Virchow (1821-1902) of Berlin, one of the leading names in modern
Medicine. There is indeed hardly any department of medical thought that
has not gained something from Virchow’s work. His great achievement
is the way in which he carried the Cell Theory into the analysis of
diseased tissues. In his _Cellular Pathology_ (1858) he analyzes
diseased tissues from the point of view of cell formation and cell
structure. Important sections of the science of Cellular Pathology have
been explored so well by Virchow that they have been little extended
by his successors. He initiated the familiar idea that the body may
be regarded as ‘a cell State in which every cell is a citizen’.
Disease is often but a civil war. The white blood corpuscles, which
have the power of engulfing and rendering innocuous bacteria and other
foreign bodies, have been compared to police or scavengers. In some
respects Virchow was strangely conservative, and notably he opposed the
evolutionary view of the origin of living forms. Virchow’s conceptions
of the functions of the white blood corpuscles were largely extended
by the Russian biologist Élie Metschnikoff (1845-1916) and the English
worker Almroth Wright (1861-).
Since Virchow and Kölliker the study of the intimate structure and
workings of the cells themselves, as distinct from the tissues,
has become a separate and independent science under the name of
_Cytology_. It may even be extended to the study of cells in disease as
_Cyto-Pathology_.
Among the major developments of Cellular Pathology and Cyto-Pathology
is the study of abnormal ‘new growths’. The most malignant types of
these belong to the group known as the ‘Cancers’. The occurrence of
most of these becomes more frequent as life advances (Fig. 135). Their
cytological features are now well known. A cancer consists essentially
of an increase of cellular tissue, following abnormally rapid
multiplication of one type of cell. The new growth is equipped with
a blood-supply which enables it to increase at the expense of other
tissues and regardless of their needs.
Cancers almost always arise at one point, and are very seldom multiple
in origin. It is fairly established that they are not infectious or
contagious, and there is no very satisfactory evidence that a tendency
to them is inherited. Our scientific knowledge of Cancers is largely
derived from animals. Cancers are ‘specific’ in the sense that those of
one animal species will not grow when inoculated into another species.
An immense amount of work has been done on inoculated Cancers, but it
has become evident that some physiological factor is involved in Cancer
incidence such that an inoculated Cancer is not entirely comparable
with so-called ‘spontaneous’ Cancer. As to what that physiological
factor can be we are still in the dark.
Although we know nothing effective as to this physiological factor,
yet experiments in the artificial production of Cancer, apart from
inoculation, have been attended with success. That various forms of
chronic irritation are associated with the onset of Cancer has long
been clinically recognized. It has been found possible to reproduce
experimentally this relation between irritation and new growth, and
so, for example, to induce Tar Cancer in mice. Nevertheless, it must
be admitted that Cancer investigation is in an unsatisfactory state,
and has yielded fewer positive results than any other department of
Pathology of comparable importance. It is possible that we do not yet
know enough of normal Cell Physiology to investigate with profit the
forms of cellular perversion known as Cancer.
[Illustration:
Drawings by Theodor Schwann to illustrate the nature and origin of
animal cells. All are highly magnified.
FIG. 102. The first step in the origin of cartilage from cellular
tissues. At the lower part the young cells are without cell-walls. In
the upper part they have formed walls and are beginning to secrete
cartilaginous substance. Nuclei and nucleoli are clearly visible.
Above is shown a piece of maturer cartilage, in which the cells are
imbedded in a mass of cartilaginous material.
FIG. 103. Pigment cells, such as are characteristic of the skin of the
frog. In the lowest cell, which is contracted, the nucleus is concealed
by the pigment. The upper two are more expanded and in them nuclei can
be seen.
FIGS. 104 & 105 show how structures of very diverse form can be
differentiated from cells of the same type.
FIG. 104. Young cells from a developing feather. These cells may
enlarge, secrete hard walls, and form the fine spongy tissue of the
inner part of the shaft of the feather. Or the cells may elongate, the
protoplasm become granular, and finally break up into fibers (Fig.
105). These form the tough fibrous matter of the outer part of the
shaft of the feather. In either case, the nucleus disappears and the
cell dies.
