THEORY OE DISEASE. 
hence, best to take the matter to be cultivated from 
the interior of the body, in preference to secretions on 
the surface, exposed to the germs of the air. A 
successful cultivation requires evidently, that the soil 
should be appropriate to the species examined. Most 
pathogenic bacteria cannot thrive as readily as the 
germs of putrefaction on a soil as simple as Pasteur’s 
or Cohn’s solution. In many cases they require a 
nourishing fluid closely resembling the blood itself. 
The successful cultivation of an isolated species, 
without the unwelcome admixture of other germs is. 
much facilitated by the employment of a solid soil 
after the fashion of Koch. 
The proof of a parasitic origin of a disease is only 
complete, when the same disease can be reproduced by 
inoculation with the cultivated bacteria. It is not 
sufficient that the animal gets sick in consequence of 
the inoculation; it must be affected with the original 
disease in question. A species of animals which can 
not take a certain disease can, therefore, not be used to 
prove the origin of that disorder. In this respect there 
are wide differences in different animals. Splenic fever, 
so fatal to herbivora, cannot be easily produced in car- 
nivora, and—it seems—never in the pig. A form of 
septicaemia common to the house-mouse cannot attack 
the field-mouse. Different species of animals constitute 
different soils for the bacterial parasites, and it is self- 
evident that a plant cannot grow in all soils. Some 
parasitic diseases of mankind cannot be transferred to 
any animal yet employed, for instance, gonorrhoea.. 
Again, in other cases, the same parasite produces a 
different reaction in different animals. The bacteria 
which give septicaemia to mice cause in rabbits but a 
local inflammation comparable to erysipelas. The sus- 
ceptibility of an animal species to a certain disease is. INOCULATION WITH BACTERIA. 
83 
sometimes a question of the quantity of disease germs. 
Both anthrax and tuberculosis are not readily communi- 
cated to dogs, except a certain number of the patho- 
genic germs be employed, while perhaps a single germ 
suffices for the invasion of the body of a rabbit. Prob- 
ably the number of disease germs is of importance also 
with reference to the variable individual susceptibility, 
especially in the natural infection, when undoubtedly 
much smaller quantities of germs enter the system than 
in experimental inoculation. The success of an inocula- 
tion with bacteria may depend also on the purity of the 
culture. For when we employ, instead of the isolated 
parasites, a mixture of different bacteria the pathogenic 
variety may be overpowered by its accidental associates, 
which by themselves are perhaps harmless to the animal 
body. Finally, the inoculation must be made in the 
proper place in order to succeed. Various germs can 
not enter with equal facility through all the gates of 
the organism. Thus the bacillus of malignant oedema 
can gain a foothold only in deep wounds and not in 
mere abrasions of the skin. The bacilli of symptomatic 
charbon are fatal when put under the skin, but nearly 
harmless when injected into the blood-vessels. Hence 
false conclusions should not be drawn when an improper 
mode of inoculation fails to lodge the parasites in the 
animal body. As an instance of such an error I might 
mention the experiments of Wolff, who concluded that 
bacteria were harmless to wounds, because abrasions in 
fhe skin of animals healed just as well, when covered 
with rotten material containing bacteria. The very fact 
that these wounds healed kindly ordinarily, although 
exposed to the germs of the air, dust, and material 
with which the animals come in contact, shows that the 
°pen surface of a wound does not grant germs a ready 
entrance into the system, at least in rabbits or guinea 8 4 
THE GERM THEORY OE DISEASE. 
pigs. Moreover, there is a real difference between the 
course of such wounds, as are unavoidably or intentionally 
exposed to bacteria, and those which are properly pro- 
tected against them, which fact Wolff overlooked. 
Having thus discussed what requirements must be 
insisted upon in order to admit the bacterial origin of 
any one disease, let us now pass in review the list of 
diseases, to which such research has been applied. It 
will be most convenient to begin with those instances 
which have been investigated more satisfactorily than 
others. 
ANTHRAX. 
The first and best known instance of a disease defi- 
nitely traced to the invasion of the body by vegetable 
parasites is splenic fever, also called anthrax, charbon, 
or—in the localized form usually seen in man, —malig- 
nant pustule. It is a disease occurring principally in 
cattle and sheep, but is inoculable in most domestic 
animals. 
In this disease rod-shaped bacteria were found in 
the blood, originally by Rayer and Davaine in 1850, 
and later independently of them by Pollender (1855) and 
Brauell (1857). Their vegetable nature was assumed, 
but not proven. Delafond (1860) seems to have been 
the first to suspect these bodies as the cause of the 
disease. Subsequently Davaine (1863) rendered this 
suspicion extremely probable, by showing that they 
were always present in the blood of this disease, that 
splenic fever could only be produced by inoculation 
with material containing them, and that those influ- 
ences which destroyed the “bacteridia” as he called 
them, deprived the blood of its special virulence. 
The absolute proof of their importance, viz.: the 
production of the disease by means of the isolated ANTHRAX. 
bacteria, lias since been furnished by Koch and re- 
peated by Pasteur and many others. 
As seen in the blood of an affected animal the 
bacillus anthracis consists of slender rods having a 
length of upwards of about three micromillimeters 
and dividing usually into segments, when they exceed 
six micromillimeters. Since the segmentation is not 
visible except on staining, we find in the fresh speci- 
men some few filaments, apparently undivided, as long 
as twenty micromillimeters. Its width, as Huber* has 
shown, varies somewhat according to the species of 
animal in which it lives —about 1 to 1.3 micromilli- 
meters. Its ends are square, or even slightly concave 
-—as seen when two segments adhere before separa- 
tion,—which shape characterizes this bacillus. It has 
no flagella and is motionless (except immediately 
after germination). As long as it grows in the bodies 
of living animals it assumes no other shape but the 
one described, and multiplies only by fission. But 
when cultivated outside of the body in blood or any 
other suitable soil it elongates into long undivided 
chains, or threads in which brilliant spores appear 
which are at last set free by the disintegration of the 
bacillary filament. The oval spores, when placed in 
proper soil, elongate at one end and change into grow- 
ing rods which then pass through the same vital cycle. 
The formation of spores is completed within about 
twenty-four hours at the temperature of the animal 
body. Cold retards this process and below 18° C. 
sporification is no longer possible. The other limit of 
temperature beyond which the production of seeds is 
checked is about 42° to 44° C., varying with the 
nature of the cultivating medium. 
The bacillus anthracis is easily destroyed. Desicca- 
*Deutche Med. Wodenschrift, 1881, p. 89. 86 
THE GERM THEORY OF DISEASE. 
tion kills it in a few days (or at the latest in a few 
weeks in larger masses not quite dry in the interior). 
A heat of 50° C. suffices for its destruction in twenty 
minutes. Want of oxygen is fatal to it in some hours. 
On the other hand the presence of oxygen in the 
form of ozone is harmless.* But while the developed 
form of this parasite is so easily killed, the spores 
offer a great resistance to damaging influences. They 
withstand permanent desiccation, or even alternate 
moistening and drying, deprivation of oxygen, like- 
wise any temperature below the boiling point (unless 
the exposure is very long). Time seems to have no 
effect upon their germinating power. No other patho- 
genic micro-organism can be as readily cultivated out- 
side of the body as the bacillus anthracis. Almost 
any animal juice, blood, broth, urine or aqueous humor 
will suffice as a soil, if only neutral or slightly alka- 
line, likewise the infusion of many vegetables and 
grasses. 
These researches into the biology of the parasite, 
mainly the work of Koch,f have established clearly 
how the disease spreads. Apart from the intentional 
inoculation the disease can be communicated by con- 
tact of any of the animal tissues or fluids which 
contain the bacilli, with wounds. As Davaine has 
shown the sting of wasps and other insects can trans- 
fer the virus from one animal to another. Man is not 
infrequently infected by handling animal material, like 
leather or wool, coming from diseased animals. In 
many cases such material is so old and dry, that it 
can no longer contain any living bacilli, but only 
spores. Probably the infection by means of the de- 
*Szpilman, Zeitschrift f. phys. Chemie. Bd. IV., p. 350. 
tCohn’s Beitraege z. Biologie d. Pflanzen, Bd. 11., Heft 11., p. 177, 
and Mittheil. aus d. k. Gesundheitsamte, p. 49. INFLUENCE OF TEMPERATURE. 
87 
veloped bacilli is a rare occurrence at the best on 
account of their destructibility. But where the dis- 
eased animal dies, the discharges from the nose, mouth, 
bladder and wounds all containing bacilli, impregnate 
the soil. If the temperature is only above 18° C. 
these bacilli soon develop spores, which then remain 
in the field almost indestructible and can infect any 
animals grazing there. Pasteur, who evidently over- 
tooked the importance of the discharges deposited on 
the surface of the soil, attributed an important role 
to earth worms in transporting the spores from the 
buried cadavers to the surface. But Koch has since 
shown that this ingenious hypothesis is unnecessary, 
ror at the depth at which animal cadavers are usually 
buried, viz.: half a metre or more below the surface, 
the temperature in most European countries does not 
I'ise above 18° C., and hence sporification would be 
impossible in the cadaver. Moreover, the want of 
oxygen would prevent the formation of spores at such 
a depth, and does indeed kill the developed bacilli 
within a short time. Hence we need not look for the 
contagion below the surface of the earth. 
Experience has shown, that the weather and the 
nature of the soil exert an unmistakable influence on 
the prevalence of anthrax. Warmth and moisture favor 
its occurrence, while those farms are most dreaded as 
“ splenic-fever districts ” which have an alkaline or 
calcareous subsoil and are either marshy or subject to 
occasional inundations. In some such localities the 
disease persists as a frequent epidemic, although 
‘Cadavers of diseased animals may never have been 
buried there. The explanation of these climatic and 
telluric influences is evident, since Koch has shown 
that the bacillus anthracis can vegetate outside of the 
body of animals under conditions actually occurring in 88 
THE GERM THEORY OF DISEASE. 
nature. In the terminology of modern pathologists 
the virus of this disease is both endogenous and ecto- 
genous. It can vegetate and multiply in the body of 
the victim, but it can also grow and increase outside 
of it. The bacillus anthracis will readily develop in 
many vegetable infusions. Such nutritive fluids it 
finds in swamps and in pools of stagnant water, in 
which dead plants are macerating, especially when the 
vegetable acids are neutralized by the alkaline constit- 
uents of the soil. At any temperature above 18° CL 
spores are formed, and when these almost indestruc- 
tible seeds have once been distributed (for instance by 
Hooding) throughout a field, the germs of the disease 
cannot be removed again from the locality by any 
means yet known. The secret of the persistence of 
the disease is the fact that the bacillus anthracis is 
not limited to a parasitic mode of life in the animal 
body, but can vegetate on the proper refuse, even 
where no animals exist. It is a plant indigenous to 
the soil of certain localities, passing but occasionally 
and accidentally into the body of animals. There is 
no evidence that the parasite is ever carried by the 
air into the animal system. 
The disease can be transferred to most animals 
commonly used for experimentation. Rodents are 
especially susceptible to it. Cats and dogs on the 
other hand often resist an inoculation, especially when 
not too young. According to Toussaint old dogs can 
be infected with certainty only by intravenous injection. 
Amongst the sheep, commonly the readiest victims of 
this disease, Chauveau found a certain species imported 
from Algiers, possessing an almost perfect immunity 
against it. The pig also seems to be unable to con- 
tract it. In man the inoculation through a wound 
produces at first only a local symptom—the malignant INOCULATION THROUGH WOUNDS. 
89 
pustule—from which he may recover without constitu- 
tional disease, on excision of the pustule or sometimes 
even spontaneously. Birds are not very liable to 
develop the disease on inoculation, though Oemler 
affirms that he has often succeeded in a variable 
percentage in chickens and other species. Pasteur on 
the other hand claims that under ordinary circum- 
stances the fowl cannot be inoculated, for the high 
temperature of its body—42° C—is not favorable to 
the development of the parasite. But on cooling the 
body of the fowl by immersing the legs in cold 
water, he could infect it successfully and could thus 
let the disease run its fatal course, or could enable 
the chicken to recover by allowing it to regain its 
normal temperature in time. The great importance of 
this experimental result is evident. It appears very 
suggestive as to the direction in which therapeutic 
endeavors should be made in parasitic diseases. But 
unfortunately Pasteur* does not communicate the 
details of his experiments, and does not even state 
how often he has made this observation. Hence Koch 
denies its accuracy, both because Oemler could inocu- 
late normal fowls (though not every time) and 
because the bacillus anthracis can yet grow at 42° C. 
Still Koch has not disproven Pasteur’s claims by any 
personal research. 
Gibierf has lately claimed that charbon can also 
be communicated to frogs (at least in some instances), 
but only when these animals are kept at a tempera- 
ture of 35° to 37° C. 
The bacillus anthracis can enter the system of a 
susceptible animal through almost any channel except 
the unbroken skin. As Buchner has shown even the 
*Comptes Rendus, 1878, No. 2. 
fComptes Rendus, 1882, vol. 94, p. 1605. THE GERM THEORY OF DISEASE. 
inhalation of dried bacilli is fatal to mice, thongh 
ordinarily this is not the mode of entrance of the 
parasite. The natural infection occurs almost wholly 
from the digestive tube, with the exception of occa- 
sional wounds and stings of insects. Toussaint* 
claims, that the lymphatic glands in the infected 
region indicate the point of entrance of the virus by 
their swelling. By means of this guide he has traced 
the origin of natural charbon to infection from the 
mouth in some twelve sheep and a couple of cows. 
Koch, however, in his latest workf disputes that the 
mouth is the usual starting point of the disease, but 
insists that in most instances the spores pass into the 
small intestines and there germinate in the alkaline 
contents, whereupon the bacilli penetrate through the 
intestinal wall. At any rate, this is the mode of 
infection in the so-called intestinal mycosis of man, 
-cases which cannot be diagnosed during life but 
which the post-mortem reveals as genuine anthrax. 
Like all infectious diseases, anthrax has a period of 
incubation. This varies in length with the size of the 
animal, as the theory of the nature of the disease 
clearly indicates. Bor in order to produce a disturb- 
ance the number of bacilli in the system must bear 
some proportion to the size of the invaded organism 
and the multiplication of the parasites is, of course, a 
question of time. Hence, while some twelve to eigh- 
teen hours elapse, before visible symptoms occur in the 
rabbit, the stage of incubation requires some two or 
three days in the case of a sheep. Moreover, this 
latent period depends on the number of the parasites 
introduced. The larger the quantity of virus injected, 
the quicker is the fatal number of parasites obtained. 
*Recherches experiment, sur la maladie charbonneuse* 1879. 
fUeber die Milzbrandimpfung, 1882. BACILLI IN THE BLOOD. 
91 
The intravenous injection o£ the blood of an animal 
afflicted with the disease reproduces characteristic an- 
thrax within some four or six hours, while on the 
other hand the inoculation of a few bacilli only pro- 
longs the period of incubation by one or more days. 
This accounts for the protracted course of the natural 
infection as compared with the quicker death from 
experimental inoculation. Tor in the natural infection 
of anthrax and other diseases the number of parasites 
entering the system is probably quite small. 
From the point of infection the bacilli pass to the 
nearest lymphatic glands, which by their swelling 
indicate the irritation caused by the growing parasites. 
It is only toward the end of the period of incubation, 
that the bacilli enter the blood in any appreciable 
number, and it is only some hours before death that 
the blood contains any large quantity of them. More- 
over, this varies in different animals. In mice there 
may be very few or even none in the circulating blood 
even at the moment of death, which accounts for some 
of the older incorrect statements regarding the occur- 
rence of splenic fever without the presence of the 
bacilli. The parasites are evidently arrested in the 
capillaries of most of the viscera, especially the spleen, 
where they continue their growth until they choke up 
these vessels completely. By appropriate staining 
Koch has shown that the “ natural’' injection by 
means of these bacilli demonstrates the topography of 
the capillaries more elegantly, than any artificial injec- 
tion. Toussaint has watched the growth of the parasites 
in the living omentum spread out under the microscope. 
Wherever an extravasation occurs the bacilli pass into 
the surrounding tissues. It is probably thus that they 
get into the secretions, which are all tinged with blood. 
In the case of pregnant animals the placenta offers a 92 
THE GEEM THEOEY OE DISEASE. 
barrier to the passage of the bacilli into the foetal 
blood, hence, as Davaine and others have shown, 
the foetus is as a rule not infected. But Strauss and 
Chamberland* have recently found that this is not 
invariably so, and that sometimes a few bacilli can be 
found in the foetal blood (of guinea pigs). 
It is not yet settled in what manner the growth of 
the parasite destroys the host’s life. The dark color 
of the blood even during life has led Pasteur and others 
to suppose that the parasites, which are known to have 
a strong affinity for oxygen, abstract this gas from the 
blood and thereby asphyxiate the animal in a slow 
manner. Still this view has not been proven experi- 
mentally. At any rate, the growth of so large a mass 
of parasites in the living blood-vessels cannot but injure 
the animal organism, be it by the abstraction of oxygen 
or nourishment, by the embolism of so many capillaries 
or by the formation of bacterial products poisonous to 
the victim. 
Anthrax is usually a fatal disease, at least in the 
herbivora. But, if the victim does recover it is not 
liable to contract the disease again. The first attack 
gives immunity against a return of the disease, at any 
rate in cattle and sheep. But this immunity does not 
occur in all animal species. Loeffler-j- quotes Oemler 
in proof of the possibility of repeated attacks of malig- 
nant pustule in man. In his own experiments he found 
that rats, which are not very susceptible animals, can 
be inoculated a number of times with either slight or 
no effect at all, and will still succumb at some later 
occasion. According to similar experiments 
(with mitigated virus) have since been made at the 
*Comptes Rendus, Yol. 95, p. 1290. 
tMittheil. aus. d, k. Gesundheitsamte, p. 156. 
jUeber d. Milzbrandimpfung. DOES THE FIRST ATTACK GIVE IMMUNITY. 
93 
laboratory of the German board of health on rabbits, 
guinea pigs and mice, showing that these animals also 
cannot acquire a perfect immunity. 
The immunity which cattle and sheep obtain by a 
first non-fatal attack of charbon suggested researches 
in the hope of producing the disease in a modified 
form. For Pasteur had just then shown that in an- 
other infectious disease chicken-cholera the virus 
can be so mitigated as to cause only a mild attack, 
which secures immunity against a subsequent return 
of the disease. In short he had proven the possibility 
of transforming a disastrous virus into a comparatively 
harmless “vaccine” matter, Toussaint was the first to 
attempt this in the case of anthrax. He heated blood 
of anthrax to 55° C. for ten minutes or filtered it 
through several layers of filter paper, or added one 
per cent, of carbolic acid and claimed to reduce 
thereby its virulence, so that an injection of it gave 
rise only to a slight disturbance, followed by immu- 
nity against the disease. But a repetition of his ex- 
periments by Loeffler proved them to be unreliable, if 
not fallacious, which is also the criticism of Pasteur on 
them. Pasteur himself soon afterwards devised a 
method by which the desired result could be accom- 
plished.* In the case of the chicken-cholera parasite 
Pasteur had reduced its virulence to animals by pro- 
longed exposure to the air without change of soil. 
This procedure could not be utilized in the case of 
the bacillus anthracis on account of the speedy transi- 
tion of the latter into the state of dormant vitality, 
viz.: by the formation of spores. But sporification is 
prevented by a temperature which by itself does not 
kill the bacilli. Kept permanently at a temperature 
communications to the Paris Academy of Sciences, 1881 
and 1882. THE GERM THEORY OF DISEASE. 
of 42°-43° C. in neutralized chicken-broth, this bacil- 
lus does not produce spores according to Pasteur. 
Under these circumstances its vitality is gradually 
lowered and within a period of one month it dies. 
Inoculated in animals during any time before its 
ultimate death the bacillus will still catfse anthrax, 
but with a severity proportionate to the vitality of the 
micro-organism. The disease can thus be obtained in 
any desired degree of intensity. The feeble attack of 
charbon from which the animal recovers, confers upon 
it an immunity somewhat proportionate to the severity 
of the experimental disease. The immunity granted 
by a single attack of the milder type is not absolute, 
however. But it can be made so by a subsequent 
inoculation with a more active virus. Pasteur soon 
extended his experiments to entire hocks of animals 
and proved on a large scale that cattle and sheep, 
which have been “vaccinated” twice at intervals of 
twelve days with the attenuated bacillus anthracis can 
now resist successfully an inoculation with the most 
active anthrax material. He has cultivated the para- 
site in the above described manner on a large scale 
and puts into the market a “first vaccine” as the 
result of twenty-four days’ attenuation, while the “sec- 
ond vaccine" is only enfeebled by a cultivation of 
twelve days at a high temperature. The power of 
reproduction of the enfeebled parasite is not materially 
lessened, nor are its appearances altered. Like the 
original bacillus anthracis it produces spores at a 
suitable temperature, but these spores and the fresh 
crop of bacilli developed from them have only the 
virulence of the enfeebled virus. Their power of 
struggling with the animal cells has been permanently 
diminished in proportion to the length .of time, during 
which they had been cultivated under circumstances PROTECTIVE VACCINATION. 
95 
unfavorable to them. The inoculation is performed by 
injecting under the skin a few grains of the chicken- 
broth containing the mitigated bacilli. The disturb- 
ance which they produce in the animal is simply a 
more or less severe fever. These discoveries have 
opened up an entirely new prospect in the manage- 
ment of infectious diseases and their importance is 
simply fundamental. 
Pasteur has published numerous statistics .of the 
wholesale employment of this protective vaccination. 
His most recent report refers to the results obtained 
in the department d’Eure et Loire.* Altogether 79,392 
sheep were vaccinated, amongst which number the 
loss by splenic fever was reduced to 0.65 per cent, 
in the course of the past year. In former years the 
average loss had been 9.01 per cent., though during 
the past year the dampness of the season would prob- 
ably have given rise only to some 3 per cent, of loss, 
as calculated on the basis of former experience. In- 
deed, in those herds in which only a part of 
the animals were protected by vaccination the loss 
amongst 1,659 unprotected sheep was only 3.9 per 
cent, while of 2,308 vaccinated animals but eight 
(0.4 per cent.) died of anthrax. Four thousand five 
hundred and sixty-two cattle had also been vaccinated, 
of which but 0.24 per cent, succumbed to the disease,, 
while former years had given a loss of 7.03 per cent. 
Very serious objections, however, have been urged 
by Kochj* against the practical application of Pas- 
teur’s researches. He does not underrate their great 
theoretical value, but denies that they are complete 
enough for immediate practical utilization. He points, 
out, first of all, that in other animals but cattle and 
*Comptes Rendus. Vol. 95, p. 1250. 
fUeber die Milzbrandimpfung. 96 
THE GERM THEORY OE DISEASE. 
sheep even the severest non-fatal attack of anthrax 
does not confer immunity. The “attenuated virus” 
which Pasteur puts into the market for the vaccina- 
tion of herds, Koch claims is not always of the 
proper strength; sometimes it is so feeble as to fail 
in its purpose of protecting the animals, while in 
other instances it was virulent enough to produce up to 
10 or even 15 per cent, of loss by the vaccination itself. 
In his repetition of Pasteur’s experiments he found that 
virus most suitable for the first vaccination of sheep, 
which still killed mice on inoculation, but failed to 
give anthrax to guinea-pigs. The second vaccination 
is just severe enough to grant immunity against 
further inoculation, and not intense enough to kill 
the sheep, if the bacilli are only enfeebled to such 
an extent as not to infect the rabbit, but can still 
vegetate in and destroy the guinea-pig. But the 
most fatal objection which Koch raises is the state- 
ment that the immunity produced by the protective 
vaccination refers only to the inoculation throuarh 
o 
wounds and not to the natural infection with anthrax 
through the intestinal canal. If this be reallv so— 
and both the observations in France, at Kapuvar 
(Hungary) and .at Packisch (Saxony), as well as 
Koch’s experiments prove that the immunity is at 
least not absolute—then the practical value of 
Pasteur’s vaccinations is as yet chimerical, Koch 
tested the immunity of eight sheep vaccinated twice 
according to Pasteur’s directions by inoculating them 
with material from an animal just dead of anthrax. 
One of the victims died, the other . seven resisted 
successfully, and had thus passed through three 
vaccinations. Twelve days later they were fed with 
spores cultivated from the material used for the last 
inoculation, in consequence of which two succumbed NATURAL MODE OE INFECTION. 
97 
to the infection. The “natural” mode of infection is 
therefore the most dangerous to the animal and 
cannot be absolutely prevented by protective vaccina- 
tion. That a difference does exist betAveen infection 
from a wound and the entrance of the parasite 
through the alimentary canal, is evident indeed from 
various experiments on cattle, animals most prone to 
the natural infection. In the different inoculations 
made by Pasteur on French farms, and by his assist- 
ant in Kapuvar (Hungary), very few of the non-pro- 
tected cattle died from the effects of the virulent 
anthrax material, and not even all took sick. Similar 
observations have also been made by Chauveau,* and 
yet all cattle-raisers dread the so-frequent natural 
infection. 
It is likely that the virulence of the bacillus 
anthracis, its power to struggle successfully with the 
animal cells, can be reduced in different manners. 
Pasteur’s assertion that it is the influence of the 
oxygen in his mode of cultivation, which enfeebles its 
vitality is not really supported by any proofs. Koch 
attributes the u attenuation ” rather to the high tem- 
perature, for the length of time necessary to deprive 
the bacillus of its virulence varies in inverse propor- 
tion to the temperature at which it is kept. Tous- 
saint’s original claim that the anthrax virus could be 
to a “vaccine” by heating it to 55° C., it is 
true, was not confirmed by the Berlin experimenters, 
but they made use only of rodents and not the 
animals—sheep—which Toussaint himself employed. 
Chauveau-I* has since repeated the experiments on 
sheep, and finds them correct, if but both the tem- 
perature and the time of exposure be taken into 
*Comptes Rendus, 1880, Yol. 90, p. 648. 
tComptes Rendus, 1882, Yol. 94, p. 1694. 98 
THE GEEM THEOEY OE DISEASE. 
account. By enclosing the blood containing the 
bacilli in very thin closed glass pipettes and immers- 
ing them entirely in the water-bath, he found that 
even 50° C. sufficed to kill the parasite if the 
exposure lasted twenty minutes. During this period 
its virulence diminishes gradually, so that when inoc- 
ulated it produces a modified form of anthrax, of a 
severity inversely proportionate to the length of time 
it was heated. The disease modified by this mode of 
procedure was found to be equally efficient as a 
protection against subsequent attacks as that produced 
by Pasteur’s method—at least as far as the experi- 
mental inoculation under the skin was concerned. 
A difference between Pasteur’s and Chauveau’s obser- 
vations is the fact, that the bacilli heated to 50° C. 
do not multiply as rapidly, when subsequently kept 
at a suitable temperature as they did prior to this 
exposure. Their power of reproduction is enfeebled 
like their virulence. In what manner the influence of 
heat or other damaging agencies can reduce the viru- 
lence of the parasite has not yet been solved. As 
long as we are ignorant of the nature of the attack 
and the defense in the struggle between parasites 
and animal tissues neither the above question, nor 
the query, as to the essence of the immunity against 
a return of the disease can be answered. 
In this connection I must refer briefly to some re- 
searches by Buchner.* His object was not merely to 
modify the properties of the bacillus anthracis, but to 
prove its identity with the common hay bacillus, an 
organism harmless to animals. He wished to demon- 
strate the truth of Naegeli’s view, that one bacterial 
variety can be converted into another by adaptation to 
the conditions of nutrition. For this purpose the 
*Sitzungsberichte der Muenchener Akademie, 1880. Heft 111. REDUCTION OF VIRULENCE. 
99 
bacillus anthracis was cultivated in a solution of meat 
extract and transferred into a fresh soil from day to 
day, while oxygen was freely supplied by shaking 
the vessel. In the course of thirty-six generations its 
virulence was so reduced, that it required very large 
quantities of the fluid to produce anthrax in mice. 
