Vaughan has shown that the presence in the body of any alien protein
causes an increased production of heat, and that there is no difference
between the production of fever by foreign proteins and by infections.
Before the day of the hypodermic needle and of experimental medicine,
the foreign proteins found in the body outside the alimentary tract
were brought in by invading microorganisms. Such organisms interfered
with and destroyed the host. The body, therefore, was forced
to evolve a means of protection against these hostile organisms.
The increased metabolism and fever in infection might operate
as a protection in two ways--the increased fever, by interfering
with bacterial growth, and the increased metabolism, by breaking up
the bacteria. Bacteriologists have taught us that bacteria grow best
at the normal temperature of the body, hence fever must interfere
with bacterial growth. With each rise of one degree centigrade
the chemical activity of the body is increased 10 per cent.
In acute infections there is aversion to food and frequently there
is vomiting. In fever, then, we have diminished intake of energy,
but an increased output of energy--hence the available potential
energy in the body is rapidly consumed. This may be an adaptation
for the purpose of breaking up the foreign protein molecules
composing the bacteria. Thus the body may be purified by a chemical
combustion so furious that frequently the host itself is destroyed.
The problems of immunity are not considered here.
As to the mechanism which produces fever, we postulate that it
is the same mechanism as that which produces muscular activity.
Muscular activity is produced by the conversion of latent energy
into motion, and fever is produced largely in the muscles by
the conversion of latent energy into heat. We should, therefore,
find similar changes in the brain, the adrenals, the thyroid,
and the liver, whatever may be the purpose of the conversion of energy--
whether for running, for fighting, for the expression of emotion,
or for combating infection.
We shall first present experimental and clinical evidence which tends
to show what part is played by the brain in the production of both
muscular and febrile action, and later we shall discuss the parts
played by the adrenals, the thyroid, and the liver. Histologic Changes
in the Brain-cells in Relation to the Maintenance of Consciousness
and to the Production of the Emotions, Muscular Activity, and Fever
We have studied the brain-cells in human cases of fever,
and in animals after prolonged insomnia; after the injection
of the toxins of gonococci, of streptococci, of staphylococci,
and of colon, tetanus, diphtheria, and typhoid bacilli; and after
the injection of foreign proteins, of indol and skatol, of leucin,
and of peptones. We have studied the brains of animals which had been
activated in varying degrees up to the point of complete exhaustion
by running, by fighting, by rage and fear, by physical injury,
and by the injection of strychnin (Figs. 2, 4, 5, and 37). We have
studied the brains of salmon at the mouth of the Columbia River
and at its headwater (Fig. 55); the brains of electric fish,
the storage batteries of which had been partially discharged,
and of those the batteries of which had been completely discharged;
the brains of woodchucks in hibernation and after fighting;
the brains of humans who had died from anemia resulting from hemorrhage,
from acidosis, from eclampsia, from cancer and from other chronic diseases
(Figs. 40 to 43, 56, 74, and 75). We have studied also the brains
of animals after the excision of the adrenals, of the pancreas,
and of the liver (Figs. 57 and 60).
In every instance the loss of vitality--that is, the loss
of the normal power to convert potential into kinetic energy--
was accompanied by physical changes in the brain-cells (Figs. 45
and 46). The converse was also true, that is, the brain-cells
of animals with normal vital power showed no histologic changes.
The changes in the brain-cells were identical whatever the cause.
The crucial question then becomes: Are these constant changes in
the brain-cells the result of work done by the brain-cells in running,
in fighting, in emotion, in fever? In other words, does the brain
perform a definite role in the conversion of latent energy into
fever or into muscular action; or are the brain-cell changes caused
by the chemical products of metabolism? Happily, this crucial
question was definitely answered by the following experiment:
The circulations of two dogs were crossed in such a manner that the
circulation of the head of one dog was anastomosed with the circulation
of the body of another dog, and vice versa. A cord encircled the neck
of each so firmly that the anastomosing circulation was blocked
(Fig. 58). If the brain-cell changes were due to metabolic products,
then when the body of dog "A" was injured, the brain of dog "A"
would be normal and the brain of dog "B" would show changes.
Our experiments showed brain-cell changes in the brain of the dog
injured and no changes in the brain of the uninjured dog.
The injection of adrenalin causes striking brain-cell changes:
first, a hyperchromatism, then a chromatolysis. Now if adrenalin
caused these changes merely as a metabolic phenomenon and not as a
"work" phenomenon, then the injection of adrenalin into the carotid
artery of a crossed circulation dog would cause no change in its
circulation and its respiration, since the brain thus injected
is in exclusive vascular connection with the body of another dog.
In our experiment the blood-pressures of both dogs were recorded
on a drum when adrenalin was injected into the common carotid.
The adrenalin caused a rise in blood-pressure, an increase
in the force of cardiac contraction, increase in respiration,
and a characteristic adrenalin rise in the blood-pressure of both dogs.
