Chapter 3 THE ADRENAL GLANDS, THE GONADS, AND THYMUS

Like the pituitary, each adrenal gland is a double gland, that is, consists of two distinct portions, united together, one might say, by the accident of birth. It would be confusing, however, to speak of each as two glands, because there are, as a matter of fact, two separate adrenal glands, one in the right side of the abdomen, and the other in the left. Each gland is composite, or duplex. How the two parts came to be united is a long story, interesting but too long to be recounted here. In fishes they are apart and independent.

Each adrenal is a cocked hat shaped affair, astride the kidneys, easily recognized because of its yellowish fatty color. Indeed, for centuries the glands were not given a separate status as organs, but were passed up as part of the fat ensheathing the kidney. In childhood and youth, in common with the other glands, they are relatively larger and more prominent than in the adult. Also, at every age, the amount of blood passing through them is very large compared to their size. Their tremendous importance in the body economy accounts for their being so favored.

The two parts of which each gland is composed, are known as the cortex or outer portion (literally the bark) and the medulla or inner portion (literally the core). No clean-cut boundary sharply delimits the two, as strands and peninsulas of tissue of one portion penetrate the other. In the history of their development in the species and the individual, and in their chemistry and function, a sharp difference contrasts them.

In the embryo, the cortex is derived from the same patch that gives rise to the sex organs, the ovaries in the female, and the testes in the male, described as the germinal epithelium. How intimately the two sets of glands are connected is neatly pointed by this fact of a common ancestor. All vertebrates possess adrenal glands. In the lowest of the vertebrates, Petromyzon, the two parts are distinct, the cells of the cortex-to-be are situated in the walls of the kidney blood vessels, projecting as peninsulas in the blood stream, the blood sweeping over and past them. The medulla-to-be consists of cells accompanying the vegetative nerves. Among reptiles, the two become adjacent for the first time, and among birds one part occupies the meshes of the other. The size of the cortex varies directly with the sexuality and the pugnacity of the animal. The charging buffalo, for example, owns a strikingly wide adrenal cortex. The fleeing rabbit, on the other hand, is conspicuous for a narrow strip of cortex in its adrenal. Human beings possess a cortex larger than that of any other animal.

No definite chemical substance has as yet been isolated from the cortex. That remains a problem for the investigator of the future. But certain observations, especially concerning the relation between the development and behaviour of the so-called secondary sex characteristics, those qualities of skin, hair and fat distribution, physical configuration and mental attitudes, which distinguish the sexes, and the condition of the gland, indicate clearly that an internal secretion will be isolated, and that it will in its activity furnish certain predictable features.

Three different layers of cells, arranged in strings, that interpenetrate to form a network directly bathed by blood, that breaks in upon them from open blood vessels, compose the cortex. Most remarkable is this method of blood supply for it is exceedingly common among the invertebrates and rare among the vertebrates.

In certain disturbances of these glands, especially when there are tumors, which supply a massive dose of the secretion to the blood presumably, peculiar sex phenomena and general developmental anomalies and irregularities are produced. If the disease be present in the fetus, taking hold before birth, and so brought into the world with the child, there evolves the condition of pseudo-hermaphroditism. The individual, if a female, presents to a greater or less extent the external habits and character of the other sex. So that she is actually taken for a man, although the primary sex organs are ovaries, often not discovered to be such except when examined after an operation or death. How closely such an occurrence touches upon the problems of sex inversion and perversion comes at once to mind.

If the process involving the adrenal cortex attacks it after birth, the symmetrical correspondence and harmony of the primary sex organs and the secondary sex characters are not affected. But there follows a curious hastening of the ripening of body and mind summed up in the word puberty, a precocious puberty, with the most startling effects. A little girl of 2, 3, or 4 years of age perhaps will come to exhibit the growth and appearance of a girl of 14. She begins to menstruate, her breasts swell, she shoots up in height and weight, sprouts the hair distribution of the adult, and the mentality of the adolescent, restless, acquiring, doubting, emerge. A tot bewitched into puberty! A boy of six or seven may suddenly, in the course of a few weeks or months, become a little man, robust, rather short and stocky, but moustached, with the muscular strength and sexual powers of a man and thinking as a man. It is all as if into some fermentable medium or solution a little yeast were dropped that changed the quiet calm of its surface into a bubbling, effervescing revolution. It suggests at once that maturation, the transformation of the child into the man or woman, must be due to the pouring into the blood and the body fluids of some substance which acts like the yeast in the fermentable solution. The adrenal cortex is one source of the maturity-producing internal secretions.

If trouble in the adrenal cortex starts after puberty, phenomena of the same type, but of a different order, exhibit themselves. A woman, say in the thirties, becomes thus afflicted. Slowly or quickly her body will be covered by an abundant growth of hair, more or less of a beard and moustache appear upon the face, her voice will become deep and penetrating, her muscles will harden, and she will show a capacity for hard physical labor. Sexually she appears to be made over, masculinity now predominates in her make-up. Virilism is the name by which the French in particular have popularized the knowledge of the condition. Virilists have to shave or be shaved regularly and are not bothered in the least by the cares, responsibilities, jealousies and anxieties of personal beauty, for the change in their spirituality makes them immune to the preoccupations of the feminine. The cause of such a transformation in a previously entirely normal woman has been found to be a tumor of the adrenal cortex.

But not only is sexuality, and the conduct of the secondary sex characters, connected with the adventures of the adrenal cortex. The development of the master tissues of the body, the brain, the pride and darling of evolution, is in some subtle way correlated with it. The adrenal cortex contains more of the phosphorus-containing substances of the general nature of those found in the central nervous system than any other gland or non-nervous tissues in the body. During human intrauterine life the adrenal glands are large and conspicuous, in the first half of the second month being twice as large as the kidneys. Most of this relatively huge size, which happens in the human alone, and not in other animals, is due to enlargement of the cortex. Should this preponderance of the cortex over the medullary portion not occur in the human, that is, if the proportions remain like those of other animals, the brain fails to develop properly, or an entirely brainless monster is generated. The human brain, therefore, probably owes its superiority over the animal brain, to the adrenal cortex, in development anyhow. The growth of the brain cells, their number and complexity is thus controlled by the adrenal cortex.

