The glands of internal secretion, the history of which, as tools of thought, I reviewed in the previous chapter, have each an interesting evolutionary story. Without some acquaintance with that story, the rough outline of their physical architecture, and the particular work they are called upon to perform in the body, no adequate understanding of their influence upon types of human nature and personality is possible.

THE THYROID GLAND

This gland consists of two maroon colored masses astride the neck, above the windpipe, close to the larynx. These are bridged by a narrow isthmus of the same tissue. They remind one of the flaps of a purse opened up. The gland has always attracted much attention because its enlargement constitutes the prominent deformity known as goitre.

To begin with, the thyroid was once a sex gland, pure and simple. In the lowest vertebrates and in the homologous tissues of the higher invertebrates, the fractions of the thyroid are intimately connected with the ducts of the sexual organs. They are indeed accessory sexual organs, uterine glands, satellites of the sex process. From Petromyzon upward that relationship is lost, the thyroid migrates more and more to the head region, to become the great link between sex and brain. How alive that function still is, is grossly shown by the swelling of the gland with sexual excitement, menstruation and pregnancy.

Relative to the body weight it is largest in the mammalia, and smallest in the fishes. It therefore grows larger as the vertebrate ascends in the scale. It has, in fact, developed in direct proportion to and side by side with the fundamental, differentiating vertebrate characteristics. Of these, the possession of a dry hairy skin instead of a moist or mucus bearing, chitinous skin, the ownership of an internal bony skeleton and a large skull, and a complicated development of brain, are the diagnostic signs. Thyroid internal secretion has a very definite controlling relation to all of them: to skin, its hairiness, moisture and amount of mucus, to the growth and size of the bones, especially the bones of the extremities and the skull, and to intelligence and the complexity of the convolutions of the brain. Injury to the thyroid, especially in growing animals, is followed by profound retrogression or arrest of development in skin, skeleton and brain.

In the fishes and the cyclostomes the thyroid is represented only by some small scrubby patches, little larger than the heads of pins, scattered along the aorta, the great blood vessels from the heart, and out a little way along each gill. It becomes larger and more compact among the amphibians and reptiles, but still remains quite small. Large and prominent among the birds and mammalia, it is largest and most prominent among the primates and man. It is hence permissible to think of the thyroid as a dictator of evolution, to crown it as the vertebrate gland par excellence, and to call the typical vertebrate brand marks secondary thyroid characteristics in precisely the sense of Darwin classing the horns of cattle as secondary sexual characteristics.

In such enthusiasm for the thyroid as a determinant of evolution, its pillar of cloud by day and column of fire by night, one should not forget the other glands of internal secretion. In them all, we may suppose, Life, tired of inventing merely prehensile, destructive and reproductive organs, hit upon the happy thought of contrivances which are in essence chemical factories to speed up the rate of variation and so of a higher evolution.

CREATOR OF THE LAND ANIMAL

According to this conception the thyroid played a fundamental part in the change of sea creatures into land animals. Experimentally, thyroid has been used to transform one into the other. Thus the occasional change of a Mexican axolotl, a purely aquatic newt, breathing through gills, into the amblystoma, a terrestrial salamander, with spotted skin, breathing by means of lungs, has long been known. Feeding the axolotl on thyroid gland produces the metamorphosis very quickly, even if the axolotl is kept in water. In the reptile house at the London Zoological Gardens full-grown examples of the common black axolotl and the pretty white variety are exhibited. Some are nearly three inches long. Alongside are shown several examples of the amblystoma stage, produced in one of the laboratories of Oxford University and at the gardens by thyroid feeding. A variation of the thyroid in the direction of increased secretion was probably responsible for the first land animals.

THYROXIN, SECRETION OF THE THYROID

Under the microscope, as in the test tube, the thyroid shows remarkable and unique features. Closed spherules lined by a single layer of cells enclosing a gelatinous material known as colloid, which stains deeply with acid dyes, comprise the units of its architecture. Essentially, it may be pictured as a series of jelly bubbles secreted by outlying cells.

A relatively high percentage of iodine is the unique distinctive fact in its chemistry. Discovered by Baumann in 1895, the presence of the element has focused the intelligence of chemists upon the gland, with the consequent demonstration of arsenic also in it. It was soon manifest that the secretion of the gland was dependent upon the iodine content for its activity. Active extracts of the thyroid like thyreoglobulin and iodothyrin were proven to contain iodine, and to become inactive when the iodine was removed. Efforts to isolate the iodine containing active principle in pure form were fruitless until the work of Kendall at the Mayo Foundation. He obtained it as a white, finely crystalline, odorless and tasteless substance, heat stable, and analyzable. The free form separates as a sheaf of fine needles. Kendall at first called it the a-iodine compound, then named it thyroxin.

There are other internal secretions of the thyroid, with a function of their own, that have no iodine. But they are secondary, and obscure. Thyroxin is accepted today as the purified internal secretion of the thyroid because all the effects of the whole gland may be elicited with it. Thyroxin produces results with doses amazingly minute compared with the quantity of whole gland necessary. Moreover, a dose of thyroxin appears to last an organism in need of it over a period of time; the other has to be administered continuously.

Studies with thyroxin carried on in recent years have rounded out the whole concept of the business of the thyroid in the body economy. One may sum it up by saying that the thyroid secretion is the great controller of the speed of living. The more thyroid one has, the faster one lives; the less one has, the more slowly one lives.

That is not to imply any direct proportion between the amount of thyroid secretion in an individual, and the length of life to which he is destined. The speed of living, in the chemical sense (which is the fundamental sense), and the rate at which the chemical reactions go on that constitute the process of life, are dependent upon the thyroid. When the reactions go faster, more oxygen and food material are burned up or oxidized, more energy is liberated, the metabolic wheel rotates more quickly, the individual senses, feels, thinks and acts more quickly.

