Theories about thyroid function had particularly gained plausibility toward the end of the nineteenth century. By then scientists had discovered that the gland secreted a physiologically active substance into the bloodstream—in other words, that it functioned through internal secretion. Until about 1900 the concept of organ replacement developed in tandem with the theory of internal secretion, and, at the time, organ replacement typically meant the replacement of an internal secretion. Thus the first organ transplants all concerned internal secretion glands and it was not until the early twentieth century that organ transplantation and the developing field of endocrinology diverged.

In the early years of its development, the concept of internal secretion helped to make the idea of organ replacement more convincing. In 1884, when Moritz Schiff began to suspect that the thyroid released a substance into the blood and thus contributed to the nourishment of the central nervous system, he was working from an older idea of internal secretion that had originated with physiologist Claude Bernard. Bernard had first proposed the concept of internal secretion in 1853 in order to differentiate between two processes: the secretion of bile from the liver into the intestine (an external secretion), and the release of glucose from the liver into the circulatory system (an internal secretion). After 1859 Bernard expanded this theory to other organs such as the spleen, thyroid, and adrenal glands. Nearly three decades later, Schiff carried forth Bernard’s work on glucose secretions from the liver and experimented with the removal of organs that had the potential of producing internal secretions, such as the thyroid and adrenal glands. Bernard’s concept was so well-accepted that applying it to the new observations on the thyroid seemed obvious.

By the early 1890s, the study of internal secretions had become a popular research topic, thanks in part to the progress of thyroid research. The growing popularity of the new concept of “organotherapy” also drew scientists’ attention toward internal secretion—an interesting development for the history of organ transplantation, since organotherapy and the concept of organ replacement eventually converged and mutually reinforced each other.