Biotech Pioneers: rDNA and Insulin

In the early 1970s, researchers, funded in part by the U.S. National Science Foundation, discovered how to combine DNA from different sources into one sequence. This breakthrough, called recombinant DNA (rDNA), was used to develop the first form of synthetic human insulin.

Synthetic insulin has since transformed care for millions of people with diabetes and paved the way for hundreds of other lifesaving therapeutics.

A biotech game-changer

Since the 1950s, scientists have known that bacteria contain extra loops of DNA, called plasmids, in addition to their chromosome. In nature, bacteria can swap these plasmids with one another, quickly transferring beneficial genes, like those that code for antibiotic resistance.

In 1973, NSF-supported researchers demonstrated that they could cut open a plasmid loop from one bacterial species, insert a gene from a different bacterial species, and close the plasmid. This created an rDNA molecule — a plasmid containing DNA combined from different sources.

Next, the researchers inserted the rDNA plasmids into bacteria and demonstrated that the bacteria could transfer the rDNA to offspring along with their own DNA.

Because DNA contains the genetic code that directs the synthesis of proteins, researchers soon realized they could use this technique to direct bacteria or other single-celled organisms (like yeast) to produce and replicate proteins from other organisms.

This breakthrough enabled applications across medicine, agriculture and manufacturing — and gave rise to the now multibillion-dollar biotechnology industry.

A 1970s-era photograph of researchers standing around a radiogram.

In the 1970s, several labs contributed to the development of rDNA technology, which set the stage for the biotechnology industry.

Credit: Crystal Rictor, CC0

A large pile of animal pancreases used to extract early insulin.

In 1923, it took 10,000 pounds of pancreas glands to make one pound of pure insulin crystals.

Credit: Lilly

The insulin challenge

In 1976, following the rDNA breakthrough, one of the researchers went on to co-found Genentech, the world's first biotechnology company. Genentech's goal was to manipulate the genes of microorganisms to produce new medicines. They saw insulin as a prime candidate for the company's first product.

At that time, diabetes in humans was treated with insulin extracted from the tissues of animals, usually pigs or cows. This insulin was limited in supply, and partly because it wasn't chemically identical to human insulin, it triggered adverse reactions in some patients.

An insulin breakthrough

By 1977, in search of an alternative to animal insulin, Eli Lilly — the main U.S. producer of animal insulin — had signed contracts with two research teams working on different methods to create synthetic insulin. Genentech partnered with City of Hope National Medical Center and joined the race in 1978, with the goal of producing synthetic insulin using its rDNA method.

The rDNA method proved highly effective, and the Genentech/City of Hope team was the first to create synthetic insulin successfully. They inserted the human insulin gene sequence into bacteria, which took up the gene and produced large amounts of insulin — identical to the molecule produced by humans.

A colorful painting of insulin molecules binding to insulin receptors.

At the top center of this detailed painting of a cell, two insulin molecules (yellow) bind to insulin receptors.

Credit: Illustration by David S. Goodsell / RCSB Protein Data Bank

A vial of insulin next to a box labeled "Humulin N".

Humulin was the first marketable product created through rDNA technology. Its licensing by the FDA in October 1982 also made it the first recombinant pharmaceutical approved for use in the United States.

Credit: Carol Edgar / Eli Lilly and Company

A milestone in diabetes care

In 1982, the U.S. Food and Drug Administration approved Humulin, the first biosynthetic human insulin product and the first medical product of any kind derived from rDNA technology. This advance — which wouldn't have been possible without NSF's early support for rDNA research — transformed diabetes care for millions of people.

NSF's investments continue to drive new technologies that improve the health and quality of life for people with diabetes. For example, researchers are developing artificial intelligence-based algorithms for wearable smart devices that provide personalized diabetes management while preserving patient privacy. And the Foundations for Digital Twins as Catalyzers of Biomedical Technological Innovation (FDT-BioTech) program, a partnership with the National Institutes of Health and the Food and Drug Administration, is supporting work on digital twins — dynamic, virtual replicas of individual patients, organs or physiological systems — that simulate disease progression and evaluate new treatments without posing a risk to patients. Such biotechnological advancements are helping to lower healthcare costs, reduce diabetes-related complications and improve patient outcomes.

A transformation for modern medicine

In addition to revolutionizing diabetes care, NSF's investments in foundational rDNA research — and the subsequent success of synthetic insulin — catalyzed the biotechnology industry. Pharmaceutical companies quickly adopted rDNA technology to replace older medical products and develop previously unavailable therapeutics, improving the outlook and quality of life for people with a wide range of conditions, including blood clots, hemophilia and cystic fibrosis.

Building on these breakthroughs, NSF's support has continued to expand the applications of rDNA with advancements that improve storage and distribution and lower costs of rDNA-based therapeutics, resolving some of the nation's most pressing health challenges and promoting American prosperity.