The Origin and Nature of Emotions
by
George W. Crile

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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.

If, in the course of abdominal operations, rough manipulations
of the parietal peritoneum be made, there will be frequently
observed a marked increase in the respiratory rate and an increase
in the expiratory force which may be marked by the production
of an audible expiratory groan. Under light ether anesthesia,
severe manipulations of the peritoneum often cause such vigorous
contractions of the abdominal muscles that the operator is greatly
hindered in his work.

Among the unconscious responses to trauma under ether anesthesia
are purposeless moving, the withdrawal of the injured part, and,
if the anesthesia be sufficiently light and the trauma sufficiently
strong, there may be an effort toward escape from the injury.
In injury under ether anesthesia every grade of response may be seen,
from the slightest change in the respiration or in the blood-pressure
to a vigorous defensive struggle. As to the purpose of these
subconscious movements in response to injury, there can be no doubt--
THEY ARE EFFORTS TO ESCAPE FROM THE INJURY.

Picture what would be the result of a formidable abdominal operation
extending over a period of half an hour or more on an unanesthetized
human patient, during which extensive adhesions had been broken up,
or a large tumor dislodged from its bed! In such a case,
would not the nervous system discharge its energy to the utmost
in efforts to escape from the injury, and would not the patient suffer
complete exhaustion? If the traumata under inhalation anesthesia
are sufficiently strong and are repeated in sufficient numbers,
the brain-cells are finally deprived of their dischargeable nervous
energy and become exhausted just as exhaustion follows such strenuous
and prolonged muscular exertion as is seen in endurance tests.
Whether the energy of the brain be discharged by injury under anesthesia
or by ordinary muscular exertion, identical morphologic changes are
seen in the nerve-cells. In shock from injury (Fig. 2), in exhaustion
from overwork (Hodge and Dolley) (Fig. 4), and in exhaustion from pure fear
(Fig. 5), the resultant general functional weakness is similar--
in each case a certain length of time is required to effect recovery,
and in each there are morphologic changes in the brain-cells. It
is quite clear that in each of these cases the altered function
and form of the brain-cells are due to an _*excessive discharge
of nervous energy_. This brings us to the next question:
What determines the discharge of energy as a result of trauma
with or without inhalation anesthesia?


The Cause of the Discharge of Nervous Energy as a Result of Trauma
under Inhalation Anesthesia and under Normal Conditions


I looked into this problem from many viewpoints and there seemed
to be no solution until it occurred to me to seek the explanation
in certain of the postulates which make up the doctrine of evolution.
I realize fully the difficulty and the danger in attempting
to reach the generalization which I shall make later and in
the hypothesis I shall propose, for there is, of course, no direct
final proof of the truth of even the doctrine of evolution.
It is idle to consider any experimental research into the cause
of phenomena that have developed by natural selection during
millions of years. Nature herself has made the experiments on
a world-wide scale and the data are before us for interpretation.
Darwin could do no more than to collect all available facts and then
to frame the hypothesis by which the facts were best harmonized.
Sherrington, that masterly physiologist, in his volume entitled
"The Integrative Action of the Nervous System," shows clearly how
the central nervous system was built up in the process of evolution.
Sherrington has made free use of Darwin's doctrine in explaining
physiologic functions, just as anatomists have extensively
utilized it in the explanation of the genesis of anatomic forms.
I shall assume, therefore, that the discharge of nervous energy is
accomplished by the application of the laws of inheritance and association,
and I conclude that this hypothesis will explain many clinical phenomena.
I shall now present such evidence in favor of this hypothesis as time
and my limitations will admit, after which I shall point out certain
clinical facts that may be explained by this hypothesis.

According to the doctrine of evolution, every function owes
its origin to natural selection in the struggle for existence.
In the lower and simpler forms of animal life, indeed, in our
human progenitors as well, existence depended principally upon
the success with which three great purposes were achieved:
(1) Self-defense against or escape from enemies; (2) the acquisition
of food; and (3) procreation; and these were virtually the only purposes
for which nervous energy was discharged. In its last analysis,
in a biologic sense, this statement holds true of man today.
Disregarding for the present the expenditure of energy for procuring
food and for procreation, let us consider the discharge of energy
for self-preservation. The mechanisms for self-defense which we
now possess were developed in the course of vast periods of time
through innumerable intermediary stages from those possessed by
the lowest forms of life. One would suppose, therefore, that we must
now be in possession of mechanisms which still discharge energy on
adequate stimulation, but which are not suited to our present needs.
We shall point out some examples of such unnecessary mechanisms.
As Sherrington has stated, our skin, in which are implanted many
receptors for receiving specific stimuli which are transmitted
to the brain, is interposed between ourselves and the environment
in which we are immersed. When these stimuli reach the brain,
there is a specific response, principally in the form of
muscular action. Now, each receptor can be adequately stimulated
only by the particular factor or factors in the environment
which created the necessity for the existence of that receptor.
Thus there have arisen receptors for touch, for temperature,
for pain, etc. The receptors for pain have been designated _nociceptors_
(nocuous or harmful) by Sherrington.

On the basis of natural selection, nociceptors could have developed
in only those regions of the body which have been exposed to injury
during long periods of time. On this ground the finger, because it
is exposed, should have many nociceptors, while the brain, though the
most important organ of the body, should have no nociceptors because,
during a vast period of time, it has been protected by a skull.
Realizing that this point is a crucial one, Dr. Sloan and I made a series
of careful experiments. The cerebral hemispheres of dogs were exposed
by removing the skull and dura under ether and local anesthesia.
Then various portions of the hemispheres were slowly but
completely destroyed by rubbing them with pieces of gauze.
In some instances a hemisphere was destroyed by burning.
In no case was there more than a slight response of the centers governing
circulation and respiration, and no morphologic change was noted
in an histologic study of the brain-cells of the uninjured hemisphere.
The experiment was as completely negative as were the experiments
on the "spinal dog." Clinically I have confirmed these experimental
findings when I have explored the brains of conscious patients
with a probe to determine the presence of brain tumors.
Such explorations elicited neither pain nor any evidence of altered
physiologic functions. The brain, therefore, contains no mechanism--
no nociceptors--the direct stimulation of which can cause
a discharge of nervous energy in a self-defensive action.
That is to say, direct injury of the brain can cause no purposeful
nerve-muscular action, while direct injury of the finger does cause
purposeful nerve-muscular action. In like manner, the deeper portions
of the spinal region have been sheltered from trauma and they, too,
show but little power of causing a discharge of nervous energy
on receiving trauma. The various tissues and organs of the body
are differently endowed with injury receptors--the nociceptors
of Sherrington. The abdomen and chest when traumatized stand first
in their facility for causing the discharge of nervous energy, _i.
e_., THEY STAND FIRST IN SHOCK PRODUCTION. Then follow the extremities,
the neck, and the back. It is an interesting fact also that different
types of trauma elicit different responses as far as the consequent
discharge of energy is concerned.

Because it is such a commonplace observation, one scarcely realizes
the importance of the fact that clean-cut wounds inflicted
by a razor-like knife cause the least reaction, while a tearing,
crushing trauma causes the greatest response. It is a suggestive fact
that the greatest shock is produced by any technic which imitates
the methods of attack and of slaughter used by the carnivora.
_*In the course of evolution, injuries thus produced may well have
been the predominating type of traumata to which our progenitors
were subjected_. In one particular respect there is an analogy between
the response to trauma of some parts of the body of the individuals
of a species susceptible to shock and the response to trauma of the
individuals in certain other great divisions of the animal kingdom.
Natural selection has protected the crustaceans against their
enemies by protective armor, _e. g_., the turtle and the armadillo;
to the birds, it has given sharp eyes and wings, as, for instance,
the wild goose to another species--the skunk--it has given a noisome odor
for its protection. The turtle, protected by its armor against trauma,
is in a very similar position to that of the sheltered brain
of man and, like the brain, the turtle does not respond to trauma
by an especially active self-protective nerve-muscular response,
but merely withdraws its head and legs within the armored protection.
It is proverbially difficult to exhaust or to kill this animal by trauma.
The brain and other phylogenetically sheltered parts likewise give no
exhausting self-protective nerve-muscular response to trauma. The skunk
is quite effectively protected from violence by its peculiar odor.
This is indicated not only by the protective value of the odor itself,
but also by the fact that the skunk has no efficient nerve-muscular
mechanism for escape or defense; it can neither run fast nor can it
climb a tree. Moreover, in encounters it shows no fear and backs
rather than runs. The armadillo rolls itself into a ball for defense.
On these premises we should conclude that the turtle,
the armadillo, and the skunk have fewer nociceptors than has
a dog or man, and that they would show less response to trauma.
In two carefully conducted experiments on skunks and two on armadillos
(an insufficient number) the energy discharged in response to severe
and protracted trauma of the abdominal viscera was very much less than
in similar experiments on dogs, opossums, pigs, sheep, and rabbits.
It was indeed relatively difficult to exhaust the skunks and armadillos
by trauma. These experiments are too few to be conclusive,
but they are of some value and furnish an excellent lead.
It seems more than a coincidence that proneness to fear,
distribution of nociceptors, and susceptibility to shock go
hand-in-hand in these comparative observations (Figs. 6, 7, and 8).