]
§ 6. _Establishment of the Doctrine of the Germ Origin of Disease._
The view that many diseases, especially those of a contagious or
infectious nature, originate from the invasion of the body by
special organisms and their multiplication within the body, came
into prominence in the second half of the nineteenth century. There
had been many previous adumbrations of this view and, in its final
establishment, more than one hand may be discerned. Above all others
who have worked in this field towers the mighty figure of Louis Pasteur
(1822-95). We shall do no grave injustice to any man if we treat the
scientific demonstration of the doctrine as the product of his superb
genius.
The opening of Pasteur’s interest in disease can be seen in his work
on fermentation. At first he was faced with the opposition of Liebig.
According to that eminent chemist, fermentation was not the result of
vital activity but was a purely chemical change (p. 207). A ferment
he regarded as an unstable organic product, the character of which
determined the manner of decomposition of the medium in which it is
placed. Pasteur demonstrated that, as there is a specific alcoholic
ferment, so there is a specific milk-souring ferment. Any nitrogenous
matter present in a fluid containing it will serve as food for the
development of a ferment, but will not of itself induce fermentation.
Ferments have, he demonstrated, the power of reproduction. Pasteur
rapidly seized on the idea of the specificity of ferments. An
albuminous sugar solution can be converted into various products by the
addition of various ferments. According as one sows, so will one reap.
The milk-souring ferment, Pasteur concluded, is organized and living,
and its action is correlated to its development and organization. No
life, no ferment; no ferment, no fermentation.
[Illustration: FIG. 106. ORGANISMS OF FERMENTATION HIGHLY MAGNIFIED
from Louis Pasteur’s _Studies on Beer_ of 1876.
1. Bacillus of Turned Wine. 2. Ferment of Soured Milk. 3. Butyric
Ferment. 4. Ferment of Ropy Wine. 5. Ferment of Vinegar. 6. Amorphous
deposit. 7. Sarcinae.
]
During the next years Pasteur applied himself to a study of ferments
and notably of those which involve deterioration of wines and beers.
This led him to perceive that there is a great multiplicity and
variety of these organisms. Now it was an old and well-known view
that fermentation, putrefaction, and the infection of disease had much
in common. It was perfectly natural, therefore, for Pasteur to regard
the latter in the light of a vital process. A great difficulty was,
however, the demand that any such doctrine made on the germ-bearing
capacity of the air. Cities were not slow to avail themselves of this
weakness, and pointed out that, according to Pasteur, the air must
be one solid mass of germs! For the opponents of Pasteur the living
organisms found in the process of fermentation or decomposition were
the result, not the cause, of the process. These organisms were
regarded by them as spontaneously generated in the fermentation
process. Thus arose a discussion of the old theme of spontaneous
generation.
By 1859--the year of publication of Darwin’s _Origin of
Species_--Pasteur was engaged in controversy as to the ‘Origin of
Life’. The discussion specially turned round what were then regarded as
the lowest forms of life, the Bacteria. Were they ever spontaneously
generated, or were they not? If a flask of broth, supposedly sterilized
by boiling, went ‘bad’ and organisms appeared in it, was it certain
that they had come from without, or could they have been spontaneously
generated by the broth itself? Life must begin somewhere. Then why
not here at this lowest stage? If this view be justifiable, Pasteur’s
doctrine of the nature of ferments must fall to the ground.
Pasteur had thus before him the task of proving a universal negative--a
task impossible in Formal Logic. But Science is not Formal Logic. In
the end he clinched the matter by an exquisitely simple experiment
which must, at once, carry conviction. A flask with a long S-shaped
neck is filled with a putrescible fluid. It is heated to boiling, to
kill all organisms, and then left in the still air of a room. Air can
enter, but any floating germs that enter naturally fall on the floor
of the S-shaped neck of the flask. Months may go by without any change
in the liquid, but once the neck is severed, so that organisms can
enter freely from the air, fermentation sets in within a few hours, and
organisms can be detected in the liquid. Only living organisms from the
air can have caused the change.
