Surgery then enters upon the scene. The great Swiss surgeon. Theodore Kocher, performed the first excision of the thyroid gland in human beings for goitre, in the same year. In 1882, J.L. Reverdin, another surgeon of Geneva, noticed that in man complete removal of the thyroid was followed by symptoms identical with those collected under the name of myxedema, and used the phrase "operative myxedema" to emphasize his conviction of the connection between them. Then Schiff, in 1884, neglected twenty-five years, came back, with an array of demonstrations, proving that the various symptoms, tremors, spasms and convulsions, following removal of the thyroid, could be prevented by a previous graft of a piece of the gland under the skin, or by the injection of thyroid juice into a vein or under the skin, or by the ingestion of thyroid juice or the raw thyroid by mouth.
A crystallization of ideas about the true function of the thyroid was now inevitable. In 1884, Sir Victor Horsley produced an experimental myxedema by removal of the thyroid in monkeys, resembling closely in its symptom-picture the disease as it occurs in human beings. Möbius, a German neurologist, came out boldly for the conception that a number of ailments could be due to qualitative and quantitative changes in the secretion of the thyroid, and that just as myxedema and cretinism were due to an insufficiency of the secretion, Parry's disease was to be ascribed to an excessive outpouring of it. The next steps were easy. In 1888, Sir Felix Semon, as an outcome of a collective investigation, established for all time that cretinism, myxedema and post-operative myxedema were one and the same.
It was bound to occur to someone that if human myxedema and animal experimental myxedema were one and the same, Schiff's procedure of prevention and cure by feeding thyroid gland by mouth in the latter could be applied to the former. The idea occurred to two men, Murray and Howitz, in 1891. Murray's patient, a Mrs. H., was shown before the Northcumberland and Durham Medical Society, an English country medical organization, in February, 1891. She was forty-two years old and had borne nine children. The illness attacking her had begun insidiously, with a gradual enlargement and thickening of her face and hands. She had become very slow in speech and gait, sensitive to cold, and languid and depressed in spirit to the point of inability to go about alone. Murray, employing the glycerin extract of the thyroid gland of a freshly killed sheep, injected twenty-four drops hypodermically, twice a week. There was an immediate and marvelous improvement, which continued steadily, Murray finding that it could be maintained by feeding the gland by mouth. The features and skin returned to the normal, speech quickened and she became able to walk about and live her life without hesitation or assistance. She lived to the age of seventy-four, dying in 1919. In the twenty-eight years, during which it was always necessary to administer the thyroid, she consumed over nine pints of thyroid, comprising the glands of 870 sheep.
Giants and dwarfs and fat people have always interested people as freaks, departures from the usual and the normal, and have formed the stock of popular museum, circus and country fair. Every mythology has concerned itself with them. The Titans among the Greeks, Og, Gog and Magog among the Hebrews, are examples of the fascination of the superlarge. John Hunter, the founder of experimental surgery, spent a fortune in chasing after the skeleton of a famous Irish Giant in 1783. Dwarfs have also fascinated—witness the short-limbed satyrs of the Greeks and the dwarf gods (Ptah and Bes) of Egypt, as well as the vogue of the court dwarf-buffoons, of whom Velasquez has left us some portraits. Fat people, obesity as a manifestation of personality, have aroused wonder and amusement the world over. The Fat Boy has always furnished good sport to the Sam Wellers.
All these characters, tall or short, fat or lean, are related to the activity of a gland of internal secretion in the head, the pituitary, which became a centre of interest in the late eighties. Because of its situation, the opinion of the ancients was that it was the source of the mucus of the nose, an opinion reinforced by the greatest anatomist of the Dark Ages, Galen, and held up to the seventeenth century. In other words, it was considered simply a gland of external secretion. Experimental removal of the pituitary was essayed by Horsley in 1886, the same man who two years before had reproduced myxedema successfully in monkeys. Others succeeded his attempt. But the conclusions drawn were uncertain or contradictory, resulting from the difficulties of the operative technique of getting at a gland placed at the base of the brain. Not until 1908 was the problem solved by Paulesco of Bucharest, who devised a way of reaching it by trepanning the skull. He was thus able to prove beyond a doubt that the pituitary gland was essential to life, and that without it no animal could continue to live for any length of time. Soon after, Harvey Gushing and his associates at Johns Hopkins Hospital discovered that removal of part of the gland was followed by a pronounced obesity and sluggishness. A basis for the understanding of obesity and growth was then established.