The discharge of energy caused by an adequate mechanical stimulation
of the nociceptors is best explained in accordance with the law
of phylogenetic association. That is, injuries awaken those reflex
actions which by natural selection have been developed for the purpose
of self-protection. Adequate stimulation of the nociceptors for pain
is not the only means by which a discharge of nervous energy is caused.
Nervous energy may be discharged also by adequate stimulation
of the various ticklish regions of the body; the entire skin
surface of the body contains delicate ticklish receptors.
These receptors are closely related to the nociceptors for pain,
and their adequate stimulation by an insect-like touch
causes a discharge of energy,--a nerve-muscular reaction,--
resembling that developed for the purpose of brushing off insects.
This reflex is similar to the scratch reflex in the dog.
The discharge of energy is almost wholly independent of the will
and is a self-protective action in the same sense as is the response
to pain stimuli. The ear in man and in animals is acutely ticklish,
the adequate stimulus being any foreign body, especially a buzzing,
insect-like contact. The discharge of nervous energy in horses
and in cattle on adequate stimulation of the ticklish receptors
of the ear is so extraordinary that in the course of evolution it
must have been of great importance to the safety of the animal.
A similar ticklish zone guards the nasal chambers, the discharge of energy
here taking a form which effectively dislodges the foreign body.
The larynx is exquisitely ticklish, and, in response to any adequate
stimulus, energy is discharged in the production of a vigorous cough.
The mouth and pharynx have active receptors which cause the rejection
of noxious substances. The conjunctival reflex, though not
classed as ticklish, is a most efficient self-protective reflex.
I assume that there is no doubt as to the relation between
the adequate stimuli and the nerve-muscular response of the various
ticklish receptors of the surface of the skin, of the ear,
the nose, the eye, and the larynx. These mechanisms were developed
by natural selection as protective measures against the intrusion
of insects and foreign bodies into regions of great importance.
The discharge of energy in these instances is in accordance
with the laws of inheritance and association. The other ticklish
points which are capable of discharging vast amounts of energy
are the lateral chest-wall, the abdomen, the loins, the neck,
and the soles of the feet. The type of adequate stimuli of the soles
of the feet, the distribution of the ticklish points upon them,
and the associated response, leave no doubt that these ticklish points
were long ago established as a means of protection from injury.
Under present conditions they are of little value to man.

The adequate stimulus for the ticklish points of the ribs,
the loins, the abdomen, and the neck is deep isolated pressure,
probably the most adequate being pressure by a tooth-shaped body.
The response to tickling in these regions is actively and obviously
self-defensive. The horse discharges energy in the form of a kick;
the dog wriggles and makes a counter-bite; the man makes efforts
at defense and escape.

There is strong evidence that the deep ticklish points of the body
were developed through vast periods of fighting with teeth and claws
(Fig. 9). Even puppies at play bite each other in their ticklish
points and thus give a recapitulation of their ancestral battles
and of the real battles to come (Fig. 10). The mere fact that animals
fight effectively in the dark and always according to the habit
of their species supports the belief that the fighting of animals
is not an intellectual but a reflex process. There are no rules
which govern the conduct of a fight between animals. The events
follow each other with such kaleidoscopic rapidity that the process
is but a series of automatic stimulations and physiologic reactions.
Whatever their significance, therefore, it is certain that man did
not come either accidentally or without purpose into possession
of the deep ticklish regions of his chest and abdomen.
Should any one doubt the vast power that adequate stimulation
of these regions possesses in causing the discharge of energy,
let him be bound hand and foot and vigorously tickled for an hour.
What would happen? He would be as completely exhausted as though he had
experienced a major surgical operation or had run a Marathon race.

A close analogy to the reflex process in the fighting of animals
is shown in the role played by the sexual receptors in conjugation.
Adequate stimulation of either of these two distinct groups
of receptors, the sexual and the noci, causes specific behavior--
the one toward embrace, the other toward repulsion. Again, one of
the most peremptory causes of the discharge of energy is that due
to an attempt to obstruct forcibly the mouth and the nose so that
asphyxia is threatened. Under such conditions neither friend
nor foe is trusted, and a desperate struggle for air ensues.
It will be readily granted that the reactions to prevent suffocation
were established for the purpose of self-preservation, but the discharge
of nerve-muscular energy to this particular end is no more specific
and no more shows adaptive qualities than do the preceding examples.
Even the proposal to bind one down hand and foot excites resentment,
a feeling originally suggested by the need for self-preservation.
No patient views with equanimity the application of shackles
as a preparation for anesthesia.

We have now considered some of the causes of those discharges of nervous
energy which result from various types of harmful physical contact,
and have referred to the analogous, though antithetical,
response to the stimulation of the sexual receptors.
The response to the adequate stimuli of each of the several receptors
is a discharge of nerve-muscular energy of a specific type; that is,
there is one type of response for the ear, one for the larynx,
one for the pharynx, another for the nose, another for the eye,
another for the deep ticklish points of the chest and the abdomen,
quite another for the delicate tickling of the skin, and still
another type of response to sexual stimuli.

According to Sherrington, a given receptor has a low threshold
for only one, its own specific stimulus, and a high threshold
for all others; that is, the doors that guard the nerve-paths
to the brain are opened only when the proper password is received.
According to Sherrington's law, the individual as a whole responds
to but one stimulus at a time, that is, only one stimulus
occupies the nerve-paths which carry the impulses as a result
of which acts are performed, _i. e_., the final common path.
As soon as a stronger stimulus reaches the brain it dispossesses
whatever other stimulus is then occupying the final common path--
the path of action. The various receptors have a definite order
of precedence over each other (Sherrington). For example, the impulse
from the delicate ticklish points of the skin, whose adequate
stimulus is an insect-like contact, could not successfully compete
for the final common path with the stimulus of a nociceptor.
The stimulus of a fly on the nose would be at once superseded by
the crushing of a finger. In quick succession do the various receptors
(Sherrington) occupy the final common path, but each stimulus is for
the time the sole possessor, hence the nervous system is integrated
(connected) to act as a whole. Each individual at every moment
of life has a limited amount of dischargeable nervous energy.
This energy is at the disposal of any stimulus that obtains possession
of the final common path, and results in the performance of an act.
Each discharge of energy is subtracted from the sum total of stored
energy and, whether the subtractions are made by the excitation
of nociceptors by trauma, by tickling, by fighting, by fear,
by flight, or by the excitation of sexual receptors, by any
of these singly or in combination with others, the sum total of
the expenditure of energy, if large enough, produces exhaustion.
Apparently there is no distinction between that state of exhaustion
which is due to the discharge of nervous energy in response
to trauma and that due to other causes. The manner of the
discharge of energy is specific for each type of stimulation.
On this conception, traumatic shock takes its place as a natural
phenomenon and is divested of its mask of mystery.


The Discharge of Energy through Stimulation of the Distance Receptors,
or through Representation of Injury (Psychic)


We will now turn from the discussion of the discharge of nervous energy by
mechanical stimuli to the discharge of energy through mental perception.
_Phylogenetic_ association may result from stimulation of the distance
receptors through sight, hearing, smell, or by a representation
of physical experiences, as well as from physical contact.
The effect upon the organism of the representation of injury
or of the perception of danger through the distance receptors is
designated FEAR. Fear is as widely distributed in nature as is its cause,
that is, fear is as widely distributed as injury. Animals under
the stimulus of fear, according to W. T. Hornaday, not only may exhibit
preternatural strength, but also may show strategy of the highest order,
a strategy not seen under the influence of a lesser stimulus.
In some animals fear is so intense that it defeats escape; this is
especially true in the case of birds in the presence of snakes.
The power of flight has endowed the bird with an easy means of escape
from snakes, especially when the encounter is in the tops of trees.
Here the snake must move cautiously, else he will lose his equilibrium;
his method of attack is by stealth. When the snake has stalked
its prey, the bird is often so overcome by fear that it cannot fly
and so becomes an easy victim (Fig. 11). The phenomena of fear
are described by Darwin as follows:

