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 a.r.s.enic 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 a.n.a.lyzable. 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 quant.i.ty 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 const.i.tute 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 role 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 ill.u.s.trates 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 quant.i.ty 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 r.e.t.a.r.ding 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 quant.i.ties 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 ill.u.s.trations, 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 s.e.x 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 coa.r.s.e, 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 s.h.a.ggy and rough, losing all l.u.s.ter, 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, a.s.sured 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 rec.u.mbent 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 dent.i.tion.

Whatever growth occurs is irregular and disproportionate. The trunk, though small compared with the head, appears ma.s.sive 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 ill.u.s.trate 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 h.o.m.ogeneous 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 s.e.x 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. Coa.r.s.e, rough dry, s.h.a.ggy 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 ent.i.tle his wife to a divorce is something courts will be called upon to decide sooner or later. But, without antic.i.p.ating, 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 la.s.situde 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 pa.s.ses 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, s.e.xual 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 s.e.xually, 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 ent.i.tled "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 a.s.sociated goitre, the combination designated as exopthalmic goitre.