Origin and Nature of Emotions
by George W. Crile
Hypertext Meanings and Commentaries
from the Encyclopedia of the Self
by Mark Zimmerman

THE ORIGIN AND NATURE

Still further negative evidence that inhalation anesthesia offers
little or no protection to the brain-cells against trauma is derived
from the following experiment: A dog whose spinal cord had been
divided at the level of the first dorsal segment, and which had
then been kept in good condition for two months, showed a recovery
of the spinal reflexes, such as the scratch reflex, etc. Such an
animal is known as a "spinal dog."  Now, in this animal, the abdomen
and hind extremities had no direct nerve connection with the brain.
In this dog, continuous severe trauma of the abdominal viscera and of
the hind extremities lasting for four hours was accompanied
by but slight change in either the circulation or in the respiration,
and by no microscopic alteration of the brain-cells (Fig. 1). Judging
from a large number of experiments on NORMAL dogs under ether,
such an amount of trauma would have caused not only complete
physiologic exhaustion of the brain, but also morphologic alterations
of all of the brain-cells and the physical destruction of many
(Fig. 2). We must, therefore, conclude that, although ether anesthesia
produces unconsciousness, it APPARENTLY PROTECTS NONE OF THE BRAIN-CELLS against exhaustion from the trauma of surgical operations; ether is,
so to speak, but a veneer. Under nitrous oxid anesthesia there is
approximately only one-fourth as much exhaustion as is produced by equal
trauma under ether (Fig. 3). We must conclude, therefore, either that
nitrous oxid protects the brain-cells against trauma or that ether
predisposes the brain-cells to exhaustion as a result of trauma.
With these premises let us now inquire into the cause of this
exhaustion of the brain-cells.

The Cause of the Exhaustion of the Brain-cells as a Result of Trauma
of Various Parts of the Body under Inhalation Anesthesia Numerous experiments on animals to determine the effect of ether anesthesia _per se_, _i. e_., ether anesthesia without trauma, showed that, although certain changes were produced, these included
neither the physiologic exhaustion nor the alterations in the
brain-cells which are characteristic of the effects of trauma.
On turning to the study of trauma, we at once found in the behavior
of individuals as a whole under deep and under light anesthesia
the clue to the cause of the discharge of energy, of the consequent
physiologic exhaustion, and of the morphologic changes in the brain-cells.

PAIN, LAUGHTER, AND CRYING[*]

[*] Address delivered before the John Ashhurst, Jr.. Surgical Society
of the University of Pennsylvania, May 3, 1912.

PAIN

Pain, like other phenomena, was probably evolved for a particular purpose--
surely for the good of the individual; like fear and worry,
it frequently is injurious. What then may be its purpose?

We postulate that pain is one of the phenomena which result
from a stimulation to motor action. When a barefoot boy steps
on a sharp stone it is important that the injuring contact be
released as quickly as possible; and therefore physical injury pain
results and impels the required action. Anemia of the soft parts
at the points of pressure results from prolonged sitting or lying
in one position, and as a result pain compels a muscular action
that shifts the damaging pressure--this is the pain of anemia;
when the rays of the blazing sun shine directly upon the retina,
pain immediately causes a protective muscular action--the lid is closed,
the head turns away--this is light pain; when standing too close
to a blazing fire the excessive heat causes a pain which results
in the protective muscular action of moving away--this is heat pain;
when the urinary bladder is acutely overdistended the resultant
pain induces voluntary as well as involuntary muscular contraction--
this is evacuation pain; associated with defecation is a characteristic
warning pain, and an active pain which induces the required
muscular action--this, like the pain accompanying micturition,
is an evacuation pain; in obstruction of the urinary passages
and of the large and the small intestine the pain is exaggerated,
as is the accompanying muscular contraction--this is a pathologic
evacuation pain; when the fetus reaches full term and labor is
to begin, it is heralded by pain which is associated with rhythmic
contractions of the uterine muscle; later, many other muscles
take part in the birth and pain is associated with all these
muscular contractions--these are labor pains; when a foreign body,
be it ever so small, falls upon the conjunctiva or cornea there
results what is perhaps the acutest pain known, and quick and active
muscular action follows--this is special contact pain. Special pain
receptors are placed in certain parts of the nose, the pharynx,
and the larynx, the stimulation of which causes special motor acts,
such as sneezing, hawking, coughing. Curiously vague pains are
associated with the protective motor act of vomiting and with the sexual
motor acts--these may be termed nausea pains and pleasure pains.
We now see, therefore, that against the injurious physical contacts
of environment, against heat and cold, against damaging sunlight,
against local anemia when resting or sleeping, the body is protected
by virtue of the muscular action which results from pain.
Then, too, for the emptying of the pregnant uterus, for the evacuation
of the intestine and of the urinary bladder as normal acts,
and for the overcoming of obstructions in these tracts,
pain compels the required muscular actions, For passing gall-stones
and urinary calculi, urgent motor stimuli are awakened by pain.
For each of these diversified pains the consequent muscular action
is specific in type, distribution, and intensity. This statement
is so commonplace that we are apt to miss the significance and
the wonder of it. It is probable that every nerve-ending in the skin
and every type of stimulation represents a separate motor pattern,
the adequate stimulation of which causes always the same response.

Let us pass on to the discussion of another and perhaps even
more interesting type of pain, that associated with infection.
Not all kinds of infection are painful; and in those infections
that may be associated with pain there is pain only when certain
regions of the body are involved. Among the infections that are not
associated with pain are scarlet fever, typhoid fever, measles, malaria,
whooping-cough, typhus fever, and syphilis in its early stages.
The infections that are usually, though not always, associated with
pain are the pyogenic infections. The pyogenic infections
and the exanthemata constitute the great majority of infections
and are the basis of the discussion which follows.

I will state one of my principal conclusions first, _i.
e_., that the only types of infection that are associated with pain
are those in which the infection may be spread by muscular action
or those in which the fixation of parts by continued muscular
rigidity is an advantage; and, further, as a striking corollary,
that the type of infection that may cause muscular action when it
attacks one region of the body may cause no such action when it
attacks another region.

The primary, and perhaps the most striking, difference between
the painless exanthemata and the painful pyogenic infections is that
in the case of the exanthemata the protective response of the body
is a chemical one,--the formation of antibodies in the blood,
which usually produce permanent immunity,--while the response to the
pyogenic infections is largely phagocytic. In the pyogenic infections,
in order to protect the remainder of the body, which, of course,
enjoys no immunity, every possible barrier against the spread
of the infection is thrown about the local point of infection.
How are these barriers formed? First, lymph is poured out, then the part
is fixed by the continuous contraction of the neighboring muscles
and by the inhibition of those muscles that, in the course of their
ordinary function, would by their contractions spread the infection.
Wherever there is protective muscular rigidity there is also pain.
On the other hand, in pyogenic infections in the substance
of the liver, in the substance of the kidney, within the brain,
in the retroperitoneal space, in the lobes of the lung, in the chambers
of the heart and in the blood-vessels of the chest and the abdomen,
in all locations in which muscular contractions can in no way assist
in localizing the disease, pyogenic infections produce no muscular
rigidity and no pain. Apparently, therefore, only those infections are
painful which are associated with a protective muscular contraction.
This explains why tuberculosis of the hip is painful, while tuberculosis
of the lung is painless.

There is a third type of pain which modifies muscular action
in a curious way. We have already stated that local pain serves
an adaptive purpose. In this light let us now consider headache.
Headache is one of the commonest initiatory symptoms of the
various infections, especially of those infections which are
accompanied by no local pain and by no local muscular action.
In peritonitis, cholecystitis, pleurisy, arthritis, appendicitis,
salpingitis, child-birth, in obstructions of the intestinal
and the genito-urinary tract, in short, in those acute processes
in which the local symptoms are powerful enough to govern
the individual as a whole,--to make him lie down and keep quiet,
refuse food and possibly reject what is already in the stomach,--
in all these conditions there is rarely a headache, but in the diseases
in which local pain is absent, such as the exanthemata, typhoid fever,
and auto-intoxication, which have no dominating local disturbances
to act as policemen to put the individual to bed and to make him
refuse food that he may be in the most favorable position to combat
the oncoming disease, in such cases in which these masterful and
beneficent local influences are absent we postulate that headache
has been evolved to perform this important service.

On the hypothesis that it is good for the individual who is acutely
stricken by a disease or who is poisoned by autointoxication to rest
and fast, and that the muscular system obeys the imperial command
of pain, and in view of the fact that the brain is not only in constant
touch with the conditions of every part of the body but that it
is also the controlling organ of the body, one would expect that in
these diseases the major pain whose purpose it is to govern general
muscular action would be located in the head and there we find it.
How curious and yet how intelligible is the fact that, though a
headache may be induced by even a slight auto-intoxication,
an abscess may exist within the brain without causing pain.
When an obliterative endarteritis is threatening a leg with
anemic gangrene, or when one lies too long in the same position on
a hard bed, there is threatening injury from local anemia, and as a
result there is acute pain, but when the obliterative endarteritis
threatens anemia of the brain, or when an embolism or thrombosis has
produced anemia of the brain, there may be no accompanying pain.
The probable explanation of the pain which results in the first instance
and the lack of pain in the second is that in the former muscular action
constitutes a self-protective response, but in the other it does not.
Diseases and injuries of the brain are notoriously difficult
to diagnosticate. This may well be because it has always been so well
protected by the skull that there have been evolved within it few
tell-tale self-protective responses, so that in the presence of injury
and disease within itself the brain remains remarkably silent.
It should occasion no surprise that there are in the brain no receptors,
the mechanical stimulation of which can cause pain, because its bony
covering has always prevented the adaptive implantation within it
of contact pain receptors. Dr. Frazier tells me that in the course
of his operations on the brains of unanesthetized patients
he is able to explore the entire brain freely and without pain.
From my own experience I am able to confirm Dr. Frazier's observation.
In addition, the two-stage operation for the excision of the Gasserian
ganglion provides an observation of extraordinary interest.
If at the first seance the ganglion is exposed, but is not disturbed
except by the iodoform gauze packing, then on the following
day the gauze may be removed, the ganglion picked up, and its
branches and root excised without anesthesia and without pain.
The same statement and explanation may be made regarding the distribution
of pain receptors for physical contact within the parenchyma of the liver,
the gall-bladder, the abdominal viscera, the spleen, the heart,
the lungs, the retroperitoneal tissue, the deep tissue of the back,
the vertebrae, and in certain portions of the spinal cord.
Just what is the distribution of the receptors for heat and for cold
I am unable to state, but this much we do know, that without
anesthesia the intestines may be cauterized freely without the least
pain resulting, and in animals the cauterization of the brain causes
no demonstrable change in the circulatory or respiratory reactions.
It is probable therefore that the distribution of the pain receptors
for physical contact and for heat are limited to those parts of the body
that have been exposed to injurious contacts with environment.

Of special significance is the pain which is due to cold,
which increases muscular tone and produces shivering. The general
increase in muscular tone produces an interesting postural phenomenon:
the limbs are flexed and the body bent forward, a position which probably
is due to the fact that the flexors are stronger than the extensors.
As muscular action is always accompanied by heat production,
the purpose of the muscular contraction and the shivering
is quite certainly caused by cold to assist in the maintenance
of the normal body temperature.

We have now discussed many of the causes of pain and in each instance
we have found an associated muscular action which apparently
serves some adaptive purpose (Figs. 24 and 25). If we assume
that pain exists for the purpose of stimulating muscular reactions,
we may well inquire what part of the nervous are is the site of
the sensation of pain--the nerve-endings, the trunk, or the brain?
Does pain result from physical contact with the nerve-endings, with
the physical act of transmitting an impression along the nerve trunk,
or with the process within the brain-cells by which energy is released
to cause a motor act?

It seems most probable that the site of the pain is in the brain-cells.
If this be so, then what is the physical process by which the
phenomena of pain are produced? The one hypothesis that can be
tested experimentally is that pain is a phenomenon resulting from
the rapid discharge of energy in the brain-cells. If this be true,
then if every pain receptor of the body were equally stimulated
in such a manner that

{illust. caption = FIG. 25.--FEAR AND AGONY. "Amid this dread
exuberance of woe ran naked spirits wing'd with horrid fear."--
Dante's "Inferno," Canto XXIV, lines 89, 90. all the stimuli
reached the brain-cells simultaneously, the cells would find
themselves in equilibrium and no motor act would be performed.
But if all the pain receptors of the body but one were equally stimulated,
and this one stimu-lated harder than the rest, then the latter
would gain possession of the final common path, the sensation
of pain would be felt, and a muscular contraction would result.
It is well known that when a greater pain is thrown into
competition with a lesser one, the lesser is completely submerged.
In this manner the school-boy initiates the novice into the mystery
of the painless plucking of hair. The simultaneous, but severe
application of the boot to the blindfolded victim takes complete
and exclusive possession of the final common path and the hair
is painlessly plucked through the triumph of the boot stimulus over
the hair stimulus in the struggle for the possession of the final
common path. Another argument in favor of this hypothesis that
pain is an accompaniment of the release of energy in the brain-
cells is found in the fact that painless stimuli received through
the special senses may completely submerge the painful stimuli
of physical injury; for although the stimuli to motor action,
which are received through the senses of sight, hearing, and smell,
cause even more powerful motor action than those caused by
physical contact stimuli, yet they are not accompanied by pain.
Examples of this triumph of stimulation of the special senses over
contact stimulation are frequently seen in persons obsessed by anger
or fear, and to a less degree in those obsessed by sexual emotion.
In the fury of battle the soldier may not perceive his wound until
the emotional excitation is wearing away, when the sensation
of warm blood on the skin may first attract his attention.
Religious fanatics are said to feel no pain when they subject themselves
to self-injury. Now, since both psychic and mechanical stimuli cause motor
action by the excitation ofprecisely the same mechanism in the brain,
and since the more rapid release of energy from psychic stimuli
submerges the physical stimuli and prevents pain, it would seem
that pain must be a phenomenon which is associated with the process
of releasing energy by the brain-cells. Were physical injury inflicted
in a quiescent state equal to that inflicted in the emotional state,
great pain and intense muscular action would be experienced.
Now the emotions are as purely motor excitants as is pain.
The dynamic result is the same the principal difference being the greater
suddenness and the absolute specificity of the pain stimuli as compared
with the more complex and less peremptory stimuli of the emotions.
A further evidence that pain is a product of the release of brain-cell
energy is the probability that if one could pierce the skin at
many points on a limb in such a manner that antagonistic points
only were equally and simultaneously stimulated, then an equilibrium
in the governing brain- cells would be established and neither
pain nor motion would follow. An absolute test of this assumption
cannot be made but it is supported by the obtainable evidence.
We will now turn to a new viewpoint, a practical as well as a
fascinating one, which can best be illustrated by two case histories:
A man, seventy-eight years old, whose chief complaint was obstinate
constipation, was admitted to the medical ward of the Lakeside Hospital
several years ago. The abdomen was but slightly distended;
there was no fever, no increased leukocytosis, no muscular rigidity,
and but slight general tenderness. He claimed to have lost in weight
and strength during the several months previous to his admission.
A tentative diagnosis of malignant tumor of the large intestine was made,
but free movements weresecured rather easily, and we abandoned
the idea of an exploratory operation. The patient gradually failed
and died without a definite diagnosis having been made by either
the medical or the surgical service. At autopsy there was found
a wide-spread peritonitis arising from a perforated appendix.
A child, several years old, was taken ill with some indefinite disease.
A number of the ablest medical and surgical consultants of a leading
medical center thoroughly and repeatedly investigated the case.
Although they could make no definite diagnosis they all
agreed that the trouble surely could not be appendicitis
because there was neither muscular rigidity nor tenderness.
The autopsy showed a gangrenous appendix and general peritonitis.
How can these apparently anomalous cases be explained?
These two cases are illustrations of the same principle that underlies
the freedom from pain which results from the use of narcotics
and anesthetics, the same principle that explains the fact that
cholecystitis may occur in the aged without any other local symptoms
than the presence of a mass and perhaps very slight tenderness;
and that accounts in general for the lack of well-expressed disease
phenomena in senility and in infancy. The reason why the aged,
the very young, and the subjects of general paresis show but few
symptoms of disease is that in senility the brain is deteriorated,
while in infancy the brain is so undeveloped that the mechanism
of association is inactive, hence pain and tenderness,
which are among the oldest of the associations, are wanting.
Senility and infancy are by nature normally narcotized.
The senile are passing through the twilight into the night;
while infants are traversing through the dawn into the day.
Hence it is that the diagnosis of injury and disease in the extremes
oflife is beset by especial difficulties, since the entire body
is as silent as are the brain, the pericardium, the mediastinum,
and other symptomless areas. For the same reason, when a patient
who is seriously ill with a painful disease turns upon the physician
a glowing eye and an eager face, and remarks how comfortable he feels,
then the end is near. This is a brilliant and fateful clinical mirage.
When one reflects on the vast amount of evidence as to the origin
and the purpose of pain, he is forced to conclude that pain is
a phenomenon of motor stimulation, and that its principal role is
the protection of the individual against the gross and the microscopic
enemies in his environment. The benefits of pain are especially
manifested in the urgent muscular actions by means of which the body
moves away from physical injury; obstructions of the hollow
viscera are overcome; rest is compelled in the acute infections--
the infected points are held rigidly quiet, the muscles of the abdomen
are fixed, and harmful peristalsis is arrested in peritonitis;
while there is absolutely no pain in the diseases or injuries
which affect those regions of the body in which in the course
of evolution no pain receptors were placed, or in those diseases
in which muscular inhibition or contraction is of no help.
In a biologic sense pain is closely associated with the emotional stimuli,
for both pain and the emotions incite motor activity for the good
of the individual. The frequent occurrence of post-operative and
post- traumatic pain is accounted for by the fact that the operation
or the injury has lowered the threshold of the brain- cells to trauma;
the brain and not the local sensitive field is the site of the pain.
I have found that, by blockingthe field of operation with
local anesthesia, post-operative pain is diminished; that is,
since the local anesthesia prevents the strong stimuli of the
trauma from reaching the brain, its threshold is not lowered.
There is a close resemblance between the phenomena of pain habit,
of education, of physical training, of love and of hate. In education,
in pain habit, in all emotional relations, a low brain- cell threshold
is established which facilitates the reception of specific stimuli;
all these processes are motor acts, or are symbolic of motor acts,
and we may be trained to perceive misfortune and pain as readily as we
are trained to perceive mathematical formulae or moral precepts.
In each and every case, readiness of perception depends, as it seems to me,
upon a modified state of the brain-cells, their threshold especially,
the final degree of perception possible in any individual being perhaps
based on the type of potential molecules of which the brain is built.
We must believe also that every impression is permanent, as only thus
could an individual animal or a man be fitted by his own experience
for life's battles. LAUGHTER AND CRYING What is laughter?
What is its probable origin, its distribution, and its purpose?
Laughter is an involuntary rhythmic contraction of certain
respiratory muscles, usually accompanied by certain vocal sounds.
It is a motor act of the respiratory apparatus primarily, although if
intense it may involve not only the extraordinary muscles of respiration,
but most of the muscles of the body. There are many degrees
of laughter, from the mere brightening of the eyes, a fleeting smile,
tittering andgiggling, to hysteric and convulsive laughter.
Under certain circumstances, laughter may be so intense and
so long continued that it leads to considerable exhaustion.
The formation of tears is sometimes associated with laughter.
When integrated with laughter, the nervous system can perform
no other function. Crying is closely associated with laughter,
and in children especially laughter and crying are readily interchanged.
We postulate that laughter and weeping serve a useful purpose.
According to Darwin, only man and monkeys laugh (Fig. 26);
other animals exhibit certain types of facial expression accompanying
various emotions, but laughter in the sense in which that word
is commonly used is probably an attribute of the primates only,
although it is probable that many animals find substitutes for laughter.
The proneness of man to laughter is modified by age, sex, training,
mental state, health, and by many other factors. Healthy, happy children
are especially prone to laughter, while disease, strong emotions,
fatigue, and age diminish laughter. Women laugh more than do men.
The healthy, happy maturing young woman perhaps laughs most, especially
when she is slightly embarrassed. What causes laughter? Good news,
high spirits, tickling, hearing and seeing others laugh; droll stories;
flashes of wit; passages of humor; averted injury; threatened breach
of the conventions; and numerous other causes might be added.
It is obvious that laughter may be produced by diverse influences,
many of which are so unlike each other that it would at first sight
seem improbable that a single general principle underlies all.
Before presenting a hypothesis which harmonizes most of the facts,
and which mayoffer an explanation of the origin and purpose of laughter,
let us return for a moment to some previous considerations--
that man is essentially a motor being; that all his responses to
the physical forces of his environment are motor; {illust. caption
= FIG. 26.--LAUGHING CHIMPANZEE. "Mike," the clever chimpanzee
in the London Zoo, evidently enjoys a joke as well as any one else.
(Photo by Underwood and Underwood, N. Y.)}

