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 interst.i.tial 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 p.u.b.erty, 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 s.e.x glands. Others act as r.e.t.a.r.ding 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 r.e.t.a.r.ded 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 ma.s.s, 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 interst.i.tial cells of the s.e.x glands placed between the s.e.x 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 Ha.s.sal'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 quant.i.ty 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 s.e.x glands. In the past, it was accepted, that with p.u.b.erty 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 b.u.t.terfly. 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 r.e.t.a.r.dant 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 a.s.serted, 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 s.p.a.ce consuming vestige of a once important structure. That was the view in that century of grandly inaccurate a.s.sertions, 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 ma.s.ses 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 ma.s.ses, 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 cla.s.sic 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 a.s.sistants. 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 s.e.xuality and mentality precocious. He became capable of true s.e.xual 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 cla.s.sed 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 cla.s.s 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 cla.s.sification and subdivision of them has been made. Yet ever since the cretin, once looked upon as an eternally d.a.m.ned 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 cla.s.s 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 s.e.x and brain. So it becomes one of the significant regulators of development, with an indirect hastening or r.e.t.a.r.dation of p.u.b.erty 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 s.e.x 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 role. 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 const.i.tuent. 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 h.o.a.rding 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 nutsh.e.l.l, 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, a.s.sisted 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 cla.s.sify them as follows:

_Name Secretion Function_ 1. Thyroid Thyroxin Gland of energy production Controller of growth of specialized organs and tissues--brain and s.e.x

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 s.e.x tone

3. Adrenals The Gland of Combat cortex Unknown a. Brain growth--tone development of s.e.x glands medulla Adrenalin b. Energy for emergency situations

4. Pineal Unknown a. Brain and s.e.x development b. Adolescence and p.u.b.erty c. Light and maturity

5. Thymus Unknown Gland of Childhood

6. Interst.i.tial Testes in male Glands of secondary glands of Ovaries in female s.e.x traits

7. Parathyroids Unknown a. Controllers of lime metabolism b. Excitability of muscle and nerve

8. Pancreas Insuline Controller of sugar metabolism