The discovery of hormones marked a fundamental shift in understanding how the body’s systems communicate and coordinate functions. Hormones are chemical messengers produced by specialized glands and secreted directly into the bloodstream. They travel through the circulatory system to affect distant target cells, regulating processes like growth, metabolism, and reproduction. This realization involved decades of experiments that moved away from purely nervous control toward sophisticated chemical signaling.
Precursors to Endocrine Understanding
Early ideas about bodily control were dominated by the nervous system, but the 19th century saw experiments suggesting a different kind of internal communication. German physiologist Arnold Berthold provided the first experimental proof of a blood-borne signal in 1849, using roosters. He observed that castrated roosters, or capons, lost their male characteristics, including the large comb and aggressive behavior.
When Berthold transplanted a testis into the abdominal cavity of a castrated rooster, the male features developed normally. Since the transplanted tissue had no nerve connection, he concluded that the testis secreted a substance into the blood to maintain masculine traits. This demonstrated an “internal secretion” acting independently of direct nervous control. The French neurologist Charles-Édouard Brown-Séquard also contributed to this concept later in the century.
Brown-Séquard showed that removing the adrenal glands led to death in animals, proving their secretions were necessary for life. His later, controversial self-experimentation in 1889 involved injecting himself with extracts from animal testes, claiming it reversed aging. Although the extracts were likely too dilute to have a true biological effect, the widely publicized event popularized the concept of glandular extracts influencing systemic health.
The Defining Experiment and Coining the Term
The conceptual breakthrough that formally established endocrinology came from British physiologists William Bayliss and Ernest Starling. Their 1902 work focused on how the pancreas is stimulated to secrete digestive juices when food enters the small intestine. Prevailing scientific thought, championed by Ivan Pavlov, held that this process was controlled solely by a nervous reflex.
Bayliss and Starling challenged this idea with a classic experiment on anesthetized dogs. They cut all the nerves leading to the duodenum, but found that when they introduced dilute acid into the isolated loop, the pancreas still secreted digestive fluid. This proved the signal was not a nerve impulse since the neural connection was severed.
The scientists then scraped the lining of the duodenum, mixed the tissue with acid, filtered the mixture, and injected the extract into the dog’s bloodstream. The pancreas immediately responded with a copious secretion of digestive juice. This demonstrated that the acid triggered the release of a chemical agent from the intestinal lining into the blood, which traveled to the pancreas to stimulate it. They named this chemical messenger “secretin,” making it the first identified hormone.
The term “hormone” was officially introduced by Starling in 1905 during lectures at the Royal College of Physicians. Deriving the word from the Greek verb hormao (“I arouse or excite”), Starling defined hormones as chemical messengers that travel via the bloodstream to coordinate the activities of distant organs. This framework provided a name and definition for the entire class of internal secretions, creating the new field of study.
Isolating the First Key Chemical Messengers
The conceptual discovery of hormones quickly led to the chemical isolation of these substances. The first hormone isolated in a pure, crystalline form was from the adrenal gland, now known as adrenaline or epinephrine. The isolation was achieved independently by two researchers around the turn of the century.
American pharmacologist John Jacob Abel first isolated a stable, but less pure, derivative of the active ingredient in 1897, naming it epinephrine. In 1901, the Japanese-American chemist Jokichi Takamine successfully purified and crystallized the substance in its stable form, naming it Adrenalin. Takamine’s achievement provided the first pure hormone for medical use, proving invaluable for controlling bleeding during surgery due to its vasoconstrictive properties.
A second important isolation followed two decades later with insulin in 1921. Canadian surgeon Frederick Banting had the idea to tie off the pancreatic duct in dogs to stop digestive enzymes, which were thought to destroy the internal secretion. Working with medical student Charles Best, they successfully isolated a working extract from the degenerated pancreas.
This extract, which they called insulin, was then purified by biochemist James Collip. The purified substance was first administered to 14-year-old Leonard Thompson in January 1922, successfully lowering his high blood sugar. This breakthrough transformed type 1 diabetes from a death sentence into a manageable chronic condition, solidifying the practical and medical importance of endocrinology.