that thoughts and words even are symbolic of motor acts;
that in the emotions of fear, of anger, and of sexual love
the whole body is integrated for acts which are not performed.
These integrations stimulate the brain-cells, the ductless glands,
and other parts, and the energizing secretions, among which are epinephrin,
thyroid and hypophyseal secretions, are thrown into the blood-stream,
while that most available fuel, glycogen, is also mobilized in the blood.
This body-wide preparation for action may be designated kinetic reaction.
The fact that emotion is more injurious to the body than is
muscular action is well known, the difference being probably caused
by the fact that when there is action the above-mentioned products
of stimulation are consumed, while in stimulation without action
they are not consumed and must be eliminated as waste products.
Now these activating substances and the fuel glycogen may be consumed
by any muscular action as well as by the particular muscular action
for which the integration and consequent stimulation were made;
that is, if one were provoked to such anger that he felt impelled
to attack the object of his anger, one of three things might happen:
First, he might perform no physical act but give expression to
the emotion of anger; second, he might engage in a physical struggle
and completely satisfy his anger; third, he might immediately engage
in violent gymnastic exercises and thus consume all the motor-producing
elements mobilized by the anger and thus clarify his body.

In these premises we find our explanation of the origin and purpose
of laughter and crying, for since they consist almost wholly
of muscular exertion, they serve precisely such clarifying purposes
as would be served by the gymnastic exercises of an angry man.
As it seems to me, the muscular action of laughter clears the system
of the energizing substances which have been mobilized in various
parts of the body for the performance of other actions (Figs. 27
to 29). If this be true, the first question that presents itself is,
Why is the respiratory system utilized for such a clarifying purpose?
Why do we not laugh with our feet and hands as well?
Were laughter expressed with the hands, the monkey might fall
from the tree and, if by the feet, man might fall to the ground.
He would at least be ataxic. In fact, laughter has the great
advantage of utilizing a group of powerful muscles which can be
readily spared without seriously interfering with the maintenance
of posture. Laughter, however, is only one form of muscular action
which may consume the fuel thrown into the blood by excitation.
That these products of excitation are often consumed by other motor
acts than laughter is frequently seen in public meetings when
the stamping of feet and the clapping of hands in applause gives
relief to the excitation (Fig. 30). Why the noise of laughter?
In order that the products of excitation may be quickly and
completely consumed, the powerful group of expiratory muscles must
have some resistance against which they can exert themselves strongly
and at the same time provide for adequate respiratory exchange.
The intermittent closure of the epiglottis serves this purpose admirably,
just as the horizontal bars afford the resistance against which muscles
may be exercised. The facial muscles are not in use for other purposes,
hence their contractions will consume a little of the fuel.
An audience excited by the words of an impassioned speaker undergoes
a body-wide stimulation for action, all of which may be eliminated
by laughter or by applause (Fig. 31).

Let us test this hypothesis by some practical examples.
The first is an incident that accidentally occurred in our laboratory
during experiments on fear which were performed as follows:
A keen, snappy fox terrier was completely muzzled by winding a broad strip
of adhesive plaster around his jaw so as to include all but the nostrils.
When this aggressive little terrier and the rabbit found themselves
in close quarters each animal became completely governed by instinct;
the rabbit crouched in fear, while the terrier, with all the ancestral
assurance of seizing his prey, rushed, upon the rabbit, his muzzle
always glancing off and his attack ending in awkward failure.

This experiment was repeated many times and each time provoked
the serious-minded scientific visitors who witnessed it
to laughter. Why? Because the spectacle of a savage little terrier
rushing upon an innocent rabbit as if to mangle it integrated
the body of the onlooker with a strong desire to exert muscular
action to prevent the cruelty. This integration caused a conversion
of the potential energy in the brain-cells into kinetic energy,
and there resulted a discharge into the blood-stream of activating
internal secretions for the purpose of producing muscular action.
Instantly and unexpectedly the danger passed and the preparation
for muscular action intended for use in the protection of the rabbit
was not needed. This fuel was consumed by the neutral muscular
action of laughter, which thus afforded relief.

A common example of the same nature is that encountered on the street
when a pedestrian slips on a banana peel and, just as he is
about to tumble, recovers his equilibrium. The onlookers secure
relief from the integration to run to his rescue by laughing.
On the other hand, should the same pedestrian fall and fracture
his skull the motor integration of the onlookers would be consumed
by rendering physical assistance--hence there would be no laughter.
In children almost any unexpected phenomenon, such as a sudden "booing"
from behind a door, is attended by laughter, and in like manner
the kinetic reaction produced by the innumerable threats of danger
which are suddenly averted, a breach of the conventions, a sudden
relief from acute nervous tension; a surprise--indeed, any excitant
to which there is no predetermined method of giving a physical response--
may be neutralized by the excitation of the mechanism of laughter.

In the same way the laughter excited by jokes may be explained.
An analysis of a joke shows that it is composed of two parts--
the first, in which is presented a subject that acts as a stimulus
to action, and the second, in which the story turns suddenly
so that the stimulus to action is unexpectedly withdrawn.
The subject matter of the joke affects each hearer according
to the type of stimuli that commonly excites that individual.
Hence it is that a joke may convulse one person while it bores another,
and so there are jokes of the classes, bankers' jokes, politicians' jokes,
the jokes of professional men, of the plebeian, of the artist, etc.
If the joke fails, the integration products of the excitation may
be used in physical resentment (Fig. 32).

Another type of laughter is that associated with the ticklish points
of certain parts of the body, the soles of the feet and certain
parts of the trunk and of the abdomen. The excitation of the
ticklish receptors, like pain, compels self-defensive motor acts.
This response is of phylogenetic origin, and may be awakened only
by stimuli which are too light to be painful. In this connection
it is of interest to note that a superficial, insect-like contact
with the skin rarely provokes laughter, and that the tickling
of the nasal, oral, and pulmonary tracts does not produce laughter.
The ticklish points that cause laughter are rather deeply placed,
and a certain type of physical contact is required to constitute
an adequate stimulus. That is, the contact must arouse a phylogenetic
association with a physical struggle or with physical exertion.
In the foot, the adequate stimuli for laughter are such contacts
as resemble or suggest piercing by stones or rough objects.. The
intention of the one who tickles must be known; if his intention
be playful, laughter results, whereas if injury be intended,
then an effort toward escape or defense is excited, but no laughter.
If deep tickling of the ribs is known to be malicious, it will excite
physical resentment and not laughter. Self-tickling rarely causes
laughter for the reason that auto-tickling can cause only a known
degree of stimulation, so that there results no excessive integration
which requires relief by the neutral muscular activity of laughter.
In fact, one never sees purposeful acts and laughter associated.
According to its severity, an isolated stimulus causes either
an action or laughter. The ticklish points in our bodies were
probably developed as a means of defense against serious attacks
and of escape from injurious contacts.

Anger, fear, and grief are also strong excitants and, therefore,
are stimuli to motor activity. It is obvious that whatever the excitant
the physico-chemical action of the brain and the ductless glands
cannot be reversed--the effect of the stimulus cannot be recalled,
therefore either a purposeful muscular act or a neutralizing act
must be performed or else the liberated energy must smoulder
in the various parts of the body.

It is on this hypothesis that the origin and the purpose of laughter
and crying may be understood. Even a superficial analysis of the
phenomena of both laughter and crying show them to be without any
external motor purpose; the respiratory mechanism is intermittently
stimulated and inhibited; and the shoulder and arm muscles, indeed,
many muscles of the trunk and the extremities are, as far as any
external design is concerned, purposelessly contracted and released
until the kinetic energy mobilized by excitation is utilized.
During this time the facial expression gives the index to
the mental state.

Crying, like laughter, is always preceded by a stimulation
to some motor action which may or may not be performed
(Figs. 33 and 34). If a mother is anxiously watching the course
of a serious illness of her child and if, in caring for it, she is
stimulated to the utmost to perform motor acts, she will continue
in a state of motor tenseness until the child recovers or dies.
If relief is sudden, as in the crisis of pneumonia, and the mother
is not exhausted, she will easily laugh if tired, she may cry.
If death occurs, the stimulus to motor acts is suddenly
withdrawn and she then cries aloud, and performs many motor
acts as a result of the intense stimulation to motor activity
which is no longer needed in the physical care of her child.
With this clue we can find the explanation of many phenomena. We can
understand why laughter and crying are so frequently interchangeable;
why they often blend and why either gives a sense of relief;
we can understand why either laughter or crying can come only
when the issue that causes the integration is determined; we can
understand the extraordinary tendency to laughter that discloses
the unspoken sentiments of love; we can understand the tears
of the woman when she receives a proposal of marriage from the man
she loves; we can understand why any averted circumstance,
such as a threatened breach of the conventions, which would have led
to embarrassment or humiliation, leads to a tendency to laughter;
and why the recital of heroic deeds by association leads to tears,
On the other hand, under the domination of acute diseases,
of acute fear, or of great exhaustion, there is usually neither
laughter nor crying because the nervous system is under the control
of a dominating influence as a result of which the body is so
exhausted that the excess of energy which alone can produce laughing
or crying is lacking.

A remarkable study of the modification of laughter and crying by disease
is found in that most interesting of diseases--exophthalmic goiter.
In this disease there is a low threshold to all stimuli.
That the very motor mechanism of which we have been speaking
is involved, is shown by an enormous increase in its activity.
There is also an increase in the size of certain at least of the
activating glands--the thyroid and the adrenals are enlarged and overactive
and the glycogen-producing function of the liver is stimulated.
The most striking phenomenon of this disease, however, is the remarkable
lowering of the brain thresholds to stimuli. In other words,
in Graves' disease the nervous system and the activating glands--
the entire motor mechanism--are in an exalted state of activity.

If this be true, then these patients should exhibit behavior
precisely contrary to that of those suffering from acute infection,
that is, they should be constantly clearing their systems of
these superabundant energizing materials by crying or laughing,
and this is precisely what happens--the flood-gates of tears are open
much of the time in Graves' disease--a disease of the emotions.

We have already interpreted pain as a phenomenon of motor activity.
When pain does not lead to muscular activity it therefore frequently
leads to crying or to moaning, just as tickling, which is equally
an incentive to motor activity, results in laughter if it does
not find full expression in action.

From the foregoing we infer that pain, the intense motor response
to tickling, and emotional excitation are all primitive biologic
reactions for the good of the individual, and that all have
their origin in the operation of the great laws of evolution.
If to this inference we add the physiologic dictum that the nervous
system always acts as a whole, and that it can respond to but one
stimulus at a time, we can easily understand that while diverse
causes may integrate the nervous system for a specific action,
if the cause be suddenly removed, then the result of the
integration of the nervous system may be, not a specific action,
but an undesigned muscular action, such as crying or laughter.
Hence it is that laughter and crying may be evoked by diverse
exciting causes. The intensity of the laughter or of the crying
depends upon the intensity of the stimulus and the dynamic state
of the individual.

The linking together of these apparently widely separated phenomena
by the simple law of the discharge of energy by association perhaps
explains the association of an abnormal tendency to tears with an
abnormally low threshold for pain (Fig. 36). In the neurasthenic,
tears and pain are produced with abnormal facility. Hence it is that,
if a patient about to undergo a surgical operation is in a state of fear
and dread before the operation, the threshold to all stimuli is lowered,
and this lowered threshold will continue throughout the operation,
even under inhalation anesthesia, because the stimulus produced by
cutting sensitive tissue is transmitted to the brain just as readily
as if the patient were not anesthetized. In like manner, the brain
may be sensitized by the administration of large doses of thyroid
extract prior to operation, the threshold to injury in such a case
continuing to be low to traumatic stimuli even under anesthesia.
Under the sensitizing influences of thyroid extract or of Graves'
disease the effect of an injury, of an operation, or of emotional
excitation is heightened. The extent to which the threshold to pain
or to any other excitant is affected by Graves' disease is illustrated
by the almost fatal reaction which I once saw result from the mere
pricking with a hypodermic needle of a patient with this disease.
As the result of a visit from a friend, the pulse-rate of a victim of this
disease may increase twenty beats and his temperature rise markedly.
I have seen the mere suggestion of an operation produce collapse.
As the brain is thus remarkably sensitized in Graves' disease, we find
that in these patients laughter, crying, emotional disturbances,
and surgical shock are produced with remarkable facility.

I hope that even this admittedly crude and imperfect consideration
of this subject will suggest the possibility of establishing
a practical viewpoint as to the origin and purpose of pain,
of tickling, and of such expressions of emotion as laughter and crying,
and that it may help us to understand their significance in health
and in disease.

THE RELATION BETWEEN THE PHYSICAL STATE OF THE BRAIN-CELLS AND
BRAIN FUNCTIONS--EXPERIMENTAL AND CLINICAL[*]

[*] Address before The American Philosophical Society, April 18, 1913.

The brain in all animals (including man) is but the clearing-house
for reactions to environment, for animals are essentially motor
or neuromotor mechanisms, composed of many parts, it is true,
but integrated by the nervous system. Throughout the phylogenetic history
of the race the stimuli of environment have driven this mechanism,
whose seat of power--the battery--is the brain.

Since all normal life depends upon the response of the brain
to the daily stimuli, we should expect in health, as well
as in disease, to find modifications of the functions and the
physical state of the component parts of this central battery--
the brain-cells. Although we must believe, then, that every
reaction to stimuli, however slight, produces a corresponding
change in the brain-cells, yet there are certain normal, that is,
non-diseased, conditions which produce especially striking changes.
The cell changes due to the emotions, for example, are so similar,
and in extreme conditions approach so closely to the changes produced
by disease, that it is impossible to say where the normal ceases
and the abnormal begins.

