CLASSIFICATION OF THE ORGANISMS WHICH CAUSE DISEASE.--BACTERIA: SIZE,
SHAPE, STRUCTURE, CAPACITY FOR GROWTH, MULTIPLICATION AND SPORE
FORMATION.--THE ARTIFICIAL CULTIVATION OF BACTERIA.--THE IMPORTANCE OF
BACTERIA IN NATURE.--VARIATIONS IN BACTERIA.--SAPROPHYTIC AND
PARASITIC FORMS.--PROTOZOA.--STRUCTURE MORE COMPLICATED THAN THAT OF
BACTERIA.--DISTRIBUTION IN NATURE.--GROWTH AND MULTIPLICATION.--
CONJUGATION AND SEXUAL REPRODUCTION.--SPORE FORMATION.--THE NECESSITY
FOR A FLUID ENVIRONMENT.--THE FOOD OF PROTOZOA.--PARASITISM.--THE
ULTRA-MICROSCOPIC OR FILTERABLE--ORGANISMS.--THE LIMITATION OF THE
MICROSCOPE.--PORCELAIN FILTERS TO SEPARATE ORGANISMS FROM A FLUID.--
FOOT AND MOUTH DISEASE PRODUCED BY AN ULTRA-MICROSCOPIC ORGANISM.--
OTHER DISEASES SO PRODUCED.--DO NEW DISEASES APPEAR?
The living organisms which cause the infectious diseases are
classified under bacteria, protozoa, yeasts, moulds, and
ultra-microscopic organisms. It is necessary to place in a separate
class the organisms whose existence is known, but which are not
visible under the highest powers of the microscope, and have not been
classified. The yeasts and moulds play a minor part in the production
of disease and cannot be considered in the necessary limitation of
space.
[Illustration: FIG. 17.--VARIOUS FORMS OF BACTERIA, _a_, _b_, _c_,
_d_, Round bacteria or cocci: (_a_) Staphylococci, organisms which
occur in groups and a common cause of boils; (_b_) streptococci,
organisms which occur in chains and produce erysipelas and more severe
forms of inflammation; (_c_) diplococci, or paired organisms with a
capsule, which cause acute pneumonia; (_d_) gonococci, with the
opposed surfaces flattened, which cause gonorrhoea. _e_, _f_, _g_,
_h_, Rod-shaped bacteria or bacilli: (_e_) diphtheria bacilli; (_f_)
tubercle bacilli; (_g_) anthrax bacilli; (_h_) the same bacilli in
cultures and producing spores; a small group of spores is shown. (_i_)
Cholera spirillæ. (_j_) Typhoid bacilli. (_k_) Tetanus bacillus;
_i_, _j_, _k_ are actively motile, motion being effected by the small
attached threads. (_l_) The screw-shaped spirochite which is the cause
of syphilis.]
The bacteria (Fig. 17) are unicellular organisms and vary greatly in
size, shape and capacity of growth. The smallest of the pathogenic or
disease-producing bacteria is the influenza bacillus, 1/51000 of an
inch in length and 1/102000 of an inch in thickness; and among the
largest is a bacillus causing an animal disease which is 1/2000 of an
inch in length and 1/25000 of an inch in diameter. Among the
free-living non-pathogenic forms much larger examples are found. In
shape bacteria are round, or rod-shaped, or spiral; the round forms
are called micrococci, the rod-shaped bacilli and the spiral forms are
called spirilli. A clearer idea of the size is possibly given by the
calculation that a drop of water would contain one billion micrococci
of the usual size. Their structure in a general way conforms with that
of other cells. On the outside is a cell membrane which encloses
cytoplasm and nucleus; the latter, however, is not in a single mass,
but the nuclear material is distributed through the cell. Many of the
bacteria have the power of motion, this being effected by small
hair-like appendages or flagellæ which may be numerous, projecting
from all parts of the organisms or from one or both ends, the movement
being produced by rapid lashing of these hairs. A bacterium grows
until it attains the size of the species, when it divides by simple
cleavage at right angles to the long axis forming two individuals. In
some of the spherical forms division takes place alternately in two
planes, and not infrequently the single individuals adhere, forming
figures of long threads or chains or double forms. The rate of growth
varies with the species and with the environment, and under the best
conditions may be very rapid. A generation, that is, the interval
between divisions, has been seen to take place in twenty minutes. At
this rate of growth from a single cholera bacillus sixteen quadrillion
might arise in a single day. Such a rate of growth is extremely
improbable under either natural or artificial conditions, both from
lack of food and from the accumulation in the fluid of waste products
which check growth. Many species of bacteria in addition to this
simple mode of multiplication form spores which are in a way analogous
to the seeds of higher plants and are much more resistant than the
simple or vegetative forms; they endure boiling water and even higher
degrees of dry heat for a considerable time before they are destroyed.