"Fear is often preceded by astonishment, and is so near akin to it that
both lead to the senses of sight and hearing being instantly aroused.
In both cases the eyes and mouth are widely opened and the
eyebrows raised. The frightened man at first stands like a statue,
motionless and breathless, or crouches down as if instinctively
to escape observation. The heart beats quickly and violently,
so that it palpitates or knocks against the ribs. * * * That the skin
is much affected under the sense of great fear we see in the marvelous
and inexplicable manner in which perspiration immediately exudes from it.
This exudation is all the more remarkable as the surface is then cold,
and hence the term, `a cold sweat'; whereas the sudorific glands
are properly excited into action when the surface is heated.
The hairs also on the skin stand erect, and the superficial
muscles shiver. In connection with the disturbed action of the heart,
the breathing is hurried. The salivary glands act imperfectly;
the mouth becomes dry, and is often opened and shut. I have also
noticed that under slight fear there is a strong tendency to yawn.
One of the best-marked symptoms is the trembling of all the
muscles of the body; and this is often first seen in the lips.
From this cause, and from the dryness of the mouth, the voice
becomes husky and indistinct, or may altogether fail.
* * * As fear increases into agony of terror, we behold, as under
all violent emotions, diversified results. The heart beats wildly,
or may fail to act and faintness ensues; there is death-like pallor;
the breathing is labored; the wings of the nostrils are widely dilated;
`there is a gasping and convulsive motion of the lips, a tremor
on the hollow cheek, a gulping and catching of the throat';
the uncovered and protruding eyeballs are fixed on the object of terror;
or they may roll restlessly from side to side. * * * The pupils
are said to be enormously dilated. All the muscles of the body
may become rigid, or may be thrown into convulsive movements.
The hands are alternately clenched and opened, often with a
twitching movement. The arms may be protruded, as if to avert
some dreadful danger, or may be thrown wildly over the head.
* * * In other cases there is a sudden and uncontrollable tendency
to headlong flight; and so strong is this that the boldest soldiers
may be seized with a sudden panic. As fear rises to an extreme pitch,
the dreadful scream of terror is heard. Great beads of sweat
stand on the skin. All the muscles of the body are relaxed.
Utter prostration soon follows, and the mental powers fail.
The intestines are affected. The sphincter muscles cease
to act and no longer retain the contents of the body.
* * * Men, during numberless generations, have endeavored
to escape from their enemies or danger by headlong flight,
or by violently struggling with them; and such great exertions
will have caused the heart to beat rapidly, the breathing to
be hurried, the chest to heave, and the nostrils to be dilated.
As these exertions have often been prolonged to the last extremity,
the final result will have been utter prostration, pallor, perspiration,
trembling of all the muscles, or their complete relaxation.
And now, whenever the emotion of fear is strongly felt, though it
may not lead to any exertion, the same results tend to reappear,
through the force of inheritance and association"[*] (Fig. 12).


[*] Darwin: Expression of the Emotions in Man and Animals.


In an experimental research, we found evidence that the physiologic
phenomena of fear have a physical basis. This evidence is found
in the morphologic alterations in the brain-cells, which are similar
to those observed in certain stages of surgical shock and in fatigue
from muscular exertion (Figs. 2, 4, 5, and 13). For the present,
we shall assume that fear is a REPRESENTATION of trauma.
Because fear was created by trauma, fear causes a discharge of the energy
of the nervous system by the law of phylogenetic association.
The almost universal fear of snakes, of blood, and of death
and dead bodies may have such a phylogenetic origin.
It was previously stated that under the stimulus of fear animals
show preternatural strength. An analysis of the phenomena of fear
shows that, as far as can be determined, all the functions of the body
requiring the expenditure of energy, and which are of no direct
assistance in the effort toward self-preservation, are suspended.
In the voluntary expenditure of muscular energy, as in the chase,
the suspension of other functions is by no means so complete.
Fear and trauma may drain to the last dreg the dischargeable
nervous energy, and, therefore, the greatest possible exhaustion
may be produced by fear and trauma.


Summation

In the discharge of energy, summation plays an important role.
Summation is attained by the repetition of stimuli at such a rate
that each succeeding stimulus is applied before the nerve-cells
have returned to the resting stage from the preceding stimulus.
If drops of water fall upon the skin from a sufficient height to cause
the slightest unpleasant sensation, and at such a rate that before
the effect of the stimulus of one drop has passed another drop
falls in precisely the same spot, there will be felt a gradually
increasing painful sensation which finally becomes unbearable.
This is summation of stimuli. When, for a long time, a patient
requires frequent painful wound dressings, there is a gradual
increase in the acuteness of the pain of the receptors.
This is caused by summation. In a larger sense, the entire behavior
of the individual gives considerable evidence of summation, _e.
g_., in the training of athletes, the rhythmic discharge of muscular
energy at such intervals that the resting stage is not reached
before a new exercise is given results in a gradual ascent
in efficiency until the maximum is reached. This is summation,
and summation plays a large role in the development of both normal
and pathologic phenomena.

We have now pointed out the manner in which at least
a part of the nervous energy of man may be discharged.
The integrative action of the nervous system and the discharge
of nervous energy by phylogenetic association may be illustrated
by their analogy to the action of an electric automobile.
The electric automobile is composed of four principal parts:
The motor and the wheels (the muscular system and the skeleton);
the cells of the battery containing stored electricity
(brain-cells, nervous energy); the controller, which is connected
with the cells by wiring (the receptors and the nerve-fibers);
and an accelerator for increasing the electric discharge
(thyroid gland?). The machine is so constructed that it acts
as a whole for the accomplishment of a single purpose.
When the controller is adjusted for going ahead (adequate stimulus
of a receptor), then the conducting paths (the final common path)
for the accomplishment of that purpose are all open to the flow of
the current from the battery, and the vehicle is integrated to go ahead.
It spends its energy to that end and is closed to all other impulses.
When the controller is set for reverse, by this adequate stimulus
the machine is integrated to back, and the battery is closed to all
other impulses. Whether integrated for going forward or backward,
if the battery be discharged at a proper rate until exhausted,
the cells, though possessing no more power (fatigue), have sustained
no further impairment of their elements than that of normal wear
and tear. Furthermore, they may be restored to normal activity
by recharging (rest). If the vehicle be placed against a stone wall,
and the controller be placed at high-speed (trauma and fear),
and if the accelerator be used as well (thyroid secretion?), though
the machine will not move, not only will the battery soon be exhausted,
but the battery elements themselves will be seriously damaged
(exhaustion--surgical shock).

We have now presented some evidence that nervous energy is
discharged by the adequate stimulation of one or more of the various
receptors that have been developed in the course of evolution.
In response to an adequate stimulus, the nervous system is
integrated for a specific purpose by the stimulated receptor,
and but one stimulus at a time has possession of the final common path--
the nerve mechanisms for action. The most numerous receptors
are those for harmful contact; these are the nociceptors.
The effect of the adequate stimulus of a nociceptor is like that of
pressing an electric button that sets great machinery in motion.

With this conception, the human body may be likened to a
musical instrument--an organ--the keyboard of which is composed
of the various receptors, upon which environment plays the many
tunes of life; and written within ourselves in symbolic language
is the history of our evolution. The skin may be the "Rosetta Stone"
which furnishes the key.


Anoci-association


By the law of phylogenetic association, we are now prepared
to make a practical application of the principles of the discharge
of nervous energy. In the case of a surgical operation, if fear
be excluded and if the nerve-paths between the field of operation
and the brain be blocked with cocain,[*] no discharge of energy will be
caused by the operation; hence no shock, no exhaustion, can result.
Under such conditions the nervous system is protected against
noci-association, resulting from noci-perception or from an adequate
stimulation of nociceptors. The state of the patient in whom all
noci-associations are excluded can be described only by coining
a new word. That word is "anoci-association" (Fig. 14).


[*] See footnote, page 4.@@@


The difference between anesthesia and anoci-association is that,
although _inhalation anesthesia_ confers the beneficent loss of
consciousness and freedom from pain, it does not prevent the nerve
impulses from reaching and influencing the brain, and therefore does
not prevent surgical shock nor the train of later nervous impairments
so well described by Mumford. _Anoci-association_ excludes fear,
pain, shock, and postoperative neuroses. _Anoci-association_ is
accomplished by combining the special management of patients
(applied psychology), morphin, inhalation anesthesia,
and local anesthesia.

We have now presented in summary much of the mass of experimental
and clinical evidence we have accumulated in support of our
principal theme, which is that the discharge of nervous energy is
accomplished in accordance with the law of phylogenetic association.
If this point seems to have been emphasized unduly, it is because
we expect to rear upon this foundation a clinical structure.
How does this hypothesis apply to surgical operations?


Prevention of Shock by the Application of the Principle of
Anoci-association



Upon this hypothesis a new principle in operative surgery is founded, _i.
e_., operation during the state of _anoci-association_. Assuming that
no unfavorable effect is produced by the anesthetic and that there is
no hemorrhage, the cells of the brain cannot be exhausted in the course
of a surgical operation except by fear or by trauma, or by both.
Fear may be excluded by narcotics and special management until
the patient is rendered unconscious by inhalation anesthesia.
Then if, in addition to inhalation anesthesia, the nerve-paths
between the brain and the field of operation are blocked with
cocain,[*] the patient will be placed in the beneficent state of
_anoci-association_, and at the completion of the operation will be
as free from shock as at the beginning. In so-called "fair risks"
such precautions may not be necessary, but in cases handicapped
by infections, by anemia, by previous shock, and by Graves'
disease, etc., anoci-association may become vitally important.