Besides its action upon the sex cells and the brain cells, the internal secretion of the adrenal cortex acts upon the pigment cells of the skin, blunting their sensitiveness to light. In degeneration of the interior of the gland, which destroys the medulla, but not the cortex, the color of the skin is left unmodified. If, however, the cortex is invaded, as happens most often in the classical tuberculosis of the adrenals which drew the attention of the Englishman Addison to them, then a darkening of the skin, which may go on to a negroid bronzing, follows. That means an increased sensitiveness of the pigment cells of the skin to light. Skin color control may therefore be looked upon as an adrenal cortex function.

So much is known about the adrenal cortex. Upon the medulla, the interior gland of the gland, there has been lavished an amount of attention beside which the cortex is to be classed as a neglected wall-flower. Nearly everything that possibly could be determined about an internal secretion has in its case been settled or plausibly guessed at. The cells manufacturing the secretion, its exact chemistry and function, its action upon the blood, the liver and spleen, the heart and lungs, the brain and nervous system, have been minutely investigated, studied and charted. Its source in the food, its fate in the body, its place in the history of the individual and the species, its importance as a weapon in the struggle for existence, and the survival of the fittest have been made the subject of an astonishing number of researches, considering the short period of scarce three decades that intensive science has centered its barrage upon it.

In the first place, the medulla contains numerous nerve cells, belonging to the vegetative, also called the sympathetic nervous system. But these nerve cells are merely minor notes of the symphony. The motif is settled by a majority of large, granular cells, which stain a distinctive yellowish-brown when the gland is fixed in a solution of bichromate of potash. All chromium salts, in fact, stain the therefore labelled chromaffin cells. The characteristic staining power appears to be dependent upon, or correlated with, the presence of the internal secretion of the medulla of the adrenal, adrenalin. For the content of adrenalin, as calculated chemically, and the depth of stain as seen under the microscope, rise and fall together. Chromaffin reaction and adrenalin content go together. The poisonous skin glands of the toad have been found to give a marked chromaffin reaction, and to contain a large amount of adrenalin. Other masses of cells in the human body, especially along the course of the sympathetic nervous system, have been shown to give the reaction and to contain adrenalin.

The erratic Brown-Séquard pounded and hammered away for more than thirty years on the importance to life of the adrenal glands, since death occurred so quickly after their removal. But it was not until Schaefer, the Scotch physiologist, (who has done more than any other living man to stimulate study of the internal secretions) found that an extract of them, when injected into a vein, produced a remarkable though temporary rise of the blood pressure, that a real enthusiasm for its investigation was generated. As the upshot, a number of other significant properties besides the first of blood-pressure raising, have been put down to its credit. Chemical tests demonstrated that it originated in the medulla. The exact amount of it present in the medulla, in the blood issuing from the adrenals and in the circulation in general have been determined. The concentration in the blood is about one part in twenty million, while there is about a hundred thousand times as much stored in the gland as reserve. In infections and intoxications, after muscular exertion, and with profound emotions, there is a decrease of it in the gland and an increase in the blood. Pain and excitement, especially fear and rage, will bring about its discharge from the gland. With its entry into the blood, there is a tremendous heightening of the tone, a tensing, of the nervous system. The nerve cells become more sensitive to stimuli, more sugar is poured into the blood from the liver, more red blood corpuscles are squeezed into the circulation from the blood lakes of the liver and spleen. There is a redistribution of the whole blood mass, a good deal of it being withdrawn from the internal viscera, and hurried to the skeleton muscles and the brain. The heart beats more strongly, the eye sees more clearly, the ear hears more distinctly, and the breathing is more rapid. The temperature rises, the hair of the head and the body becomes erect, the skin gets moist and greasy. It will help a fatigued muscle to regain its normal tone. In short, it has a reinforcing action upon the nutritive properties of the blood, the tone of the muscles, and the activity of the brain and the vegetative nerves.

Chemists set themselves the task of discovering just what was the substance possessed of such extraordinary and hitherto unimagined properties. The pure adrenalin was isolated, capable of evoking all the reactions of the impure adrenal extract mixtures. The final triumph was the preparation of it artificially in the laboratory, its synthesis. When a substance can be synthesized in the chemist's laboratory, it means that its composition has become thoroughly understood. Here at last was an example of those mysterious internal secretions, the existence of which had indeed been postulated and proven, but which had never actually been inspected by the eye of mortal man. To have it in a test-tube, indeed to possess it in large quantities in bottles, to be able to manipulate and examine it without fear of the co-action of admixed impurities, to see it with the eye, and to taste it with the tongue, was truly a marvel. The miracle aroused at once scores of researches.

THE GLAND OF COMBAT AND FIGHT

Considering its effects, one is reminded at once of the similarity to the expression of a primitive emotion like anger or fear. So, by turning a relation upside down, it was argued that if artificial adrenalin could produce all these effects of an emotion like fear, the emotion itself should produce an increase of the natural adrenalin in the blood. This was found to be the case. Cannon of Harvard has built up an entire theory of the adrenal as the gland of emergencies upon the basis of these effects. In the facing of crises the adrenal functions as the gland of combat. And indeed, as I have mentioned, the more combative and pugnacious an animal, the more adrenal it has, while the timid and meek and weak have less.

The Glands of Combat, the glands of emergency energy, the glands of preparedness,-such are the adrenal glands when viewed from the adrenalin standpoint. A picture of its activity in the evolutionary scheme of struggle and survival is something like the following: meeting an enemy, the animal is put in danger. It must fight or flee for its life. In either case, certain conditions must be fulfilled, if the body of the animal endangered is to be saved. To prevent injury to itself, and to do as much injury as possible to the foe-that becomes its immediate urge and necessity. Of the two animals, if in one the heart should begin to beat more strongly, the blood pressure to rise, the blood to flow more rapidly through the attacking instruments, the muscles, the teeth and claws, the brain and its eyes, while the other animal experiences none of these, the former will be the victor in fight or flight. Adrenalin may be looked upon as the invention for the mobilization at a moment's notice, or as we say, after generations of use, by instinct, of all these visceral and blood advantages in the struggle of combat or flight.

