they have previously grown outside the body in blood-
serum. Bacteria have also been injected into a vein
carefully ligated above and below, and here, without
coagulation, the blood exerts bactericidal properties.
The general germicidal effect of the blood-serum can
also be watched outside of the body. Here mixed
with it some species of bacteria die quickly, some
slowly, and some lose only a portion of their number,
those remaining alive after a time rapidly increasing.
The number of bacteria introduced is of great impor-
tance, for the serum with its contained substances seems
capable of destroying only a certain number, and after
that loses its bactericidal properties.
120 BACTERIOLOGY.
If the bactericidal effect of the serum outside the
body always went hand-in-hand with the immunity of
the individual from which it was taken, the immediate
cause of immunity would be solved and our search be
directed to find the source and nature of these germi-
cidal substances; but this is not wholly the case, for
while in many instances it is so, in others it is as un-
doubtedly not true. We must, therefore, add to the
serum the activity of the cells, which produce constantly
the substances which are partly given up to the blood
and fluids of the body and partly retained in their own
bodies. This deleterious action of the blood in bac-
teria can be increased by infection. Some good ob-
servers have found that blood in animals naturally
immune to certain parasitic bacteria, which had little
or 110 bactericidal effect, became possessed of it after a
moderate infection; this seeming to indicate a protective
effort of the body cells to withstand bacterial invasion.
Concerning the nature of these non-specific protective
substances, named alexines by Buchner, we have as yet
little positive knowledge, but certain properties of them
are known. They are largely precipitated by a 40 per
cent, solution of sodium sulphate, but not by alcohol.
These substances would seem to belong to the so-called
living proteids, and resemble certain of the globulins
in their properties, but they are evidently extremely
complex in their nature. Many of them become inert
on standing for several months, even at low tempera-
tures, and after a few weeks at blood-heat. A tem-
perature above 62 to 70 C. soon totally destroys
them. Freezing does not affect them. A bactericidal
serum affects in a deleterious manner the red blood-
cells of a different species of animals.
INFECTION, IMMUNITY, AND RECOVERY. 121
Their source must apparently be attributed to the cells,
but probably certain cells only produce them. The red
blood-cells, for instance, seem rather to destroy than to
increase them. The nuclein derived from the cells, al-
though it has a general bactericidal action, and may enter
into the alexines, yet as it has different properties it can-
not itself be one of these bodies. The cells which have
abundant nuclear substance, such as the leucocytes and
lymph-cells, seem especially to be a source of the alex-
ines. Buchner and others have found that through
the irritation of bacterial filtrates the leucocytes were
attracted in great numbers to the region of injection,
and that the fluid here, which was rich in leucocytes,
was more bactericidal than that of the blood-serum
elsewhere. The same fluid acted also more perfectly
when it contained numbers of leucocytes than when
they were filtered off. Substances similar to the alex-
ines are apparently derived from the leucocytes, and
their attraction to the injected area gives to that loca-
tion greater protective power. Some claim to have
demonstrated that along with increased leucocytosis
there is a general increase in the alexines in the blood,
still it has not yet been positively established that the
alexines are derived solely from the leucocytes, nor
from all leucocytes, and a mere increase in them does
not always mean an increase in alexines. The attrac-
tion between the leucocytes and the bacteria is due to
the chemical attraction between them and the bacterial
body substance and its poisons. Some chemical sub-
stances not derived from bacteria have this quality
also, called positive chemotaxis, while others repel the
leucocytes negative chemotaxis. The original theory
of Metchnikoff, that the leucocytes were the only actual
/
122 BACTERIOLOGY.
protective bodies which warded off disease, and that
they did this by attacking the bacteria, was founded
on the observation that certain of the white cells pos-
sessed the power of taking up into themselves patho-
genic bacteria, and that they were there destroyed. It
was later observed that these cells had the property of
taking from the blood many lifeless foreign elements,
thereby keeping the blood-channels free of foreign par-
ticles. The question thereby arose as to whether these
cells engulfed and then killed the bacteria, or whether
perhaps other influences killed or injured them before
the cells took them up. The theory then became some-
what modified, more knowledge was obtained, and it is
now believed that the bacterial substances attract the
cells, and that when these cells are brought together the
general, and perhaps the specific, bactericidal property
of the blood in their neighborhood is thereby increased.