The cultivation during about half a year deprived it 
entirely of the power of vegetating in the animal 
body. Conversely the genuine hay bacilli were grown 
in fresh rabbit’s blood after adaptation to an alkaline 
soil by cultivation in egg albumen. Nourished in this 
manner they ultimately acquired virulence and pro- 
duced in mice a disease like anthrax. But these 
results have been severely criticized by Koch.* Since 
Buchner did not use staining methods he could not 
prove at all the identity or non-identity of one or the 
other species. For minor differences in form cannot 
be recognized in the fresh specimen. Koch claims 
further, that there is no positive proof that the micro- 
organisms met with ultimately in either series of ex- 
periments were the result of a transformation, while 
there is reason to believe that they got there by sub- 
stitution. In view of the importance of these results 
—if true—Koch demands absolute security against the 
accidental admission of other germs, which guarantee 
Buchner has not given. In Koch’s experiments the 
bacillus anthracis was cultivated in one hundred and 
fifteen successive generations on a solid soil (potato- 
slice) without losing its virulence to any extent. Koch 
Points out also that the virulent bacillus supposed to 
fiave resulted from a gradual transformation of the 
hay bacillus, may not have been the bacillus anthracis, 
bat another parasite the germs of which are very 
freely disseminated throughout nature. The disease 
*Mittheilungen, etc., p. 68. 100 
THE GEEM THEOEY OE DISEASE. 
this produces malignant oedema—-cannot be distin- 
guished from anthrax in mice, although there is quite 
a difference in larger animals. These remarks of 
Koch’s apply equally to the experiments of Koehler,* 
who also claimed, that he had transformed the bacillus 
subtilis into a virulent parasite by continued cultivation 
in blood. 
Buchner, however, has since published new 
corroborative of his former results. But even in these 
I can detect a serious flaw, viz.: the use of non-steril- 
ized fluids. The bacillus anthracis was sown in solu- 
tions of meat-extract containing an addition of finely 
subdivided yolk of egg with some free alkali. By 
cultivation in this fluid continued for a few days it 
changed in appearance and properties. It lost its vir- 
ulence to animals, it grew no longer in the form of 
flakes at the bottom of the fluid, but was diffused 
throughout the solution or even formed a scum on the 
surface like the true hay bacillus. Moreover, it ac- 
quired a distinct though sluggish mobility. In short, 
Buchner claims that he can thus transform the anthrax 
parasite through a series of intervening steps into the 
hay bacillus. Though these later experiments appear 
more precise than his former ones, they still lack the 
necessary stamp of scientific accuracy to be accepted 
without further confirmation. 
An affection the nature of which has been as well 
investigated as that of anthrax ought to be a “test 
disease” for therapeutic action. But unfortunately 
nothing can be done as yet for the cure of this dis- 
ease. When it remains localized at first, as in man, a 
sufficiently early excision of the pustule stops the 
progress, though a spontaneous recovery may also 
*Der Heupilz, etc. Inang. Hiss. Goettingen, 1881. 
tSitzungsberichte der Muenchener Akademie, 1882. Heft. 11. CHICKEN CHOLEEA, 
101 
'occur, but when the bacilli have once invaded the 
blood-vessels, we can do nothing more to aid the ani- 
mal tissues in their struggle. Having learned the 
remarkable antiseptic properties of corrosive sublimate, 
Koch has tried its use in experimental anthrax. Since 
it interferes with tile growth of the parasite when 
present to the extent of one part in 600,000, and 
arrests the development completely in the strength of 
one part in 330,000, a sufficient quantity can be injected 
into animals to demonstrate its antiseptic property 
without killing them. .But the introduction of 0.5 to 
1 milligram of corrosive sublimate under the skin of 
guinea pigs weighing 600 to 700 grams influenced 
neither the previous nor the subsequent inoculation 
with the bacillus anthracis. Probably the mercurial 
salt enters into new combinations with the animal 
fluids, which are not equally destructive to the parasite. 
CHICKEN CHOLEEA 
is a second instance of a disease traced to the 
invasion of the body by bacteria in a manner beyond 
dispute. It is an affection peculiar to fowl, though 
transferable to other birds and even to some mam- 
mals. The most striking symptom is somnolence, 
which augments up to the death of the animal 
occurring in from one to three days. The autopsy 
shows as the most striking lesion a violent inflamma- 
tion of the intestines. In this disease micro-organisms 
had been seen by Moritz, Perroncito and by Toussaint, 
Ant their significance has been mainly proven by 
Pasteur* by cultivation, isolation and inoculation of 
the parasites. He describes them as small “vibrios” 
*ln several communications to the Paris Academy of Sciences in 
1880 and 1881. 102 
THE GERM THEORY OF DISEASE. 
of the shape of a figure 8, in other words diplococci, 
but gives no further details of their appearance. 
They abound in the blood and tissues of the diseased 
fowl. They are contained in the evacuations of the 
animal and pass thus from one to another, entering 
through the alimentary canal. Artificial inoculation,, 
however, can be made through any wound. 
The parasites grow readily in neutralized (and 
sterilized) chicken-broth, but not at all in simpler 
solutions like urine or yeast decoction. In fact 
Pasteur uses the latter fluid, known as a good soil for 
many bacteria, as a test for the purity of his 
culture. For while the disease-germs do not grow in 
it, any accidental bacterial “impurities” will readily 
develop there. Chicken-broth is rendered turbid in 
some hours by the cholera bacteria, but the growth 
ceases about the fourth day (at the proper tempera- 
ture), whereupon the parasites settle to the bottom 
in the form of minute separate micrococci. Pasteur 
has traced this limitation of development to exhaus- 
tion of the soil, and not to the excretion of products 
injurious to the parasites. For when he filtered 
them off through a layer of plaster of paris, and 
thereupon evaporated the chicken-broth at a low tem- 
perature in the vacuum, the re-solution of this residue 
in a fresh solution did not render the fluid unfit 
as a soil for another crop. Pasteur tested also the 
effect upon animals of the fluid in which the bacteria 
had grown, but from which they had been removed 
by filtration. He found that the injection of this 
fluid in the proper quantity could produce the prin- 
cipal symptom of the disease, viz.: somnolence, from 
which, however, the chicken recovered in some 
hours. But this was not the disease, not an infection, 
simply a temporary poisoning by one of the bac- MITIGATED VIRULENCE. 
103 
terial products. Evidently tire parasites secrete cer- 
tain substances, both in the animal body and in the 
cultivating flask, which exert a soporific effect upon 
fowls. The blood of the animal thus poisoned, con- 
tains no micrococci and is not infectious. 
Inoculation, however, of the cultivated parasite re- 
produced the disease in all its virulence, no matter 
how often it had been transplanted from one flask to 
another. In guinea-pigs the inoculation provoked 
only a localized abscess without further impairment of 
the animal’s health, but the pus of this abscess 
contained the parasite in its unaltered virulence to 
fowls. In the rabbit, however, a constitutional fatal 
disease is produced, which Toussaint* claims is but a 
form of septicaemia. Though Pasteur denies this, it 
seems to me but a quibble about words, as long as 
neither affection is absolutely characterized by any 
local lesion. 
The special interest in chicken cholera centers in 
Pasteur’s discovery how to modify and mitigate the 
virulence of the parasites. It was the first experi- 
mental proof, that “ the virus ” of a disease can be 
altered in strength. Pasteur observed, that while the 
parasite retained all its properties, when kept in the 
state of vegetation by frequent change of soil, its 
prolonged sojourn in an exhausted soil enfeebled it. 
When the exhaustion of the chicken-broth prevented 
it from growing any longer, its vitality began to fail 
in proportion to the length of time. When generation 
succeeds generation the influence of time is not felt, 
but when the growth ceases the micro-organism ages. 
In the course of some nine months it dies. Pasteur 
attributed this reduction of vitality to the influence of 
ihe atmospheric oxygen. Por when he sealed his 
*Comptes Rendus, 1881, Vol. 93, p. 219. 104 
THE GEEM THEOEY OF DISEASE. 
vessels hermetically, time seemed to exert no influence 
upon the vitality o£ these parasites. 
The inoculation of fowls Avith the ageing parasite 
produces a modified disease, the severity of Avhich 
diminishes with the time the micro-organism has been 
kept in an unchanged soil. The attack becomes less 
fatal to the animals and in its milder form amounts 
simply to a localized necrosis of the muscle AAdiere 
the inoculation is made. A muscular sequestrum is 
formed, which is removed by slight suppuration. In 
the mildest form produced by means of the most 
“ attenuated ” virus even the local lesion is but Arery 
slight, and the animal always recovers. After the 
parasite has once attained a certain degree of attenu- 
ation, it can be kept at that standard of virulence by 
further cultivation in a fresh soil, if only transferred 
to a neAV flask as soon as it has exhausted the first 
solution. If allowed to remain again in one and the 
same fluid without change, its vitality is further 
reduced. On the other hand Pasteur could again 
augment its virulence by cultivating it in the body of 
animals, which it is yet capable of destroying. When 
the virus has ceased to be fatal to foAvds it can still 
kill the more susceptible sparrow, especially when but 
a feAV days of age. By thus passing the parasite 
through the body of a young sparrow to an old 
sparrow and thence to a chicken it regains again suffi- 
cient virulence to struggle successfully with the fowl’s 
tissues. 
A chicken which has recovered from an attack of 
cholera is no longer susceptible to the disease. The 
parasite, which has once been overcome by the 
animal’s body cannot gain a foothold a second time 
though a more virulent virus may yet affect the 
animals. In other Avords the immunity granted by a IMMUNITY BY EEPEATED VACCINATION. 
105 
mild attack of tlie disease is not absolute. But it 
can be made so by repeated vaccination. Pasteur 
claims, indeed, that the immunity can be acquired 
by the animal without any suffering. For by choos- 
ing the most attenuated parasite for the first inocu- 
lation the animal is scarcely affected. Though it 
would yet succumb to the introduction of the most 
powerful virus, it can, however, withstand without 
danger a second vaccination with a - medium grade of 
parasites. This second, or at the most a third inoc- 
ulation with more virulent material gives it thence- 
forth absolute immunity against the disease without 
any of the attacks having been severe. 
I have not been able to learn whether Pasteur’s 
vaccinations have yet been practiced on any extensive 
scale for combatting this scourge of the barnyards. 
But he has also indicated another plan of exterminat- 
ing the disease which seems more economical. The 
parasite is conveyed from chicken to chicken mainly 
in the excretions which become mingled with the 
food. The micrococcus can be readily killed by 
dilute acids, one part of sulphuric acid in a thousand 
of water being sufficient for this purpose. Hence by 
removing the infected and diseased animals and flood- 
ing the grounds with such acidulated water the source 
of infection is taken away. 106 
THE GERM THEORY OF DISEASE, 
LECTURE Y. 
Surgical Infections. Aseptic Wounds.—Suppuration.—Abscesses.— 
Furuncles. Osteomyelitis. Pyaemia. Decomposition of Pus.. 
—Traumatic Fever. Putrid Poisoning. Septicaemia. 
SURGICAL INFECTIONS. 
Under this, heading it may be convenient to group 
together a number of disorders, which may occur as 
complications of open wounds. This classification is 
of course an arbitrary one. For the only common 
bond of union in the nature of these diseases is the 
fact, that they are due to germs, which usually enter 
the body through wounds. The scarcity of these 
affections in certain localities and their prevalence in 
others when once started there, suggested the view to 
former surgeons, that they took their start in some- 
thing in the air entering the wounds. Indeed this 
explanation forces itself upon the observer on reflect- 
ing upon the invariable benignant course of wounds 
not in communication with the air, i. e., fractures of 
bones and ruptures of soft parts without destruction 
of the continuity of the skin. This observation 
naturally led to the introduction of subcutaneous- SURGICAL INFECTIONS. 
107 
surgery, which, wherever applicable, produces wounds, 
that heal as kindly as those not extending to the 
surface of the body. But the credit of having clearly 
recognized that the “ something ” in the air so dan- 
gerous to wounds, are living beings, bacteria or their 
germs, and that it must be the aim of the surgeon 
to exclude these from the wound, belongs to Joseph 
Lister. Just prior to his own studies on wounds, 
Pasteur had demonstrated in the most conclusive 
manner, that all putrefaction is due to micro-organ- 
isms, and that the germs of these beings are dissemi- 
nated throughout the air. It is an evident surgical 
observation that the occurrence of putrefactive 
processes in wounds retards their healing. It had 
been shown, moreover, by numerous experimenters, 
that the injection of putrid substances into the bodies 
of animals produces disorders resembling the compli- 
cations of wounds most dreaded by the surgeon, viz: 
progressive inflammations and septicaemia. Starting 
from these premises, Lister began experimenting with 
various forms of dressings for wounds, with the 
intention of keeping out the germs of the air, and to 
destroy them if they had gained access. For this 
purpose antiseptic substances—principally carbolic acid 
—were employed. Lister does not claim to have 
been the first to employ carbolic acid in wounds, but 
in spite of all attempts to belittle his methods he 
was the first to use carbolic acid loiih the distinct aim 
of making the dressing a barrier to the entrance of 
germs. His methods were not born complete, but 
were more and more perfected in the course of pains- 
taking observations. Lister does not seem to have 
made many microscopic observations of wounds with 
reference to the presence of germs, he acted rather 
with a happy intuition on the basis of the results of 108 
THE GERM THEORY OE DISEASE. 
liis predecessors. His own practical results, however, 
have more than justified his anticipations. They have 
brought us to the threshold of a new era in surgery. 
The surgeon of yore did his best in the performance 
of the necessary operation, but the results following 
his wounds he could not control. The surgeon of 
to-day, however, is responsible for the course of the 
wound he inflicts. Any untoward accident starting 
from the wound is due to his want of care. 
A wound which follows a truly aseptic course, i. e., 
from which germs are wdiolly excluded, is not a source 
of danger to the organism, provided it does not 
destroy life directly, by involving some organ of vital 
importance. Such an aseptic wound is almost pain- 
less; its edges are not red, inflamed or swollen. If 
there is any discharge at all, it is only an oozing of 
clear fluid, for the very appearance of pus indicates, 
that it is not wholly aseptic. The wounded surfaces 
will invariably grow together, if they can be put in 
contact, while if a gap exists, this is filled up by 
granulations without any other disturbance of the 
wound. No constitutional disturbance is created by 
such a wound. If fever exists at all, it is very slight 
and not accompanied by any interference with the 
general health. The occurrence of such a mild fever 
without disturbance of the well-being of the patient— 
termed by Yolkmann aseptic fever—is not indicative 
of the presence of germs in the wound. It is prob- 
ably due to the absorption of extravasated blood. 
This description of an ideal wound, is not a crea- 
tion of the fancy; it applies accurately to every wound 
successfully protected by a typical Lister dressing, or 
some other thoroughly aseptic mode of treatment, for 
instance by the application of iodoform. lYhenever a 
wound pains, is inflamed, secretes pus and produces ASEPTIC WOUNDS. 
disturbance of the health, the dictates of antiseptic 
surgery have not been carried out. It is not the loss 
of continuity which causes the local disturbance or 
the constitutional disease, but it is the vegetation of 
bacteria in the wound which proves so disastrous. 
The truly aseptic wound, even if of considerable 
magnitude does not annoy the patient as much as 
does a scratch on your finger, unheeded by most of 
you, yet appealing to your attention by reason of the 
uncomfortable itching, and the tenderness—slight 
though it be—in its vicinity. The faint redness of 
the edges of such a scratch indicates that the surface 
of this miniature wound is irritated by “something.” 
Although I do not know of any direct observations, I 
have no doubt that this “something” is the vegeta- 
tion of bacteria in, and under the scab. Tor Koch 
found, that even the track of the hypodermic needle 
remains visible in the tissues, by reason of the 
growth of bacteria along this capillary channel.* 
The presence of bacteria is never quite indifferent 
as far as the healing of a wound is concerned. Yet 
since there are different species of bacteria the amount 
and nature of the disturbance depends upon the 
variety present. Cheynef found a micrococcus, the 
dimensions of which he does not detail, occasionally 
in wounds which apparently followed an aseptic course. 
Its presence may be indicated by a sour smell, but it 
does not seem to irritate the wound perceptibly. Mi- 
cro-organisms had also been found formerly in some 
aseptic wounds by Kanke and by Schueller, but the 
results of these observers are less accurate, since 
they did not use any staining methods in order to 
determine the form of the bacteria. Moreover, doubts 
*Mittheilungen a. d. k. Gesundheitsamte, p. 118. 
jAntiseptic Surgery, chap. XII. 110 
THE GEKM THEORY OF DISEASE. 
are permissible, whether these authors dealt with com- 
pletely aseptic wounds at a time, when antiseptic sur- 
gery was a comparatively new feature in Germany. 
But according to the observations of Cheyne on Lis- 
ter’s patients the majority of aseptic wounds harbor no 
bacteria whatever. 
When suppuration occurs it is always due to some 
irritation of the wound. But it cannot be said that 
pus is produced only through the action of bacteria. 
It is, on the contrary, quite likely that the presence of 
any chemical substance sufficiently irritating leads to 
suppuration. Recently Uskoff* has attempted to learn 
whether suppuration is invariably accompanied by bac- 
teria. In order to decide this point injections of 
different fluids were made under the skin of animals, 
and if any suppuration followed, the pus and sections 
from the inflamed tissues were examined microscopic- 
ally with Koch’s mode of illumination after staining. 
Fluids innocuous by themselves, like water or milk, 
produced abscesses only when injected repeatedly in 
large quantities. In such pus micrococci were invari- 
ably found. The fluids had been heated, but the 
author himself doubts his success in sterilizing them. 
Possibly the bacteria entered through the wound 
made by the needle. Orthmanf has just published a 
repetition of these experiments, in which he learned that 
the injection of non-irritating fluids—if performed with 
strict aseptic precautions—never causes abscesses, no 
matter how large the quantity. But when irritating 
substances like turpentine or croton oil were applied, 
the abscesses which followed did not contain any bac- 
teria, nor were these found in the surrounding tissues. 
Hence it is proven, that suppuration follows any suf- 
*Yirchow’s Archiv. f. path. Anatomie, Vol. 86, p. 150. 
tYlrchow’s Archiv, Bd. 90., p. 549. SUPPURATION—ABSCESSES. 
ficient irritation of tlie tissues, be it by the growth, of 
certain bacteria, or by the presence of any irritant 
chemical substance. 
It is quite questionable whether mechanical irrita- 
tion alone suffices to produce suppuration. At any 
rate it is well known, that foreign bodies can remain 
within the tissues without causing purulent inflamma- 
tion, provided only they contain no germs. Suppura- 
tion is likewise not the inevitable consequence of the 
presence of a dead tissue in the interior of the body. 
Thus obliteration of the artery of the testicle, or of the 
kidney, causes death of these organs, but if bacteria 
be excluded the dead tissue is gradually absorbed 
without suppuration. Occasionally the flaps of an 
aseptic amputation wound mortify from insufficient blood 
supply, but no further disturbance is caused by this 
accident if the antiseptic dressing fulfills its purpose. 
It has likewise been learned in various recent patho- 
logical studies, that bits of tissue hardened in alcohol 
can be put under the skin, or into the peritoneal cav- 
ity, with antiseptic precautions, and are absorbed there 
without producing inflammation. 
SUPPURATION 
can be caused, however, by the presence of certain bac- 
teria in the tissues, as has been definitely demonstrat- 
ed by Ogston.* In 100 instances of acute abscesses, 
previously unopened, this observer never failed to find 
micrococci in the pus. These organisms, of various 
sizes, from to TTVo a millimeter, were united 
either in chains or in groups. The mode of group- 
ing seemed to indicate a difference in the species, for 
it was reproduced on cultivating the micrococcus either 
Medical Journal, March 12th, 1881. 112 
THE GERM THEORY OF DISEASE. 
in or outside of the body. But no difference could 
be detected between the action of the chain or the 
cluster form. The number of microccoci present in 
the pus varied immensely in different instances. Ogs- 
ton gives the extremes as 900 to 45,000,000 of micro- 
cocci per cubic millimeter of pus, though his counting 
method does not deserve much confidence. The mi- 
croccoci were mostly found in the fluid, but sometimes 
in the pus cells. They possessed an apparently active 
vital movement. In stained sections of the tissues 
around the abscess, coccus-infiltration was observed. 
In the pus coming from catarrhal mucus membranes 
the same organisms were found. They were likewise 
never absent in the pus of ulcers and suppurating 
wounds (96 observations), and indeed their number 
was proportionate to the intensity of the suppuration. 
Whenever a wound smelled suspiciously other bacteria 
were also present in large numbers. In thirteen chronic 
abscesses, however, no micro-organisms were found by 
means of the staining methods and Abbe’s condenser. 
Whether they had been there originally the author does 
not try to decide. 
The injection of the pus from the chronic abscesses 
proved harmless to animals. It was absorbed without 
reaction. Similarly innocuous was the injection of pus, 
the microccoci of which had been killed by the addi- 
tion of an equal quantity of a 5 per cent, solution of 
carbolic acid, or by exposure to 55 °C. Pus, how- 
ever, of acute abscesses, containing living micrococci, 
invariably produced disastrous consequences, when in- 
jected under the skin of guinea-pigs and mice. It 
was only when less than of a minim was employed, 
that no reaction followed. Any larger quantity pro- 
duced symptoms of blood-poisoning. The animals 
refused food, cowered down and were listless, but usu- THE MICROCOCCI OF PUS. 
113 
ally recovered after the lapse of from five to seven days. 
The blood contained numerous micrococci during their 
illness, but not after their recovery. The spot, where 
the pus had been injected became red and swollen, 
and within a few days an abscess was formed, in the 
pus of which the micrococci existed in large numbers. 
These parasites were also seen growing in the midst 
of the surrounding tissues, upon which they seemed 
to exert a destructive influence, for the tissues were 
more waxy in aspect than normally. But by the 
time the growth of the abscess was checked and it 
became surrounded by a wall of granulation tissue, 
this seemed to act as a barrier to the further invasion 
of the tissues by the micrococci. On the inner sur- 
face of the abscess-wall they formed a thin, not con- 
tinuous, layer. 
Ogston’s attempts to cultivate these micrococci out- 
side the body were at first unsuccessful. Although he 
used as soil a variety of fluids the micro-organisms did 
not grow at all—or at least not actively—in any of 
them. He attributes this to the fact that these beings 
are anaerobes—in the sense of Pasteur—and cannot 
thrive in the presence of free oxygen. In confirma- 
tion of his view he states that the micrococci growing 
on the surface of wounds exposed to the air, do 
not produce inflammatory reaction with such certainty, 
when injected under the skin, as does the pus of 
closed abscesses. Cheyne has since doubted the cor- 
rectness of this view, because he has sometimes suc- 
ceeded in growing the micrococci from abscesses in 
cucumber infusions. He is of the opinion, that they 
did not grow in Ogston’s experiments, because they 
are often dead in the pus, when an abscess is opened. 
But since Ogston states, that the micrococci possessed 
active movements, this objection is not valid. Besides 114 
THE GERM THEORY OE DISEASE. 
Cheyne seems to have made use o£ thicker strata of 
fluid than Ogston, and the latter states that the 
micrococci do sometimes grow in the depth of the cul- 
tivating solution. Moreover Ogston did succeed in 
cultivating these bacteria away from the air in the 
interior of eggs, and the micrococci which had grown 
successively in two eggs were as virulent to animals as 
the original pus. 
These researches establish definitely, that suppuration 
is almost always due to the growth of a certain 
micrococcus. It is easy to understand how this 
parasite can obtain access to wounds, especially when 
we consider, that its entrance into them can be pre- 
vented with certainty by the antiseptic precautions of 
Lister. Though the influence of the air may enfeeble 
the parasite in the pus on the surface, it cannot reach 
it in the interior of the tissues, which it invades. 
There its virulence can only be checked by the resis- 
tance of the living cells of the body. This resistance 
shows itself both in the limitation of the spreading 
of an abscess, and in the harmlessness of injections 
of minute quantities of pus. It is not so clear how 
the parasite gets into the system in order to produce 
an abscess. There is no evidence that it ordinarily 
reaches the locality where it grows, through the circu- 
lation. It is more likely that the micrococcus enters 
from some surface through a slight abrasion, for ob- 
servant surgeons can frequently trace abscesses to such 
overlooked scratches. 
It is not unlikely that other bacteria besides the 
micrococcus of Ogston may produce suppuration in 
certain cases. Thus Pasteur describes a different 
“vibrio” as the cause of suppuration. In a paper read 
at the French Academy of Medicine (April 30, 1878) 
he describes this bacterium as a short rod —in his SUPPURATION FURUNCLES. 
115 
words, sausage-like—at first freely moving, but at rest 
after growing for some time, slightly constricted in its 
centre and not unlike the common bacterium termo. 
Since Pasteur’s description of the form of bacteria is 
never very close, it would be difficult to identify this 
micro-organism. He has met with it in the hydrant 
water of Paris, and cultivated it in meat infusion. It 
is said to be either aerobic or anaerobic, according to 
the circumstances. When injected into the bodies of 
guinea-pigs it gave rise to abscesses the pus of which 
contained these micro-organisms. The inoculation with 
this pus started fresh abscesses. When large numbers of 
the parasite were used for inoculation portions of them 
were taken up by the circulation and deposited in other 
tissues, causing thus metastatic abscesses. Since the 
occurrence of multiple suppuration in different localities 
in consequence of infection from a primary seat of 
purulent inflammation characterizes pycemia, Pasteur 
does not hesitate to consider this parasite as the cause 
of that disease. It is interesting to note that the 
injection of a large quantity of these bacteria is not 
harmless, even when their vitality has been destroyed 
by boiling. Their dead bodies are sufficiently irritant 
to provoke a suppurative inflammation, but such an 
abscess has no tendency to spread, and its pus is not 
infectious to other animals. Pasteur supposes, that the 
dead bacteria act as foreign bodies; but as foreign 
bodies are not irritant, if insoluble, it is more likely, 
that the living bacteria act upon the tissues by the 
secretion of some acrid substance, of which some remains 
in their dead bodies. 
Pasteur has also found another micro-organism as 
the cause of suppuration, viz.: in furuncles. He figures 
it as a micrococcus in twos or fours, which he detected 
in the pus of unopened boils. His description applies 116 
THE GERM THEORY OF DISEASE. 
fully to the micrococcus found by Ogston in abscesses. 
Yet it must be remembered that a furuncle differs 
from an abscess to the extent of containing a necrosed 
plug in its centre. Whether this is a peculiarity due 
to the location of the furuncle in the skin or not, is 
not yet decided. Pasteur* cultivated this micro-organ- 
ism in chicken broth, or yeast infusion. When injected 
into the bodies of rabbits and guinea-pigs it produced 
abscesses. Its introduction, however, into the blood- 
vessels proved harmless in these animals. The same 
micro-organism was detected by Pasteur in the pus of 
suppurative inflammation of the marrow-cavity of 
bones, or 
OSTEOMYELITIS. 
It seems that he examined only one case of this, 
disease. In this instance the pus was literally an 
emulsion of micrococci. A similar observation has been 
made by Schueller.f The parasitic origin of osteomy- 
elitis has also been claimed by on the basis 
of experiments. The injection of caustic substances, 
and irritants into the marrow of bones did not suffice 
to produce osteomyelitis in dogs, as long as the injec- 
tion was performed antiseptically. The only result was 
a proliferation of the bone tissue obliterating the 
cavity—technically termed sclerosis. But a true sup- 
purative osteomyelitis could be brought on by the 
injection of putrid solutions into the marrow, though 
not in every instance. The material employed had 
rotted in closed vessels without access of oxygen, and 
contained mainly a long form of bacilli bearing spores 
at their ends. Kocher was evidently of the opinion, 
Rendus de 1’ Academie d’ Sciences, 1880. Yol. 90, p. 1033- 
tCentralblatt f. Chirurgie, 1881, No. 42. 
t 
fArchiv f. klin. Chirurgie. Yol. 23, p. 101. OSTEOMYELITIS PYAEMIA. 
