Five ENDOCRINOLOGY 101 The doctor who sits at the bedside of a rat Asks real questions, as befits The place, like where did that potassium go, not what Do you think of Willie Mays or the weather? So rat and doctor may converse together. Josephine Miles “The Doctor Who Sits at the Bedside of a Rat” Since the Enlightenment, however, wonder has become a disreputable passion in workaday science, redolent of the popular, the amateurish, and the childish. Scientists now reserve expressions of wonder for their personal memoirs, not their professional publications. Katharine Park and Lorraine Daston Wonders and the Order of Nature Before going on to describe my research and academic career, I wanted to provide the reader with a short “course” in endocrinology, which I still, after all these years, think is wonderful. Let’s face it—the public, the media, and I love hormones. They do such wonderful things. For example, the sex hormones are responsible at puberty for turning on bodily sexual phenotype. A new born baby not secreting thyro- id hormone from its own thyroid will never show normal brain differentiation because crucial connections between neurons in the brain require the presence of this hormone to be completed. The mother’s thyroid hormones take care of the baby’s brain growth while the baby is still in the uterus, but after birth, the baby’s thyroid must secrete its own hormones. Unless treated before six months of age with thyroid hormone, this child will grow up severely dam- aged, what one used to call a “cretin,” with irreversible low intelligence and severe skeletal and muscular growth impairment. We no longer see cretins in our country, where even the least expe- rienced physician recognizes the early signs of lack of thyroid hormone in an infant. But when I went to China in 1983 with a group of endocrinologists, we saw cretins in the pediatric ward in a hospital in Beijing. They had grown up in rural areas where they were not diagnosed as hypothyroid until it was too late. This was a poignant experience for me, reminding me of my long ago dissertation work on thyroid hormone function. The study of the secretions of the endocrine glands began in a formal sense late during the late nineteenth and early twentieth century. At that time, the concept of a hormone evolved. Scientists theorized that some cells or or- 54 A LAB OF MY OWN gans in the body influenced other cells distant from them, not by direct con- nections such as nerves, but by releasing a substance, called a hormone, into the blood stream, whence it would travel to a distant organ and influence cells in these distant sites. But the practice of endocrinology, began much earlier. Remember the technique of castration of domestic animals to foster docility and to increase muscle fat and tenderness, the castration of men to provide eunuchs for ha- rems, or the castration of boys to maintain soprano voices for church chorus- es. Human beings were carrying out this surgery without knowing why it worked. Well, how did the transition occur between what must have been the accidental finding of the relation between the lack of the testes and decreased sex drive or high pitched voices and the understanding that the testes manu- factured and secreted a substance responsible for the masculine phenotype? The concept of a hormone can be traced to experiments during 1902, when the William Bayliss and Ernest Starling asked how it is possible that swallowing a meal, resulting in the food entering the stomach and the initial part of the small intestine, could cause the pancreas, an organ some distance away, to secrete enzymes into the intestine? These enzymes are necessary to break down proteins into amino acids, which are small enough to be absorbed into the blood stream. Two possibilities occurred to Bayliss and Starling: (1) nerve fibers could carry the information from the stomach or intestine to the pancreas, or (2) maybe a substance existed, which was carried in the blood from intestine to pancreas acting as a signal to increase secretion. They demonstrated that a substance they named “secretin” was formed in the inner lining of the duode- num in response to stomach acid reaching the small intestine after a meal. This hormone secretin could influence pancreatic secretion of enzymes by means of a humoral rather than a neural mechanism (secretin traveled in the bloodstream to the pancreas from the duodenum). In 1905, Starling introduced the generic term hormone (from the Greek- “I excite”) to describe such blood-borne messengers. Thus, by the beginning of the twentieth century, the blood was recognized as a carrier of hormonal signals in addition to being a transporter of nutrients to all cells and waste substances to the intestines, lungs, or kidneys to be excreted. An interesting clinical association with regard to the ovaries was also made in the late nineteenth century, which has had therapeutic ramifications that are still being explored. A Scottish surgeon, George Beatson, noted that in sheep, milk production by the breast seemed to be associated with morpho- logical changes in the ovaries. This suspected link induced him to remove the ovaries from a woman with advanced breast cancer, after which she lived for nearly four years. Subsequently, the role of circulating estrogens in breast cancer was demonstrated, leading to the present use of an estrogen antagonist, tamoxifen, in women with estrogen dependent breast cancer. .