NEWER PHYSIOLOGY AND PATHOLOGY.

By Prof. SAMUEL BELL, M.D.

Physiology has for many decades been a science founded on experiment,

and pathology has been rapidly pressing forward in the same direction.

To read the accounts of how certain conclusions have been arrived at

in the laboratory, by ingenious devices and by skillful manipulations,

is as fascinating as any tale of adventure.

When the microscope began its work, how discouraging was the vastness

and complexity of the discoveries which it brought to light; how many

years has it been diligently used, and how uncertain are we still

about many of its revelations! But what a happy conjecture of man, and

as proper environment takes place we may reach better results! Let me

give an illustration:

Some thirty years ago, Virchow began his studies and lectures upon

cellular pathology. The enthusiasm which he awakened spread over the

whole medical world. The wonderful attention to detail, the broad

philosophy which signalized his observations, were alike remarkable.

His class room was packed with students from every country, who

thought it no hardship to struggle for a seat at eight o'clock in the

morning. With his blackboard behind him and specimens of pathology

before him, and microscopes coursing upon railway tracks around the

tables which filled the room, he was the embodiment of the teacher;

his highest honor was as discoverer. The life and importance of the

cell, both in health and disease, it has been his work to discover and

to teach. The point of view from which he has classified tumors is

founded on this basis, and remains the accepted method. The light

which he cast upon the nature of inflammation has not yet been

obscured, and while other phenomena appear, the multiplication of

cells and nuclei and the formation of connective tissue in the process

of inflammation will always call to mind his labors.

To one of Virchow's pupils, Prof. Recklinghausen, we chiefly owe our

knowledge of the phenomena of diapedesis as a part of the inflammatory

activity. How incredible it seems that masses of living matter can

make their way through the walls of blood vessels which do not rupture

and which have no visible apertures!

Virchow fixed his attention upon the forms and activities of the

cells, their multiplication and degradation, and how they build up

tissues, both healthy and morbid.

To another matter with which, both literally and metaphorically, the

air is filled, we must also make allusion. The existence of

micro-organisms in countless numbers is no new fact, but the influence

they may exert over living tissues has only lately become the subject

of earnest attention. So long as they were not known to have any

practical bearing upon human welfare, they interested almost nobody,

but when, however, it was shown that putrefaction of meat is due to

the agency of the _bacterium termo_, and the decomposition of albumen

to the _bacillus subtilis_; when anthrax in cattle and sheep was found

to depend on the _bacillus anthracis_, and that in human beings it

caused malignant pustules; when suppuration of wounds was found to be

associated with micrococci; and when it was announced that by a

process of inoculation cattle could be protected against anthrax, and

that by carbolic spray and other well known precautions the

suppuration of wounds could be prevented--all the world lent its ears

and investigation at once began.

Because labors in bacteriology promised to be fruitful in practical

results, the workers speedily became innumerable, and we are

accumulating a wondrous store of facts. How long now is the list of

diseases in which germs make their appearance--in pneumonia, in

endocarditis, in erysipelas, in pyæmia, in tuberculosis, and so on and

so on. One of the most striking illustrations is the gonococcus of

gonorrhoea, whose presence in and around gives to the pus cells

their virulent properties, and when transferred to the eye works such

lamentable mischief. Without their existence the inoculation of pus in

the healthy eye is harmless; pus bearing the gonococci excites the

most intense inflammation. Similar suppurative action in the cornea is

often caused by infection of cocci. The proof of causation may be

found in the fact that the most effective cure now practiced for such

suppuration is to sterilize them by the actual cautery. Rosenbach says

that he knows six distinct microbes which are capable of exciting

suppuration in man. Their activity may be productive of a poison, or

putrefactive alkaloid, which is absorbed.

