Endocrinology

Endocrinology started as a discipline in Europe by Arnold Adolph Berthold (1803-1861). He found that castrated cockrels did not develop combs and wattles and did not exhibit male behavior. Replacing gonads to the abdominal cavity of the same animal or another castrated bird cured the animal. It would however take until 1935 for pure crystalline testosterone to be produced.

Castration of animals, however, probably dates back considerably in time. Intentional production of eunuchs was first recorded in the 21st century BCE by the Sumerians. Such individuals have over the millennia performed various services such as courtiers, treble singers, religious specialists, government officials, military commanders, and guardians of women in harems.

The modern view of the presence of a hormone that acts on a receptor on the remote target organ did not come automatically. Berthold guessed wrongly that a substance from the gonad conditioned the blood that then acted on the body. The Chinese were however purifying sex and pituitary hormones from human urine by 200 BCE and used this for medicinal purposes, although no information of eventual effects were provided in the source.

Diabetes mellitus was first described by the Persian, Avicenna, in 1025 by noting that urine tasted sweet and by the increased appetite and lowered sexual interest. Graves' disease, or hyperthyroidism, the combination of goitre and exophtalmus, was first reported in the 12th century by the physician Zayn al-Din al-Jurjani. Robert Graves, an Irish physician, described it in 1835 and Carl Adolph von Basedow described it independently in Germany 1840.

These diseases did however not provide direct clues of a missing hormone. Such a description for Diabetes mellitus came in 1889 when Josef von Mering (1849-1908) and Oskar Minkowski (1858-1931) at the University of Strasbourg surgically removed the pancreas of a dog and found that blood sugar increased followed by coma and eventually death.

In 1922, Frederick Banting (1891-1941) and Charles Best (1899-1978), and John Macleod (1876-1935) at the University of Toronto, found that if one homogenized the pancreas and injected this into the blood of a diabetic dog the symptoms were reversed. This was not a trivial problem because of the presence of protein digestive enzymes in the pancreas. Banting knew form the literature that by ligating the main exit duct of the pancreas, cells producing the digestive enzyme trypsin were digested but cells from the Islets of Langerhans, that now are known to produce insulin, were not digested. Thus given sufficient time he could extract the insulin from the remains of the tissue. The Islets of Langerhans were discovered in 1869 by the German pathologist Paul Langerhans and constitute about 1-2% of the tissue. They are distributed all through the tissue.

In 1922, Banting, Best and Collip used bovine insulin in patients. It then went commercial via Eli Lilly, Hoechst and Nordisk Insulinlaboratorium in Denmark in 1923. In 1978 came the recombinant human insulin from Genentech with the advantage of having the correct amino acid sequence that minimizes immune reactions to the drug. It was approved in 1982.

Banting and Macleod got the Nobel Prize in Physiology and Medicine 1927 for their work on diabetes. Banting shared the money with Best, who did not get the prize. The hormone insulin was later amino acid sequenced by Frederick Sanger (born 1918 ) in 1955. This was a result that led to the general conclusion that proteins had specific sequences of amino acids that in turn led to the genetic code. Sanger got his first Nobel Prize in chemistry 1958. The second Nobel Prize in chemistry he received for his DNA sequencing method in 1980.

Data from Wikipedia