In the eighties, there came to the clinic of Pierre Marie in Paris, a pupil of the great Charcot, various women complaining of headache. They also told him about an enlargement of their hands and feet, and an alarming change in the bones of the face. He differentiated the affection from its imitators, and created its present designation of "acromegaly" (enlargement of the extremities). Also he correlated their relationship to the giants who have been mentioned. Acromegalics have been also likened to the Neanderthal Man, who had probably, as the gorillas may have, an excess of the pituitary in their systems. For four years he studied the morbid phenomena in the tissues of these sufferers at last consigned to their end. First one, and then another, and then a third and a fourth exhibited a striking hypertrophy of the pituitary body and a consequent widening of the portion of the base of the skull which cradles the gland. He proceeded to say so in the graduating thesis of his pupil, Souza Leite. The inference was inevitable that the entire process was to be put down to an overactivity of the pituitary. Ever since, too, the growth of the skeleton has been accepted as controlled by that gland.
About this time another set of old observations came to life again, related to those of Docent Berthold on the auto-grafting of the testes of a cock, with complete retention of its sexual characters, which he said, must be due "to the productive action of the testes, i.e., to its effect upon the blood, and thence to the corresponding effect of such blood upon the entire organism." Of course, stock raisers and poultry fanciers have noted the interesting outcome of castration for about as long as their professions have existed. And for ages the diminution of sexual activity as a predecessor to the decadence of senility has been harped upon. Rejuvenation, especially in connection with sexual activity, as well as with tissue and spiritual elasticity, has been one of the haunting phantoms of the imagination for as long as we have records of articulate humanity. Together with El Dorado, the Elixir of Youth has shared the honors with the Philosopher's Stone. The idea of employing the chemical materials of the sex glands, the testes or the ovaries, to bring back youth, to restore juvenility, had not, as far as we know, occurred to anyone who at any rate put himself on record, by word or deed, until 1889. The hero of the new departure was the hero of so many daring adventures among speculative experiments, Brown-Séquard.
At this time the wanderer was an aged sage, seventy-two years old, fit, as custom goes, only for retirement and resignation to the fate of all flesh. The old passion of experimenting upon himself as well as upon the guinea-pigs, dogs, cats and monkeys, by which he was always surrounded, was as alive and kicking as ever. I suppose he had been thinking for years concerning some method for the resumption of youth, for we find him exclaiming, when the opportunity loomed of a great laboratory on Agassiz Island, Long Island, on one of his recurrent flights to New York: "Would that I were thirty!" And other passages in his personal communications refer again and again to his consciousness of growing old. The miracles that were being performed by injecting thyroid and feeding thyroid in animals probably acted as the spark to an inflammable mass of ideas long smouldering in the subcellars of his mind. The effects were reported to the Society of Biology in Paris, one memorable evening, June 1, 1889, in two notes on the results of the hypodermic injection in man of the testis juice of monkeys and dogs, and certain generalizations deduced therefrom. Such juices, he stated, had a definite energy-mobilizing or, as he put it, dynamogenic action upon the subject himself, stimulating amazingly his general health, muscular power and mental activity.
These experiments, their nature, the manner in which they were conducted, the character and age of the experimenter, and the results claimed, were exquisitely good stuff for ridicule. Cartoonists and reporters leaped upon the theme with the avidity of the true-blue interviewer. Paris, where to be ridiculed is to be killed in public with the most ignominious of deaths, reacted as only the French temperament can react. The wits of the salons crackled, the bourgeoisie chortled, the proletariat roared. The Elixir of Life had been discovered and it was excellent sport.
But Brown-Séquard remained unshaken. He had all the roués of Paris running to him, and consequent charges of quackery and charlatanism. How much of these unsavory epithets really applied to him will not be determined until we have a better acquaintance with his more intimate life. A biography and collection of his letters is needed. But it is certain that the general principles he arrived at, aided as much by the wings of intuition as by the clues of incomplete and incompletely controlled experiments, survive as the foundations of whatever we know about the internal secretions, and all our present viewpoints. He summed these up in 1891 as follows: