The Chemistry of Sleep

I

‘FOR here is shewed by what means sleepe is caused; that is by vapours and fumes rising from the stomache to the head, where through coldness of the brain they being congealed doe stop the conduites and waies of the senses, and so procure sleepe.’ As fanciful as this three-hundred-years-old explanation of sleep may sound, we surely have in it something more solid than in the empty theories which have passed current for some time and assigned sleep to a self-evident ‘torpor of the sensorium,’ an obvious ‘resting-state of consciousness,’ or a vague ‘rise of stimulus thresholds.’ Although scientists have, until comparatively recently, avoided the subject as one for socalled psychologists to spin their webs about, happily, with the advance of physiological chemistry, sleep is being studied under the microscope and in the test-tube, with the result that the investigators are now able to give us a much truer idea of what it really is.

This interesting condition is no longer indefinitely considered a wandering abroad of the soul, but is now known to be a temporary poisoning of the brain-cells by the waste products resulting during the day from the activity of the body-cells in general. Thus when a muscle-cell or a nervecell acts, nutritive material stored within its walls is broken down into substances that are of no value and merely impede further action of the cell unless removed. Normally these waste products are washed out by the blood-stream which at the same time provides new cell-food, and is finally itself purified by the excretory organs, — the lungs and the kidneys. In the course of the day, however, production is in excess of removal, and then the clogging effect of these substances is manifested by fatigue in muscles and brain, the extreme degree of which results, in the latter organ, in the inability to act which we know as sleep. The third of our time thus spent out of commission is therefore really due to the inadequacy of the excretory organs for purifying the blood; and if for the word ‘stomache’ we substitute ‘body,’ it is interesting to note that the above ancient quotation very closely foreshadows, in a figurative sense, the circumstances as we understand them to-day.

That there is a close relation between fatigue and sleep is superficially evident to every one who has felt the difficulty of keeping awake after strenuous exercise, and noted the greater depth of sleep following such fatigue as compared with the light sleep when not previously tired. What the conditions are under the surface at such times has to some extent been made clear by microscopical examination of the nervecells of pigeons, sparrows, and bees, when fatigued at night and when rested in the morning. At night there was a marked shrinkage of the cells, particularly of their nuclei, in which the shrinkage varied from eight to seventy-five per cent of original volume, while the protoplasm still in the cell was riddled with empty spaces. In the morning the normal appearance and size had been regained. This striking evidence that fatigue is accompanied by loss of cellmaterial needs no comment. That such visible changes are accompanied by chemical reactions is also certain, for the fatigued cells stain differently from the non-fatigued ones; staining with different substances being a regular laboratory process of demonstrating chemical changes in cells.

If a small muscle, like that from the calf of the leg of a frog, is artificially stimulated at regular short intervals by an electric current of constant strength, we find that its contractions grow gradually shorter and shorter and soon cease altogether, — the muscle is asleep. It is no longer sensitive to a current of this strength, and can only be aroused by a stronger one. Now, however, if we pass a nutritive fluid through the blood-vessels of the muscle to supply new cell-material, and, what is of much greater importance at this period, to wash out its waste products, we find that the muscle again awakes and is sensitive to the original strength of stimulus. Thus normally in the body when we are exhausted, the muscles have acted under the stimulation of the will until so clogged with this waste material that they can no longer respond to nerve-impulses, and must rest until their normal condition is again restored by the circulation. One third of the respiratory act is rest; and even the heart, which we usually consider an organ that never rests, sleeps six hours in twenty-four, for one fourth of the time to make one beat and begin another is spent in inaction and repair.

That the waste products resulting from such action in muscle and nervecells, or fatigue-products as we may now call them, can really cause sleep and are not merely an incidental accompaniment of it, is proved by the experiment of injecting the blood of an exhausted dog into a normal one, which then exhibits all the symptoms of fatigue and falls asleep. The injection of the blood of a non-fatigued dog into a normal one has no effect, because it has not been saturated with these toxic waste products from the cells. Also tending to prove that sleep is due more to the accumulation of waste than to the exhaustion of nutritive material in the cell, is the experiment of the bloodless frog. As the blood was removed from this animal there was substituted a very dilute salt solution, of no nutritive value whatever. This fluid removed the waste from the cells, however; so the frog lived for several days, and during the first ten or twelve hours was difficult to distinguish from normal frogs.