The nature of instinct, in its relation to the glands of internal secretion, is a problem for another chapter. But we may note that the James-Lange theory of an emotion regards it as a consciousness of the very changes in the organism adrenalin causes. Since adrenalin is the starter of the whole process, and since McDougal has defined emotion as the feeling aspect of an instinct, just as an instinct may be defined as the motor aspect of an emotion, the adrenals as emotion-genetic, and instinct-genetic, play a part in the most profound processes of the subconscious and unconscious.

THE MECHANISM OF FEAR

We may therefore visualize a mechanism of fear. An instant excess of adrenalin occurs in the blood of, say, a cat when it is alarmed by the sight of a dog. In that cat, at the image of its hereditary enemy, certain brain cells vibrate. A nerve tract, in use as the line for that particular message in a hundred thousand generations of cats, whirrs its yell to the medulla of the adrenal gland. Through the tiny, solitary veins of the glands, an infinitesimal quantity of the reserve adrenalin responds. And with what an effect! The blood, that primary medium of life, the precious fluid that is everything, must all, or nearly all, be sent to the firing line, the battle trenches, the brain and muscles, now or never. So the blood is drafted from the non-essential industries-from the skin where it serves normally to regulate the heat of the body-from the digestive organs, the stomach and intestine, which must forsooth stop now, since if the organism will die, their last effort of digestion has been done-from the liver and spleen, great chemical factories in normal times, but now of no moment. Besides, should they be wounded, it is better they should be bloodless, and so run the least chance of bleeding to death, or getting infected, for the more tissue there is around, the greater the danger of infection. So, like the skin, the liver which usually holds in its great lakes and vessels about a quarter of all the blood in the body, is almost drained and blanched. At the same time, its great storehouses of sugar open their sluices and pour into the blood, increasing its sugar content by about a third because the combustion of sugar is the easiest way of getting energy free in the cells, sugar being the most quickly burned up of all the foods, and so the great food of the muscles and the heart. The poisons of fatigue, acid products of the contraction of muscles, are antagonized and neutralized by substances formed in the course of the oxidation of the sugar. Adrenalin, too, is directly fatigue antagonist. It causes the blood to clot faster than under ordinary circumstances. It erects the hair of the animal, and dilates the pupils of the eyes. There is an increase of the apparent size, all of which are to intimidate the enemy, like an Indian's painting of his face blue and green. It also-but what else does it not do?

The story of adrenalin would have delighted the heart of Samuel Butler. His "Note Books," opulent as they are, would have been the richer in pages and pages with his comments on it. Contending as he did with the pompous, dogmatic mechanism worship of the new scientific clique of his time on the one hand, and the superstitions of the old theological caste on the other, he had to fight the hardest kind of guerrilla warfare in defense of the Purpose of Life. Adrenalin, that weapon of a gland tracing its ancestry back to the begetter of the brain itself, for brain and adrenal gland both have evolved from the small nerve ganglia of the invertebrates, would have backed up to the hilt his argument, which he had to elaborate on the indirect grounds of analogy and induction. Essential for defense, and for protection,- an organ in which everything necessary for the stratagems of retreat, or the offensives of attack, are supplied ad libitum, while everything non-essential or detrimental to the matter of the moment is inhibited, arrested and suppressed-no more perfect sample of the design with which Life is drenched could be imagined by the most closeted of passionate idealists.

FAILURE OF THE ADRENALS

As the gland of acute stress and strain, the adrenals in modern life are called upon to function more heavily and frequently than in the past. As a matter of fact, the life of the beast of jungle and field, as well as of savage and barbarian, is just as full of emergencies and shocks as that of the average city man or woman. In the case of the latter, however, inhibitions, education, and the conditions of modern living, improper food, sedentary indoor confinement, and universal rack and noise, have undoubtedly made greater and greater demands upon the adrenal glands. Chemical quantitative studies have shown that by repeated stimulation, the adrenal glands may be exhausted of their reserve supply of secretion, which returns only insufficiently if not enough time is given for recuperation. There results a condition of temporary or chronic adrenal insufficiency, supposedly an insufficient functioning of the gland as a whole. In persons so afflicted there appears a fatigability, a sensitiveness to cold, cold hands and feet, which are sometimes mottled bluish-red, a loss of appetite and zest in life, and a mental instability characterized by an indecision, and a tendency to worry, a weepishness upon the slightest provocation.

A certain number of the temporary breakdowns or nervous prostrations, which seem to be growing more common or fashionable, may be sometimes traced to such a deficiency of normal response to the needs of everyday conflict by the adrenal gland. In some, mental and physical elasticity are totally lost, and even the slightest exertion in either field often causes so much weariness and exhaustion as to be prohibited. Depression and even melancholia are associated with the fear of not being able to accomplish good work hitherto easy and enjoyed. Sometimes they are obsessed with the thought that they have lost their nerve completely, and so dread to commit themselves in even the most trivial of situations. The vacillating frame of mind is so distressing at times as to arouse thoughts of suicide. When these symptoms concur in the type of personality whom I shall describe as the unstable adrenal-centered individual, there is evidence for explaining the process as the effect of an insufficiency of secretion by the adrenal gland.

Shock, collapse, heart failure and sudden death following abnormal emotion, like an attack of rage, or the terrors of a railroad accident, or bad news, or excessive exertion like running a long race or climbing a high mountain when in poor general health, as the phrase goes, or in the terminal stages of infections like epidemic influenza or Asiatic cholera, have been put down to an acute insufficiency of the adrenal gland. A lowered temperature, blood pressure, and blood vessel tone, exhibited in tests of the response of the skin to stroking, are present in all of these and point the same moral.

In the second half of the 19th century, an American physician, Beard, described Neurasthenia, a general disturbance of the body and mind, not properly classifiable as a disease, but serious enough to incapacitate or at least greatly limit the sufferer. The neurasthenic is to be recognized by the fact that the most painstaking objective examination of his organs reveals nothing the matter with them. Yet, according to his complaint, everything is the matter with him. He cannot sleep when he lies down, he cannot keep awake when he stands up. He cannot concentrate, but still he is pitifully worried about his life. The slightest irritant causes him to go off the handle. As he works himself up into his hysterical state as a reaction to a disagreeable person or problem, irregular blotches may appear on his face and neck. Generally, his hands and feet are clammy and perspiring, his face is abnormally flushed or pallid, the eyes are worried or starey, unwonted wandering sensations involving now this area of the body, or now that obsess him. As the blood pressure is too low for the age, the circulation is nearly always inadequate and palpitation of the heart is a frequent complaint. So frequent, that attention is often centered upon the heart, a diagnosis of heart disease is made, and the unfortunate is doomed for life-to brood over horrible possibilities. The brooding over themselves and their troubles is one of the distinctive features of the whole complex. Neurasthenia may masquerade as any organic disease. An individual with a soil for a neurasthenic reaction to life will become neurasthenic when confronted by any stone wall, including a serious ailment within himself.

