b. Bacteria which produce in their growth in dead
organic matter sufficient poisons to cause sickness if
they are absorbed into the animal body.

2. Facultative Saprophytes. These are bacteria which
can develop either as parasites or saprophytes. The
different varieties vary as to the amount of poison
which they produce. Some grow luxuriantly in dead



RELATION OF BACTERIA TO DISEASE. 91

organic material under very diverse conditions, others
only under specially favorable conditions. In the body
they also vary some grow extensively in the blood,
while others are limited to one or more tissues, some
being widely disseminated throughout the body, while
others are localized in or upon a certain portion of it.

3. Strict parasites, or bacteria which, so far as we
know, grow only in the living animal or vegetable
organism. These again vary in the amount of poison
which they produce and in the local or general infec-
tion they give rise to.

Adaptation of Bacteria to the Soil upon which They are
Grown. Those bacteria which grow both in living and
dead substances vary from time to time as to their
readiness to develop in either the one or the other.
As a general rule, bacteria grown in any one medium
become more and more accustomed to that and other
media more or less analogous to it, while, on the other
hand, they are less easily cultivated on media widely
different from that in which they have developed. Thus
we have a culture of tubercle bacilli, which, after having
grown for three years in the bodies of guinea-pigs, will
no longer develop on dead organic matter, while a
bacillus which was obtained from the same stock, but
grown on bouillon for three years, will no longer de-
velop in the animal body. From the same stock,
therefore, two varieties have developed, the one being
now practically a saprophyte and the other a parasite.

The Local Effects Produced by Bacteria and their Prod-
ucts. Nearly all the forms of acute inflammation are
seen to follow the development of bacteria. Thus in-
flammation and serous exudation into the subcutaneous
tissues follow injections of the pneumococcus or anthrax



92 BACTERIOLOGY.

bacillus. The development of the streptococcus or
pneumococcus in the endocardium or pleural cavity is
followed by a serous exudation, frequently with more or
less fibrin production. The formation of pus results,
more especially from the streptococcus, pneumococcus,
and staphylococcus; but also nearly all forms of bacteria,
when they accumulate in one locality, may produce
purulent inflammation. The colon, typhoid, and influ-
enza bacilli frequently cause the formation of abscesses.

Catarrhal inflammation, with or without pus, follows
the absorption of the products of many bacteria, such as
the gonococcus, pneumococcus, streptococcus, and in-
fluenza bacillus, etc. The hemorrhagic exudation seen
in pneumonia is due to the pneumococcus; it is observed
also in anthrax and other infections. Cell necrosis is
produced frequently by the products of the diphtheria
and of the typhoid bacilli and by those of other bac-
teria. Specific proliferative inflammation follows the
localization of the products derived from the tubercle
bacillus and the leprosy bacillus.

Not only can one species of bacteria produce several
forms of inflammation, but the same organism will vary
as to the kind or kinds of inflammation it will produce;
this depending, first, upon its own characteristics at the
time as to virulence, etc., and, second, upon the con-
ditions in the infected animal, such as its health and
power of resistance, the period of infection, and the
circumstances under which the animal remains. Such
variations, therefore, are in no case specific, for different
poisons will produce changes which appear identical.

The Manner in which Bacteria Produce Disease. The
actual mechanical presence of the bacteria is only of
importance when, as in septicaemia or pyiiemia, tliey exist



RELATION OF BACTERIA TO DISEASE. 93

in such enormous numbers as to interfere mechanically
with the circulation or cause minute thrombi, and later
emboli, which finally produce infarction and abscesses
in different parts of the body. These dangerous effects
are chiefly due, first, to their alteration of the nutritive
substances in the body into others which are valueless,
and, second, to their production of substances which
are more or less directly poisonous.

