Overview
This lecture covers the history of insulin discovery, the challenges faced by early researchers, and how Banting, Best, and their collaborators contributed to developing usable insulin for diabetes treatment.
Early Understanding of Diabetes
- Diabetes was recognized as early as Ancient Egypt and India, with symptoms like excessive urination and sweet-tasting urine.
- The term "diabetes mellitus" originated in Greece (diabetes = "to flow") and Latin (mellitus = "honey").
- Early treatments aimed to reduce sugar in urine, mainly through strict, low-carbohydrate diets.
Advances in Physiology and Pancreas Research
- Claude Bernard discovered glycogen in the liver, explaining glucose presence in urine without high-carb intake.
- Paul Langerhans identified pancreatic islets (Islets of Langerhans), later linked to hormone production.
- Minkowski and von Mering proved removing a pancreas caused diabetes in dogs, suggesting a vital pancreatic hormone.
The Hormone Concept and Insulin Hypotheses
- Charles Brown-Sequard introduced the concept of glands secreting hormones into the bloodstream.
- Researchers hypothesized the Islets of Langerhans produced an "anti-diabetes" hormone (later called insulin, 1909).
- Multiple attempts at pancreatic extracts (by Zuelzer, Kleiner, Paulescu) failed due to side effects and inconsistency.
Challenges Before Banting and Best
- Early extracts were ineffective and dangerous, preventing a successful diabetes treatment.
- Pre-insulin treatments involved severe starvation diets that offered limited benefits.
Banting and Best’s Contributions
- Banting hypothesized that separating Islet cells from digestive pancreatic enzymes could yield effective insulin.
- With Charles Best, Banting conducted experiments using atrophied and fetal animal pancreas, and later whole pancreas, for extracts.
- Key improvements: using alcohol-based extraction, and focusing on fetal/whole pancreas for higher potency.
Final Breakthrough: Purification and Human Trials
- Biochemist James Collip joined and developed a purification method using higher alcohol concentrations.
- Early human trials with unpurified extract had limited effects and side effects; purified insulin proved effective.
- Leonard Thompson became the first patient successfully treated with purified insulin, dramatically improving.
- By late 1922, insulin was recognized as a revolutionary treatment for diabetes and rapidly adopted in clinical use.
Key Terms & Definitions
- Diabetes mellitus — A metabolic disease characterized by high blood sugar and sweet urine.
- Islets of Langerhans — Clusters of pancreatic cells including insulin-producing beta cells.
- Insulin — Hormone produced by pancreatic beta cells, lowers blood sugar.
- Glucagon — Hormone produced by pancreatic alpha cells, raises blood sugar.
- Hypoglycemia — Dangerously low blood sugar, sometimes called insulin shock.
Action Items / Next Steps
- Review the role of each key figure in insulin discovery and their experimental challenges.
- Read about how pharmaceutical companies mass-produced insulin and impacted modern medicine (to be covered in next lecture).