[*] See footnote, page 4.@@@


Graves' Disease


By applying the principle of the discharge of nervous energy by
phylogenetic association, and by making the additional hypothesis
that in the discharge of nervous energy the thyroid gland is stimulated
through the nervous system, we can explain many of the phenomena
of Graves' disease and may possibly discover some of the factors
which explain both its genesis and its cure.

In the wild state of animal life in which only the fittest
survive in the struggle for existence, every point of advantage
has its value. An animal engaged in battle or in a desperate
effort to escape will be able to give a better account of itself
if it have some means of accelerating the discharge of energy--
some influence like that of pouring oil upon the kindling fire.
There is evidence, though perhaps it is not conclusive,
that such an influence is exerted by the thyroid gland.
In myxedema, a condition characterized by a lack of thyroid secretion,
there is dulness of the reflexes and of the intellect, a lowered
muscular power, and generally a sluggish discharge of energy.
In Graves' disease there is an excessive production of thyroid secretion.
In this disease the reflexes are increased, the discharge of
energy is greatly facilitated, and metabolism is at a maximum.
The same phenomena occur also after the administration of thyroid
extract in large doses to normal subjects. In the course of
sexual activities there is an increased action of the thyroid,
which is indicated by an increase in its size and vascularity.
That in fear and in injury the thyroid, in cases of Graves'
disease, is probably stimulated to increased activity is indicated
by the increased activity of the thyroid circulation, by an increase
in the size of the gland, by the histologic appearance of activity
in the nuclei of the cells, and by an increase of the toxic symptoms.
Finally, Asher has stated that electric stimulation of the nerve supply
of the thyroid causes an increased secretion. The origin of many cases
of Graves' disease is closely associated with some of the causes
of the discharge of nervous energy, depressive influences especially,
such as nervous shocks, worry and nervous strain, disappointment in love,
business reverses, illness and death of relatives and friends.
The association of thyroid activity with procreation is well known,
hence the coincidence of a strain of overwork or of fear with
the sexual development of maturing girls is obviously favorable
to the incidence of Graves' disease. The presence of a colloid goiter
is a suitable soil for the development of Graves' disease, and I
fully recognize also the evidence that infection or auto-intoxication
may be contributing factors and must be assigned their role.

I have never known a case of Graves' disease to be caused by success
or happiness alone, or by hard physical labor unattended by
psychic strain, or to be the result of energy voluntarily discharged.
Some cases seem to have had their origin in overdosage with thyroid
extract in too vigorous an attempt to cure a colloid goiter.
One of the most striking characteristics of Graves' disease is
the patient's loss of control and his increased susceptibility
to stimuli, especially to trauma and to fear and to the administration
of thyroid extract. It has been shown that the various causes
of the discharge of nervous energy produce alterations in the nervous
system and probably in the thyroid gland. This is especially
true of the fear stimulus, and has been clearly demonstrated
in the brains of rabbits which had been subjected to fear alone
(Fig. 13). Of special interest was the effect of daily fright.
In this case the brain-cells showed a distinct change, although the animal
had been subjected to no fear for twenty-four hours before it was killed
(Fig. 13 C. Now, a great distinction between man and the lower
animals is the greater control man has acquired over his actions.
This quality of control, having been phylogenetically most recently
acquired, is the most vulnerable to various NOCUOUS influences.
The result of a constant noci-integration may be a wearing-out
of the control cells of the brain. In a typical case of Graves'
disease a marked morphologic change in the brain-cells has
been demonstrated (Fig. 15). As has been previously stated,
the origin of many cases of Graves' disease is associated
with some noci-influence. If this influence causes stimulation
of both the brain and the thyroid, its excessive action may cause
impairment of the brain and also hyperplasia of the thyroid.
As self-control is impaired, fear obtains an ascendency and,
_pari passu_, stimulates the thyroid still more actively (Fig. 16).
Finally, the fear of the disease itself becomes a noci-stimulus.
As the thyroid secretion causes an increase in the facility
with which nervous energy is discharged, a pathologic reciprocal
interaction is established between the brain and the thyroid.
The effect of the constantly recurring stimulus of the noci-influence
is heightened by summation. This reciprocal goading may
continue until either the brain or the thyroid is destroyed.
If the original noci-stimulus is withdrawn before the fear of the
disease becomes too strong, and before too much injury to the brain
and the thyroid has been inflicted, a spontaneous cure may result.
Recovery may be greatly facilitated by complete therapeutic rest.
A cure implies the return of the brain-cells to their normal state,
with the reestablishment of the normal self-control and the
restoration of the thyroid to its normal state, when the impulses
of daily life will once more have possession of the final
common path and the noci-influence will be dispossessed.
The discovery of the real cause of a given case of Graves' disease is
frequently difficult because it may be of a painful personal nature.
Of extreme interest is the fact that, in the acute stage,
the patient may be unable to refer to the exciting cause without
exhibiting an exacerbation of the symptoms of the disease.
I presume no case should be regarded as cured until reference
can be made to its cause without an abnormal reaction.
It has been established that in Graves' disease injury to any part
of the body, even under inhalation anesthesia, causes an exacerbation
of the disease. Fear alone may cause an acute exacerbation.
These acute exacerbations are frequently designated "hyperthyroidism"
and are the special hazard of operation.

In applying the principle of anoci-association in operations on
patients with Graves' disease there is scarcely a change in the pulse,
in the respiration, or in the nervous state at the close of the operation.
I know no remedy which can obviate the effect of the inflowing
stimuli from the wound after the cocain[*] has worn off.[t] It
is necessary, therefore,


Beats 70 80 90 100 110 120



Ether ******* ******** ******** ******** ********



N2O ******* ******** ******** ******** *



Anoci. ******* ******** ******** ** not to venture too far
in serious cases. Since the adoption of this new method
(anoci-association) my operative results have been so vastly improved
that I now rarely regard any case of Graves' disease as inoperable,
at least to the extent of contraindicating a double ligation (Fig. 17).


[*] See footnote, page 4.@@@

[t] In later papers and in "Anoci-association" (Crile and Lower)
methods of combating postoperative hyperthyroidism are fully discussed.


If we believe that, in accordance with the law of phylogenetic association,
a continuous stimulation of both the brain and the thyroid gland,
accelerated by summation, plays a role in the establishment
of the pathologic interaction seen in Graves' disease, then it
is but the next step to assume that if the nerve connection between
the brain and the thyroid be severed, or if the lobe be excised
and the patient reinforced by a sojourn in a sanatorium or in some
environment free from former noci-associations, he may be restored
to normal health, provided that the brain-cells, the heart,
or other essential organs have not suffered irreparable damage.
There are still many missing links in the solution of this problem,
and the foregoing hypotheses are not offered as final, although from
the viewpoint of the surgeon many of the phenomena of this
disease are explicable.


Sexual-Neurasthenia


The state of sexual neurasthenia is in many respects analogous
to that of Graves' disease. In the sexual reflexes, summation leads
to a hyperexcitability by psychic and mechanical stimuli of a
specific type which is analogous to the hyperexcitability in Graves'
disease under trauma and fear; the explanation of both conditions
is based on the laws of the discharge of energy by phylogenetic
association and summation. It would be interesting to observe
the effect of interrupting the nerve impulses from the field of
the sexual receptors by injections of alcohol, or by other agencies,
so as to exclude the associational stimuli until the nervous
mechanism has again become restored to its normal condition.
Interpretation of Some of the Phenomena of Certain Diseases of the
Abdomen in Accordance with the Hypothesis of Phylogenetic Association


The law of phylogenetic association seems to explain many
of the phenomena of certain lesions in the abdominal cavity.
The nociceptors in the abdomen, like nociceptors elsewhere, have been
established as a result of some kind of injury to which during
vast periods of time this region has been frequently exposed.
On this premise, we should at once conclude that there are no
nociceptors for heat within the abdomen because, during countless years,
the intra-abdominal region never came into contact with heat.
That this inference is correct is shown by the fact that the
application of a thermocautery to the intestines when completing
a colostomy in a conscious patient is absolutely painless.
One would conclude also that there are no touch receptors in the
abdominal viscera, and therefore no sense of touch in the peritoneum.
Just as the larynx, the ear, the nose, the sole of the foot,
and the skin have all developed the specific type of nociceptors
which are adapted for their specific protective purposes, and which,
when adequately stimulated, respond in a specific manner in accordance
with the law of phylogenetic association, so, the abdominal viscera
have developed equally specific nociceptors as a protection against
specific nocuous influences. The principal harmful influences
to which the abdominal viscera have been exposed during vast periods
of time are deep tearing injuries by teeth and claws in the innumerable
struggles of our progenitors with each other and with their enemies
(Fig. 9); peritonitis caused by perforations of the intestinal
tract from ulcers, injuries, appendicitis, gall-stones, etc.;
and overdistention of the hollow viscera by various forms of obstruction.
Whatever may be the explanation, it is a fact that the type
of trauma which results from fighting corresponds closely with
that which causes the most shock in the experimental laboratory.
Division of the intestines with a sharp knife causes no pain,
but pulling on the mesentery elicits pain. Ligating the stump
of the appendix causes sharp, cramp-like pains. Sharp division
of the gall-bladder causes no pain, but distention, which is
the gall-bladder's most common pathologic state, produces pain.
Distention of the intestine causes great pain, but sharp cutting or burning
causes none. In the abdominal viscera, as in the superficial parts,
nociceptors have presumably been developed by specific harmful
influences and each nociceptor is open to stimulation only by a
stimulus of the particular type that produced it.