In view of the similarity of brain-cell changes it is not strange
that in the clinic as well as in daily life, we are confronted
constantly by outward manifestations which are so nearly
identical that the true underlying cause of the condition in
any individual case is too often overlooked or misunderstood.
In our laboratory experiments and in our clinical observations
we have found that exhaustion produced by intense emotion,
prolonged physical exertion, insomnia, intense fear, certain toxemias,
hemorrhage, and the condition commonly denominated surgical shock,
produce similar outward manifestations and identical brain-cell changes.

It is, therefore, the purpose of this paper to present the definite
results of laboratory researches which show certain relations
between alterations in brain functions and physical changes
in the brain-cells.

Fear.--Our experiments have shown that the brain-cell changes due
to fear may be divided into two stages: First, that of hyperchromatism--
stimulation; second, that of hypochromatism--exhaustion (Figs. 5 and
13). Hyperchromatism was shown only in the presence of the activating
stimuli or within a very short time after they had been received.
This state gradually changed until the period of maximum exhaustion
was reached--about six hours later. Then a process of reconstruction
began and continued until the normal state was again reached.

Fatigue.--Fatigue from overexertion produced in the brain-cells
like changes to those produced by fear, these changes being
proportional to the amount of exertion (Fig. 4). In the extreme
stage of exhaustion from this cause we found that the total
quantity of Nissl substance was enormously reduced.
When the exertion was too greatly prolonged, it took weeks or
months for the cells to be restored to their normal condition.
We have proved, therefore, that in exhaustion resulting from emotion
or from physical work a certain number of the brain-cells are
permanently lost. This is the probable explanation of the fact
that an athlete or a race-horse trained to the point of highest
efficiency can reach his maximum record but once in his life.
Under certain conditions, however, it is possible that, though some
chromatin is forever lost, the remainder may be so remarkably developed
that for a time at least it will compensate for that which is gone.

Hemorrhage.--The loss of blood from any cause, if sufficient to reduce
the blood-pressure, will occasion a change in the brain-cells, provided
that the period of hypotension lasts for more than five minutes.
This time limit is a safeguard against permanent injury
from the temporary hypotension which causes one to faint.
If the hemorrhage be long continued and the blood-pressure be low,
there will be a permanent loss of some of the brain-cells. This
explains why an individual who has suffered from a prolonged
hemorrhage will never again be restored to his original powers.

Drugs.--According to their effect upon the brain-cells, drugs
may be divided into three classes: First, those that stimulate
the brain-cells to increased activity, as strychnin (Fig. 37);
second, those that chemically destroy the brain-cells, as alcohol
and iodoform (Figs. 38 and 39); third, those that suspend the functions
of the cells without damaging them, as nitrous oxid, ether, morphin.
Our experiments have shown that the brain-cell changes induced
by drugs of the first class are precisely the same as the cycle
of changes produced by the emotions and by physical activity.
We have found that strychnin, according to the dosage, causes convulsions
ending in exhaustion and death; excitation followed by lassitude;
stimulation without notable after-results; or

{illust. caption = A, Section of Cerebellum of Normal Dog. C, Section of
Cerebellum of Dog after Repeated Doses of Strychnin. FIG. 37.--
BRAIN-CELLS SHOWING STAGE OF HYPERCHROMATISM FOLLOWED BY CHROMATOLYSIS
RESULTING FROM THE CONTINUATION OF THE STIMULUS. (Camera lucida
drawings.)increased mental tone; while the brain-cells accurately
display these physiologic alterations in proportional hyperchromatism
in the active stages, and proportional chromatolysis in the stages
of reaction. The biologic and therapeutic application of this fact
is as obvious as it is important.

In our experiments, alcohol in large and repeated dosage caused
marked morphologic changes in the brain-cells which went as far
even as the destruction of some of the cells (Fig. 39). Ether,
on the other hand, even after five hours of administration,
produced no observable destructive changes in the brain-cells.

The effect of iodoform was peculiarly interesting, as it was the only
drug that produced a rise of temperature. Its observed effect upon
the brain-cells was that of wide-spread destruction.

Infections.--In every observation regarding the effect of pyogenic
infections on dogs and on man we found that they caused definite
and demonstrable lesions in certain cells of the nervous system,
the most marked changes being in the cortex and the cerebellum
(Fig. 40). For example, in fatal infections resulting from
bowel obstruction, in peritonitis, and in osteomyelitis, the real
lesion is in the brain-cells. We may, therefore, reasonably conclude
that the lassitude, the diminished mental power, the excitability,
irritability, restlessness, delirium, and unconsciousness which may
be associated with acute infections, are due to physical changes
in the brain-cells.

Graves' Disease.--In Graves' disease the brain-cells show marked
changes which are apparently the same as those produced by overwork,
by the emotions, and by strychnin. In the postmortem examination
of one advanced case it was found that a large number of brain-cells
were disintegrated beyond the power of recuperation, even had
the patient lived. This is undoubtedly the reason why a severe case
of exophthalmic goiter sustains a permanent loss of brain power.

Insomnia.--The brains of rabbits which had been kept awake for one
hundred hours showed precisely the same changes as those shown
in physical fatigue, strychnin poisoning, and exhaustion from
emotional stimulation. Eight hours of continuous sleep restored
all the cells except those that had been completely exhausted.
This will explain the permanent ill effect of long-continued insomnia;
that is, long-continued insomnia permanently destroys a part
of the brain-cells just as do too great physical exertion,
certain drugs, emotional strain, exophthalmic goiter, and hemorrhage.
We found, however, that if, instead of natural sleep, the rabbits
were placed for the same number of hours under nitrous oxid anesthesia,
not only did the brain-cells recover from the physical deterioration,
but that 90 per cent. of them became hyperchromatic.
This gives us a possible clue to the actual chemical effect of sleep.
For since nitrous oxid owes its anesthetic effect to its influence
upon oxidation, we may infer that sleep also retards the oxidation
of the cell contents. If this be true, then it is probable
that inhalation anesthetics exert their peculiar influence upon
that portion of the brain through which sleep itself is produced.
If nitrous oxid anesthesia and sleep are chemically identical, then we
have a further clue to one of the primary mechanisms of life itself;
and as a practical corollary one might be able to produce artificial
sleep which would closely resemble normal sleep, but which would
have this advantage, that by using an anesthetic which interferes with
oxidation the brain-cells might be reconstructed after physical fatigue,
after emotional strain, or after the depression of disease.

In the case of the rabbit in which nitrous oxid was substituted
for sleep, the appearance of the brain-cells resembled that in
but one other group experimentally examined--the brain-cells
of hibernating woodchucks.

Insanity.--Our researches have shown that in the course of a fatal
disease and in fatal exhaustion, however produced, death does not
ensue until there is marked disorganization of the brain tissue.
In the progress of disease or exhaustion one may see in different
patients every outward manifestation of mental deterioration,
manifestations which, in a person who does not show any other sign of
physical disease, mark him as insane. Take, for example, the progressive
mental state of a brilliant scholar suffering from typhoid fever.
On the first day of the gradual onset of the disease he would
notice that his mental power was below its maximum efficiency;
on the second he would notice a further deterioration, and so
the mental effect of his disease would progress until he would
find it impossible to express a thought or to make a deduction.
No one can be philanthropic with jaundice; no one suffering
from Graves' disease can be generous; no mental process is possible
in the course of the acute infectious diseases. Just prior to death
from any cause every one is in a mental state which, if it could
be continued, would cause that individual to be judged insane.
If the delirium that occurs in the course of certain diseases
should be continued, the patient would be judged insane.
In severe cases of Graves' disease the patient is insane.
Individuals under overwhelming emotion may be temporarily insane.
Every clinician has seen great numbers of cases in which insanity
is a phase of a disease, of an injury, or of an emotion.
The stage of excitation in anesthesia is insanity.
The only difference between what is conventionally called insanity
and the fleeting insanity of the sick and the injured is that of time.
We may conclude, therefore, what must be the brain-picture of the person
who is permanently insane. This _a priori_ reasoning is all that
is possible, since the study of the brain in the insane has thus far
been confined to the brains of those who have died of some disease.
And it is impossible to say which changes have been produced by the
fatal disease, and which by the condition which produced the insanity.
The only logical way by which to investigate the physical basis
of insanity would be to make use of the very rare opportunities
of studying the brains of insane persons who have died in accidents.

Our experiments have proved conclusively that whether we call a person
fatigued or diseased, the brain-cells undergo physical deterioration,
accompanied by loss of mental power (Figs. 40 to 43). Even to the minutest
detail we can show a direct relationship between the physical state
of the brain-cells and the mental power of the individual, that is,
the physical power of a person goes _pari passu_ with his mental power.
Indeed, it is impossible to conceive how any mental action,
however subtle, can occur without a corresponding change in the
brain-cells. It is possible now to measure only the evidences of
the effects on the brain-cells of gross and violent mental activity.
At some future time it will doubtless be possible so to refine
the technic of brain-cell examinations that more subtle changes
may be measured. Nevertheless, with the means at our disposal
we have shown already that in all the conditions which we
have studied the cells of the cortex show the greatest changes,
and that loss of the higher mental functions invariably accompanies
the cell deterioration.

A MECHANISTIC VIEW OF PSYCHOLOGY[*]

[*] Address delivered before Sigma Xi, Case School
of Science, Cleveland, Ohio, May 27, 1913, and published
in _Science_, August 29, 1913.

Traditional religion, traditional medicine, and traditional psychology
have insisted upon the existence in man of a triune nature.
Three "ologies" have been developed for the study of each nature
as a separate entity--body, soul, and spirit--physiology, psychology,
theology; physician, psychologist, priest. To the great minds
of each class, from the days of Aristotle and Hippocrates on,
there have come glimmerings of the truth that the phenomena
studied under these divisions were interrelated. Always, however,
the conflict between votaries of these sciences has been sharp,
and the boundary lines between them have been constantly changing.
Since the great discoveries of Darwin, the zoologist, biologist,
and physiologist have joined hands, but still the soul-body-spirit
chaos has remained. The physician has endeavored to fight the gross
maladies which have been the result of disordered conduct;
the psychologist has reasoned and experimented to find the laws
governing conduct; and the priest has endeavored by appeals to an
unknown god to reform conduct.

The great impulse to a deeper and keener study of man's relation,
not only to man, but to the whole animal creation, which was given
by Darwin, has opened the way to the study of man on a different basis.
Psychologists, physicians, and priests are now joining hands as never
before in the great world-wide movement for the betterment of man.
The new science of sociology is combining the functions of all three,
for priest, physician, and psychologist have come to see that man
is in large measure the product of his environment.

My thesis to-night, however, will go beyond this common agreement,
for I shall maintain, not that man is in _*large measure_ the product
of his environment, but that environment has been the actual CREATOR
of man; that the old division between body, soul, and spirit
is non-existent; that man is a unified mechanism responding in every
part to the adequate stimuli given it from without by the environment
of the present and from within by the environment of the past,
the record of which is stored in part in cells throughout
the mechanism, but especially in its central battery--the brain.
I postulate further that the human body mechanism is equipped, first,
for such conflict with environment as will tend to the preservation
of the individual; and, second, for the propagation of the species,
both of these functions when most efficiently carried out tending
to the upbuilding and perfection of the race.

Through the long ages of evolution the human mechanism has been
slowly developed by the constant changes and growth of its parts
which have resulted from its continual adaptation to its environment.
In some animals the protection from too rough contact with
surroundings was secured by the development of an outside armor;
in others noxious secretions served the purposes of defense,
but such devices as these were not suitable for the higher animals
nor for the diverse and important functions of the human race.
The safety of the higher animals and of man had to be preserved
by some mechanism by means of which they could become adapted
to a much wider and more complex environment, the dominance over
which alone gives them their right to be called "superior beings."
The mechanism by the progressive development of which living
beings have been able to react more and more effectually to their
environment is the central nervous system, which is seen in one
of its simplest forms in motor plants, such as the sensitive
plant and the Venus fly-trap, and in its highest development only
in the sanest, healthiest, happiest, and most useful men.

The essential function of the nervous system was primarily to secure
some form of motor activity, first as a means of securing food,
and later as a means of escaping from enemies and to promote procreation.
Activities for the preservation of the individual and of the species
were and are the only purposes for which the body energy is expended.
The central nervous system hag accordingly been developed for the purpose
of securing such motor activities as will best adapt the individuals
of a species for their self-preservative conflict with environment.

It is easy to appreciate that the simplest expressions of nerve response--
the reflexes--are motor in character, but it is difficult to understand
how such intangible reactions as love, hate, poetic fancy, or moral
inhibition can be also the result of the adaptation to environment
of a distinctively motor mechanism. We expect, however, to prove
that so-called "psychic" states as well as the reflexes are products
of adaptation; that they occur automatically in response to adequate
stimuli in the environment; that, like the reflexes, they are
expressions of motor activity, which, although intangible and unseen,
in turn incite to activity the units of the motor mechanism of the body;
and finally, that any "psychic" condition results in a definite depletion
of the potential energy in the brain-cells which is proportionate
to the muscular exertion of which it is the representative.

That this nerve mechanism may effectively carry out its
twofold function, first, of self-adaptation to meet adequately
the increasingly complicated stimuli of environment; and second,
of adapting the motor mechanism to respond adequately to its demands,
there have been implanted in the body numerous nerve ceptors--
some for the transmission of stimuli harmful to the mechanism--
nociceptors some of a beneficial character--beneceptors; and still
others more highly specialized, which partake of the nature of both
bene- and nociceptors--the distance ceptors, or special senses.

A convincing proof that environment has been the creator
of man is seen in the absolute adaptation of the nociceptors
as manifested in their specific response to adequate stimuli,
and in their presence in only those parts of the body which throughout
the history of the race have been most exposed to harmful contacts.
We find they are most numerous in the face, the neck, the abdomen,
the hands, and the feet; while in the back they are few in number,
and within the bony cavities they are lacking.

Instances of the specific responses made by the nociceptors might be
multiplied indefinitely. Sneezing, for example, is a specific response
made by the motor mechanism to stimulation of nociceptors in the nose,
while stimulation of the larynx does not produce a sneeze, but a cough;
stimulation of the nociceptors of the stomach does not produce cough,
but vomiting; stimulation of the nociceptors of the intestine
does not produce vomiting, but increased peristaltic action.
There are no nociceptors misplaced; none wasted; none that do not
make an adequate response to adequate stimulation.

Another most significant proof that the environment of the past
has been the creator of the man of to-day is seen in the fact
that man has added to his environment certain factors to which
adaptation has not as yet been made. For example, heat is
a stimulus which has existed since the days of prehistoric man,
while the _x_-ray is a discovery of to-day; to heat, the nociceptors
produce an adequate response; to the _x_-ray there is no response.
There was no weapon in the prehistoric ages which could move at
the speed of a bullet from the modern rifle, therefore, while slow
penetration of the tissues produces great pain and muscular response,
there is no response to the swiftly moving bullet.

The response to contact stimuli then depends always on the presence
of nociceptors in the affected part of the body and to the type
of the contact. Powerful response is made to crushing injury by
environmental forces; to such injuring contacts as resemble the impacts
of fighting; to such tearing injuries as resemble those made by teeth
and claws (Fig. 9). On the other hand, the sharp division of tissue
by cutting produces no adaptive response; indeed, one might imagine
that the body could be cut to pieces by a superlatively sharp knife
applied at tremendous speed without material adaptive response.

These examples indicate how the history of the phylogenetic experiences
of the human race may be learned by a study of the position
and the action of the nociceptors, just as truly as the study
of the arrangement and variations in the strata of the earth's
crust discloses to us geologic history.

These adaptive responses to stimuli are the result of the action
of the brain-cells, which are thus continually played upon by
the stimuli of environment. The energy stored in the brain-cells
in turn activates the various organs and parts of the body.
If the environmental impacts are repeated with such frequency that
the brain-cells have no time for restoration between them, the energy
of the cells becomes exhausted and a condition of shock results.
Every action of the body may thus be analyzed into a stimulation
of ceptors, a consequent discharge of brain-cell energy,
and a final adaptive activation of the appropriate part.
Walking, running, and their modifications constitute an adaptation
of wonderful perfection, for, as Sherrington has shown,
the adaptation of locomotion consists of a series of reflexes--
ceptors in the joints, in the limb, and in the foot being stimulated
by variations in pressure.

As we have shown, the bene- and nociceptors orientate man to all
forms of physical contact--the former GUIDE HIM TO the acquisition
of food and to sexual contact; the latter DIRECT HIM FROM contacts
of a harmful nature. The distance ceptors, on the other hand,
adapt man to his distant environment by means of communication
through unseen forces--ethereal vibrations produce sight; air waves
produce sound; microscopic particles of matter produce smell.
The advantage of the distance ceptors is that they allow time
for orientation, and because of this great advantage the majority
of man's actions are responses to their adequate stimuli.
As Sherrington has stated, the greater part of the brain has been
developed by means of stimuli received through the special senses,
especially through the light ceptors, the optic nerves.