Likening one energy machine to another, the thyroid may be compared to the accelerator of an automobile. That is a rough and superficial comparison because an accelerator lets in more of the fuel to be burned up, while the thyroid makes the fuel more combustible. It thus resembles more the primer, for a rich mixture of gasoline and air burns at a greater velocity than a poor one. But the action of thyroid could really be simulated only by some substance that could be introduced into the best possible of gasoline mixtures, to increase its combustibility by a hundred per cent or more. For that is what thyroid will do to our food. Nor has it only this destructive or combustion side. Withal there is at the same time a constructive action, for the process frees energy to be used for heat, motion or other need. The thyroid, therefore, in addition to its rÔle as an accelerator, acts, too, as the efficient lubricator for energy transformations. So we see it as accelerator, lubricator and transformer of our energies.

THE GLAND OF ENERGY PRODUCTION

The isolation of thyroxin has made possible the determination of the influence of the thyroid hormone upon the evolution of energy in any higher animal organism. There is, for every individual, a constant, known as the metabolic rate, or the combustion rate, a reading of the rate at which his cells are consuming material for heat. The metabolic rate is thus a gauge of the energy pressure within the organism. It may be calculated by measuring the amount of carbon dioxide gas exhaled during a unit of time, and the number of calories of heat radiated by the skin simultaneously. A simplified device has lately rendered it practicable to make actual determinations by a few five-minute readings of the rate of oxygen absorption by the lungs. Plummer, also connected with the Mayo Foundation, has shown that what would amount to less than a grain of the thyroxin would more than double the amount of energy produced in a unit of time. To be exact, one milligram of thyroxin increases the metabolic rate two per cent. That illustrates some of the power of the internal secretion of the thyroid and its importance to normal life.

THE MOBILIZATION OF ENERGY

But not only is the height of pressure of energy in the cells controlled by the thyroid. The mobility of that energy is also controlled. Without it, rapid and large fluctuations of energy output, and elasticity and flexibility of energy mobilization for any sudden mental or muscular act, let alone an emergency, become impossible. A woman suffering with myxedema, the condition described by the English physician Gull as a cretinoid state supervening in the adult life of woman, has an insufficient amount of thyroxin in her blood and tissues. She is clumsy and awkward and will stumble when endeavoring to walk upstairs. Any effort is almost paralyzed because the range of fluctuation of energy, the ability to mobilize energy, in turn dependent upon an ability to increase the metabolic rate, is limited. In slang phrase, she cannot step on it. Her existence is set to go at a rate in the neighborhood of forty per cent below the normal. By the administration of thyroxin, her metabolic rate can be raised to any desired figure, the spark can be adjusted, so to speak, to any point we like, and it can be so maintained for years.

In the normal animal, to be sure, the internal secretion of the thyroid is not absolutely essential to life. So it contrasts with the hormone of the minute parathyroids placed so closely to it, a minimum dose of which is absolutely a prerequisite for continued life. The fundamental chemical reactions within the cells occur in the complete absense of thyroxin. But they go on in a relatively fixed, rigid and unvarying way, confined within the narrow limits of a constant figure. Under such conditions, the level of energy production is bound to be low, and to remain low, and the modus of its mobilization slow and unwieldy. With thyroid is introduced the trick of catalysis, or the speeding up of the vital chemical reactions, through the agency of an intermediate which accelerates the process. It is par excellence the great catalyst of energy in the body. (A catalyst is an intermediary like the trace of water, which will bring about an explosion between dry oxygen and hydrogen that without it have stayed inert with the strongest currents of electricity.) Thus it supplies a mechanism not only for quantity output of that subtle reality we label energy, but also an apparatus for varying the available amount of it, and for permitting the maximum range in ease and rapidity of its utilization. The thyroid is still another device of life for procuring more and more variation and differentiation, its goal, as far as we can peer through the opalescent screen upon which its manifestations quiver.

From another point of view, the thyroid may be looked upon as the organ evolved for maintaining the same amount of iodine in the blood as there is in sea water. Sea water was our original habitat, since, like Venus, we have all come up out of the sea.

The more intimate study of the composition of the blood has revealed the most astonishing parallelism between it and the compounds of sea water. The blood is sea water, to which has been added hemoglobin as a pigment for carrying oxygen to the cells not in direct contact with the atmosphere, nutrients to take the place of the prey our marine ancestors gobbled up frankly and directly, and white cells to act as the first line of defense. To keep the concentration of iodine in the blood a constant, the thyroid evolved, since there is no iodine in most foods and very little in those which do contain it.

That a minimum amount of iodine in the food is necessary to health is shown by the existence of goitre regions. Around some of the Great Lakes in the United States, for instance, the water does not contain enough iodine. As a result, numerous cases of goitre occur. Iodine in the form of sodium iodide in small doses will act as a prophylactic. The amount of iodine in the blood is about one or two parts to ten millions, and that of the liver is about three or four parts to ten millions. Since the liver is the most complex and active chemical factory in the body, its appropriation of a greater amount of iodine for itself is understandable.