When these spores are placed in conditions favorable for bacterial
life, the bacterial cells grow out from them and the usual mode of
multiplication continues. This capacity for spore formation is of
great importance, and until it was discovered by Cohn in 1876, many of
the conditions of disease and putrefaction could not be explained.
Spores, as the seeds of plants, often seem to be produced when the
conditions are unfavorable; the bacterium then changes into this form,
which under natural conditions is almost indestructible and awaits
better days.
The bacteria are divided into species, the classification being based
on their forms, on the mode of growth, the various substances which
they produce and their capacity for producing disease. The
differentiation of species in bacteria is based chiefly upon their
properties, there being too little difference in form and size to
distinguish species. The introduction of methods of culture was
followed by an immediate advance of our knowledge concerning them.
This method consists in the use of fluid and solid substances which
contain the necessary salts and other ingredients for their food, and
in or on which they are planted. The use of a solid or gelatinous
medium for growth has greatly facilitated the separation of single
species from a mixture of bacteria; a culture fluid containing
sufficient gelatine to render it solid when cooled is sown with the
bacteria to be tested by placing in it while warm and fluid, a small
portion of material containing the bacteria, and after being
thoroughly mixed the fluid is poured on a glass plate and allowed to
cool. The bacteria are in this way separated, and each by its growth
forms a single colony which can be further tested. It is self-evident
that all culture material must be sterilized by heat before using, and
in the manipulations care must be exercised to avoid contamination
from the air. The refraction index of the bacterial cell is so slight
that the microscopic study is facilitated or made possible by staining
them with various aniline dyes. Owing to differences in the cell
material the different species of bacteria show differences in the
facility with which they take the color and the tenacity with which
they retain it, and this also forms a means of species differentiation.
The interrelation of science is well shown in this, for it was the
discovery of the aniline dyes in the latter half of the nineteenth
century which made the fruitful study of bacteria possible.
From the simplicity of structure it is not improbable that the
bacteria are among the oldest forms of life, and all life has become
adapted to their presence. They are of universal distribution; they
play such an important part in the inter-relations of living things
that it is probable life could not continue without them, at least not
in the present way. They form important food for other unicellular
organisms which are important links in the chain; they are the agents
of decomposition, by which the complex substances of living things are
reduced to elementary substances and made available for use; without
them plant life would be impossible, for it is by their
instrumentality that material in the soil is so changed as to be
available as plant food; by their action many of the important foods
of man, often those especially delectable, are produced; they are
constantly with us on all the surfaces of the body; masses live on the
intestinal surfaces and the excrement is largely composed of bacteria.
It has been said that life would be impossible without bacteria, for
the accumulation of the carcasses of all animals which have died would
so encumber the earth as to prevent its use; but the folly of such
speculation is shown by the fact that animals would not have been
there without bacteria. It has been shown, however, that the presence
of bacteria in the intestine of the higher animals is not essential
for life. The coldest parts of the ocean are free from those forms
which live in the intestines, and fish and birds inhabiting these
regions have been found free from bacteria; it has also been found
possible to remove small animals from their mother by Cæsarian section
and to rear them for a few weeks on sterilized food, showing that
digestion and nutrition may go on without bacteria.
Certain species of bacteria are aërobic, that is, they need free
oxygen for their growth; others are anaërobic and will not grow in the
presence of oxygen. Most of the bacteria which produce disease are
facultative, that is, they grow either with or without oxygen; but
certain of them, as the bacillus of tetanus, are anaërobic. There is,
of course, abundance of oxygen in the blood and tissues, but it is so
combined as to be unavailable for the bacteria. Bacteria may further
be divided into those which are saprophytic or which find favorable
conditions for life outside of the body, and the parasitic. Many are
exclusively parasitic or saprophytic, and many are facultative, both
conditions of living being possible. It has been found possible by
varying in many ways the character of the culture medium and
temperature to grow under artificial conditions outside of the body
most, if not all, of the bacteria which cause disease. Thus, such
bacteria as tubercle bacilli and the influenza bacillus can be
cultivated, but they certainly would not find natural conditions which
would make saprophytic growth possible.