As a result of the excitation of nociceptors, with which pain
is associated, the routine functions, such as peristalsis, secretion,
and absorption are dispossessed from the control of their respective
nervous mechanisms, just as they are inhibited by fear. This hypothesis
explains the loss of weight, the lassitude, the indigestion,
the constipation, and the many alterations in the functions of the various
glands and organs of the digestive system in chronic appendicitis.
It readily explains also the extraordinary improvement in the digestive
functions and the general health which follows the removal
of an appendix which is so slightly altered physically that only
the clinical results could persuade one that this slight change could
be an adequate cause for such far-reaching and important symptoms.
This hypothesis explains certain gall-bladder phenomena likewise,--
indigestion, loss of weight, disturbed functions, etc.,--and it
may supply the explanation of the disturbance caused by an active
anal fissure, which is a potent noci-associator, and the consequent
disproportionate relief after the trivial operation for its cure.
Noci-association would well explain also the great functional disturbances
of the viscera which immediately follow abdominal operations.

Postoperative and traumatic neuroses are at once explained on
the ground of noci-association, the resulting strain from which,
upon the brain-cells, causes in them physical lesions.
If one were placed against a wall and were looking into the gun muzzles
of a squad of soldiers, and were told that there were nine chances
out of ten that he would not be killed outright when the volley
was fired, would it help him to be told that he must not be afraid?
Such an experience would be written indelibly on his brain.
This corresponds closely to the position in which some surgical patients
are placed. In railway wrecks, we can readily understand the striking
difference between the after-effects in the passengers who were conscious
at the time of the accident and those who were asleep or drunk.
In the latter the noci-perceptors and receptors were not aroused,
hence their immunity to the nervous shock. In the functional disturbances
of the pelvic organs, association and summation may play a large role.
On this hypothesis many cases of neurasthenia may well be explained.
From the behavior of the individual as a whole we may well conclude
that summation is but a scientific expression for "nagging."
Many other pathologic phenomena may be explained in a similar manner.
Thus we can understand the variations in the gastric analyses in a
timid patient alarmed over his condition and afraid of the hospital.
He is integrated by fear, and as fear takes precedence over all
other impulses, no organ functionates normally. For the same reason,
one sees animals in captivity pine away under the dominance of fear.
The exposure of a sensitive brain to the naked possibility of death from
a surgical operation may be compared to uncovering a photographic plate
in the bright sunlight to inspect it before putting it in the camera.
This principle explains, too, the physical influence of the physician
or surgeon, who, by his PERSONALITY, inspires, like a Kocher,
absolute confidence in his patient. The brain, through its power
of phylogenetic association, controls many processes that have wholly
escaped from the notice of the "practical man." It is in accordance
with the law of association that a flower, a word, a touch, a cool breeze,
or even the thought of a fishing rod or of a gun, is helpful.
On the contrary, all suggestions of despair or misfortune--
a corrugated brow, the gloomy silence of despair, or a doubtful word--
are equally depressing. In like manner, one could add many
illustrations of the symbolism that governs our daily lives.
Thus we see that through the laws of inheritance and noci-association,
we are able to read a new meaning into the clinical phenomena
of various diseases.


Observations on Patients whose Associational Centers are Dulled,
and on Diseases and Injuries of Regions not Endowed with Nociceptors


Reversing the order of our reasoning, let us now glance at the patient
who is unconscious and who, therefore, has lost much of the power
of association. His mouth is usually dry, the digestive processes
are at a low ebb, the aroma of food causes no secretion of saliva,
tickling the nose causes no sneezing; he catches no cold.
The laryngeal reflex is lost and food may be quietly inhaled;
the entire process of metabolism is low. The contrast between a man
whose associational centers are keen and a man in whom these centers
are dulled or lost is the contrast between life and death.

In accordance with the law of adaptation through natural selection,
phylogeny, and association, one would expect no pain in abscess
of the brain, in abscess of the liver, in pylephlebitis,
in infection of the hepatic vessels, in endocarditis.
This law explains why there are no nociceptors for cancer,
while there are active nociceptors for the acute infections.
It is because nature has no helpful response to offer against cancer,
while in certain of the acute pyogenic infections the nociceptors
force the beneficent physiologic rest.

Could we dispossess ourselves of the shackles of psychology,
forget its confusing nomenclature, and view the human brain,
as Sherrington has said, "as the organ of, and for the adaptation
of nervous reaction," many clinical phenomena would appear in
a clearer light.


Natural Selection and Chemical Noci-association in the Infections


Thus far we have considered the behavior of the individual as a whole
in his response to a certain type of noci-influences. We have been voicing
our argument in terms of physical escape from GROSS physical dangers,
or of grappling with GROSS NERVE-MUSCULAR enemies of the same or of
other species. To explain these phenomena we have invoked the aid
of the laws of natural selection and phylogenetic association.
If our conclusions be correct, then it should follow that in the same
laws we may find the explanation of immunity, which, of course,
means a defensive response to our MICROSCOPIC enemies. There should
be no more difficulty in evolving an efficient army of phagocytes
by natural selection, or in developing specific chemical reactions
against _*microscopic enemies_, than there was in evolving the various
nociceptors for our nerve-muscular defense against our _*gross enemies_.
That immunity is a chemical reaction is no argument against
the application of the law of natural selection or of association.
What essential difference is there between the chemical defense of
the skunk against its NERVE-MUSCULAR enemies and its chemical defense
(immunity) against its MICROSCOPIC ENEMIES?

The administration of vaccines becomes the adequate stimulus which
awakens phylogenetic association of a chemical nature as a result
of which immune bodies are produced.

In discussing this subject I will raise only the question whether
or not the specific character of the inaugural symptoms of some
infectious diseases may be due to phylogenetic association.
These inaugural symptoms are measurably a recapitulation of the leading
phenomena of the disease in its completed clinical picture.
Thus, the furious initiative symptoms of pneumonia, of peritonitis,
or erysipelas, of the exanthemata, are exaggerations of phenomena
which are analogous to the phenomena accompanying physical injury
and fear of physical violence. Just as the acute phenomena of fear,
or those which accompany the adequate stimulation of nociceptors,
are recapitulations of phylogenetic struggles, so may the inaugural
symptoms of an infection be a similar phylogenetic recapitulation
of the course of the disease. A certain amount of negative
evidence is supplied by a comparison of the response to a dose
of toxins with the response to a dose of a standard drug.
No drug in therapeutic dosage except the iodin compounds causes
a febrile response; no drug causes a chill; on the other hand,
all specific toxins cause febrile responses and many cause chills.
If a species of animal had been poisoned by a drug during vast periods
of time, and if natural selection had successfully established
a self-defensive response, then the administration of that drug would
cause a noci-association (chemical), and a specific reaction analogous
to that following the administration of Coley's toxins might be expected.
Bacterial noci-association probably operates through the same
law as that through which physical noci-association operates.
Natural selection is impartial, however. It must be supposed that it
acts impartially upon the microscopic invader and upon the host.
On this ground one must infer that, in accordance with the same law
of natural selection, the bacteria of acute infections have met
by natural selection each advance in the struggle of the host
for immunity. Hence the fast and furious struggle between man
and his microscopic enemies merely indicates to what extent natural
selection has developed the ATTACK and the DEFENSE respectively.
This struggle is analogous to the quick and decisive battles
of the carnivora when fighting among themselves or when contending
against their ancient enemies. But when phylogenetically strange
animals meet each other, they do not understand how to conduct a fight:
natural selection has not had the opportunity of teaching them.
The acute infections have the characteristics of being ancient enemies.
On this hypothesis one can understand the high mortality of measles
when it is introduced into a new country. By natural selection,
measles has become a powerful enemy of the human race, and a race
to which this infection is newly introduced has not had the advantage
of building up a defense against it by the law of natural selection.
May not the phenomena of anaphylaxis be studied on associational lines?
Then, too, there may be chemical noci-associations with enemies
now extinct, which, like the ticklish points, may still be active
on adequate stimulation. This brief reference to the possible
relation of the phenomena of the acute infections to the laws
of natural selection and of specific chemical noci-association has
been made as a suggestion. Since the doctrine of evolution explains
all or nothing, I have included many phenomena to see how reasonable
or unreasonable such an explanation might be.