When thyroxin is administered in a single dose, there is a distinct lag in the absorption of it by the tissues. A single dose does not generate its maximum effect until the tenth day. This effect continues for about ten days. Then there is a gradual decrease in the intensity of reaction for another ten days. So that the length of time a single administration of thyroxin functions within the body is about three weeks. Again we have occasion to notice a protective device of the cells. Since the presence of thyroxin in the tissues determines the rate at which they burn themselves up, it is obvious that if there were no mechanism for retarding its action, and at need varying it, they really would set fire to themselves. That is to say, if the tissues held a maximum of the thyroid internal secretion, and had to take up more and more as it was fed out to them by the thyroid through the blood, the pressure of energy production would attain the state of a boiler without a safety valve. Even if self-destruction were avoided by the ingestion of the largest quantities of energy-bearing foods, rest for the cells would be difficult, if not impossible.

The thyroxin in the tissues diminishes after a period of great exertion, the thyroxin probably being carried back to the thyroid gland and kept there as reserve until further demand. So it has been discovered that during the winter months, the thyroid glands of beef, sheep and hogs all contain much less iodine than during the summer months. During the winter months, manifestly, more energy is required to maintain body temperature, hence the gland surrenders more of its secretion to the tissues and so keeps less of it itself. There must be, too, a certain wearing out of the potency of the iodine with time. Even dead inorganic catalysts, made of simple elements, wear out after having been used time and time again.

Though the thyroid is the supreme energizer, life is incompatible with a certain excess of it. Death can be produced by successive daily injections of its internal secretion. But it has, besides the energizing effect, certain formative and nervous influences equally marvelous. As illustrations, there are the cases of thyroid deprivation in human beings, cretinism and myxedema, as well as those in which it is believed there occurs an excess of the thyroid secretion in the blood and tissues, the condition of _hyper_thyroidism.

CRETINISM AS THYROID DEFICIENCY

Not that there is any arresting contrast of startling difference between the phenomena presented by different species. The younger the animal, the grosser the morbid symptoms witnessed. The animal fails to grow. The bones and cartilage, except of the skull, fail to develop. The abdomen projects and becomes large and flabby. The sex organs atrophy. There is sterility. Pregnant rabbits abort, hens produce very small eggs or none at all. These are the results of removing the thyroid in animals.

Apathetic, indifferent, dirty, awkward, apparently idiotic, describe the human cretins. Their skin is rough and coarse, peeling in sheets. In some it is considerably knarled and creased as in the aged, and in others swollen, hard and resistant. The hair becomes shaggy and rough, losing all luster, and tends to grow irregularly and fall out. The temperature becomes subnormal and an anemia supervenes. There is a distinct reduction in the resistance to infections and intoxications.

Cretinism in the human is a condition in which the burning taper we call Life flickers and smoulders and smokes. Thirty years ago it was an example of the most hopeless idiocy. Whole populations were afflicted with it. But neither man of science, nor bigot-fanatic, assured by the Divine Confidence of its meaning as a visitation, believed it could be modified an iota. Today, that inept word "cure" may be applied to our power of attack upon it, provided it is permitted to attack early enough. Modification, in the direction of the most surprising betterment, is the miracle that has been wrought.

The history of a cretin runs somewhat as follows: A baby is born, which in all appearances seems normal. Perhaps the nose is a trifle squatter than even the average new-born's flat nose. There may also be abnormal sleepiness, greater even than that of the normal baby in the first month or two in that there is no spontaneous awakening from the coma for food. But in most cases this is put down to normal variability, or maybe to that limbo of all a baby's troubles: weakness. After some months, it is noticed that the infant is failing to grow at the normal rate, either physically or mentally. Examination at this time reveals a curious thickening of the dental ridges. Then the tongue takes the centre of the scene, by becoming unusually thick and prominent, to the point of projecting beyond the mouth at all times, and interfering with breathing, when the infant is in a recumbent position.

More and more of the characteristics of the affection turn up. The queer, repulsive, pitiful face of the cretins, which makes them all seem brothers or twins, shapes itself. A yellowish, white or waxy pallor; rough, dry, scaly, bloated skin; swollen, often wrinkled brow; watery eyes, often almost concealed by the thickened eyelids; the depressed pug nose with its wide, thick nostrils; large, erect ears; the wobbly, drooling tongue, sticking out at one, yet not in derision; the hair thin, and like tow in texture rather than human; eyebrows and eyelashes are scant, and often absent; the nails short, thin and brittle; the teeth, very late in coming, may be represented by a few sharp points, irregular, decaying quickly, sometimes not succeeded at all by those of the second dentition.

Whatever growth occurs is irregular and disproportionate. The trunk, though small compared with the head, appears massive against the background of the diminutive extremities. The back is somewhat humped, arching at the waist-line, while the abdomen protrudes like a balloon, with a hernia, often, at the navel. The extremities are short, bowed, cold, and livid, covered with rolls of the infiltrated skin, rolls which cannot be smoothed out. Hands and feet are broad, pudgy, and floppy, the fingers stiff, square and spade-like, the toes spread apart, like a duck's, by the solid skin. Above the collar bones there are frequently great pads of fat which sometimes encircle the narrow bull neck.

The mental state varies with the degree of deprivation of the internal secretion of the thyroid. In the worst cases it is repulsively vegetable. Even the intelligence common to the higher animals is wanting. The cretins of the "human plant" kind, as they have been nicknamed, will not recognize mother or father or any person about them, or even a person from an object, and manifest no interest in anything or anybody, not even toys. Hunger and thirst they manifest by grunts and inarticulate sounds, or by screaming. They neither smile, cough, nor laugh, but sit like sphinxes, breathing, but not reacting.

There are, of course, all grades and varieties. There are those who recognize parents and familiar faces, and exhibit some evidence of affection for them, acquire a limited vocabulary, and then cease, no progress possible even with the alphabet. They attain the size and age of two or three years and there stop altogether, as if a permanent brake were applied to the wheels of their growth. Some higher types may even come to speak connected sentences, and exhibit a certain mild spontaneity, though stupid and slow and abnormally deliberate, resembling the acquired form of thyroid deprivation or insufficiency, for which Ord invented the name myxedema.

I have filled in with some detail this thumbnail sketch of thyroid deprivation as it occurs in infancy to illustrate how wide a sweep the gland's lariat embraces. Skin, hair, bones, muscle and fat, brain and intelligence, growth and development, are modified precisely as the size and shape of certain crystals are modified by the presence or absence of ingredients in an apparently homogeneous solution. A fertilized ovum, in which the predecessor of the thyroid gland is present, that is to say, in which there is the seed and soil for its sprouting, looks the same as one without that formative material. Yet, when the time comes for the internal secretion of the thyroid to put in its oar in the metabolic game, its presence or absence makes all the difference in the world to the individual.

In the middle of the nineteenth century, when the concentration of phosphorus in the brain was established as significant, the cry for the emphasis of that fact was—without phosphorus no thought is possible. We can much more relevantly declare that without thyroid, no thought, no growth, no distinctive humanity or even animality is possible. For the epigram about phosphorus was bombast, since it can be declaimed with equal truth that without oxygen, without carbon, without nitrogen, without any of the food elements that go to make up the chemical composition of brain matter, no thought is possible. Indeed, if one were set upon the indictment of a single chemical element as the begetter of consciousness, the prisoner at the bar would have to be copper. There is more copper in the brain by a considerable degree than in any other organ of the body. Which perhaps will be exceedingly regretted by the patrons of the aristocracy of the soul who would have it as an emanation of a deposit in the brain of silver at least, if not gold. They are like the old lady who would never permit herself to be cured of her ailments except by gold plated pills. Copper, however, is not necessary to intelligence. Without thyroid there can be no complexity of thought, no learning, no education, no habit-formation, no responsive energy for situations, as well as no physical unfolding of faculty and function, and no reproduction of kind, with no sign of adolescence at the expected age, and no exhibition of sex tendencies thereafter.

EFFECTS OF FEEDING THYROID

How subtly the internal secretion affects every phase and aspect of child as well as adult, by doing something to the speed of activities in their cells, is told straightway by the effects of it when eaten or introduced into the skin or blood of various people. A cretin, idiotic, dwarfish, deformed, hopeless, an incessantly prodding burden of sorrow to the mother, who looks upon the masterpiece she had labored to bring forth, and beholds a terrible gargoyle, becomes transformed when fed thyroid.

In a few days the cretin will get warmer, and require much less wrapping and bed-clothing. With the improvement in circulation, the color becomes better and the extremities lose their coldness. In a week or so, irritability and resentment at disturbance appear. He will begin to recognize and know his parents, smile and play. There is a gradual return to the normal of the facial appearance, and a resumption of growth. All kinds of marvelous growth effects occur. Twenty teeth may be cut in six months. Coarse, rough dry, shaggy hair becomes fine, silken, long and curly. The skin becomes soft, moist and roseate. Inches in height may be added every month. Bright, active, even talkative, are the descriptive terms an observer would apply after a few months. A complete remaking of body and soul is apparently affected.

Yet, should the administration of the thyroid cease, an almost immediate reversion to the original vegetative condition is inevitable. After a few days, reactiveness slows down, the child will speak only when spoken to, will sit quietly in a chair all day and act semi-anesthetized. Gradually hair and skin return to the previous cold-blooded animal state, and the whole picture of the cretin is in full bloom. Supplying the internal secretion of the gland promptly repeats the transformation.

One wonders what is to be the ultimate fate of these reformed cretins. Since the tale of the opening of life to them, once considered hopeless idiots, is scarce a generation old, we have no data, as yet, as to the character of their children or grandchildren, their adventures and vicissitudes, in short, their life history. Those of whom we have any record are normal and healthy school children or workers, alive to the interests of childhood or their occupation and social circles. No one outside their family knows that they are cretins, and the most acute observer would be hard put to it to suspect. What a theme for the reflections upon appearances the eminent Victorians loved!

There are possibilities the imagination may envisage. One may suppose such a cretin, with all his other ductless glands intact, grown successfully to manhood under careful medical guidance. No one but himself is aware of his affliction, outside of his medical advisers. Luck aids him to rise in the world, or perhaps he has been born with a spoon of the precious metals in his mouth. Adolescence, love and marriage dance their sequence. Our hero of course keeps his dread secret to himself. Whether such an omission of confidence would entitle his wife to a divorce is something courts will be called upon to decide sooner or later. But, without anticipating, the honeymoon involves a trip to the South Seas. A storm and a wreck throws them alone on an island, tropical, easy to live on, and rescue in the course of a few months certain. The man, to his horror, discovers that he has saved of his medicaments only a pill box containing half a dozen of thyroid tablets, his requirement being one a day. He sees them go day by day. Finally they are all gone. He feels his faculties slipping hour by hour. Shall he tell her? Indecision grips him, and he delays until the day when his consciousness sinks to the point where his mind no longer grasps his problem. The wife must endure the spectacle of the enchantment of her husband, and his change from gallant lover to dull animal ogre. A new version of Beauty and the Beast!

Cretinism as one manifestation of a soul without thyroid or without enough thyroid is not all. The first great successes with thyroid were achieved in adults, particularly adult women, exhibiting a peculiar obesity, coldness, loss of hair and teeth and a remarkable lassitude and torpor that might be summed up as a chronic drowsiness, like a saturation of the blood with some narcotic drug. Or there may be a melancholia, or a lack of ability to seize the finer points of a mental process, or an argument treated in the abstract. Children are said to be lazy, slow or dull. They experience an irritating difficulty in understanding questions and expressing their wants and desires, and so are declared to be vicious, or stupid.

All these are grades of the degeneration which Ord, the Englishman, named myxedema. At its worst it is a sort of bloating and drying of the body and the mind. Then there is infantilism, which is helped by the giving of thyroid extract. It differs from the ordinary cretinism in that, while one is reminded of the latter by the physical stunting and the other stigmata, there is a certain amount of intelligence which enables the individual to hold his own while he is a child. He becomes a grown-up baby: at twenty prefers the company of children of ten, and passes under the evil influence of designing so-called normal persons. So dominated he will lie, steal, start fires, commit almost any crime, with no inherent flair for criminality, but because of a lack of independent judgment and inability to resist suggestion, and a desire to please friends. He is simply an overgrown child who still loves to play with toys, laughs and cries, becomes angry or afraid, unreasonably and ridiculously, and yells for mamma when thwarted or scared.

So much for what happens when there is not sufficient of the thyroid secretion in the blood and tissues. Now to consider the effects of an excess of it, the condition called hyperthyroidism, as the insufficiency of it is labelled subthyroidism. Too much thyroxin can be introduced into the system of a normal individual, or even a cretin by the simple administration of too large doses or over too long a time. Also a train of symptoms similar to those evoked by an oversecretion of the thyroid may be mobilized by the taking of too much iodine. Great sorrow, great joy, a sudden severe jolt to the nervous equilibrium, sexual excitement, an overwhelming anger or grief may leave in their wake a permanent hyperthyroidism. The symptoms are the reverse of cretinism and myxedema. There is an over-excitability of the nerves in place of sluggishness, and an over-reactivity of the whole organism to its environment. The heart's action is too fast, and under the slightest stimulus gets faster to the point of obtruding itself into the conscious mind as a palpitation. Instead of the lowered temperature and coldness of the cretin, there is a heightened temperature, one or two degrees above the normal, and a feeling of heat. The individual has a high warm color, does not sleep well, becomes or remains thin no matter how much he or she eats, is abnormally susceptible sexually, may suffer from a definite insomnia, is emotional, and perspires freely. Alert, neurotic or high-strung, magnetic, and imaginative are some of the descriptive adjectives applicable. The eyes are bright and prominent, large and beautiful, when they have not reached the stage entitled "pop-eyed." Or they may even become so protuberant and bulging as to develop the expression of one staring aghast at some ineffable horror. The latter is the feature of only the severest types, when there is an associated goitre, the combination designated as exopthalmic goitre.

There are, too, individuals in whom hyperthyroidism and hypothyroidism are mixed, or rather alternate. At one time they present the phenomena of the one, at another of the other. They are the people who complain of the cyclic quality of their moods and purposes. Their mood will be a heaven of exaltation and exhilaration, and then descend into a slough of despond from which they feel themselves inextricable. They are always talking about the ups and downs of their mental states. Headache and languor and fatigability, dry skin and lack of appetite for food or exertion on one day or for one week, give way on the next day, or for the next week, to an energetic gayety, and sweaty, flushed skin, a prominent appetite for food and every sort of activity. Driven to be forever on the go, for one period, in the next they feel like lying down most of the day, with no inclination for any life whatever. The stage of depression may go as far as a melancholia, the stage of stimulation as far as mania. They may simulate manic-depressive or cyclic insanity. Something restrains them, and holds them bound as in a vise in the one cycle. And then they are driven on beyond themselves by some invisible whip in the next.

THYROID AS DIFFERENTIATOR

Besides the action of the thyroid as energizer, lubricator, and growth catalyzer, it has a remarkable power as a differentiator of tissues. It determines the embryonic etchings of the different organs which in their totality comprise the unique individual. Every multicellular animal must first have existed as a single cell, the impregnated ovum. With the body and personality of the ovum, the creature is one and continuous, literally something the single cell has made of itself by sub-dividing and differentiating. In the process, the cell mass often goes through stages which stand out as individualities in themselves, that appear on the surface absolutely unrelated. So the caterpillar and the butterfly, to the naÏve child, seem as far apart as worm and bird. In the case of the frog, the tadpole as a first sketch seems completely an impossible and wild absurdity. Yet we know that there is an orderly progression of events, a propagation of cells, a forward going arrangement of chemical reactions, that results in expansion and intricate complication of the organism. Just what the forces at work in this most mysterious of all natural processes are, has been an intellectual mystery that the best minds of the race have attempted to get rid of with words like pangenesis (Darwin). Words of Black (Mediterranean or Greek and Latin) origin, as Allen Upward has named them, always cover a multitude of ignorances. The glands of internal secretion, here, as in so many other dark places, provide the open sesame to certain long closed doors of biology. They offer themselves to us as the first definitely tangible agents which are known to keep the process of growth going, and undoubtedly initiate the marvelous unfolding of tissues and functions, organs and faculties summed up as development or differentiation.

Thus by the direct feeding of thyroid at particular points in the differentiating history most curious effects have been elicited. If the gland is made part of the nutriment, the bathing environment, of the tadpole, a hastening of its metamorphosis is attained. The tadpole lives not out its day as a tadpole, but precociously turns into a frog. But such a frog! It is a miniature frog, a dwarf frog, a frog seen by looking through the wrong end of the telescope, a frog not magnified, but micrified. Frogs have been so created the size of flies. There has occurred a splitting of the two reactions which ordinarily go hand in hand: the reaction of growth which is just brute increase of total mass or weight and volume, and the reaction of differentiation which is the finer process. The picture is a frog, but a frog the size of a tadpole, a frog which has missed its childhood, adolescence and youth, skipping over these transition stages into the adult age, as a pigmy.

It is all as if a baby were suddenly to grow a beard and moustache, evolve and shed teeth, and acquire the manner of an earnest citizen, and yet retain the height and weight of a baby. That the spectacle of such a superbaby is not quite the most fantastic of all improbabilities is shown by the condition of progeria, first recorded by the Briton, Hastings Guilford. A queer spectacle in which a child incontinently grows old without having lived—in the course of a few weeks or months. You look upon him and see senility on a small scale, but with all its peculiarities: wrinkled skin, apathy, gray hair and all the rest of it. All we can say about it is that it is probably due to a paralysis of all the glands of internal secretion, a removal of their influence upon the cells. Contrariwise to the feeding of thyroid, removal of the thyroid of tadpoles will prevent their development into frogs. If iodine is then fed to them, say mixed with flour, normal metamorphosis will occur. If Body is the tool chest which we carry about with us, as Samuel Butler said, then to the thyroid belongs the name of tool-maker.

Another function of thyroid that must be taken into consideration is what has been spoken of as its antitoxic function—in plainer English, its power to prevent poisoning, or to increase resistance against poisons, including the bacteria and other living agents which cause the infectious diseases. Each molecule of food, ingested for assimilation into our substance, accumulates a history of wanderings and pilgrimages, attachments and transformations beside which the gross trampings of a Marco Polo become the rambling steps of a seven-league booted giant. In the course of its peregrinations, it becomes a potential poison, potential because it is never allowed to grow in concentration to the danger point. The thyroid plays its rÔle of protector like all the internal secretory machines. In an animal deprived of a thyroid the feeding of meat shortens life—a single sample of how it works to guard against intoxication from within. The feeding of thyroid will also raise the ability of the cells to stand poisons introduced from without—intoxications of all sorts. Alcohol and morphine will affect in much smaller doses the subthyroid person than the normal or the hyperthyroid. As regards the infections, which directly or indirectly kill most of us, the injection of thyroid will increase the content in the blood of the protective antibodies which preserve us, temporarily at any rate, against malignant invaders. The opsonins, for example, those substances which butter the bacteria so that the appetite of the white cells for them is properly roused, are mobilized by thyroid feeding or injection. Other substances in the blood which destroy and dissolve bacteria are also increased. The thyroid probably performs these functions by sending its secretion to the cells directly responsible for the immunity reactions, and stimulating them to activity.

A sketch of the thyroid like the foregoing shows it as the wondrous controller of vitality and growth, and indefatigable protector against intoxicants and injuries. When it is sufficiently active, life is worth while; when it is defective, life is a difficult threatening blackness. That would make it out as the gland of glands. It is tremendously important, without a doubt, in normal everyday life. But no more so than the other members of the cast. The position of star it may claim, but in vain. The other glands of internal secretion to be sketched will each, when the marvels of its business in the cell-corporation are considered, present itself as candidate for the honors of the president. Justice should give fair credit to all the organs which fabricate the reagents of individuality, and the regulators of personality.

THE PITUITARY

In the human skull, the pituitary is a lump of tissue about the size of a pea lying at the base of the brain, a short distance behind the root of the nose. It is of a grayish-yellow color, unpretentious and insignificant enough in appearance, and so long neglected by the scientists who boast their immunity to the glamor of the spectacular. Guesses at its nature date back to Aristotle.

Like most of its colleagues among the glands of internal secretion, it is really two glands in one, two glands with but a single name. At least it consists of two different parts, distinct in their origin, history, function and secretions, but juxtaposed and fused into what is apparently a homogeneous entity. They are conveniently spoken of as the anterior gland and the posterior gland.

In the embryo, the anterior gland is derived by a proliferation of cells from the mouth area. The posterior gland represents an outgrowth of the oldest part of the nervous system. When it is traced back along the tree of the vertebrate species, it is found to be present in all of them. An ancient invention, its precursor has been identified in worms and molluscs and even among the starfish. "The pituitary is practically the same, from myxine to man." A trusted veteran, therefore, among the internal secretory organs, its importance can be surmised.

To understand the story of the pituitary, variously acquired bits of information concerning it have been assembled and fitted together like the fragments of a picture puzzle, as Cushing has so well put it. Here and there pieces stick out, obviously out of place. The relations of some of them to one another or to the whole design are not at all clear. Parts appear to have been irrevocably lost, or not yet to have turned up. Chance bystanders will select odd figures and articulate them into a new harmony. Yet out of the jumble of fragments, a fairly respectable insight has been gained in less than a half century.

The pituitary is cradled in a niche at the base of the skull which, because of its form, is known as the Sella Turcica or Turkish saddle. So situated, an operative approach to it is overwhelmingly difficult. On the other hand, X-ray studies are favored. "Nature's darling treasure" it might be called, since there has been provided a skull within the skull to shelter it.

Under the most highly magnifying lenses of the microscope, three kinds of cells have been distinguished. The anterior gland is a collection of solid columns of cells, surrounded by blood spaces into which their secretion is undoubtedly directly poured. A gelatinous material, presumed to be the internal secretion of the gland, has, in fact, been observed emerging from the cells into the blood spaces. The posterior lobe, or gland, consists of secreting cells producing a glassy substance which finds its way into the spinal fluid that bathes the nervous system. The spinal fluid itself is a secretion of another gland at the base of the brain, the choroid. Nerves and internal secretion are associated here with a closeness symbolic of their general relations.

From each portion of the gland (to stick to the accepted nomenclature of speaking of the two glands as one) an active substance has been isolated. Robertson, an American chemist, separated from the anterior lobe a substance soluble in the fat solvents, like ether and gasoline, which he christened tethelin. But P.E. Smith has shown that the active material is soluble neither in boiling water nor in boiling alcohol, the typical fat solvent. A number of facts favor the idea of the anterior lobe cells as stimulants of growth of bone and connecting and supporting tissues generally. From the posterior lobe, pituitrin, believed its internal secretion, has been obtained in solution.

Pituitrin is a substance of many marvelous functions. In general, it controls the tone of the tissues, of involuntary or smooth muscle fibres of the blood vessels and the contractile organs of the body like the intestines, the bladder and uterus. When injected, it will slowly raise the blood pressure and keep it raised for some time, and will increase the flow of urine from the kidneys and of milk from the breasts. It will also cause an intense continued contraction of the bladder and the uterus. It is also said to control the salt content of the blood upon which its electrical conductivity and other properties depend. Normally, there is a certain fixed ratio of the salts in the blood, which keeps them like the ratio in sea-water. Again, we have an example of the curious atavism of the internal secretions. The thyroid, remember, keeps the iodine concentration of the blood like that of the ocean, our original habitat. Pituitrin likewise does its part to maintain our internal environment as near as possible to what was once the surrounding medium. A substance somewhat similar has been found in the skin glands of toads.

The extraordinarily well protected position of the pituitary, its persistence throughout life, and its abundant blood supply, emphasize its vital importance. No other gland of internal secretion can adequately substitute for it. Complete expiration means death, in two or three days, with a peculiar lethargy, unsteadiness of gait and loss of appetite, emaciation, and a fall of temperature, so that the animal becomes cold-blooded, its temperature the same as that of the atmosphere it occupies. If only part of the anterior lobe is taken away, there occurs a remarkable degeneration of the individual. The degeneration is not a mucinous infiltration of the skin and the internal organs which occurs with thyroid deprivation, but a fatty degeneration, with a tendency to inversion of sex. A singular somnolence, a dry skin, loss of hair, a dull mentality, sometimes epilepsy, and a noticeable craving for and tolerance of sweets appear. These are but a few of the observations obtained in experimental sub-pituitarism, that is, underaction or insufficient secretion of the pituitary, produced by removing part of the anterior gland.

If such an experimental sub-pituitarism is started in infancy, for instance in puppies, there is a cessation, or marked hindering and slowing of growth. That is, dwarfs are artificially created. Apropos, pathologists have shown that in several true human dwarfs the gland is rudimentary or inadequate. All of which goes hand in hand with the evidence that the skeleton stands directly under the domination of the pituitary.

REGULATOR OF ORGANIC RHYTHMS

There are certain other singular by-effects of the gland in its relation to the periodic phenomena of the organism like hibernation, sleep, and the critical sex epochs of both sexes. In hibernation, or winter sleep, the animal in cold weather passes into a cataleptic state in which it continues to breathe, more deeply but more slowly than when awake, but shows no other signs of consciousness or life. A lowered blood pressure and a marked insensitivity to painful and emotional stimuli go with it. There is a preliminary storage of starch in the liver, and of fat throughout the fat depots of the body. These are so like what happens after part of the pituitary is removed, that a comparison of the two becomes inevitable. Common to both conditions is a drop in the rate of tissue combustion or metabolism, which can be relieved by injection of an extract of the pituitary, a rise of temperature occuring simultaneously. Moreover, examination of the glands of internal secretion of hibernating species, like the woodchuck, during the period of hibernation, shows changes in all of them, but most marked in the pituitary, the shrunken cells staining as if they too were asleep, or in a resting stage. The characteristic alive qualities of these cells return, without relation to food or climate, when the animal comes to in the spring, at the vernal equinox. Hibernation may, perhaps, be put down to a seasonal wave of inactivity of the pituitary gland.

Now winter sleep may be looked upon as an exaggeration of ordinary night sleep, the latter differing from the former only in its brevity. In the natural sleep of non-hibernating species there occurs, too, a fall in temperature. Moreover, they all, even man, have a certain capacity for winter sleep, as the experiences of travellers and explorers in the arctic regions indicate. In certain parts of Russia, where there is a scarcity of food during the winter months, the peasants pass weeks at a time in a somnolent state, arousing once a day for a scant meal. Just as the sex glands influence the body and mind profoundly with a certain cyclic periodicity of activity and inactivity (rut, heat, menstrual period and so on), which has been demonstrated to have a very close functional relationship with the pituitary, so sleep and hibernation will bear interpretation as products of a temporary dormancy of the same gland. We have, then, to set up in the place of Morpheus and Apollo, the new gods of the internal secretion of a chemical-making bit of the brain, as an explanation of the rhythms of sleep and wakefulness.

There are individuals who go about outside of hospital walls, quasi-normally, who are semi-hibernators or partial hibernators, and who are really in a state of subpituitarism. They are people who may have something wrong or inferior with their pituitary, but not to the extent of interference with their daily life. They go about with their type stamped upon them for the seeing eye. The classical type is obese, with fat distributed everywhere, but more so in the lower abdomen and the lower extremities. They are slow and dull, and sexually inactive, often impotent. They are sometimes tall, but most often dwarfish, and may be subject to epileptic seizures. They recall the picture of what happens to young dogs partially deprived of the pituitary. Dickens delivered a perfect likeness of an extreme degree of the condition in the Fat Boy of the "Pickwick Papers," whose employment with Mr. Wardle consisted in alternate sleeping and eating.