Bacteria may be very sensitive to the presence of certain substances
in the fluid in which they are growing. Growth may be inhibited by the
smallest trace of some of the metallic salts, as corrosive sublimate,
although the bacteria themselves are not destroyed. If small pieces of
gold foil be placed on the surface of prepared jelly on which bacteria
have been planted, no growth will take place in the vicinity of the
gold foil.
Variations can easily be produced in bacteria, but they do not tend to
become established. In certain of the bacterial species there are
strains which represent slight variations from the type but which are
not sufficient to constitute new species. If the environment in which
bacteria are living be unusual and to a greater or less degree
unfavorable, those individuals in the mass with the least power of
adaptibility will perish, those more resistant and with greater
adaptability will survive and propagate; and the peculiarity being
transmitted a new strain will arise characterized by this
adaptability. Bacteria with slight adaptability to the environment of
the tissues and fluids of the animal body can, by repeated
inoculations, become so adapted to the new environment as to be in a
high degree pathogenic. In such a process the organisms with the least
power of adaptation are destroyed and new generations are formed from
those of greater power of adaptation. When bacteria are caused to grow
in a new environment they may acquire new characteristics. The anthrax
bacilli find the optimum conditions for growth at the temperature of
the animal body, but they will grow at temperatures both above and
below this. Pasteur found that by gradually increasing the temperature
they could be grown at one hundred and ten degrees. When grown at this
temperature they were no longer so virulent and produced in animals a
mild non-fatal form of anthrax which protected the animal when
inoculated with the virulent strain. The well known variations in the
character of disease, shown in differences in severity and ease of
transmission, seen in different years and in different epidemics, may
be due to many conditions, but probably variation in the infecting
organisms is the most important.
The protozoa, like the bacteria, are unicellular organisms and contain
a nucleus as do all cells. They vary in size from forms seen with
difficulty under the highest power of the microscope to forms readily
seen with the unaided eye. Their structure in general is more complex
than is the structure of bacteria, and many show extreme
differentiation of parts of the single cells, as a firm exterior
surface or cuticle, an internal skeleton, organs of locomotion, mouth
and digestive organs and organs of excretion. They are more widely
distributed than are the bacteria, and found from pole to pole in all
oceans and in all fresh water. There are many modes of multiplication,
and these are often extremely complicated. The most general mode and
one which is common to all is by simple division; a modification of
this is by budding in which projections or buds form on the body and
after separation become new organisms. In other cases spores form
within the cell which become free and develop further into complete
organisms. These simple modes of multiplication often alternate in the
same organism with sexual differentiation and conjugation. There is
never a permanent sexual differentiation, but the sexual forms develop
from a simple and non-sexual organism. Usually the sexual forms
develop only in a special environment; thus the protozoon which in man
is the cause of malaria, multiplies in the human blood by simple
division, but in the body of the mosquito multiplication by sexual
differentiation takes place. Under no conditions is multiplication so
rapid as with the bacteria, and in general the simpler the form of
organism the more rapid is the multiplication. It is common to all of
the protozoa to develop forms which have great powers of resistance,
this being due in some cases to encystment, in which condition a
resistant membrane is formed on the outside, in others to the
production of spores. A fluid environment is essential to the life of
the protozoa, but the resistant forms can endure long periods of
dryness or other unfavorable environmental conditions. The universal
distribution of the protozoa is due to this; the spores or cysts can
be carried long distances by the wind and develop into active forms
when they reach an environment which is favorable. Their distribution
in water depends upon the amount of organic material this contains. In
pure drinking water there may be very few, but in stagnant water they
are very numerous, living not on the organic material in solution in
this, but on the bacteria which find in such fluid favorable
conditions for existence. The food of protozoa consists chiefly of
other organisms, particularly bacteria, and they are classed with the
animals. The protozoa are the most widely distributed and the most
universal of the parasites. The infectious diseases which they produce
in man, although among the most serious are less in number than those
produced by bacteria. So marked is the tendency to parasitism that
they are often parasitic for each other, smaller forms entering into
and living upon the larger. Variation does not seem to be so marked in
the protozoa as in the bacteria, though this is possibly due to our
greater ignorance of them as a class. We are not able, except in rare
instances, to grow them in pure culture, and study innumerable
generations under changes in the environment, as the bacteria have
been studied.