A moment's consideration of the different changes
which take place in the tissues after the injection of
fine sterile sand and of an equal quantity of a dead
culture of the tubercle or typhoid bacillus would suf-
fice to convince any one that it was the poison produced
by the bacillus, and not its mechanical interference,
which caused disease. These poisonous products, as
already described in the previous chapter, can be
separated from the culture fluid in which the bac-
teria have grown or they can be extracted from their
bodies. These products without the bacteria them-
selves injected into animals cause essentially the same
lesions as are produced by the bacteria when they de-
velop in the animal body. When the body, as a whole,
is invaded by bacteria the abstraction from the body
of such substances as they consume exerts probably a
considerable influence; but even here it is the poisons
elaborated by bacteria from the body substances and
given up to the blood and tissue cells which are of most
importance. The substances contained in or produced
by the bacteria, with few exceptions, attract the leuco-
cytes, and when great masses of bacteria die suppura-
tion usually follows.

The General Symptoms Caused by Bacterial Poisons
Absorbed into the Circulation. Fever is produced under



94 BACTERIOLOGY.

favorable conditions by all bacterial poisons. The first
requisite is that sufficient poison be absorbed; but, on the
other hand, it must not be absorbed with such rapidity as
to overwhelm the injected animal, for a moderate dose
may raise the temperature, while a very large dose
lowers it, as occurs sometimes when a very large sur-
face, such as the peritoneum, is suddenly involved.

Centanni 1 obtained through warmth and alcohol
from the bodies of bacteria a substance called pyro-
toxin, which was with difficulty dialyzed. From dif-
ferent bacteria not only the physiological but also the
chemical properties of the pyrotoxin were the same.
Not only did this cause fever, but also, when persisted
in, it produced emaciation, quickened heart-action,
apathy, dyspnoea, etc.

The bacterial poisons produce an increase in the
number of leucocytes and a lessening in the amount of
haemoglobin in the blood. The deleterious effects on
the nutrition are partly due to the direct effect of the
poison and partly to the diseased conditions of the
organs of the body, such as the spleen, kidney, and
liver. Degeneration of the nerve cells is frequently
noticed after infectious diseases; especially is this true
of diphtheria. Several bacterial poisons have been
found to produce convulsions; the best example of this
is the tetanus toxin.

The true bacterial poisons are, as already stated,
neither alkaloids nor albumins. Some of them, such
as the diphtheria and tetanus toxins, are peculiar in
their effects, while others, such as those produced by
the pneumococcus and streptococcus, can scarcely be
distinguished. They are destroyed by heat at 70 C.

1 Deutsche med. Wochenschrift, 1894, Nos. 7 and 8.



RELATION OF BACTERIA TO DISEASE. 95

Bacteria also produce secondary poisons, which stand
a temperature of 100 to 120 C.

The Influence of Quantity in Infection. With bacteria
the number introduced has an immense influence upon
the probability of infection taking place.

If we introduce into a culture medium, which, like
the body, is only fairly suitable for growth, a few
bacteria, it is not improbable that they may all die;
whereas if a greater number are introduced, while there
will at first be a slight diminution of these, those that
die seem to neutralize the substances which were dele-
terious; then those bacteria which survive begin to in-
crease, and soon they multiply enormously. The same
is true for parasitic bacteria in the body. A few only
gaining entrance, they may die; a larger number being
introduced, some may or may not survive ; but if
a still greater quantity is injected it is almost certain
that there will be some surviving members, which, after
the destruction of antagonistic substances, and on be-
coming accustomed to their environment, will begin to
grow and produce disease.

With those bacteria whose virulence is great i. e.,
those which are capable of growing with great ease in
the body fluids a very few organisms will produce
disease almost as quickly as a million, allowance only
being made for the short time required for the few
to become equal in number to the million. At the
other extreme of virulence, however, many millions
may have to be introduced to permit of the develop-
ment of any of the organisms in the body. With these
bacteria we are thus able to produce either no effect
whatever, a local effect, or in some cases a general sep-
ticaemia, by regulating the amount of infection intro-



96 BACTERIOLOGY.

duced. In the majority of cases in man the number of
bacteria received is comparatively small; but by the
rupture of an abscess into a cavity or into the circula-
tion, or by the opening of the intestinal contents into the
peritoneum, the quantity introduced may be enormous.