The death of the bacteria liberates this positive chemo-
taxic substance, and the disintegration of the white
blood-cells gives rise to the bactericidal bodies. Thus
we find that phagocytosis is most marked when the dis-
ease is on the decline or the infection mild, but that in
rapidly increasing progressive infection it is absent.
This would seem to indicate that the course of the in-
fection is often already determined before the leucocytes
become massed at the point of its entrance. The first
determining influence is given by the condition of the
tissues and the bactericidal substances contained in
them, and then, later, in cases where the infection is
checked, comes the additional bactericidal substance
given off by the attracted leucocytes. In so far as the
tissues themselves are unsuitable for the development
of bacteria they are sufficient to ward off infection, but
INFECTION, IMMUNITY, AND RECOVERY. 123
in proportion as they are incapable of doing this they
are assisted by the substances contained in the leuco-
cytes. If the tissues are wholly adapted .for the
growth of the bacteria, neither they nor the leuco-
cytes, nor both combined, can furnish sufficient pro-
tective substances to prevent the bacterial increase.
The entrance of bacteria into the leucocytes, which is
not infrequent, may mean their destruction; but, on
the other hand, the bacteria may increase in the white
blood-cells and destroy them, and they may be killed
without entering the cells. The simple absorption by
the cells is not necessarily a destructive process. No
explanation can as yet be given of natural immunity
to bacterial poisons, except that it may be connected
with some general property of the tissue. There is far
less variation among different species in their resistance
to the bacterial poisons than in their suitability for the
growth of the living bacteria which produce them
Possibly certain organs, such as those which are rich
in nuclei n for example, the lymph-glands, the liver,
etc. may have some destructive power with regard to
poisons. The nature of the cell substance is known
to have much to do with its relations to certain poisons.
Thus the tetanus poison acts chiefly on the nerve cells
and leaves the others almost or altogether unaffected.
By what means are virulent bacteria enabled to in-
crease in the body, notwithstanding its protective powers,
when non-virulent organisms of the same species are
incapable of so doing? This is but little understood,
but experiment shows in the first place that both viru-
lent and non-virulent forms are equally resistant to
general destructive agencies; and, second, that the bac-
teria are capable of producing substances (lysines) which
124 BACTERIOLOGY.
neutralize in some way the protective substances (alex-
ines). The virulence of bacteria would, therefore, de-
pend partly upon their ability to produce these lysines,
which act perhaps as the ferments upon the alexines, or
perhaps combine with them. That bacteria under certain
conditions form specific poisons, and under others, even
when they grow luxuriantly, do not, is clearly shown by
our experiments on the production of diphtheria toxin.
Here, as previously stated, it was found that when
the bouillon was either a little too alkaline or too acid,
though the bacilli grew rapidly, they did not produce
specific toxins. By growing the bacilli for a time in
such bouillon they eventually became able to develop
toxin in a soil in which they previously failed to do so.
Similar cultivation in the body may be assumed to
increase their ability to produce specific poison after a
while under what would at first be adverse conditions.
With regard to the increase and decrease of general,
and perhaps also of specific immunity, we have reason
to believe that as the protective substances are produced
by the living cells, anything which lowers the general
vitality must lessen the vitality of the cells, and thus
their ability to produce protective substances in the
amount possible in a normal condition. The attraction
of leucocytes to any point by some new infection might
increase the germicidal action of the tissues, and so in-
fluence the first infection.
Specific Immunity. The following theories have been
advanced concerning the nature of specific immunity:
The theory that a second infection is impossible because
the first used up substances which were necessary to the
growth of the bacteria is untenable for many reasons.
Thus it can be demonstrated that the injection of a
INFECTION, IMMUNITY, AND RECOVERY. 125
small amount of specific serum, which robs the tissues
of nothing, produces the same immunity. Again, the
injection into the body of a sufficient number of patho-
genic bacteria gives rise to an infection in all cases.