But still the most satisfactory proof that these fatigue-products are the direct cause of sleep lies in an individual examination of some of the principal ones, such as carbon dioxide and lactic acid. As is well known, carbon dioxide is the poisonous part of expired air. It is produced in large quantities in nervous and other tissues, but in the main by muscular action, for it has been found that, during a day in which muscular work is done, a man expires nearly twice as much carbon dioxide as during a resting day. The amount of its output is also very much diminished during sleep, when the muscles are not in action. It is known by laboratory experiment to have a clogging effect upon the action of muscle-tissue, but for us it is of greater interest to know its effect upon the brain-cells, which it reaches through the blood and affects in conjunction with that, already formed there.

Here carbon dioxide acts by exclusion of oxygen, the presence of which is always so necessary to vital action; all movement, digestion, and even thought, being due to chemical processes in which oxygen plays a most important part. The temperature of the gray matter at the surface of the brain has been found to be at times higher than that of any part of the body, and this would indicate that this tissue is the seat of more active chemical processes than any other, since heat in the body is also always due to chemical action. The brain therefore requires a relatively greater supply of oxygen than the other organs do, and is correspondingly more sensitive to its lack.

With reference to the possibility of this gas producing sleep, or at least of the lack of oxygen doing so, we have, besides the familiar instances of its extreme effect of suffocation in ill-ventilated prisons or other places, the experiment of breathing from a closed vessel and counting aloud. With a certain low per cent of oxygen and a corresponding increase of carbon dioxide, the counting ceased and unconsciousness occurred, although, as in sleep, the other functions of the body were not altered.

Lactic acid, the other important fatigue and sleep-producing substance, is also produced by muscular and nervous activity. In the familiar occurrence of the souring of milk it prevents its own production by interfering with the action of bacteria which produce it from sugar of milk. A similar process occurs in muscle, the cells of which when in activity produce lactic acid from a kind of sugar stored in them; but the accumulating acid is unfavorable to this process and therefore retards muscular action. That it can lower the activity of brain-cells to a point below consciousness has been determined even on man, in whom doses of it have been shown to produce fatigue and finally sleep. Perhaps it is this agent to which the well-known sleep-producing effect of milk is due.

II

Besides these direct proofs that sleep is produced by toxic waste products whose removal does not keep pace with their formation, there is much interesting indirect evidence that it is due to the same influence. Thus it is known that the brain is one of the first organs to feel the effect of a diminished amount of blood or of a depraved quality of this fluid, and hence, in old age, or under the influence of a deficient quantity of food, or through the action of some exhausting disease, there is generally more sleep than when the physical health is not deteriorated. In many diseases, such as malaria, diabetes, and chronic inflammation of the kidneys, a most prominent symptom is an unusual amount of sleep. In all three of these diseases, either on account of toxins secreted by bacteria or of trouble with the excretory organs, the system becomes saturated with various poisonous products, and a common termination of them is coma. This is a sleep from which the patient either cannot be aroused at all by any form of stimulation, or only with great difficulty, according to the depth of the coma. This fact of itself suggests the milder toxic nature of normal sleep.

Certain forms of neurasthenia are accompanied by a disposition to inordinate sleep, and fatigue with its toxic products intensifies this tendency. In sleeping-sickness the patient, over a period of six to eighteen months, develops the tendency to sleep more and more, until he will not feed, and ultimately dies. This is a disease peculiar to parts of Africa, and is caused by a parasite introduced into the blood by a variety of fly. The chief seat of development of this organism, however, is the cerebro-spinal fluid, which fills the cavities within the brain and spinal cord. Here it produces a toxin which directly affects the nerve-cells and produces the characteristic sleep and death. Indeed there is much evidence that, natural death in old age is due to lack of resistance to an accumulation of normal waste products, and death in many diseases is undoubtedly due to lack of resistance to unnatural toxins produced by bacteria or pathological processes, and thus we have its relation to sleep — ‘that ape of death.’