Beard's Neurasthenia leaped at once into the limelight. It was seized upon and applauded in Europe as a good new name for an old condition, observed particularly in Americans abroad to rest from the fatigues of the get-rich-quick games of industrial speculators. In fact, the name of the American Disease was given to it. Various theories about the effects of climate, sunlight per square inch and unit of time, oxygen content of the air, and so on, were offered up upon the altar of scientific explanation. Sir Arbuthnot Lane, famous protagonist of Lane's intestinal kink, said that all Americans were neurasthenic. Neurasthenia became one of the most popular of diagnoses, and remains so today.

Neurasthenia, regarded as a reaction of people to the stress and strain of life, has without a doubt increased. The most casual of observers will tell you that the generation of the Great War is a neurasthenic generation. It takes its pleasures too intensely, its pains too seriously, its troubles too flippantly. But what is neurasthenia? Beard himself regarded it as a chronic fatigue and loss of tone of the nervous system, a literal interpretation of his term. That the conception, as far as it goes, is valid is proved by the fact that it is the neurasthenics who furnish the majority of the clientele of the cults, the Christian Scientists, the osteopaths and the chiropractors, and who are the subjects of the faith and miracle cures, like those of Lourdes. That is because their particular disease, or what appears to them to be their very own disease-and they certainly cherish their ailments-is but an expression of, a compensation for, indeed a consolation for, the underlying feelings of insufficiency or inferiority. Were there no moral code, were there no social system, nor the consequent inculcated conscience to be responsible to, there would be no such disguising symptom as the disease which preoccupies the consciousness. The feeling of insufficiency would be there, and would be recognized as in itself the disease. To the physiologist and the psychologist, the feeling of insufficiency is the disease, no matter how spectacular the overlaying phenomena-a cripple on crutches or a man blind and speechless. Shell shock is now acknowledged to belong to this group.

Now one of the outstanding effects of disease of the adrenal glands is the feelings of muscular and mental inefficiency. And as a matter of fact, a good number of observations conspire for the idea that a certain number of neurasthenics are suffering from insufficiency of the adrenal gland. The chronic state of the acute phenomenon, known as the nervous breakdown, really represents in them a breakdown of the reserves of the adrenals, and an elimination of their factor of safety. In the light of that conception, the great American disease-dementia americana-is seen to be adrenal disease-and the American life to be the adrenal life, often making too great demands upon that life, and so breaking down with it.

ADRENAL EXCESS

The converse of adrenal insufficiency, that of adrenal excess, also exists. In certain types of the middle-aged, a high blood pressure, accompanied by a great capacity for work, has been shown to be associated with hypertrophy of the cortex. In women, there is a degree of masculinity, as the adrenal in women makes for masculinity, neutralising more or less the specifically feminine influences of the internal secretions of the ovary. Such women possess a vigor and energy above the normal, and command responsible positions in society, not only among their own sex, but also among men. They are the ones who, in the present overturn of the traditional sex relationships, will become the professional politicians, bankers, captains of industry, and directors of affairs in general.

THE GONADS

(Sexual, Puberty or Interstitial Glands)

The gonads is the name applied to the generative or reproductive glands considered collectively. In the male, they are the testes; in the female, the ovaries. They are, therefore, sometimes called the sexual glands. As they possess definite canals for the removal of their gross secretion, the specific reproductive cells, ova or spermatozoa, to a surface of the body, they are first of all glands of external secretion. But they have been also found to hold secretory cells not concerned with the making of the reproductive corpuscles, but, as all the evidence indicates, with the manufacture of an internal secretion. These interstitial cells form the interstitial gland. A classic example of a gland of internal secretion lodged in the interstices of a gland of external secretion is thus furnished by the gonads.

ORIGIN OF SEX TRAITS

The history of sex goes back far in the scheme of life. The immortality of the ameba was at one time one of the indisputables of biology. Then some observations were made which threw doubt upon a long accepted fact, now declared a dogma. Lately, opinion has veered back to immortality. But in the case of a close relative of the ameba, the one-celled animal known as the paramecium, union with another paramecium, true conjugation, has been proved necessary to prevent death sooner or later. Sex here appears in its most primitive form, on the basis of exchange of necessary materials, between individuals to prevent death, their own having been, so to speak, worn out, in the course of metabolism.

Specifically different sexes come later, when mortality is a universal fate, as a means of rebirth and escape from death. Then the sexes develop their latest function, most prominent among the younger vertebrates, of acting as nature's most potent method of variation and differentiation. In the pursuit of the different, nature has exalted sex, and the intensity of the sex life. As far as the preservation of a species is concerned, and the reproduction of the individual, the asexual methods, budding, for example, would have done well enough. But when it comes to enacting a different individual apart from the effects of environment, sex stands out as the favored method of Life.

The development of the sexes and the sexual life brought a new element of conflict into the living world. Before the advent of the sexes the conflict was essentially for the means of existence, food alone. But with the sexual life came a conflict for sex pleasure, a competition among members of the same species for the same individual as their sex partners. The result was the introduction of a factor in evolution which Darwin examined so closely in the "Descent of Man."

The sex conflict has been the cause for the origin and the survival of certain physical and mental traits, helpful in sex attraction, sex combat, the growth of the embryo, and the nutrition and safety of the young of a species,-in short, the whole process of sexual selection. The proportions of the skeleton, the distribution of hair and fat, the construction of organs of attack and defense, the color of the skin, the cyclic processes of preparation for impregnation, the oestrus or heat period in animals, the menstrual period in the human being, the psychic reactions to danger and combat have all been thus determined. That man is bearded while woman is not,-that woman has potentially functional breasts while man has not,-the aggressive pugnacity of man contrasted with the more passive timidity of woman, have all been evolved in the sex struggle, surviving because most effective in that struggle. These so-called secondary sexual characteristics are an expression of the influence of the internal secretion of the gonads, or the interstitial glands. Some call them puberty glands, because their ripening initiates puberty.

