Insulin is a peptide hormone produced by the beta cells within the pancreas. Its primary function is to regulate the concentration of glucose in the bloodstream by promoting the uptake of glucose into muscle, fat, and liver cells, ensuring the body maintains a stable blood sugar level. For patients whose bodies cannot produce this hormone, a replacement source is necessary. For decades following its discovery, this therapeutic substance was sourced almost entirely from the pancreases of cattle and pigs.
The Discovery of Insulin and Early Sources
Following the isolation of insulin in the early 1920s, the challenge became producing the hormone on an industrial scale. Pharmaceutical manufacturers turned to slaughterhouses, where animal pancreases were readily available as a byproduct of the meat industry. Cows and pigs became the primary source because their insulin structure was remarkably similar to that of humans.
The volume of raw material required for this process was immense, highlighting the limitations of the animal-based approach. To produce a small amount of purified insulin, enormous quantities of pancreatic glands had to be processed. For example, it took approximately two tons of pig pancreases to yield eight ounces of pure insulin. This reliance meant insulin production was linked to the supply and slaughter rates of livestock.
Extracting Porcine Insulin The Manufacturing Process
The industrial process of extracting therapeutic insulin from porcine pancreases was a complex, multi-stage biochemical endeavor focused on separating the hormone from surrounding tissue and other proteins. The process began at the slaughterhouse, where pancreatic glands were collected immediately after the animals were killed. They were then flash-frozen to prevent natural digestive enzymes from degrading the insulin molecule before being transported to the processing facility.
Once at the manufacturing plant, the frozen glands were ground into a fine slurry and subjected to acid-alcohol extraction. This technique involves mixing the homogenized tissue with an acidic, alcoholic solution. The acid dissolves the insulin molecule from the tissue mass, while the alcohol precipitates out unwanted fats and proteins. This initial extract, containing the crude insulin, then underwent a series of purification steps.
The solution was subjected to multiple rounds of filtration and precipitation, often involving adjustments to the pH level to selectively isolate the insulin. Purification utilized column chromatography, where the crude extract was passed through specialized materials that separate molecules based on size or charge. Manufacturers could isolate the insulin molecule from other pancreatic hormones like glucagon and somatostatin through control of pH, temperature, and solvent concentration. The final stages involved crystallization, where the insulin was precipitated as a pure, medical-grade powder formulated into the injectable drug.
Porcine vs Human Insulin Molecular Differences
Although porcine insulin was effective in treating diabetes, it was not an exact biological match for the human hormone due to a difference in their molecular structure. The human insulin molecule is composed of 51 amino acids arranged in two chains, A and B, connected by disulfide bonds. Porcine insulin possesses this same two-chain structure, but it differs from human insulin by only one amino acid.
This subtle variation occurs at position B30 of the B-chain, where human insulin features threonine, while porcine insulin has alanine. While this single substitution does not impair the hormone’s ability to regulate blood sugar, it introduces a minute foreign protein into the patient’s body. The repeated injection of this altered protein could trigger an immune response in some patients. This reaction often manifested as the gradual development of antibodies that bind to the injected porcine insulin. Over time, these antibodies could reduce the treatment’s effectiveness, leading to insulin resistance and requiring higher doses.
The Shift to Recombinant Human Insulin
The biological limitations and logistical challenges of animal-sourced insulin spurred the development of a more advanced, synthetic alternative starting in the late 1970s. This transition culminated with the introduction of recombinant DNA technology, which allowed scientists to produce human insulin structurally identical to the hormone made by the human pancreas. The process involves isolating the human gene that codes for insulin and inserting it into the genetic material of a host organism, such as the bacterium Escherichia coli or yeast.
These genetically modified microorganisms are grown in large fermentation tanks. They follow the instructions of the inserted human gene, effectively becoming microscopic insulin factories. The bacteria or yeast multiply rapidly and produce vast quantities of pure human insulin protein, which is then harvested and purified. This biotechnological approach offered several advantages over animal extraction, including an unlimited, consistent supply not dependent on the meat industry. Because the product is a perfect structural match to human insulin, it virtually eliminated the risk of allergic reactions and antibody development seen with animal-derived versions. The shift to recombinant human insulin in the 1980s marked the end of animal-based insulin as the primary therapeutic option.