Insulin, a hormone produced by the pancreas, plays a central role in regulating blood glucose levels. It acts as a key, allowing glucose from the bloodstream to enter cells for energy or storage. Before the availability of insulin therapy, individuals with diabetes faced severe health complications, including diabetic ketoacidosis, which often led to premature death. The discovery and subsequent production of insulin transformed diabetes from a rapidly fatal condition into a manageable chronic disease.
The Discovery and Early Need for Insulin
Before the 1920s, a diagnosis of type 1 diabetes was a virtual death sentence, particularly for children, who rarely survived more than a year or two. Treatments were limited to severe dietary restrictions, often involving starvation diets, which only temporarily delayed the inevitable decline. This grim reality underscored an urgent medical need for an effective treatment to control blood sugar.
Work to isolate insulin began in 1921 at the University of Toronto. Frederick Banting, a young surgeon, conceived the idea of isolating insulin from the pancreas, and with the assistance of Charles Best, a medical student, they began experiments. John Macleod, a professor, provided laboratory space and resources, while James Collip, a biochemist, refined the purification process. Their efforts led to the isolation of a pancreatic extract that lowered blood glucose in diabetic dogs.
The first human trials in 1922, initially on a 14-year-old boy named Leonard Thompson, demonstrated the extract’s life-saving potential. This immediate success propelled the extract, soon named insulin, into widespread medical use. The discovery provided hope and a lifeline for millions, changing the prognosis for people with diabetes.
Why Porcine and Bovine Insulin?
Following its discovery, the challenge was to produce enough insulin for global demand. Researchers quickly identified that the pancreases of common farm animals, specifically pigs (porcine) and cows (bovine), were the most practical sources. These animals were already being processed in large numbers by the meat industry, providing a consistent supply of pancreatic glands.
The choice of porcine and bovine pancreases was also based on their biological compatibility with human insulin. Pig insulin differs from human insulin by only one amino acid. Bovine insulin has a slightly greater difference, varying by three amino acids compared to human insulin. This close structural similarity meant that animal-derived insulin could bind to human insulin receptors and lower glucose, minimizing adverse reactions for most patients.
The abundance of these animal organs and high insulin concentration made them the most feasible for large-scale production. This availability allowed for rapid scaling of insulin manufacturing to meet global demand.
The Manufacturing Process of Animal-Derived Insulin
The historical production of insulin from animal pancreases was a complex process. The initial stage involved the collection of pancreatic glands from slaughterhouses. These glands had to be transported quickly and kept cold to prevent the degradation of insulin by enzymes. Upon arrival at the manufacturing facility, the glands were minced.
Insulin was then extracted from this pancreatic pulp using a solution of acidified alcohol. This acidic alcohol solution served multiple purposes: it denatured the proteolytic enzymes that would otherwise break down insulin, extracted the insulin from the tissue, and helped to precipitate other proteins and impurities. After the initial extraction, the mixture was filtered to remove solid tissue debris, leaving an insulin-containing liquid extract.
Further purification steps were necessary to isolate and concentrate the insulin. This involved a series of precipitation and crystallization processes, often utilizing different pH adjustments and the addition of salts or organic solvents. The precipitated insulin was then redissolved and recrystallized to achieve higher purity levels. Final stages often included filtration through membranes to remove particulate matter and ensure sterility, resulting in a product that was typically 90-95% pure. This process, however, yielded small amounts of insulin per pancreas, requiring thousands of glands to meet demand.
Evolution to Modern Insulin Production
Despite its life-saving impact, animal-derived insulin had limitations. The slight structural differences between animal and human insulin could trigger allergic reactions or immune responses, reducing effectiveness or causing skin reactions. Variability in purity levels across batches also posed challenges, as even highly purified animal insulin could contain trace animal proteins. Furthermore, reliance on animal pancreases meant that the supply was inherently limited by the meat industry and subject to fluctuations, raising concerns about long-term sustainability and ethical considerations.
The advent of recombinant DNA technology in the late 1970s marked a significant shift in insulin production. This technology allowed for the genetic engineering of bacteria or yeast to produce human insulin. Scientists inserted the human gene for insulin into these microorganisms, enabling them to synthesize human proinsulin, which could then be converted into active human insulin.
This biotechnological advancement offered numerous advantages. Recombinant human insulin is structurally identical to the insulin naturally produced by the human body, significantly reducing the risk of allergic reactions and immune responses. The production process is also more consistent, yielding a purer and more predictable product. Moreover, it eliminated the reliance on animal sources, ensuring a virtually limitless and ethically sustainable supply. While animal-derived insulin is largely phased out for new patients today, some individuals who have used it for many years may continue to do so under medical supervision.