We have just stated that by means of the distance ceptors animals
and man orientate themselves to their distant environment.
As a result of the stimulation of the special senses chase and escape
are effected, fight is conducted, food is secured, and mates are found.
It is obvious, therefore, that the distance ceptors are the primary
cause of continuous and exhausting expenditures of energy.
On the other hand, stimuli applied to contact ceptors lead to short,
quick discharges of nervous energy. The child puts his hand
in the fire and there is an immediate and complete response
to the injuring contact; he sees a pot of jam on the pantry shelf
and a long train of continued activities are set in motion,
leading to the acquisition of the desired object.

The contact ceptors do not at all promote the expenditure of energy
in the chase or in fight, in the search for food or for mates.
Since the distance ceptors control these activities, one would expect to
find that they control also those organs whose function is the production
of energizing internal secretions. Over these organs--the thyroid,
the adrenals, the hypophysis--the contact ceptors have no control.
Prolonged laboratory experimentation seems to prove this postulate.
According to our observations, no amount of physical trauma inflicted upon
animals will cause hyperthyroidism or increased adrenalin in the blood,
while fear and rage do produce hyperthyroidism and increased adrenalin
(Fig. 44) (Cannon). This is a statement of far-reaching importance
and is the key to an explanation of many chronic diseases--
diseases which are associated with the intense stimulation of
the distance ceptors in human relations.

Stimuli of the contact ceptors differ from stimuli of the distance
ceptors in still another important particular. The adequacy of stimuli
of the contact ceptors depends upon their number and intensity,
while the adequacy of the stimuli of the distance ceptors depends
upon the EXPERIENCE of the species and of the individual.
That is, according to phylogeny and ontogeny this or that sound,
this or that smell, this or that sight, through association
recapitulates the experience of the species and of the individual--
awakens the phylogenetic and ontogenetic memory. In other words, sights,
sounds, and odors are symbols which awaken phylogenetic association.
If a species has become adapted to make a specific response to a
certain object, then that response will occur automatically in an
individual of that species when he hears, sees, or smells that object.
Suppose, for example, that the shadow of a hawk were to fall
simultaneously on the eyes of a bird, a rabbit, a cow, and a boy.
That shadow would at once activate the rabbit and the bird to an
endeavor to escape, each in a specific manner according to its
phylogenetic adaptation; the cow would be indifferent and neutral;
while the boy, according to his personal experience or ontogeny,
might remain neutral, might watch the flight of the hawk with interest
or might try to shoot it.

Each phylogenetic and each ontogenetic experience by an indirect
method develops its own mechanism of adaptation in the brain;
and the brain threshold is raised or lowered to stimuli by
the strength and frequency of repetition of the experience.
Thus through the innumerable symbols supplied by environment the distance
ceptors drive this or that animal according to the type of brain
pattern and the particular state of threshold which has been developed
in that animal by its phylogenetic and ontogenetic experiences.
The brain pattern depends upon his phylogeny, the state of threshold
upon his ontogeny. Each BRAIN PATTERN is created by some particular
element in the environment to which an adaptation has been made
for the good of the species. The _*state of threshold_ depends
upon the effect made upon the individual by his personal contacts
with that particular element in his environment. The presence
of that element produces in the individual an associative recall
of the adaptation of his species--that is, the brain pattern developed
by his phylogeny becomes energized to make a specific response.
The intensity of the response depends upon the state of threshold--
that is, upon the associative recall of the individual's
own experience--his ontogeny.

If the full history of the species and of the individual
could be known in every detail, then every detail of that
individual's conduct in health and disease could be predicted.
Reaction to environment is the basis of conduct, of moral standards,
of manners and conventions, of work and play, of love and hate,
of protection and murder, of governing and being governed, in fact,
of all the reactions between human beings--of the entire web of life.
To quote Sherrington once more: "Environment drives the brain,
the brain drives the various organs of the body."

By what means are these adaptations made? What is the mechanism through
which adequate responses are made to the stimuli received by the ceptors?
We postulate that in the brain there are innumerable patterns
each the mechanism for the performance of a single kind of action,
and that the brain-cells supply the energy--electric or otherwise--
by which the act is performed; that the energy stored in the brain-cells
is in some unknown manner released by the force which activates
the brain pattern; and that through an unknown property of these brain
patterns each stimulus causes such a change that the next stimulus
of the same kind passes with greater facility.

Each separate motor action presumably has its own mechanism--
brain pattern--which is activated by but one ceptor and by
that ceptor only when physical force of a certain intensity
and rate of motion is applied. This is true both of the visible
contacts affecting the nociceptors and of the invisible contacts
by those intangible forces which affect the distance ceptors.
For example, each variation in speed of the light-producing
waves of ether causes a specific reaction in the brain.
For one speed of ether waves the reaction is the perception
of the color blue; for another, yellow; for another, violet.
Changes in the speed of air waves meet with specific response
in the brain patterns tuned to receive impressions through the
aural nerves, and so we distinguish differences in sound pitch.
If we can realize the infinite delicacy of the mechanisms adapted
to these infinitesimal variations in the speed and intensity of
invisible and intangible stimuli, it will not be difficult to conceive
the variations of brain patterns which render possible the specific
responses to the coarser contacts of visible environment.

Each brain pattern is adapted for but one type of motion,
and so the specific stimuli of the innumerable ceptors play
each upon its own brain pattern only. In addition, each brain
pattern can react to stimuli applied only within certain limits.
Too bright a light blinds; too loud a sound deafens. No mechanism
is adapted for waves of light above or below a certain rate of speed,
although this range varies in different individuals and in different
species according to the training of the individual and the need
of the species.

We have already referred to the fact that there is no receptive
mechanism adapted to the stimuli from the _x_-ray, from the
high-speed bullet, from electricity. So, too, there are innumerable
forces in nature which can excite in man no adaptive response,
since there exist in man no brain patterns tuned to their waves,
as in the case of certain ethereal and radioactive forces.

On this mechanistic basis the emotions may be explained as activations
of the entire motor mechanism for fighting, for escaping, for copulating.
The sight of an enemy stimulates in the brain those patterns formed
by the previous experiences of the individual with that enemy, and also
the experiences of the race whenever an enemy had to be met and overcome.
Each of these many brain patterns in turn activates that part of
the body through which lies the path of its own adaptive response--
those parts including the special energizing or activating organs.
Laboratory experiments show that in an animal driven strongly
by emotion the following changes may be seen: (1) A mobilization
of the energy-giving compound in the brain-cells, evidenced by a
primary increase of the Nissl substance and a later disappearance
of this substance and the deterioration of the cells (Figs. 5 and 13);
(2) increased output of adrenalin (Cannon), of thyroid secretion,
of glycogen, and an increase of the power of oxidation in the muscles;
(3) accelerated circulation and respiration with increased
body temperature; (4) altered metabolism. All these are adaptations
to increase the motor efficiency of the mechanism. In addition,
we find an inhibition of the functions of every organ and tissue that
consumes energy, but does not contribute directly to motor efficiency.
The mouth becomes dry; the gastric and pancreatic secretions are
lessened or are completely inhibited; peristaltic action stops.
The obvious purpose of all these activations and inhibitions is
to mass every atom of energy upon the muscles that are conducting
the defense or attack.

So strong is the influence of phylogenetic experience that though
an enemy to-day may not be met by actual physical attack,
yet the decks are cleared for action, as it were, and the weapons
made ready, the body as a result being shaken and exhausted.
The type of emotion is plainly declared by the activation
of the muscles which would be used if the appropriate physical
action were consummated. In anger the teeth are set, the fists
are clenched, the posture is rigid; in fear the muscles collapse,
the joints tremble, and the running mechanism is activated
for flight; in sexual excitement the mimicry is as obvious.
The emotions, then, are the preparations for phylogenetic activities.
If the activities are consummated, the fuel--glycogen--and the activating
secretions from the thyroid, the adrenals, the hypophysis are consumed.
In the activation without action, these products must be eliminated
as waste products and so a heavy strain is put upon the organs
of elimination. It is obvious that the body under emotion might be
clarified by active muscular exercise, but the subject of the emotion
is so strongly integrated thereby that it is difficult for him
to engage in diverting, clarifying exertion. The person in anger
does not want to be saved from the ill effects of his own emotion;
he wants only to fight; the person in fear wants only to escape;
the person under sexual excitement wants only possession.

All the lesser emotions--worry, jealousy, envy, grief, disappointment,
expectation--all these influence the body in this manner, the consequences
depending upon the intensity of the emotion and its protraction.
Chronic emotional stimulation, therefore, may fatigue or exhaust
the brain and may cause cardiovascular disease, indigestion, Graves'
disease, diabetes, and insanity even.

The effect of the emotions upon the body mechanism may be compared
to that produced upon the mechanism of an automobile if its engines
are kept running at full speed while the machine is stationary.
The whole machine will be shaken and weakened, the batteries and weakest
parts being the first to become impaired and destroyed, the length
of usefulness of the automobile being correspondingly limited.

We have shown that the effects upon the body mechanism of the action
of the various ceptors is in relation to the response made by the brain
to the stimuli received. What is this power of response on the part
of the brain but CONSCIOUSNESS? If this is so, then consciousness
itself is a reaction to environment, and its intensity must vary
with the state of the brain and with the environmental stimuli.
If the brain-cells are in the state of highest efficiency, if their
energy has not been drawn upon, then consciousness is at its height;
if the brain is fatigued, that is, if the energy stored in the cells
has been exhausted to any degree, then the intensity of consciousness
is diminished. So degrees of consciousness vary from the height
maintained by cells in full vigor through the stages of fatigue
to sleep, to the deeper unconsciousness secured by the administration
of inhalation anesthetics, to that complete unconsciousness
of the environment which is secured by blocking the advent to
the brain of all impressions from both distance and contact ceptors,
by the use of both local and inhalation anesthetics--the state
of anoci-association (Fig. 14).

Animals and man may be so exhausted as to be only semi-conscious.
While a brain perfectly refreshed by a long sleep cannot immediately
sleep again, the exhausted brain and the refreshed brain when subjected
to equal stimuli will rise to unequal heights of consciousness.
The nature of the physical basis of consciousness has been
sought in experiments on rabbits which were kept awake from
one hundred to one hundred and nine hours. At the end of this
time they were in a state of extreme exhaustion and seemed
semi-conscious. If the wakefulness had been further prolonged,
this state of semi-consciousness would have steadily changed
until it culminated in the permanent unconsciousness of death.
An examination of the brain-cells of these animals showed physical
changes identical with those produced by exhaustion from other causes,
such as prolonged physical exertion or emotional strain (Figs. 45
and 46). After one hundred hours of wakefulness the rabbits were
allowed a long period of sleep. All the brain-cells were restored
except those that had been in a state of complete exhaustion.
A single seance of sleep served to restore some of the cells,
but those which had undergone extreme changes required prolonged rest.
These experiments give us a definite physical basis for explaining
the cost to the body mechanism of maintaining the conscious state.
We have stated that the brain-cell changes produced by prolonged
consciousness are identical with those produced by physical exertion
and by emotional strain. Rest, then, and especially sleep,
is needed to restore the physical state of the brain-cells which
have been impaired, and as the brain-cells constitute the central
battery of the body mechanism, their restoration is essential
for the maintenance of normal vitality.

In ordinary parlance, by consciousness we mean the activity
of that part of the brain in which associative memory resides,
but while associative memory is suspended the activities of the brain
as a whole are by no means suspended; the respiratory and circulatory
centers are active, as are those centers which maintain muscular tone.
This is shown by the muscular response to external stimuli made
by the normal person in sleep; by the occasional activation of motor
patterns which may break through into consciousness causing dreams;
and finally by the responses of the motor mechanism made to the injuring
stimuli of an operation on a patient under inhalation anesthesia only.

Direct proof of the mechanistic action of many of life's phenomena
is lacking, but the proof is definite and final of the part
that the brain-cells play in maintaining consciousness;
of the fact that the degree of consciousness and mental
efficiency depends upon the physical state of the brain-cells;
and finally that efficiency may be restored by sleep,
provided that exhaustion of the cells has not progressed too far.
In this greatest phenomenon of life, then, the mechanistic theory
is in harmony with the facts.

Perhaps no more convincing proof of our thesis that the body is
a mechanism developed and adapted to its purposes by environment
can be secured than by a study of that most constant manifestation
of consciousness--pain.

Like the other phenomena of life, pain was undoubtedly evolved
for a particular purpose--surely for the good of the individual.
Like fear and worry, it frequently is injurious. What then may
be its purpose?

We postulate that pain is a result of contact ceptor stimulation
for the purpose of securing protective muscular activity.
This postulate applies to all kinds of pain, whatever their cause--
whether physical injury, pyogenic infection, the obstruction
of hollow viscera, childbirth, etc.

All forms of pain are associated with muscular action, and as in every
other stimulation of the ceptors, each kind of pain is specific
to the causative stimuli. The child puts his hand in the fire;
physical injury pain results, and the appropriate muscular
response is elicited. If pressure is prolonged on some parts
of the body, anemia of the parts may result, with a corresponding
discomfort or pain, requiring muscular action for relief.
When the rays of the sun strike directly upon the retina, light pain
causes an immediate protective action, so too in the evacuation
of the intestine and the urinary bladder as normal acts, and in
overcoming obstruction of these tracts, discomfort or pain compel
the required muscular actions. This view of pain as a stimulation
to motor action explains why only certain types of infection are
associated with pain; namely, those types in which the infection
may be spread by muscular action or those in which the fixation
of parts by continued muscular rigidity is an advantage.
As a further remarkable proof of the marvelous adaptation
of the body mechanism to meet varying environmental conditions,
we find that just as nociceptors have been implanted in only those
parts of the body which have been subject to nocuous contacts,
so a type of infection which causes muscular action in one part
of the body may cause none when it attacks another.

This postulate gives us the key to the pain-muscular phenomena
of peritonitis, pleurisy, cystitis, cholecystitis, etc., as well as to
the pain-muscular phenomena in obstructions of the hollow viscera.
If pain is a part of a muscular response and occurs only
as a result of contact ceptor stimulation by physical injury,
infection, anemia, or obstruction, we may well inquire which part
of the nerve mechanism is the site of the phenomenon of pain.
Is it the nerve-ending, the nerve-trunk, or the brain? That is,
is pain associated with the physical contact with the nerve-ending,
or with the physical act of transmission along the nerve-trunk,
or with the change of brain-cell substance by means of which
the motor-producing energy is released?

We postulate that the pain is associated with the discharge of energy
from the brain-cells. If this be true, then if every nociceptor in
the body were equally stimulated in such a manner that all the stimuli
should reach the brain-cells simultaneously, then the cells would
find themselves in equilibrium and no motor act would be performed.
But if all the pain nerve ceptors but one were equally stimulated,
and this one more strongly stimulated than the rest, then this
one would gain possession of the final common path--would cause
a muscular action and the sensation of pain.

It is well known that when a greater pain or stimulus is thrown
into competition with a lesser one, the lesser is submerged.
Of this fact the school-boy makes use when he initiates
the novice into the mystery of the painless pulling of hair.
The simultaneous but severe application of the boot to the blindfolded
victim takes complete but exclusive possession of the final common
path and the hair is painlessly plucked as a result of the triumph
of the boot stimulus over the pull on the hair in the struggle
for the final common path.

Persons who have survived a sudden, complete exposure to superheated steam,
or whose bodies have been enwrapped in flame, testify that they
have felt no pain. As this absence of pain may be due to the fact
that the emotion of fear gained the final common path, to the exclusion
of all other stimuli, we are trying by experimentation to discover
the effects of simultaneous painful stimulation of all parts of the body.
The data already in hand, and the experiments now in progress,
in which anesthetized animals are subjected to powerful stimuli
applied to certain parts of the body only, or simultaneously to
all parts of the body, lead us to believe that in the former case
the brain-cells become stimulated or hyperchromatic, while in the latter
case no brain-cell changes occur. We believe that our experiments
will prove that an equal and simultaneous stimulation of all parts
of the body leaves the brain-cells in a state of equilibrium.
Our theory of pain will then be well sustained, not only by common
observation, but by experimental proof, and so the mechanistic view
will be found in complete harmony with another important reaction.

We have stated that when a number of contact stimuli act simultaneously,
the strongest stimulus will gain possession of the final common path--
the path of action. When, however, stimuli of the distance ceptors
compete with stimuli of the contact ceptors, the contact-ceptor
stimuli often secure the common path, not because they are stronger
or more important, but because they are immediate and urgent.
In many instances, however, the distance-ceptor stimuli are strong,
have the advantage of a lowered threshold, and therefore compete
successfully with the immediate and present stimuli of the
contact ceptors. In such cases we have the interesting phenomenon
of physical injury without resultant pain or muscular response.
The distance-ceptor stimuli which may thus triumph over even powerful
contact-ceptor stimuli are those causing strong emotions--as great
anger in fighting; great fear in a battle; intense sexual excitement.
Dr. Livingstone has testified to his complete unconsciousness
to pain during his struggle with a lion; although he was torn
by teeth and claws, his fear overcame all other impressions.
By frequently repeated stimulation the Dervish secures a low
threshold to the emotions caused by the thought of God or the devil,
and his emotional excitement is increased by the presence of others
under the same stimulation; emotion, therefore, secures the final
common path and he is unconscious of pain when he lashes, cuts,
and bruises his body. The phenomena of hysteria may be explained
on this basis, as may the unconsciousness of passing events
in a person in the midst of a great and overwhelming grief.
By constant practice the student may secure the final common path for
such impressions as are derived from the stimuli offered by the subject
of his study, and so he will be oblivious of his surroundings.
Concentration is but another name for a final common path secured
by the repetition and summation of certain stimuli.