117 
that the parasites producing osteomyelitis were identi- 
cal with the agents of putrefaction. But he furnishes 
no proof for this view, as he does not give any 
description of the micro-organisms found in the pus. 
It is more in conformity with our present knowledge 
to suppose that the fluids employed, which were not 
pure cultures, contained some pathogenic germs. These 
were evidently few in number and not always present, 
for he did not get osteomyelitis in every instance of 
infection. Kocher calls attention to the fact that the 
disease—osteomyelitis—may vary very much in intensity 
and that it has a tendency to be complicated with 
secondary suppurations in other parts of the body. It 
is thus very difficult to draw a sharp line between 
complicated osteomyelitis and typical 
PYAEMIA. 
The clinical diagnosis of this latter form of blood- 
poisoning is beset with difficulties at the best. The 
only characteristic symptoms are the irregular fluctu- 
ations in the course of the fever, preceded usually by 
severe chills. But unless pyaemia begins with a 
distinct chill it is impossible to state the moment of 
its onset, and if the patient survives, the diagnosis is 
again involved in doubt. The disease is sharply char- 
acterized only by the post-mortem examination, which 
reveals secondary—or so-called metastatic—foci of 
suppuration in different internal organs, and suppura- 
tive inflammation of serous membranes. 
The former view which gave the name to this 
disease, viz; that these metastatic suppurations are 
due to the entrance of pus into the veins from the 
original wound, has long been disproven by Virchow 
and others. Ordinary pus does not provoke pyaemia, 
when injected into the vessels. It requires the 118 
THE GEEM THEOEY OF DISEASE. 
presence of a specific “ something ” in the pus h> 
produce this result. This was most apparent in the 
experiments of Chauveau,* in which fresh, so-called 
healthy pus was injected into the carotid artery of 
horses and asses. The injection produced purulent 
inflammation in the organs directly reached by the 
pus, viz: the brain and eye, but the suppuration did 
not extend secondarily to other organs. 
It has indeed long been known, that micro-organ- 
isms occur invariably in pyaemia. Reindfleisch stated 
in 1866, that the smaller metastatic deposits of the 
size of a pin’s head, found especially in the substance 
of the heart in the form of softened yellow spots, 
consist entirely of “vibriones.” He gives no further 
description of these parasites, even in the last edition 
of his “ Pathological Anatomy.” Subsequently both 
Yon Recklinghausen and Waldeyer found colonies of 
micrococci in the blood-vessels and in the tissues in 
pyaemia. Micrococci have also been seen by Yogt in 
the blood of the living pygemic patient, distributed 
irregularly throughout the fluid. In the wounds 
which gave rise to pyaemia bacteria were abundantly 
found by Birch-Hirschfeld, particularly in the form 
of micrococci in zoogloea masses. Similar observations 
had also been made by Klebs, who found bacterial 
masses adherent to the surface of the wound. He 
described both rod-shaped and globular organisms, 
and considering them genetically related to each other, 
termed them microsporon septicum. But he has 
never given satisfactory proof, that the various forms 
he described are really different stages of the same 
organism. He traced, however, the entrance of micro- 
cocci into the interspaces of the tissues surrounding 
the wounds, and into eroded veins. It is well known, 
*Revue Scientifique, 1875. PYiEMIA. 
119 
that pyaemia often starts from a thrombosis of a vein 
next to the wound. In the clot of such veins Klebs 
and others have found micrococcus colonies, and the 
same micro-organisms are met with in the particles 
torn off from this clot by the blood current, and 
deposited in various parts of the system in the form 
of emboli. All these observations have been con- 
firmed by other authors* and I do not know of any 
instances in which micro-organisms were not found in 
the pysemic foci, when properly sought for. But I 
can find no description of them of a kind to identify 
the bacteria of human pyaemia with certainty. The 
latest author—Littenf—examined thirty-five instances 
of—as he calls them—septic diseases. His descrip- 
tion proves them to have been wdiat would commonly 
be called pyaemia. In all these instances bacterial 
emboli were invariably found in the centre of the 
metastatic deposits in the different organs. Their 
anatomical relationship clearly pointed them out as 
the starting-points of the secondary suppurations. 
Especially in the interior of the eye when involved in 
metastatic inflammation could the importance of the 
micro-organisms be clearly established. The bacteria 
were also found related to the minute hemorrhages so 
frequently observed in pyaemia. Generally an embolic 
plug of bacteria was found in the vessels from which 
the blood exuded—but not always. Bitten speaks of 
micrococci-colonies almost wholly, but in some 
instances encountered also rod-shaped bacteria.—All 
observers admit that the place where bacteria—usually 
micrococci—can be most easily demonstrated is in the 
inflamed cardiac valves, since endocarditis is such a 
common lesion found in pyaemia. 
*Orth, Martini, Heiberg, Litten and many others. 
fUeber septische Erkrankungen. Zeitschrift f. klin. Medizin, Yol. 
11, pp. 378 and 558. 120 
THE GERM THEORY OF DISEASE, 
Numerous liave been the attempts to provoke pyaemia 
experimentally in animals. But the older observations 
can be passed over in silence. They have widened our 
views of infectious diseases and have proven an incen- 
tive to further work, but they were not accurate enough 
to satisfy our present requirements. Many experiments 
have been made by different parties -in the hope of 
obtaining pyaemia by the injection of putrid substances. 
Since these substances contain many varieties of bac- 
teria, variable and inconstant results were obtained. 
Amongst other infectious diseases, true pyaemia did 
sometimes appear in consequence of such injections, 
but it was not even attempted to identify the corres- 
ponding parasites or to learn whether they were 
specific in that disease. Again, in other instances 
observers attempted to grow the bacteria taken from 
pyaemic patients, outside of the body. But they 
invariably chose as cultivating fluids Pasteur’s or 
Cohn’s mineral solutions, in which pathogenic para- 
sites cannot thrive at all. Hence the crop of bacteria 
which they did get was really the progeny of germs, 
unintentionally introduced. In spite of all precautions 
to prevent the accidental access of foreign germs to 
their flasks, these observers raised bacteria from 
pysemic pus, with no assurance that this pus—exposed 
to the an did not contain a variety of micro-organ- 
isms. When the blood was used for the inoculation 
of the cultivating solution—as in the experiments of 
Wolff*— negative results followed invariably, because 
the mineral solution could not nourish the’ pathogenic 
bacteria. Hence very little light was thrown upon the 
etiology of pyaemia by such uncertain and conflicting 
results. 
Tli© first definite statements ns resrnrds n well clmr- 
*Virchow’s A,rchiy, Yol. 81, p. 193. 121 
PYAEMIA. 
apterized form of pyaemia in animals are those by 
Koch.* He obtained in rabbits a disease characterized 
by inflammation and subsequently suppuration —at 
the inoculated spot, with metastatic deposits in internal 
organs, swelling of the spleen, and peritonitis. This 
disease could be transmitted from one animal to 
another by injection of the blood of the first victim. 
Its original production was a matter of accident. In 
a series of injections of putrid substances he got this 
form of disease in one instance and could thence 
transmit it to other animals. Its cause was found to 
be the growth of a micrococcus in colonies in the 
blood-vessels of the affected parts. The parasites 
were quite small, about 0.25 micromillimeters in 
diameter, and had a tendency to form thrombi in the 
vessels. They spin around the blood corpuscles in a 
characteristic manner and render them adhesive. Thus 
the corpuscles adhere to each other and form thrombi, 
from which fragments may be torn off by the blood- 
current and carried along until they are caught in 
some vessel too small to permit their passage. In 
these embolic masses the micrococci continue to grow. 
Since the micrococci are so readily arrested in the 
vessels on account of their influence upon the adhe- 
siveness of the corpuscles, they cannot exist in large 
numbers in the circulating blood in spite of their 
active growth. They were found, however, in the 
fibrinous deposits on the surface of the abdominal 
organs. No attempt was made to cultivate them 
artificially. But their invariable presence in the dis- 
ease, and their behavior in the causation of thrombosis 
and embolism are sufficient proof that they produce 
the disease. These results have since been fully con- 
firmed by Semmer.f 
*Traumatic Infective Diseases, p. 4 c 
fCentralblatt f. d. med. Wiss., 1881, No. 41. 122 
THE GERM THEORY OE DISEASE. 
It cannot be stated with certainty, whether there are 
different forms of pyaemia or not, due to different 
parasites. As has been mentioned before, Pasteur 
recognizes as the cause of pyaemia a short sausage- 
shaped “vibrio,” exceedingly flexible and movable in 
its earlier stage, but later on motionless. He com- 
pares it to bacterium termo, like which it is constricted 
in its centre. It is evidently different from the micro- 
coccus of Koch. Its injection under the skin produces 
abscesses. When these are numerous or large, it is 
apt to be carried along by the blood-current and 
deposited in internal organs, where it provokes sec- 
ondary suppuration. The same result follows its direct 
introduction into the blood-vessels. But Pasteur lacks 
in precision both in the description of the micro-organ- 
ism and—more so—of the morbid lesions. His paper* 
is really a mere sketch, which could hardly be ac- 
cepted as conclusive, if published by any one not so 
favorably known in this department as Pasteur. It 
might seem from his researches, as if pyaemia could 
be produced by the entrance into the circulation of 
any parasite capable of causing suppuration. But in 
proof of the specific nature of the pyaemic virus, it 
must be remembered that the micrococcus found by 
Pasteur in furuncles proved harmless on injection 
into the blood-vessels. Yet in the same animals it 
caused suppuration when put under the skin. Acute 
abscesses also do not cause pyaemia when unopened, 
though Ogston found the corresponding micrococci in 
the blood. They were eliminated by the kidneys and 
could be seen in the urine without disease of the 
kidney. All experimental and clinical observations 
force upon us the view that pyaemia is produced by 
the presence of a specific micro-organism in the 
*Moniteur Scientifique, 1878, p. 611. DECOMPOSITION OP PUS. 
123 
blood-vessels, gaining entrance into tlie system through 
some wound. 
DECOMPOSITION OF PUS. 
We have shown above, that in wounds from which 
germs have been excluded the healing processes occur 
undisturbed. The entrance, however, of micro-organ- 
isms into the wound starts an irritation of its walls. 
Possibly there may be some forms of bacteria which 
do not irritate much if at all, for micrococci have been 
found, especially by Cheyne, in some aseptic wounds. 
If the only parasites present are the micrococci which 
produce suppuration, the struggle between them and the 
living animal cells ends in the victory of the latter. 
If the pus can only escape, the wound heals invari- 
ably, although slower than it would without such 
infection. But in wounds exposed to the air, or 
touched with impure instruments, other bacteria soon 
develop. According to the testimony of many observ- 
ers such wounds may contain as great a variety of 
micro-organisms, as are found in any rotten fluid. 
The decomposition of the pus is the inevitable conse- 
quence of their presence. The energy of these putre- 
factive changes depends of course upon the relative 
number of bacteria present. This varies considerably. 
Whenever the pus or secretion of the open wound can 
drain off freely the bacteria are scant in number, while 
stagnating fluids teem with micro-organisms. Of course 
the mode of dressing is not without influence upon 
the growth of the bacteria. AVe do not know whether 
the putrefactive-bacteria exert a direct influence upon 
the exposed tissues. Even if that be not the case, the 
products of decomposition—which they engender—irri- 
tate the wound in an unmistakable manner. This 
reveals itself in redness and sensitiveness of the edges 124 
THE GEHM THEORY OF DISEASE. 
of the wound and in retardation of the healing pro- 
cess. The significance of the occurrence of putrefac- 
tion-bacteria in wounds can be best appreciated on 
comparing the healing of two abscesses, one opened 
in an aseptic manner, the other operated upon without 
such precautions. In both cases the micrococci of 
suppuration are present, but these parasites are always 
overpowered by the living tissues, if the pus can 
escape. Hence in the aseptic abscess the suppuration 
diminishes at once, as soon as it is opened. Indeed 
if it be opened at an advanced period, when the 
abscess is well circumscribed, and there remains no 
coccus-infiltration in the surrounding tissues, there 
occurs very little oozing of pus after the original con- 
tents have been evacuated. Without further pain the 
cavity is closed, in a time proportionate to its size. 
If no antiseptic precautions have been intentionally 
observed in the opening of the abscess, the course of 
it is always less favorable, though the exact history 
varies with the extent of the infection. In proportion 
to the number of putrefaction-bacteria and the decom- 
position to which they give rise, is the healing 
retarded. The suppuration is more profuse, and there 
is more tenderness of the wound, than in the aseptic 
case, and the duration of the regenerative process is 
always prolonged. 
Moreover the presence of the putrefaction-bacteria is 
one of the factors in the causation of 
TRAUMATIC FEVER. 
The fever following wounds is no doubt engendered 
by different influences in different cases. A febrile 
disturbance may result from wounds kept perfectly 
aseptic by reason of a protective dressing, or on 
account of their subcutaneous position, as in simple TRAUMATIC FEVER. 
125 
fractures. But this fever is very slight and can be 
recognized only by means of the thermometer, and not 
by any sensations of the patient. The cause of this 
aseptic fever—as it has been termed by Yolkmann and 
Genzmer—is probably the re-absorption of products, 
especially ferments, liberated through the mechanical 
destruction of tissues. Experiments by Koehler, Edel- 
burg and others have also shown, that the fibrin-fer- 
ment set free during the coagulation of blood, can act 
as a fever-producing agent. The fever from aseptic 
wounds is never of long duration. 
The prolonged fever following all extensive wounds 
which do not pursue an aseptic course, is of a differ- 
ent significance. We do not know how far the micro- 
coccus producing suppuration is reponsible for it. It 
is true that when this parasite first invades the tissues 
in the formation of an abscess, it causes a fever pro- 
portionate to the extent of the invasion. But this 
fever ceases very quickly when pus can find free exit. 
A more potent cause accounting for traumatic fever, 
is the absorption of the products of decomposition 
from the surface of the wound. It is indeed a com- 
mon observation that the constitutional symptoms are 
more marked, the more offensive the wound, and the 
more imperfect the drainage of its secretion. Unlike 
aseptic fever, the fever due to an impure wound is 
accompanied by other disturbances, such as restless- 
ness, want of appetite, and depression of spirits. It 
is not claimed that these symptoms are due to the 
entrance of bacteria into the blood. They can be pro- 
duced in animals by the injection of the products of 
putrefaction without the presence of micro-organisms. 
Since the earlier experiments of Gaspard at the begin- 
ning of this century, numerous observers have studied 
the effects of putrid material upon the body. But in 126 
THE GERM THEORY OF DISEASE. 
none of the earlier researches was there any distinction 
made between the poisoning with decomposed sub- 
stances, and the infection due to the various forms of 
bacteria present in the putrid solution. Panum was 
the first to point out the difference in the nature of 
these two processes in 1855.* 
PUTRID OR SEPTIC POISONING 
can be produced with the products of decomposi- 
tion of nitrogenous organic substances without the 
presence of living micro-organisms. In the experi- 
ments of Panum, in which macerations of rotten 
tissues were used, the solution was filtered by means 
of a suction pump through two layers of the finest 
Swedish filter paper, after which procedure the micro- 
scope could detect no bacteria in the filtrate. Culture 
experiments had not been used, hence doubts might 
be permitted whether a few isolated bacteria might 
not have passed through the filter. But in other 
experiments the absence of bacteria was fully guaran- 
teed by eleven hours’ continuous boiling of the 
infusion. By the boiling the strength of the poison- 
ous fluid was reduced to about one-fifth of its orioinal 
virulence, but this loss was probably caused by the 
adhesion of the poison itself to some flakes of albumen 
which were coagulated by the heating. For the pre- 
cipitated albumen proved intensely virulent on inocu- 
lation. The best criterion as to whether the symptoms 
resulting from the injection of the solution were those 
of poisoning or those of infection was the length of 
time elapsing until any consequences appeared. A 
chemical poison disturbs the functions of the tissues, 
as soon as it conies in contact with them, while a 
*His researches were published originally in the Danish, and 
republished in 1874 in Virchow’s Archiv., Vol. 60, p. 828 PUTEID OE SEPTIC POISONING. 
127 
struggle between the tissues and invading parasites 
becomes apparent only after the latter have multiplied 
to a sufficient extent. In the experiments of Panum 
there was no period of incubation. When enough of 
the putrid poison was introduced into the veins, death 
—preceded by convulsions and suffocation—was almost 
instantaneous, while the smallest quantity of the 
material capable of disturbing the animal system 
visibly, showed its effects within two hours, which 
period is far too short for any extensive multiplication 
of living beings. A medium dose produced the most 
characteristic symptoms of putrid poisoning, for while 
it did not kill too quickly to permit fair observation, 
the effects were of course more marked than from 
minimum doses, which did not preclude recovery. In 
these instances (in dogs) there occurred, within half 
an hour to two hours, an intense intestinal irritation 
showing itself in severe vomiting and purging.. This 
was accompanied by prostration and collapse. Char- 
acteristic, also, was the peculiar condition of the skin, 
which seenied too large for the animal, and could be 
gathered into folds, which remained for quite a time. 
When the animals recovered, these symptoms subsided 
slowly within twenty-four hours and were followed by 
very slow convalescence. In the fatal cases death 
came on in from four to twenty-four hours. The 
autopsy showed congestion of, and extravasation into, 
the lining membrane of the intestines, ecchymoses 
under the serous surfaces, and the blood in g, black 
and fluid condition. The cadavers began to putrefy in 
a remarkably short time. The fatal dose of this 
poison was very small. Twenty-four centimeters of 
the putrid maceration necessary to kill a dog contained 
but seven centigrams solid residue, of which but an 
unknown portion could have been the poisonous 
substance. 128 
THE GERM THEORY OF DISEASE. 
These researches of Pannm explain many of the 
symptoms observed in patients suffering from foul 
wounds. But they do not account for the most char- 
acteristic phenomenon—the fever. Panum did not find 
a rise of temperature the constant effect of his injec- 
tions. But fever had been obtained in most of the 
experiments of the older French and • German 
observers (Gaspard, Sedillot, and others; later on 
Billroth and Weber) in which various putrid fluids 
were introduced into the system. Though no attempt 
was made to exclude living germs in the former 
observations, the occurrence of fever within a few 
hours after the injection can only be attributed to 
the action of chemical poisons. The symptoms of 
putrid poisoning are by no means identical in the 
descriptions of different authors. The explanation of 
these discrepancies, however, is quite simple. The 
rotten material was not the same in all cases, and it 
was employed in widely different stages of putrefac- 
tion. The putrid poison is not a single chemical 
substance, it is a mixture of a number of unknown 
products. Thus Panum found, that on evaporating an 
alcoholic extract of his dried maceration-fluid, he 
could take up in water from this residue a substance, 
which produced a quiet sleep in a dog without further 
sickness. 
Bergmann and Schmiedeberg* obtained from putrid 
yeast a crystalline base which they termed Sepsin. 
One centigram of this substance produced in dogs an 
immediate fever with the intestinal symptoms charac- 
teristic of putrid poisoning. But sepsin cannot be 
found in all putrid matter. X nder Bergmann’s guid- 
ance a number of his pupilsf studied the various 
*Centralblatt, 1868. 
tQuoted by Hiller: Die Lehre von der Faeulniss, 1879. pp. 106 et seq PUTRID OR SEPTIC POISONING. 
129 
conditions, under which poisons are produced by putre- 
faction, and the manifold symptoms they engender, 
but without determining the chemical nature of these 
complex substances. 
A singular observation, made by all the experi- 
menters, is the rapid decomposition of the cadavers of 
animals dead from putrid poisoning. This is likewise 
true of human corpses dead from blood poisoning. 
This fact has been quoted as an argument against the 
germ-theory and upon it have been based vague specu- 
lations to prove, that the presence of bacteria is merely 
a consequence of septic diseases. But it is the more 
conservative plan to admit that we cannot account for 
it Satisfactorily as yet. 
If the above-mentioned symptoms be really the 
effect of a chemical poison, which—unlike living para- 
sites—cannot reproduce itself, it is to be inferred, that 
the blood of animals, suffering from putrid poisoning, 
is unable to transmit the disease to other animals, when 
injected in limited quantity. This was found to be 
true in the experiments of Gutman and Semmer.* A 
contrary observation, however, had previously been 
reported in a short communication by Hiller, -j- This 
author, believing the septic poison to be of the nature 
of a chemical ferment, attempted to extract it from 
dried rotten blood by means of glycerine, the solvent 
power of which for ferments is well known. The gly- 
cerine-extract produced in rabbits the symptoms of 
septic poisoning, viz; fever beginning with chills, 
diarrhoea, prostration, and emaciation leading to col- 
lapse and finally death. But the same train of symp- 
toms could be reproduced by inoculating a second 
animal with the glycerine-extract of the fresh blood of 
*Yircho'w’s, Yol. 88, p. 99. 
fCentralblatt f. Chirurgie, 1876, Nos. 14 and 15. 130 
THE GERM THEORY OF DISEASE. 
the first victim. Like other observers, to be referred 
to later on, he found that the virulence of the blood 
apparently increased in the animals successively in- 
jected, so that in the case of the tenth animal, or as it 
might be called the tenth generation, of a drop of 
the glycerine-extract proved fatal. But I am in doubt 
whether these observations can really range as septic 
poisoning. The claim, that an extraneous chemical 
ferment can reproduce itself in the animal system, is 
so opposed to our general knowledge, that it requires 
a better substantiation in order to be accepted. 
Though Hiller claims, that the microscope could 
detect no bacteria in the glycerine extracts, I am not 
satisfied that they were not there. Bor Koch ha& 
since shown that it may be almost impossible to find 
certain bacteria in the blood, except by the use of 
staining methods. How much more difficult is hence 
the detection of bacteria in a fluid possessing as high 
an index of refraction as glycerine. Moreover Hiller 
observed a period of incubation of several days at 
first, though in the later generations this was reduced 
to some hours. I would hence be more inclined to 
consider the disease observed by Hiller to be a form 
of real 
SEPTICAEMIA. 
It is scarcely possible to give at present an abso- 
lute definition of this disease. When it occurs as the 
consequence of a foul wound, it appears simply as a 
traumatic fever indefinitely prolonged, so that the 
exact moment of its onset can not be stated. After 
really aseptic wounds, on the other hand, it does not 
occur. In other instances, in which the poison enters 
the system through some slight wound, which had not 
caused any traumatic fever, or in which the mode of SEPTICAEMIA. 
131 
entrance of the virus cannot be traced, the disease 
begins with distinct chills. But then these latter 
cases amount always to a mixture of septicaemia with 
pyaemia, the so-called septico-pyaemia. In fact a pure 
uncomplicated septicaemia seems to be very rare in 
human pathology. Its symptoms are described as a 
more or less continuous fever with depression and 
prostration and often intestinal irritation. It cannot 
be said to be always fatal in man, though mostly so. 
The autopsy in the pure cases reveals nothing but 
swelling of the spleen. But in the majority of 
instances pyaemic changes, i. e. metastatic suppurations, 
are likewise found, showing that during life the dis- 
tinction between the two diseases is scarcely possible 
in man. Yet there occur rare cases of blood-poison- 
ing, which cannot be considered as putrid poisoning, 
because there is no wound with sufficient decomposi- 
tion of the discharge to furnish the septic poison, 
while true pyaemia is excluded by the absence of metas- 
tatic deposits. These we cannot but consider as typi- 
cal instances of septicaemia, however rare they may be. 
But I have not been able to find a single record of 
such a case in which either the presence or absence 
of bacteria was determined. The examination of the 
living blood would be insufficient, for during life 
pyaemia cannot be excluded with certainty. Moreover 
you will learn presently that in the experimental 
septicaemia of animals bacteria cannot always be 
found in the living circulating blood. 
Many endeavors have been made to communicate 
human septicaemia to animals, but here as in pyaemia 
none of the results are really conclusive. Even if 
some of the observers did. get septicaemia in their 
animals, they did not characterize it sufficiently in 
their description. Their only object was to see, 132 
THE GEEM THEOEY OF DISEASE. 
whether the animals would get sick at all. But with 
material taken from other sources, i. e., such as is 
furnished by rotten refuse of different kinds, several 
different diseases may be produced in animals, which 
all merit the name septicaemia. For by analogy with 
the corresponding disease of man, we can apply that 
term, whenever we meet with an infective fever contin- 
uing until death without other prominent symptoms, 
and characterized by the absence of all lesions, except 
swelling of the spleen. Moreover in the light of 
modern developments, we should restrict the term to 
those conditions in which bacteria are actually found 
in the blood. According to this definition we can 
recognize at least four different forms of septicaemia 
in animals due to different parasites of which I shall 
give the following synopsis; 
I. Septicaemia due to very delicate bacilli, produced 
originally in the mouse by Koch * These bacilli are 
about 0.8 to 1 micromillimeter in length, and about 
one-tenth as thick. They are so delicate, that they 
can be scarcely seen without staining. While 
growing they form dense masses, but never chains. 
Koch has seen spores in them occasionally. They 
have been cultivated later on by Koch and Loefflerj* 
on the surface of a mixture of gelatine, peptone and 
meat-extract. The colonies, which they form on this 
substratum are characterized by a delicate arborescent 
shape. In the body of the infected animal they are 
found only within the blood-vessels. They often 
penetrate into the white corpuscles and multiply until 
the whole corpuscle forms but a cluster of bacilli. 
The inoculation of mice with these bacilli proves inva- 
riably fatal in from 40 to 70 hours—with a period of 
lnfective Diseases, p. 33. 
tMittheilungen aus dem Gesundheitsamte, p. 169. DIFFERENT FORMS OF SEPTICAEMIA. 
133 
incubation of about 24 hours. The disease can be 
transmitted to pigeons and sparrows, but not to field- 
mice. In the dog, cat, rabbit and white rat these 
bacteria provoke only a local inflammation resembling 
erysipelas. 
11. Septiciemia due to oval micrococci, the greater 
diameter of which is about one micromillimeter. 
Koch* studied this form of disease first in rabbits, 
which are killed by these parasites in from 20 to 40 
hours. No lesions were found after death but small 
scattered echymoses in different parts, and swelling of 
the spleen. Many small veins are choked with the 
micrococci and when they burst, allow the bacteria to 
extend into the tissues. This septicaemia could also 
be transmitted to mice. 
111. Septicaemia produced by Koch and Gaffky-j* in 
rabbits and mice by means of a parasite too short to 
be called a bacillus, and too elongated to be termed 
coccus. These bacteria, about 1.4 by 0.7 micromilli- 
meters in size, show an unstained central portion, 
when colored with aniline dyes, which gives them 
almost the appearance of a diplococcus although they 
have no central constriction. They show no active 
motion. They were cultivated in beef-broth or on the 
surface of a gelatine mixture containing meat infusion 
and peptone. On this substratum the colonies assume 
the form of characteristic globules. Rabbits are 
killed by them in 16 to 20 hours without other 
lesions than enlargement of the spleen and of the 
lymphatic glands. They neither plug the vessels, nor 
do they leave them and enter the tissues. The 
disease could be produced besides in bats and birds, 
while it was impossible to inoculate successfully 
guinea-pigs, white rats, cats and dogs. 
*Loc. cit., p. 53. 
tMittheilungen, p. 93. THE GERM THEORY OF DISEASE. 