We know that these interstitial glands, to stick to that name, (rather than to the name of the puberty glands, since they serve not only to induce puberty but to maintain maturity) are the actual primary dictators of the process by which male and female are distinguished, if not created. Castration was probably the first surgical operation carried out for experimental purposes, suggested no doubt by a curiosity concerning its effects. Trepanning of the skull, the geologic record indicates, was done even by the cave man. But as an experimental operation, castration seems to hold the primary position in the annals of surgery.

Its effects noted, the satisfaction of one of the lower human instincts, jealousy, popularised it. From the days of Semiramis, eunuchs have been commonplace figures of the East, their function definite: to guard the harems of the powerful. The age of Abdul Hamid witnessed no diminution of the barbaric tortures by which children are prepared for the profession. It is to the credit of England that in its dominions in the Orient the practice has been abolished. But it goes on even today. According to the best authorities, four out of five of these victims at the auto-da-fe of a vicious human instinct die immediately or soon after from exhaustion due to pain and infection. Not all of the ancient nations countenanced the brutal horror. The Hebrews placarded castration an unpardonable sin, making it a sin to castrate even animals. Nor was any man so mutilated permitted to worship in the house of the Lord (Deuteronomy xxiii, 11). Yet we have evidence that the latter Jewish kings employed foreign eunuchs in their harems, who often held the most important positions as ministers of the court.

Besides the eunuchs, another group of people have presented material for the study of the interstitial glands. These are the Skoptzi of Russia and the Lipowaner of Roumania. Among them castration is a religious ritual. Mankind has always been most brutal to itself in the name of the ideal. These sects were founded because in the eighteenth century an antipode of Joseph Smith and Brigham Young discovered this passage in Matthew xix, 12.

"For there are some eunuchs which were so born from their mother's womb, and there are some eunuchs which were made eunuchs of men: and there be eunuchs which have made themselves eunuchs for the kingdom of heaven's sake. He that is able to receive it, let him receive it."

He decided that he was inspired to spread the gospel of castration. A sect was founded who thought that surgery was the easiest way to enter the gates of Paradise, and they multiplied and fructified. The sect exists today, and some of the most interesting studies of the internal secretion of the interstitial glands have been made among them.

Related to acquired eunuchism is the condition of eunuchoidism, the eunuchs which were so born from their mother's womb. Baron Larey, the great surgeon of Napoleon's armies, was their first painter. He was the only altruist Bonaparte said he had ever met in his life. He portrayed a group of soldiers with peculiarly high-pitched voices, smooth and hairless skins, and atrophied generative organs. A somewhat similar picture is evolved in certain types of insufficiency of the pituitary gland. Features of the picture are exhibited with disturbances of the other internal secretory glands also, like the thymus.

But a host of experiments and data prove the interstitial glands to be the direct controllers of elementary sexuality and the specific sex traits of male and female. Beginning with Berthold back in the first half of the nineteenth century, who studied the fowl, a number of observations have been made on the effects of excision, translocation and transplantation of these glands.

The results of the experiments and observations can be summed up as follows: if the male individual is castrated before puberty, that is, before the advent of the sexual life, secondary sex qualities do not develop. In males, the generative organs do not grow, hair on the face does not appear, hair elsewhere on the body remains generally scanty, the voice continues as high-pitched as the child's, there is more or less muscle weakness, obesity, and mental sluggishness. In other words, we have an effeminate man, technically a eunuch. In the castrated female, the pelvis does not grow to the normal feminine size, the breasts do not swell as they should, more or less hair comes out on the face, the voice is low-pitched, and tends to be rather husky, the legs are longer, and again, the mentality is dulled. That is, a masculine sort of woman is produced.

In short, the castrated male takes on a feminine type, and the castrated female, a male type. In either case there is also an infantilism, a retention of the infantile mental traits, a lack of development of the adult mental attitudes and reactions. Now, if in the castrated male is transplanted an ovary, the positive characteristics of the female are evoked, such as enlarged mammary glands, and a tendency to secretion of milk. Experiments have also been reported in which a uterus was also placed in such an animal, with a means of entry, and pregnancy followed. If in the castrated female a testicle is planted, the masculine traits become much more marked and striking. A direct exchange of the male and female r?les can thus be achieved. Castration after puberty cannot modify profoundly structures like the skeleton which are already completed. Yet it may unquestionably bring about definite retrogressive changes in the secondary sex characters: reduction or loss of virility, diminution of facial and body hair, and a general presenility or hastening of senility.

How remarkably these interstitial cells influence the entire structure and vitality of the organism is indicated by these facts. How much they have to do with sexual impulses, sexual excitement, and sexual desire, what the Freudians have popularized as the libido, and how subtly they act upon the coming and duration of adolescence and maturity, as well as sexual precocity and peversions, we shall consider in a later chapter. But it is enough now to remember that these interstitial glands are the primary dictators of the genital sense and flair of the individual. In any attempt at measurement of men and women, the quality and quantity of the internal secretion of the interstitial cells must be respected as a fundamental consideration. The womanly woman and the manly man, those ideals of the Victorians, which crumbled before the attack of the Ibsenites, Strindbergians and Shavians in the nineties, but which must be recognized as quite valid biologically, are the masterpieces of these interstitial cells when in their perfection. They are such solely because of the right concentration in the blood of the substances manufactured not only by these cells, but by all the glands of internal secretion. For it cannot be repeated and emphasized too often that the interstitial cells of the sex glands are most sensitive to all kinds of other influences, and, in particular, the other internal secretory organs. They may indeed be watched as an index scale or barometer of the general tone of the whole internal secretion system. Sex variations offer a variety of clues to variations, disturbances, predominances and abnormalities in all the components of the ductless gland association.

To take a single instance, the development of the long bones is dependent upon the handling of food lime by the body. Eunuchs and eunuchoids, that is, individuals with insufficient internal secretion of the interstitial cells, have longer bones and more fragile bones than the normal. Vice versa, those with an excess of the secretion have shorter and thicker bones. The earlier the onset of menstruation, which means puberty, the shorter the extremities, as the action of the internal secretion of the ovaries closes the story of the growth of the long bones.

