Finally, let us take a third example. In no field of physiology has our knowledge grown more, have the results been more spectacular, or have the practical rewards to mankind been greater than in that associated with the hormones formed by the endocrine or ductless glands. Since the development of the doctrine of the bacterial origin of disease, probably nothing has stirred up modern medicine more than the doctrine of internal secretion. We are told that we are what we are - bodily, mentally, sexually, emotionally - largely as a result of a balance or unbalance of chemical products from the glands of internal secretion. Let us, then, review briefly the physiological side of the modern work upon one of these interesting organs. As so much has been recently written about the hormones of the adrenals, thyroid, and pancreas, we will take one of the less known, but no less important glands - the parathyroids.

The parathyroid glands are quite minute organs, four in number, and anatomically closely associated with the thyroid gland. The first clue to their function was obtained, as has been the case with many of the endocrine organs, by studying the effects of complete removal of these organs from an animal. This operation results in the manifestation of a condition known as tetany (Tetania parathyreopriva); this is in no way synonymous with tetanus. It was often observed in man as the result of the removal of thyroid tumors in the days before the physiological significance of the parathyroids was recognized. The symptoms of removal of these glands vary somewhat in different animals. In the dog, which has served for most experimental work, there is a stiffness of the muscles, associated with fibrillary contractions or tremors, and later cramp-like and clonic contractions, with eventually convulsive fits. Since death always results after complete extirpation of all parathyroid tissue in untreated animals, it is obvious that these small structures are essential for life.

The function of these glands remained obscure for a long time. About twenty years ago, it was found that after a removal of the parathyroid glands in dogs, the calcium content of the blood was greatly reduced in amount. This naturally led to an attempt to restore the calcium of the body to normal artificially, by injection of a calcium salt; and it was found that this treatment would relieve the condition of tetany and restore the animal to normal for a short period of time. The whole train of symptoms of tetany was held to be due to a lowered calcium content of the blood, which is normally controlled by the parathyroid glands.

The above theory of the relationship of the parathyroids to calcium metabolism did not, however, go unchallenged. Another theory gained considerable vogue for a while; namely, that the parathyroids act in the body as detoxifying agents and that the symptoms after their removal are due to the accumulation of toxic products normally rendered innocuous by them. Indeed, certain substances, called guanidine and methyl guanidine, were stated to occur in the blood of parathyroidectomized animals in abnormally large amounts.

The proof that the parathyroid glands perform their function by the production of a hormone which is intimately related to the metabolism of calcium has come only in the last few years. This proof consists in the extraction of the hormone from the glands of cattle - in a crude form, to be sure - the use of this hormone to bring about complete and lasting relief from the symptoms of removal of the glands, and the demonstration that the activity of the hormone is proportional to its calcium-mobilizing effect. After removal of these glands in dogs, all abnormal symptoms can be suppressed and life prolonged indefinitely by repeated injection of the extract containing the hormone. The effect is as remarkable as that of insulin in diabetes. The calcium content of the blood of a normal unoperated dog is also increased by injection of the hormone, which is similar to the action of insulin in decreasing the blood sugar of a normal non-diabetic animal. This action on the calcium of the normal has been utilized for the biological standardization of the parathyroid hormone.

Concerning the chemical nature of this parathyroid hormone, very little is known as yet. No doubt, success will come in the future in the isolation of the active principle as a pure chemical individual, as has already happened for insulin and the hormones of the adrenal medulla and the thyroid and the ovary. This will be a great step forward, and will undoubtedly aid in solving the fascinating problem as to how this hormone acts to regulate the calcium content of the blood. The final step in our knowledge of the hormone will be a determination of its chemical constitution and a synthesis in the laboratory. We cannot do more than mention here that this parathyroid hormone has already been used successfully in the treatment of various conditions of tetany in children, due, presumably, to an underfunctioning of the parathyroid glands. It is possible that the hormone may be of service in many conditions where the metabolism of calcium is disturbed.

In conclusion, it is important to recognize the tremendous amount of laborious work which must be done before even small minor points in regard to the functioning of the animal organism can be settled. The public hears of only the final result, and even then only if it happens to be something of paramount importance for the welfare of mankind. The slow, steady growth of our knowledge of a subject, contributed throughout the ages by hundreds of workers, many now entirely forgotten, is never properly appreciated. In this connection Starling has written: "Every discovery, however important and apparently epoch-making, is but the natural and inevitable outcome of a vast mass of work, involving many failures, by a host of different observers, so that if it is not made by Brown this year, it will fall into the lap of Jones, or of Jones and Robinson simultaneously, next year or the year after." To which may be added what Abel has said:"the lap into which the ripe fruit falls generally has a very good head atop of it."