The discovery of insulin treatment nearly a century ago transformed Type 1 diabetes from a rapid death sentence into a manageable, chronic condition. This life-saving hormone was initially isolated from the pancreases of animals, providing the first viable means to regulate blood sugar in people who could not produce their own. For decades, the global supply relied almost entirely on animal sources, primarily cows and pigs, serving as the only lifeline for millions of patients. A major technological shift in the late 20th century, however, rendered this historical source largely obsolete.
The Original Solution: Animal Insulin
Early insulin production involved extracting the hormone from the pancreatic glands of slaughtered livestock. Pharmaceutical companies purchased these organs from abattoirs, collecting them in massive quantities to meet global demand. The glands were chopped, mashed, and subjected to chemical extraction and purification processes, often using alcohol, to isolate the active insulin protein.
Porcine (pig) and bovine (cow) insulin were the two main types used for human treatment. Porcine insulin was structurally closer to human insulin, differing by only one amino acid, while bovine insulin differed by three. Because of this closer structural match, porcine insulin was often the preferred product, generally resulting in fewer adverse reactions in patients.
Primary Reasons for Discontinuation
The reliance on animal organs presented significant medical and logistical challenges that ultimately led to the search for alternatives. The primary medical drawback was the slight structural difference between animal and human insulin molecules; even a single amino acid difference could trigger an immune reaction in some patients.
These structural discrepancies often led to immunogenicity, causing the formation of anti-insulin antibodies. These antibodies could bind to the injected insulin, neutralizing its effect and making dosing requirements unpredictable and difficult to manage. Furthermore, early extraction methods struggled with purity, meaning the final product contained non-insulin proteins that exacerbated allergic responses and local inflammation.
Logistically, the supply chain was fragile and unsustainable for a global medication. Providing insulin required the pancreases of millions of animals annually, making the supply vulnerable to fluctuations in the meat industry. This posed an eventual risk of shortage, prompting researchers to develop an inexhaustible, non-animal source.
The Technological Shift: Recombinant Human Insulin
The solution to the supply and purity problems arrived with the advent of recombinant DNA technology in the late 1970s. This process involved genetic engineering, allowing scientists to insert the human gene for insulin production into a host organism, typically the bacterium Escherichia coli (E. coli) or yeast. These transformed microorganisms acted as miniature insulin factories, producing insulin molecularly identical to the hormone made by the human pancreas.
In 1978, the first genetically engineered human insulin was successfully produced using E. coli. Eli Lilly and Company commercialized this biosynthetic product, branded as Humulin, which received approval in 1982. This breakthrough immediately solved the core issues of animal insulin, providing an unlimited, sustainable supply free of animal proteins and impurities.
The new manufacturing process eliminated the immunogenic response caused by the slight differences in animal insulin, as the recombinant product was human insulin itself. The ability to produce human insulin with precision and at scale secured the global supply and improved patient safety and predictability.
Modern Advancements: Insulin Analogs
While recombinant human insulin was a massive improvement, it still had limitations in mimicking the body’s natural insulin release. Scientists subsequently developed insulin analogs, which are human insulin molecules subtly altered through genetic modification to change their therapeutic characteristics. These structural modifications involve substituting, adding, or inverting specific amino acids in the insulin chain.
The goal of these modifications is to create products with specific pharmacokinetic and pharmacodynamic profiles—how the drug is absorbed, acts, and is eliminated. For instance, rapid-acting analogs allow for much faster absorption for mealtime coverage. Conversely, long-acting basal analogs, such as insulin glargine, are modified to dissolve slowly over an extended period, providing a steady, peakless background level of insulin for up to 24 hours.
These modern analogs offer superior glycemic control and greater flexibility for patients than the original human insulin formulations. The highly predictable action and varied durations of these engineered insulins finalized the obsolescence of animal insulin, pushing diabetes care into an era of precision medicine.