There are at present two prominent theories in regard to the

infections which produce disease. The first is based upon chemical

processes, the second upon the multiplication of living organisms. The

chemical theory maintains that after the infectious element has been

received into the body it acts as a ferment, and gives rise to certain

morbid processes, upon the principle of catalysis. The theory of

organisms, or the germ theory, maintains that the infectious elements

are living organisms, which, being received into the system, are

reproduced indefinitely, and excite morbid processes which are

characteristic of certain types of disease. This latter theory so

readily explains many of the facts connected with the development and

reproduction of infectious diseases, that it has been unqualifiedly

adopted by a large number of investigators. The proofs of this theory

had not, however, advanced beyond the demonstrations of the presence

of certain forms of bacteria in the pathological changes of a very

limited number of infectious diseases, until February, 1882, when Koch

announced his discovery of the tubercle bacillus, since which time

nearly every disease has its supposed microbe, and the race is,

indeed, swift in which the would-be discoverers press forward with new

germs for public favor.

The term bacteria or microbe refers to particles of matter,

microscopic in size, which belong to the vegetable kingdom, where they

are known as fungi. If we examine a drop of stagnant water under the

microscope, amplifying say four hundred diameters, we see it loaded

with minute bodies, some mere points, others slightly elongated into

rods, all actively in motion and in various positions, a countless

confusion. If evaporation now takes place, all is still. If we now

apply moisture, the dried-up granules will show activity, as though

they had not been disturbed.

All these different organisms have become familiar to us under the

generic term bacteria, which is a very unfortunate application, as it

really applies to only a single class of fungi. Cohn calls them

schizomycetes, and makes the following classifications:

1. _Sphero-bacteria_, or microbes.

2. _Micro-bacteria_, or bacteria.

3. _Desmo-bacteria_, or bacilli.

4. _Spiroteria_, or spirillæ.

The _spiro-bacteria_, or micrococci, are the simplest of the fungi,

and appear as minute organisms of spherical form. They multiply by

fission, a single coccus forming two, these two producing four, and so

on. They present a variety of appearances under the microscope. From

single isolated specimens (which under the highest magnifying power

present nothing beyond minute points) you will observe them in pairs,

again in fours, or in clusters of hundreds (forming zoöglea) and still

adhering together, forming chains. When a given specimen is about to

divide, it is seen to elongate slightly, then a constriction is

formed, which deepens until complete fission ensues.

Micrococci possess no visible structure. They consist of a minute

droplet of protoplasm (mycroprotein) surrounded by a delicate cell

membrane. Certain forms are embedded in a capsule (diameter 0.0008 to

0.0001 millimeter).

These little organisms, when observed in a fluid like blood, sputum,

etc., are found to present very active movements, although provided

with no organs of locomotion.

This Brownian motion is possessed by almost every minute particle of

matter, organic and inorganic, and is not due to any inherent power of

the individual. They are almost omnipresent, abounding in the air, the

earth, the water, are always found in millions where moist organic

matter is undergoing decomposition, and are associated with the

processes of fermentation--in fact, they are essential to it. The

souring of milk succeeds the multiplication of these germs. Certain

varieties are pigmented, and we observe colonies of chromogenic cocci

multiplying upon slices of boiled potato, eggs, etc., presenting all

the colors of the rainbow. All of these germs are not the cause of

disease. Certain species, however (termed pathogenic), are always

associated with certain diseased conditions.

The _bacteria-termo_--micro-bacteria--are slightly elongated, and

inasmuch as they multiply by division, frequently appear coupled

together, linked in pairs, and in chains. They are generally found in

putrefying liquids, especially infusions of vegetable matter. They

possess mobility to a remarkable degree. Observing a field of

bacteria-termo under the microscope, they may be seen actively engaged

in twining and twisting. A flagellum has been demonstrated as attached

to one or both extremities. This is too minute to be generally

resolved, even if it is a common appendage.

