Insulin's Story: Cone Snail Venom, a Coin Toss in Toronto and E. coli

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The cone snail Conus geographus hunts by releasing a weaponized insulin that sends a fish's blood sugar crashing and leaves it sluggish enough to engulf. This episode follows insulin from that reef to the islets of Langerhans, spotted by Paul Langerhans as a Berlin medical student in 1869. It explains how beta cells release insulin to move glucose into cells through GLUT4 transporters, how glucagon from alpha cells does the reverse, and why insulin, 51 amino acids in an A chain and a B chain, is stored as a stable six-molecule hexamer around a zinc atom, which long forced patients to inject hours before a meal.

In the summer of 1921 at the University of Toronto, surgeon Frederick Banting got lab space from a skeptical John Macleod, and students Charles Best and Clark Noble flipped a coin for the first shift. Best won and stayed all summer. On July 30, 1921, their dog pancreas extract cut a diabetic dog's blood sugar by 40 percent in an hour. After clashes with biochemist James Collip, the team partnered with Eli Lilly, where chemist George B. Walden's isoelectric precipitation made mass production possible by late 1922. In 1978 Genentech and City of Hope put the human insulin gene into E. coli, and recombinant human insulin reached the market in 1982.

• Type 1 diabetes as immune destruction of beta cells versus type 2 as cells resisting insulin's signal
• Why stomach acid and enzymes break down an insulin pill before it reaches the blood
• Research linking brain insulin resistance to Alzheimer's disease, which some call type 3 diabetes
• Frederick Sanger's 1951 sequencing of insulin and Dorothy Hodgkin's 1969 crystal structure
• Fast-acting and long-acting analogs, and research on growing insulin in genetically modified safflower