If one wishes to trace the idea of internal secretion by cells to an individual, it is convenient, if not pedantic, to give the credit to Theophile de Bordeu, a famous physician of Paris in the eighteenth century. Bordeu came to Paris as a brilliant provincial in his early twenties and by the charm of his manner and daring therapy fought his way to the most exclusive aristocratic practice of the court. Naturally a courtier, taking to the intrigues of the royal court like a duck to water, making enemies on every hand as well as friends, and with a fastidious and impatient clientele, he yet found time to dabble in the wonders of the newly perfected microscope and to speculate upon the meaning of the novelties revealed by it in the tissues. He coined the thought of a gland secretion into the blood.

It was in the year 1749 that he came to Paris from the Pyrenees, a young medical graduate, destined to become the most fashionable practitioner of his time. At the age of twenty-three he was holding the professorship of anatomy at his alma mater, Montpelier, where his father was a successful physician. At twenty-five he was elected corresponding member of the Royal Academy of Sciences. A handsome presence and a Tartarin de Tarascon disposition assured his success from the start. The medical world was then composed of the emulsion of charlatanry and science Molière ridiculed. Success stimulated envy and jealousy. One of the richest of the older medical men set himself the job of procuring his scalp. On a trumped-up charge of stealing jewels from a dead patient—a favorite accusation against the doctors of the eighteenth century—he had Bordeu's license taken away from him. The good graces of certain women to whom Bordeu had always appealed, and who indeed supplied the funds to get him started in Paris, rammed through two acts of Parliament to reinstate him. Nothing daunted, he returned to his quest for a court clientele, and was rewarded finally by having the moribund Louis XV as a patient.

This was the man with whom the modern history of the internal secretions begins. Not content with adventures among the courtiers and desperadoes of the most corrupt court in the most corrupt city of the world, he went in for research. The high power microscope that came into vogue when he was studying, revealed vague wonders which he described in a monograph, "Researches into the mucous tissues or cellular organs." But what makes him interesting is a slender volume on the "Medical Analysis of the Blood," published in the year of the American Declaration of Independence. The sexual side of men and women aroused Bordeu's most ardent enthusiasms. Starting with observations on the characters of eunuchs and capons, as well as spayed female animals, he formulated a conception of sexual secretions absorbed into the blood, settling the male or female tint of the organism and setting the seal upon the destiny of the individual. Thus he must be donated the credit of anticipating the most modern doctrine on the subject.

The generation after him witnessed the triumph of the cell as the recognized unit of structure of the tissues, the brick of the organs. It was soon found that the cells of the more familiar glands, like the sweat or tear glands, resembled the cells of the more mysterious structures named the thyroid in the neck, or adrenal in the abdomen, of which the function was unknown. What had hitherto prevented classification of the latter as glands was the fact that they possessed no visible pathways for the removal of their secretion. So now they were set apart as the ductless glands, the glands without ducts, as contrasted with the glands normally equipped with ducts. Since, too, they were observed to have an exceedingly rich supply of blood, the blood presented itself as the only conceivable mode of egress for the secretions packed within the cells. So they were also called the blood or vascular glands.

The names which became most popular were those which represented a contrast of the glands with the ducts, conveying their secretion to the exterior, as the glands of EXTERNAL SECRETION and the glands without the ducts, the secretions of which were kept within the body, absorbed by the blood and lymph to be used by the other cells, as the glands of INTERNAL SECRETION. How different these two classes of glands are may be realized by imagining the existence of great factories manufacturing food products, which would diffuse through their walls into the atmosphere, to be absorbed by our bodies.

There are certain terms for the glands of internal secretion which are used interchangeably. They are spoken of often as the endocrine glands and as the hormone producing glands. Endocrine is most convenient for it stands for both the gland and its secretion. Hormone is employed a good deal in the literature of the subject. But it applies specifically to the internal secretion, and not to the gland.

THE EXPERIMENTAL PIONEER

All this clarification of the concept of the glands of internal secretion occurred in the first quarter of the nineteenth century. However, no inkling of their real importance to the body, of which quantitatively they form so insignificant a part, was apparently revealed to anyone. Not even the most daring speculation or brilliant guess work in physiology engaged them as material. Thus Henle, the great anatomist, calmly affirmed that these glands "have no influence on animal life: they may be extirpated or they degenerate without sensation or motion suffering in the least." Johann Müller, the most celebrated physiologist of his day and contemporary of Henle, wrote in 1844 and coolly stated, "The ductless glands are alike in one particular—they either produce a different change in the blood which circulates through them or the lymph which they elaborate plays a special rôle in the formation of blood or of chyle." In other words, they were dismissed as curious nonentities, of no real significance to the running of the body. Laennec, the French founder of the Art of Diagnosis in Medicine, once said that nothing about a science is more interesting than the progress of that science itself. He might have added that nothing either was more interesting than the contradictions in that progress. For while these grand moguls of their sciences were enunciating their dogmas, pioneers here and there were already setting the mines that were to explode them.

The experimental method, to the value of which biologists were just beginning to awaken, was destined to be the vehicle of Time's revenges. An application of it to the mysteries of sex was the immediate occasion. Sex and sex differences have always more or less obsessed the imagination of mankind. The volumes of theories about them would constitute a respectable museum. Certain gross facts, however, were known. The effects of loss of the sex glands upon the configuration of the body and the predominating constitution in animals and eunuchs have always attracted attention. The proverbs and stories of all nations are full of references to them. But up to the nineteenth century no controlled experimental work was ever carried out regarding them. It was in 1849, that A.A. Berthold of Göttingen, a quiet, sedate lecturer, carried out the pioneer experiment of removing the testes of four roosters and transplanting them under the skin. It was Berthold's idea to test whether a gland with a definite external secretion, and a duct through which that secretion was expelled, but which yet had powers over the body as a whole that were to be attributed only to an internal secretion, could not be shown, by a clean-cut experiment, to possess such an internal secretion. He succeeded perfectly. For he found that, though, in thus separating the gland from its duct and so cutting off its external secretion, the action of the cells manufacturing that secretion was destroyed, the general effects upon the body were not those of castration. The animals retained their male characteristics as regards voice, reproductive instinct, fighting spirit and growth of comb and wattles. Whereas if the glands were entirely removed, these male traits, peculiar to the rooster, were completely lost. The inference was the existence of an internal secretion.

To Berthold belongs the honor of being the first experimental demonstrator who proved the reality of a gland with a true internal secretion and the power it exercised through the blood upon the entire organism. Besides, he showed that a typical gland of external secretion could also have an internal secretion, a possibility never before considered. That two kinds of cells could live within the same gland: one set usually recognized as producing the external secretion, the other evolving the internal secretion, was an astounding original conception.