In this connection we must also note that sleep may be produced by compression of the carotid arteries; a process which reduces the amount of oxygen in the brain by the simple process of diminishing the amount of blood which carries it there. But the important point for us is that a certain degree of compression is much more effective in the evening than in the morning, as if at this time the braincells were less irritable on account of the accumulated waste of the day, and could therefore not so well endure a suspension of the blood-supply.

Finally, with the indirect evidence it is to be mentioned that the tendency to sleep after meals has recently been ascribed to the effect of the first products of digestion, which it is claimed are similar in their action to fatigueproducts. The condition, however, is no doubt to a great extent due to the withdrawal of blood from the brain to aid digestion; for the amount of blood in the body does not seem to be sufficient to satisfy all the demands made upon it at the same time; hence it must be distributed to the best advantage with the surplus where needed most. Indeed, there has developed a wonderfully delicate and elaborate nervous mechanism known as the vasomotor, or blood-vessel-moving system, whose sole function is to control this distribution of blood to the various organs.

This matter of blood-supply, so evident in the lethargy after meals, is indeed of importance in producing and maintaining all normal sleep. By toxic waste products the irritability of braincells is lowered, even to a point below consciousness for some centres; and this condition is then made general by a diminution of the bloodor, more directly, the oxygen-supply, to all the brain. That this diminution really obtains during sleep has been established beyond a doubt. It has already been noted that the compression of the carotid arteries, the most important vessels by which blood is supplied to the brain, produces an artificial sleep. Also the fontanelle of the baby, the opening in the top of the skull where the bones have not yet grown together, rises when the baby is awake, and sinks during sleep. This rise and fall can be due to nothing but a corresponding change in the volume of the brain caused by an alteration of the bloodsupply. The famous experiment of a man on a balanced table which sank at the head end when he was thinking, and rose when he was mentally inactive, or asleep, is very much to the point. Fainting, with its production of a state so similar to deep sleep, is due to the increased amount of blood in the vessels of the abdomen and a corresponding loss in the brain.

Similar observations to those made upon babies have been made upon adults with defects of the skull due to accident or surgical operation, and the additional data obtained by the proper apparatus, that during sleep the volume of the arm or leg increases on account of the expansion of the blood-vessels at the surface of the body in general. The sleepiness following exposure to heat or cold is no doubt due to this derivation of the blood from the central organs of the body to the surface, in order to cool or warm it as the occasion may demand. It is also important, to note that the increase of blood at the surface and corresponding diminution in the brain, follows pretty closely the course of intensity of sleep. Thus it has been determined, by making noises of different height, and by different degrees of electrical stimulation, that the first two hours of sleep are by far the deepest, and it is during this period that there is the least blood at the head. It will be of interest now to know why this anæmia of the brain occurs at the time of sleep.

III

The vasomotor system for controlling the distribution of the blood is ruled by a definite centre, or collection of nerve-cells, at the base of the brain. From here nerves go to all parts of the body, and control the size of blood-vessels by action on the muscles in their walls. As occasion arises for an increased supply of blood to a particular organ, the condition of the organ at the moment originates a message to the vasomotor centre, which then increases the size of the vessels supplying the organ, and its particular function, such as secretion by a gland, results. This centre is not only busy with the demands of the internal organs, but it is also subject to the influence of the special senses. Thus, through their effect upon this centre, sensations of heat, cold, or pain in the skin cause an increase of blood-supply there, for protective purposes. Even recognition of sounds, objects, odors, and tastes receives attention in this busy office. This was demonstrated for several of these sensations by the experiment in which the varying volume of the arm was determined during sleep. On this occasion the sound of a music-box, though not sufficient to awake the sleeper, did affect this centre, which caused a considerable diminution of the volume of the arm as the blood was returned to the head in this unconscious act of attention.

It is evident that, busy all day long with unceasing attenton to organic and special sensations, this must be one of the first centres to become fatigued; or at least, because of the clogging effect of its own waste products, it must be one of the first to feel the effect of those produced in other tissues and brought to it by the blood: a theory with which we must credit Professor Howell of Johns Hopkins University. Since this centre acts by maintaining the arteries at all times in a condition of construction, except as different organs make demand for more blood, when it is fatigued and loses control, the arteries will automatically expand all over the body, and a part of the blood of the brain will naturally gravitate into them. As experiments on animals indicate that, the blood in the brain and spinal cord is only one per cent of that in the entire body, no great variation in the size of blood-vessels is necessary to reduce considerably the amount of this fluid in the brain.

Usually, however, there is not complete exhaustion of the vasomotor centre. When sleepy we withdraw ourselves as far as possible from external stimuli, and, if wise, have avoided any excess which would cause unusual internal sensations. Then this centre, no longer subject to the stimuli whose tonic influence has caused it to maintain the arteries in general in a constricted condition, is in a situation as helpless as that due to extreme fatigue. As in the latter case, the blood-vessels in the lower part of the body automatically expand, and sleep at once results from diminished bloodor oxygen-supply to the brain.

Naturally, sleep continues until the blood and the brain-cells are restored to normal condition, or until some unusual or intense stimulation affects the vasomotor centre, and awakes us by causing a premature return of blood to the head. For the above reasons it is apparent how we may go to sleep at times without noticeable fatigue; but because of the greater sensitivity of the vasomotor centre then, on account of lack of fatigue-products, such sleep must, necessarily be light.

As proof that wakefulness depends upon ever-present and ever-varying stimulation, we may cite a case reported by a famous German professor of an idiot boy who could receive no other sensations than those to be had through one eye and one ear. When these entrances to nerve-centres were closed, the boy always went immediately to sleep, and remained so until aroused by the removal of the barriers to stimuli. It may also be mentioned in this connection that prisoners in solitary confinement, unless they find a source of mental activity in some external stimulation, spend an unusual amount of time in sleep. Personal experience of sleepiness in dull weather, dull society, solitude, or under the unvarying stimulation of a monotonous sound, are too common to relate.

IV

It may seem that the condition of brain anæmia, or lack of blood, is not one well adapted to restore the cells to normal activity. But it should be borne in mind that the condition is only relative, and not by any circumstance absolute. Moreover, less blood at this time really seems natural if we remember that during inaction there is no demand for supplies to carry on the function of the cells, but only to replace the comparatively small amount of material not restored during activity. Likewise, there is not so great a demand for the removal of waste products as when they are being continuously produced.

But if cell-restoration during sleep is a task so relatively small compared with maintaining the normal condition of the cell during action, the question arises whether, in order to complete this restoration, it is necessary for us to spend as much time in sleep as we do. Perhaps, on account of popular opinion and personal habit, we waste much time in this jelly-fish condition that could be more profitably spent in active pursuit of our ambitions. The answer of course depends on the nature of our occupation. If there is much muscular effort involved, with a correspondingly large amount of waste in the cells and blood, eight hours or more are probably necessary. But if our work is of a sedentary nature and mainly of the brain, there is naturally a smaller quantity of accumulated waste, and less time is required for its removal. Many are the instances of great men, past and present, who have lived healthfully and worked unceasingly and strenuously on only four or five hours of sleep, or half the laborer’s portion. Surely we are not to suppose that those men were or are physically different from others, but rather that by inclination or necessity they have developed a habit of sleeping intensely for a short period, instead of lightly for a longer period, with resulting gain of time and efficiency.

Depth of sleep and degree of restoration go hand in hand. We have already mentioned the fact that, as determined by sounds and by electrical stimulat ion, the first two hours of normal sleep are by far the most intense, and the remaining period is a state very near consciousness. The mere fact that all through this latter period of five or six hours we are sensitive to stimuli very many times weaker than those necessary to affect us in the first two hours, proves a greater, almost complete, restoration of sensitiveness, or physiological irritability, at the early period of intense sleep. Bearing directly on this point are recent reliable experiments, in which exact tests were made of muscular strength and other conditions, that show that after long loss of sleep in man, — ninety hours, — the amount of sleep necessary for complete recovery was only from sixteen to thirty-five per cent of that lost. This low figure, although partly due to restoration in waking hours, certainly speaks in no hesitating manner for the possibilities of sleep-concentration.

The above considerations would therefore invite us to spend only that time in bed in which sleep is deep and dreamless .and really valuable. If nine or ten hours are spent in bed every night, it will be the personal experience of most persons, unless they have engaged in considerable muscular exercise previous to sleep, that much of this time is spent in getting to sleep, and in repeated waking and dozing and dreaming during the morning hours. Therefore about a third of the time is wasted, for about this proportion of it is spent in an inert condition in the morning that is not true sleep in the sense that there is necessary repair being made, but is merely a condition of suspended animation due to lack of sensory stimulation, toward which the conditions of the bedroom are so favorable, and which we have seen greatly aided in producing sleep in the first place. That even after a night of most refreshing sleep a considerable degree of stimulation is necessary to bring one out of the above condition, is evident from the common experience t hat, even after habit, or an alarm has caused one to rise, one is still half-asleep. We must yawn, rub our eyes, and stretch for some time, and are not fully awake until after the stimulation of tire bath or the morning coffee has sufficiently returned the blood to our heads.

Irregularity of sleep is one of the greatest evils of present conditions. Work or pleasure demands our attention for several nights, and sleep is neglected until exhaustion compels us to resort to it for recovery. But such overstrain, as we shall see more clearly later, is laying the foundation for insomnia, with its keen annoyance and grave injury. If we concentrate our sleep into short and intense periods of strict regularity, the results will in every way be more satisfactory. Just as resistance to muscle-fatigue, which is due to the same products as sleep, is established by short regular periods of intense exercise alternating with complete rest, which break down the cells of the muscle to an extreme degree and rebuild them in a manner increasingly better adapted to resist these toxic waste products, so a resistance to sleep, or the extreme effect of the same products on brain-cells, is also established by periods of intense activity and complete repose. Exact experiments have often shown that artificial increase of oxygen before and during athletic activity greatly increases efficiency, and that proper regard for diet also wonderfully improves physical endurance. Hence a vigilance with regard to sanitary conditions and maintenance of the most complete health will greatly facilitate resistance to sleep and also its concentration.

Just as the intensity of our everyday muscular movements is a matter of personal habit and environment, so is the intensity of sleep subject to the same influences, and it results in corresponding individual efficiency. Thus the savage, with his lack of interests and of necessity for the great activity imposed by the harder fight for survival among civilized people, sleeps much and often. Our early forefathers, for lack of artificial light, slept as do the animals, from sun to sun. There are still traces of a related influence in rural districts to-day where the evening excitement of town life does not exist and the retiring hour is very early. In the long dull winters of Russia the stolid peasants hibernate as truly as do our own bears. But in general the tendency in evolution and civilization has been to concentrate sleep-periods, and make them shorter in total time and more regular. Such a tendency can be due only to individual improvement, however, and for the healthy normal human being of sedentary occupation to indulge in siestas or to spend much more than a fourth of his time in sleep, is lazy neglect of his duty to himself and the race, and a reversion toward the stage of the amœba. Rest there must always be, on account of the mode of action of living matter; but with increasing cell-efficiency it may not in the future have to be of the extreme type that we know as sleep.

V

Having now gained a bird’s-eye view of the nature and causes of sleep and some notion of its relativity, or its changing intensity from moment to moment, let us see how this information will aid us in understanding a few of its variations, such as dreams, somnambulism, and insomnia.

Dreams usually occur in the morning, and are normally a product of light sleep, representing the gradual reinstatement of consciousness after the earlier and more profound slumber. Observations made upon patients with cranial defects show that when we are dreaming, the brain is greater in volume than in deep sleep, and less than when we are awake. Thus this intermediate volume of blood would indicate that dreams are an intermediate stage between unconsciousness and wakefulness, and their incomplete and irregular intelligence would indicate the same thing. This increased circulation is usually due to sensory stimulation affecting the vasomotor centre and causing a return of blood to the head, with resultant increased consciousness. That these stimuli may so affect the individual without waking him was proved by the experiment in which the varying volume of the arm was determined during sleep; for, as already indicated, this volume and the corresponding amount of blood in the brain were affected by all sorts of stimuli from without and within. Thus we see how exposure of a portion of the limbs may cause one to dream of taking a cold drive; and tickling the lips or nose may cause dreams of agony. The discomforts of indigestion are usually the cause of the more intense dreams known as nightmares.

It is evident that, contrary to popular belief, dreams in themselves do not contribute to light or broken sleep in which they are present. Such a condition is due to the ever-present stimuli which, according to their strength or the degree of irritability of the cells, maintain even in sleep a varying degree of consciousness of which the dreams are merely a manifestation. Therefore the fatiguing effect often also attributed to dreams is not due to them, but to the lighter degree of sleep and less complete cell-restoration which they accompany, and which are due to some irritation.

In certain cases these stimuli may only affect the spinal cord and cause reflex actions. Thus, for instance, if the feet become cold they are drawn up to a warmer part of the bed, or the arm may be used to brush away flies, or if the position of the sleeper becomes irksome it may be changed. In still other cases, however, the stimuli may be so powerful, or the cells so irritable, that the brain-centres for voluntary movement are aroused to action. The individual may then make journeys during his sleep or even perform hazardous adventures, ultimately returning to bed and not remembering them on awaking. Thus we have the phenomena of somnambulism as other phases of the relativity of sleep, or degree of effective stimulation and blood-supply. Habitual busy talking in sleep is usually a forerunner of this condition. Perhaps the next phase is that represented by a soldier sleeping while standing on duty, and this is followed by the phase in which an individual walks or keeps his position on horseback while asleep. In other instances apparently conscious actions, such as solving a mathematical, legal, or other problem, and even writing out the solution during sleep, would indicate that certain centres higher than those for voluntary actions, such as that involved in journeys, were also being exercised, while at the same time many others, under the influence of toxic waste or lacking in local blood-supply, were asleep.

Such actions of somnambulism are usually performed under the influence of a ‘fixed’ idea, which means that during waking hours the sleeper had been thinking much of the action or question involved. Under such an influence the continuous presence of excess of waste products, or alteration in their character, seems to increase rather than to lower the irritability of the cells. Such a condition is well expressed by the term ‘ irritable weakness,’ and is not unknown in muscular tissue. There is also an alteration of the blood-supply. We have shown that in acts of attention to sensations there is a general return of the blood to the head even in sleep, for under the conditions of nature such stimulation, especially when painful, demands alertness and increased activity on the part of the animal. But, furthermore, it has been pretty well established that attention, even when not directed toward any particular region of the body, is “accompanied by local increased blood-supply to the particular brain-centres involved. This better condition for activity in these centres, as compared with that in others, would explain how, in concentration of attention and its often amusing phases of absence of mind, or even in hypnosis, we are oblivious to many sensations which at times of general attention, or of blood-supply, would be very striking. Now, when a ‘fixed’ idea takes possession of one, it is most probable that this condition of local increased blood-supply continues over into sleep on account of exhaustion of the muscles controlling the size of the blood-vessels. Somnambulism, therefore, is a local insomnia. This circumstance of varying blood-supply for different centres, besides explaining the various phases of somnambulism, makes clear the related condition in which mother, nurse, or physician may be sound asleep even to loud noises, but wide awake to the slightest change in their charges.

This conception of the relativity of sleep is further supported by the fact that the senses go to sleep in a definite order. Thus sight is the first sense lost , even when the eyelids have been removed or on account of disease cannot be closed. As is to be inferred from preceding passages, the other senses are not altogether abolished; their acuteness is simply lessened. But, within this limit, taste is the first to fade, and then smell; touch follows, and hearing is dulled last of all. We thus have an indication of the most favorable point of attack at which to arouse a sleeper. In awaking, the senses return in reverse order. The sequence in which the muscles lose their power is in general also well marked, and bears a distinct relation to the importance of their functions. Thus the muscles which move the arms and legs become relaxed before those which support the head, and the latter before those which maintain the erectness of the back.

Bearing still further on the question of the depth of sleep is the general condition throughout the body at this time, in which — as in the case of the special senses — the functions of the various organs are not completely suspended, but only diminished inactivity.