[Illustration:
FIG. 107. PASTEUR’S CRUCIAL EXPERIMENT to prove that fermentation or
putrefaction is the result of the action of air-borne organisms. The
S-shaped flask contains a putrescible fluid such as meat broth. The
flask containing the broth is subjected to prolonged heating to destroy
all organisms. It is then left in position with the mouth open. Days,
weeks, months, even years, may pass without sign of putrefaction. No
organisms reach the broth, since any that enter the open mouth fall on
the floor of the neck and remain there. Sever the neck of the flask so
that organisms can fall from the air directly on to the surface of the
fluid and these multiply. In a few hours putrefaction sets in. This
is shown by the formation of a film or scum on the surface just below
the severed neck. Microscopically the broth is seen to be teeming with
organisms.
]
The first disease which Pasteur was able to demonstrate as causatively
related to a living organism was a condition that was devastating the
silk-worm industry of France. In 1866 he proved the contagiousness of
the disease, showed that it was due to a living organism, and followed
the organism through the life-history of moth, egg, worm, and chrysalis.
In 1870 the Franco-Prussian war broke out. Pasteur now decided to make
investigations into the diseases of beer, his object being to improve
the French brews and to carry the war into the enemy’s camp by making
them equal to the German! He succeeded in isolating special organisms,
mostly yeasts, which produced defects in beer (Fig. 106). This work
naturally led to an enlargement of his views on the nature and action
of micro-organisms.
About this time Pasteur was elected a member of the French Academy
of Medicine, a very unusual honor for one not a medical man. Lister
had already begun his teaching, based partly on the work of Pasteur,
and indeed his first important paper on antiseptic surgery had been
published in the very year of the Franco-Prussian war. On entering the
Academy Pasteur found himself faced by all kinds of ancient prejudices
and misconceptions in connection with his new doctrine, and especially
with his denial of spontaneous generation. Among his supporters was the
physiologist, Claude Bernard (p. 213). His work proceeded to more and
more triumphant issues.
The first disease that affects man on which Pasteur was able to throw
light was Anthrax, in relation to which his work interdigitates with
that of Robert Koch and some other observers. Anthrax is a deadly
and highly contagious condition which commonly affects cattle, but
sometimes spreads to man. As early as 1855, a German observer had
noted microscopic rod-like objects in the blood of beasts dead of
the disease. In 1868 an older French contemporary of Pasteur had
shown that a bacillus is not simply the inseparable companion of the
disease, but also is its cause and its only constantly acting cause. At
this time the losses of cattle from Anthrax in France were enormous.
The character of the outbreaks had been studied and seemed wholly
unexplained by what was known of the bacillus. Farmers found that they
lost cattle in fields from which infected animals had been excluded for
months or even years. How was it to be explained?
The explanation was, in fact, advanced in 1876 by the German observer,
Robert Koch of Berlin (1843-1910), whose work was now beginning.
He showed that the anthrax bacilli under certain conditions formed
‘spores’, that is to say small encysted bodies, exceedingly resistant
to heat and to other changes of external conditions (Fig. 108). This
discovery opened up a new field which was cultivated by Koch and
Pasteur and their followers.
[Illustration: FIG. 108. BACILLI OF ANTHRAX, from a culture, highly
magnified.
The rod-like organisms are growing typically in chains. Some of
the rods have white clear spots in them. These are the highly
resistant ‘spores’.
]
While making his studies on ferments in 1863, Pasteur had witnessed the
formation of spores in the organisms of butyric fermentation, but had
failed to grasp their significance. In 1869 he had again found spores
forming in the organisms of silk-worm disease, and had shown that they
resisted prolonged drying. On the basis of their resistance he had
explained the persistence and latency of the silk-worm disease. Other
observers had had similar experiences. The investigations of none of
them, however, approached in brilliance and completeness those of Koch.