WHEN THE PITUITARY OVERACTS

All grades of overaction of the pituitary exist. Then its peculiar power to act as a stimulant to the growth of bone and the soft supporting and connecting tissues like tendons and ligaments comes into play. If the overaction or excess of secretion begins in childhood or adolescence, that is, before puberty, there results a great elongation of the bones, so that a giant is the consequence. Now giants have always appealed to the imagination of the little man, and have had all kinds of wonderful abilities ascribed to them by him. The giants and ogres of folk-lore and fairy tales are favored with the most extraordinary mental advantages. Direct and analytic acquaintance with the giants of our own day, as well as a probing of their conduct in the past, has shown that normal giants—persons of exceptional size free from physical or mental deformities—are rare. There are people with hyper-pituitarism who exhibit the highest mental powers. In them is an increased activity of the posterior lobe in association with enlargement and hyperfunction of the anterior, overgrowth is not so marked, and the individual is lean and mentally acute. But the ordinary giant is one in whom there is degeneration of the pituitary after too much action of the anterior and too little of the posterior glands. A tumor or disease process in the gland is most often responsible.

If the overaction of the anterior happens after puberty, when the long bones have set, and can not grow longer, a peculiar diffuse enlargement of the individual occurs, especially of his hands and feet and head. The nose, ears, lips and eyes get larger and coarser. As these people are rather big and tall to begin with, the effect produced is that of a heavy-jawed, burly, bulking person, with bushy overhanging eyebrows, and an aggressive manner. For there is, too, something distinctive about their mentality which has been as often portrayed as those of the pathologic giant. Rabelais' most famous character, Gargantua, belongs to the group. We recruit more drum-majors than prime ministers from among these people. They often suffer much from torturing boring headaches, and a consequent despondency and feeling of hopelessness which colors gray the entire spiritual spectrum. Up to a certain point these sufferers have a remarkable alertness and capacity. When conscious of the malady, they often meet it with a doggedly courageous optimism, which is another characteristic, although women occasionally commit suicide.

In both the semi-hibernators who remind one of cattle, and in the giant or acromegalic types who remind one of the anthropoid ape, there develops a distinct diminution of sexual life. An abnormal process in the anterior gland, whether of oversecretion or of undersecretion, may interfere with the proper functioning of the posterior gland, the secretion of which is tonic not only to the brain cells, but also to the sex cells. Thus, young animals deprived of the pituitary will not, if male, grow spermatozoa, nor ripe ova in the female. Moreover, the feeding of pituitary increases sexual activity. In the case of hens, this has been demonstrated to be about thirty per cent by a pretty experiment. At a time of the year when eggs diminish, six hundred and fifty-five hens laid two hundred and seventy-three eggs upon an ordinary diet. When pituitary was added to their food for four days, the number of eggs rose to three hundred and fifty-two, an increase of seventy-nine. In addition, the fertility of the chicks born of these eggs was augmented, especially if both parents had been fed on pituitary. There are other aspects of the relation of the pituitary to sex, which will be treated in another chapter.

THE BONY CRADLE OF THE PITUITARY

Always, in attempting to understand the pituitary, it is necessary to remember that it is tightly packed in the bony cradle, the Turkish Saddle or Sella Turcica. Should some stimulus, local, or in the blood, arouse the gland to growth, a good deal will depend upon whether it has room to grow in, or it will make room by eroding the bone. With space for the formation of a large anterior and posterior pituitary gland, there will be created the long, lean individual, with a tendency to high blood pressure and sexual trends, great mental activity, initiative, irritability and endurance. An outstanding trait of these favorites of fortune is that they remain thin no matter how much food they consume, and they have the best of appetites. They often are subject to severe headaches because of intermittent swelling of the gland against the bone of its container.

If the bony container is or becomes too small for its contents, it is interesting that along with the other signs of pituitary insufficiency, such as undersize, obesity, and asymmetry, there developes conspicuous moral and intellectual inferiority. The unfortunates suffer from compulsions and obsessions and lack inhibitions. They are the pathological liars with little or no initiative or conscience—amoral, not merely theoretically, but instinctively and unconsciously, with all the certitude and perfection of the unconscious accomplishment.

THYROID AND PITUITARY

The thyroid and the pituitary have often been compared. The anterior gland and the thyroid arise from almost the same spot in the embryonic oesophagus, the thyroid being an outgrowth in front, the anterior pituitary an outgrowth behind of the same soil. They both control growth marvelously, also the differentiation, the mass and intricacy of the tissues. But they differ in the site of their control. The thyroid bears more directly upon the inner and outer coverings of the body, the skin, the skin glands and the hair, the mucous membranes, and the irritability and the preparedness for response of the nerves. The pituitary acts more upon the framework of the body, the skeleton and the mechanical supports and movers. Bone and ligament, muscle and tendon seem to be within its immediate sway. The secretion or secretions of the pituitary diffuse directly into the fluid bathing the nervous system, supplying beneficent stimulants and aiding in the abstraction of harmful waste. So while the thyroid raises the energy level of the brain, and the whole nervous system, as a byproduct of its general awakening effect upon all the cells of the body, the pituitary probably stimulates the brain cells more directly, perhaps in the manner of caffeine or cocaine.

The difference between the thyroid and the pituitary might be put this way: that while the thyroid increases energy evolution and so makes available a greater supply of crude energy, by speeding up cellular processes, the pituitary assists in energy transformation, in energy expenditure and conversion, especially of the brain, and of the sexual system. In short, the thyroid facilitates energy production, the pituitary its consumption. The pituitary appears therefore as the gland of continued effort. Hence fatigability, an inability to maintain effort, is one of the prominent complaints when there is destruction or an insufficiency of it for one reason or another. As such, it contrasts with the glands of emergency effort, known as the adrenals.