_Desmo-bacteria_ (or bacilli) are rod-like organisms, occurring of

various lengths and different thicknesses. In a slide of the bacillus

of tuberculosis and anthrax, we notice at intervals dots which

represent the spores from which, as the rods break up, future bacilli

are developed.

Then we have _spiro-bacteria,_ the spirilla and the spirochetæ; the

former having short open spirals, the latter long and closely wound

spirals. The _spirillum, volutans_ is often found in drinking water,

and in common with some other specimens of this class is provided with

flagellæ, sometimes at both extremities, which furnish the means of

rapid locomotion. The spiro-bacteria multiply by spores, although

little is at present known of their life history. They frequently are

attached together at their extremities, forming zigzag chains.

We have seen that bacteria differ greatly in appearance from the

elongated dot of the bacterium proper, to the elongated rod or

cylinder of the bacillus, and the long spirals of spiro-bacteria. It

is unfortunate that they are not sufficiently constant in habit to

always attach themselves to one or the other of these genera. The

micrococcus has a habit of elongating at times until it is impossible

to recognize him except as a bacterium; while bacilli, again, break up

until their particles exactly resemble micrococci.

Bacteria cannot exist without water; certain forms require oxygen,

while others thrive equally well without it; some thrive in solution

of simple salts, while others require albuminoid material.

Bacteriology, with its relation to the science of medicine, is of

importance to every investigating physician; it covers our knowledge

of the relation of these minute organisms to the ætiology of disease.

What has been gained as to practical application in the treatment of

disease? This question is not infrequently asked in a sneering manner.

We can, in reply, say that the results are not all in the future. It

is encouraging that results have been attained which have had a very

important practical bearing, and that these complaints come generally

from individuals least acquainted with scientific investigations in

bacteriology.

In the study of the relation of a given bacterium to a certain

disease, it becomes necessary to attend carefully to three different

operations: First, the organism supposed to cause the disease must be

found and isolated. Second, it must be cultivated through several

generations in order that absolute purity may be secured. Lastly, the

germ must be again introduced into a healthy living being. If the

preceding steps be carried out, and the original disease be

communicated by inoculation, and the germs be again found in the

diseased body, we have no alternative; we must conclude that we have

ascertained the cause of the disease. The importance of being familiar

with the ætiology of the disease before we can expect to combat it

with any well-grounded hope of success is evident.

If the sputum of a phthisical patient be submitted to the skilled

microscopist, he is nearly always able to demonstrate bacilli, but

this goes for very little. Because bacilli are found in phthisis, it

is no more certain that they are the cause of phthisis than it is

certain that cheese mites are the cause of cheese. Well, suppose we

were to inject sputum from a phthisical person into the lower animal

and tuberculosis follows, and then announce to the profession that we

have demonstrated the relation of the cause and effect between bacilli

and phthisis? Why we would start such an uproar of objections as would

speedily convince us that there was much work yet in the domain of

bacteriology.

The scientific investigators would say you have injected with the

sputum into the blood of your unfortunate patient, pus, morphological

elements, and perhaps half a dozen other forms of bacteria, any one of

which is just as likely to produce the disease as the bacillus you

have selected.

The first important step is, first isolate your bacillus. If I were to

take a glass plate, one side of which is coated with a thick solution

of peptonized gelatin, and allow the water to collect, the gelatinous

matter will become solid. If now, with a wire dipped in some

tuberculous matter, I draw a line along the gelatin, I have deposited

at intervals along this line, specimens of tubercle bacilli. If this

plate be now kept at a proper temperature, after a few days, wherever

the bacilli have been caught, a grayish spot will appear, which,

easily seen with the naked eye, gradually spreads and becomes larger.

These spots are colonies containing thousands of bacilli. Let us

return to our gelatin plate.

We find a spot which answers to the description of a colony of

tubercle bacilli. We now take a minute particle from this colony on a

wire and convey it to the surface of some hardened blood serum in a

test tube. We plug the tube so that no air germs may drop in, and

place it in an incubator at the proper temperature. After several

days, if no contamination be present, a colony of bacilli will appear

around the spot where we sowed the spores. Let us repeat the process.

