Insulin is a small protein hormone produced by the pancreas that regulates glucose concentration in the bloodstream. It signals cells to absorb and utilize glucose for energy, lowering blood sugar levels. Individuals with Type 1 diabetes do not produce enough insulin, requiring regular therapeutic injections. Bovine insulin, derived from cattle pancreases, was one of the first widely available sources of this medication and was used for decades before being replaced by advanced forms of the drug.
Defining Bovine Insulin’s Structure and Source
Bovine insulin is a polypeptide hormone extracted from the pancreatic glands of cows. Like human insulin, it consists of 51 amino acids arranged into two chains (A-chain of 21 residues and B-chain of 30 residues) connected by disulfide bonds. The slight structural difference between bovine and human insulin is confined to just three specific amino acid positions. This similarity allowed the bovine hormone to function effectively in the human body.
The difference occurs at two sites on the A-chain and one on the B-chain. At position A8, bovine insulin features alanine (human has threonine), and at A10, it has valine (instead of isoleucine). The third variation is alanine at the B30 position (instead of threonine). Although minor, these three substitutions created a foreign molecular profile when injected into a human patient.
Pivotal Role in Early Diabetes Treatment
The therapeutic use of bovine insulin began following the work of Frederick Banting and Charles Best in 1921, who successfully isolated an effective extract from animal pancreases. Before this discovery, a diagnosis of Type 1 diabetes was almost universally fatal, often within a few years. The immediate challenge was to develop a method for large-scale production of a sufficiently pure and potent extract for human use.
Early extracts were crude and caused severe local inflammation and abscesses at the injection sites. Biochemist James Collip played a significant role in refining the purification process, utilizing a series of alcohol-based extractions, filtrations, and concentration steps to create a cleaner product. This refined extract was first successfully administered to a human patient, Leonard Thompson, in January 1922, marking a watershed moment in medical history.
The pancreases of cattle and pigs became the primary commercial sources for decades, providing the only viable treatment option for millions of people with diabetes. The raw material was subjected to extraction and purification steps, yielding therapeutic insulin. This transformed a terminal illness into a manageable chronic condition through regular injections.
The Shift Away Due to Immune Response
The slight molecular difference between bovine and human insulin led to the animal hormone’s obsolescence. The body’s immune system sometimes recognized the bovine protein as foreign, leading to immunogenicity. This foreign recognition could manifest as local tissue irritation, allergic reactions, and the formation of anti-insulin antibodies (AIABs).
The development of these antibodies was problematic because they could bind to the injected bovine insulin, potentially interfering with its ability to lower blood glucose. Bovine insulin was considered more immunogenic than porcine insulin, which differs from human insulin by only one amino acid. This heightened immune reaction necessitated a search for an alternative that would be perfectly recognized by the human body.
The technological solution arrived with the advent of recombinant DNA technology in the late 1970s, which allowed scientists to genetically engineer bacteria to produce insulin with an amino acid sequence identical to that of human insulin. This biosynthetically produced human insulin, often sold under the brand name Humulin, eliminated the three-amino-acid mismatch that caused the immunogenic response. Switching patients from animal-sourced insulin to this new human version often resulted in a significant decline in anti-insulin antibody levels, marking the end of bovine insulin’s long tenure as the standard treatment for diabetes.