The Evolution of Insulin: From Discovery to Biotechnology Innovation

In the early 1920s, groundbreaking research by Frederick Banting and Charles Best led to a pivotal discovery in the treatment of diabetes mellitus. They demonstrated that a pancreatic extract could effectively manage diabetes, revolutionizing the way the disease was treated. By 1923, this pancreatic extract—derived from pig and beef organs, with insulin as its active ingredient—was commercialized by Eli Lilly. Just three years later, the extract was crystallized, marking a significant milestone in medical science.

Frederick Sanger’s Breakthrough in Protein Sequencing

The 1940s and 1950s marked a new era in biochemistry with the pioneering work of English chemist Frederick Sanger. In 1943, Sanger began investigating the amino acid sequence of insulin at Cambridge University. At that time, insulin was one of the few proteins available in pure form, readily obtainable from the British pharmacy chain Boots. After years of dedicated research, Sanger succeeded in determining the precise amino acid sequence of insulin. In 1951 and 1952, he discovered that insulin consists of two peptide chains: an A chain containing 21 amino acids and a B chain with 30 amino acids.

This groundbreaking discovery made insulin the first protein to have its complete amino acid sequence determined. Sanger's work proved that all human proteins possess a unique chemical sequence composed of the 20 standard amino acids. For his monumental contributions to the understanding of protein chemistry, Sanger was awarded the Nobel Prize in Chemistry in 1958. In 1977, he became the only individual to win the Nobel Prize in Chemistry twice, a testament to his enduring legacy in the field.

The Synthesis of Insulin: Advancements in Biotechnology

With the chemical structure of insulin now fully understood, scientists were able to begin synthesizing this vital hormone in the laboratory. By 1963, researchers succeeded in synthesizing insulin, paving the way for greater precision in treatment. However, the insulin derived from animals, although effective, had slight differences from human insulin. Pig insulin differs by one amino acid, while beef insulin differs by three. These small variations, while seemingly insignificant, were responsible for allergic reactions in some diabetic patients.

The Dawn of Genetically Engineered Human Insulin

In 1978, a groundbreaking achievement in biotechnology took place. Researchers at the City of Hope National Medical Center, in collaboration with Genentech, a biotech company led by biochemist Herbert Boyer, succeeded in synthesizing human insulin using recombinant DNA technology. This process involved inserting the human insulin gene into bacterial DNA, creating genetically modified bacteria that acted as biological factories. These bacteria multiplied rapidly, producing virtually limitless supplies of human insulin.

This innovation marked a turning point in diabetes treatment. In 1982, Eli Lilly introduced Humulin, the first commercially available human insulin, replacing animal-derived insulin. Humulin was a game-changer in the management of diabetes, offering a safer and more reliable alternative to animal insulin.

The Legacy of Insulin Innovation

The journey of insulin—from its initial discovery to the development of synthetic and genetically engineered forms—has been a testament to the power of scientific collaboration and innovation. The work of Banting, Best, Sanger, Boyer, and countless others has not only revolutionized diabetes treatment but also paved the way for advancements in biotechnology and genetic engineering. Today, the ability to produce insulin through biotechnology has transformed the lives of millions of people worldwide, offering a more effective and accessible treatment for diabetes than ever before.

A three-dimensional model of the insulin molecule. By convention, the following colors represent specific elements: white = hydrogen; black (shown here as dark gray) = carbon; blue = nitrogen; red = oxygen; yellow = sulfur.