IY. A form of septicaemia obtained by Pasteur* 
by inoculating rabbits with the saliva from a child 
with hydrophobia. He called it at first a specific 
“ new disease,” not being able to recognize it as 
hydrophobia. But since it can be produced by the 
saliva of many normal persons and possesses no other 
characteristics it may just as well be termed septicae- 
mia. The parasites appear in the form of a figure 8 
about 0.5 microlnillimeters in length, and are sur- 
rounded by a delicate halo. When cultivated in veal 
broth they are slightly larger at first than in the 
blood, and form chains, but resolve themselves after a 
few days—to use the words of Pasteur—into small 
round granulations. Gaffky supposes that this “new 
disease” of Pasteur is identical with his septictemia, 
but on comparing the descriptions I find striking dif- 
ferences. Instead of Gaffky and Koch’s negative 
lesions, Pasteur found hemorrhages in the lungs, con- 
gestion and echymosis of the trachea, and local swell- 
ing and inflammation at . the inoculated spot, besides 
swelling of numerous lymph glands. The disease 
killed rabbits in from eighteen to forty-eight hours. 
It could not be transferred to pigeons (unlike Gaff- 
ky’s septicaemia) or guinea-pigs. Probably the same 
form of septicaemia has been studied by Sternbergf 
of this country. He produced it likewise in rabbits 
by the injection of human saliva, but found only the 
saliva of some individuals—not of all—active. The 
symptoms and lesions observed were identical with 
those described by Pasteur. The description of the 
micrococcus is more accurate, since Sternberg used 
staining methods. It agrees on the whole also with 
Pasteur’s observation. The photographs published by 
*Comptes Rendus, Vol. 92, p. 15. 
"(■National Board of Health. Bulletin Apr. 30, 1881, No. 44, SEPTICAEMIA DUE TO SPECIFIC PARASITES. 
135 
iSternberg, although not very sharp, are different from 
those of Koch and Gaffky’s septicaemia (form III.) 
The parasite could be cultivated in rabbits’ bouillon or 
dogs’ serum. 
It is not likely, that this completes the list of septi- 
caemia diseases occurring in different animals. As 
long as we employ the term septicaemia with this 
provisional loose significance, we might include under 
this head all febrile affections not characterized by 
any localized symptoms or lesions and due to the pres- 
ence of some form of bacteria in the blood. Hence 
logically the term might even be applied to anthrax. 
In the earlier researches on septicaemia it was sup- 
posed that the parasites causing the disease were 
identical with the bacteria of putrefaction. This view 
can no longer be sustained. The blood of the animal 
just dead of septicaemia teems with the characteristic 
micro-organisms, but gives no evidence of putrid 
decomposition. On the contrary it loses its virulence, 
when allowed to rot in the ordinary manner. While 
the fresh blood of the septicaemic animal can repro- 
duce the disease in almost incredible dilution, the 
occurrence of putrefaction soon deprives it of its spe- 
cific pathogenic property, and reduces its poisonous 
quality to that of ordinary rotten blood. Evidently 
the specific septicaemic bacteria are overpowered and 
crowded out of existence by the invasion of the same 
soil by the less dangerous organism of putrefaction. 
Sternberg found also, that virulent saliva could no 
longer produce septicaemia after it had undergone 
putrefaction. The non-identity of the septicaemic bac- 
teria and the common putrefactive forms is further 
shown by the inconstant results on inoculating animals 
with decomposing animal refuse. If the quantity 
injected be not large enough to kill speedily by septic 136 
THE GEEM THEORY OE DISEASE. 
poisoning, trne septicaemia occurs only in a certain 
variable proportion of the experiments. The disease 
resulting may be either one of the above forms. But, 
when once produced, the disease can be transmitted 
indefinitely and with absolute certainty to further ani- 
mals of the same or any other susceptible species. 
In those instances, in which the parasites were culti- 
vated outside of the animal body, they retained all 
morphological and functional characteristics indefinitely 
and never changed into other forms, and never pro- 
duced putrefaction of the soil in which they grew. 
All these facts harmonize only with the view that 
each form of septicaemia is produced by a separate 
and distinct parasite, not identical with putrefaction- 
bacteria, though found occasionally and accidentally in 
the same soil with the latter. 
The blood of septicaemic animals possesses an aston- 
ishing degree of virulence. The infectious power of 
the blood is much greater than that of the original 
putrid material which served as the source of the virus. 
Coze and Feltz were the first to point out that the 
infectiousness of the virus seems to increase on being 
transmitted through a series of animals. This progres- 
sive virulence of the septicaemic “poison”—if we can 
use that term—attracted general attention, however, 
only after the striking experiments of Davaine reported 
to the French Academy of Medicine in the years 1872 
and 1873. Davaine produced septicaemia by the inocu- 
lation of blood in a certain stage of decomposition. 
Like Koch later on he does not seem to have suc- 
ceeded in every instance. But when once produced 
the disease could be transmitted indefinitely. It can- 
not be decided now, which of the above described 
forms of septicaemia, if any, Davaine observed. For 
very little reference was made by Davaine, or those PROGRESSIVE VIRULENCE OF SEPTICEMIC VIRUS. 
who confirmed his experiments, to the existence of 
bacteria in the blood. It was simply stated that they 
were there, but not which variety or in what number. 
It must be remembered that staining methods were 
not known at that time and that the delicate septicsemic 
bacteria can be overlooked in the blood without them. 
At any rate it was a disease fatal to rabbits in sixteen 
to sixty hours without producing any lesions but 
swelling of the spleen; and it could be transmitted to 
guinea-pigs, mice and rats, but not to fowls and 
pigeons. 
On transmitting the disease from animal to animal 
through twenty-five successive generations, it was found 
that the dilution of the blood used for inoculation 
could be continuously diminished without danger of 
failure, until at last the one-thousand-millionth part 
of a drop sufficed to kill a rabbit. This progressive 
virulence was apparently confirmed in the subsequent 
experiments of various French observers (Yulpian, 
Bouley and others), of dementi and Thin and of 
Dreyer. But Koch has since pointed out, that the 
“progressive virulence” is an unnecessary and un- 
founded assumption. In his earlier experiments and 
in his later researches with Gaffky it was learned that 
the greatest possible virulence of the blood was 
obtained in the second, or at the latest, the third 
animal successively inoculated, in other words as soon 
as the blood represents a “ pure culture ” of the para- 
site. In the first, and sometimes the second generation 
of victims other bacteria are yet associated with the 
specific parasites, but these non-pathogenic forms 
introduced from the original source of the virus do 
not persist in the blood of more than the first two 
successive animals. At any rate he could not success- 
fully employ a smaller quantity of blood for hypo- 138 
THE GERM THEORY OE DISEASE. 
-dermic injection, when taken from any of the later 
generations than when obtained from the second, or 
at the most, the third animal. As he points out 
Davaine really admits the same truth in his own 
account of his researches, stating “that the septicaeraic 
virus acquires immediately its greatest virulence.” 
The alleged law of the progressive virulence of the 
septic blood is therefore a misinterpretation of the 
facts. In the researches of the other authors men- 
tioned, who claimed to corroborate Davaine’s discovery, 
there is no statement, whether they really tested the 
utmost extent of the virulence in the earlier gener- 
ations. 
It has been doubted whether the extreme virulence 
of septic blood in almost infinitesimal quantities 
could really be attributed to the bacteria found in 
it. But this query answers itself, when a well-stained 
specimen of blood is examined. It is evident in such 
a specimen that the parasites are many times more 
numerous than the red corpuscles. Now since animal 
blood contains over five millions of red corpuscles per 
-cubic millimeter, and since one drop amounts to some 
thirty cubic millimeters, there are parasites enough 
present to account for the virulence of Davaine’s 
minimal quantities. 
There are several facts, however, in connection with 
septicaemia, which are as yet wholly unexplained. One 
of these is the harmlessness of the blood taken from 
the septicaemic animal before death. This was espe- 
cially emphasized by dementi and Thin as well as 
Dreyer in their repetitions of Davaine’s experiments. 
They could reproduce the disease only with the blood 
taken from the animal at the moment of death, or 
within some hours after life was extinct. Koch does 
not seem to have tested this point, taking the blood VIRULENCE OF SEPTICEMIC BLOOD, 
139 
used for inoculation only from the animal just dead. 
But Gaffky states that in one instance the blood 
proved virulent, though removed from a septicsemic 
rabbit two hours before the animal expired. The 
harmlessness of the blood during life indicates, that 
the parasites have not yet entered the circulating fluid. 
But the full explanation of this fact will only be pos- 
sible after further studies. For up to the present all 
researches have really had no other object than merely 
to demonstrate that the disease is really due to para- 
sites. No attempt has yet been made to study the 
behavior of the bacteria in the body. 
More puzzling even is the fact, that the virulence 
of septic blood is not always destroyed by boiling. 
This was discovered by the French observers but more 
fully emphasized by dementi and Thin. Quite 
recently it has again been confirmed by Rosenberger* 
who added further details. He experimented with the 
septicaemia of rabbits due to the short oval bacteria of 
Gaffky (form III). The virulence of the blood of 
the dead animal was much reduced by boiling, but 
not destroyed. On injecting the boiled blood in large 
quantity the original disease was reproduced and the 
blood of the animal, thus infected, was found to be as 
virulent, as that of any other septicsemic animal and 
contained the original form of bacteria. Yet Rosen - 
berger claims that the heating destroyed the bacteria. 
For the infection of a sterilized meat-broth with a 
drop of fresh septicaemic blood produced a vigorous 
crop of the characteristic bacteria, while from the 
heated blood none could be cultivated. A similar 
paradoxical result was obtained by the same author in 
another infectious disease, which we shall discuss later 
on, viz; malignant oedema. This disease, characterized 
*Oentralblatt No. 4, 1882. 140 
THE GERM THEORY OE DISEASE. 
by the presence of an unmistakable bacillus growing 
in the tissues can be produced by inoculating animals 
with the serous effusion of a former victim. Here also 
the virulence of the morbid fluid was reduced, though 
not destroyed by boiling. Here also the bacilli were 
apparently killed by heat, for they could not be culti- 
vated outside of the body after boiling the fluid, and 
yet they were reproduced in their characteristic forms 
in an animal on inoculation with the boiled fluid. 
The author attempts to explain these unexpected 
results by denying the specific nature of the parasites 
and attributing the cause of the disease to chemical 
poisons, considering the bacteria only as associated 
with, and not as productive of the disease. But this 
explanation is a forced one and inadequate besides. 
It seems to me more logical to admift, that such puz- 
zling observations can only be explained by further 
researches and not by speculative reasoning for which 
the basis is yet wanting. SURGICAL INFECTIONS—ERYSIPELAS. 
141 
LECTURE VI. 
Surgical Infections (continued).—Erysipelas.—Progressive Gangrene. 
Progressive Phlegmons.—Malignant (Edema.—Symptomatic Char- 
bon (Quarter Evil).—Immunity from Intravenous Injection.—Tuber- 
culosis: The Disease is Infectious.—The Bacillus Tuberculosis. 
Inoculation with the Isolated Bacilli.—The Mode of Spreading of 
the Disease.—Methods of Staining the Bacilli.—The Significance of 
their Presence in the Sputum. 
ERYSIPELAS. 
In this disease it was found some ten years ago by 
Lukomsky,* that micrococci occur in the affected portion 
of the skin and subcutaneous tissue. In sections 
cleared with acetic acid, they were seen to plug the 
lymphatic vessels. They were also met with outside 
of them and in the blood-vessels, but this observation, 
not in harmony with the more recent researches, is to 
be accounted for by the fact, that his cases were 
mostly complicated with other diseases. Various other 
observations have since been published by different 
authors (Billroth and Ehrlich, Tillmanns, Nepveu, 
Bellien), which have not, however, added materially to 
*Yirchow’s Archiv, Bd. 60, p. 418. 142 
THE GERM THEORY OF DISEASE. 
our knowledge, because they were not sufficiently 
systematic. But precise statements have appeared by 
Koch* and by Fehleisen.-j* Both have examined the 
skin of the cadaver as well as small pieces of skin 
snipped from the living patient. In all these 
micrococci 0.8 to 0.4 micromillimeters in diameter 
were found, forming slightly curved chains. In stained 
sections it could be seen, that in a narrow zone just 
outside of the border of the erysipelatous redness, they 
grew in the lymphatic vessels and to a less extent in 
the interstices of the tissue. The infiltration extended in 
depth down to the subcutaneous tissue. This infiltra- 
tion is evidently the forerunner of the erysipelatous 
process and precedes the inflammatory change by some 
hours. At the very edge of the disease, where the 
inflammatory changes are most active, the cocci are met 
with in still greater numbers. Here they exist all 
throughout the tissues and are found, also, in the 
interior of the round cells. But, as the centre from 
which the disease originated, is approached the para- 
sites disappear completely. There is only one way of 
interpreting these observations. The parasites vege- 
tate in the interior of the lymph vessels and lymph 
spaces and produce thereby an inflammatory reaction 
of the tissues which destroys them in turn. Some 
former observers, for instance Nepveu, have also found 
micrococci in the blood of erysipelas, but this was not 
corroborated by Fehleisen, when the blood was taken 
from the healthy parts. 
Numerous attempts have been made to inoculate 
animals with erysipelas. Lukomsky,§ Orth j and Till- 
*Mittheilungen, etc., p. 38. 
■fDeutche Zeitschrift f. Chirurgie. Bd. 16, p. 391. 
five cadavers and bits of skin from sixteen living 
patients. 
§Loco cito. 
1| Archiv f. experimentelle Pathologic, Bd. 1., S. 87. INOCULATION OF EEYSIPELAS. 
maims* succeeded in only very few instances in produc- 
ing erysipelas in rabbits with the contents of erysip- 
elatous blisters in man. In most instances their 
results were negative. The explanation of this uncer- 
tain effect is the absence or relative scarcity of the 
parasites in the serum of the blisters. Their real 
site is only in the lymphatic spaces. In other cases 
again the faulty method was employed of trying to 
grow the pathogenic bacteria in Pasteur’s fluid which 
cannot nourish them. 
But all former uncertainty in transferring erysipelas 
from man to animals loses its significance in view of 
Fehleisen’s'j- invariable success in reproducing the 
disease by inoculation with the cultivated micrococci. 
Excised bits of skin, removed of course with all pre- 
cautions to avoid extraneous infection, were put into a 
gelatinous solution of meat-extract and peptone and 
kept at the proper temperature. There spread from 
the implanted tissue a whitish growth, at first in the 
form of scattered dots, coalescing afterwards to form 
a delicate scum. This pure cultivation of the erysip- 
elas-micrococci could be maintained—perhaps indefi- 
nitely—by transfer to a fresh soil. The parasites grew 
as well on the surface of solidified blood serum, but 
also even on potatoes. The inoculation of nine rabbits 
reproduced the disease in eight instances, the ninth 
animal possessing apparently an immunity. In thirty- 
six to forty-eight hours fever began and a typical 
erysipelas spread from the inoculated ear through a 
variable part of the cutaneous surface. All the animals 
recovered in from six to ten days. In one of the 
rabbits the affected ear was amputated beyond the 
border of the inflammation and the spread of the 
*Archiv f. Klinische Chirurgie, Bd. 23, S. 437. 
■fDie iEtiologie des Erysipels, 1883. 144 
THE GERM THEORY OF DISEASE. 
disease checked thereby. Fehleisen has likewise suc- 
cessfully inoculated seven human individuals with 
erysipelas. His justification of this dangerous experi- 
ment was the old observation made by various 
surgeons, that sometimes tumors, which cannot be 
removed by the knife, disappear after an attack of 
erysipelas over that region. He seems to have accom- 
plished that object in only one case definitely, viz.: a 
relapsing carcinoma of the breast. But while his 
other patients were not particularly benefited, none 
suffered any permanent harm. The micrococci which 
he employed for inoculation had been grown on solid 
soil for from four to seventeen generations. Some 
fifteen to sixty hours after the vaccination there 
occurred a chill, followed by fever, and coincident 
with it the typical erysipelas appeared, running 
thereupon its usual course. A second inoculation 
repeated inside of three months had no effect, while 
in one instance a spontaneous erysipelas which occurred 
a few months previously also frustrated the artificial 
infection. Fehleisen concludes, therefore, that an attack 
of erysipelas confers an immunity upon its victim which 
lasts some three months. Common observation indeed 
teaches that the immunity is not of long duration. 
A disease closely resembling erysipelas in man 
can be produced in the rabbit also by means of 
another parasite. The minute bacilli which cause 
septicaemia (form I, p. 132) in mice, produce only a 
local reaction and not a constitutional disease in larger 
animals. In the cat, dog and rat the resulting 
inflammation is slight and of short duration. But in 
the rabbit these bacilli start a spreading inflammation 
of the skin attended with fever—only, however, if the 
inoculation is made in the ear or the cornea. In 
some few instances this leads to the death of the PEOGEESSIVE PHLEGMONS. 
145 
-animal. It is only in the severest attacks, that the 
bacilli enter the blood; ordinarily they are confined to 
the inflamed tissue. Loeffler,* who studied this form 
•of erysipelas, found it followed by a distinct immunity 
against a second inoculation. Amongst thirty-three 
rabbits he met with but two exceptions, and in these 
cases an absolute immunity was granted by the second 
attack. But this immunity does not follow the erysip- 
elas, until after the lapse of some two or three weeks 
and during this time the inoculation may yet succeed 
in a distant part, although ineffectual in the locality, 
where it was first practised. In this curious instance 
the “power of resistance” spreads gradually over the 
cutaneous surface of the animal. 
A third form of erysipelas has been observed, 
though only in one instance, by Koch in his earlier 
studies, j- It was produced in the rabbit by a delicate 
bacillus, larger, however, than the former one. 
Of the other surgical infections occurring in man, 
progressive phlegmons and hospital gangrene, the 
bacterial origin has not yet been proven. But some 
similar diseases have been studied experimentally in 
animals by Koch. By inoculation with putrid blood he 
obtained in some instances a progressive destruction 
■of the tissues in mice resembling hospital 
When once obtained it could be transferred from one 
animal to another. Its cause was found to be the 
vegetation of a micrococcus about half a micromilli- 
meter in diameter, growing in chains. Its presence 
proved destructive to the tissues even at some distance 
beyond the vegetation, probably by the diffusion of 
■some poisonous product. Beyond the gangrenous 
*Mittheilungen aus dem k. Gesundheitsamte, p. 169. 
fTraumatic Infective Diseases, p. 56. 
lnfective Diseases, p. 40. THE GERM THEORY OF DISEASE. 
portion the tissues were found in a violent state of 
inflammation. 
In rabbits Koch* has studied a form of spreading 
abscess which seems quite common in these animals as 
I find a reference to it in the records of many 
other authors. The cheesy contents of these abscesses 
do not consist of pus, but of a finely granular material 
which does not take up aniline colors. A very small 
micrococcus measuring only 0.15 micromillimeters was 
found, however, in zoogloea masses on the walls of the 
abscesses and growing beyond into the tissues. This 
growth continues, until the death of the animal, which 
occurs within twelve to fifteen days. Koch considers 
the granular contents of the abscess to be the dead 
zoogloea masses. But since these contents are infec- 
tious to other animals he suspected the formation of 
spores, though he could not actually detect them. It 
must be remembered in this connection that spores 
have not yet been demonstrated in any other variety 
of micrococci. 
In none of the instances of surgical infection thus 
described do we know how the contagion spreads. We 
can identify the parasites, we know that - they will 
grow, if introduced into a wound and—what is the 
most valuable to us—we can exclude them by the 
strict antiseptic treatment of wounds. But we do not 
know yet, how they leave the body of one patient in 
order to reach another. As long as we cannot trace 
them thus in their migration, we cannot say with cer- 
tainty, whether any one of these diseases is only 
infectious or also contagious in the ordinary sense of 
the word. Bor the clinical experience as regards the 
contagiousness of these affections is so ambiguous, 
that there exists as yet a diversity of opinion amongst 
•■TjOCO cito, p. 44. MALIGNANT (EDEMA. 
147 
surgeons. It is quite probable, that most, if not all, 
parasites causing the surgical infections, can vegetate 
outside of the body. The virus would therefore be 
both endogenous and ectogenous. At any rate the 
prevalence of these forms of bacteria and their fre- 
quent occurrence in putrid soils harboring a variety of 
forms, render this view plausible, though it has not 
yet been strictly proven, at least under the conditions 
actually occurring in nature. 
Another disease, which might rank amongst the 
surgical infections, though perhaps not common in 
man, is 
MALIGNANT (EDEMA. 
This disorder had previously been studied by Pas- 
teur,* who called it septicaemia. But since the disease 
is characterized by a progressive oedema without the 
primary presence of the parasites in the blood, the name 
proposed by Koch,f —“ Malignant (Edema,”— seems 
more appropriate. It is invariably fatal within twenty- 
four to forty-eight hours. From the point of inocula- 
tion there spreads pretty rapidly an effusion of red- 
dish serum and at the autopsy the parasites are found 
abundantly in this fluid and in the tissues as far as 
the oedema goes. In larger animals very few, if any, 
occur in the blood, but in mice there are enough of 
them existing in the circulation, to render it impossi- 
ble to distinguish this disease from anthrax. It has 
probably been mistaken for anthrax in many instances 
by former observers, which accounts for some inaccu- 
rate statements. The parasite is about flie same 
length as the bacillus anthracis, but slightly thinner 
and possesses rounded ends. It is often, though not 
of the Academy of Medicine, April 30th, 1878. 
fMittheilungen, etc. 148 
THE GERM THEORY OF DISEASE. 
always in a state of slight motion and, when it forms 
long filaments of coherent segments, the movements 
are serpentine. 
Pasteur has cultivated this parasite in meat solution, 
hut only in the absence of oxygen, for according to 
him it is anaerobic and is killed by free oxygen, 
except when in the state of spores. Gaffky doubts 
this statement, as it can be found growing in the 
lungs of an infected mouse, where oxygen is not 
deficient. Still he could not cultivate it on the sur- 
face of gelatine, though he did grow it in the interior 
of boiled potatoes. . 
The spores of this bacillus are Avidely disseminated 
throughout nature. They are to be found in different 
waters, as well as in most of the surface soil, also 
occasionally in dust. These bacilli have also been 
found in the blood of strangulated animals on keep- 
ing the cadavers at a high temperature, evidently 
developed after death from pre-existing spores on 
some of the surfaces. We should hence expect this 
disease to be very common among susceptible animals, 
especially the rodents. But on the other hand, though 
the parasite exists almost everywhere, it cannot get a 
foothold in the system through a mere surface scratch. 
It is necessary to put it into the subcutaneous tissue 
in order to infect an animal, but with this precaution 
the success of the experiment is invariable. In the 
diseased tissues the signs of putrefaction are often 
present during life, viz.: a putrid odor and gas bub- 
bles. But Gaffky has shown that this is a complica- 
tion due fo the presence of putrefaction-bacteria and 
that it may be avoided by inoculation with the iso- 
lated bacilli. 
Two lamentable instances lately reported from the 
Berlin Medical Clinic by Brieger and Ehrlich* have 
Klinische Wochenschrift, No. 44, 1882. EMPHYSEMA INFECTIOSUM. 
149 
taught us, that this parasite can also affect the human 
system. Two patients suffering from typhoid fever, 
and at the time in a state of collapse, received subcu- 
taneous injections of tincture of musk. In both an 
oedema appeared at the spot of the injection on the 
thigh and spread up to the trunk, ending fatally 
without any augmentation of the existing fever. In 
the effused serosity the characteristic bacilli were 
found and identified by the successful inoculation of 
animals. The spores were probably contained in the 
tincture of musk, which through accident could- not be 
examined microscopically. But the same syringe and 
bottle had been used on other patients without bad 
results. The authors suppose, therefore, that normally 
the human organism can withstand the attack of this 
parasite, but may lose its power of resistance when 
enfeebled by other causes. 
It would be of importance to decide whether this 
disease—malignant oedema—is identical with an affec- 
tion peculiar to cattle, viz.; 
EMPHYSEMA INFECTIOSUM 
commonly known as the Quarter Evil or Black Leg, 
the Rnuschbrand of the Germans, the Charhon Symp- 
tomatique of the French. As the latter name indi- 
cates, it has usually been mistaken for true charbon 
and indeed is even yet called anthrax fever. Its 
symptoms and the description of the parasites corres- 
pond with those of malignant oedema, but the identity 
can only be proven by actual experiment. It is 
essentially a progressive oedematous tumor with the 
presence of gas bubbles in the effusion and is almost 
always fatal. In the serosity a rod-shaped parasite 
has been found by Feser. But the closest study of 150 
THE GERM THEORY OF DISEASE. 
it lias been made by Arloing, Cornevin and Thomas 
in numerous communications to the French Academy 
of Sciences since 1880. Like the parasites of malig- 
nant oedema, the bacteria of this disease resemble the 
bacillus anthracis, but have rounded ends and possess 
an unmistakably active motion. Sometimes a clear 
granule is seen at one end, perhaps a spore. These 
rods are found in the interior of the emphysematous 
tumor, in the lymphatic glands, and to a less extent in 
the viscera. Very few are seen in the blood, but 
some ovoid brilliant corpuscles, isolated, or joined in 
twos or threes, were met with in the circulating fluid. 
The significance of the latter was not determined. 
For inoculating purposes Arloing, Cornevin and 
Thomas used the fluid obtained by bruising the 
emphysematous tissues. They do not seem to have 
cultivated the parasites outside of the body. The dis- 
ease could be transferred to cattle and sheep, guinea- 
pigs and rabbits. In rats only local gangrene - was 
caused without fatal issue. Dogs and fowls proved 
insusceptible. Like in malignant oedema, it was neces- 
sary to put the parasites deep into the tissues; they 
could not enter through surface wounds. Inoculation 
with a minute quantity produced sometimes only 
slight local symptoms without death. t)f the most 
interest are the studies of the French authors on 
intravenous injection of the parasite. The fluid used 
was deprived of all other grosser particles by filtra- 
tion. The intravenous injection gave rise to a slight 
temporary fever and sickness, but by itself never 
proved fatal. But if an extravasion of blood is caused 
during this time by some contusion, the bacilli 
develop in the tissues and produce the usual localiza- 
tion, terminating fatally. If this accident does not 
happen, the intravenous injection is not dangerous to IMMUNITY BY PEOTECTIYE VACCINATION. 
151 
life, but confers absolute immunity upon the animals 
against subsequent inoculation in the tissues. In 
several series of public experiments Arloing, Cornevin 
and Thomas have demonstrated that cattle and sheep 
■can thus be protected against the disease. 
A more convenient method, however, for protective 
inoculation was obtained by attenuating the virus and 
then injecting it hypodermically. The fluid contain- 
ing the parasites is dried at 32° C., and the residue 
taken up by twice the amount of water. This mixture 
is then kept at 100° C., during six hours. Another 
portion similarly treated, but heated only up to 85° 
C., is used for a second inoculation eight days later 
to render the comparative immunity absolute. The 
authors state, that the parasites contained spores before 
they were heated, and indeed it seemed very unlikely, 
that the developed bacilli could withstand this high 
temperature. At any rate it is a fact of much inter- 
est, that the virulence of spores also may be modified 
by such treatment. The virus thus mitigated may yet 
prove dangerous, if used too freely, but a subcutaneous 
injection of one centigram (of the dry material) for 
sheep, and two or three times that amount for cattle, 
just suffices for protection without risk from the 
vaccination itself. 
Another method of attenuating the virus has been 
proposed by Nocard and Mollereau.* It consists in 
the action of oxygenated water (peroxide of hydro- 
gen), When mixed with oxygenated water the para- 
site is killed after the lapse of some hours, but prior 
to its death passes through all stages of diminished 
virulence. When enfeebled so far as not to cause the 
death of an animal, it gives the latter a comparative 
immunity, which can be rendered absolute by repeated 
of the Academy of Medicine, Jan. 2nd, 1883. 152 
THE GERM THEORY OF DISEASE. 
inoculation with a stronger virus. The communication 
is so far principally of theoretical interest in showing, 
the effect of oxygen in its active form upon micro- 
organisms. Practically this method has only been 
tested upon some guinea-pigs and one goat. 
% 
TUBERCULOSIS. 
