In some animals this excess storage is greater than in other animals.

Those animals whose self-preservation is dependent on purely mechanical or chemical means of defense--such animals as crustaceans, porcupines, skunks or cobras--have a relatively small amount of convertible (adaptive) energy stored in their bodies.

On the contrary, the more an animal is dependent on its muscular activity for self-preservation, the more surplus available (adaptive) energy there is stored in its body. It may be true that all animals have approximately an equal amount per kilo of chemical energy-- but certainly they have not an equal amount stored in a form which is available for immediate conversion for adaptive ends.

Adaptive Variation in the Rate of Energy Discharge

What chance for survival would a skunk have without odor; a cobra without venom; a turtle without carapace; or a porcupine shorn of its barbs, in an environment of powerful and hostile carnivora?

And yet in such an hostile environment many unprotected animals survive by their muscular power of flight alone. It is evident that the provision for the storage of "adaptive" energy is not the only evolved characteristic which relates to the energy of the body.

The more the self-preservation of the animal depends on motor activity, the greater is the range of variation in the rate of discharge of energy.

The rate of energy discharge is especially high in animals evolved along the line of hunter and hunted, such as the carnivora and the herbivora of the great plains.

Influences That Cause Variation in the Rate of Output of Energy in the Individual

Not only is there a variation in the rate of output of energy among various species of animals, but one finds also variations in the rate of output of energy among individuals of the same species.

If our thesis that men and animals are mechanisms responding to environmental stimuli be correct, and further, if the speed of energy output be due to changes in the activating organs as a result of adaptive stimulation, then we should expect to find physical changes in the activating glands during the cycles of increased activation.

What are the facts? We know that most animals have breeding seasons evolved as adaptations to the food supply and weather.

Hence there is in most animals a mating season in advance of the season of maximum food supply so that the young may appear at the period when food is most abundant. In the springtime most birds and mammals mate, and in the springtime at least one of the great activating glands is enlarged--the thyroid in man and in animals shows seasonal enlargement. The effect of the increased activity is seen in the song, the courting, the fighting, in the quickened pulse, and in a slightly raised temperature. Even more activation than that connected with the season is seen in the physical state of mating, when the thyroid is known to enlarge materially, though this increased activity, as we shall show later, is probably no greater than the increased activity of other activating glands.

In the mating season the kinetic activity is speeded up; in short, there exists a state--a fleeting state--of mild Graves' disease.

In the early stages of Graves' disease, before the destructive phenomena are felt, the kinetic speed is high, and life is on a sensuous edge.

Not only is there a seasonal rhythm to the rate of flow of energy, but there is a diurnal variation--the ebb is at night, and the full tide in the daytime. This observation is verified by the experiments which show that certain organs in the kinetic chain are histologically exhausted, the depleted cells being for the most part restored by sleep.

We have seen that there are variations in speed in different species, and that in the same species speed varies with the season of the year and with the time of day. In addition there are variations also in the rate of discharge of energy in the various cycles of the life of the individual. The young are evolved at high speed for growth, so that as soon as possible they may attain to their own power of self-defense; they must adapt themselves to innumerable bacteria, to food, and to all the elements in their external environment.

Against their gross enemies the young are measurably protected by their parents; but the parents--except to a limited extent in the case of man--are unable to a.s.sist in the protection of the young against infectious disease.

The cycle of greatest kinetic energy for physiologic ends is the period of reproduction. In the female especially there is a cycle of increased activity just prior to her development into the procreative state.

During this time secondary s.e.xual characters are developed-- the pelvis expands, the ovaries and the uterus grow rapidly, the mammary glands develop. Again in this period of increasing speed in the expenditure of energy we find the thyroid, the adrenals, and the hypophysis also in rapid growth.

Without the normal development of the ovary, the thyroid, and the hypophysis, neither the male nor the female can develop the secondary s.e.xual characters, nor do they develop s.e.xual desire nor show seasonal cycles of activity, nor can they procreate.

The secondary s.e.xual characters--s.e.xual desire, fertility--may be developed at will, for example, by feeding thyroid products from alien species to the individual deprived of the thyroid.

At the close of the child-bearing period there is a permanent diminution of the speed of energy discharge, for energy is no longer needed as it was for the self-preservation of the offspring before adolescence, and for the propagation of the species during the procreative period. Unless other factors intervene, this reduction in speed is progressive until senescent death.

The diminished size of the thyroid of the aged bears testimony to the part the activating organs bear in the general decline.

We have now referred to variations in the rate of discharge of energy in different species; in individuals of the same species; in cycles in the same individual--such as the seasons of food supply, the periods of wakefulness and of sleep, the procreative period, and we have spoken of those variations caused artificially by thyroid feeding, thus far having confined our discussion to the conversion for adaptive purposes of latent into kinetic energy in muscular and in procreative action. We shall now consider the conversion of latent into kinetic energy in the production of heat,[*] and endeavor to answer the questions which arise at once: Is there one mechanism for the conversion of latent energy into heat and another mechanism for its conversion into muscular action?

What is the adaptive advantage of fever in infection?

[*] We use the terms "heat" and "muscular action" in the popular sense, though physicists use them to designate one and the same kind of energy.

The Purpose and the Mechanism of Heat Production in Infections

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, teta.n.u.s, 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 princ.i.p.al 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 a.n.a.logous 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 circ.u.mstances 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 const.i.tuents 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 antic.i.p.ation 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 princ.i.p.ally 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.