The ovaries are a most important factor in the regulation of the power of the organism to keep lime in the bones. If they over-secrete in an excess which cannot be taken care of by the other glands of internal secretion, the body loses lime, a softening and curving of the bones occurs, and the most horrible deformities and tortures for the sufferer. Taking out the ovaries has cured some of the afflicted. Administration of the antagonizing gland extracts has helped others. An Italian, Bossi, in 1907, used adrenal gland curatively. More recently, a British student of the subject, Blair Bell, was given the direction of the treatment, at long range, of a number of cases in India, the land of chronic pregnancy with insufficient food, and consequent oversecretion of the ovaries, with the typical softening of the bones. At his suggestion pituitary was used successfully.

Some of the glands of internal secretion act as accelerators to the sex glands. Others act as retarding antagonists. Among the most important of the latter is

THE THYMUS

The thymus is the gland which dominates childhood. It appears to do so by inhibiting the activity of the testes or ovaries. Castration causes a persistent growth and retarded atrophy of the thymus. Removal of the thymus hastens the development of the gonads.

Situated in the chest, astride the windpipe, it descends and covers over the upper portion of the heart, overlapping the great vessels at the base of the heart. It is a brownish red mass, which when cut presents the spongy effect of a sweetbread. The more intimate view of detail revealed by the higher powers of the microscope shows conglomerations of the white cells of the blood known as lymphocytes. But scattered through the substance of the gland, between these lymphocytes, like the interstitial cells of the sex glands placed between the sex cells, are peculiarly staining cells in whorls. Of which there are many more in the thymus of embryonic and early postnatal life, known after their discoverer as Hassal's Corpuscles. They are believed by some to elaborate the specific internal secretion of the thymus. Present in all vertebrates, there seems to be more of it in the carnivora than in the herbivora, like the thyroid.

Concerning the exact function of the thymus, we are a good deal at sea. The latest opinion about the results of extirpation even in young and growing animals is that they are nil. Yet there is a certain justification for proclaiming the thymus the gland of childhood, the gland which keeps children childish and sometimes makes children out of grown-ups. There is a quantity of data for that proposition. In the first place, the curve of rise of growth of the gland seems to coincide with the period of childhood, the curve of its decline with the period of adolescence and the rise of the sex glands. In the past, it was accepted, that with puberty the thymus atrophied and was replaced by some sort of fatty tissue. Nowadays, it is held that secretion cells persist throughout life. When the extent of this persistence is too great, the gland being from five to ten times as large as the normal, a number of other features become prominent to make the extraordinary individual, the status lymphaticus, who amid the hazards of life will react in an extraordinary way. He will be taken up in the consideration of internal secretion personalities.

Then there are the varied and remarkable phenomena of thymus enlargement and hyperactivity in childhood itself. When an enlarged thymus is present in an infant, the initiation of breathing in the new-born, the introduction of the newcomer to the oxygen of the air, may be an exceedingly prolonged, difficult, matter. Such a baby is said to be born blue, and the breathing may be stridorous for days, becoming normal for a time, to be followed later by spells of trouble in breathing, breathlessness or breathlessness with blueness, and threatened extinction. Sometimes these spells come out of a clear sky in an apparently healthy child. That some poison, probably an oversecretion of the thymus, is responsible is shown by the relief obtainable by X-ray shrinkage of the gland, or the surgical removal of a part of it.

Moreover, the gland is influenced by and influences the factors of body weight and growth with an extreme readiness and lability. Deficient general undernutrition leads to rapid decline in its weight. Back in 1858, the pioneer student of the thymus, Friedleben, declared that the size and condition of the thymus is an index to be the state of nutrition of the body. Underfeeding for four weeks will reduce it to one thirtieth the normal. It seems to act as a storage and reserve organ, affording some protection against the limitation of growth by lack of food material. In exhausting or wasting disease, the weight of the gland sinks much more quickly than other glands. Scattered instances have been reported of children growing, putting on inches in height and expanding mentally, when thymus was fed to them, in whom every other measure previously tried had failed. A French study of over four hundred idiotic children with normal thyroids reported that over three fourths had no thymus at all. Everything points to the most direct and close relation between the gland and nutrition and growth, but with nothing tangibly definite like our knowledge of the thyroid and the pituitary.

There is evidence that the thymus is involved in the health and efficiency of muscle cells and muscularity. Certain tumors of the thymus, presumably destructive of the gland substance proper, and thus cutting off its secretion, are accompanied by a singular muscle weakness and atrophy of the muscle cells, entirely out of proportion to the general damage suffered by the other cells of the body when affected by the poison of a malignant growth. Also, the thymus has been discovered diseased in certain mysterious progressive muscular wastings. A remarkable fatigability of muscles, which appears after the slightest exertion, is a feature. The feeding of thymus has caused muscle cramps which apparently depends upon an increased excitability of the muscle nerve endings.

Feeding of thymus to some of the lower creatures of the animal kingdom will completely hold up differentiation. Take the unfolding of the specialized tissues and organs which transform the tadpole into the frog and the chrysalis into the butterfly. A tadpole kept supplied with enough thymus in a nutrient medium will swell into an extraordinary giant tadpole, but will not change into a frog. Recently, this experiment has been contradicted. Yet this effect corresponds to the conception of its importance in childhood as a retardant of precocity, physical and mental. Clinical observations emphasize that in childhood it is the chief brake upon the other glands of internal secretion which would hasten development and differentiation, checking them perhaps for a given time and so profoundly influencing growth.

THE PINEAL

The pineal is another gland which has been credited with similar abilities and a like holding-the-reins-tight-in-childhood function among the cells. Like the thymus, it has been supposed one of the distinctive organs of childhood and to die with it. Generations of anatomists solemnly asserted, repeating each other's mistakes with the aplomb of the historians who declare that history repeats itself, that the pineal body was a useless, wastefully space consuming vestige of a once important structure. That was the view in that century of grandly inaccurate assertions, the nineteenth. Not that they relegated it with that statement to the limbo of the dull and the uninteresting. Quite the contrary. They conferred upon it a distinguished romance and mystery by identifying it as the last heir and vestigial remnant of a third eye, situated in the back of the head, which may still be observed in certain reptiles. Imagine it! Somewhere, stuck away in a cranny of the floor of your head and mine, is this descendant of an organ that once sparkled and shone, wept and glared, took in the stars and hawks and eagles, and now is condemned to eternal darkness and an ineffectual sandiness. Today, we have not discarded that view of its history, but we know a little more regarding its composition and function.