Recapitulation


The following are the principal points presented: In operations
under inhalation anesthesia the nerve impulses from the trauma
reach every part of the brain--the cerebrum that is apparently
anesthetized as well as the medulla that is known to remain awake--
the proof being the PHYSIOLOGIC exhaustion of and the PATHOLOGIC
change in the nerve-cells. Under ether anesthesia the damage
to the nerve-cells is at least four times greater than under
nitrous oxid. Inhalation anesthesia is, therefore, but a veneer--
a mask that "covers the deep suffering of the patient." The cause
of the exhaustion of the brain is the discharge of nervous energy
in a futile effort to energize the paralyzed muscles in an attempt
to escape from the injury just as if no anesthetic had been given.
The exhaustion is, therefore, of the same nature as that from overexertion,
but if the nerve-paths connecting the field of operation
and the brain be blocked, then there is no discharge of nervous
energy from the trauma, and consequently there is no exhaustion,
however severe or prolonged the operation may be.

Fear is a factor in many injuries and operations. The phenomena
of fear probably are exhibited only by animals whose natural defense
is nerve-muscular. The skunk, the porcupine, the turtle, have little
or no fear. Fear is born of the innumerable injuries which have
been inflicted in the course of evolution. Fear, like trauma,
may cause physiologic exhaustion of and morphologic changes
in the brain-cells. The representation of injury, which is fear,
being elicited by phylogenetic association, may be prevented
by the exclusion of the noci-association or by the administration
of drugs like morphin and scopolamin, which so impair the associational
function of the brain-cells that immunity to fear is established.
Animals whose natural defense is in muscular exertion, among which is man,
may have their dischargeable nervous energy exhausted by fear alone,
or by trauma alone, but most effectively by the combination of both.
What is the mechanism of this discharge of energy? It is the adequate
stimulation of the nociceptors and the physiologic response for the purpose
of self-preservation. According to Sherrington, the nervous system
responds in action as a whole and to but one stimulus at a time.
The integration of the individual as a whole occurs not alone in injury
and fear, but also, though not so markedly, as a result of other
phylogenetic associations, such as those of the chase and procreation.
When adequate stimuli are repeated with such rapidity that the new
stimulus is received before the effect of the previous one has
worn off, a higher maximum effect is produced than is possible
under a single stimulus, however powerful.

Sexual receptors are implanted in the body by natural selection,
and the adequate stimuli excite the nerve-muscular reactions
of conjugation in a manner analogous to the action of the adequate
stimuli of the nociceptors. The specific response of either
the sexual receptors or the nociceptors is at the expense
of the total amount of nervous energy available at the moment.
Likewise in daily labor, which, in the language of evolution,
is the chase, nervous energy is expended. Under the dominance
of fear or injury, however, the integration is most nearly
absolute and probably every expenditure of nervous energy which is
not required for efforts toward self-preservation is arrested;
hence fear and injury drain the cup of energy to the dregs.
This is the potential difference between fear and desire,
between injury and conjugation.

What is the practical application of this? In operative surgery
there is introduced a new principle, which removes from surgery much
of the immediate risk from its trauma by establishing ANOCI-ASSOCIATION;
it places certain of the phenomena of fear on a physical basis;
it explains to us the physical basis for the impairment of the entire
individual under worry or misfortune; it makes evident the physical
results of the daily noci-associations experienced by the individual
as a social unit. On the other hand, it explains the power
of therapeutic suggestion and of other influences which serve
for the time to change the noci-integration; it shows the physical
basis for the difference between hope and despair; it explains
some of the phenomena of Graves' disease, of sexual neurasthenia,
possibly of hay-fever and of the common cold. The principle is probably
equally applicable to the acute infections, in each of which chemical
noci-association gives rise to many of the phenomena of the disease
and it explains their cure by natural immunity and by vaccines.
This hypothesis should teach us to view our patients as a whole;
and especially should it teach the surgeon gentleness. It should
teach us that there is something more in surgery than mechanics,
and something more in medicine than physical diagnosis and drugs.


Conclusion


The brain-cells have existed for eons and, amid the vicissitudes
of change, they have persisted with perhaps less alteration than has
the crust of the earth. Whether in man or in the lower animals,
they are related to and obey the same general biologic laws,
thus being bound to the entire past and performing their function
in accordance with the law of phylogenetic association.

For so long a time have we directed our attention to tumors,
infections, and injuries that we have not sufficiently considered
the vital force itself. We have viewed each anatomic and pathologic
part as an entity and man as an isolated phenomenon in nature.
May we not find in the laws of adaptation under natural selection,
and of phylogenetic association, the master key that will disclose
to us the explanation of many pathologic phenomena as they have
already explained many normal phenomena?

And may medicine not correlate the pathologic phenomena of the sick
man with the forces of evolution, as the naturalists have correlated
the phenomena of the sound man, and thus may not disease, as well
as health, be given its evolutionary setting?



PHYLOGENETIC ASSOCIATION IN RELATION TO THE EMOTIONS[*]


[*] Address before the American Philosophical Society, Philadelphia,
April 22, 1911.


The surgeon is familiar with the manifestations of every variety
of the human emotions in the various stations of life, from infancy
to senility, in health and in disease. Not only does he come
into intimate contact with the emotions displayed by the victims
of disease and of accidents, but he also observes those manifested
by the relatives and friends of the families of his patients.
Moreover, he is unhappily forced to notice the emotional effect
upon himself when he is waging an unequal battle against death--
the strain and worry at a crisis, when a life is in the balance
and a single false move may be fatal, is an experience known only
to the operating surgeon.

For the data for this paper, therefore, in which I shall for the most
part limit my discussion to the strongest of all emotions--FEAR--I have
drawn largely from my personal experience as a surgeon, as well
as from an experimental research in which I have had the valuable
assistance of my associates, Dr. H. G. Sloan, Dr. J. B. Austin,
and Dr. M. L. Menten.

I believe it can be shown that it is possible to elicit the emotion
of fear only in those animals that utilize a motor mechanism
in defense against danger or in escape from it. For example,
the defense of the skunk is a diabolic odor which repels its enemies;
the skunk has no adequate equipment for defense or escape by
muscular exertion, and the skunk therefore shows little or no fear.
Again, certain species of snakes are protected by venom;
they possess no other means of defense nor have they adequate
motor mechanisms for escape and they show no fear. Because of
their strength other animals, such as the lion, the grizzly bear,
and the elephant, show but little fear (Fig. 6). Animals which have
an armored protection, such as the turtle, show little fear.
It is, therefore, obvious that fear is not universal and that the
emotion of fear is felt only by those animals whose self-preservation
is dependent upon an uncertain adequacy of their power of muscular
exertion either for defense or for flight (Fig. 7).

What are the principal phenomena of fear? They are palpitation
of the heart, acceleration of the rate and alteration of the rhythm
of the respiration, cold sweat, rise in body temperature,
tremor, pallor, erection of the hair, suspension of the principal
functions of digestion, muscular relaxation, and staring of the eyes
(Fig. 12). The functions of the brain are wholly suspended except those
which relate to the self-protective response against the feared object.
Neither the brain nor any other organ of the body can respond
to any other lesser stimulus during the dominance of fear.

From these premises it would appear that under the influence
of fear, most, perhaps all, of the organs of the body are divided
sharply into two classes: First, those that are stimulated,
and, second, those that are inhibited. Those that are stimulated
are the entire muscular system, the vasomotor and locomotor systems,
the senses of perception, the respiration, the mechanism for erecting
the hair, the sweat-glands, the thyroid gland, the adrenal gland
(Cannon), and the special senses. On the other hand,
all the digestive and procreative functions are inhibited.
What is the significance of this stimulation of some and inhibition
of other organs? As far as we know, the stimulated organs
increase the efficiency of the animal for fight or for flight.
It is through skeletal muscles that the physical attack or escape
is effected; these muscles alone energize the claws, the teeth,
the hoofs, and the means for flight. The increased action of the
muscles of the heart and the blood-vessels increases the efficiency
of the circulation; the secretion of the adrenal gland causes a rise
in the blood-pressure; the increased action of the thyroid gland causes
an increased metabolic activity; there is evidence that glycogen
is actively called out, this being the most immediately available
substance for the production of energy; the increased activity
of the respiration is needed to supply the greater need of oxygen
and the elimination of the increased amount of waste products;
the dilatation of the nostrils affords a freer intake of air;
the increased activity of the sweat-glands is needed to regulate
the temperature of the body which the increased metabolism causes to rise.
The activity of all the organs of perception--sight, hearing, smell--
is increased in order that the danger may be more accurately perceived.
It cannot be a mere coincidence that the organs and the tissues
that are stimulated in the emotion of fear are precisely those that
are actually utilized in a physical struggle for self-preservation.