Seldom, if ever, has any medical discovery been 
received immediately with such intense interest as the- 
modest announcement by Robert Koch* within the 
past year, that he had traced tuberculosis to the pres- 
ence of a bacterial parasite. And yet the ground had 
been fully broken for this discovery, it was recognized 
by all competent pathologists, that this is an infectious 
disease and attempts had even been made by others to- 
demonstrate the parasite presumably the cause of 
tuberculosis. But while these previous researches could 
not command universal respect on account of their 
want of precision, Koch’s statements were .so positive 
and his high reputation gave them such a speedy 
circulation, as to provoke a remarkable enthusiasm, but- 
on the other hand also some bigoted opposition. 
Since Yillemin showed in 1865 that tuberculosis is- 
inoculable in the lower animals by means of products 
of the disease, this statement has been completely 
confirmed by all other experimenters. In susceptible 
animals, like rabbits and guinea-pigs, the introduction 
of tubercular nodules, or of pus from tuberculous 
inflammation, into any part of the body invariably 
results in the eruption of tubercles at that spot and 
very often also in the production of a general tubercu- 
losis of internal organs. In other animals . not se 
liable to take the disease spontaneously, as cat and. 
Klinische Wochenschrift No. 15, Apr. 10, 1882. TUBEECULOSIS BY INOCULATION. 
153 
dog, its experimental production is not so certain to 
succeed, unless large quantities of tubercular material 
are used and are implanted into the interior of the 
body. But. it has been claimed that tuberculosis will 
also result in rabbits from inoculation with non-tuber- 
cular matter, or from the simple introduction of 
foreign bodies under the skin. If this were true it 
would denote that no “specific virus” is requisite in 
order to originate tuberculosis. Such an important 
claim should therefore receive due critical attention. 
As regards the fact itself there can be no doubt.. 
Numerous observers have seen animals become tuber- 
culous after placing setons, or bits of glass or wood 
under the skin. But rabbits and guinea-pigs contract 
this disease often, even without such apparent cause, 
especially in close confinement and when kept in 
laboratories in which experiments have been made 
upon tuberculosis. Thus Formad* who has lately 
referred to this point, found most of his animals tuber- 
culous in a previous study upon diphtheria.f If this 
is hence such a common disease in his laboratory and 
stables, there is nothing surprising in the fact, that 
amongst the animals inoculated with material of non- 
tubercular origin many should also take the disease. 
But in localities, where tuberculosis does not prevail 
amongst the animals, the effects of inoculation are 
evident and not at all ambiguous. Under those cir- 
cumstances while every rabbit, which is infected 
purposely gets tuberculous, the disease does not 
appear after simple wounds or the introduction of 
foreign bodies. The study of tubercular infection in 
a locality, thoroughly infected with the disease is as 
difficult and unsatisfactory, as would be a research on 
Med. Times, Nov. 18, 1882. 
•[National Board of Health Bulletin, Supplement No. 17, 1882. THE GERM THEORY OF DISEASE. 
the virus of small-pox during an epidemic of that 
affection. Every unprotected individual inoculated 
with variolous crust would be sure to take small-pox, 
but a great many, who received injection of some 
harmless material, might also be stricken with the 
disease, because the virus would be disseminated through 
the air, as well as by the lancet of the experimenter. 
Cohnheim and Fraenkel, who found every animal 
tuberculous in the laboratory of the Berlin patho- 
logical institute, no matter how slight had been the 
wound previously inflicted, got the disease only, when 
they purposely produced it by proper infection, on 
repeating these experiments in their separate private 
dwellings. Now it may seem strange to medical men 
that tuberculosis is so infectious and can be communi- 
cated so. easily unintentionally through the air or the 
cage of the animal, for such is not the experience as 
far as man is concerned. But it is true, nevertheless, 
of rodents. All animals are not equally susceptible to 
tuberculosis or any other disease. 
Even in infected localities the specific nature of the 
tubercular virus can be proven by inoculation in parts, 
where the disease does not localize itself spontane- 
ously. The eye according to all observers is very 
rarely, if ever, the seat of tuberculosis in animals. 
But in the hands of numerous observers* the intro- 
duction of tubercular material into the anterior cham- 
ber of the eye never failed to produce tuberculosis of 
the iris. Other fluids or solid fragments, not of tuber- 
*Cohnheim, Die Tuberculose vom Standpunkte der Infectionslehre, 
1879.—P. Haensell, Archiv f. Ophthalm. Bd. XXV, H. 4, p. 1. Deutsch- 
mann, ibidem, p. 280, and Bd. XXVI, H 2, p. 99.—A. Costa Pruneda, 
ibid., Bd. XXVI, H. 3, p. 1/ 4. Salomonsen, Nordisk Medicinsk Archiv., 
1879, No. 19.—Samuelsohn, Bericht d. Heidelberger Gesellschaft, in 
Centralblatt f. Augenheilkunde, Feb. 1880.—Baumgarten, Centralblatt f. 
d. med. Wiss., 1881, No. 15.—Schuchard, Virchow’s Archiv, Vol. 88, p. 28. INOCULABILITY OF PRODUCTS. 
155 
cular origin, may destroy the eye by suppurative 
inflammation, when put into the anterior chamber, but 
they never start a tubercular process. In properly 
executed experiments with tubercular material there 
results a slight temporary—if any—-inflammation. But 
after the lapse of some twelve days the guinea-pig* 
thus inoculated invariably shows an eruption of gray 
nodules in the iris, which gradually coalesce and 
destroy the eyeball. Gross appearances, as well as the 
microscope, characterize this process as tuberculosis. 
In most, though' not all instances, general tuberculosis 
of other organs follows in the course of some weeks. 
Sometimes, however, the process remains localized. In 
either case the nature of the disease is the same, but 
in the latter instance the resistance of the animal to 
the tubercular invasion is greater. No matter whether 
the disease remains localized or becomes disseminated 
throughout the system, the virus is the same, only 
the reaction of the animal varies. 
Indeed, all of the numerous recent researches, con- 
ducted with proper care, lead to the conclusion, that 
the best criterion of the tubercular nature of any 
morbid process is the inoculabilty of the products. 
Whatever can reproduce tubercle on inoculation, con- 
tains the tubercular virus and is tubercle. The 
structure of the morbid products is by means as 
•characteristic of the nature of the disease as their infec- 
tiousness, for notable differences occur in the amount 
of reticulum of the tubercular nodule, in the pres- 
ence or absence of giant-cells and even in the 
general architecture of the disease-growth in different 
animal species and even in the different organs of one 
and the same animal. Thus the pearl-tumors of cattle 
are so different in their structure from tubercles in 
*l5 to 20 days in the rabbit. 156 
THE GERM THEORY OE DISEASE. 
man and other animals, that the microscope alone conlcl 
not decide on their tubercular nature. But inoculation- 
experiments prove their identity. It has furthermore 
been shown in such experiments by Cohnheim and by 
Schueller,* that we must range amongst the localized 
tubercular processes not only the chronic inflamma- 
tion of joints, as had previously been claimed, but 
also the scrofulous lymph-glands and lupus. 
The nature of the tubercular virus was first investi- 
gated by Klebsf and by his pupil Reinstadler. £ The 
assumption, that it was constituted *by bacteria was 
tested by culture-experiments in albumen, in which 
the growth of granules and mobile short rods was 
observed. There can be no doubt now, since Koch’s 
latest researches, that ihe bacilli, really the cause of 
tuberculosis, were not seen at all by these authors, for 
they could not have grown under the circumstances. 
Still it was claimed by Klebs, that he reproduced the 
disease with the cultivated parasites. No satisfactory 
explanation can be given of such results, which are 
undoubtedly erroneous, except that the material used 
for inoculation still contained some of the true tuber- 
cle-bacilli, which the author overlooked in the absence 
of staining methods, or that unintentional infection 
occurred through insufficient disinfection of the instru- 
ments. Schueller claims to have corroborated Klebs’ 
investigation, but to his own experiments the same 
criticism applies, as well as to those of Toussaint,§ 
who seeks the cause of the disease in a micrococcus. 
At any rate the methods employed by these authors 
-Experimentelle und histolog. Untersuchungen neber d. Entstehung 
u. Ursachen d. skrophuloesen n. tuberculoesen Gelenkleiden, 1880. 
fCommunication to the Congress of German Naturalists at Munich. 
1877. 
JArchiv f. Experiment Pathologie Bd. 11, p. 103. 
§Comptes Rendus, 1881. MICRO-ORGANISMS IN TUBERCULOSIS. 
157 
seem altogether insufficient, when compared with the 
preciseness displayed and the spirit of severe criticism 
exercised by Koch in his celebrated publication.* 
More accurate, undoubtedly, was the observation of 
Baumgarten,f who saw in all tubercular nodules bacilli 
evidently identical with those Koch described at the 
same time. But this author did not go beyond their 
detection, he did not demonstrate their importance. 
The bacilli, which Koch discovered can be recoo-_ 
O 
nized only with great difficulty without staining, on 
account of their delicacy and minuteness. Since they 
cannot be rendered visible at all by the ordinary 
methods of staining, we can readily understand why 
they had not been previously seen (except by Baum- 
garten, who treated the sections with caustic potash 
solution). The special method, which Koch used for 
their detection we shall describe later on in connec- 
tion with the examination of the sputum. The bacilli 
thus stained appear as slender rods one quarter or 
half as long as a red blood-corpuscle, and extremely 
thin. They can be identified with greater certainty 
by means of their behavior to aniline colors, rather 
than by their shape and size alone. For with the 
exception of the bacilli of leprosy, from which they 
differ in shape, no other bacteria have as yet been 
found, which possess the same peculiarities with refer- 
ence to staining. When examined fresh, these never 
show any active movements. These parasites are found 
most abundant at the border of any progressive tuber- 
cular infiltration, partly in the interior of cells, partly 
free between them, but they exist also throughout the 
entire tubercular growth, though to a less extent. 
Their number is in some proportion to the activity of 
Klin. Wochenschrift, No. 15, 1882. 
•fCentralblatt f. d. med. Wissenschaften, No. 15, 1882 158 
THE GERM THEORY OF DISEASE. 
the morbid process. When the latter is arrested, very 
few bacilli can be found. The imperfect staining of 
these few indicates, that they are dead. Wherever 
giant-cells occur, they contain some bacilli in their 
interior, though here also the parasites may disappear 
by disintegration. Not infrequently the bacilli appear 
granular and contain from two to four oval spores. 
The importance of these micro-organisms with refer- 
ence to tuberculosis is evident, when we learn that 
Koch found them in every instance in the examination 
of eleven cases of human miliary tuberculosis, twelve 
of caseous bronchitis, one of tubercle of the brain, two 
of intestinal tuberculosis, three of scrofulous glands 
and four instances of fungous arthritis of man. They 
were never missed in ten cases of pearl-disease of 
cattle, some two dozen different animals dead of spon- 
taneous tuberculosis and about 200 animals inoculated 
with the disease. Koch’s researches have been made 
on such an extensive scale, that the confirmation by 
other authors,* of the invariable presence of these 
bacilli in the tubercular products can hardly add any 
more to their conolusiveness. 
The bacillus tuberensis has been cultivated by Koch 
on the surface of solidified blood-serum. The tuber- 
cular nodules from fresh internal organs of animals 
and of man were placed on this soil, whereupon the 
colonies of bacilli in their interior kept on growing 
and gradually extended in the form of white scales 
over the surface of the serum. The growth is very 
slow, so that it requires about ten days before it is at 
all apparent. The slow growth and the dryness of 
these scales distinguish such a pure culture from all 
other bacteria. Moreover the growth is limited to a 
*Ehrlich, Sternberg, Balmer and Frsentzel, Gibbes, Williams, Licht- 
heim and others. INOCULATION WITH THE ISOLATED BACILLUS. 
159 
temperature of 30 to 41° C. In the course of several 
weeks the growth of a colony was completed, but the 
cultivation was continued by transferring a fragment 
of this first culture to a fresh soil. The parasite could 
thus be grown for months without any change in its 
properties. 
The inoculation of animals with the isolated para- 
sites did not fail to produce tuberculosis in a single 
instance out of some two hundred experiments. The 
effect was the same, no matter how long the bacilli 
had been cultivated outside of the animal body. jn 
some instances this was continued for some 140 days 
Injection of the isolated parasites into the anterior 
chamber of the eye, into the peritoneal cavity, into 
the blood-vessels or simply under the skin, rendered 
every animal tubercular, not only the susceptible rab- 
bits and guinea-pigs, but also the more resistant rats 
cats and dogs. In the less susceptible animals, how- 
ever, it was requisite to put the parasites into some 
protected locality, like those mentioned. The mere 
inoculation of superficial wounds did not suffice, for 
on account of the slow growth of the tubercle-bacilli 
they cannot gain a foothold through surface abrasions, 
but are eliminated. The infection with the isolated 
parasites leads to quicker and more extensive results 
than when the crude tubercular material is employed 
on account of the greater number of bacilli in the 
former case. In all of Koch’s experiments the orig- 
inally localized disease was followed by disseminated 
tuberculosis. There is always a tubercular infiltration 
and later on ulceration at the site of the infection 
from which the disease then spreads to the rest of the 
system. 
The manner, in which the disease spreads most 
commonly in man, is assumed by Koch to be the fol- 160 
THE GERM THEORY OF DISEASE. 
lowing: Tlie sputum of most consumptives contains 
the bacilli. However readily the developed bacilli 
may succumb to the influence of time, desiccation or 
damaging agents, the spores, which are often, though 
not invariably, contained in the sputa, share the inde- 
structibility of bacterial spores in general. The drying 
of the expectorated matter and its subsequent conver- 
sion into dust by the foot, that treads on it, or any 
other force, disseminates these spores throughout the 
atmosphere. Whenever they settle on a suitable soil 
the bacilli develop. We are evidently exposed to this 
infectious dust in all localities where consumptives have 
ever lived and expectorated, i. e., all over the civilized 
world. It reaches the interior of the lungs and if it 
can find the proper conditions for development, its 
growth begins. That sputum does retain its infec- 
tiousness on drying, Koch proved by inoculating ani- 
mals successfully with material dried since eight weeks. 
The experiments of Tappeiner* on the other hand had 
previously shown, that the inhalation of tubercular 
matter, for instance, a spray of an emulsion of sputum, 
does lead, invariably, to the infection of the animal, 
even in the more resistant dogs. Finally the evidence 
seems complete, when we remember that the disease is 
always localized primarily, at the point of infection 
and that in the great majority of instances tubercu- 
losis begins in the lungs. But Koch does not claim 
that this is the only mode of the dissemination of the 
disease. Ransomej- has found micro-organisms in the 
condensed breath of consumptives, which gave the 
color-reaction of the bacillus tuberculosis. But the 
number, thus exhaled, must be small compared with 
* Communication to the German Congress of Naturalists at 
Munich, 1877. 
Medical Journal, Dec. 16, 1882. TUBERCULOSIS A SPECIFIC INFECTION. 
161 
the large amount of bacilli in the sputum. The dis- 
ease besides can be communicated by the consumption 
of tubercular material, as has been proven in animals 
by quite a number of different observers. In such 
instances it begins in the intestines or mesenteric 
glands. It is not probable, that the virus can multiply 
outside of the animal body, on account of the high 
temperature it requires, the complicated nourishment 
it needs, and the slow growth even under the most 
favorable circumstances. 
Koch’s researches have as yet received no adequate 
confirmation. Korab* claims to have cultivated the 
bacilli and inoculated animals with them successfully, 
but does not state any details. His object was to 
prove the destructive properties of Helenin on the 
tubercle parasites. Sternbergf had but partial success 
in the repetition of Koch’s works, but admits the 
incompleteness of his own researches. The mere 
presence of the parasite in tubercular products has 
been confirmed by all observers. On the other hand 
objections mostly of a speculative nature have been 
urged against Koch’s work, none of them, however, 
founded on actual observation. The query, raised by 
some authors as to the bacterial nature of the bacilli, 
has no sense at all in view of their easy demonstration. 
Tormad has recalled the old time-worn arguments of 
the occurrence of tuberculosis in animals without 
“specific” infection, but has ignored that others have 
trodden the same ground before him and have been 
completely refuted. At any rate no one has yet shown, 
that the disease can ever exist without the presence of 
the bacillus tuberculosis. £ 
Rendus, No. 10. Yol. 95, 1882. 
{Medical News, Nov. 18, 1882. 
{While these lectures go to press an important confirmation of 162 
THE GERM THEORY OE DISEASE. 
Apart from the fundamental scientific importance of 
Koch’s work, it has almost at once led to immediate 
practical results. Koch’s own statement, that the 
bacilli are often present in the sputum of consump- 
tives, has been confirmed by a host of other observers, 
so that the microscopic examination of the sputum 
possesses now a decided diagnostic value.* It is nec- 
essary hence to become acquainted with the mode of 
demonstrating the bacilli. 
The tubercle bacilli do not take up the ordinary 
aniline colors readily. They require some “ mordant ” 
to fix the dye on them, but when once stained, they 
hold the color more tenaciously than other bacteria or 
animal cells. Koch’s original staining method required 
the use of a solution of methyl blue (one part con- 
centrated alcoholic solution in 200 parts of water) with 
the addition of tq-otto P potassic hydrate or some 
other alkali. Specimens were kept in it for twenty- 
four hours, which time could be shortened by heating 
gently. By means of a concentrated filtered solution 
of Vesuvin in water, the blue color was then removed 
from all structural elements but the bacilli, which 
now appeared blue on a brown ground. This method 
seems tedious and not easy to employ. Ehrliclif has 
Koch’s work has just appeared by Watson Cheyne. In a preliminary 
report (Lancet, March 17th, 1888) to the “Association for the Advance- 
ment of Medicine by Research,” he states, that he has tested the viru- 
lence of pure cultures of the alleged parasites of tuberculosis, received 
personally from Toussaint and from Koch. The former material, con- 
taining micrococci, was found absolutely inert, though Toussaint had 
rendered animals tubercular by inoculation with it. This result Cheyne 
refers to a gross self-deception due to insufficient disinfection of the 
syringe employed, as well as of the locality, in which the animals were 
kept. On proper attention to the hygiene of the animals and the disin- 
fection by heat of all the utensils, Cheyne found that no animal ever 
*Vide Gradle and Woltmann, Philadelphia Med. News, Feb. 17,1883, 
j"Deutsche Med. Wochenschrift, No. 19, 1882. HOW TO STAIN BACILLI IN THE SPUTUM. 
163 
since substituted aniline oil or “ crude aniline ” as a 
mordant for the alkali with the use of fuchsin as the 
first color. The specimen is then decolorized in nitric 
acid diluted with twice the amount of water, until all 
visible color has just left it, whereupon it is washed. 
Again the tubercle bacilli are the last elements to 
yield their tint, but their detection is facilitated by 
restaining the ground blue. They now appear as 
ruby red rods on a blue ground. In the case of 
sputum a minute particle is spread and dried in a 
thin film upon a cover glass and the film thereupon 
hardened by passing it through a flame. An instan- 
taneous staining can now be accomplished by placing 
it in a watch glass filled with the solution and heat- 
ing, until it simmers. The experience of different 
authors has shown this to be the quickest way to 
prepare the solution, viz: to dissolve aniline oil in 
water, to filter and to keep on hand, and to add to a 
watch-glassful of this fluid some eight drops of a sat- 
urated alcoholic solution of fuchsin. The specimen is 
then decolorized as above described. Gibbes* has 
suggested the addition of more alcohol to this fluid 
in order to keep it stable, but I have had the neatest 
result with a modification of Ehrlich’s process which 
I have published with Mr, Woltmann in the “Medical 
News.”f Two grams of fuchsin are dissolved in a 
became tuberculous, except when purposely infected with Koch’s bacilli, 
or material containing them. The animals, which had become infected 
with true tuberculosis in the hands of Toussaint, showed the usual abund- 
ance of Koch’s bacilli, in the tubercular organs, but no micrococci. 
Twenty-five rabbits received foreign substances, under the skin, in the 
anterior chamber of the eye and in the peritoneal cavity, of which not 
one became tubercular, because they were kept in healthy stables. 
Koch’s statements on the other hand Cheyne was able to confirm word 
by word as regards the appearance and color-reaction of the bacilli. 
*Lancet, Aug. 5,1882. 
|Feb’y 17, 1883. 164 
THE GERM THEORY OF DISEASE. 
mixture of fixe grams aniline oil and twenty grams of 
alcohol, to which twenty grams of water are gradually 
added. This fluid, once filtered, can be kept as stock, 
but I have since found, that it will not remain clear 
for more than three or four weeks. For use it is 
simply diluted with twenty or thirty times as much 
water and the specimen kept in it at least two hours. 
A warmth of 40° to 60° C. favors the staining, but 
when the bacilli are few in number, they are apt to 
be overlooked unless a very deep color is imparted to 
them by an exposure up to twenty-four hours. Here- 
upon it is decolorized in dilute nitric acid, washed 
and the ground stained by dropping on a two per cent, 
solution of aniline blue and washing again after one 
minute’s exposure. It can now be examined at once 
in water or mounted permanently in Canada balsam. 
The detection of isolated bacilli in such a specimen is 
quite difficult without an Abbe’s condenser, but with 
its use they can scarcely be overlooked. Still I have 
assured myself, that an insufficient staining will allow 
the bacilli, if few in number, to escape detection and 
I consider it best, therefore, to deepen the color as 
much as possible in the examination of sputum for 
diagnostic purposes. It seems most plausible to me, 
that those observers (Guttmann, perhaps also Pfeiffer) 
their distribution in the disease, their cultivation and virulence. He 
adds, furthermore, the different forms in which the disease appears clini- 
cally depend on the variable resistance of the individual to the parasitic 
invasion. Whenever the parasites can vegetate luxuriantly, the disease 
appears as catarrhal pneumonia rapidly destructive to the lung tissue, 
while the slower forms of fibrous pneumonia remain localized for a time 
on account of the production of a barrier of granulation tissue around 
the tubercular nodules, which hinders the further spreading of the 
bacilli from the affected spot. According to Cheyne the bacilli grow pri- 
marily in the interior of the alveolar epithelial cells, the proliferation 
of which forms the essential basis of the tubercular nodule. He could 
trace the giant cells to a coalescence of separate epithelial cells. Hence HOW TO STAIN SPUTUM. 
165 
who missed the bacilli relatively often in the sputum 
of consumptives, did not stain their specimens suffi- 
ciently. I say this with more confidence, since I have 
become acquainted with another method, which stains 
the bacilli so deeply, that it is impossible to overlook 
them. 
The mordant, used in this case is carbolic acid, to 
a five per cent, aqueous solution of which is added 
about one fifth or eighth the quantity of a saturated 
alcoholic solution of fuchsin. The fluid precipitates 
some of the dye on standing, hence it is preferable 
to mix the two constituents at the time when 
required, no filtering being necessary. The dried 
sputum is allowed to float in this fluid, or a drop of 
it is simply placed on the film of the cover-glass. 
The staining does not require a full minute, if the 
specimen be heated. But the heat must not reach the 
boiling point and, when once stained, the specimen 
cannot be again exposed to heat without damage. 
The bacilli, thus treated, do not retain the color quite 
as tenaciously, as when stained with the aniline 
method, hence a little more caution is requisite, while 
decolorizing with nitric acid. But on the other hand 
the tint given to the bacilli is so intense, that there 
is no’object to restain the ground with a contrasting 
color. Even without a condenser the bacilli, though 
according to him the starting point of the disease in pulmonary phthisis 
is the alveolar surface, and the spreading of the process is partly due to 
the continued vegetation of the bacilli in extending from each center, 
partly to the infection of fresh alveoli, by mechanical transfer of the 
sputum. 
Another publication lately issued is by Spina (Studien ueber Tuber- 
culose, 1883). It claims to be a complete refutation of Koch’s work. 
Spina'finds the tubercle bacilli not characterized by any color-reaction, 
fails to detect them in the tubercles of interior organs and obtains no 
characteristic result from inoculation with the cultivated micro-organ- 
isms. But as Koch has justly said in a reply (Deutsche Med. Wochen- 166 
THE GERM THEORY OF DISEASE. 
there be but one in the field, attract the eye immedi- 
ately. Since the application of this method does not 
consume more than three or five minutes, and the 
material requisite is so conveniently procured, I would 
recommend it most for the clinical examination of 
sputum. But it has this drawback. With the aniline 
method or Koch’s original procedure the difference in 
the reaction of the tubercle-bacilli and other bacteria 
is absolute, while on staining by means of the car- 
bolated solution the difference is only relative. 
While the tubercle-bacilli are the last elements to 
yield their color to the acid, still they too begin to 
fade, when some other kinds of bacteria have not yet 
had all their color abstracted by the acid. Hence there 
may be some stained bacteria left in the specimen. I 
found in most sputa a micrococcus in chains and a 
bacillus a trifle longer and much thicker than the 
real tubercle-bacilli. The latter, however, are stained 
much darker and can be recognized besides by their 
shape and size. While therefore this method enables 
us to decide instantly, whether the sought for bacilli 
are absent in a sputum, any doubt as to their identity 
in case of their presence may be removed by the use 
of the more characteristic aniline method. The bacilli,. 
thus stained in the sputum, are of the appearance 
above described, the rods being often curved or two 
of them forming a figure Y. Frequently they are 
granular on account of the spores they contain, which 
spores are distinctly stained. Sometimes irregular 
groups of spores are seen. The bacilli may be very 
schrift, No. 10, 1868), Spina’s experiments are but a caricature of his 
own. He shows a want of familiarity with staining and examining 
methods, his cultivating soil was not in a proper condition and the 
inoculation experiments were performed on tivo rabbits. What a con- 
trast between such hasty work and Koch’s researches extending over two> 
years and involving over 200 different animals! TUBERCLE-BACILLI IN THE SPUTUM. 
167 
few in number, perhaps only one in several fields of 
the microscope, or on the other hand a few dozen 
may be found in every field with a power of 500 to 
900 diameters. When numerous they form small 
groups, otherwise they are scattered throughout the 
field. 
Koch’s original statement, that the tubercle-bacilli 
are often present in the sputum of consumptives ha 
been fully confirmed by the published observations of 
some fifteen to twenty different authors, while no 
voice has as yet been heard to the contrary. These 
same authors have all examined some few—or in other 
cases, quite a number—-of specimens of sputa from 
other non-tuberculous diseases, without finding these 
bacilli. This accumulated evidence, based on the neg- 
ative results of at least 150 to 200 examinations of 
non-tuberculous cases, proves absolutely, that the 'pres- 
ence of the characteristic tubercle-bacilli in the sputum 
indicates pulmonary tuberculosis. When they are 
present, there can be no question as to the existence 
of the disease. But are they invariably present? The 
claims of different authors do not all agree on this 
point, Guttmann* examined one hundred slides, in 
one fourth of which only the parasites could be found. 
He does not state how many different cases these 
specimens represent. From his own description I 
infer, that he did not stain for a sufficient length of 
time and hence overlooked the imperfectly colored 
bacteria in many instances. 
Pfeifferf examined daily the sputa of four patients 
during twenty-five days. In the mildest case the 
bacilli were found in all but seven slides, in the 
severest instances they were missed only three times. 
*Berliner Klin. Wochenschrift, No. 52, 1882. 
■("Berliner Klin. Wochenschrift, No. 3, 1883. 168 
THE GERM THEORY OF DISEASE. 
Altogether they were absent sixteen times out of one 
hundred examinations. Even in this case I suspect 
they were overlooked occasionally, since Pfeiffer used 
at first gentian-violet for staining, and only later the 
deeper color of fuchsin. On the other hand they 
were found every time by Ehrlich* in 26 phthis- 
ical patients, by Gibbesf in 19 instances, by Balmer 
and EraentzelJ in 120 consumptives, by Ziehl§ in 
73 cases, by D’Espine|| in 20 patients, by 
in 62 cases, by West (a) in 50 instances, by Wipham (6) 
in 20 consumptives, by Dreschfeld(c) in 46 consump- 
tives, and by myself (in conjunction with Mr. Wolt- 
mann) in some thirty to thirty-five consecutive 
tubercular patients. But it is not always evident in 
the publications quoted, whether they were encountered 
at every examination of one and the same patient. 