If our premises are sustained, then we can recognize in man no will,
no ego, no possibility for spontaneous action, for every action must
be a response to the stimuli of contact or distance ceptors, or to their
recall through associative memory. Memory is awakened by symbols which
represent any of the objects or forces associated with the act recalled.
Spoken and written words, pictures, sounds, may stimulate the brain
patterns formed by previous stimulation of the distance ceptors;
while touch, pain, temperature, pressure, may recall previous
contact-ceptor stimuli. Memory depends in part upon the adequacy
of the symbol, and in part upon the state of the threshold.
If one has ever been attacked by a snake, the threshold to any
symbol which could recall that attack would be low; the later
recall of anything associated with the bite or its results would
produce in memory a recapitulation of the whole scene, while even
harmless snakes would thereafter be greeted with a shudder.
On the other hand, in a child the threshold is low to the desire
for the possession of any new and strange object; in a child,
therefore, to whom a snake is merely an unusual and fascinating object,
there is aroused only curiosity and the desire for the possession
of a new plaything.

If we are to attribute to man the possession of a governing
attribute not possessed by other parts of the animal creation,
where are we to draw the boundary line, and say "here the ego--
the will--the reason--emerges"? What attribute, after all, has man
which in its ultimate analysis is not possessed by the lowest
animals or by the vegetable creation, even? From the ameba,
on through all the stages of animal existence, every action is
but a response to an adequate stimulus; and as a result of adequate
stimuli each step has been taken toward the higher and more
intricate mechanisms which play the higher and more intricate parts
in the great scheme of nature.

The Venus fly-trap responds to as delicate a stimulus as do
any of the contact ceptors of animals, and the motor activity
resulting from the stimulus is as complex. To an insect-like touch
the plant responds; to a rough contact there is no response; that is,
the motor mechanism of the plant has become attuned to only such
stimuli as simulate the contact of those insects which form its diet.
It catches flies, eats and digests them, and ejects the refuse
(Fig. 47). The ameba does no less. The frog does no more,
excepting that in its place in creation a few more reactions are
required for its sustenance and for the propagation of its species.
Man does no more, excepting that in man's manifold relations
there are innumerable stimuli, for meeting which adequately,
innumerable mechanisms have been evolved. The motor mechanism
of the fly-trap is perfectly adapted to its purpose.
The motor mechanism of man is adapted to its manifold uses,
and as new environmental influences surround him, we must believe
that new adaptations of the mechanism will be evolved to meet
the new conditions.

Is not this conception of man's activities infinitely more wonderful,
and infinitely more comprehensible than is the conception that his
activities may be accounted for by the existence of an unknown,
unimaginable, and intangible force called "mind" or "soul"?

We have already shown how the nerve mechanism is so well adapted
to the innumerable stimuli of environment that it can accurately
transmit and distinguish between the infinite variations of speed
in the ether waves producing light, and the air waves producing sound.
Each rate of vibration energizes only the mechanism which has
been attuned to it. With marvelous accuracy the light and sound
waves gain access to the nerve tissue and are finally interpreted
in terms of motor responses, each by the brain pattern attuned
to that particular speed and intensity. So stimuli and resultant
actions multiplied by the total number of the motor patterns
in the brain of man give us the sum total of his life's activities--
they constitute his life.

As in evolutionary history the permanence of an adaptation of the body
mechanism depends upon its value in the preservation of the life
of the individual and upon its power to increase the value of
the individual to the race, so the importance and truth of these
postulates and theories may well be judged on the same basis.

The fundamental instincts of all living matter are self-preservation
and the propagation of the species. The instinct for self-preservation
causes a plant to turn away from cold and damaging winds toward
the life-giving sun; the inert mussel to withdraw within its shell;
the insect to take flight; the animal to fight or to flee; and man
to procure food that he may oppose starvation, to shelter himself
and to provide clothes that he may avoid the dangers of excessive
cold and heat, to combat death from disease by seeking medical aid,
to avoid destruction by man or brute by fight or by flight.
The instinct to propagate the species leads brute man by crude methods,
and cultured man by methods more refined, to put out of his way sex
rivals so that his own life may be continued through offspring.
The life of the species is further assured by the protective
action exercised over the young by the adults of the species.
As soon as the youngest offspring is able successfully to carry on his
own struggle with environment there is no longer need for the parent,
and the parent enters therefore the stage of disintegration.
The average length of life in any species is the sum of the years
of immaturity, plus the years of female fertility, plus the adolescent
years of the offspring.

The stimuli resulting from these two dominant instincts are now
so overpowering as compared with all other environmental stimuli
that the mere possession of adequate knowledge of the damaging effects
of certain actions as compared with the saving effects of others will
(other things being equal) lead the individual to choose the right,--
the self- and species-preservative course of action, instead of the wrong,--
the self- and species-destructive course of action.

The dissemination of the knowledge of the far-reaching
deleterious effects of protracted emotional strain, of overwork,
and of worry will automatically raise man's threshold to
the damaging activating stimuli causing the strong emotions,
and will cause him to avoid dangerous strains of every kind.
The individual thus protected will therefore rise to a plane
of poise and efficiency far above that of his uncontrolled fellows,
and by so much will his efficiency, health, and happiness be augmented.

A full acceptance of this theory cannot fail to produce in those
in whose charge rests the welfare of the young, an overwhelming
desire to surround children with those environmental stimuli only
which will tend to their highest ultimate welfare.

Such is the stimulating force of tradition that many who
have been educated under the tenets of traditional beliefs
will oppose these hypotheses--even violently, it may be.
So they have opposed them; so they opposed Darwin; so they
have opposed all new and apparently revolutionary doctrines.
Yet these persons themselves are by their very actions proving
the efficiency of the vital principles which we have enunciated.
What is the whole social welfare movement but a recognition
on the part of municipalities, educational boards, and religious
organizations of the fact that the future welfare of the race
depends upon the administration to the young of forceful
uplifting environmental stimuli?

There are now, as there were in Darwin's day, many who feel that man
is degraded from his high estate by the conception that he is not
a reasoning, willing being, the result of a special creation.
But one may wonder indeed what conception of the origin of man can
be more wonderful or more inspiring than the belief that he has
been slowly evolved through the ages, and that all creatures
have had a part in his development; that each form of life has
contributed and is contributing still to his present welfare
and to his future advancement.

Recapitulation

Psychology,--the science of the human soul and its relations,--
under the mechanistic theory of life, must receive a new definition.
It becomes a science of man's activities as determined by the
environmental stimuli of his phylogeny and of his ontogeny.

On this basis we postulate that throughout the history of the race nothing
has been lost, but that every experience of the race and of the individual
has been retained for the guidance of the individual and of the race;
that for the accomplishment of this end there has been evolved through
the ages a nerve mechanism of such infinite delicacy and precision
that in some unknown manner it can register permanently within
itself every impression received in the phylogenetic and ontogenetic
experience of the individual; that each of these nerve mechanisms
or brain patterns has its own connection with the external world,
and that each is attuned to receive impressions of but one kind,
as in the apparatus of wireless telegraphy each instrument can
receive and interpret waves of a certain rate of intensity only;
that thought, will, ego, personality, perception, imagination,
reason, emotion, choice, memory, are to be interpreted in terms
of these brain patterns; that these so-called phenomena of human
life depend upon the stimuli which can secure the final common path,
this in turn having been determined by the frequency and the strength
of the environmental stimuli of the past and of the present.

Finally, as for life's origin and life's ultimate end,
we are content to say that they are unknown, perhaps unknowable.
We know only that living matter, like lifeless matter, has its own
place in the cosmic processes; that the gigantic forces which operated
to produce a world upon which life could exist, as a logical sequence,
when the time was ripe, evolved life; and finally that these cosmic
forces are still active, though none can tell what worlds and what
races may be the result of their coming activities.

A MECHANISTIC THEORY OF DISEASE[*]

[*] Oration in Surgery. Delivered at the 147th Annual Meeting of the
Medical Society of New Jersey, at Spring Lake, N. J., June 11, 1913.

In this address the paragraphs which were taken from the preceding
paper, "A Mechanistic View of Psychology," have been omitted,
those portions only being republished in which the premises have
been applied in a discussion of certain medical problems rather
than of psychological problems.

The human body is an elaborate mechanism equipped first for such
conflict with environment as will tend to the preservation
of the individual, and second for the propagation of the species,
both of these functions, when most efficiently carried out,
tending to the upbuilding and perfection of the race.
From the date of Harvey's discovery of the circulation of the blood,
to the present day, the human body has been constantly compared
to a machine, but the time for analogy and comparison is past.
I postulate that the body is itself a mechanism responding in every
part to the adequate stimuli given it from without by the environment
of the present and from within by the environment of the past,
the memory of which is stored in the central battery of the mechanism--
the brain.
*   *    *    *    *    *    *    *    *    *
*   *    *    *    *    *    *    *    *    *

If the full history of the species and of the individual
could be known in every detail, then every detail of that
individual's conduct in health and disease could be predicted.
Reaction to environment is the basis of conduct, of moral standards,
of manners and conventions, of work and play, of love and hate,
of protection and murder, of governing and being governed, in fact,
of all the reactions between human beings--of the entire web of life.
As Sherrington has stated, "Environment drives the brain, the brain
drives the various organs of the body," and here we believe we find
the key to a mechanistic interpretation of all body processes.

On this basis we may see that the activities of life depend upon
the ability of the parts of the body mechanism to respond adequately
to adequate stimulation. This postulate applies not only to stimuli
from visible forces, but to those received by the invasion of
the micro-bodies which cause pyogenic or non-pyogenic infections.
In the case of dangerous assaults by visible or invisible enemies,
the brain, through the nerves and all parts of the motor mechanism,
meets the attack by attempts at adaptation. Recovery, invalidism,
and death depend upon the degree of success with which the attacking
or invading enemies are met. Questions regarding disease become,
therefore, questions in adaptation, and it is possible that,
when studied in the light of this conception, the key to many hitherto
unsolved physical problems may be found.

Perhaps no more convincing proof of our thesis may be secured
than by a study of that ever-present phenomenon--pain. In whatever
part of the body and by whatever apparent cause pain is produced,
we find that it is invariably a stimulation to motor activity--
whose ultimate object is protection. Thus by the muscular action
resulting from pain we are protected against heat and cold;
against too powerful light; against local anemia caused by prolonged
pressure upon any portion of the body. So, too, pain of greater
or less intensity compels the required emptying of the pregnant
uterus and the evacuation of the intestine and the urinary bladder.

It should be noted that in every instance the muscular activity
resulting from pain is specific in its type, its distribution,
and its intensity, this specificity being true not only of pain
which is the result of external stimulation, but also of the pain
associated with certain types of infection.

Pain, however, is not the only symptom of the invasion of
the body by pyogenic or parasitic organisms. Fever, invariably,
and chills, often, accompany the course of the infections.
Can these phenomena also be explained as adaptations of the motor
mechanism for the good of the individual?

As the phenomena of chills and fever are most strikingly exhibited
in malaria, let us study the course of events in that disease.
It is known that the malarial parasite develops in the red
blood-corpuscles, and that the chills and fever appear when
the cycle of parasitic development is complete and the adults
are ready to escape from the corpuscles of the blood plasma.
Bass, of New Orleans, has proved that the favorable temperature
for the growth of the malarial organism is 98'0, and that at 102'0
the adult organisms will be killed, though the latter temperature
is not fatal to the spores. The adult life of the malarial
parasite begins after its escape into the blood plasma, and it is
there that the organism is most susceptible to high temperature.
We must infer, therefore, that the fever is an adaptation on the part
of the host for despatching the enemy.

What, then, may be the protective part played by the chill?
A chill is made up of intermittent contractions of all the external
muscles of the body. This activity results in an increase
of the body heat and in an anemia of the superficial parts
of the body, so that less heat can be lost by radiation.
By this means, therefore, the external portions of the body contribute
measurably to the production of the beneficent and saving fever.

It must be remembered that this power of adaptation is not peculiar
to man alone, but that it is a quality shared by all living creatures.
While the human body has been adapting itself for self-protection
by producing a febrile reaction whereby to kill the invading organisms,
the invaders on their side have been adapting themselves for a life
struggle within the body of the host. In these mortal conflicts
between invaders and host, therefore, the issue is often in doubt,
and sometimes one and sometimes the other will emerge victorious.

We must believe that a similar adaptive response exists in all
parasitic infections--the cycles varying according to the stages in
the development of the invaders. If the bacteria develop continuously,
the fever is constant instead of intermittent, since the adequate
stimulus is constantly present.

Bacteriology has taught us that both heat and cold are fatal
to pathogenic infections; for this reason either of the apparently
contradictory methods of treatment may help, _i. e_., either hot
or cold applications. It should be borne in mind, however, that we have
to deal not only with the adult organisms, but with the spores also.
The application of cold may keep the spores from developing,
while heat may promote their development, and the course of the disease
may vary, therefore, according to our choice of treatment.

From this viewpoint, we can understand the intermittent temperature
in a patient who is convalescing from an extreme infection,
as peritonitis, pylephlebitis, multiple abscess of the liver, etc.
In these conditions there may occur days of normal temperature,
followed by an abrupt rise which will last for several days--
this in turn succeeded by another remittance. This cycle may be
repeated several times, and on our hypothesis we may believe it
is caused by the successive development to maturity of spores
of varying ages.

If these premises are sound, the wisdom of reducing the temperature
in case of infection may well be questioned.

On this mechanistic basis the emotions also may be explained
as activations of the entire motor mechanism for fighting,
for escaping, for copulating.
*   *    *    *    *    *    *    *    *    *
*   *    *    *    *    *    *    *    *    *

The emotions, then, are the preparation for phylogenetic activities
(Fig. 48). If the activities were consummated, the fuel--glycogen--
and the activating secretions from the thyroid, the adrenals,
the hypophysis, would be consumed. In the activation without
action these products must be eliminated as waste products
and so a heavy strain is put upon the organs of elimination.
It is obvious that the body under emotion might be clarified
by active muscular exercise, but the subject of the emotion is so
strongly integrated thereby that it is difficult for him to engage
in diverting, clarifying exertion.
*   *    *    *    *    *    *    *    *    *
*   *    *    *    *    *    *    *    *    *

So, as we have indicated already, certain deleterious effects are
produced when the body mechanism is activated without resultant action.
For example, the output of adrenalin is increased, and, as a consequence,
arteriosclerosis and cardiovascular disease may occur in persons
who have been subjected to prolonged emotional strain, since it
has been proved that the prolonged administration of adrenalin
will cause these conditions. We have stated that the emotions cause
increased output of glycogen. Glycogen is a step toward diabetes,
and therefore this disease, too, is prone to appear in persons
under emotional strain. It is most common in those races which
are especially emotional in character, so we are not surprised
to find it especially prevalent among Jews. So common is this
particular result of prolonged emotion that some one has said,
"When the stocks go down in New York, diabetes goes up."
Nephritis, also, may result from emotional stress, because of the strain
put upon the kidneys by the unconsumed activating substances.
The increased heart action and the presence of these activating
secretions may cause myocarditis and heart degeneration.
Claudication also may result from the impaired circulation.

The emotions may cause an inhibition of the digestive secretions
and of intestinal peristalsis. This means that the digestive processes
are arrested, that putrefaction and autointoxication will result,
and that still further strain will thus be put upon the organs
of elimination. Who has not observed in himself and in others when under
the influence of fear, anger, jealousy, or grief that the digestive
processes and general well-being are rapidly and materially altered;
while as tranquillity, peace, and happiness return the physical
state improves accordingly?

Dentists testify that as a result of continued strong emotion the character
of the saliva changes, pyorrhea develops, and the teeth decay rapidly.
Every one knows that strong emotion may cause the hair to fall
out and to become prematurely gray.

As to the most important organ of all--the brain--every one is
conscious of its impaired efficiency under emotional strain,
and laboratory researches show that the deficiency is accounted
for by actual cell deterioration; so the individual who day by day
is under heavy emotional strain finds himself losing strength slowly--
especially do his friends note it. By summation of stimuli
his threshold becomes lowered until stimuli, which under normal
conditions would be of no effect, produce undue responses.
"The grasshopper becomes a burden," and prolonged rest and change
of environmental conditions are necessary for restoration.

If in a long emotional strain the brain is beaten down;
if the number of "low-efficiency" cells increases, the driving
power of the brain is correspondingly lessened and therefore
the various organs of the body may escape through the very
inefficiency of the brain to produce in them forced activity.
On the other hand, if the brain remains vigorous, the kidneys
may take the strain and break down; if the kidneys do not break,
the blood-vessels may harden; if the blood-vessels are not affected,
the thyroid may become hyperplastic and produce Graves' disease;
if the thyroid escapes, diabetes may develop; while if the iron
constitution of the mechanism can successfully bear the strain
in all its parts, then the individual will break his competitors,
and their mechanisms will suffer in the struggle.