Are any other organs stimulated by fear except those that can
or that do assist in making a defensive struggle? I know of none.
On the other hand, if an animal could dispense with his bulky
digestive organs, whose functions are suspended by fear, if he could,
so to speak, clear his decks for battle, it would be to his advantage.
Although the marvelous versatility of natural selection apparently
could devise no means of affording this advantage, it nevertheless shut
off the nervous current and saved the vital force which is ordinarily
consumed by these non-combatants in the performance of their functions.
Whatever may be the origin of fear, its phenomena are due to a
stimulation of all the organs and tissues that add to the efficiency
of the physical struggle for self-preservation and an inhibition
of the func-


{illust. caption = FIG. 19--THE BROAD JUMP. Note the similarity
of the expression to the facial expression of fear and of anger
(Figs. 12 and 21). (Wm. J. Brownlow, drawn from photo.)
tions of the leading organs that do not participate in that struggle--
the non-combatants, so to speak. Fear arose from injury,
and is one of the oldest and surely the strongest emotion.
By the slow process of vast empiricism nature has evolved the
wonderful defensive motor me-chanism of many animals and of man.
The stimulation of this mechanism leading to a physical struggle is action,
and the stimulation of this mechanism without action is emotion.
We may say, therefore, that fear is a PHYLOGENETIC FIGHT OR FLIGHT (Fig.
18). On this hypothesis all the organs and parts {illust. caption
= FIG. 20.-FINISH OF RELAY RACE.

Compare the facial expression of the runners with those in Figs.
12, 19, 22. These pictures illustrate the fact that the same
mechanism is stimulated in emotion as in physical action.
(Photo by Underwood and Underwood, N. Y.)}


of the body are integrated, connected, or correlated for the
self-preservation of the individual by the activity of his motor mechanism
(Figs. 12, 19, and 20). We fear not in our hearts alone, not in our
brains alone, not in our viscera alone--fear influences every organ
and tissue; each organ or tissue is stimulated or inhibited according
to its use or hindrance in the physical struggle for existence.
By thus concentrating all or most of the nerve force on the nerve-muscular
mechanism for defense, a greater physical power is developed.
Hence it is that under the stimulus of fear animals are able to perform
preternatural feats of strength. For the same reason, the exhaustion
following fear will be increased as the powerful stimulus of fear drains
the cup of nervous energy even though no visible action may result.
An animal under the stimulus of fear may be likened to an automobile
with the clutch thrown out but whose engine is racing at full speed.
The gasoline is being consumed, the machinery is being worn,
but the machine as a whole does not move, though the power of its
engine may cause it to tremble.

When this conception is applied to the human beings of today,
certain mysterious phenomena are at once elucidated. It must be borne
in mind that man has not been presented with any new organs to meet
the requirements of his present state of civilization; indeed, not only
does he possess organs of the same type as those of his savage fellows,
but of the same type also as those possessed by the lower animals even.
In fact, man has reached his present status of civilization with
the primary equipment of brutish organs. Perhaps the most striking
difference between man and animals lies in the greater control
which man has gained over his primitive instinctive reactions.
As compared with the entire duration of organic evolution,
man came down from his arboreal abode and assumed his new role
of increased domination over the physical world but a moment ago.
And now, though sitting at his desk in command of the complicated
machinery of civilization, when he fears a business catastrophe
his fear is manifested in the terms of his ancestral physical battle
in the struggle for existence. He cannot fear intellectually,
he cannot fear dispassionately, he fears with all his organs,
and the same organs are stimulated and inhibited as if, instead of it
being a battle of credit, of position, or of honor, it were a physical
battle with teeth and claws. Whether the cause of acute fear
be moral, financial, social, or stage fright, the heart beats wildly,
the respirations are accelerated, perspiration is increased,
there are pallor, trembling, indigestion, dry mouth, etc.
The phenomena are those which accompany physical exertion
in self-defense or escape. There is not one group of phenomena
for the acute fear of the president of a bank in a financial
crash and another for the hitherto trusted official who suddenly
and unexpectedly faces the imminent probability of the penitentiary;
or one for a patient who unexpectedly finds he has a cancer
and another for the hunter when he shoots his first big game.
Nature has but one means of response to fear, and whatever its cause
the phenomena are always the same--always physical.

If the stimulus of fear be repeated from day to day, whether in
the case of a mother anxious on account of the illness of a child;
a business man struggling against failure; a politician under contest
for appointment; a broker in the daily hazard of his fortune;
litigants in legal battle, or a jealous lover who fears a rival;
the countless real as well as the baseless fears in daily life,
in fact, all forms of fear, as it seems to me, express themselves
in like terms of ancestral physical contests. On this law,
fear dominates the various organs and parts of the body.

Anger and fear express opposite emotional states. Fear is the
expression of a strong desire to escape from danger; anger, of a
strong desire to attack physically and to vanquish opposition.
This hypothesis is strongly supported by the outward expressions
of fear and of anger. When the business man is conducting a struggle
for existence against his rivals, and when the contest is at
its height, he may clench his fists, pound the table, perhaps show
his teeth, and exhibit every expression of physical combat.
Fixing the jaw and showing the teeth in anger merely emphasize
the remarkable tenacity of phylogeny. Although the development
of the wonderful efficiency of the hands has led to a modification
of the once powerful canines of our progenitors, the ancestral use
of the teeth for attack and defense is attested in the display of anger.
In all stations of life differences of opinion may lead to argument
and argument to physical combats, even to the point of killing.
The physical violence of the savage and of the brute still lies
surprisingly near the surface (Fig. 21).

We have now presented some of the reasons based largely on gross animal
behavior why fear is to be regarded as a response to phylogenetic
association with physical danger. In further support of this hypothesis,
I shall now present some clinical and experimental evidence.
Although there is not convincing proof, yet there is evidence that
the effect of the stimulus of fear upon the body when unaccompanied
by physical activity is more injurious than is an actual physical
contest which results in fatigue without gross physical injury.
It is well known that the soldier who, while under fire,
waits in vain for orders to charge, suffers more than the soldier
who flings himself into the fray; and that a wild animal endeavoring
to avoid capture suffers less than one cowering in captivity.
An unexpressed smouldering emotion is measurably relieved by action.
It is probable that the various energizing substances needed in
physical combat, such as the secretions of the thyroid, the adrenals
(Cannon), etc., may cause physical injury to the body when they
are not consumed by action (Fig. 22).

That the brain is definitely influenced--damaged even--
by fear has been proved by the following experiments:
Rabbits were frightened by a dog but were neither injured nor chased.
After various periods of time the animals were killed and their
brain-cells compared with the brain-cells of normal animals--
wide-spread changes were seen (Fig. 13). The principal clinical phenomena
expressed by the rabbit were rapid heart, accelerated respiration,
prostration, tremors, and a rise in temperature. The dog showed
similar phenomena, excepting that, instead of such muscular relaxation
as was shown by the rabbit, it exhibited aggressive muscular action.
Both the dog and the rabbit were exhausted but, although the dog
exerted himself actively and the rabbit remained physically passive,
the rabbit was much more exhausted.

Further observations were made upon the brain of a fox
which had been chased for two hours by members of a hunt club,
and had been finally overtaken by the hounds and killed.
Most of the brain-cells of this fox, as compared with those of a
normal fox, showed extensive physical changes (Fig. 4).

The next line of evidence is offered with some reservation,
but it has seemed to me to be more than mere idle speculation.
It relates to the phenomena of one of the most interesting diseases
in the entire category of human ailments--I refer to exophthalmic goiter,
or Graves' disease, a disease primarily involving the emotions.
This disease is frequently the direct sequence of severe
mental shock or of a long and intensely worrying strain.
The following case is typical: A broker was in his usual health up
to the panic of 1907; during this panic his fortune and that of others
were for almost a year in jeopardy, failure finally occurring.
During this heavy strain he became increasingly nervous and by
imperceptible degrees there developed a pulsating enlargement of
the thyroid gland, an increased prominence of the eyes, marked increase
in perspiration--profuse sweating even--palpitation of the heart,
increased respiration with frequent sighing, increase in blood-pressure;
there were tremor of many muscles, rapid loss of weight and strength,
frequent gastro-intestinal disturbances, loss of normal control
of his emotions, and marked impairment of his mental faculties.
He was as completely broken in health as in fortune.
These phenomena resembled closely those of fear and followed
in the wake of a strain which was due to fear.

In young women exophthalmic goiter often follows in the wake
of a disappointment in love; in women, too, it frequently follows
the illnesses of children or parents during which they have had
to endure the double strain of worry and of constant care.
Since such strains usually fall most heavily upon women, they are
the most frequent victims of this disease. Now, whatever the exciting
cause of exophthalmic goiter, whether it be unusual business worry,
disappointment in love, a tragedy, or the illness of a loved one,
the symptoms are alike and closely resemble the phenomena of one
of the great primitive emotions. How could disappointment in love
play a role in the causation of Graves' disease? If the hypothesis
which has been presented as an explanation of the genesis and
the phenomena of fear be correct, then that hypothesis explains
also the emotion of love. If fear be a phylogenetic physical
defense or escape which does not result in muscular action,
then love is a phylogenetic conjugation without physical action.
The quickened pulse, the leaping heart, the accelerated respiration,
the sighing, the glowing eye, the crimson cheek, and many other
phenomena are merely phylogenetic recapitulations of ancestral acts.
The thyroid gland is believed to participate in such physical activities.
Hence it may well follow that the disappointed maiden who is intensely
integrated for a youth will, at every thought of him, be subjected
by phylogenetic association to a specific stimulation analogous
to that which attended the ancestral consummation. Moreover, a happy
marriage has many times been followed by a cure of the exophthalmic
goiter which appeared in the wake of such an experience.