Balmer and Eraentzel insist on repeating the search 
for the bacilli at least on three different days, in case 
they are not seen the first time. Liohtheim (d) also 
claims to have detected them in every case, though 
not on every examination. He does not say how 
often. In our experience we have never examined any 
specimen of sputum in vain, if bacilli were found at 
any time in the expectoration of that patient, provided 
only the staining was sufficient. Still I have just 
searched three times for the bacilli without being 
certain of their presence, in the sputum of a patient 
♦Deutsche Med. Wochenschrift, No. 19, 1882. 
fLancet, Aug. sth, 1882. 
jßerliner Klin. Wochenschrift, No. 45, 1882. 
§Deutsche Med. Wochenshrift, No. 5, 1883. 
)| Quoted in Lancet, Jan. 13, 1883. 
•[[Lancet, Feb. 3rd, 1883. 
(а) Lancet, Feb. 10th, 1883. 
(б) Lancet, Feb. 10,1883. 
(c) British Med. Journal, Feb. 17th, 1883. 
(d) Fortschritte der Medicin, No. 1, 1883. BACILLI IN SPUTUM OF PHTHISICAL PATIENTS. 
169 
dying o£ a rapid catarrhal pneumonia, though no 
autopsy could be performed to confirm the diagnosis. 
Dettweiler and Meissen* also saw two cases, —as they 
say— of unmistakable phthisis, out of eighty-seven 
patients in the sputum of which the bacilli were not 
detected. Reviewing this evidence, therefore, we can 
assert, that the bacilli can be found in the sputum of 
the overwhelming majority of phthisical patients, cer- 
tainly over ninety, if not ninety-five per cent., and that 
in most cases they can be detected at the first examina- 
tion. Their presence in the sputum is hence one of the 
most constant,—if not the most constant—sign of 
pulmonary tuberculosis. Moreover this sign is the 
most delicate test for the disease, for different 
observers, myself included, have met with cases, 
revealed by microscopic .examination, in which the 
physical exploration gave an ambiguous result at the 
time, while the subsequent course of the disease con- 
firmed the diagnosis. This sign is besides the earliest 
objective indication of pulmonary tuberculosis, for 
Hillerf has detected the characteristic bacilli in the 
blood and scant expectoration of two patients, afflicted 
with the initial pulmonary haemorrhage, while in a 
third case of this kind there was not enough sputum 
to be examined. Lichtheim has also diagnosed acute 
phthisis dating back but a fortnight, by means of the 
microscope. Examination of the sputum should, there- 
fore, be resorted to in all doubtful cases. 
The bacillus tuberculosis has also been detected by 
Lichtheim in the stools in intestinal tuberculosis, 
while EosensteinJ and Babes§ have found it in the 
Klin. Wochenschrift, Nos. 7 and 8, 1883. 
Med. Wochenschrift, No. 47, 1882. 
jCentralblatt f. d. med. Wissenschaften, Feb. 3rd, 1883. 
gCentralblatt, March 3rd, 1883. 170 
THE GERM THEORY OF DISEASE. 
urine in tuberculosis of the urinary organs. Finally 
Fraenkel *has availed himself of the presence of the 
bacillus tuberculosis as an evidence of the tubercular 
nature of doubtful laryngeal ulcerations. In some 
twenty cases he could detect the parasites, at least 
once in three examinations, on searching for them in 
the secretion removed with a laryngeal brush. 
Klin. Wochenschrift, Nos. 8 and 4, 1883. GLANDERS. 
171 
LECTURE VII. 
Glanders.—Typhoid Fever.—Relapsing Fever.—Small-Pox.—Cow-Pox. 
Sheep-Pox.—Measles.—Malaria.— Diphtheria.— Leprosy.—Syphilis. 
—The Milk-Epidemic in Aberdeen. 
GLANDERS 
lias recently been added to tlie list of diseases of known 
origin. The most decisive researches were made at the 
laboratory of the German board of health by Loeffler and 
Schuetz.* In the ulcerated tissues and typical nodules 
taken from the horse, bacilli were found in limited 
numbers in and outside of the cells. They resembled 
the Bacillus Tuberculosis in shape and size, but were 
readily stained by methyl-blue. They could be cul- 
tivated on the surface of solidified serum of the horse 
and sheep. Their inoculation produced in rabbits 
and guinea-pigs a fatal disease, beginning with nodu- 
lar growths, which extended from the spot of inocula- 
tion to internal organs. The identity of this affection 
with genuine glanders was proven by reproducing the 
disease in its typical form in the animal, which it 
commonly attacks, viz: the horse. Since this disease 
* Deutsche Med. Wochenschrift, No. 52, 1882. 172 
THE GEEM THEOEY OF DISEASE. 
can also affect tlie human being, the—as yet small— 
list of human evils traceable to bacterial invasion is 
thus increased by one. 
A corroboration of these researches has appeared 
independently by Israel,* who had for some time pre- 
viously found the same micro-organism in the pus and 
nodules of glanders of the horse. He had also culti- 
vated them on the surface of solidified serum and 
obtained with the pure culture an affection in rabbits, 
which possessed all the characteristic lesions of glan- 
ders. He has had no chance as yet to inoculate 
horses. In the pus of closed abscesses in glandered 
horses the bacilli were not seen. Almost at the same 
time there has also appeared a French publication by 
Bouchard, Capiton and Charrin,! who have found mic- 
ro-organisms in the disease, but who do not give a 
sufficient description of their appearance to enable one 
to identify them with the bacilli of the Germans. Still 
they have cultivated them successfully in broth and 
have obtained in sixty-one different rodents a disease 
identical with the form in which glanders appears in 
them on direct inoculation with the tissues of the 
diseased horse. 
TYPHOID FEVER, 
In this disease various observers (Recklinghausen, 
Klein and others) have found colonies of micrococci in 
the blood-vessels and in the midst of the tissues. But 
this is by no means always the case; quite often these 
micro-organisms are not present in the cadaver. More- 
over, since they do not differ in appearance from the 
colonies of micrococci found in other diseases of the 
septic type, there is no good reason why they should 
Klinische Wochenschrift, No. 11, 1888. 
■(■ Bulletin of the Academie de Medicine, No. 51, 1882. TYPHOID FEVER. 
173 
be considered as related to the cause of the disease. 
Perhaps they represent only a complication. 
A well-characterized bacillus, however, has been 
found in this disease by Eberth.* It is a short, thick 
rod, of delicate contour, with rounded ends, often with 
vacuole-like spots in its interior, perhaps spores. He 
has found it chiefly in the intestinal follicles, but also 
in the mesenteric glands and the spleen. It stains 
easily, when the fluid is scraped off the fresh tissue 
and dried on a cover-glass, but Eberth could not 
demonstrate it well in stained sections. Hence he 
used acetic acid as a reagent, whereby he could only 
detect it in groups, but not, when scattered through 
the tissue. He found it only in about one half of his 
cases of typhoid fever, of which he examined twenty- 
three instances in his first publication. It was present 
especially during the earlier part of the course of the 
disease. While its absence in one half of the cases is 
as yet unexplained, it can hardly be denied that this 
parasite has some important relation to the disease, 
since its frequent presence has been confirmed by 
others, while Eberth, who has sought for it, has never 
met with it in any other disease. Independently of 
Eberth, Koch f has discovered the same bacillus, which 
he illustrates in some photographs. Like Eberth, he 
found it in only about half of the cases. Since he 
succeeded in staining it well by using warm solutions, 
it is not likely that its presence in the negative cases 
was overlooked. He detected it in the liver, spleen 
and kidney as well as the intestinal follicles. The 
same bacilli Avere seen also by Meyer £ (under Fried- 
lander’s guidance) in seventeen of twenty-three cases. 
* Virchow’s Archiv. Bd. 81., p. 58, and Bd. 83, p. 486. 
* f Mittheilungen, &c. p. 45. 
f Dissertation, 1881. Abstracted in Centraiblatt No. 26, 1882. 174 
THE GERM THEORY OF DISEASE. 
They were only sought for in the intestinal canal, where 
they exist in the interior of the swollen patches and in 
the lymphatic spaces of the external tunics, while they 
were not found in cadavers dead of other diseases. 
They have been detected, furthermore, by Coats* and 
bv Cooke;‘j- each in one case. The causal relation of 
this parasite to the disease can of course not be 
affirmed until proven by inoculation experiments, how- 
ever plausible this suspicion may appear. 
has described a different bacillus in typhoid 
fever. It forms long filaments, up to 0.08 millimeters, 
but extremely thin (0.2 micromillimeters). These 
threads increase somewhat in thickness during their 
growth, then divide into short segments, in which 
spores appear thereupon. They were detected both 
in the ulcerated Peyerian patches and in various 
intestinal organs as well as in the blood-vessels. But 
since staining methods were not used, their alleged 
discovery in internal organs must be received with cau- 
tion, to say the least. In the intestinal lesions they 
disappear towards the end of the disease. Klebs 
claims to have cultivated these bacilli in solutions of 
isinglass and inoculated with them a few different ani- 
mals. Some of the rabbits were killed thereby in 
two days and at the autopsy the bacilli were found in 
the interior of the intestinal follicles—again in un- 
stained sections. Although there was neither any 
symptom nor any lesion characteristic of typhoid fever 
in these few animals, Klebs does not hesitate to call 
his “ bacillus typhus ” the cause of the disease. Koch— 
certainly a competent critic—doubts altogether the 
importance of Klebs’ bacilli, because he could find 
*Brit. Med. Journal, March, 1882. 
tßrit. Med. Journal,' July, 1882. 
t Archiv. f. experiment. Pathologie, Bd. XIII. TYPHOID FEVER. 
175 
them only in the necrotic tissue, which offers no resist- 
ance to the invasion of any parasites coming from the 
intestinal surface, that hot-bed of micro-organisms. 
Meyer, likewise, has met with these filaments only in 
the necrotic patches open to post-mortem invasion. 
Tizzoni * has isolated bacteria from drinking water 
by filtration, during an epidemic of typhoid fever. 
Injected under the skin of animals these gave rise to 
the intestinal symptoms of the disease and in the 
lesions the same micrococci and delicate mycelia were 
found as in the disease of man. It would be unfair 
to criticise this work without reading the original, but 
the abstract to which I have access does not let it 
appear very trustworthy. 
A similar want of reliability is apparent in the pub- 
lication of Brantlecht.f In the urine of typhoid patients 
and in drinking water, suspected as the source of 
infection, he found a species of bacteria, forming in 
the water an iridescent scum on standing in closed 
vessels in the warmth. On cultivation in solutions 
of gelatine containing phosphate of ammonium, he 
obtained whitish flakes consisting of very thin but 
long, immovable filaments, which segmented into short 
rods and ultimately into granules, perhaps representing 
spores. Their growth was quite slow. The injection of 
these bacteria under the skin of rabbits produced a slight 
rise of temperature, one of 0.5 to 1.5° C. (which means 
nothing in the rabbit) lasting less than two days. 
But this was followed by emaciation, rarely by diar- 
rhoea, leading to the death of the animal in four to 
eight weeks. At the autopsy (in sixty-nine cases) 
catarrh of the small intestines, swelling of the mesen- 
teric glands and of the spleen was observed. But all 
* Abstracted in Revue des Sciences Med., October, 1881, p. 718, 
t Virchow’s Archiv., Bd. 84, p. 80. 176 
THE GERM THEORY OE DISEASE. 
these lesions are not characteristic of typhoid fever in- 
man while the intestinal ulcerations which Brantlecht 
did not find, are positive evidence of the disease. 
Since, hence, neither symptoms nor lesions corres- 
ponded to the disease in man, since the fluids were 
anything but pure cultures and since the parasites 
were not even looked for in the human tissues, there 
is really no light thrown upon the cause of the dis- 
ease by these researches. It may be of interest to add, 
however, that the bacteria which Brantlecht studied, 
gradually lost their virulence by continued artificial 
cultivation and the mild, non-fatal attack, which they 
then produced gave the animals immunity against a 
second inoculation. Whatever the disease, which he 
obtained in rabbits, may have been, the mode of infec- 
tion, which we suspect on just grounds in typhoid 
fever, viz; through the intestinal canal, did not suc- 
ceed with any certainty in that disorder. 
Maragliano * has examined the blood of fifteen typhoid 
fever patients during life—partly from the finger, partly 
drawn from the spleen. During the height of the 
fever he found numerous round, granules and to a less 
extent bacilli, which he compares with those of Klebs 
and Eberth without distinguishing between the two 
different kinds. 
RELAPSING FEVER 
is invariably accompanied by the presence of a para- 
site in the blood—the Spirochcete of Ohermeier, who 
discovered it in 1878. The regular occurrence of this 
spirillum during the fever has been confirmed by so 
many different authors in hundreds of cases, that its 
significance cannot be doubted. Some exceptions have 
* Centralblatt f. d. Med. Wiss., No. 41, 1882, RELAPSING EEYER. 
177 
also been reported, but there is no evidence that those 
authors sought for them with sufficient care, certainly 
not with the aid of staining methods. It is a slender 
twisted filament about twelve to forty-three micromilli- 
meters long, comparable in shape to a corkscrew, there 
being some four to ten narrow turns. In the living 
state it shows usually a lively movement, an eel-like 
twisting, varying with a rotation around a central 
axis, as well as telescopic changes in length due to 
winding and unwinding of the coils. As the blood 
clots on the slide, the spirilla seek the clear spaces 
filled with serum (Vandyke Carter*), The parasite 
seems adhesive and often sticks to blood corpuscles. 
On the slide, kept moist, it has a tendency to form 
densely-matted clusters, which are also found at times 
in the post-mortem blood. The parasite has, so far, 
been found only in the blood and has never been met 
with in any other disease but recurrent fever. It 
begins to appear some hours before the first attack of 
fever, when careful scrutiny will detect a few in each 
slide. During the febrile paroxysm they increase in 
number, until they may exceed the number of red- 
corpuscles, but at the close of the attack, they disap- 
pear suddenly. They are not to be found after this 
time, until a few hours before the characteristic relapses 
of the diseases. They persist for some hours or days 
in the blood of the cadaver, provided the patient 
died during the paroxysm. Both Carter in India 
and various European authors have reported cases of 
infection traceable to the performance of an autopsy 
upon patients. 
It is difficult to see the spirilla in the fresh 
state on account of their delicacy. But in the dried 
film on the cover-glass they can be better demon- 
*Spirillum Fever—lBB2. 178 
THE GERM THEORY OF DISEASE. 
strated after clearing with glacial acetic acid or 
they may be stained in the usual way with aniline 
colors. In the interior of capillaries in sections they 
do not take up aniline colors, except brown, and that 
but feebly. 
very decisive has been learned in culture 
-experiments made by different observers. Both Koch 
and Carter saw the spirilla elongate considerably and 
increase noticeably in thickness on keeping them in 
warm glass cells in pure serum or serum diluted with 
aqueous humor. They formed dense clusters, gave 
indications of segmentation or showed the formation of 
bright granules. Yet an unmistakable multiplication 
was not observed. They may remain alive for five or 
eight days under these circumstances, or even longer 
according to other observers, showing occasional, but 
sluggish movements. Ultimately they form an aggre- 
gation of granules or disappear entirely. Their 
gradual appearance could not be watched in blood 
taken prior to a relapse, in which no developed spi- 
rilla existed as yet. If the germs did pre-exist in the 
blood, they could not develop under the circumstances. 
Albrecht* took samples of blood at short intervals 
before the expected relapse and found successively 
free granules, accumulating into groups of six to ten, 
elongation of these into the form of chains and tran- 
sition from such granular chains of zig-zag shape 
into perfect spirilla. But he has never seen the con- 
tinuous development of any one living specimen. 
Hence the periodicity of the appearance of the spirilla, 
their prompt vanishing at the end of the attack and 
the mode of propagation of the parasites are as yet 
unsolved problems. 
Although the isolation of the spirilla has not yet 
*Archiv. f. klin. Medicin, Vol. 29, p. 77. RELAPSING FEVEE—SMALL POX. 
179 
been accomplished, the disease has been reproduced 
by inoculation with blood containing the parasites, 
while the blood o£ the same patients, taken at times 
when no spirilla were present, was wholly inactive. 
Attempts by Obermeier and his various successors have 
shown the ordinary domestic animals to be insuscep- 
tible to the disease, but both Carter and Koch* have 
succeeded in the monkey. Carterf inoculated twenty- 
two monkeys with human blood containing the para- 
sites and obtained infection sixteen times. In seven 
of eleven attempts the disease was also transmitted 
from one animal to another. Why exceptions occurred 
was not learned. Blood taken from the same patients 
both human and animal during the afebrile period 
proved harmless. In the monkey neither the charac- 
teristic relapses nor complications occur, the fever, 
though sometimes fatal, being of shorter duration than 
in man. But the nature of the inoculated disease is 
definitely established by the presence of the spirilla in 
the blood during the attack. That the blood contain- 
ing the spirilla is infectious has furthermore been 
proven by in successful inoculations 
of human beings. The disease confers no immunity 
upon man or monkey. Both Carter and Koch suc- 
ceeded in inoculating the same animals twice. 
The eruptive fevers of man, so eminently contagious, 
have not yet been experimentally studied to any satis- 
factory extent, as far as the nature of the virus is 
concerned. In 
SMALL-POX 
microccoci were discovered by Luginbuehl§ in sec - 
*Mittheilungen, etc., p. 166. 
tSpirillum Fever, p. 429. 
jAbstr. in Centralblatt f. d. med. Wissensschafter, 1876, No. 11. 
§Abstr. in Schmidt’s Jahrbuecher, Vol. 166., p. 217. 180 
THE GERM THEORY OF DISEASE. 
tions cleared with acetic acid. They formed colonies 
between the corium and epithelium of the skin, prin- 
cipally in the papules, but also to a less extent 
between them. More extensive and numerous have 
been the observations by Weigert.* It was he who 
principally introduced the staining methods for bac- 
teria, though he did not at that time use the best 
illumination. He detected microccoci in zoogloea 
masses in every instance of papules not too far 
progressed, where they existed at the border of 
the corium and epidermis. These cocci formed 
also embolic masses in the blood-vessels of internal 
organs. Both in the skin and in the viscera each 
developed colony was surrounded by necrotic tissue* 
evidently the result of the parasitic action. The 
micrococci colonies in internal organs in variola are 
also illustrated by photographs in Koch’s “ Mitthei- 
lungen aus dem kaiserlichen Gesundheitsamte.” Micro- 
cocci in twos and fours have likewise been seen by 
Klebsf in the tracheal mucous of small-pox patients, and 
in the contents of vaccine pustules. Ko culture experi- 
ments have as yet been reported in this disease. It 
is not improbable, that the micrococci, which constitute 
the granules in 
COW-POX VIRUS 
represent the mitigated small-pox parasites. In 
spite of numerous failures in the hands of a French 
commission headed by Chauveau and of other experi- 
menters (Klein) we cannot deny, that Ceely and that 
Babcock did really succeed, though but a few times, 
in inoculating the heifer with small-pox virus and 
producing thereby genuine cow-pox, transmissible as 
*Abstr. in Schmidt’s Jahrbuecher, Yol. 166, p. 217. 
fArchiv. f. experimentelle Path., Yol. X. COW-POX. 
181 
such to the human arm. Evidently the conditions 
necessary for the transformation of the small-pox 
poison -into the mitigated form of cow-pox virus are 
not yet understood. Perhaps the most light is thrown 
upon the subject by the recent researches of Voigt,* 
who found that the virus of the human disease must 
be passed through several animal generations—the 
bodies of some six cows in succession—until its viru- 
lence is sufficiently reduced to produce in man but 
the localized form of disease, which suffices for 
immunity. The hope seems reasonable, that the condi- 
tions of mitigation can be better studied, after the 
active elements have once been isolated. 
In the vaccine lymph numerous micrococci are 
found, according to the testimony of all observers. 
The same granules have been invariably seen by Pohl- 
Pincusf in the extirpated papules and pustules pro- 
duced by vaccination in the calf. They existed both 
in colonies and scattered throughout the epithelium. 
In the slight inflammatory reaction caused by a second 
vaccination of the animal after the lapse of a fortnight, 
these micrococci could not gain a foothold. Although 
these parasites have never been separately cultivated 
it was shown long ago by Chauveau in experiments 
now classical, £ that the active principle of the lymph 
of cow-pOx, horse-pox, and sheep-pox consists of gran- 
ules insoluble in the serum. For when he carefully 
poured a stratum of water upon a layer of lymph in 
tiny tubes, he obtained a diffusion of the dissolved 
material into the water, but this clear solution could not 
produce pustules like the insoluble residue. On the 
other hand on diluting the lymph with water there 
in the “ Medical News ” Oct. 21st, 1882. 
|Wirkung der Vaccination, x\bstr. in Centralblatt, No. 25, 1882. 
jGomptes Rendus, 1868. 182 
THE GERM THEORY OF DISEASE. 
was no enfeeblement noticeable in its action, as there 
would be were the active agent in the fluid state. 
When the lymph was diluted with fifty times as much 
water, the effect of an inoculation with this mixture 
became uncertain, but when a pustule did develop it 
possessed all its typical characteristics. These results 
can only be interpreted as indicating the corpuscular 
nature of the active agent. The virus of 
SHEEP-POX 
has been isolated by Toussaint* in the form of ba- 
cilli of the length of three to four micromillimeters. 
They could be grown in broth in which they showed 
lively movements, elongated and then divided into two 
segments of unequal length, in which there appeared 
one or two spores. The inoculation of sheep gave rise 
to pustules, which do not seem to have been as well 
developed, as those produced by the original lymph. 
In the urine of patients with 
MEASLES 
Leßelf has just discovered a “vibrio” about one micro- 
millimeter thick and of variable length, endowed 
with slow movement and producing spores. The same 
bacteria were also found in the furfuraceous scales of 
the skin and were not met with in other diseases. A 
different observation at least equally reliable is that by 
who detected micrococci in the living blood 
of measles, but only in severe cases. The same micro- 
organism existed in the cutaneous lesions of all pa- 
* Comptes Rendus, Vol. 92, p. 362. 
fComptes Rendus, No. 1, 1883. 
Med. Times, No. 384, 1882. MALARIAL FEVERS. 
183 
tients. He does not seem to have made use of stain 
ing methods, however. 
MALARIAL FEVERS 
have proven an encouraging field for etiological re- 
searches. The older results of Salisbury and others, 
who attributed the cause of these disorders to palmel- 
loid growths, have not been confirmed at all by any 
modern research conducted with more rigorous methods. 
In 1879 Klebs and Tommasi-Crudeli * announced the 
discovery of a “ bacillus malarise,” the spores of which 
were obtained from the soil and the air of malarial 
districts. These spores, slightly less than a micromilli- 
meter in size grew into long threads, subsequently 
segmenting, in solutions of gelatine and in min- 
iature mud-swamps. Their growth required the pres- 
ence of oxygen. Their injection into the bodies of 
rabbits produced a fever lasting several days, with 
some diurnal fluctuations of the temperature. These 
animals, when killed, showed considerable enlargement 
of the spleen and the presence of black pigment in 
that organ and in the blood. In the blood, the spleen 
and the marrow of the bones, the bacilli were found 
in the form of threads 0.06 to 0.084 millimeters long 
and 0.6 micromillimeters wide. Now this may be 
malaria, but since we do not know in what form the 
disease does appear in rabbits, the experiments furnish 
really no convincing proof. Sternberg f on repeating 
them with bacilli obtained from the mud at New 
Orleans, could not confirm these results, but that is 
not saying, that he refuted them, as he himself admits, 
for he may not have had the same micro-organism. 
Marchiafava and Cuboni J have subsequently detected 
* Archiv. f. experimentelle Path., Vol. 11. 
■(■ National Board of Health, Supplement No. 14, July, 1881. 
J Archiv. f. experimentelle Path., Bd. 13. 184 
THE GEEM THEOEY OF DISEASE. 
granules in tlie blood of malarial patients, which they 
tried to identify with the spores of Klebs and Tom- 
masi-Crudeli. They also saw a few bacilli. They 
injected the blood of human patients into the veins of 
dogs and obtained a somewhat intermittent fever. 
Marchand * published later some casual observations, 
made some years previously on a malarial patient, in 
whose blood he found granules and a few movable rods 
with spore-like swellings at the ends corresponding 
to Klebs’ description, but only during the paroxysm. 
Ziehlf detected similar bacilli, few in number, in the 
blood of three fever patients. After the cure of two 
of these by quinine the micro-organisms disappeared. 
Of twenty-five other non-malarial individuals examined 
in this respect, only one showed the presence of these 
bacilli in the blood. It was a case of diabetes, possi- 
bly of malarial origin, for it was cured by quinine, 
whereupon the bacilli disappeared. Finally has 
cultivated the spores of malarial earth (under Klebs’ 
guidance) in artificial swamps, and in solutions of 
gelatine, and claims that the power of these bacilli, to 
produce an intermittent fever in rabbits, diminishes on 
continued artificial cultivation. But I can find no evi- 
dence at all in his article, that the bacteria cultivated 
really produced anything like a malarial affection. 
Hence however plausible the doctrine of the “ Bacillus 
Malarias” may sound, the experimental supports fur- 
nished by the school of Klebs are as yet insufficient 
and not convincing. 
An entirely different micro-organism Laveran§ claims 
to have detected in the blood of some forty out of 
* Virchow’s Archiv., Band 88, p. 104. 
tDeutsche Med. Wochenschrift, Nov. 25,1882. 
% Archiv. f. experimented Path., Vols. 15 and 16. 
§Comptes Rendns, Vol. 93, No. 17. DIPHTHERIA. 
185 
sixty malarial patients and never in other diseases. 
He describes three forms, viz.: 1. Oval corpuscles, 
slightly larger than red blood-disks drawn out at both 
ends and pigmented in the center. 2. Spherical cor- 
puscles about six micromillimeters in size with numer- 
ous pigment granules and, when in motion, extending 
out long delicate processes from the periphery. 3. 
Granulated spherical motionless globules about 0.01 
millimeters in size, apt to change into irregular plates. 
He considers these three fanciful forms but different 
phases in the development of an animal parasite. But 
as he has neither cultivated nor isolated the alleged 
parasite and has not even shown, that it is not an 
altered blood-corpuscle, no further conclusions of 
course can be drawn from his researches. The same 
suspense of judgment must be maintained with refer- 
ence to the statements of Bichard,* who claims to 
have made similar observations on the existence of 
this parasitic animal in the malarial blood. 
DIPHTHERIA. 
In the pseudo-membranes of‘this disease bacteria of 
different kinds occur in large numbers. This, indeed, 
might be expected in the case of dead tissues, kept 
warm and moist and exposed to the invasion of the 
numerous micro-organisms abounding on mucous sur- 
faces. The most constant bacteria met with are 
micrococci partly in zoogloea masses of a yellowish 
hue. They were first described by Oertel (1868) and 
their presence has been confirmed since by many 
observers. A very full description is given of them 
by Wood and Formad.f They are of various sizes 
and are distributed throughout the false membranes, 
*Comptes Rendus, Yol. 24, p. 49. 
■[National Board of Health Bulletin, Supplement No. 17, Jan., 1882. 186 
THE GEEM THEOEY OE DISEASE. 
being partly between, partly in the interior o£ the 
remnants of cells. Wood and Formad speak of them 
as round granules, while Oertel in his late publica- 
tion* describes them as slender rods 1 by 0.3 micro- 
millimeters and larger ones 4.2 by 1.1 micromillime- 
ters, joined in pairs and in chains, also in zoogloea 
form. There is as yet, however, no proof, that these 
micrococci are the cause of the disease. Their presence 
in the exposed dead tissue is no evidence, for the 
membrane represents but the necrotic mucous lining. 