Take a particle from this colony, and transfer it to another tube.

This is our second culture. This must be repeated until we are

satisfied that we have secured a _pure_ culture. If this be carried to

the twenty-fifth generation, we may be assured that there remains no

pus, no ptomaines, nothing but the desired bacilli.

It is a proper material now for inoculation, and if we inoculate some

of the lower animals, for instance the monkey, we produce a disease

identical with phthisis pulmpnalis. Bacteria also afford peculiar

chemical reactions. For example, nitric acid will discharge all the

color from all bacilli artificially dyed with anilin, except those of

tubercle and anthrax. One species is stained readily with a dye that

leaves another unaltered. Thus we are enabled in the laboratory to

determine whether the bacilli found in sputum, for example, are from

tubercle or are the bacteria of decomposition.

From what I have said of the tubercle bacillus, it would seem

thoroughly demonstrated that it is the cause of tubercle in these

animals. But we must walk cautiously here. These are not human beings,

who know that like results would follow their inoculation. The animals

used by Koch are animals very subject to tubercle.

We must, from the very nature of our environment, be constantly

inhaling these germs as we pass through the wards of our hospitals;

yes, they are floating in the air of our streets and dwellings. It

becomes necessary then for us to inquire: If bacteria cause disease,

in what manner do they produce it? The healthy organism is always

beset with a multitude of non-pathogenic bacteria. They occupy the

natural cavities, especially the alimentary canal. They feed on the

substances lying in their neighborhood, whether brought into the body

or secreted by the tissues. In so doing they set up chemical changes

in their substances. Where the organs are acting normally these fungi

work no mischief. The products of decomposition thus set up are

harmless, or are conveyed out of the body before they begin to be

active.

If bacteria develop to an inordinate degree, if the contents of organs

are not frequently discharged, fermentative processes may be set up,

which result in disease. Bacteria must always multiply and exist at

the expense of the body which they infest, and the more weakened the

vital forces become, the more favorable is the soil for their

development.

Septicæmia is caused by the absorption of the products of

putrefaction, induced before bacteria can multiply inside or outside

the body. Bacteria must find a congenial soil. The so-called cholera

bacillus must gain access to the intestinal tract before it finds

conditions suitable to colonization. It does not seem to multiply in

the stomach or in the blood, but once injected into the duodenum

develops with astonishing rapidity, and the delicate epithelial cells

of the villi become swollen, soften and break down, exposing the

mucosa.

It has been shown that _bouillon_ in which Loeffler's diphtheria

bacillus has grown, and which has been passed through unglazed

porcelain filters, shows the presence of a poison which is capable of

producing the same results upon inoculation as the pure culture of the

bacillus itself. Zarniko, working upon the same organism, obtained a

number of positive results that led him to declare this bacillus is

the cause of epidemic diphtheria, in spite of many assertions to the

contrary. Chantmesse and Widal record the results of their work as to

what will most easily and effectively destroy the bacillus of

diphtheria.

The only three substances that actually checked and destroyed its

vitality were phenic acid (5 per cent.), camphor (20 per cent.), olive

oil (25 per cent.), in combination. For the last I substitute

glycerine, because this allows the mixture to penetrate farther into

the mucous membrane than oil, the latter favoring a tendency to pass

over the surface. This mixture when heated separates into two layers,

the upper one viscid and forming a sort of "glycerol," the lower

clear. The latter will completely sterilize a thread dipped in a pure

culture of the diphtheria bacillus. Corrosive sublimate was not

examined because in strong enough doses it would be dangerous and in

weaker ones it would be useless.