This whole train of deleterious results of body activation without
action may be best observed and studied in that most emotional
of diseases--exophthalmic goiter. In this disease the constantly
stimulated distance ceptors dispossess the contact ceptors from
the common path, and drive the motor mechanism to its own destruction,
and the patient has the appearance of a person in great terror,
or of a runner approaching the end of a Marathon race (Figs. 16
and 48 to 54).

Exophthalmic goiter may result from long emotional or mental stress
in those cases in which the thyroid takes the brunt of the strain upon
the mechanism. As adrenalin increases blood-pressure, so thyroid
secretion increases brain activity, and increased brain activity
in turn causes an increased activation of the motor mechanism
as a whole.

We know that a deficiency or lack of thyroid secretion will inhibit
sexual emotion and conception, will produce stupidity and inertia;
will diminish vitality. On the other hand, excessive thyroid secretion
drives the entire mechanism at top speed; the emotions are intensified;
the skin becomes soft and moist, the eyes are brilliant and staring;
the limbs tremble; the heart pounds loudly and its pulsations often
are visible; the respiration is rapid; the stimulation of the fear
mechanism causes the eyes to protrude (Fig. 16); the temperature
mounts at every slight provoca-tion and may reach the incredible
height of 110'0 even. In time, the entire organism is destroyed--
literally consumed--by the concentration of dynamic energy.
It is interesting to note that in these patients emotion gains complete
possession of the final common path; they are wild and delirious--
but they never have pain.

All the diseases caused by excessive motor activity may be called
kinetic diseases. Against the conditions in life which produce
them man reacts in various ways. He intro-

{illust. caption = FIG. 51.--CROSS-COUNTRY RACE. Winner of six-mile
cross-country race showing typical expression of exhaustion.
(Underwood and Underwood, N. Y.) duces restful variety
into his life by hunting and fishing; by playing golf and tennis;
by horseback riding; by cultivating hobbies which effectually.
turn the current of his thoughts{illust. caption = FIG. 52.--{A B
and C} from the consuming stress and strain of his business
or professional life. These diversions are all rational
attempts to relieve tension by self-preservative reactions.
For the same reason man attempts to relieve the strain of
contention with his fellow-man by unions, trusts, corporations.
In spite of all efforts, however, many constitutions are
still broken daily in the fierce conflicts of competition.
We know how often the overdriven individual endeavors to minimize
the activities of his motor mechanism by the use of agents which diminish
brain activity, such as alcohol, tobacco, and various narcotics.
Occasionally also, some person, who can find no respite from his own
relentless energies, seeks relief in oblivion by suicide.

Most fortunately, two fundamental instincts--self-preservation and
the propagation of the species--act powerfully to prevent
this last fatal result, and instead the harassed individual
seeks from others the aid which is lacking within himself.
He may turn to the priest who seeks and often secures the final
common path for faith in an over-ruling Providence, a faith which in
many incontrovertible instances has proved sufficient in very truth
to move mountains of lesser stimuli; or he turns to a physician,
who too often treats the final outcome of the hyperactivity only.
The physician who accepts the theory of the kinetic diseases,
however, will not only repair as far as he may the lesions caused
by the disordered and forced activities, but will, by compelling and
forceful suggestion, secure the final common path for right conduct,
that is, for a self- and species-preservative course of action
as opposed to wrong conduct-a self- and species-destructive
course of action.

By forcefully imparting to his patient the knowledge of the far-reaching
effects of protracted emotional strain, of overwork, and of worry,
the physician will automatically raise his threshold to the damaging
activating stimuli which have produced the evil results.
Even though some parts of his organism may have been permanently disabled,
a patient thus protected may yet rise to a plane of poise and
efficiency far above that of his uncontrolled fellows.

In extreme cases it does not seem unreasonable to believe that the
uncontrolled patient might be rescued by the same principle which has
proved effective in saving patients from the emotional and traumatic strain
of surgical operations--the principle of anoci-association. That is,
by disconnecting one or more of the activating organs from the brain,
the motor mechanism might be saved from its self-destruction.

Under this hypothesis, that man in disease, as in health,
is the product of his phylogeny as well as of ontogeny, the sphere
of the physician's activities takes on new aspects of far-reaching
and inspiring significance. Prognosis will become definite in proportion
to the physician's knowledge not only of the ontogenetic history of
the individual patient, but also of the phylogenetic history of the race.
As that knowledge increases, as he appreciates more and more keenly
the significance of environment in its effect upon individual development,
in so far will the physician be in a position to contribute mightily
to the welfare of the race.

THE KINETIC SYSTEM[*]

[*] Address delivered before the New York State Medical Society, April 28,
1914, to which has been added a further note regarding studies
of hydrogen ion concentration in the blood.

In this paper I formulate a theory which I hope will harmonize a large
number of clinical and experimental data, supply an interpretation
of certain diseases, and show by what means many diverse causes
produce the same end effects.

Even should the theory prove ultimately to be true, it will in the mean
time doubtless be subjected to many alterations. The specialized
laboratory worker will, at first, fail to see the broader clinical view,
and the trained clinician may hesitate to accept the laboratory findings.
Our viewpoint has been gained from a consideration of both lines
of evidence on rather a large scale.

The responsibility for the kinetic theory is assumed by myself,
while the responsibility for the experimental data is shared fully
by my associates, Dr. J. B. Austin, Dr. F. W. Hitchings, Dr. H. G. Sloan,
and Dr. M. L. Menten.[t]

[t] From H. K. Cushing Laboratory of Experimental Medicine,
Western Reserve University, Cleveland.

Introduction

The self-preservation of man and kindred animals is effected
through mechanisms which transform latent energy into kinetic energy
to accomplish adaptive ends. Man appropriates from environment
the energy he requires in the form of crude food which is refined
by the digestive system; oxygen is taken to the blood and carbon
dioxid is taken from the blood by the respiratory system;
to and from the myriads of working cells of the body, food and oxygen
and waste are carried by the circulatory system; the body is cleared
of waste by the urinary system; procreation is accomplished through
the genital system; but none of these systems was evolved primarily
for the purpose of transforming potential energy into kinetic energy
for specific ends. Each system transforms such amounts of potential
into kinetic energy as are required to perform its specific work;
but no one of them transforms latent into kinetic energy for the purposes
of escaping, fighting, pursuing, nor for combating infection.
The stomach, the kidneys, the lungs, the heart strike no physical
blow-their role is to do certain work to the end that the blow may
be struck by another system evolved for that purpose. I propose
to offer evidence that there is in the body a system evolved primarily
for the transformation of latent energy into motion and into heat.
This system I propose to designate "The Kinetic System."

The kinetic system does not directly circulate the blood,
nor does it exchange oxygen and carbon dioxid; nor does it perform
the functions of digestion, urinary elimination, and procreation;
but though the kinetic system does not directly perform these functions,
it does play indirectly an important role in each, just as the kinetic
system itself is aided indirectly by the other systems.

The principal organs which comprise the kinetic system are
the brain, the thyroid, the adrenals, the liver, and the muscles.
The brain is the great central battery which drives the body;
the thyroid governs the conditions favoring tissue oxidation;
the adrenals govern immediate oxidation processes; the liver fabricates
and stores glycogen; and the muscles are the great converters
of latent energy into heat and motion.

Adrenalin alone, thyroid extract alone, brain activity alone,
and muscular activity alone are capable of causing the body temperature
to rise above the normal. The functional activity of no other gland
of the body alone, and the secretion of no other gland alone, can cause
a comparable rise in body temperature--that is, neither increased
functional activity nor any active principle derived from the kidney,
the liver, the stomach, the pancreas, the hypophysis, the parathyroids,
the spleen, the intestines, the thymus, the lymphatic glands,
or the bones can, _per se_, cause a rise in the general body
temperature comparable to the rise that may be caused by the activity
of the brain or the muscles, or by the injection of adrenalin
or thyroid extract. Then, too, when the brain, the thyroid,
the adrenals, the liver, or the muscles are eliminated, the power
of the body to convert latent into kinetic energy is impaired or lost.
I shall offer evidence tending to show that an excess of either
internal or external environmental stimuli may modify one or more
organs of the kinetic system, and that this modification may cause
certain diseases. For example, alterations in the efficiency
of the cerebral link may yield neurasthenia, mania, dementia;
of the thyroid link, Graves' disease, myxedema; of the adrenal link,
Addison's disease, cardiovascular disease.

This introduction may serve to give the line of our argument.
We shall now consider briefly certain salient facts which relate to
the conversion of latent into kinetic energy as an adaptive reaction.
The experimental data are so many that they will later be published
in a monograph.

The amount of latent energy which may be converted into kinetic
energy for adaptive ends varies in different species, in individuals
of the same species, in the same individual in different seasons;
in the life cycle of growth, reproduction and decay;
in the waking and sleeping hours; in disease and in activity.
We shall here consider briefly the reasons for some of those variations
and the mechanisms which make them possible.

Biologic Consideration of the Adaptive Variation in Amounts
of Energy Stored in Various Animals

Energy is appropriated from the physical forces of nature
that constitute the environment. This energy is stored in
the body in quantities in excess of the needs of the moment.
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 assist 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 sexual 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 sexual characters, nor do they develop sexual desire
nor show seasonal cycles of activity, nor can they procreate.
The secondary sexual characters--sexual 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, 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.

Summary of Brain-cell Studies

In our crossed circulation experiments we found that neither waste
products nor metabolic poisons could be considered the principal
cause of the brain-cell changes. We found that in the production
both of muscular action and of fever there were brain-cell changes
which showed a quantita-tive relation to the temperature changes
or to the muscular work done. We observed that under deep
morphinization the febrile response or the muscular work done was
either diminished or eliminated and that the brain-cell changes were
correspondingly diminished or eliminated. We found also that brain-cell
changes and muscular work followed electric stimulation alone.
I conclude, therefore, that the brain-cell changes are work changes.

We shall next consider other organs of the kinetic system in their
relation to muscular activity, to emotion, to consciousness,
to sleep, to hibernation, and to heat production.

The Adrenals

In our extensive study of the brain in its relation to the production
of energy and the consequent exhaustion caused by fear and rage;
by the injection of foreign proteins, of bacterial toxins,
and of strychnin; by anaphylaxis; by the injection of thyroid extract,
of adrenalin, and of morphin, we found that, with the exception
of morphin, each of these agents produced identical changes in
the brain-cells. As we believed that the adrenals were intimately
associated with the brain in its activities, we concluded that
the adrenals also must have been affected by each of these agents.
To prove this relation, we administered the above-mentioned
stimuli to animals and studied their effects upon the adrenals
by functional, histologic, and surgical methods, the functional
tests being made by Cannon's method.

Functional Study of the Adrenals.--Our method of applying
the Cannon test for adrenalin was as follows: (_a_) The blood
of the animals was tested before the application of the stimulus.
If this test was negative, then (_b_) the stimulus was applied
and the blood again tested. If this second test was negative,
a small amount of adrenalin was added. If a positive reaction
was then given, the negative result was accepted as conclusive.
(_c_) If the control test was negative, then the stimulus was given.
If the blood after stimulation gave a positive result for adrenalin,
a second test of the same animal's blood was made twenty-five minutes
or more later. If the second test was negative, then the positive
result of the first test was accepted as conclusive.

We have recorded 66 clear-cut experiments on dogs, which show that
after fear and rage, after anaphylaxis, after injections of indol
and skatol, of leucin and creatin, of the toxins of diphtheria and
colon bacilli, of streptococci and staphylococci, of foreign proteins,
and of strychnin, the Cannon test for adrenalin was positive.
The test was negative after trauma under anesthesia, and after
intravenous injections of thyroid extract, of thyroglobin,
and of the juices of various organs injected into the same animal from
which the organs were taken. Placental extract gave a positive test.
The test was sometimes positive after electric stimulation
of the splanchnic nerves. On the other hand, if the nerve supply
to the adrenals had been previously divided, or if the adrenals
had been previously excised, then the Cannon test was negative
after the administration of each of the foregoing adequate stimuli.
Blood taken directly from the adrenal vein gave a positive result,
but under deep morphinization the blood from the adrenal vein
was negative, and under deep morphinization the foregoing adequate
stimuli were negative.

In brief, the agencies that in our brain-cell studies were found to
cause hyperchromatism followed by chromatolysis gave positive results
in the Cannon test for adrenalin (Fig. 62). The one agent which was
found to protect the brain against changes in the Nissl substance--
morphin--gave a negative result in the Cannon test for adrenalin.
After excision of the adrenals, or after division of their nerve supply,
all Cannon tests for adrenalin were negative.

Histologic Study of the Adrenals.--Histologic studies of the adrenals
after the application of the adequate stimuli which gave positive
results to the Cannon test for adrenalin are now in progress,
and thus far the histologic studies corroborate the functional tests.

In hibernating woodchucks, the cells of the adrenal cortex were found
to be vacuolated and shrunken. In one hundred hours of insomnia,
in surgical shock, in strong fear, in exhaustion from fighting,
after peptone injections, in acute infections, the adrenals undergo
histologic changes characteristic of exhaustion (Figs. 66 to 67).

We have shown that brain and adrenal activity go hand in hand,
that is, that the adrenal secretion activates the brain, and that
the brain activates the adrenals. The fundamental question which now
arises is this: Are the brain and the adrenals interdependent?
A positive answer may be given to this question, for the evidence
of the dependence of the brain upon the adrenals is as clear as is
the evidence of the dependence of the adrenals upon the brain.
(1) After excision of the adrenals, the brain-cells undergo
continuous histologic and functional deterioration until death.
During this time the brain progressively loses its power
to respond to stimuli and there is also a progressive loss
of muscular power and a diminution of body temperature.
(2) {illust. caption = FIG. 66.In our crossed circulation experiments
we found that adrenalin alone could cause increased brain activity,
while histologically we know that adrenalin alone causes an increase
of the Nissl substance. An animal, both of whose adrenals
had been excised, showed no hyperchromatism in the brain-cells
after the injection of strychnin, toxins, foreign proteins, etc.
(3) When the adrenal nerve supply is divided (Cannon-Elliott), then
there is no increased adrenal activity in response to adequate stimuli.

From these studies we are forced to conclude not only that the brain
and adrenals are interdependent, but that the brain is actually
more dependent upon the adrenals than the adrenals upon the brain,
since the brain deteriorates progressively to death without the adrenals,
while the adrenal whose connection with the brain has been broken
by the division of its nerve supply will still produce sufficient
adrenalin to support life.

From the strong affinity of the brain-cells for adrenalin which was
manifested in our experiments we may strongly suspect that the Nissl
substance is a volatile, extremely unstable combination of certain
elements of the brain-cells and adrenalin, because the adrenals alone
do not take the Nissl stain and the brain deprived of adrenalin
also does not take Nissl stain. The consumption of the Nissl
substance in the brain-cells is lessened or prevented by morphin,
as is the output of adrenalin; and the consumption of the Nissl
substance is also lessened or prevented by nitrous oxid.
But morphin does not prevent the action of adrenalin injected
into the circulation, hence the control of morphin over energy
expenditure is exerted directly on the brain-cells. Apparently morphin
and nitrous oxid both act through this interference with oxidation
in the brain. We, therefore, conclude that within a certain range
of acidity of the blood adrenalin can unite with the brain-cells
only through the mediation of oxygen, and that the combination
of adrenalin, oxygen, and certain brain-cell constituents
causes the electric discharge that produces heat and motion.
In this interrelation of the brain and the adrenals we have what is,
perhaps, the master key to the automatic action of the body.
Through the special senses environmental stimuli reach the brain
and cause it to liberate energy, which in turn activates certain
other organs and tissues, among which are the adrenals. The increased
output of adrenalin activates the brain to still greater activity,
as a result of which again the entire sympathetic nervous system
is further activated, as is manifested by increased heart action,
more rapid respiration, raised blood-pressure, increased output
of glycogen, increased power of the muscles to metabolize glucose, etc.

If this conclusion be well founded, we should find corroborative evidence
in histologic changes in that great storehouse of potential energy,
the liver, as a result of the application of each of the adequate
stimuli which produced brain-cell and adrenal changes.

The Liver

Prolonged insomnia, prolonged physical exertion, infections, injections of
toxins and of strychnin, rage and fear, physical injury under anesthesia,
in fact, all the adequate stimuli which affected the brain and
the adrenals, produced constant and identical histologic changes
in the liver--the cells stained poorly, the cytoplasm was vacuolated,
the nuclei were crenated, the cell membranes were irregular, the most
marked changes occurring in the cells of the periphery of the lobules
(Figs. 69 and 70). In prolonged insomnia the striking changes
in the liver were repaired by one seance of sleep.

Are the histologic changes in the liver cells due to metabolism or toxic
products, or are they "work" changes incident to the conversion of latent
into kinetic energy? Are the brain, adrenals, and liver interdependent?
The following facts establish the answers to these queries:

(1) The duration of life after excision of the liver is about
the same as after adrenalectomy--approximately eighteen hours.

(2) The amount of glycogen in the liver was diminished in all the
experiments showing brain-adrenal activity; and when the histologic
changes were repaired, the normal amount of glycogen was again found.

(3) In crossed circulation experiments changes were found in the liver
of the animal whose brain received the stimulus.