The rise was seen first in the dog whose brain alone received adrenalin
and about a minute later in the dog whose body alone received adrenalin
(Fig. 59). Histologic examinations of the brains of both dogs
showed marked hyperchromatism in the brain receiving adrenalin,
while the brain receiving no adrenalin showed no change.
Here is a clear-cut observation on the action of adrenalin
on the brain, for both the functional and the histologic
tests showed that adrenalin causes increased brain action.
The significance of this affinity of the brain for adrenalin begins
to be seen when I call attention to the following striking facts:
1. Adrenalin alone causes hyperchromatism followed by chromatolysis,
and in overdosage causes the destruction of some brain-cells.
2. When both adrenal glands are excised and no other factor
is introduced, the Nissl substance progressively disappears from
the brain-cells until death. This far-reaching point will be taken
up later (Fig. 60).
Here our purpose is to discuss the cause of the brain-cell changes.
We have seen that in crossed brain and body circulation trauma
causes changes in the cells of the brain which is disconnected
from the traumatized body by its circulation, but which is
connected with the traumatized body by the nervous system.
We have seen that adrenalin causes activation of the body connected
with its brain by the nervous system, and histologic changes in
the brain acted on directly by the adrenalin, but we found no notable
brain-cell changes in the other brain through which the products
of metabolism have circulated.
In the foregoing we find direct evidence that the products of
metabolism are not the principal cause of the brain-cell changes.
We shall now present evidence to show that for the most part
the brain-cell changes are "work" changes. What work? We postulate
that it is the work by which the energy stored in the brain-cells is
converted into electricity or some other form of transmissible energy
which then activates certain glands and muscles, thus converting latent
energy into beat and motion. It has chanced that certain other studies
have given an analogous and convincing proof of this postulate.
In the electric fish a part of the muscular mechanism is replaced
by a specialized structure for storing and discharging electricity.
We found "work" changes in the brain-cells of electric fish
after all their electricity had been rapidly discharged
(Fig. 61). We found further that electric fish could not discharge
their electricity when under anesthesia, and clinically we
know that under deep morphin narcosis, and under anesthesia,
the production both of heat and of muscular action is hindered.
The action of morphin in lessening fever production is probably
the result of its depressing influence on the brain-cells, because
of which a diminished amount of their potential energy is converted
into electricity and a diminished electric discharge from the brain
to the muscles should diminish heat production proportionally.
We found by experiment that under deep morphinization brain-cell
changes due to toxins could be largely prevented (Fig. 62);
in human patients deep morphinization diminishes the production
of muscular action and of fever and conserves life when it is
threatened by acute infections. The contribution of the brain-cells
to the production of heat is either the result of the direct
conversion of their stored energy into heat, or of the conversion
of their latent energy into electricity or a similar force,
which in turn causes certain glands and muscles to convert latent
energy into heat.
A further support to the postulate that the brain-cells contribute
to the production of fever by sending impulses to the muscles
is found in the effect of muscular exertion, or of other forms of
motor stimulation, in the presence of a fever-producing infection.
Under such circumstances muscular exertion causes additional fever,
and causes also added but identical changes in the brain-cells. Thyroid
extract and iodin have the same effect as muscular exertion and infection
in the production of fever and the production of brain-cell changes.
All this evidence is a strong argument in favor of the theory that
certain constituents of the brain-cells are consumed in the work
performed by the brain in the production of fever.
That the stimulation of the brain-cells without gross activity
of the skeletal muscles and without infection can produce heat
is shown as follows:
(_a_) Fever is produced when animals are subjected to fear without
any consequent exertion of the skeletal muscles.
(_b_) The temperature of the anxious friends of patients will rise
while they await the outcome of an operation (Fig. 63).
(_c_) The temperature and pulse of patients will rise as a result
of the mere anticipation of a surgical operation (Fig. 64).
(_d_) There are innumerable clinical observations as to the effect
of emotional excitation on the temperature of patients.
A rise of a degree or more is a common result of a visit from
a tactless friend. There is a traditional Sunday increase
of temperature in hospital wards. Now the visitor does not bring
and administer more infection to the patient to cause this rise,
and the rise of temperature occurs even if the patient does
not make the least muscular exertion as a result of the visit.
I once observed an average increase of one and one-eighth degrees
of temperature in a ward of fifteen children as a result of a Fourth
of July celebration.
Is the contribution of the brain to the production of heat due
to the conversion of latent energy directly into heat, or does
the brain produce heat principally by converting its latent energy
into electricity or some similar form of transmissible energy which,
through nerve connections, stimulates other organs and tissues,
which in turn convert their stores of latent energy into heat?
According to Starling, when the connection between the brain
and the muscles of an animal is severed by curare, by anesthetics,
by the division of the cord and nerves, then the heat-producing power
of the animal so modified is on a level with that of cold-blooded animals.
With cold the temperature falls, with heat it rises. Such an animal
has no more control over the conversion of latent energy into heat
than it has over the conversion of latent energy into motion.
Electric stimulation done over a period of time causes brain-cell changes,
and electric stimulation of the muscles causes a rise in temperature.