Koch found that spores always form in the blood and tissues of animals
dead of Anthrax, provided that
(1) the temperature is suitable, and (2) there is sufficient
oxygen. These two conditions, temperature and oxygen, were found to
be necessary. Below 18° Centigrade spores are not formed; at 30°
Centigrade they occur at the end of thirty hours; at 35° Centigrade
in twenty hours. The rapidity with which spores are formed is,
therefore, proportional to the amount of heat. Oxygen was also found
to be indispensable. Anthrax blood, if deprived of oxygen, ceases to
be virulent in twenty-four hours without putrefaction. When the blood
is allowed to putrefy the virulence also disappears if putrefaction
exhausts the oxygen quickly enough to prevent the spores having time to
form. If the spores have already formed, putrefaction does not kill
them, nor does it prevent them from developing later if circumstances
become favorable. The persistence of the disease and its return in
an infected country was thus explained. It was the spore which was
the agent of preservation, which persisted where the conditions of
temperature and of aeration had permitted it to form, and which always
held itself in readiness to make new victims.
The matter was carried further by Pasteur in 1877. At that time he
did not know of all the work of Koch. He succeeded in obtaining pure
cultures of Anthrax. The question was then still being debated in
France as to whether Anthrax was caused by a ‘virus’, that is to say a
non-living poison, or by a microbe. Pasteur had long been a believer in
the microbic theory, and it seemed to him probable that the blood of an
animal infected with Anthrax, if sown in a suitable medium, would stock
it solely with anthrax bacilli which he could then keep pure for an
indefinite time in successive cultures, as he had done with yeast and
other ferments.
Experiment proved this to be the case, and showed that the anthrax
organism multiplied abundantly in urine made neutral or slightly
alkaline. From that time the problem was solved. Take a series of
cultures of the organism, transferring each time one drop from the
preceding culture into 50 c.c. of fresh urine. The first dilution
is 1/1000, the second one in a million, the third one in a thousand
million. After ten cultures it falls to such a figure that the
original drop of blood has been drowned in an ocean. Everything that
it carried with it, to which we might attribute the production of
Anthrax--red corpuscles, white corpuscles, granules of all sorts--is
either destroyed by the change of medium or is widely disseminated in
this ocean and is lost. Only the organism can escape the dilution. Why?
Because it has multiplied in each of the cultures. A drop from the last
culture killed a rabbit or guinea-pig as surely as a drop of anthrax
blood. It was, therefore, to the organism that the virulence belonged.
A conclusion of the first rank was firmly established.
With a ‘pure culture’ of Anthrax in his possession Pasteur was able
to experiment in a way which none had previously attempted. The most
interesting stage of his work was now entered upon. He perceived that
there are some species of animals which are refractory to Anthrax.
Such are the birds. Nevertheless, the blood of a bird, when drawn
from the animal, is an excellent culture medium for the bacterium.
Why does it resist infection in the animal? Pasteur showed that the
anthrax organism will not live in the bird because the living-blood
in full circulation is filled with an infinite number of corpuscles
which, in order to live and perform their physiological function, need
free oxygen. When, therefore, the anthrax organism enters normal blood
of living birds, it meets competitors ready to seize the oxygen for
their own use. But the blood of other animals besides birds contains
corpuscles eager for oxygen. Why can anthrax grow in them and not
in birds? This question Pasteur answered by a convincing series of
experiments (1878). The normal temperature of birds is higher than that
of mammals and is, moreover, higher than that at which the growth of
the anthrax organism is most vigorous. Thus the blood corpuscles of
the bird have the anthrax bacteria at a disadvantage. But if, by a cold
bath, the temperature of a bird be lowered to that of a mammal, and if
anthrax organisms be injected into the blood-stream, they will grow and
flourish at the expense of the bird.
The experiments with Anthrax on fowls led to experiments on the same
creatures with another disease, the virulence of which was known
to vary, Chicken Cholera. Thus arose naturally Pasteur’s ideas and
observations in the department of Immunity (p. 261).