The Degree of Virulence Possessed by Bacteria. Bac-
teria as found in nature differ, as has already been stated,
as to the amount of poison they produce and the ease and
rapidity with which they grow in any nutritive sub-
stance. Both of these properties not only vary greatly in
different members of the same species, but each variety
of bacteria may to a large extent be increased or dimin-
ished in virulence. The specific poisons produced by
bacteria can be best studied in diphtheria and tetanus.
We note, first, that different individual bacilli of diph-
theria and tetanus have, when freshly obtained, wide
variations in the amount of toxin which they produce
i.e., a diphtheria bacillus obtained from a case of diph-
theria will produce in suitable nutrient broth a poison
of such strength .that 1 c.c. will kill an average sized
guinea-pig, while the poison from another bacillus will
kill with a much less quantity, or 0.005 c.c. Further,
the bacilli obtained from some sources retain their power
of producing poison, when grown on artificial media, for
years unaltered, while others lose much of this in a few
months. This is equally true of the tetanus bacilli.

The power to produce toxin can be taken from bacilli
by growing them under adverse circumstances, such as
cultivation at the maximum temperature at which they
are capable of development. Some bacilli are easily
attenuated; others are robbed of their virulence only
with great difficulty. Increase of toxin-production is
more difficult, and it is only possible to obtain it to a



RELATION OF BACTERIA TO DISEASE. 97

certain extent. The means usually employed are the
frequent replanting of cultures and their growth in cap-
sules placed in the bodies of susceptible animals. But
with all our efforts we are usually only able to restore
approximately the degree of toxin-formation which the
cultures originally possessed. The adaptation of bac-
teria to any nutritive substance, living or dead, so that
they will grow more readily, is more easily brought
about, provided they will grow at all. The streptococcus
from erysipelas and the pneumococcus from pneumonia
are typical of this class of bacteria. Inoculate a rabbit
with a few streptococci obtained from a case of human
sepsis, and, as a rule, no result follows ; inject a few
million, and usually a local induration or abscess ap-
pears ; but if one hundred million are administered
septicaemia develops. From this rabbit now inoculate
another, and we find that a dose slightly smaller suffices
to produce the same effect; in the next animal inoculated
from this still less is required, and so on, until in time,
with suitable cultures, a very minute number will surely
develop and produce death. The same increase in
virulence can be noted when septic infection is carried
in surgery or obstetrics from one human case to another.
By allowing bacteria to continue to develop under cer-
tain fixed conditions they become accustomed to them,
and less adapted for all that differ.

Somewhat distinct, again, from that class of bacteria
which multiply rapidly are those which, like the tubercle
and leprosy bacilli, develop slowly. Here increase of
virulence is shown, as before, by the production of dis-
ease through the introduction of very small numbers
into the body, but increase in rapidity of development
cannot progress except to within certain limits. A sin-

' 7



98 BACTERIOLOGY.

gle streptococcus may, through its rapid multiplication,
produce death in eighteen hours ; a single tubercle
bacillus, on the other hand, cannot produce sufficient
numbers in less than two weeks. The virulence of the
septicsemic class of bacteria is not at all the same when
measured in different animals, and it is largely for this
reason that the virulence in test animals does not
usually correspond with the severity of the case from
which the organism was derived. We should re-
member in this connection the varying power of resist-
ance in different animals and of the same individual
at different times.

Mixed Infection. The combined effect upon the tissues
of the products of two or more varieties of pathogenic
bacteria, and also of the influence of these different forms
on each other, are of great importance in the produc-
tion of disease. The infection from several different
organisms may occur at the same time, or one may fol-
low the other or others so-called secondary infection.
Mixed infection arises usually from the inoculation of
more than one variety of bacteria simultaneously.
Thus, an abscess is often due to several forms of
pyogenic cocci. If a wound is infected from such a
source the inflammation produced will probably be
caused by all the varieties present in the original in-
fection. Peritonitis following intestinal injuries must
necessarily be due to more than one organism. Thus,
whenever two or more varieties of bacteria are trans-
ferred to a new soil, mixed infection takes place if
more than one variety is capable of developing in that
locality.