What and where is the romantic object? It is a cone-shaped bit of tissue hidden away at the base of the brain in a tiny cave behind and above its larger colleague, the pituitary. Microscopic scrutiny reveals that it is made up in part of nerve cells containing a pigment similar to that present in the cells of the retina, thus clinching the argument for its ancient function as an eye. But the outstanding and specifically glandular cells are large secreting affairs, which too reach back to the tidewater days of our vertebrate ancestors, when Eurypterus and other Crustaceans were engrossed with the fundamental problems of brain versus belly. Besides these, there are the singular masses upon which has been fastened the unnecessarily opprobious epithet of brain sand. These, noted and commented upon from the earliest times, consist of collections of crystals of lime salts, sometimes small, lying about in discrete irregular masses, and sometimes grouped into larger mulberry-like concretions, varying much in size. These brain sand particles have become of practical importance in the detection of pineal disease because they, like all lime salts, will stop the X-rays, and so can be photographed.

For a long time, indeed up to scarcely more than a few decades or so ago, the pineal was believed to have no present function at all, or at least no ascertainable or accessible duty in the body economy. That it might perhaps be, in a sense, a gland of internal secretion was a despised theory. Then a classic case, the most extraordinary and curiosity-piquing sort of case, with symptoms involving the pineal gland, in a boy, was reported by the German neurologist, Von Hochwart. That boy provoked a little army of researches. He came to the clinic complaining about his eyes and other troubles which pointed pretty definitely to a brain tumor as the diagnosis to pigeon-hole him. Nothing extraordinary about him in that respect. But the story told by his parents was quite extraordinary, even to the jaded palate of the clinic professor and his assistants. They said that he was a little over five years old, a statement conclusively proved correct at his death. Up to the time at which his illness began, he had been quite normal in size, intelligence and interests. But with the onset of his misfortune, he had begun to grow, and rapidly until now he looked and corresponded in all measurements to a normal boy of twelve or thirteen. Hair developed all over his skin, most prominently and abundantly in the typically hairy places of adults. His voice became low-pitched, and most remarkable of all, his sexuality and mentality precocious. He became capable of true sexual life and is said to have asked many questions about the fate and condition of the soul after death. On one occasion he remarked reflectively: "It is odd how much better I feel when I let other children play with my toys than when I play with them myself." Other statements attributed to him imply the most astounding maturity of thought and mental process. Headaches finally came, and he died about four weeks later. The cause of the whole bizarre tragedy was found to be a tumor of the pineal gland.

As has happened before in medical history, no sooner was the one prodigy reported, than a score of others of the same ilk sprang into the limelight. Cases of precocious genital development, especially, some of them occurring as early as the second year of life, were linked with them. It is an interesting point to be noted that in these, as in those started by an overaction of the adrenal cortex, it is premature masculinity that is stimulated. The adrenal cortex must be classed as a gland of masculinity. The pineal possibly acts as a brake upon the adrenal cortex.

Very soon after the report of Von Hochwart's prodigy appeared, an experimental research on the pineal was begun in New York. The pineal glands of a number of young bullocks were obtained and used for feeding, to see whether an overaction of the internal secretion could be produced. Guinea pigs, kittens and rabbits were used. The experiments covered about two years in time. Of a dozen small kittens, the subjects outgrew the controls rapidly in activity, size, intelligence, and resistance to intercurrent disease. Of ten small rabbits, the controls weighed about a third less than the subjects, which were strikingly clean, active, fat and salacious.

Feeding of the gland was then extended to a particular class of defective children, children with well-shaped heads, normal eyes, symmetrically functioning limbs, excellent digestion, strong muscles and generally, normal, sometimes rapid growth. It is to them, particularly when mental normality has progressed up to the eighth, tenth or twelfth year and stopped, that the term "moron" has been applied. They have been a hopeless lot, belonging to the limbo of the incurables. Moreover, they, emphatically the physically normal ones, differ from one another enormously in the extent to which mental operations are possible. As all transitions and degrees exist, no definite classification and subdivision of them has been made. Yet ever since the cretin, once looked upon as an eternally damned defective, was transformed by thyroid feeding into an apparently normal being, there has been no dearth of effort to find the right kind of internal secretion to fit their desperate situations, but in vain. In defectives with definitely, organically damaged brains, no result of course was to be expected. In those of any class over fifteen, no response has been elicited by feeding pineal gland. In the others the results have been contradictory.

A set of observations have related the pineal to muscle function, inviting comparison of it with the thymus. There is a singular muscle shrinking and deforming disease, known as progressive muscular dystrophy, hitherto a complete and unsolved mystery. Newer studies of the pineal in this disease during life by means of the X-ray have shown it calcified, that is, buried in lime salts, which signifies put out of business. Recently thus another hint as to its function has been ferreted out.

The tadpole as a reagent to test out the growth effects of different glands of internal secretion has also been employed for the pineal. Ten-day-old tadpoles fed on pineal present a marked translucency of the skin due to a retraction of the skin pigment cells. Now without a doubt a number of as yet unknown growth and metabolic effects follow exposure of the body to the complete gamut of light rays. The interesting suggestion follows that the pineal influences the body by varying the degree of light ray reaction.

The pineal, the ghost of a once important third eye at the back of our heads, still harks back in its function to a regulation of our susceptibility to light, and its effect upon sex and brain. So it becomes one of the significant regulators of development, with an indirect hastening or retardation of puberty and maturity according as it works in excess, or too indolently. It appears thus the blood brother of the adrenal cortex which also influences the skin pigment and so susceptibility of the organism to light, brain growth and sex ripening. It is interesting that Descartes, in 1628, considered the pineal the seat of the soul.