The victims of Graves' disease present a counterpart of
emotional exhaustion. That the emotions in Graves' disease are
abnormally acute is illustrated by my personal observation
of the death of a subject of this disease from fear alone.
Whatever the exciting cause of this disease, the symptoms are the same;
just as in fear, the phenomena are the same whatever the exciting cause.

Figures 12 and 16 show the resemblance between the outward appearances
of a patient with Graves' disease and of a person obsessed by fear.
Fear and Graves' disease have the following phenomena in common:
Increased heart-beat, increased respiration, rising temperature,
muscular tremors, protruding eyes, loss in weight; Cannon has found
an increased amount of adrenalin in the blood in fear and Frankel
in Graves' disease; increased blood-pressure; muscular weakness;
digestive disturbances; impaired nervous control; hypersusceptibility
to stimuli; in protracted intense fear the brain-cells show marked
physical changes, and in Graves' disease analogous changes are seen
(Figs. 13 C and 15). In Graves' disease there seems to be a composite
picture of an intense expression of the great primitive emotions.
If Graves' disease be a disease of the great primitive emotions,
or rather of the whole motor mechanism, how is the constant flow
of stimulation of this complicated mechanism supplied? It would
seem that there must be secreted in excessive amount some substance
that activates the motor mechanism. The nervous system in Graves'
disease is hypersusceptible to stimuli and to thyroid extract.
It might follow that even a normal amount of thyroid secretion would
lead to excessive stimulation of the hypersusceptible motor mechanism.

This condition of excessive motor activity and hyperexcitability may
endure for years. What is the source of this pathologic excitation?
The following facts may give a clue. In suitable cases of Graves'
disease, if the thyroid secretion is sufficiently diminished by a removal
of a part of the gland or by interrupting the nerve and the blood supply,
the phenomena of the disease are diminished immediately, and in favorable
cases the patient is restored to approximately the normal condition.
The heart action slows, the respiratory rate falls, the restlessness
diminishes, digestive disturbances disappear, tremors decrease,
there is a rapid increase in the body weight, and the patient gradually
resumes his normal state. On the other hand, if for a period
of time extract of the thyroid gland is administered to a normal
individual in excessive dosage, there will develop nervousness,
palpitation of the heart, sweating, loss of weight, slight protrusion
of the eyes, indigestion; in short, most of the phenomena of Graves'
disease and of the strong emotions will be produced artificially
(Figs. 15 and 23). When the administration of the thyroid extract
is discontinued, these phenomena may disappear. On the other hand,
when there is too little or no thyroid gland, the individual
becomes dull, stupid, and emotionless, though he may be irritable;
while if a sufficient amount of thyroid extract be given to such
a patient he may be brought back to his normal condition.

Hence we see that the phenomena of the emotions may within certain
limits be increased, diminished, or abolished by increasing,
diminishing, or totally excluding the secretion of the thyroid gland.

Graves' disease may be increased by giving thyroid extract and by fear.
It may be diminished by removing a part of the gland, or by
interrupting the blood and nerve supply, or by complete rest.
In addition, at some stage of Graves' disease there is an
increase in the size and in the number of the secreting cells.
These facts regarding the normal and the pathologic supply of thyroid
secretion point to this gland as one of the sources of the energizing
substance or substances, by means of which the motor phenomena
of animals are executed and their emotions expressed.

Anger is similar to fear in origin and, like fear, is an integration
and stimulation of the motor mechanism and its accessories.
Animals which have no natural weapons for attack experience neither
fear nor anger, while the animals which have weapons for attack
express anger principally by energizing the muscles used in attack.
Although, as has already been stated, the efficiency of the hands
of man has largely supplanted the use of the teeth, he still shows
his teeth in anger and so gives support to the theory that this
emotion is of remote ancestral origin and proves the great persistence
of phylogenetic association. On this conception we can understand
why it is that a patient consumed by worry--which to me signifies
interrupted stimulation, a state of alternation between hope
and fear--suffers so many bodily impairments and diseases even.
This hypothesis explains the slow dying of animals in captivity.
It explains the grave digestive and metabolic disturbances which
appear under any nerve strain, especially under the strain of fear,
and the great benefits of confidence and hope; it explains the nervousness,
loss of weight, indigestion--in short, the comprehensive physical
changes that are wrought by fear and by sexual love and hate.
On this hypothesis we can understand the physical influence
of one individual over the body and personality of another;
and of the infinite factors in environment that, through phylogenetic
association, play a role in the functions of many of our organs.
It is because under the uncompromising law of survival of the fittest
we were evolved as motor beings that we do not possess any organs or
faculties which have not served our progenitors in accomplishing their
survival in the relentless struggle of organic forms with one another.
We are now, as we were then, essentially motor beings, and the only way in
which we can meet the dangers in our environment is by a motor response.
Such a motor response implies the integration of our entire being
for action, this integration involving the activity of certain glands,
such as the adrenals (Cannon), the thyroid, the liver, etc., which throw
into the blood-stream substances which help to form energy, but which,
if no muscular action ensues, are harmful elements in the blood.
While this motor preparation is going on, the entire digestive
tract is inhibited. It thus becomes clear why an emotion is more
harmful than action.

Any agency that can sufficiently inspire faith,--dispel worry,--
whether that agency be mystical, human, or divine, will at once
stop the body-wide stimulations and inhibitions which cause
lesions which are as truly physical as is a fracture.
The striking benefits of good luck, success, and happiness;
of a change of scene; of hunting and fishing; of optimistic
and helpful friends, are at once explained by this hypothesis.
One can also understand the difference between the broken body
and spirits of an animal in captivity and its buoyant return to its
normal condition when freed.

But time will not permit me to follow this tempting lead, which has
been introduced for another purpose--the proposal of a remedy.

Worries either are or are not groundless. Of those that have
a basis, many are exaggerated. It has occurred to me to utilize
as an antidote an appeal to the same great law that originally
excited the instinctive involuntary reaction known as fear--
the law of self-preservation.

I have found that if an intelligent patient who is suffering from
fear can be made to see so plainly as to become firmly convinced
that his brain, his various organs, indeed his whole being,
could be physically damaged by fear, that this same instinct of
self-preservation will, to the extent of his conviction, banish fear.
It is hurling a threatened active militant danger, whose injurious
influences are both certain and known, against an uncertain,
perhaps a fancied, one. In other words, fear itself is an injury
which when recognized is instinctively avoided. In a similar manner
anger may be softened or banished by an appeal to the stronger
self-preserving instinct aroused by the fear of physical damage,
such as the physical injury of brain-cells. This playing of one
primitive instinct against another is comparable to the effect
produced upon two men who are quarreling when a more powerful enemy
of both comes threateningly on the scene.

The acute fear of a surgical operation may be banished by the use
of certain drugs that depress the associational power of the brain and
so minimize the effect of the preparations that usually inspire fear.
If, in addition, the entire field of operation is blocked by local
anesthesia so that the associational centers are not awakened,
the patient will pass through the operation unscathed.

The phylogenetic origin of fear is injury, hence injury and fear cause
the same phenomena. In their quality and in their phenomena psychic
shock and traumatic shock are the same. The perception of danger
by the special senses in the sound of the opening gun of a battle,
or in the sight of a venomous snake, is phylogenetically the same
and causes the same effects upon the entire body as an operation under
anesthesia or a physical combat in that each drives the motor mechanism.
The use of local anesthetics in the operative field prevents
nerve-currents from the seat of injury from reaching the brain and there
integrating the entire body for a self-defensive struggle. The result,
even though a part of the brain is asleep and the muscles paralyzed,
is the same as that produced by the interception of the terrifying
sound of the gun, or of the sight of the dangerous reptile,
since the stimulation of the motor mechanism is prevented.

By both the positive and the negative evidence we are forced
to believe that the emotions are primitive instinctive reactions
which represent ancestral acts; and that they therefore utilize
the complicated motor mechanism which has been developed by the forces
of evolution as that best adapted to fit the individual for his
struggle with his environment or for procreation.

The mechanism by which the motor acts are performed and the mechanism
by which the emotions are expressed are one and the same.
These acts in their infinite complexity are suggested by association--
phylogenetic association. When our progenitors came in contact
with any exciting element in their environment, action ensued then
and there. There was much action--little restraint or emotion.
Civilized man is really in auto-captivity. He is subjected
to innumerable stimulations, but custom and convention frequently
prevent physical action. When these stimulations are sufficiently
strong but no action ensues, the reaction constitutes an emotion.
A phylogenetic fight is anger; a phylogenetic flight is fear;
a phylogenetic copulation is sexual love, and so one finds in this
conception an underlying principle which may be the key to an
understanding of the emotions and of certain diseases.



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

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