The theory of Metchnikoff, that the leucocytes or
wandering cells of the body, after an infection with a
certain variety of bacteria, become influenced in some
way, so that they attack especially that form of infection
again and destroy the bacteria (phagocytosis), can no
longer be considered as more than a very partial ex-
planation, and can only be accepted by assuming as
proven a number of hypotheses.
The retention theory of Wernich and Chaveau, some-
what modified, has much to support it. The blood-
serum of animals recovering from an infection was found
to have changed chemically to such an extent as to be
capable of being demonstrated experimentally, and
these changes were shown to persist for a number
of weeks or months or even years. Similarly the serum
of immunized animals retains for a long time its immu-
nizing substances We are, therefore, compelled to ac-
cept the fact, that when an infection is passed through
there are more or less protective chemical substances
left in the blood, which remain there for a considerable
time. Kruse believes that these substances have the
power of neutralizing the bacterial poisons which are
given off by the bacteria upon their entrance into the
body, and of thus robbing them of their deleterious
effects on the alexines; the body fluids in this way
remaining unsuitable soil for the growth of the bac-
teria, the alexiues being bactericidal. If only a small
amount of antilysines are present some of the alexines
are destroyed and the bacteria are not all killed or
126 BACTERIOLOGY.
weakened. Those remaining active are then further
acted upon by the alexines in the tissues and by the
substances given off by the leucocytes. If these pro-
tective substances are insufficient the infection is estab-
lished. R. Pfeiffer's experiments with cholera and
typhoid cultures injected into the peritoneal cavity of
the guinea-pig along with specific protective serum
showed that the bacteria were altered and destroyed by
the serum within a few minutes, just as if they had
been non-virulent bacteria, and this without the assist-
ance of the phagocytes. In this case non-virulent bac-
teria die because they produce no ly sines to destroy the
alexines, while those which are virulent do not thrive,
because although they produce lysines, the antilysines
in the serum destroy them, being thus acted upon by
alexines in like manner to the non-virulent bacteria.
As to the development of the specific protective sub-
stances, the most plausible theory seems to us to be that
they are formed by the activity of the cells from the
bacterial poisons, the lysiues. These substances are
stated by Pfeiffer and Marx to be most abundant in the
spleen, lymphatic glands, and bone-marrow.
Ehrlich and others believe antitoxin to be a portion
of the substance of certain cells, which, having been
stimulated by their effort to replace portions of their
substances destroyed by previous doses of toxin, have
reproduced it in excess. This cell substance, being
free in the fluids of the body, combines with the toxin,
and thus neutralizes it. But it is difficult by this
theory to explain many known facts, such as the one
that a fully neutralized mixture of toxin and antitoxin
is still capable of producing in the body more anti-
toxin. Others hold that the antitoxins, as the other
INFECTION, IMMUNITY, AND RECOVERY. 127
protective substances, are always present in the body,
and that under special need, as when bacterial inva-
sion takes place, they are thrown out by the cells in
larger quantities, and this is especially true of the
special substances needed for existing infection. The
antitoxin then acts by fortifying the cells so that they
are enabled to resist the action of the toxin. In favor
of this view is the fact that the cells of certain ani-
mals are undoubtedly proof against these toxins, and
yet so far as chemistry in its present development can
detect, these cells are the same as similar but sensitive
cells in other animals. Another theory is that the
toxin, in some way in the body fluids, is changed into
antitoxin. This is made slightly plausible by the fact
that by the action of electricity there have been obtained
substances from toxins which are slightly antitoxic.
The practical point to remember is that whether or not
the theories are correct, there is no doubt that the pro-
tective substances exist.
CHAPTER VII.
INFECTION.
THE spread of infection is influenced by: 1. The
number of species of animals subject to infection.
Many human infectious diseases do not occur in ani-
mals, and many animal infections are not found in man.
Thus, so far as we know, gonorrhoea, syphilis, measles,
smallpox, typhoid fever, etc., do not occur in animals
under ordinary conditions; while tuberculosis, anthrax,
glanders, hydrophobia, and some other diseases are
common to both man and animals.
2. The quantity of the infectious material thrown off
from the body and the prevalence of the disease.