THE PARATHYROIDS

Sometimes imbedded within the substance of the thyroid in the neck, sometimes placed directly behind it upon the windpipe, are four tiny glands, each about the size of a wheat seed, the parathyroids. For long they were swamped in the nearness of their great neighbor, and considered merely a variable part of it. There are some who contend that even today. But it has been proven that they are separate, individual glands, with a structure and function of their own, and a definite importance to the body economy.

On the animal family tree they appear early, contemporaneously with the thyroids. In the embryo they develop from about the same sites. And very often they look very much alike under the microscope, especially when the cells are in certain quiescent stage of secretion. Yet they are wholly independent in nature, activity and business.

First experimenters upon the effects of removal of the thyroid were confused by contradictory findings with different animals because in some they would take out the parathyroids at the same time without knowing it, and in others they would not. That possibility suggested, more careful dissectors accomplished the job of extirpating the thyroid while leaving the parathyroids intact and vice versa. In consequence some definite information about the parathyroids is available, even though their internal secretion has never been isolated, or its existence established as more than an inference.

When the parathyroids are removed, an astounding increase in the excitability of the nerves follow. It is as if the animal were thoroughly poisoned with strychnine. The slightest stimulus will make him jump, or throw him into a spasm. When the excitability of the nerves is measured by an electrical instrument it is found augmented by from five hundred to one thousand per cent. The reflexes, those automatic responses of brain and spinal cord to certain stimuli and situations, become enormously sensitive, so that merely letting the light into a darkened room will make the subject of the experiment go into a series of convulsions.

On the chemical side, an explanation for these nervous phenomena has been advanced. Lime in the blood and cells appears to be necessary in a number of ways. In the making of bone and teeth, in the coagulation of the blood, in the keeping of fluid within the blood vessels, and in maintaining the tone of the nerves, it plays a major r?le. Now the parathyroids, among all the glands of internal secretion, seem to act as the prime regulators of the amount of lime held within the blood and cells. For when the parathyroids have been completely and aseptically excised, without injuring any other organ, immediately the body begins to lose lime. Something has gone out of it that helped it to bind lime, and without that essential something, the internal secretion presumably of the parathyroids, the lime departs. As a conspicuous consequence the teeth fail to develop properly, particularly as to their enamel, for which lime is an essential constituent. Hair is lost, there is a general wasting, the nails get brittle, and the bones soften, and the animal dies. Supplying lime directly, particularly by direct injection into the blood, will relieve the symptoms.

In man, a condition of nervous over-excitability has been described as tetany. It occurs most often in the young, the pregnant, or in vomiting after operations. All sorts of tests have related the malady to the phenomena succeeding parathyroid deprivation, and they are now looked upon as aspects of it. Individuals have been reported suffering from an insufficiency of the internal secretion of parathyroids, with a sudden extreme depression, nervousness and restlessness, an inability to sleep or sit still, and a tremulous handwriting. Such reports round out the evidence for the importance of the parathyroids in an understanding of the factors which control growth, especially as regards lime utilization, for without lime properly handled no building of cells is possible. Also the parathyroids are necessary to a steadiness of muscle and nerve.

THE PANCREAS

The business of the parathyroids concerns the keeping of lime in the body. Another gland, the pancreas or sweetbreads, this time within the abdomen, a close neighbor of the solar plexus, alias the abdominal brain, is occupied with holding and hoarding sugar in the body, particularly in the liver, the great sugar warehouse. This matter of retaining sugar and controlling its output is one of the utmost significance for growth and metabolism, the resistance to infections, the response to emergency situations, and in general to the mobilization of energy for physical and mental purposes. For without sugar sufficiently at hand for the cells, no muscle work or nerve work, the essentials of the struggle for existence, are possible.

The pancreas is an organ with both an internal and external secretion. The external secretion, long known, evolved by the major portion of the gland, is poured into the small intestine to play the star in digestion. Scattered here and there among the definitely glandular cell groups creating the external secretion are smaller collections of cells, called the islets of Langerhans, which have been demonstrated to elaborate the internal secretion. There are about a million of these islands in each gland. The hormone has been called insuline. Unlike most of the glands with a double secretion in which the internal is absolutely independent, and so to speak, unconscious of the external, these two of the pancreas are often disturbed together, perhaps because trouble easily hits them both together.

Quite the most well-known disease due to disturbed internal secretory function of the pancreas is diabetes. An enormous amount of work has been spent upon the various aspects of it as a mystery. Hundreds of papers in a dozen languages upon the subject are in existence. In a nutshell, they have established pretty well that diabetes is a disease in which there is an excess of sugar in the blood and urine because of an insufficient amount of the secretion of the islands of Langerhans in the pancreas. Removal of the pancreas makes the body, essentially the liver, unable to retain sugar, as well as unable to burn up sugar for energy. The situation is comparable to a locomotive with its coal bins leaking, and the coal itself acting as if made of slate or some equally uncombustible or only partially combustible material.

The control of sugar mobilization from the liver, where it is stored as glycogen or animal starch, is divided between the pancreas and the adrenals, the pancreas acting as the brake, the adrenals as the accelerator of the mechanism. Adrenal and pancreas are therefore direct antagonists, the pans of the scale which represents sugar equilibrium in the organism. Diabetes may be regarded as a disturbance of the adrenal-pancreas balance, assisted by events which produce adrenal overwork like great or prolonged emotion, or by strain of the pancreas, effected by over-eating for example.

There are other minor glands of internal secretions. But those considered are by far the most important and the most recently explored. In a summary, one would classify them as follows:

Name Secretion Function

1. Thyroid Thyroxin Gland of energy production

Controller of growth

of specialized organs

and tissues-brain

and sex

2. Pituitary- Gland of energy consumption

and utilization-continued

effort

anterior Unknown Growth of skeleton and

supporting tissues

posterior Pituitrin Nerve cell and involuntary

muscle cell, brain and sex tone

3. Adrenals The Gland of Combat

cortex Unknown a. Brain growth-tone

development of

sex glands

medulla Adrenalin b. Energy for emergency

situations

4. Pineal Unknown a. Brain and sex development b. Adolescence and puberty c. Light and maturity

5. Thymus Unknown Gland of Childhood

6. Interstitial Testes in male Glands of secondary glands of Ovaries in female Sex traits

7. Parathyroids Unknown a. Controllers of lime

metabolism

b. Excitability of

muscle and nerve

8. Pancreas Insuline Controller of sugar metabolism