VI

Just as we have seen that normal sleep varies in depth according to the degree of irritability of the cells and of intensity of ever-present stimuli, it is evident that, by a sufficient degree of irritability or stimulation, sleep may be prevented altogether. Thus, as instances of this condition, we may mention the wakefulness due to hunger, heat, cold, heavy covering, over-eating, or over-fatigue. In the summer, intense heat at night is out of the ordinary routine of sensations. Then a succession of restless nights may engender a fear of sleeplessness which keeps the brain congested and so encourages the cause of the fear; for we have seen that in sleep there is less blood in the brain. Also at such times humidity may interfere with the perspiration, and that part of the toxic waste which is normally removed by this route, accumulates—producing all sorts of discomfort, and even serious conditions.

There are, however, more serious and permanent conditions of insomnia.

We have shown that in somnambulism under the influence of a ‘fixed’ idea, there may be a local insomnia on account of an irritative toxic condition and a continuous increased blood-supply at particular centres. So under the influence of overwork of the brain, or a powerful emotion such as sorrow or worry, irritative toxic conditions or chronic increased blood-supply may be more general, and any degree of sleep whatever is prevented. Just as a muscle after extreme exercise may exhibit a condition of ‘irritable weakness,’ manifested by cramps and irregular contractions due to excess of waste products which under certain conditions of kind and amount are irritative in their action, so brain-tissue under constant irritation from such a condition and almost excited into action, is over-sensitive upon the addition of ordinary stimuli. Thus we have a sort of ‘ hair-trigger’ arrangement, which makes the ever-present stimuli from skin and internal organs effective enough to maintain wakefulness. This condition is intensified by the continuous increased blood-supply due to the fatigue of muscles controlling the size of vessels which are kept overdistended by the worry or other mental activity. By a similar action, wakefulness is produced by certain substances used as food or medicine, but which are irritating in their local action or increase the frequency of the heart’s beat, such as alcohol, tea, or coffee.

Naturally, with continuous insomnia the brain-cells have no rest, are not restored, and serious conditions arise. Their gravity is indicated by the fact that dogs kept from sleeping die at the end of the fourth or fifth day, and their brain-cells show the changes characteristic of extreme fatigue. With man, the tired brain is unable to supply the proper innervation for other organs, and there appear such signs of nervous trouble as irregular heart action, dyspepsia, and other digestive disturbances. Any tendency to unusual involuntary loss of sleep should therefore receive the immediate attention of a reliable physician.

In conclusion, we would emphasize the fact that sleep is only to a certain extent a necessary evil, and that it is due to shortcomings of the body that are only a matter of degree and show possibilities for improvement. As already indicated, the only factors that limit human endeavor — fatigue, sleep, disease, and death — are all due to the inability of the organism to deal with excess of chemically definite toxic products, more or less the same in each case and varying mainly in amount. The possibilities for improvement in these lines have been demonstrated by the establishment at will of a greater resistance to fatigue, by a wonderful diminution of disease through artificial increase of the natural protective processes of the body; and even death itself has been stayed by such natural methods of prolonging life as those of Metchnikoff.

Sleep should offer no greater difficulties to this pleasant possibility of its removal, and indeed we have shown that the evolutionary tendency is to a shorter period. Being due to a comparatively low resistance of the brain-cells to waste products that are not neutralized rapidly enough in the blood or removed by the excretory organs, the opportunity for improvement is as great as in a muscle, in which fatigue, or its sleep, is due to exactly the same conditions. Therefore the same method is to be employed, namely, periods of intense activity followed by complete rest, which in this case is intense sleep. Thus the brain-cells are broken down to an extreme degree, and rebuilt in a modified form that is increasingly less susceptible to the action of fatigue-products, while at the same time the excretory functions arc correspondingly improved by greater exercise. Finally, as considerable effort of the will is necessary to maintain the routine of muscular training, so the tendency to mental inactivity in unnecessary repose is to be met by a firm habit which concentrates and intensifies sleep and affords us more available time, with corresponding greater efficiency and progress.