From these premises we must consider that the brain, the adrenals,
and the liver are mutually dependent on one another for the conversion
of latent into kinetic energy. Each is a vital organ, each equally vital.
It may be said that excision of the brain may apparently cause death
in less time than excision of the liver or adrenals, but this statement
must be modified by our definition of death. If all the brain
of an animal be removed by decapitation, its body may live on for at
least eleven hours if its circulation be maintained by transfusion.
An animal may live for weeks or months after excision of the cerebral
hemispheres and the cerebellum, while an overtransfused animal may
live many hours, days even, after the destruction of the medulla.
It is possible even that the brain actually is a less vital organ
than either the adrenals or the liver.

In our research to discover whether any other organs should be
included with the brain, the adrenals, and the liver in this mutually
interdependent relation, we hit upon an experiment which throws
light upon this problem.

Groups of rabbits were gently kept awake for one hundred hours
by relays of students, an experiment which steadily withdrew
energy but caused not the slightest physical or emotional injury
to any of them; no drug, toxin, or other agent was given to them;
they were given sufficient food and drink. In brief, the internal
and external environments of these animals were kept otherwise normal
excepting for the gentle stimuli which insured continued wakefulness.
This protracted insomnia gradually exhausted the animals completely,
some to the point of death even. Some of the survivors were killed
immediately after the expiration of one hundred hours of wakefulness,
others after varying intervals.

Histologic studies were made of every tissue and organ in the body.
Three organs, the brain, the adrenals, and the liver, and these three only,
showed histologic changes. In these three organs the histologic changes
were marked, and were almost wholly repaired by one seance of sleep.
In each instance these histologic changes were identical with
those seen after physical exertion, emotions, toxins, etc.[*] It
would appear, then, that these three organs take the stress of life--
the brain is the "battery," the adrenals the "oxydizer," and the liver
the "gasoline tank."  This clear-cut insomnia experiment corresponds
precisely with our other brain-adrenal observations.

[*] Further studies have given evidence that the elimination of the acids
resulting from energy-transformation as well as the conversion
of energy stored in the kinetic organs causes histologic changes
in the liver, the adrenals, and possibly in the brain.

With these three kinetic organs we may surely associate also the
"furnace," the muscles, in which the energy provided by the brain,
adrenals, and liver, plus oxygen, is fabricated into heat and motion.

Benedict, in his monumental work on metabolism, has demonstrated
that in the normal state, at least, variations in the heart-beat
parallel variations in metabolism. He and others have shown also that
all the energy of the body, whether evidenced by heat or by motion,
is produced in the muscles. In the muscles, then, we find the fourth
vital link in the kinetic chain. The muscles move the body,
circulate the blood, effect respiration, and govern the body temperature.
They are the passive servants of the brain-adrenal-liver syndrome.

Neither the brain, the adrenals, the liver, nor the muscles, however,
nor all of these together, have the power to change the rate of
the expenditure of energy; to make possible the increased expenditure
in adolescence, in pregnancy, in courting, and mating, in infections.
No one of these organs, nor all of them together, can act as a
pace-maker or sensitizer. The brain acts immediately in response
to the stimuli of the moment; the adrenals respond instantly
to the fickle brain and the effects of their actions are fleeting;
the liver contains fuel only and cannot activate, and the muscles
in turn act as the great furnace in which the final transformation
into available energy is made. The Thyroid

Another organ--the thyroid--has the special power of governing
the RATE OF DISCHARGE of energy; in other words, the thyroid is the
pace-maker. Unfortunately, the thyroid cannot be studied to advantage
either functionally or histologically, for there is as yet no available
test for thyroid secretion in the blood as there is for adrenalin,
and thyroid activity is not attended by striking histologic changes.
Therefore the only laboratory studies which have been satisfactory
thus far are those by which the iodin content of the thyroid
has been established. Iodin is stored in the colloid lacunae
of the thyroid and, in combination with certain proteins,
is the active agent of the thyroid.

Beebe has shown that electric stimulation of the nerve supply of
the thyroid diminishes the amount of iodin which it contains, and it
is known that in the hyperactive thyroid in Graves' disease the iodin
content is diminished. The meagerness of laboratory studies, however,
is amply compensated by the observations which the surgeon has been
able to make on a vast scale--observations which are as definite
as are the results of laboratory experiments.

The brain-cells and the adrenals are securely, concealed from
the eye of the clinician, hence the changes produced in them
by different causes escape his notice, but the thyroid has always
been closely scrutinized by him. The clinician knows that every
one of the above-mentioned causes of increased brain-cell, adrenal,
liver and muscle activity may cause an increase in the activity
of both the normal or the enlarged thyroid; and lie knows only too
well that in a given case of exophthalmic goiter the same stimuli
which excite the brain, the adrenals, the liver, and the muscles
to increased activity will also aggravate this disease.

The function of the thyroid in the kinetic chain is best evidenced,
however, by its role in the production of fever. Fever results
from the administration of thyroid extract alone in large doses.
In the hyperactivity of the thyroid in exophthalmic goiter one sees
a marked tendency to fever, in severe cases there is daily fever.
In fact, in Graves' disease we find displayed to an extraordinary
degree an exaggeration of the whole action of the kinetic mechanism.

We have stated that in acute Graves' disease there is a tendency
to the production of spontaneous fever, and that there is a magnified
diurnal variation in temperature which is due to an increased output
of energy in even the normal reaction producing consciousness. In Graves'
disease there is, therefore, a state of intensified consciousness, which is
associated with low brain thresholds to all stimuli--both to stimuli
that cause muscular action and to stimuli that cause fever. The intensity
of the kinetic discharge is seen in the constant fine tremor.
It is evident that the thresholds of the brain have been sensitized.
In this hypersensitization we find the following strong evidence as to
the identity of the various mechanisms for the production of fever.
In the state of superlative sensitization which is seen in Graves'
disease we find that the stimuli that produce muscular movement,
the stimuli that produce emotional phenomena, and the stimuli that
produce fever are as nearly as can be ascertained equally effective.
Clinical evidence regarding this point is abundant, for in
patients with Graves' disease we find that the three types
of conversion of energy resulting from emotional stimulation,
from infection stimulation, and from nociceptor stimulation
(pain), are, as nearly as can be judged, equally exaggerated.
In the acute cases of Graves' disease the explosive conversion
of latent energy into heat and motion is unexcelled by any other
known normal or pathologic phenomenon. Excessive thyroid secretion,
as in thyrotoxicosis from functioning adenomata, and excessive
thyroid feeding, cause all the phenomena of Graves' disease except
the exophthalmos and the emotional facies (Figs. 15 and 23).
The ligation of arteries, the division of its nerve supply,
or the excision of part of the gland, may reverse the foregoing picture
and restore the normal condition. The patient notes the effect
on the second day and often within a week is relatively quiescent.
On the contrary, if there is thyroid deficiency there results
the opposite state, a reptilian sluggishness.

At will, then, through diminished, normal, or excessive administration
of thyroid secretion, we may produce an adynamic, a normal,
or an excessively dynamic state. By the thyroid influence,
the brain thresholds are lowered and life becomes exquisite;
without its influence the brain becomes a globe of relatively
inert substance. Excessive doses of iodin alone cause
most of the symptoms of Graves' disease. As we have stated,
the active constituent of the thyroid is iodin in a special
protein combination which is stored in the colloidal spaces.
Hence one would not expect to find changes in the cells of the thyroid
gland as a result of increased activity unless it be prolonged.

We have thus far considered the normal roles played by the brain,
the adrenals the liver, the muscles, and the thyroid in transforming
latent into kinetic energy in the form of heat and motion as an
adaptive response to environmental stimuli.

The argument may be strengthened, however, by the discussion of
the effect of the impairment of any of these links in the kinetic
chain upon the conversion of latent into kinetic energy.

Effect Upon the Output of Energy of Impaired or Lost Function
of Each of the Several Links in the Kinetic Chain

(1) _The Brain_.--In cerebral softening we may find all the organs
of the body comparatively healthy excepting the brain.
As the brain is physically impaired it cannot normally stimulate
other organs to the conversion of latent energy into heat or
into motion, but, on the contrary, in these cases we find feeble
muscular and intellectual power. I believe also that in patients
with cerebral softening, infections such as pneumonia show a lower
temperature range than in patients whose brains are normal.

(2) _The Adrenals_.--In such destructive lesions of the adrenals
as Addison's disease one of the cardinal symptoms is a subnormal
temperature and impaired muscular power. Animals upon whom double
adrenalectomy has been performed show a striking fall in temperature,
muscular weakness,--after adrenalectomy the animal may not be able
to stand even,--and progressive chromatolysis.

(3) _The Liver_.--When the function of the liver is impaired
by tumors, cirrhosis, or degeneration of the liver itself,
then the entire energy of the body is correspondingly diminished.
This diminution of energy is evidenced by muscular and mental weakness,
by diminished response and by gradual loss of efficiency which finally
reaches the state of asthenia.

(4) _The Muscles_.--It has been observed clinically that if the muscles
are impaired by long disuse, or by a disease such as myasthenia gravis,
then the range of production of both heat and motion is below normal.
This is in agreement with the experimental findings that anesthetics,
curare, or any break in the muscle-brain connection causes diminished
muscular and heat production.

(5) _The Thyroid_.--In myxedema one of the cardinal symptoms
is a persistently subnormal temperature and, though prone
to infection, subjects of myxedema show but feeble febrile response
and readily succumb. This clinical observation is strikingly
confirmed by laboratory observations; normal rabbits subjected
to fear showed a rise in temperature of from one to three degrees,
while two rabbits whose thyroids had been previously removed and who
had then been subjected to fright showed much less febrile response.
Myxedema subjects show a loss of physical and mental energy
which is proportional to the lack of thyroid. Deficiency in any
of the organs of the kinetic chain causes alike loss of heat,
loss of muscular and emotional action, of mental power, and of the power
of combating infections--the negative evidence thus strongly supports
the positive. By accumulating all the evidence we believe we
are justified in associating the brain, the adrenals, the thyroid,
the muscles, and the liver as vital links in the kinetic chain.
Other organs play a role undoubtedly, though a minor one.

Studies in Hydrogen Ion Concentration in Activation of the Kinetic System

Having established the identity of some, at least, of the organs
which constitute the kinetic chain, we endeavored to secure still
further evidence regarding the energy-transforming function of these
organs by making studies of the H-ion concentration of the blood,
as one would expect, _prima facie_, that the normal reaction would
be altered by kinetic activation.[*]

[*] The H-ion observations were made in my laboratory by Dr. M. L. Menten.

H-ion concentration tests were made after the application
of the adequate stimuli by which the function of the kinetic
organs had been determined, and we studied also the effect upon
the acidity of the blood of strychnin convulsions after destruction
of the medulla; of deep narcotization with morphin before anesthesia;
of deep narcotization with morphin after the H-ion concentration
had already been increased by fear, by anger, by exertion,
by injury under anesthesia, or by anesthesia alone.

The complete data of these experiments will be later reported in
a monograph; here it is sufficient to state that anger, fear, injury,
muscular exertion, inhalation anesthesia, strychnin, alcohol, in fact,
all the stimuli which we had already found to produce histologic
changes in the brain, the adrenals, and the liver-excepting
bacterial toxins--caused increased H-ion concentration.
Of striking significance is the fact that morphin alone caused
no change in the H-ion concentration, while if administered before
the application of a stimulus which by itself produced increased
H-ion concentration, the action of that stimulus was neutralized
or postponed. If, however, morphin was administered after increased
acidity had been produced by any stimulus, or by inhalation anesthesia,
then the time required for the restoration of the normal alkalinity
was much prolonged, and in some instances the power of acid
neutralization was permanently lost.

After excision of the liver, the normal H-ion concentration
was maintained for periods varying from one to several hours,
after which the concentration (acidity) began to increase as
the vitality of the animal began to decline, the concentration
(acidity) increasing rapidly until death. After excision of
the adrenals the blood remained normal for from four to six hours,
when the H-ion concentration increased rather suddenly,
the increase being synchronous with the incidence of the phenomena
which immediately preceded death.

In none of these cases was it determined whether the increased
H-ion concentration was due to other causes of death or whether
death was due to the increased acidity.

It is also significant that after the application of each of
the adequate stimuli which increased the H-ion concentration
of the blood in other parts of the body the blood from the adrenal
vein showed a slight diminution in acidity, as, in most instances,
did the blood from the hepatic vein also.

In fact, the H-ion concentration of the blood in the adrenal vein
was less than in the blood of any other part of the circulation.

Kinetic Diseases

If our conclusions are sound, then in the kinetic system we find
an explanation of many diseases, and having found the explanation,
we may find new methods of combating them.

When the kinetic system is driven at an overwhelming rate of speed,--
as by severe physical injury, by intense emotional excitation,
by perforation of the intestines, by the pointing of an abscess
into new territory, by the sudden onset of an infectious disease,
by an overdose of strychnin, by a Marathon race, by a grilling fight,
by foreign proteins, by anaphylaxis,--the result of these acute
overwhelming activations of the kinetic system is clinically
designated shock, and according to the cause is called traumatic shock,
toxic shock, anaphylactic shock, drug shock, etc.

The essential pathology of shock is identical whatever the cause.
If, however, instead of an intense overwhelming activation,
the kinetic system is continuously or intermittently overstimulated
through a considerable period of time, as long as each of the links
in the kinetic chain takes the strain equally the result will be
excessive energy conversion, excessive work done; but usually,
under stress, some one link in the chain is unable to take the strain
and then the evenly balanced work of the several organs of the kinetic
system is disturbed. If the brain cannot endure the strain,
then neurasthenia, nerve exhaustion, or even insanity follows.
If the thyroid cannot endure the strain, it undergoes hyperplasia,
which in turn may result in a colloid goiter or in exophthalmic goiter.
If the adrenals cannot endure the strain, cardiovascular disease
may develop. If the liver cannot take the strain, then death from
acute acidosis may follow, or if the neutralizing effect of the liver
is only partially lost, then the acidity may cause Bright's disease.
Overactivation of the kinetic system may cause glycosuria and diabetes.

Identical physical and functional changes in the organs of
the kinetic system may result from intense continued stimulation
from any of the following causes: Excessive physical labor,
athletic exercise, worry or anxiety, intestinal autointoxication,
chronic infections, such as oral sepsis, tonsillitis, and adenoids;
chronic appendicitis, chronic cholecystitis, colitis, and skin infections;
the excessive intake of protein food (foreign protein reaction);
emotional strain, pregnancy, stress of business or professional life--
all of which are known to be activators of the kinetic system.

From the foregoing statements we are able to understand
the muscular weakness following fever; we can understand why
the senile have neither muscular power nor strong febrile reaction;
why long-continued infections produce pathologic changes in the organs
constituting the kinetic chain; why the same pathologic changes
result from various forms of activation of the kinetic system.
In this hypothesis we find a reason why cardiovascular disease may
be caused by chronic infection, by auto-intoxication, by overwork,
or by emotional excitation. We now see that the reason why we find
so much difficulty in differentiating the numerous acute infections
from each other is because they play upon the same kinetic chain.
Our postulate harmonizes the pathologic democracy of the kinetic organs,
for it explains not only why, in many diseases, the pathologic
changes in these organs are identical, but why the same changes
are seen as the result of emotional strain and overwork.
We can thus understand how either emotional strain or acute or chronic
infection may cause either exophthalmic goiter or cardiovascular disease;
how chronic intestinal stasis with the resultant absorption of
toxins may cause cardiovascular disease, neurasthenia, or goiter.
Here is found an explanation of the phenomena of shock, whether the
shock be the result of toxins, of infection, of foreign proteins,
of anaphylaxis, of psychic stimuli, or of a surgical operation
with its combination of both psychic and traumatic elements.

This conception of the kinetic system has stood a crucial test by making
possible the shockless operation. It has offered a plausible explanation
of the cause and the treatment of Graves' disease. Will the kinetic
theory stand also the clinical test of controlling that protean
disease bred in the midst of the stress of our present-day life?
Present-day life, in which one must ever have one hand on the sword and
the other on the throttle, is a constant stimulus of the kinetic system.
The force of these kinetic stimuli may be lessened at the cerebral
link by intelligent control--a protective control is empirically
attained by many of the most successful men. The force of the kinetic
stimuli may be broken at the thyroid link by dividing the nerve supply,
reducing the blood supply, or by partial excision; or if the adrenals
feel the strain, the stimulating force may be broken by dividing
their nerve supply, reducing the blood supply, or by partial excision.
No theory is worth more than its yield in practice, but already we
have the shockless operation, the surgical treatment of Graves'
disease, and the control of shock and of the acute infections
by overwhelming morphinization (Figs. 62, 72, and 73).

Conclusions

To become adapted to their environment animals are transformers of energy.
This adaptation to environment is made by means of a system of organs
evolved for the purpose of converting potential energy into heat
and motion. The principal organs and tissues of this system are
the brain, the adrenals, the thyroid, the muscles, and the liver.
Each is a vital link, each plays its particular role, and one cannot
compensate for the other. A change in any link of the kinetic
chain modifies proportionately the entire kinetic system which is
no stronger than its weakest link.

In this conception we find a possible explanation of many diseases
one which may point the way to new and more effective therapeutic
measures than those now at our command.

ALKALESCENCE, ACIDITY, ANESTHESIA--A THEORY OF ANESTHESIA[*]

[*] Paper delivered before the Virginia Medical Association,
Washington, D. C., October 29, 1914.

