In January 1922 a fourteen-year-old boy named Leonard Thompson lay in Toronto General Hospital, wasted to about 65 pounds by diabetes. At the time the disease was a death sentence for children. Doctors injected him with an extract from animal pancreases. The first, impure dose did little, but a purified dose a few weeks later brought his blood sugar down and he began to recover. The extract was insulin, and his story begins with a simple idea: the body sends some of its most important messages by chemicals in the blood.

Chemical messengers

The nervous system sends fast electrical signals along fixed pathways. The endocrine system works differently. Glands release hormones into the bloodstream, which carries them to nearly every cell, yet only cells with matching receptors respond to a given hormone, the way only one key fits a lock. Hormone signals are slower than nerve signals but often last much longer. In 1902 the British physiologists William Bayliss and Ernest Starling showed that a chemical from the intestine, which they named secretin, could trigger the pancreas even when the nerves were cut. Starling introduced the word hormone in 1905, from a Greek word meaning to set in motion.

The command center

The hypothalamus, which Level 1 met as the body's thermostat, is also where the nervous and endocrine systems meet. The hypothalamus directs the pituitary gland, a pea-sized gland just beneath it. The pituitary was once called the master gland because its hormones control the thyroid, the adrenal glands, the ovaries and the testes, and because it releases growth hormone. But it takes its orders from above. Many of these chains are held in check by negative feedback: when thyroid hormone in the blood runs high, the hypothalamus and pituitary ease off the signal that drives the thyroid.

The thyroid and iodine

The thyroid, in the front of the neck, makes hormones that set the body's overall pace of energy use. Those hormones contain iodine, and without enough iodine in the diet, the thyroid can swell into a goiter, a visible lump in the neck. In regions with iodine-poor soils, such as parts of the Alps and the Great Lakes area of North America, goiter was once common. Iodine shortage in pregnancy can also harm a child's developing brain. In the 1920s Switzerland and the United States began adding iodine to table salt, one of the cheapest and most effective health measures ever devised.

Blood sugar

Scattered through the pancreas are clusters of cells called islets. After a meal, as glucose in the blood rises, their beta cells release insulin. Insulin lowers blood glucose by helping cells take it in and the liver store it. Between meals, other islet cells release glucagon, which raises glucose by telling the liver to release its stores. Together the two hormones keep blood sugar within a narrow range.

Diabetes is the failure of that balance. In type 1 diabetes, the immune system destroys the insulin-making cells, so the person must take insulin to survive. In type 2 diabetes, the body's cells respond poorly to insulin, and over time the pancreas may struggle to keep up. Type 2 accounts for about 90 percent of cases and is linked to genes, excess weight and inactivity; it is often managed with diet, exercise and medicine.

The Toronto team behind insulin, Frederick Banting and Charles Best working with John Macleod and James Collip, won quick fame. The 1923 Nobel Prize went to Banting and Macleod, who each shared the money with a colleague they felt had been overlooked. The discoverers sold the patent to the University of Toronto for a token sum so that the drug would be widely available.

Stress hormones

The adrenal glands sit on top of the kidneys. In an emergency they release adrenaline, also called epinephrine, which within seconds raises the heart rate, widens the airways and floods the blood with glucose: the fight or flight response. They also release cortisol, which works over hours, raising blood sugar and damping inflammation. Adrenaline acts within seconds, while cortisol works more slowly. Cortisol that stays high for months, as in some kinds of chronic stress or disease, is linked to high blood pressure, weakened immunity and other harms.

Worked example: a day of blood sugar

Anna eats pancakes for breakfast. Within half an hour her blood glucose climbs, her beta cells release insulin, and her muscle, fat and liver cells absorb the sugar. By midafternoon, hours after lunch, her glucose starts to drift down and glucagon tells her liver to release stored sugar. Her friend Sam has type 1 diabetes and makes no insulin. Without an injection, his glucose after the same breakfast would keep rising until his kidneys could no longer reclaim it all and sugar spilled into his urine, which is why the disease's full name, diabetes mellitus, refers to honey. So Sam counts the carbohydrates and doses insulin, often guided by a small sensor on his arm. If he takes too much, his glucose falls too low; adrenaline makes him shaky and sweaty, a warning to eat something sugary at once. In one morning, both friends show negative feedback at work, one naturally and one with help.