In diphtheria, typhoid fever, cholera, pulmonary
tuberculosis, septic endometritis, influenza, and gonor-
rhoea enormous numbers of infectious bacteria are cast
off through the discharges from the mouth, intestines,
and genito urinary secretions, causing great danger of
infection. On the other hand, in tubercular perito-
nitis, cerebro- spinal meningitis, septic endocarditis,
gonorrhoeal rheumatism and the like, there is little or
no danger of infecting others, as few or no bacteria are
cast off.
3. The resistance of the infectious bacteria to the
deleterious effects of drying, light, heat, etc.
In this case the presence or absence of spores is of
the greatest importance. The spore-bearing bacilli,
INFECTION. 129
such as tetanus, anthrax, etc., being able to withstand
destruction for a long time, retain their power of pro-
ducing infection for months or even years after elimi-
nation from the body. The bacteria which form no
spores show great variation in their resistance to out-
side influences. Some of these, such as the influenza
bacilli and the gonococci, the virus of syphilis and
hydrophobia, are extremely sensitive; the pneumococci,
cholera spirilla, glanders bacilli, etc., are a little hardier;
then follow the diphtheria bacilli, and after them the
typhoid and tubercle bacilli and the staphylococci.
4. The ability or the lack of ability to grow outside
of the infected tissues.
Such bacteria as the pneumococcus, tubercle, influ-
enza, and lebrosy bacilli do not develop, as far as we
know, outside of the body under ordinary conditions.
Others, like the diphtheria bacillus and the strepto-
coccus, may under certain conditions, as in milk in
warm places, develop and produce infection. Others,
again, such as the streptococcus and staphylococcus,
typhoid and anthrax bacillus, the cholera spirillum,
and some anaerobics, may develop under peculiar con-
ditions existing in water or soil.
While for the pathogenic bacteria, as a rule, the
saprophytes met with in the soil and water are antago-
nistic, yet in some cases and especially is this true of
the anaerobic bacteria they are helpful. Such bacilli
as tetanus are believed to require the associaton of an-
aerobic bacteria to permit of their development in the
soil in the presence of oxygen.
A large number of the infectious bacteria are able to
develop in or upon some portion of the skin or mucous
membrane, either after or before disease, and without
9
130 BACTERIOLOGY.
causing infection. As complete a knowledge of these
facts as possible is necessary if we are to combat the
spread of infection. In the superficial layers of the
epithelium and on the surface of the skin we find the
different pyogenic cocci, which are capable of infecting
a wounded or injured part or causing inflammation in
the glands. Acne, the pustules in smallpox, the pus
on a burned surface, boils, etc., all come from the
pyogenic cocci. In surgical cases the skin has to be
as thoroughly disinfected as possible, to prevent the
formation of stitch-hole abscesses and wound- suppura-
tion.
In the secretion of the mucous membrane covering
the pharynx and nasopharynx there is always an abund-
ance of bacteria. In one hundred throats examined by
the writer in New York City, streptococci and staphylo-
cocci could be found in over 90 per cent., and pneumo-
cocci were very frequently discovered. Many other
varieties of bacteria, such as the influenza bacilli, are
probably often present in small numbers. In those con-
stantly in contact with cases of diphtheria, and in those
convalescent from diphtheria, virulent diphtheria bacilli
are frequently found in the throat.
After exposure to cold or injury of any kind, owing
to the presence of these bacteria, the persons harboring
them may develop tonsillitis, tonsillar abscess, or diph-
theria; or the bacteria may invade the bronchial mucous
membrane or the lungs. The diphtheria bacilli, and
perhaps other bacteria, transmitted to others may be-
come the source of infection to them, though the person
who spreads the infection may remain unaffected.
The stomach, on account of the acidity of its con-
tents, is'Vomparatively free from bacteria. The normal
INFECTION. 131
intestines, on the other hand, contain great numbers of
bacteria. Among these the colon bacillus is constantly
present, and often the streptococcus and other patho-
genic bacteria. After typhoid fever the bacilli may
remain in the intestinal contents for weeks and in the
bladder and gall-bladder for months. The bacteria
swallowed to a considerable extent escape destruction
in the stomach, and thus appear in the intestines. Some
good observers have stated that bacteria can be absorbed
through the intestinal wall into the chyle and blood.