If we regard the living things on earth from the narrow point of view
as to whether they are necessary or useless or hostile to man, the
protozoa must be regarded as about the least useful members of the
biological society. It is very possible that such a conclusion is due
to ignorance; so closely are all living things united, so dependent is
one form of cell activity upon other forms that it is impossible to
foretell the result of the removal of a link. The protozoa do not seem
to be as necessary for the life of man as are the bacteria; they
produce many of the diseases of man, many of the diseases of animals
on which man depends for food; they cause great destruction in plant
life, and in the soil they feed upon the useful bacteria. It is well
to remember, however, that fifty years ago several of the organs of
the body whose activity we now recognize as furnishing substances
necessary for life were regarded as useless members and, since they
became the seat of tumors, as dangerous members of the body. The only
organ which now seems to come into such a class is the vermiform
appendix, and its lowly position among organs is due merely to an
unhappy accident of development.
The class of organisms known as the filterable viruses or the
ultra-microscopic or the invisible organisms have a special interest
in many ways. The limitation in the power of the microscope for the
study of minute objects is due not to a defect in the instrument but
to the length of the wave of light. It is impossible to see clearly
under the microscope using white light, objects which are smaller in
diameter than the length of the wave which gives a limit of 0.5µ. or
1/125,000 of an inch. By using waves of shorter length, as the
ultra-violet light, objects of 0.1µ. or 1/250000 of an inch can be
seen; but as these methods depend upon photography for the
demonstration of the object the study is difficult. The presence of
objects still smaller than 0.1 m. can be detected in a fluid by the
use of the dark field illumination and the ultra-microscope, the
principle of which is the direction of a powerful oblique ray of light
into the field of the microscope. The objects are not visible as such,
but the dispersion of the light by their presence is seen.
The demonstration that infectious diseases were produced by organisms
so small as to be beyond demonstration with the best microscopes was
made possible by showing, that some fluid from a diseased animal was
infectious; and capable of producing the disease when inoculated into
a susceptible animal. The fluid was then filtered through porcelain
filters which were known to hold back all objects of the size of the
smallest bacteria and the disease produced by inoculating with the
clear filtrate. There are a number of such filters of different
degrees of porosity manufactured, and they are often used to procure
pure water for drinking, for which use they are more or less,
generally however, less efficacious. The filter has the form of a
hollow cylinder and the liquid to be filtered is forced through it
under pressure. For domestic use the filter is attached by its open
end to the water tap and the pressure from the mains forces the water
through it. In laboratory uses, denser filters of smaller diameters
are used, and the filter is surrounded by the fluid to be tested. The
open end of the filter passes into a vessel from which the air is
exhausted and filtration takes place from without inward. The test of
the effectiveness of the filter is made by adding to the filtering
fluid some very minute and easily recognizable bacteria and testing
the filtrate for their presence. These filters have been studied
microscopically by grinding very thin sections and measuring the
diameter of the spaces in the material. These are very numerous, and
from 1/25000 to 1/1000 of an inch in diameter, spaces which would
allow bacteria to pass through, but they are held back by the very
fine openings between the spaces and by the tortuosity of the
intercommunications. When the coarser of such filters have been long
in domestic service in filtering drinking water, bacteria may grow in
and through them giving greater bacterial content to the supposed
bacteria-free filtrate than in the filtering water.
That an animal disease was due to such a minute and filterable
organism was first shown by Loeffler in 1898 for the foot and mouth
disease of cattle. This is one of the most infectious and easily
communicable diseases. The lesions of the disease take the form of
blisters which form on the lips and feet and in the mouths of cattle,
and inoculation with minute quantities of the fluid in the blisters
produces the disease. Loeffler filtered the fluid through porcelain
filters, hoping to obtain a material which inoculated into other
cattle would render them immune, and to his surprise found that the
typical disease was produced by inoculating with the filtrate.