Alkalis and bases compose the greater part of the food of man
and animals, the blood in both man and animals under normal conditions
being slightly alkaline or rather potentially alkaline; that is,
although in circulating blood the concentration of the OH-ions--
upon which the degree of alkalinity depends--is but little more
than in distilled water, yet blood has the power of neutralizing
a considerable amount of acid (Starling, Wells). At the time of death,
whatever its cause, the concentration of H-ions in the blood increases,--
the concentration of H-ions being a measure of acidity,--that is,
the potential or actual alkalinity decreases and the blood becomes
actually neutral or acid.

To determine what conditions tend to diminish the normal alkalinity
of the blood, many observations were made for me in my laboratory
by Dr. M. L. Menten to determine by electric measurements
the H-ion concentration of the blood under certain pathologic
and physiologic conditions.

As a result of these researches we are able to state that the H-ion
concentration of the blood--its acidity--is increased by excessive
muscular activity; excessive emotional excitation; surgical shock;
in the late stages of infection; by asphyxia; by strychnin convulsions;
by inhalation anesthetics; after excision of the pancreas, and in the late
stages of life after excision of the liver and excision of the adrenals.
Morphin and decapitation cause no change in the H-ion concentration.
Ether, nitrous oxid, and alcohol produce an increased acidity
of the blood which is proportional to the depth of anesthesia.

Many of the cases studied were near death, as would be expected,
since it is well known that a certain degree of acidity is
incompatible with life.

Since alkalis and bases preponderate in ingested food;
since alkalinity of the blood is diminished by bodily activity;
and since at the point of death the blood is always acid, we may
infer that some mechanism or mechanisms of the body were evolved
for the purpose of changing bases into acids that thus energy
might be liberated.

These observations lead naturally to the question, May not
acidity of itself be the actual final cause of death?
We believe that it may be so from the facts that--(1)
The intravenous injection of certain acids causes death quickly,
but that convulsions do not occur, since the voluntary muscles
lose their power of contraction; and (2) the intravenous injection
of acids causes extensive histologic changes in the brain,
the adrenals, and the liver which resemble the changes invariably
caused by activation of the kinetic system (Figs. 74 and 75). In view
of these facts may we not find that anesthesia and many instances
of unconsciousness are merely phenomena of acidity?

As has been stated already, we have found that the H-ion concentration
of the blood--its acidity--is increased by alcohol, by ether,
and by nitrous oxid. In addition our tests have shown that under
ether the increase of the H-ion concentration--acidity--is more
gradual than under nitrous oxid, an observation which accords well
with the fact that nitrous oxid more quickly induces anesthesia
than does ether.

Further striking testimony in favor of the hypothesis that
the production of acidity by inhalation anesthetics is the method
by which anesthesia itself is produced is found in the fact
that although lethal doses of acid cause muscular paralysis,
yet this paralysis may be mitigated by adrenalin--which is alkaline.
This observation may explain in part the remarkable success of
the method of resuscitation devised by me, in which animals "killed"
by anesthetics and asphyxia are revived by the use of adrenalin.

In animals under inhalation anesthesia Williams found that no
nerve-current could be detected by the Einthoven string galvanometer,
a fact which might be explained by postulating that nerve-currents
can flow from the brain to the muscles and glands only when there
is a difference of potential. Any variation from the normal
alkalinity of the body must change the difference in potential.
Since the nerve-currents in animals under anesthesia are not demonstrable
by any apparatus at our command, and since anesthesia produces acidity,
then we may infer that acidity reduces the difference in potential.
As long as there is life, a galvanometer of sufficient delicacy
would perforce detect, a nerve-current until the acidity increased
to such a point as to reduce the difference in potential to zero--
the point of death. If at this point a suitable alkali--
adrenalin solution--can be introduced quickly enough, the vital difference
in potential may be restored and the life processes will be renewed.
Bearing especially on this point is the fact that if adrenalin
in sufficient quantities be administered simultaneously with an acid,
it will not only prevent the fall in blood-pressure usually
caused by the acid, but will also prevent the histologic changes
in the brain, adrenals, and liver which are usually caused by
the intravenous injection of acids.

This hypothesis regarding the cause of anesthesia and unconsciousness
explains and harmonizes many facts. It explains how asphyxia,
overwhelming emotion, and excessive muscular exertion, by causing acidity,
may produce unconsciousness. It explains the acidosis which results
from starvation, from uremia, from diabetes, from Bright's disease,
and supplies a reason for the use of intravenous infusions of sodium
bicarbonate to overcome the coma of diabetes and uremia (Fig. 76).
It may explain the quick death from chloroform and nitrous oxid;
and may perhaps show why unconsciousness is so commonly the immediate
precursor of death.

One of the most noticeable immediate effects of the administration
of an inhalation anesthetic is a marked increase in the rapidity
and force of the respiration. The respiratory center has evidently
been evolved to act with an increase of vigor which is proportional--
within certain limits--to the increase in the H-ion concentration,
whereas the centers governing the voluntary muscles are inhibited.
In this antithetic reaction of the higher cortical centers and the lower
centers in the medulla to acidity we find a remarkable adaptation
which prevents the animal from killing itself by the further increase
in acidity which would be produced by muscular activity. That is,
as the acidity produced by muscular action increases and threatens life,
the respiratory action, by which carbon dioxid is eliminated and
oxygen supplied, is increased, while the driving power of the brain,
which produces acidity, is diminished or even inhibited entirely;
that is, the state of unconsciousness or anesthesia is reached.
We conclude first that, without this life-saving regulation,
animals under stress would inevitably commit suicide; and, second,
that it is probable that the remarkable phenomenon of anesthesia--
the coincident existence of unconsciousness and life--is due to this
antithetic action of the cortex and the medulla.

In the human, as in the animal, the degree of acidity parallels
the depth of inhalation anesthesia.

Within a few seconds after beginning nitrous oxid anesthesia the acidity
of the blood is increased. This rapid acidulation is synchronous
with almost instantaneous unconsciousness and increased respiration.
If the oxygen in the inhaled mixture be increased, a decrease in
acidity is again synchronous with lighter anesthesia and a decrease
in the respiratory rate.

If these premises be sound, we are justified in asserting that the state
of anesthesia is due to an induced acidity of the blood. If the acidity
is slight, then the anesthesia is slight and the force of the nerve
impulses is lessened, but the patient is still conscious of them.
As the acidity increases associative memory is lost, and the patient
is said to be unconscious: the centers governing the voluntary muscles
are not inhibited, however, and cutting the skin causes movements.
If the acidity is further increased, there is loss of muscular tone
and even the strong contact ceptor stimuli of a surgical operation
do not cause any muscular response, and, finally, the acidity may be
increased to the point at which the respiratory and circulatory centers
can no longer respond by increased effort, and anesthetic death--
that is, ACID death--follows.

Certain clinical phenomena are clarified by this theory and serve
to substantiate it. For example, it is well known that inhalation
anesthesia precipitates the impending acidosis which results
from starvation, from extreme Graves' disease, from great exhaustion,
from surgical shock, and from hemorrhage, and which is present
when death from any cause is imminent.

We see, therefore, that anesthesia is made possible, first, by the fact
that inhalation anesthetics cause acidity, and, second, by the antithetic
adaptation of the higher centers in the brain and of the centers
governing respiration and circulation.

In deep contrast to the action of inhalation anesthetics is that
of narcotics. Deep narcotization with morphin and scopolamin is
induced slowly; the respiratory and pulse-rate are progressively lessened--
and there is no acidity.

By our researches we have established in what consists the generic
difference between inhalation anesthetics and narcotics.
In our experiments no increase in the H-ion concentration was produced
by morphin or by scopolamin, no matter how deep the narcotization.
In animals already narcotized by morphin the production of acid by any
of the acid-producing stimuli was delayed or prevented. On the other hand,
in animals in which an acidity had already been produced by ether,
by shock, by anger, or by fear, the later administration of morphin
delayed or inhibited entirely the neutralization of the acidity.
In other words, morphin interferes with the normal mechanism by
which acidity is neutralized possibly because its inhibiting action
on the respiratory center is sufficient to overcome the stimulating
action of acidity on that center, for, as we have stated,
the neutralization of acidity is in large measure accomplished
by the increased respiration induced by the acidity itself.

SUMMARY

Acidity inhibits the functions of the cerebral cortex,
but stimulates those of the medulla. This antithetic reaction
to the stimulus of increased H-ion concentration is an adaptation
to prevent animals from committing suicide by over-activity,
for the mechanism for the initiation and control of the
transformation of energy is in the higher centers of the brain,
while an essential part of the mechanism for the neutralization
of acidity--the centers governing circulation and respiration--
is in the medulla. This explains many clinical phenomena--
why excessive acidity causes paralysis, why there is great thirst
after inhalation anesthesia, after excessive muscular activity,
excessive emotion--after all those activities which we have found
to be acid-producing, for water, like air, neutralizes acids.
The excessive use of alcohol, anesthetics, excessive work,
intense emotion, all produce lesions of the kidney and of the liver.
The explanation is found in the fact that all these stimuli
increase the acidity of the blood. and that, if long continued,
the neutralizing mechanism must be broken down and so the end-products
of metabolism are insufficiently prepared for elimination.

In view of these considerations we may well conclude that the maintenance
of the normal potential alkalinity of the blood is to be estimated
as the keystone of the foundation of life itself.

INDEX

ABDOMEN, diseases of, phylogenetic association and, 44 Acidity,
227 Adaptive energy, 176 variation in rate of energy discharge,
177 Adrenalin, Cannon's test for, 134, 196 injection of,
changes in brain-cells from, 186 Adrenals, 196 brain and,
relation of, 1.98 diseases of, effect of, on output of energy,
216 functional study of, 196 histologic study of, 198 Alcohol,
changes in brain-cells from, 116 Alkalescence, 227 Anemia, pain of,
77 Anesthesia, 2, 227 anoci-association and, differentiation, 34 effect
of trauma under, upon brain that remains awake, 3 inhalation,
cause of exhaustion of brain-cells as result of trauma under,
8 theory of, 227 Anger, 63, 70 Anoci-association, 34 anesthesia
and, differentiation, 34 Graves' disease and, 36 prevention
of shock by application of principle of, 36 Aristotle, 127 Asher,
:37 Associational centers, dulled, 47 Austin, 2, 55, 173

BASS, 159 Beebe, 213 Benedict, 212 Biologic consideration of
adaptive variation in amounts of energy stored in various animals,
176 Brain, adrenals and, relation of, 198 diseases of, effect of,
on output of energy, 216 effect of trauma under anesthesia oil,
3 functions, physical state of brain-cells and, relation between,
111 influence of fear on, 64 Brain-cells, cause of exhaustion
of as result of trauma under inhalation anesthesia, 8 changes in,
from alcohol, 116 from drugs, 113 from fatigue, 112 from fear,
112 from hemorrhage, 113 from injection of adrenalin, 186 from iodoform,
116 from strychnin, 113 in Graves' disease, 116 in infections,
116 in insanity, 120 in insomnia, 119 histologic changes in,
in relation to maintenance of consciousness and to production
of emotions, muscular activity, and fever, 182 physical state,
brain functions and, relation between, 111

CANNON, 57, 64, 68, 73, 133, 138, 196, 202 Cannon's test
for adrenalin, 134, 196 Cells, brain-, cause of exhaustion of,
as result of trauma under inhalation anesthesia, 8 changes in,
from alcohol, 116 from drugs, 113 from fatigue, 112 from fear,
112 from hemorrhage, 113 from injection of adrenalin, 186 from iodoform,
116 from strychnin, 113 in Graves' disease, 116 in infections,
116 in insanity, 120 in insomnia, 119 histologic changes in, in relation
to maintenance of consciousness and to production of emotions,
muscular activity, and fever, 182 physical state, brain functions and,
relation between, Ill Chemical noci-association in infections,
48 Cold pain, 83 sweat, 27 Contact pain, special, 78 Crying,
90 in exophthalmic goiter, 106

DARWIN, 12, 26, 30, 91, 127, 153 on phenomena of fear, 26 Disease,
mechanistic theory of, 157 Distance receptors, discharge of energy
through stimulation of, 25 Dog, spinal, 4 Dolley, 2, 10 Drugs,
changes in brain-cells from, 113

ELIOT, 1 Elliott, 202 Energy, adaptive, 176 Energy, discharge, rate of,
adaptive variation in, 177 nervous, cause of discharge of,
12 as result of trauma under inhalation anesthesia, 12 discharge of,
role of summation in, 30 through representation of injury,
25 through stimulation of distance receptors, 25 psychic discharge,
25 output of, effect of diseases of adrenals on, 216 of brain on,
216 of liver on, 216 of muscles on, 216 of thyroid on, 217 rate
of out put, influences that cause variation in, 177 Environment,
128, 130 Evacuation pain, 77 Exophthalmic goiter, 66 crying in,
106 fear and, resemblance between, 68 laughing in, 106

FATIGUE, changes in brain-cells from, 112 Fear, 26, 52, 55 changes
in brain-cells from, 112 Darwin on phenomena of, 26 Graves'
disease and, resemblance between, 68 influence of, on brain,
61 phenomena of, 56 Fly-trap, Venus', 151 Frankel, 68 Frazier,
82 Functional study of adrenals, 196

GOITER, exophthalmic, 66 crying in, 106 Goiter, exophthalmic, fear and,
resemblance between, 68 laughter in, 106 Graves' disease, 66
anoci-association and, 36 changes in brain-cells in, 116 crying in,
106 fear and, resemblance between, 68 laughter in, 106

HARVEY, 1,57 Headache, 80 Heat pain, 77 production in infections,
purpose and mechanism, 180 Hemorrhage, changes in brain-cells from,
113 Hippocrates, 127 Histologic changes in liver, 205 study of adrenals,
198 Hitchings, 173 Hodge, 10 Hornaday, 26 Hydrogen ion concentration
in activation of kinetic system, 217 Hyperthyroidism, 42

INFECTIONS, changes in brain-Cells in, 116 chemical noci-association in,
48 heat production in, purpose and mechanism, 180 pain of,
79 Inhalation anesthesia, cause of exhaustion of brain-cells as result
of trauma under, 8 trauma under, cause of discharge of nervous energy
as result of, 12 Insanity, changes in brain-cells in, 120 Insomnia,
changes in brain-cells in, 119 effect of, 205

Iodoform, changes in brain-cells from, 116

KINETIC diseases, 219 reaction, 93 system, 173

LABOR pains, 79 Laughter, 90 causes of, 91 in exophthalmic goiter,
106 Law, Sherrington's, 24 Light pain, 77 Liver, diseases of, effect of,
on output of energy, 216 histologic changes in, 205 Livingstone,
148 Lower, 42

MALARIA, 159 McKenzie, 162 Mechanistic theory of disease, 157 view
of psychology, 127 Medical problems, phylogenetic association
in relation to, 1 Menten, 2, 55, 173, 218, 227 Muscles, diseases of,
effect of, on output of energy, 216

NAGGING, 46 Nausea pains, 78 Nervous energy, cause of discharge of,
12 as result of trauma under inhalation anesthesia, 12 discharge of,
role of summation in, 30 through representation of injury,
25 through stimulation of distance receptors, 25 psychic discharge,
25 Neurasthenia, sexual, 43 Neuroses, postoperative, 46 traumatic,
46 Noci-association, chemical, in infections, 48 Nociceptors,
14 diseases and injuries of regions not endowed with, 47

PAIN, 77, 107, 144, 158 cold, 83 contact, special, 78 evacuation,
77 heat, 77 labor, 78 light, 77 nausea, 78 of anemia, 77 of infection,
79 pleasure, 78 post-operative, 89 site of, 83 traumatic, 89 Personality,
47 Phylogenetic association, diseases of abdomen and, 44 in relation
to certain medical problems, 1 to emotions, 55 Pleasure pains,
78 Postoperative neuroses, 46 pain, 89 Propagation of species,
152 Psychic discharge of energy, 25 Psychology, mechanistic view, 127

REACTION, kinetic, 93 Receptors, distance, discharge of energy
through stimulation of, 25 sexual, 53 ticklish, 19

SELF-PRESERVATION, 152 Sexual neurasthenia, 43 Sexual receptors,
53 Sherrington, 12, 13, 14, 24, 25, 48, 52, 132, 136, 158 Sherrington's
law, 24 Shock, prevention of, by application of principle of
anoci-association, 36 Sloan, 2, 14, .55, 173 Spinal dog, 4 Starling,
195, 227 Strychnin, changes in brain-cells from, 113 Summation,
role of, in discharge of nervous energy, 30 Sweat, cold, 27

TEST, Cannon's, for adrenalin, 134, 196 Thyroid gland, 213 diseases of,
effect of, on output of energy, 217 Ticklish receptors,
19 Trauma, cause of exhaustion of brain-cells as result of,
under inhalation anesthesia, 8 effect of, under anesthesia,
upon brain that remains awake, 3 under inhalation anesthesia,
cause of discharge of nervous energy as result of, 12 Traumatic neuroses,
46 pain, 89

VAUGHAN, 180 Venus' fly-trap, 149, 151

WEEPING, 90 Welch, 1 Wells, 227 Williams, 231 Worry, 74

          The End