History & Evolution of Peptide Medicine

The history of peptide medicine cannot begin anywhere other than Toronto, 1921. Frederick Banting, a young orthopedic surgeon with no research experience, approached University of Toronto physiology professor John Macleod with an idea: ligate the pancreatic ducts of dogs to cause acinar cell degeneration, leaving the islets of Langerhans intact, then extract the islet secretion and test it in diabetic dogs. Macleod was skeptical — eminent European researchers had repeatedly failed to isolate the internal secretion of the pancreas — but provided Banting with laboratory space, 10 dogs, and the assistance of a medical student, Charles Best. The results they obtained over the summer of 1921 were extraordinary: their extract dramatically lowered blood glucose in pancreatectomized dogs that otherwise would have died within days (Bliss, PMID 3521889).

By December 1921, biochemist James Collip joined the team and developed a purification method producing an extract pure enough for human administration. On January 11, 1922, Leonard Thompson, a 14-year-old boy weighing 65 pounds and drifting toward diabetic coma at Toronto General Hospital, received the first human injection. The initial preparation caused a severe allergic reaction, and the injection was halted. Collip worked frantically for 12 days to improve purification. On January 23, Leonard received the second injection — and his blood glucose normalized. He lived another 13 years, dying from pneumonia in 1935, having lived a relatively normal life that was impossible for any type 1 diabetic before insulin.

The Nobel Prize in Physiology or Medicine 1923 was awarded to Banting and Macleod (controversially excluding Best and Collip). Banting shared his prize money with Best; Macleod shared his with Collip. By 1923, Eli Lilly had licensed the production process and was manufacturing insulin at industrial scale — one of the first examples of the pharmaceutical industry taking an academic discovery to global clinical impact in record time. Early insulin was extracted from beef and pork pancreas, and the purification limitations meant early preparations were immunogenic. The first highly purified "single-component" insulins arrived in the 1970s; biosynthetic human insulin (produced in bacteria via recombinant DNA technology) was introduced in 1982 — the first recombinant DNA pharmaceutical approved by the FDA.

The insulin story established the template for all subsequent peptide drug development: identify an endogenous peptide hormone, understand its biology, find a way to produce it in therapeutic quantities, and develop a delivery system that allows it to reach its target. This template, with increasing sophistication, has been followed for every therapeutic peptide in the century since.