Naturally the first idea was that the disease was caused by some
soluble poison and not by a living organism, but this was disproved in
a number of ways. The most powerful poison known is obtained from
cultures of the tetanus bacillus of which 0.000,000,1 of a gram (one
gram is 15.43 grains) kills a mouse, or one gram kills ten million
mice. Loeffler found that 1/30 gram of the contents of the vesicles
killed a calf of two hundred kilograms weight, and assuming that the
essential poison was present in the fluid in one part to five hundred
it would be several hundred times more powerful than the tetanus
poison. Further, the disease produced by inoculation of the filtrate
was itself inoculable and could be transmitted from animal to animal.
It was also found that when the virus was filtered several times it
ceased to be inoculable, showing that each time the fluid was passed
through the filter some of the minute organisms contained in it were
held back.
It is not known whether these organisms belong to the bacteria or
protozoa, and naturally nothing is known as to their form, size and
structure. Up to the present about twenty diseases are known to be due
to a filterable virus, and among these are some of the most important
for animals and for man. Among the human diseases, yellow fever,
poliomyelitis, and dengue are so produced; of the animal diseases in
addition to foot and mouth disease, pleuropneumonia, cattle plague,
African horse sickness, several diseases of fowls and the mosaic
disease of the tobacco plant have all been shown to be due to a
filterable virus. Of these organisms the largest is that which
produces pleuropneumonia in cattle, and this alone has been
cultivated. It gives a slight opacity to the culture fluids, and when
magnified two thousand diameters appears as a minute spiral or round
or stellate organism having a variety of forms. Its size is such that
it passes the coarse, but is held back by the finer, filters and it is
possible that this does not belong to the same class with the
others.[1] The diseases produced by the filterable viruses taken as a
class show much similarity. They run an acute course, are severe, and
the immunity produced by the attack endures for a long time.
Considered in its biological relations, infection is the adaptation of
an organism to the environment which the body of the host offers. It
is rather singular that variations in organisms represented by such
adaptation do not more frequently arise, in which case new diseases
would frequently occur. It cannot be denied that new diseases appear,
but there is no certain evidence that they do, and there is equally no
evidence that diseases disappear. From the meagre descriptions of
diseases, usually of the epidemic type, which have come down to us
from the past, it is difficult to recognize many of the diseases
described. The single diseases are recognized by comparing the causes,
the lesions and the symptoms with those of other diseases, and new
diseases are constantly being separated off from other diseases having
more or less common features. Many new diseases have been recognized
and named, but it is always more than probable that previously they
were confounded with other diseases. Smallpox is such a characteristic
disease that one would think it would have been recognized as an
entity from the beginning, but although the description of some of the
epidemics in remote times conform more or less to the disease as we
know it, the first accurate description is in the eighth century by
the Arabian physician Rhazes. Cerebro-spinal meningitis was not
recognized as a separate disease until 1803, diphtheria not until
1826, and the separation between typhoid and typhus fever was not made
before 1840. Nor is it sure that any diseases have disappeared,
although there seems to have been a change in the character of many.
It is difficult to reconcile leprosy as it appears now with the
universal horror felt towards it, due to the persistence of the old
traditions. It is possible, however, that the disease has not changed
its character, but that such diseases as smallpox, syphilis, and
certain forms of tuberculosis were formerly confounded with leprosy,
thus giving a false idea of its prevalence.
In certain cases the adaptation of the organism is for a narrow
environment; for example, the parasitism may extend to a simple
species only, in others the adaptation may extend to a number of
genera. In certain cases the adaptation is mutual, extending to both
parasite and host and resulting in symbiosis, and this condition may
be advantageous for both. Certain of the protozoa harbor within them
cells of algæ utilizing to their own advantage the green chlorophil of
the algæ in obtaining energy from sunlight and in turn giving
sustenance to the algæ. Although the algæ are useful guests, when they
become too numerous the protozoan devours them. It is evident that
symbiosis is the most favorable condition for the existence of the
parasite, and an injurious action exerted by the parasite on the host
unfavorable. The death of the host is an unfortunate incident from the
parasite's point of view in that it is deprived of habitation and food
supply, being placed in the same unfortunate situation as may befall a
social parasite by the death of his host.
FOOTNOTE:
[1] Flexner has recently succeeded in isolating and cultivating the
organism of poliomyelitis, but the organism is so small that its
classification is not possible.