Indeed, when the healthy mucous membrane of the 
mouth or trachea is destroyed by caustics, for instance 
ammonia, the eschar into which it is converted—really 
a pseudo-membrane —contains the same micrococci, as 
are found in true diphtheria, as Wood and Formad 
have learned. Moreover in the scrapings of the healthy 
tongue the same micrococci can be seen. Of more 
significance is the detection of the same—or similar 
micrococci in the blood of the living patient during 
severe attacks. But since these parasites were found 
only in the more severe cases and not in all instances 
of the disease, were seen also in the blood of other sep- 
tic disorders, and since no cultures have been made 
with the fresh blood, there is not yet enough evidence 
for any decision. In the internal organs bacteria are 
not found with any regularity in diphtheria. Oertel 
in Ziemssen’s Cyclopaedia states, that he has usually 
met with micrococci in the kidneys in this disease. 
Eberth, Gaucher and Litten have each seen one 
instance of bacterial presence in the inflamed kidney in 
diphtheria, but in other cases, more numerous, they 
have not been detected by competent investigators. 
In the heart, spleen and liver bacterial colonies have 
*Vortraege in Aerztlichen Yerein zu Muenchen, Zur iEtiologie der 
Infections krankheiten, 1881, p. 225. INOCULATION WITH DIPHTHERIA. 
187 
been, but not invariably found. Tlieir arrangement 
resembled strikingly the lesions of pyaemia. Hence 
the occasional presence of bacteria in the viscera pre- 
sents probably but an accidental complication of diph- 
theria. 
Many of the attempts at inoculation of animals with 
diphtherial material throw no light whatever upon the 
nature of this disease. For quite often the membranes 
were put under the skin of animals, where they started 
a destructive inflammation, resembling hospital gan- 
grene. Now this is not at all diphtheria, as we see it 
clinically. It is true the Germans speak of “diph- 
theria of wounds,” but it is yet to be proven, that this 
process is identical as to its cause with the diphtheria 
of mucous membranes. Clinically we speak of diph- 
theria only, when there occurs a spreading destruction 
of a mucous membrane, converting it into a pseudo- 
membrane. This alone is the essence of the disease, 
every thing else is secondary. Such a destruction of 
the epithelial and often also of the deeper layers of a. 
mucous lining appears as a false membrane, no mat- 
ter whether it be caused by mechanical or chemical 
influences or by the specific diphtherial virus, hut in 
the latter case only will the process extend, while 
chemical injuries give rise to the same appearance, 
limited, however, to the spot originally involved. 
Hence the application of caustics and of heat to 
mucous surfaces causes the same pseudo-membranes, 
which neither the naked eye nor the microscope 
can distinguish from the genuine diphtherial pro- 
ducts. But these false membranes do not increase 
beyond their original size. In order to recognize 
the diphtheritic virus, we must therefore apply it 
to mucous membranes as a test. This has been done, 
but such an inoculation does not always take effect. 188 
THE GEEM THEORY OP DISEASE. 
Trendelenburg succeeded but eleven times in fifty-two 
trials, on placing human pseudo-membranes into the 
trachea of rabbits and pigeons. Wood and Formad 
had but two successes in thirty-six inoculations with 
material taken from mild cases of the disease, while 
with more virulent membranes from epidemic cases five 
infections occurred in ten attempts. Twice they also 
transferred the membrane from one animal to another. 
Now this is sufficient to prove the inoculability of the 
disease. As regards the explanation of the failures, we 
must take into account the varying susceptibility of 
animals, for the rabbit is not known to take diphthe- 
ria spontaneously, as well as our ignorance as regards 
the diphtherial virus and whether it is not “ crowded 
out” of the false membranes by other bacteria. The 
inoculability of the disease does not prove bacteria to 
be the cause, however likely this may be. As regards 
culture experiments I can only find a record of them 
in the numerous publications by Letzerich and the 
report by Wood and Formad. The former author, 
working with the most defective methods and jumping 
at conclusions on the basis of few and most inade- 
quate experiments, cannot demand any belief for his 
assertions. Such productions can only bring the germ- 
theory into discredit. The American observers, how- 
ever, have cultivated micrococci from the diphtherial 
membranes by methods perfectly reliable,—only the 
material from which they took their germs, the mem- 
branes, contained of course any number of accidental 
germs. Hence there is no proof positive, that the 
crop which they did get, represented the parasites of 
diphtheria. Moreover they cultivated apparently the 
same micrococci from scrapings of the tongue. They 
found that these micrococci could not grow indefi- 
nitely in a broth of rabbit, but that the vegetation BACTERIAL ORIGIN OF DIPHTHERIA. 
189 
became feebler in each successive transfer to a fresh 
soil. The micrococci of tongue scrapings showed the 
feeblest power of multiplication, while the bacteria 
from the membranes of severe cases of diphtheria 
could be cultivated through some eight or nine succes- 
sive generations. As they claim, other bacteria did 
not enter their flasks. This limitation of the power of 
reproduction is so entirely different from what has 
been observed in other bacteria, that it requires con- 
firmation and further study before it can be accepted 
as proven. All other bacteria, that have been studied, 
retain their unlimited power of reproduction on trans- 
fer to a fresh soil, if this soil is at all adequate for 
their vegetation. 
The inoculation of eight rabbits in the trachea with 
the micrococci cultivated by Wood and Form ad, gave a 
wholly negative result, while in thirteen other instances 
injection into the muscles showed likewise, that these 
bacteria could not cause anything like diphtheria. How 
the authors can hence identify these micrococci with 
the cause of diphtheria, I cannot understand. They 
also believe to have isolated the micrococci in another 
manner, viz: by filtration of the urine of diphtherial 
patients and inoculation with the filter-paper. But 
they do not state, what kinds of bacteria the urine 
contained, relying on the worthless statements by 
Letzerich, that there are only micrococci present, and 
with the paper thus employed they produced pycemia 
in two rabbits and nothing at all in two others. 
While these researches cannot therefore prove the 
bacterial origin of diphtheria, this presumption is not 
disproven by the experiments of Satterthwaite and 
Curtis.* For the latter observers, who claim, that 
they can obtain results identical with those produced 
* Report to the New York Board of Health, 1877. I did not have 190 
THE GERM THEORY OF DISEASE. 
by pseudo-membranes, by the inoculation with putrid 
fluids, did not at all produce diphtheria in animals, 
but only some form of blood-poisoning or local inflam- 
mation and destructive phlegmons. They injected under 
the skin or into the muscles and hence did not 
search for the diphtherial virus by any adequate test. 
Klebs,* who has by this time discovered the germs 
of almost every disease, has found in the diphtherial 
membranes the 11 ‘ micrococcus diphthericus ” in the 
form of “micrococci balls” (zooglcea?), which become 
transformed into minute rods and ultimately into deli- 
cate mycelium growing in the tissues. Like all of 
Klebs’ bacteria, these forms were cultivated in solu- 
tions of isinglass. Their injection produced blood- 
poisoning without any characteristic appearances of 
diphtheria. 
Some ten years ago Eberth produced—what he 
called—diphtheria of the cornea, by inoculation with 
membranes, later on also with pysemic pus. The 
same result was then obtained by Dolschenkow,f Leber 
and others with common putrid material and also with 
mould-fungi. But this is simply a necrosis of the 
cornea due to bacterial invasion and bears no resem- 
blance whatever to true diphtheria. 
Entirely different are the observations of Talamon.J 
In the false membranes examined fresh he found an 
organism, which could be regarded as a higher fungus. 
He did not examine any sections of human tissues 
and hence cannot state anything about its occurrence 
anywhere, except in the membranes. In some of the 
viscera, however, of the inoculated animals the same 
the original, but know it from the quotation by Wood and Formad 
(loc. cit.) and Jacobi “On Diphtheria.” 
* Archiv. f. experimentelle Pathologie, Vol. IV. 
fYide Centralblatt, 1873. 
fProgres Medical, Feb. 17 and June 25, 1881. talamon’s fungus in diphtheria. 
191 
fungus was found. No staining methods were used 
and hence no reliable details were brought forth. 
With the membranes culture solutions were infected, 
what kind, and in what arrangement is not stated. 
As the result he observed the development of a con- 
tinuous mycelium some two to five micromillimeters 
thick, arid partitioned off by transverse septa. The 
places of bifurcation resembled the branches of a 
tuning-fork or lyre. In other less favorable cases 
there were only thick rods arranged like crutches, 
some fifteen to forty micromillimeters long. The 
spores were oval, three to five micromillimeters in 
size and often grouped in zoogloea masses. There 
were also “ conidia ” rectangular in shape, several times 
as large as the spores, arranged frequently in chains. 
All these forms were of gigantic dimensions, when 
compared with bacteria. Why, hence, did they escape 
the observation of other investigators? I can only 
find a record of some observations by Nix,* who saw 
similar fungi in diphtherial membranes in Norway 
without knowing of Talamon’s work. 
Talamon inoculated a variety of animals with his 
cultures. Various rabbits, guinea-pigs, frogs and 
chickens died, containing these fungi in their tissues. 
But in none of these instances were there any appear- 
ances of diphtheria. In four pigeons, however, he 
obtained genuine pseudo-membranes in the mouth, 
which contained the fungi. In some kittens, dead of 
spontaneous diphtheria, acquired in the laboratory, the 
same micro-organisms were detected in the membranes 
and viscera. Talamon’s statements are so startling, that 
it is best to wait for further confirmation, or at least 
for more precise details, than he has published so far. 
* Abstr. in Jahresbericht ueber die Leistungen in der Med., 1881, 
Bd. I, Abth. 11, p. 389. 192 
THE GERM THEORY OF DISEASE. 
LEPROSY. 
As far as mere observation can prove, this affection 
is one of bacterial origin. More cautiously speaking, it 
can be stated, that characteristic bacilli are invariably 
found in leprous growths, but their importance has 
not yet been established absolutely, as it only can be 
by isolation and inoculation. They were discovered by 
Hansen * and further studied by Neisser,f Cornil, 
and by Koebner.J They have been found in every 
case of leprosy examined by these authors and several 
others.§ The “bacillus leprse” is a very delicate rod, 
about one half the length of a red blood disc and one 
fourth as wide as long, tapering at the ends. The 
rod may be thickened by several nodosities the 
spores. It is found scattered or in interlaced groups, 
or in articulated chains, mainly in the interior of the 
cells and only in the leprous infiltrations of the 
tissues, not in healthy parts. The so-called lepra-cells 
or globi constitute the remnants of degenerated ani- 
mal cells, choked with large clusters of bacilli. The 
parasites exist in all the leprous tissues, but have not 
been found in the blood except by Koebner (and by 
Gaucher in a rather doubtful manner). In the skin 
the bacilli appear as separate short rods, but in inter- 
nal organs Cornil]| describes them as long unsegmented 
filaments. The bacilli, which have some active motion, 
while alive, can be recognized only with difficulty in 
the fresh specimen, better after the application of 
* Norwegian publication in 1873, and Virchow’s Archiv., 1880, Bd. 
79, I. 
f Virchow’s Archiv., Bd. 85, p. 514. 
X Virchow’s Archiv., Bd. 88, p. 282. 
§ Dr. Schmidt of New Orleans claims to have been unable to demon- 
strate them, but his slides, which I have seen, were stained imper- 
fectly and diffusely and were not examined with a proper condenser. 
||Bull, of the Paris Academie de Med., No. 3, 1881. LEPROSY SYPHILIS. 
193 
dilute potash solution (1 in 12). In sections of hard- 
ened tissues they stain well with fuchsin, less per- 
fectly with violet. Koebner recommends drying the 
tissues before they are hardened in alcohol. Cover- 
glass films of fluid can be stained readily, but the 
bacilli are not visible until the specimen has been 
partly decolorized in alcohol. 
The bacilli have been cultivated in serum on hollow 
slides by Neisser, and lately on the surface of blood- 
serum and gelatine mixtures by Hansen.* Their 
growth is rather slow, and requires a high tempera- 
ture. In meat-broth Hansen could not get them to 
vegetate. Their spores appear at first as nodular thick- 
enings of the filaments; later on they may be set free. 
The decisive experiment of inoculating animals with 
isolated bacilli has not yet succeeded, though attempted 
by Neisser, Koebner and Hansen,—probably because the 
domestic animals possess an immunity against the 
disease. Even in a monkey Koebner has failed to obtain 
any infection by means of transplanted nodules. 
Since it is believed in the East, that the disease 
exists amongst fishes, Koebner has also tried some of 
these animals, but likewise with no success. Leprosy 
can hence not yet be ranged amongst the diseases of 
proven bacterial origin. 
It is of interest to note, that in three diseases, classed 
by pathologists as “infectious granulation tumors,” 
viz: tuberculosis, glanders and leprosy, the invariable 
presence of bacilli has been demonstrated. In the 
fourth member of that group, viz; 
SYPHILIS, 
our knowledge is as yet imperfect. Klebsf has culti- 
* Virchow’s Archiv., Bd. 90, p. 542. 
t Archiv. f. experimentelle Path., Yol. X. 194 
THE GEEM THEOEY OF DISEASE. 
vated in egg albumen grannies and sliort twisted rods 
on placing bits of an excised chancre into it. This 
micro-organism he termed “ Helicomonas.” He could 
not demonstrate its presence, however, in any un- 
opened lesion. Inoculation experiments with the origi- 
nal syphilitic products succeeded only in the monkey, 
not in other animals, and then but occasionally. In 
one case, however, he had an undoubted success, as 
his description indicates to any one familiar with the 
disease. But on inoculating with the cultivated heli- 
comonads, the experiments were all of the most ambig- 
uous kind. In view of the unreliability of Klebs’ 
culture experiments, there is' hence no conclusion to 
be drawn from this research. 
Subsequently Aufrecht* described large oval micro- 
cocci in the interior of specific condylomata. Essen- 
tially the same things have been seen by Birch- 
Hirschfeld.f He spoke in his first communication of 
short rods, but corrected himself afterwards and now 
recognizes only oval micrococci, mostly in pairs and 
sometimes in the form of chains. They are readily 
shown by staining with fuchsin. He claims to have 
found them invariably in more than twelve gummatous 
tumors of internal organs, in three excised specific 
Avarts, in an extirpated chancre and in a syphilitic 
papule. They were not seen in the blood. 
Different again is the description by Morrison,£ of 
what he found in the secretions of fifteen different 
syphilitic lesions. Some of these were papules not 
ulcerated, and hence not exposed to the air. More- 
over, sections were made from one chancre and two 
papules. The sections and dried cover-glass films 
*Centralblatt f. d. med. Wissenschaften, No. 13, 1881. 
|Centralblatt, Nos. 33 and 44,1882. 
Med. Journal, Jan. Ist, 1883. SYPHILIS MILK-FEVER EPIDEMIC. 
195 
were put into acetic acid, then transferred to alcohol 
and dried and thereupon stained with methyl-blue 
or with fuchsin and decolorized in dilute nitric acid 
(1 in 6). In all specimens he found small rods 
(quite thick in his drawing), usually in groups. In 
the pus of soft chancres he found longer, but very 
thin bacilli, different from those in genuine syphilis. 
Of culture experiment and inoculation I can find a 
record only in the publication of Martineau and Ham- 
onic,* which appeals to the imagination rather than to 
criticism. Pasteur’s solution of tartrate of ammonium, 
in which no one has as yet succeeded in growing 
pathogenic bacteria, was infected with a piece from 
an excised chancre. In twenty-two hours it swarmed 
with “ bacteridia.” These were injected into a pig, 
their progeny was found in the blood on the next day, 
and a month later 1 there appeared a papulo-squamous 
eruption and falling out of the bristles. A somewhat 
similar result, following the inoculation with a piece of 
the original chancre, is to prove, that this disease of 
the pig is really syphilis. Fresh cultures made from 
the bacteria in the blood of these infected animals 
did not prove infectious to other animals. So much 
for the etiology of syphilis from that source! 
THE MILK-FEYER EPIDEMIC IN ABERDEEN 
was an instance of a hitherto unknown affection, occur- 
ring suddenly in an epidemic form, and traceable to 
the accidental diffusion of the bacteria producing it. 
The disease, described by I. Cossar Ewart, f attacked 
within a short time some three hundred people. It 
began with a chill followed by high fever, often with 
*Comptes Rendus, No. 10, Vol. 95. 
|Brit. Med. Journal, Nov. 4, 1882. 196 
THE GERM THEORY OE DISEASE. 
delirium, while the characteristic symptom was a swell- 
ing of the deep cervical glands. In twenty-four to 
forty-eight hours it had usually terminated, leaving 
behind considerable exhaustion. Sometimes relapses 
were observed involving other lymphatic glands. The 
cause of the epidemic was traced to the use of milk 
coming from one dairy. This milk had been watered. 
In the diluted milk and in the cistern from which 
the water was taken, a bacillus resembling the bacillus 
anthracis was detected. In one of the patients the 
swollen glands suppurated and in the pus the same 
bacilli were found. Rats inoculated with the para- 
sites died in eighteen to twenty-four hours. The 
bacilli were found vegetating in the tissues. But the 
description does not indicate, whether the experimental 
disease in the rats presented the same symptoms and 
lesions as the human affection. Hence the evidence 
as to the bacterial origin of the epidemic is not con- 
clusive, though very suggestive. 197 
LOCAL DISORDERS, 
LECTURE YIII. 
Local Diseases. Inflammations. Gonorrhoea and Gonorrhoeal Con- 
junctivitis. Trachoma. Croupous Pneumonia. Endocarditis.— 
Inflammations of Diathetic Origin.—Sympathetic Ophthalmia.— 
Whooping-Cough.—Rhinoscleroma.—Pterygium.—Carious Teeth.— 
The Poison of Rhus Toxicodendron.—The Importance and Future 
of the Germ-Theory.—Parasitic Mould-Fungi.—Actinomycosis. 
Most of the diseases, the aetiology of which we have 
thus far reviewed, are classified in the books as consti- 
tutional disorders. The revelations of the germ-theory, 
however, point out that the distinction between consti- 
tutional and local diseases can no longer be strictly 
maintained in the former sense. Of course a disease 
strictly localized and not affecting the rest of the sys- 
tem, is a local disorder, no matter from what point of 
view we regard it. But some of the affections, which 
have been considered of constitutional significance, for 
instance typhoid fever, erysipelas and—as we shall see 
presently croupous pneumonia, amount really to a 
localization of the parasite in some part, with only 
secondary involvement of the system at large, due 
probably to the absorption of morbid products, be 
they generated by the bacteria or set free by the 198 
THE GEEM THEOEY OF DISEASE. 
activity of the diseased tissues. Strictly constitu- 
tional are only those affections, in which the virus 
exists in the blood throughout the entire body, for 
instance anthrax and septicaemia. At any rate the line 
between the two classes of diseases cannot be drawn 
sharply, because in some local affections the active 
agent enters the blood secondarily, to be deposited 
somewhere else. However, these are all merely sug- 
gestions. Our knowledge is yet too imperfect to dis- 
cuss the subject much on the basis of facts. 
The most frequent of all local disorders—inflamma- 
tion—has been traced to parasitic influence in some 
few instances. We have discussed previously, that the 
suppurative inflammation of wounds and of abscesses 
is generally produced by the micrococci described by 
Ogston. It must be remembered, however, that sup- 
purative inflammation is a reaction of the tissues,, 
which can be induced by a sufficient irritation of 
chemical nature, as well as by the presence of certain 
bacteria, only the former cause is not so common. 
Undoubtedly various different species of bacteria can 
produce suppurative reaction of the tissues. Thus, 
besides the micrococcus of Ogston, we have learned that 
the pyaemia micrococcus of Koch and the “vibrio” of 
Pasteur, the micrococcus of progressive gangrene (Koch) 
all start suppuration. As we shall further see, a simi- 
lar result follows the invasion of the tissues by a 
higher fungus, the actinomyces. Probably other 
parasitic causes of suppuration may yet be discovered. 
In some instances of parasitic disease the occurrence 
of suppuration is probably a secondary matter, due to- 
the subsequent entrance of other germs. Thus tuber- 
culosis in the viscera does not always result in the 
formation of pus, in some organs like the brain— 
never, while in localities exposed to the air, as the- GONOEEHCEA. 
199 
lungs, the growth of the bacillus tuberculosis is com- 
plicated by some other influence causing suppuration. 
A special form of suppurative inflammation, which has 
always been recognized as due to a specific virus, viz: 
GONOKEHCEA, 
has been traced definitely to the invasion by a distinct 
and well-characterized parasite. Neisser* described as 
the “gonococcus” a large round granule, mostly in 
pairs (forming thus a characteristic biscuit-shaped 
diplococcus) and often in zoogloea colonies of ten to 
twenty or more. It exists partly free, partly on the 
surface of the pus cells, less often the epithelial cells. 
He found it only in the pus of gonorrhoea (thirty-five 
cases in the male and two in the female), and of the 
eye-disease due to gonorrhoeal infection, viz.; blen- 
norrhoeal conjunctivitis, and never in purulent fluids of 
other origin. Neisser’s statements have since been 
confirmed by Leistikowf and by Sternberg with refer- 
ence to gonorrhoea, and by Hirschberg and Krause}; 
and by Haab§ with reference to the contagious inflam- 
mation of the conjunctiva. But it must be added 
Hirschberg and Krause have also seen similar micro- 
organisms, though less in number, in the pus of sim- 
ple purulent conjunctivitis. 
The gonococci have been cultivated by Leistikow 
and by Krause! j on the surface of solidified blood- 
serum, on which they form a thin moist scum grow- 
ing very slowly. A singular observation was made 
with reference to the temperature. The first crop, 
*Centralblatt, No. 28, 1879. 
fCharite Annalen, Berlin. 1882. Over two hundred cases. 
JCentralblatt f. Augenheilkunde, Feb. and Sept., 1881. 
§Centralblatt f. Augenheilkunde, Sept. 1881. 
||Centralblatt f. Augenheilkunde, May, 1882. 200 
THE GEEM THEOEY OE DISEASE. 
obtained by infecting the soil with the specific pus, 
could not be cultivated except by exposure to a high 
temperature. But when a pure culture was once 
started, its growth did not cease at the ordinary tem- 
perature of the room. The virulence of these pure 
cultures, however, could not be proven, since none of 
the accessible animals could be infected with gon- 
orrhoea or purulent conjunctivitis by means of either 
the original pus or the isolated parasites. The inocu- 
lation of the cultivated gonococci into the conjunctiva 
or under the skin of animals, proved harmless. No 
animal has yet been found susceptible to human 
gonorrhoea. 
A positive result, however, was obtained by Bokai,* 
on injecting the cultivated gonococci into the urethrae 
of some medical students. In three cases out of six a 
genuine gonorrhoea resulted. But not sufficient details 
are stated to render the observations absolutely con- 
vincing. A similar experiment without the least flaw, 
has been successfully conducted by Bockhart.f The 
micrococci had been cultivated upon the surface of a 
gelatinous solution of meat extract and peptone. Of 
the fourth generation a small quantity was injected 
with due precautions into the healthy urethra of a 
bedridden demented patient, whose death was expected 
within a short time. Inside of three days there began 
a typical gonorrhoea, which lasted until the death of 
the patient on the tenth day. In the pus the charac- 
teristic cocci were found. At the autopsy the micro- 
cocci were seen in stained sections between the epi- 
thelial cells of the urethral mucous membrane, never 
in the epithelial cells, but frequently in the interior 
of pus cells, especially in the nuclei. They had veg- 
*Allgemeine Med. Centralzeitung, 1880, No. 74. 
'[■ Abstracted in Centrablatt f. Chirurgie, No. 9, 1883. MICROCOCCI THE CAUSE OE GONORRHCEA. 
201 
etated in the lymphatic spaces of the submucous tissue, 
plugging the whole caliber of some of the lymph 
vessels. Although but one experiment was made 
by Bockhart, the faultless methods employed, entitle it 
to full credit. Such a positive observation cannot be 
overthrown by the failure of another author in the 
same direction. Sternberg,* confirming Neisser as 
regards the invariable presence of the characteristic 
micro-organisms in gonorrhoeal pus, has cultivated 
these bacteria in rabbit broth and placed pellets of cot- 
ton saturated with the culture fluids into the urethra 
of five men (twice in one case) with wholly negative 
results. Since he has certainly worked with sufficient 
care, I can think of but two suggestions which might 
explain his failures. His cultures had all been long 
continued, the thirteenth and even thirtieth generations 
being employed. Now we cannot foretell, whether the 
micrococci retain their virulence forever in culture 
fluids, hence it would be preferable to test the first 
or second generation obtained from the original 
source. Moreover, it is very difficult, if possible, to 
guarantee, that in the course of thirteen to thirty 
successive cultivations in fluids, there has not been an 
entrance of foreign germs, perhaps not distinguishable 
by the microscope from the bacteria under observa- 
tion. On the other hand with the use of fluids for 
cultivating purposes everything depends on the purity 
of the first material. Sternberg states, that the micro- 
cocci which he cultivated from gonorrhoeal pus, could 
transform urea into carbonate of ammonia, were in 
fact identical with the “ micrococcus ureee.” In view 
of Bockhart’s positive result, is it not reasonable to 
suspect, that Sternberg had the accident of starting 
his culture with pus containing both the gonococci 
News, Jan. 20th and 27th, 1883. 202 
THE GERM THEORY OF DISEASE. 
and the “ micrococci urese ” and that the latter sur- 
vived alone! 
In connection with the origin of purulent conjunc- 
tivitis a very important experiment by Sattler* should 
be mentioned. The question has often been raised, 
whether the purulent ophthalmia of the new-born 
child can have any other cause, but the existence of 
a specific vaginitis of the mother. In order to decide 
this point Sattler put into the eye of a babe six days 
old the normal lochial discharge of a perfectly healthy 
mother, producing thereby a mild purulent conjunc- 
tivitis. The lochial secretion contained a large variety 
of bacteria, but not enough of the Gonococci to be 
certain of their presence. But in the conjunctival pus 
the characteristic micrococci were found in abundance. 
In spite of its interest this one experiment does not 
seem to me a sufficient basis for further conclusion. 
Conjunctival blenorrhoea is not rarely followed by 
TRACHOMA. 
More commonly, however, this disease begins as 
such. In the granulations, characteristic of this 
morbid process, Sattler f found invariably a coccus, 
slightly smaller than the gonococcus, either single or 
in pairs or small groups with an interspace between 
the separate granules, but never in zoogloea masses. 
It was seen principally on the surface of the—appar- 
ently free—nuclei, filling the trachomatous granula- 
tions. But it extended also into the depth by 
vegetation in the lymph spaces, which were partly 
obliterated in long-standing cases. In the pus of the 
*Bericht der Heidelberger Ophthalmologischen Gesellschaft, 1882, 
p. 54. 
fßericht der Heidelberger Ophthalmologischen Gesellschaft, 1881 
and 1882. TEACHOMA. 
203 
conjunctival sac the micrococci were not always 
present. Sattler has cultivated these parasites both in 
fluids on microscopic slides and on the surface of a 
gelatine-serum mixture. On the latter soil the culture 
appears as a delicate dust growing very slowly. The 
third generation of these cultivated micrococci was put 
with some friction into a healthy human conjunctival 
sac, producing thereby a typical, but mild, trachoma. 
The case was observed during several weeks, and then 
the diseased portion removed by excision. Previously 
Sattler had also obtained the same result by the inoc- 
ulation with the characteristic micrococci cultivated in 
a fluid soil. No success, however, was had on inocu- 
lating animals. That the disease, thus produced, was 
really characteristic trachoma was guaranteed both by 
competent clinical observation, and by the inability to 
obtain the specific disease by placing putrid refuse 
and cultures of other bacteria on the human conjunc- 
tiva. In these experiments Sattler of course took the 
precaution to attempt inoculation only, when the 
corneal epithelium was intact. For through an 
abrasion of the latter a dangerous suppurative inflam- 
mation might have been started by the putrefaction- 
bacteria. 