Forms of infection which are allied to both mixed
and secondary infection are those occurring in the



RELATION OF BACTERIA TO DISEASE. 99

mucous membranes of the respiratory and digestive
tract. In these situations pathogenic bacteria of slight
virulence are always present even in health. Thus
in the upper air-passages there are usually found strep-
tococci, staphylococci, andpneumococci. When through
a cold, or the invasion of another infective agent, as
the diphtheria bacillus, the epithelium of the mucous
membrane of the throat is injured or destroyed, the pyo-
genic cocci already present are now enabled in this dis-
eased membrane to grow, produce their poison, and
even invade deeper tissues. The intestinal mucous
membrane is invaded in a similar way by the colon
bacilli and other organisms after injury by the typhoid
bacilli or cholera spirilla. Generally speaking, all in-
flammations of the mucous membranes contain some of
the elements of mixed infection. Blood infection, on
the other hand, is usually due to one form of bacteria,
as even when several varieties are introduced, only
one, as a rule, is capable of development. The same
is true to a somewhat less extent of inflammation of
the connective tissue. The additional poison given off
by the associated bacteria aid infection by causing a
lowering of the vital resistance of the body.

The bacteria are also at times directly influenced by
the products of associated organisms. These may
affect them injuriously, as, for example, the pyogenic
cocci in anthrax; or they may be necessary to their
development, as in the case of anaerobic bacteria. JSTot
infrequently the tetanus bacilli or spores would not be
able to develop in wounds were it not for the presence
of aerobic bacteria introduced with them. This is shown
outside the body, where tetanus bacilli will not grow in
the presence of oxygen unless aerobic bacteria are asso-



100 BACTERIOLOGY.

elated with them. Again, it is found that the associa-
tion of one variety with another may increase its viru-
lence. Thus Roux and Yersiu believe that they have es-
tablished the fact that streptococci and diphtheria bacilli
mutually increase each other's virulence. On the other
hand, the absorption of the products of certain bacteria
immunizes the body against the invasion of other bac-
teria, as shown by Pasteur that attenuated chicken
cholera cultures produce immunity against anthrax.

The Modes of Entrance of Infection. The various fluids
and tissues of the body differ greatly in their chemical
constituents, their reaction, their protection from in-
fection, their access to free oxygen, their temperature,
and in other less well-known respects. These varia-
tions are sufficient to render certain portions of the
body suitable for the growth of some bacteria and
unsuitable for others. This fact is of immense im-
portance in the transmission or prevention of disease.
Thus, for example, let us rub very virulent strepto-
cocci, typhoid bacilli, and diphtheria bacilli into an
abrasion on the hand. The typhoid bacillus produces
no lesion, the diphtheria bacillus but a very minute
infected area, but the streptococcus gives rise to a severe
cellulitis or fatal septicaemia. Now place the same
bacteria on an abrasion in the throat. The typhoid
bacillus is again harmless; the diphtheria bacillus pro-
duces inflammation, a pseudomembrane, and toxaemia,
and the streptococcus causes an exudate, an abscess, or
a septicaemia. Finally, introduce the same bacteria into
the intestines, and now it is the typhoid bacillus which
produces its characteristic lesions, while the strepto-
coccus and diphtheria bacillus are usually innocuous.

If we tried in this way all the parasitic bacteria we



RELATION OF BACTERIA TO DISEASE. 1Q1

would find that certain varieties are capable of develop-
ing and thereby producing disease only on the mucous
membrane of the throat, others of the intestine, others
of the urethra ; some develop only in a wound or in
the blood, while others, again, under favorable condi-
tions, seem able to grow in or upon almost any region
of the body.



CHAPTER V.

IMMUNITY.

THAT certain races of animals and men, and certain
individuals among these, are more refractory to disease
than others, is a fact which has long been known.
Experience and observation have taught us, further,
that the same individuals are at one time more resistant
to disease than at another. This inborn or spontaneous
refractory condition is termed natural immunity, in con-
tradistinction to that acquired by recovery from disease.

As in bacteria, we distinguish between the ability to
produce poison and the power to multiply in the body,
so here we may distinguish between immunity to poison
and immunity to the development of bacteria.

