The History of Insulin: The First Peptide Drug

Before Insulin, a Death Sentence

Before 1922, a diagnosis of type 1 diabetes was fatal, usually within months. The only available treatment was a severe low-calorie, near-zero-carbohydrate diet, which could extend life by a year or so at the cost of slow starvation. Researchers had long suspected that the pancreas produced some internal secretion that regulated blood sugar, but every attempt to isolate it had failed or produced extracts too impure and toxic for clinical use [1].

A Summer of Experiments in Toronto

In May 1921, a young surgeon named Frederick Banting, working with a physiology student, Charles Best, in the laboratory of Professor John J.R. Macleod at the University of Toronto, began a series of experiments extracting fluid from the pancreas of dogs. Through the summer, they demonstrated that the extract could lower blood sugar in dogs made diabetic by removing their pancreas. Early extracts, however, caused severe toxic reactions when tested, a problem that stalled the work until biochemist James Collip, on sabbatical from the University of Alberta, joined the team and developed a far cleaner purification method [1].

January 1922: The First Human Treatment

On January 11, 1922, Leonard Thompson received the first injection of pancreatic extract. It produced only a modest effect and an allergic reaction, the extract still contained impurities. Twelve days later, on January 23, Collip’s newly purified extract was administered. The results were dramatic: Thompson’s blood glucose fell from dangerously high levels toward normal, and his other symptoms resolved. He lived another 13 years on insulin, at a time when a diabetes diagnosis had meant almost certain death within months [1].

Insulin as the First Protein Ever Sequenced

Insulin’s role in scientific history did not end with its discovery. In the early 1950s, British biochemist Frederick Sanger spent nearly a decade working out insulin’s complete amino acid sequence, including the exact placement of its disulfide bonds linking its two peptide chains, published in 1955 [2]. This was the first time any protein’s precise sequence had ever been determined, a foundational moment for molecular biology that earned Sanger the 1958 Nobel Prize in Chemistry. Insulin was not just the first peptide hormone used therapeutically; it was also the molecule that first proved proteins have a defined, decodable chemical structure at all.

From Animal Extract to Genetically Engineered Drug

For more than 50 years after Thompson’s treatment, insulin for patients was extracted and purified from cow and pig pancreases, a supply-constrained process that also caused allergic reactions in some patients due to small structural differences from human insulin. That changed in 1978, when the biotechnology company Genentech produced human insulin using recombinant DNA technology, synthesizing the gene for the hormone and inserting it into E. coli bacteria to manufacture the exact human sequence. In 1982, the FDA approved this recombinant insulin, marketed as Humulin, making it the first genetically engineered pharmaceutical product ever approved.

Why This History Still Matters in Peptide Research

Insulin’s arc, natural extraction, purification, structural sequencing, and finally recombinant synthesis, is the same arc that shapes how research peptides are made and understood today. For the modern chemistry that descended from Sanger’s structural work, see our overview of how research peptides are made, and for how insulin sits at the intersection of two categories often confused with each other, see our post on peptide vs hormone.

Concepts Related to the History of Insulin