The facts obtained in regards to the streptococcus of erysipelas are

reported as follows: That both chemical and experimental evidence

teach the extreme ease of a renewed attack of the disease; that it is

possible to kill guinea pigs by an intoxication when they are immune

to an inoculation of the culture in ordinary quantities. And this

latter fact should warn experimenters trying to obtain immunity in man

by the inoculation of non-pathogenic bacteria, because the same

results may be reached.

A new theory in regard to fevers and the relation of micro-organisms

is suggested by Roussy, viz.: That it is a fermentation produced by a

diastase or soluble ferment found in all micro-organisms and cells,

and which they use in attacking and transforming matter, either inside

their substance or without it.

The resemblance of the malaria parasite to that of recurrent fever is

noted in the work of Sacharoff. He states that there exists in the

blood of those suffering from recurrent fever a hæmatozoon, which is

most prominent after the fever has begun to fall, when it is of

enormous proportions, twenty or more diameters of a red blood

corpuscle, although smaller ones may still be found. The parasite

consists of a delicate amoeboid body containing a multitude of dark,

round, uniform, sharply outlined, movable granules. Besides these, the

protoplasm contains a generally grayish homogeneous nucleus as large

as one or two red blood corpuscles. The protoplasm sends out

pseudopodia (with granules), which sometimes separate and appear as

small delicate pieces of protoplasm. They vary in size, and are often

swallowed by the red blood corpuscles in which they grow, and finally

develop into the above mentioned amoeboid bodies.

Prof. J. Lewis Smith has made a great many autopsies of children dead

from cholera infantum, and almost invariably found the stomach and

liver in a comparatively healthy condition. Ganghen, who has given

this subject considerable study, denies the existence of any specific

germ in the summer diarrhea of infants, but claims to have found three

different germs in the intestines of children suffering from cholera

infantum, each producing a chemical poison which is capable of

producing vomiting, purging, and even death. A great variety of germs

are found in drinking water, and no doubt countless numbers are taken

into the digestive tract, and the principal reason why pathological

conditions do not occur more frequently is on account of the

germicidal qualities of the gastric juice.

The comma bacillus of Koch, and the typhoid fever germ of Eberth, are

especially destroyed in normal gastric juice. When the germs are very

numerous, they run the gauntlet of the stomach (as the gastric juice

is secreted only during digestion); and once in the alkaline

intestinal canal they are capable of setting up disease, other

conditions contributing--ill health, deranged digestion, etc.

Mittnam has made a study of bacteria beneath the nails, and reports,

after examining persons following different occupations, having found

numerous varieties of micro-organisms; which are interesting from a

scientific standpoint relative to the importance of thoroughly

cleansing the hands before undertaking any surgical procedure. He

found, out of twenty-five experiments, 78 varieties of bacteria, of

which 36 were classed as micrococci, 21 diplococci, 18 rods, 3

sarcinæ, and 1 yeast. Cooks, barbers, waiters, etc., were examined.

The blood, defibrinated and freshly drawn, has marked germicidal

action; for bacteria its action is decidedly deadly, even hours after

it has been drawn from the body. Especially were anti-germic qualities

noticed upon pathogenic bacteria. Buchner put the bacilli of anthrax

in a quantity of blood, and in two hours the number was reduced from

4,800 to 56, and in three hours only 3 living bacteria remained. Other

bacteria were experimented upon in blood with similar results, but the

destruction of the organism from putrefaction was much less marked,

and on some varieties the blood had little or no action.

It is not the object of these remarks to even give a _résumé_ of the

_status præsens_ of bacteriology, but simply to stimulate thought in

that direction. The claims of some of the ultra-bacteriologists may

never be realized, but enough has been accomplished to revolutionize

the treatment of certain diseases, and the observing student will do

well to keep his eye on the microbe, as it seems from the latest

investigations that its star is in the ascendant. And who can

prognosticate but that in the next decade an entire revolution in the

ætiology and treatment of many diseases may take place?

Detroit, Mich.

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Scientific American Supplement, No. 787, January 31, 1891 · 第 56 / 71 题