Q.How was Insulin obtained before the advent of rDNA technology? What were the problems encountered?

Before recombinant DNA technology arrived, insulin was extracted directly from the pancreases of slaughtered cattle and pigs. The process involved collecting pancreatic tissue from these animals, grinding it up, and purifying the insulin protein through chemical methods. This animal-sourced insulin was then administered to diabetic patients who could not produce their own.

The major problem was that animal insulin, though similar to human insulin, is not identical in amino acid sequence. Pig insulin differs from human insulin by one amino acid, and cattle insulin by three. This difference meant the immune system of many patients recognized the injected insulin as foreign and mounted an immune response against it. Patients often developed allergies or other adverse reactions, making long-term treatment difficult and sometimes dangerous. …

Diabetes mellitus, a condition where the body cannot regulate blood sugar due to insufficient or ineffective insulin, has plagued humanity for centuries. The discovery of insulin in 1921 transformed diabetes from a death sentence into a manageable disease, but obtaining enough of this life-saving hormone remained a formidable challenge for decades.

In the pre-rDNA era, insulin came exclusively from animal sources. The pancreases of cattle (bovine insulin) and pigs (porcine insulin) were collected from slaughterhouses, and the insulin was painstakingly extracted and purified from these organs. This was the only method available to produce insulin for the millions of diabetic patients who depended on daily injections to survive.

The process worked, but it was far from ideal. Imagine the scale required: thousands upon thousands of animal pancreases were needed to meet even a fraction of global demand. A single patient required insulin derived from multiple animals over their lifetime, and as diabetes prevalence grew, the supply chain struggled to keep pace.

The problems were both medical and logistical:

Immunological reactions: Many patients developed allergies to the foreign animal proteins. The immune system recognized these slightly different insulin molecules as "non-self" and mounted defensive responses. Patients experienced allergic reactions ranging from mild skin irritation at injection sites to more severe systemic responses. Some individuals developed insulin resistance over time as their bodies produced antibodies against the animal insulin, rendering the treatment progressively less effective. …

Method — compare human insulin vs animal insulin amino-acid-by-amino-acid

Human insulin's A and B chains differ from pig insulin by 1 amino acid, and from cattle insulin by 3.

Even a 1-amino-acid mismatch is enough for the immune system to flag the molecule as "foreign" → allergic/immune reactions. …