When the intestinal canal is injured, or its circulation
hindered by strangulation, etc., the bacillus coli and
some other bacteria may penetrate through the injured
walls and cause peritonitis or general infection. Under
certain conditions, as during the debility due to hot
weather, the bacteria in the intestines cause, through
their products, irritation, and in children even serious
intestinal inflammation.
The kidneys, bladder, and urethra may be the source
of infection and may give rise to disease in others.
Long after an acute gonorrhnea has passed gonococci
may remain in sufficient numbers to cause a new in-
flammation or produce infection in others. A cystitis
may run on chronically for years, and then suddenly
become acute or spread infection to the kidneys. After
typhoid fever the urine may contain abundant typhoid
bacilli for weeks and be little thought of as a source of
infection. A persistent gonorrhoeal vaginal infection
may lead to a gonorrhoeal endometritis, or salpingitis, or
peritonitis, under suitable conditions. The staphylococci
in the skin and the colon bacilli and pyogenic cocci in
the faecal discharges may also be carried into the uterus
and produce septic infection.
132 BACTERIOLOGY.
Inherited Infection and Susceptibility to or Immunity
from Infection. The passage of bacteria from the
mother's blood through the placenta to the foetus has
been demonstrated for numerous bacteria, among the
most important of which may be mentioned the pneu-
mococcus, streptococcus, and tubercle bacillus. The
detection of the tubercle bacillus by Gartner and others
under these circumstances prevents us from denying the
possibility that tuberculosis developing in children may
have been due to infection taking place before birth.
The fact, however, that calves removed from tubercu-
lous cattle and fed on milk free from tubercle bacilli do
not develop tuberculosis, while those left with tubercu-
lous cattle become tuberculous, indicates that tubercu-
losis in man also is usually, at least, due to infection
after birth. The infection from spermatozoa is con-
ceivably possible in tuberculosis if the testicles are
affected; the same may be said of syphilis; but except
for syphilis, in which the nature of the infective agent
is unknown, we believe that such infection is, if ever
present, extremely rare.
Natural immunity pertains more to species than in-
dividuals, and such immunity is handed down by the
parents to their offspring. If the immunity of one or
both parents has been acquired by them during their
lifetime previous to the birth of the offspring the im-
munity conferred is slight or none at all. This is espe-
cially true of the male side. In the case of the female
parent another factor comes into play after the fructi-
fication of the ovum viz., the absorption of products
from the fluids of the mother, for the placenta is no
barrier to soluble substances. Thus, sheep which have
been immunized to anthrax have moderately immune
INFECTION. 133
young. On the other hand, animals vaccinated with
cowpox have not been found to have immune offspring.
Toxins injected into the parents apparently do not pass
the placenta; but antitoxins do, giving thus a slight
transitory passive immunity. A slight immunity is
also given by immune mothers through their milk, a
small amount of antitoxic substance being absorbed.
CHAPTER VIII.
THE EFFECT OF LIGHT, ELECTRICITY, PRESSURE,
AGITATION, DRYING, AND ASSOCIATION WITH OTHER
MICRO-ORGANISMS UPON BACTERIA.
VERY little is known about the influence of electricity
on bacteria. The majority of the observations hereto-
fore made on this subject would seem to indicate that
there is no direct action of the galvanic current on
bacteria; but the effect of heat and the electrolytic in-
fluence on the culture liquid may produce changes which
finally sterilize it. Gottstein and Spilker have recently
made experiments with an induction current from a
dynamo machine. They passed the current through
a spiral wire, which was wrapped around a test-tube
of glass containing the micro-organisms to be tested,
suspended in water. The bacillus prodigiosus, sus-
pended in sterilized distilled water and contained in
test-tubes having a capacity of 250 c.c., was subjected
to a current of 2.5 amperes -{- 1.25 volts for twenty-
four hours. The temperature did not go above 30 C.
No growth occurred when the organism tested was sub-
sequently planted in nutrient gelatin. It was found that
stronger currents were effective in a shorter time, but
in no case was sterilization effected in less than an hour.
These experiments, however, have not been confirmed.
Meltzer has shown that while slight agitation of