If Pasteur can be said to have laid the foundations of the knowledge
of the nature of infection, it is to Koch that we owe the main basis
of the technique by which diseases are now studied. He it was who
elevated Bacteriology into the position of a separate science. Soon
after his work on Anthrax he published a remarkable research which
placed our knowledge of wound infection on a firm footing. He is thus
among those who helped to create modern surgical technique. Many other
communications came from him. None was of more far-reaching importance
than his demonstration of the organism of Tuberculosis in 1882. All
subsequent work in connection with Consumption and allied conditions
has been rendered possible only by this discovery of Koch. Other
investigations associated with his name are on Cholera and on Sleeping
Sickness. Koch was unquestionably the greatest bacteriologist that the
world has seen. His genius was limited as compared to that of Pasteur,
but his exquisite technical skill and acumen have never been excelled.
Since the time of Pasteur and Koch, the study of infectious disease
has developed along various special lines. The work of these two
men, however, has determined the direction of those lines, and
they themselves are the most typical, as well as the greatest,
representatives of the most important of all movements in modern
Medicine.
§ 7. _Anaesthesia._
The aspect of surgical practice was dramatically changed during
the course of the nineteenth century by two discoveries, that of
Anaesthesia and that of the Antiseptic method. It will be convenient to
consider Anaesthesia first.
There were from the earliest times many devices for producing more
or less complete unconsciousness during surgical operations. An idea
of the extremes to which surgeons at the beginning of the nineteenth
century were put in this matter can be gathered from a glance at some
of their devices (Fig. 108a).
The new era began in 1846 when the dentist, William Thomas Green Morton
(1819-68), demonstrated at the Massachusetts General Hospital the
simplicity and safety of Ether anaesthesia. The idea immediately caught
on. Before the year was out Ether was being used for surgical purposes
in England. In January, 1847, Sir James Young Simpson (1811-70) was
using it in Edinburgh for obstetric purposes. A few months later he
adopted Chloroform, which had been prepared by Liebig in 1832.
The use of the drugs spread very rapidly and almost as rapidly changed
the character of surgical technique. Until the adoption of anaesthesia,
speed was of primary importance in surgical procedure. Excessive speed
now became a matter of less importance, and operative neatness and
completeness took its place as the chief quality of good surgery.
Moreover, operations of a more drastic character could be undertaken
since the shock to the patient was minimized. Women in labor were found
to bear Chloroform peculiarly well and safely, and its use in midwifery
steadily spread despite some foolish and fanatical opposition.
Soon after the introduction of anaesthetics efforts were made by
various methods to secure a painless state of a part without involving
unconsciousness. The first successes were obtained in 1884 at Vienna
with applications of solutions of the alkaloid (p. 325) Cocaine,
first to the eye, then to the nose and other parts. Cocaine, or some
derivative of it, has ever since been much used in Medicine. It was
soon being given by injection under the skin for small superficial
operations. Next, good results from injecting solutions of it into the
nerves were obtained by several American surgeons, earliest of whom
was W. S. Halsted (1852-). His work of 1885 was extended in 1898 by
Harvey Cushing (1869-). Yet another American surgeon, J. L. Corning
(1855-), introduced the method of so-called ‘spinal anaesthesia’.
This is secured by injecting a solution of Cocaine or one of its
derivatives into the spinal canal and thereby inducing insensibility to
pain (‘analgesia’) below the site of injection. In 1908 the American G.
W. Crile (1864-) introduced a valuable method of combining local and
general anaesthesia, whereby he minimized the effects of ‘shock’ (pp.
310-11) during the progress of the operation.
From first to last almost all the pioneer work upon anaesthetics and
analgesics has been of American origin. Even the word _anaesthesia_
is an American invention. It was introduced or at least familiarized
by Oliver Wendell Holmes (1809-94), the distinguished and brilliant
author of the ‘Breakfast Table’ series. Laughing Gas was first applied
to dental purposes a short time before Ether was given its surgical
application, and its introduction for this purpose was the work of the
American dentist Horace Wells (1815-45), of Hartford, Connecticut.
[Illustration:
FIG. 108a. SCREW adapted to the lower limb, as used by surgeons in the
eighteenth century and the early nineteenth century, to compress the
nerves in order to secure analgesia during amputation. Its application,
however, was extremely painful in itself and injurious to the part
operated on.
]
§ 8. _The Revolution in Surgery._