With regard to variations in susceptibility, certain
known facts have been ascertained. Thus, cold-blooded
animals are generally insusceptible to infection from
those bacteria which produce disease in warm-blooded
animals, and vice versa. This is readily explained by
the inability of the bacteria which grow at the tem-
perature of warm-blooded animals to thrive at the
temperature existing in cold-blooded animals. But dif-
ferences are observed not only between warm-blooded
and cold-blooded animals, but also between the several
races of warm-blooded animals. The anthrax bacillus
is very infectious for the mouse and guinea-pig, while
the rat is not susceptible to it unless its body resistance



IMMUNITY. 103

is reduced by disease and the amount of infection is
great. The inability of a micro-organism to grow
in the body of an animal does not usually indicate,
however, an insusceptibility to its poison; thus, for in-
stance, rabbits are less susceptible than dogs to the effects
of the poison elaborated by the pneumococci, but these
bacteria develop much better in the former than in
the latter. Differences in susceptibility are sometimes
very marked among different varieties of the same race
of animals, as, for instance, between different kinds of
rats and pigeons to anthrax. In animals, as a whole,
it is noticed experimentally that the young of all species
are less resistant to infection than the older and larger
ones.

The difficulty experienced by the large majority of
bacteria in developing in the tissues of the healthy
body can be to a great extent removed by any cause
which lowers the general or local vitality of the tissues.
Among the causes which bring about such lessened re-
sistance of the body are hunger and starvation, bad
hygienic surroundings, exhaustion from overexertion,
exposure to cold, the deleterious effects of poisons, bac-
terial or other, acute and chronic diseases, vicious
habits, drunkenness, etc. Purely local injuries, such
as wounds, contusions, etc., also give sometimes a point
of entrance for infection, or at least a point of less re-
sistance, where the bacteria may develop and produce
local inflammation. This is noted in infection by the
tubercle and typhoid bacilli, pyogenic cocci, etc.
Local affections, such as endocarditis, may also afford
a weak spot for the bacteria to seize upon. The pres-
ence of foreign bodies in the tissues in like manner
predisposes them to bacterial invasion. Interference



104 BACTERIOLOGY.

with free circulation of blood and retention in the body
of substances which should be eliminated also tend to
lessen the vitality. In these and other similar ways
animals which are otherwise refractory may acquire a
susceptibility to disease.

Immunization and Healing by Non-specific Means. Just
as all conditions which are deleterious to the body lessen
its power of resistance to bacterial invasion, so all con-
ditions which are favorable to it increase its resistance,
and thus aid in preventing and overcoming infection.
The internal use of antiseptics against bacteria has
not proved successful, for the reason that an amount
too small to inhibit bacterial growth is found to be
poisonous to the tissue cells. The efficacy of quinine
in malaria and mercury in syphilis is, possibly, an ex-
ception to the rule, but in both cases we are dealing
probably with animal parasites, not ordinary bacteria.
Such substances as nuclein and others contained in
blood-serum, when introduced into the body in consider-
able quantity, aid somewhat in inhibiting or preventing
the growth of many bacteria. Even bouillon, salt
solution, and small amounts of urine have a slight in-
hibitory action. The hastening of elimination of the
bacterial poisons by free intestinal evacuation and en-
couragement of the functions of the skin and kidneys
are also of some avail. The enzymes formed by certain
bacteria have been found to exert a slight bactericidal
action, not only on the germs which have directly or
indirectly produced them in the body, but also on other
varieties. JSTone of these enzymes are sufficiently pro-
tective to be of practical value nor equal in power to the
protective substances formed by the tissues from the
bacterial products.



IMMUNITY. 105

The Use of Local Treatment in Inhibiting Bacterial In-
vasion. The total extirpation of the infected area by
surgical means, if thoroughly carried out, removes the
disease entirely; but, unfortunately, this procedure is
rarely possible. When incomplete it is frequently
helpful; but it may be harmful, for by creating and
exposing fresh wounded surfaces to infection it may
lead to the further development of the disease. Again,
it may be useless, for by removing only a portion of
the bacteria it may leave those which have already
reached the deeper tissues or blood to go on devel-
oping. In some cases, like anthrax and infection
from bites of rabid animals, total removal of the
virus is possible, either by the knife or thorough cauter-
ization, and will prevent a general infection. So also
in tetanus, the invasion being limited, surgical inter-
ference may be of great use by removing not only the
bacilli themselves but also that portion of their poison
which has not as yet been absorbed from the tissues.