Of non-suppurative inflammations very few have as 
yet been traced to bacterial invasion. Perhaps the 
best known instance is 
CROUPOUS PNEUMONIA. 
In eight successive cases of this disease Friedlaen- 
der* found invariably an oval micrococcus, about one 
micromillimeter long and two-thirds as wide, often 
joined in pairs. If could be seen in stained sections 
* Virchow’s Archiv, Vol. 87, p. 319. 204 
THE GEEM THEOEY OF DISEASE. 
in the exsudate filling the alveoli, but its principal 
site was in the interior of the lymphatic vessels. 
Indeed it gave the latter the appearance of brilliant 
cords in sections simply cleared with acetic acid.* 
The significance of these micro-organisms, however, 
must remain undecided, until inoculation experiments 
succeed. Griffini and Cambria have also investigated 
the aetiology of pneumonia, finding a bacillus in the 
blood and sputa. But in the short abstract -j- acces- 
sible to me, I can find no evidence, that they have 
proven anything at all—either in favor of or against 
the bacterial origin. 
Our knowledge as regards other non-suppurative 
inflammations is as yet very meagre. In fact I cannot 
point to another clinical instance of a non-suppurative 
inflammatory process, definitely traced to the influence 
of bacteria, except some secondary complications during 
infectious diseases, of which the most common is 
ENDOCARDITIS. 
This affection, so frequent in the course of pyaemia, 
presents always the occurrence of bacteria in the 
inflamed tissue and in the fibrinous concretions on its 
surface. KoesterJ has traced the parasitic invasion of 
the cardiac valves to embolic plugs of bacteria in the 
smaller blood-vessels. He suggests, that the move- 
ments of the valves during the play of the heart favor 
the arrest and deposition in this region of any foreign 
particles existing in the blood. While numerous 
pathologists have seen and described the occurrence of 
parasites in the pysemic form of endocarditis I can find 
the same micro-organisms are figured by Koch in a 
photograph. Mittheilungen, etc., p. 46. 
■[Medical News, Dec. 28rd, 1882. 
fYirchow’s Archiv. Vol. 72, p. 257. INFLAMMATION OF DIATHETIC ORIGIN. 
205 
no further details reported except the statement, that 
they are usually micrococci. In other forms of endo- 
carditis not of pysemic orign, bacteria have also, but 
not invariably, been seen. Klebs insists especially on 
the presence of micrococci (or monads, as he calls 
them) in the rheumatic heart affections, thus leading 
to the inference, that rheumatism is also a parasitic 
disease. 
In various inflammations, formerly attributed to a 
“diathesis” we have now reason to think, that they 
originate through the deposition of parasites, existing 
in the circulation and that these bacteria develop mainly 
in those tissues, where they find the best conditions 
for their vegetation. That such a deposition of 
circulating parasites can occur I can illustrate by 
two examples. When Arloing, Cornevin and Thomas 
injected the bacilli of symptomatic charbon into the veins 
of cattle, the parasites could not develop to any extent 
and the animals did not suffer much. But whenever 
an extravasation of blood occurred in the muscles 
through an injury, the bacilli found the necessary 
conditions for their vegetation in the tissues and pro- 
duced their usual disastrous effects. Another illustration, 
even more to the point, has been furnished by Schuel- 
ler. In healthy rabbits the contusion of a joint gave 
rise to but a temporary irritation. But on injecting 
tubercular material into the veins, the circulating virus 
was deposited in the injured joints and there resulted 
a chronic tubercular inflammation of the joint. Evi- 
dently the injury rendered those tissues a favorable 
soil for the growth of the bacilli. 
A tissue in which inflammations of diathetic origin 
are quite commonly seen is the cornea. But on 
account of the scarcity of human material no demon- 
strations of the presence of bacteria have yet been 206 
THE GEEM THEORY OF DISEASE. 
furnished. Clinically we can observe a primary sup- 
purative inflammation of the cornea, in which micro- 
cocci have been seen by Leber. Since similar forms 
have been obtained by inoculations on animals, there 
can be little doubt, that this at least is a parasitic 
keratitis. Probably the parasites always enter in this 
form through some abrasion of the epithelium. But 
we know also of several other clinical forms of corneal 
disease, which must be regarded as manifestations of 
a diathesis or of the existence of some infectious virus 
in the body. There is thus a scrofulous, a syphilitic, a 
variolous, probably also a malarial keratitis. But I 
must repeat, however suggestive the topic is, it has 
not yet been worked up. 
In the so-much dreaded sympathetic forms of eye 
disease the infectious virus, probably their cause, reaches 
the second eye, not through the circulation, but by creep- 
ing up through the interspaces or between the sheaths 
of one optic nerve to the chiasm and thence descending 
along the other optic nerve. Such at least is a just 
inference from the researches of Knies* and of Leber, f 
but the positive demonstration is yet wanting. 
Of non-inflammatory diseases I may refer briefly to 
WHOOPING-COUGH, 
in which has regularly found short bacilli 
in the sputum on staining films of it. He has not 
met with these forms in the expectoration of other 
diseases. But of course the mere detection is not 
sufficient to demonstrate their importance. The older 
fanciful statements by Letzerich as regards the causa- 
tion of this disease by fungi have not been corrobo- 
rated and are now discredited by everybody. 
of Ophthalmology, Yol. 9, p. 125. 
fArchiv. f. Ophthalmologie, Bd. 27, H. I, p. 325. 
fßerliner Klinische Wochenschrift, No. 1, 1888. EHINOSCLEEOMA PTEEYGIUM. 
207 
RHINOSCLEROMA, 
a rare form of progressive induration of the tissues 
has been examined by Frisch* in twelve specimens, 
partly fresh, partly hardened. In all of these he 
found very short bacilli partly between, but mainly in 
the interior of the large swollen cells characteristic 
of the disease. The bacteria were cultivated on the 
surface of gelatine mixtures, but their inoculation did 
not succeed in animals. In a case of 
PTERYGIUM 
Poncetf has detected an extensive colony of bacteria 
under the head of the triangular growth, between it 
and the corneal tissue. He gives no description of 
them, but his drawing makes them appear as micro- 
cocci. Their relation to the growth was such that 
they must have preceded its development. However 
incomplete this observation is, it is certainly sugges- 
tive in pointing out the role of bacteria in a disease, 
where they never were suspected. 
Such hints as this one render it desirable to search 
for bacteria in all growths and tumors characterized 
by progressiveness. But no reliable observation has 
as yet been reported. ' 
CARIOUS TEETH 
have been known to harbor bacteria ever since, and 
even prior to the researches of Leber and Rottenstein 
in 1867. These authors found that the concretions on 
teeth—the so-called tartar contained besides the 
earthy salt, the remnants of the leptothrix buccalis, 
the articulated filaments found in every human mouth. 
*Wiener Med. Wochenschrift, 1882, No. 32. 
fArchives d’ Ophthalmologic, Dec., 1880. _ 208 
THE GEEM THEORY OF DISEASE. 
The same micro-organisms penetrate into the tissues 
of the decaying teeth. But it would be hazardous to 
say that they cause the decay, seeing that the decayed 
portion represents practically dead refuse exposed to 
bacterial invasion. Of more significance are the 
recent observations by Miller,* who saw the dentine 
canals in stained sections filled with micro-organisms. 
Besides the leptothrix there were large bacilli and 
micrococci. The invasion extended just beyond the 
border of the carious portion. Still Miller does not 
claim that the parasites are the only cause of the 
decay, but seeks the primary impulse rather than in 
the action of acids. 
Finally, as the last example of bacterial agency, 
and one which seems rather surprising, I may refer 
to the effect of the 
POISON IYY (RHUS TOXICODENDRON) 
upon the human body. In the minute vesicles, form- 
ing part of the eruption caused by handling this 
plant, Burrill f has repeatedly seen numerous granules, 
closely resembling micrococci. The same granules 
wTere found in the natural juice of the poison-ivy 
leaves, and it was further determined that the diluted 
juice can provoke the irritation of the skin. There 
are, however, no proofs presented in the paper, that 
these granules were really micrococci, which question, 
either staining or cultivating methods would have 
decided. The most convincing observation, which Bur- 
rill presents, is the successful infection of a fresh part 
of the skin with the exudation of the inflamed spot. 
The array of facts thus far presented, furnishes a 
* Archiv f. experimentelle Pathologie, Bd. 16, p. 291. 
f American Microscopical Journal, Oct., 1882. THE FOUNDATION OE THE GERM THEORY. 
209 
broad basis for a future germ-theory. No matter, 
whether further research will show, that many more, 
or—be it few other contagious diseases, are due to the 
agency of bacteria, the proof is absolute, that the 
invasion by these micro-organisms is the cause of 
anthrax, chicken cholera, the various forms of septicae- 
mia in animals, tuberculosis, glanders, some forms of 
suppurative inflammation, malignant oedema, erysipelas, 
gonorrhoea and trachoma. In these diseases there is 
no further chance for dispute. To any one familiar 
with the facts no logical escape seems possible from 
the conclusion, that they represent a parasitic inva- 
sion of the tissues by bacteria. Whenever the 
method of research is beyond criticism and when 
the author places his facts fully and plainly before 
the public, as has been done in these cases, we 
can no longer question, whether these are facts, we 
can only impeach the observer’s veracity. Less satis- 
factory is our knowledge regarding human pyaemia, 
relapsing fever and leprosy. Sufficient evidence has 
accumulated to prove, that certain parasites are invari- 
ably present in those diseases. In the present state 
of our knowledge the supposition, that these parasites 
cause those diseases is the most plausible one, but it 
is not yet a demonstrated certainty. Typhoid fever 
and pneumonia belong, perhaps, to the same class, but 
the evidence bearing on them is not yet so extensive. 
In very many other instances occasional observations 
have been made, which at least suggest further 
research in that direction. In these lectures I have 
not presented every isolated observation scattered 
throughout the literature, nor have I taken account of 
some few researches, which bear altogether too much 
the stamp of unreliability. 
What has( been done up to the present time repre- 210 
THE GEEM THEOEY OF DISEASE, 
sents only the foundation of the germ theory. We 
have scarcely progressed beyond the certainty, that 
various diseases are really due to bacterial invasion of 
the body. Next in order should be the investigation 
into the life-history of each parasite. In each 
instance it is to be learned, whether the virus multi- 
plies only in the body of the victim, or whether it 
can also lead a non-parasitic life under the conditions 
occurring in nature. It is to be determined further 
on, in what manner the virus escapes from the body of 
the patient, how it becomes diffused throughout the 
world, and through what channels it enters the system 
of the fresh victim. All these investigations seem 
comparatively easy with our means and methods. It 
is only the knowledge gained by such systematic work, 
that will enable us to limit the dissemination of vege- 
table parasites and to protect ourselves against their 
attacks. 
More incomplete even is our information regarding 
the nature of the struggle between the parasitic 
invaders and the animal cells. We are not certain yet 
in any one instance, in what manner the vegetation of 
the parasites injures the tissues, and we are ignorant 
likewise of the mode by which the tissues resist the 
invasion. We know only the anatomical appearances, 
which indicate in some cases, that the inflammatory 
response of the tissues is the mode of self-protection. 
For instance, the extension of the vegetation of the 
microcococci of pus, and of the tubercle-bacilli (at 
least in fibrous pneumonia) is hindered by breast- 
works, thrown up by the tissues in the form of granu- 
lation-tissue. We know also, that in some instances 
the parasites perish in the body of the resisting vic- 
tim. In the skin, in which the erysipelatous inflam- 
mation has passed its height, the micrococci have 211 
STRUGGLE BETWEEN TISSUES AND BACTERIA. 
disappeared; in the center of chronic tubercular pro- 
cesses the bacilli can scarcely be recognized, and in 
the blood of animals recovering from anthrax the 
parasites of that disease are found dead. Such dead 
bacteria appear granular instead of homogeneous and 
do not take up aniline colors to any extent. But how 
they are destroyed we do not know. 
The study, which promises the greatest immediate 
benefits to mankind, is that of the nature of the 
resistance of the tissues to the parasites. An insight 
into this will probably give us the clue to the immun- 
ity against a second invasion of the parasites, which 
the tissues have just vanquished. Eor it is only a 
complete analysis of this process, that will enable us 
to aid the tissues in their struggle, i. a, jto cure the 
disease, especially since the hope of finding some 
remedy, which kills bacteria, but is harmless to animal 
tissues, has never been realized. Whether the artificial 
production of immunity by vaccination with mitigated 
parasites will ever become practical in many diseases, 
can of course not be foretold. It seems puerile at 
present, to discuss the desirability of such wholesale 
vaccination, as long as the possibility has not yet 
been demonstrated. 
How far the germ theory of diseases is to extend 
in the future, can scarcely be foreseen. In all conta- 
gious diseases, in all disorders in which the virus can 
multiply, we cannot but assume the living nature of 
that virus, be it in the form of bacteria or of other 
parasites, for we do not know of any non-living mat- 
ter, that can reproduce its kind. This consideration 
shows, how untenable is the hypothesis, once put forth 
by Billroth, that bacteria act but as the carriers of 
some “ morbific virus,” which they do not produce 
themselves. The view, largely promulgated by Beale, 212 
THE GERM THEORY OF DISEASE. 
that disease germs represent degenerated bioplasm, 
stray fragments of the animal organization, which—to 
use a metaphor—have entered upon a life of disorder 
and are incapable of returning to their former condi- 
tion of discipline—this ingenious yiew is after all but 
the outgrowth of a fertile imagination, not based upon 
any demonstrated facts. The germ theory is not lim- 
ited to contagious diseases. After all the contagious- 
ness of a disorder depends upon, whether the parasites 
are eliminated in such a manner as to become at 
once disseminated through the air. Indeed there is 
reason to think that some parasitic diseases cannot be 
readily transferred from one victim to another. Trich- 
inosis is the type of a parasitic invasion, yet it cannot 
be transferred by inoculation. It is hence but logical 
to search for parasites in all diseases, of which the 
cause is not fully understood. Apart from the para- 
sitic affections it is scarcely possible to point out any 
disease, the aetiology of which is absolutely sett]ed 
except instances of poisoning and deformities of a 
mechanical nature. But it is narrow-minded to think, 
that the detection of parasites explains everything. 
The question of predisposition, obscure as it is, cannot 
be ignored. It shows more sagacity to investigate, 
why the bacillus tuberculosis does not attack all 
beings, exposed to it, than to scoff at its significance, 
because many can resist its attacks. Moreover we are 
not to forget that the parasites are not the disease, 
but only its cause. The disease itself is an alteration 
of the physiological processes, as a response to some 
unwonted influence. Of course it may and it often 
does happen, that the reaction of the tissues is the 
same to different forms of irritation, be they living 
parasites or other agencies. Hence a symptom or a 
lesion may by itself not always have the same mode 
of origin in different instances. BACTERIA NOT THE ONLY PARASITES. 
213 
Bacteria are not the only parasites of the animal 
body. Apart from the animal parasites, of more 
importance perhaps in tropical climates, instances have 
been observed in which higher fungi vegetate in the 
animal system. But this is a much less common 
occurrence than bacterial invasion. Not only are such 
fungoid growths found in the skin on mucous surfaces, 
and occasionally in the meatus of the ear, but in- 
stances have also been reported of parasitic fungi in 
internal organs, especially the lungs. In birds indeed 
this seems to be quite a common occurrence,* while 
the diseases of insects have all been traced to such 
parasitic fungi. But quite a number of observations 
on man are also scattered throughout pathological 
literature. 
Some twelve years ago Grohe and Block observed 
the growth of mould-fungi with death of the animals, 
on injecting spores into the circulation. This experi- 
ment could not be repeated by various observers, until 
Grawitzf claimed to have transformed the common 
harmless mould-fungi into virulent parasites by adapt- 
ing them gradually to the high temperature and 
the conditions of nutrition in an alkaline soil, 
occurring in the animal body. Spores thus pre- 
pared were injected into the blood-vessels, became 
arrested in the capillaries, especially of the kidney and 
liver, and germinated there, producing mycelia. The 
portions of tissues involved are thereby killed, but 
without much inflammatory action. If a sufficient 
quantity of spores has been injected the animal dies 
in from three to five days; if the quantity was 
insufficient the fungi are destroyed and the necrotic 
-•'Compare Bollinger, Ueber d. Pilzkrankheiten niederer u. hoeherer 
Thiere. Yortraege im Aerztlichen Yerein zu Muenchen, 1880. 
tVirchow’s Archiv, Yol. 81, p. 355. 214 
THE GERM THEORY OF DISEASE. 
spots are absorbed. But it has since been shown by 
Gaffky and Koch* and by Lichtheim,'j* that Grawitz 
did not transform harmless fungi into virulent para- 
sites, but that his cultures became vitiated by the 
unrecognized entrance of fungi naturally pathogenic 
to animals. While the common forms of Penicillium 
and Aspergillus glaucus are harmless and cannot be 
made dangerous, the Aspergillus fumigatus and A. 
llavescens are always pathogenic, because they can 
readily vegetate in the animal system. On account of 
the favorable influence, which warmth exerts upon 
their growth, they are very apt to creep into alleged 
pure cultures of other mould-fungi kept warm. Such 
instances of fungoid infections are not comparable, 
however, to bacterial invasions, since the fungi do not 
multiply in the animal body, but simply germinate 
and grow up to a certain phase of their development. 
has attempted to study the question of 
immunity in such fungoid infections, for the first non- 
fatal infection seemed to protect his animals against a 
second injection of larger quantities. But on repeating 
these experiments with pure cultures, Loeffler§ could 
not confirm Grawitz’ statements. 
The fungus, however, which has of late attracted 
mainly the interest of pathologists, produces a clinical 
disorder not unfrequently observed in man and some 
domestic animals, viz: 
ACTINOMYCOSIS. 
This disease in man and its fungus were first 
described by Israeli) It was further studied by 
*Mittheilungen aus dem Gesundheitsamte, p. 126. 
|Berliner Klinische Wochenschrift, Nos. 9 and 10, 1882. 
fYirchow’s Archiv, Yol. 84, p. 87. 
§Mittheilungen, etc., p. 181. 
jj Virchow’s Archiv, Yol. 74, p. 15, and Yol. 78, p. 421. 215 
ACTINOMYCOSIS. 
Ponfick* and identified by him with the affection, previ- 
ously described by Bollinger in cattle. It occurs also in 
swine. Since over thirty cases have been observed in 
man by German authors within the last four years, it 
cannot be very rare. Moreover the diagnosis can only 
be made by microscopic examination and hence it has 
probably been often overlooked. In man it appears 
in the form of purulent tumors or abscesses, which 
may spread both by continuity and by metastasis. It 
can thus simulate chronic Pysemia. The germs enter 
often through carious teeth, or through the tonsils, 
and the tumors then appear first at the angle of 
the jaw. This is also their most common site in cat- 
tle, but in these animals the disease is apt to remain 
localized. In man its diffusion through the system 
can be prevented by timely surgical interference. In 
other cases the disease began in peripheral parts of 
the body. Twice it has been observed in the lungs 
of cows presenting the gross appearances of tuber- 
culosis. -j* In the scant pus of the tumors yellow 
granules are seen, which the microscope resolves into 
a network of matted mycelial filaments, partly straight, 
partly wavy, and partitioned off by septa. At the 
periphery of these filaments oval and club-shaped 
bodies are attached in a striking radiating manner, 
whence the name radiating fungus or Actinomyces. 
The club-shaped bodies probably represent the conidia, 
for on cultivation appearances of budding can be ob- 
served. Between the filaments numerous small gran- 
ules are often found, which perhaps are independent 
micrococci, the presence of which complicates the pro- 
cess. The cultivation of the fungus has not yet suc- 
■fPflng. Centralblatt f. d. Med. Wiss., No. 14, 1882, and Hink. Cen- 
tralblatt, No. 46, 1882. 
*Die Actinomycose. Festschrift, 1881. 216 
THE GERM THEORY OF DISEASE. 
ceeded outside of the body to any satisfactory extent, 
and hence its botanical position is still undetermined. 
There can be no doubt, however, as to the causative 
influence of the parasite on account of its invariable 
presence in this disease, while it has never been de- 
tected under other circumstances. The fungus exists 
in the interior of the diseased tissues as well as in 
the pus, apparently eating its way into healthy parts. 
In one instance Ponfick could trace the growth 
through the walls of a vein, so that the blood-current 
could detach fragments which formed emboli in dis- 
tant parts, explaining thus the occurrence of metas- 
tasis. Johne* and Ponfick have successfully inocu- 
lated calves and have thereby reproduced the char- 
acteristic disease. Rabbits and dogs were found 
insusceptible to it. 
Actinomycosis presents a notable instance of the 
discovery of a disease, hitherto unrecognized, and of 
the immediate insight into its nature by the use of 
the microscope for the detection of parasites. 
*Centralblatt, No. 15,1881. INDEX. 
Abbe’s Condenser 25 
Abscesses ’ , Ill 
Abscess, spreading—in rabbits 146 
Acetic acid fermentation 71 
Actinomyces 215 
Actinomycosis 214 
Aerobes and Anaerobes 36 
Anthrax, 84 
aetiology of ■... 87 
bacilli of 85 
immunity against 93 
. in chickens 89 
incubation of 90 
protective vaccination in... 93 
Antiseptics 51 
Antiseptic surgery 107 
Archebiosis 17 
Aseptic wounds 108 
Aspergillus.... 214 
Attenuation of bacillus anthracis .93, 97 
Attenuation of bacillus of sympto- 
matic charbon; 150 
Attenuation of chicken cholera bac- 
teria 103 
Attenuation of disease germs 63 
Bacillus, 20 
anthracis 85 
attenuation of.93, 97 
Bacillus anthracis, transformation 
into hay bacillus - 99 
Bacillus of glanders 171 
malignant oedema 147 
septicaamla 132 
symptomatic charbon 149 
lepra 192 
in milk-fever 196 
measles 182 
rhinoscleroma 207 
sheep-pox 182 
Bacillus in syphilis 194 
malarise 183 
sporifleation of 29 
subtilis...; 67 
typhosus 173 
tuberculosis 157 
Bacillus tuberculosis in sputum 167 
Bacillus tuberculosis—its diagnostic 
significance 189 
Bacillus tuberculosis in urine 162 
Bacillus tuberculosis, staining the—.l7o 
Bacillus of whooping-cough 207 
Bacteria, classification of 19 
composition of 31 
cultivation of 55 
on solid soils 59 
definition of 6 
detection of—in tissues... 23 
desiccation of 13 
duration of life of 47 
effects of agitation on 50 
cold on 39 
heat on 40 
examination of 22 
influence of—on digestion 76 
isolation of 81 
movements of 27 
multiplication of 8, 28 
nutrition of 31 
protection against 13 
products of 48 
reproduction of 28 
the cause of putrefaction.. 10 
varieties of 58 
variability of properties of 63 
Bacteria in the air 44 
In the intestinal canal 76 
carious teeth 208 
the breath 76 218 
THE GERM THEORY OF DISEASE. 
Bacteria in the soil of the earth 74 
on the surface of the body. 75 
of blue milk 73 
blue pus 73 
phosphorescence 74 
Bacterium termo 67 
Butyric acid fermentation 71 
fermentation of glycerine.. 72 
Carbolic acid, action on bacteria.... 53 
Carious teeth 208 
Charbon, see Anthrax 
Charbon, symptomatic 149 
Chicken cholera 101 
modified 103 
protective inocula- 
tion 104 
Cohn’s fluid 32 
Cold, action of, on bacteria 39 
Conjunctivitis, gonorrhoeal 199 
Cultivation of bacteria 55 
on solid soil 59 
Desiccation of bacteria 43 
Diathesis 205 
Diphtheria 185 
of wounds 187 
Disease germs, research for 80 
variability of the 
virulence of 63 
Disinfectants 51 
Endocarditis 204 
Emphysema infectiosum 149 
Erysipelas 141 
Erysipelatous Inflammations 144 
Fermentation, definition of 9 
alcoholic 70 
acetic 71 
butyric 71 
lactic 70 
of glycerine 71 
producing pigments. 72 
of urine 68 
viscous 71 
Ferments 66 
Fever, aseptic 125 
malarial 183 
relapsing 176 
traumatic 124 
typhoid 172 
Flagellum 26 
Floating matter in the air 14 
Fungi, in diphtheria 190 
pathogenic 214 
Furuncles 115 
Gangrene, progressive 145 
Gelatine soils 60 
Germs in the healthy body 78 
Glanders 171 
Glycerine, fermentation of 71 
Gonorrhoea 199 
Gonorrhoeal conjunctivitis 199 
Granulated lids 202 
Heat, influence of—on bacteria 40 
—on spores 41 
Illumination with Abbe’s condenser.. 24 
Immunity, theory of 49 
Inflammation 198 
suppurative 112 
Inoculation with cultivated bacteria. 82 
Keratitis 206 
Lactic acid fermentation 70 
Leprosy 192 
Leptothrix bucallis 76, 208 
Malarial fever 188 
Mercuric bichloride, action on bac- 
teria 52 
Micrococcus 19 
prodigiosus 72 
urese 68 
in cow-pox 180 
endorcarditis .... 204 
diphtheria 185 
measles 182 
osteomyelitis 116 
pyaemia 118, 121 
pneumonia 204 
syphilis 194 
small-pox 179 
chicken cholera 101 
of erysipelas 142 
furuncles 115 
gonorrhoea 199 
progressive gangrene. 145 
pus 112 
spreading abscess 146 
septicaemia 133 
trachoma 202 
Milk, blue 78 
Milk-fever epidemic 195 
Mitigated disease-germs 63, 93, 103 
Mould-fungi 213 
Mutability of bacterial species 61 
Nitrification 74 
Ofdema, malignant 147 
Osteomyelitis n& 
Oxygen, influence of—on bacteria... 34 
Oxygen, influence of—on fermenta- 
tions 35 
Oxygen, compressed, action on bac- 
teria 39 
Oxygenated water, action on bac- 
teria 151 
Ozone, action on bacteria 39 
Parasites in Nature 4 
Pasteur’s fluid 32 INDEX 
219 
Pebrine 5 
Penicillium 214 
Phosphorescence 74 
Pigments produced by fermenta- 
tions 72 
Pneumonia 203 
Poison Ivy 208 
Progressive gangrene 145 
Predisposition 57 
Pterygium 207 
Purulent infection 114 
Pus, blue 73 
micrococci in 112 
decomposition of 123 
Putrefaction, definition of 8 
chemistry of 67 
without oxygen 37 
Putrid poisoning 126 
Pyaemia 117 
experimental 121 
Kauschbrand 149 
Relapsing fever 176 
Bhinoscleroma 207 
Rhus toxicodendron 208 
Sepsin 128 
Septic poisoning 126 
Septicaemia 130 
different forms of 132 
Septicaemia virus, progressive viru- 
lence of 137 
Sheep-pox 182 
Silk worm disease 5 
Small-pox 179 
Spirillum 20 
of relapsing fever 176 
Spirochaete 20, 176 
Splenic fever, see Anthrax 
Spontaneous generation 16 
Spores 29 
resistance of 18, 30 
Stability of bacterial species 61 
Starch, fermentation of 69 
Staining methods for bacteria 23 
Staining methods for the bacillus 
leprae 193 
Staining methods for the bacillus 
tuberculosis 162 
Staining methods for the bacillus of 
syphilis 194 
Sterilizing 12 
Sugar, fermentation of ' 70 
Suppuration 11l 
without micro-organ- 
isms 110 
Surgical infections 106, 141 
Symptomatic charbon 149 
Sympathetic eye-diseases 206 
Syphilis 193 
Traumatic fever 124 
Tuberculosis 152 
Typhoid fever 172 
Urine, fermentation of 68 
Vaccination in anthrax 93 
chicken cholera 104 
symptomatic charbon. 150 
Vaccine 180 
Variola 179 
Vibrio 20 
of pus 114 
Viscous fermentation 71 
Whooping-cough 207 
Zoogloea-form 20