The First Recombinant Insulin
| Category | Research |
|---|---|
| Also known as | Humulin, recombinant insulin history, Genentech insulin |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | historyinsulinrecombinant-dnabiotechnologygenentech |
Overview
Recombinant human insulin — marketed as Humulin — was the first recombinant DNA–based pharmaceutical to reach the market. Approved by the FDA in 1982, it represented a convergence of the new biotechnology industry (Genentech, founded in 1976) and a classical pharmaceutical company (Eli Lilly, which had commercialized animal-derived insulin since 1923).
Before Humulin, insulin was produced from bovine and porcine pancreases collected from slaughterhouses. Although effective, animal insulin differs from human insulin by one or more amino acids and can elicit antibody responses, allergic reactions, and lipodystrophy. Supply was also tied to the beef and pork industry, creating periodic shortages and cost pressures.
The Genentech team, led by Herbert Boyer and with scientific contributions from David Goeddel and collaborators, expressed the two insulin chains separately in Escherichia coli, then combined them to form the active hormone. Eli Lilly scaled up production, performed the clinical trials, and launched the product as Humulin R (regular) and Humulin N (NPH) in 1982.
Key People
- Herbert Boyer (b. 1936): Co-founder of Genentech and architect of the recombinant DNA platform.
- Robert Swanson (1947–1999): Co-founder of Genentech and its first CEO.
- David Goeddel: First scientist hired at Genentech; led the insulin expression work.
- Ronald Chance and Bruce Frank: Eli Lilly scientists who refined production.
- Walter Gilbert and colleagues: Harvard group that pursued a parallel recombinant insulin project.
Timeline
- 1973: Cohen and Boyer demonstrate recombinant DNA technology.
- 1976: Genentech is founded.
- 1978: Genentech announces recombinant insulin production in E. coli.
- 1980: Genentech's IPO, a landmark in biotechnology finance.
- 1982: FDA approves Humulin; Eli Lilly begins commercial sales.
- 1990s: Insulin analogs (lispro, aspart, glargine) emerge from recombinant platforms.
- 2000s–2020s: Recombinant insulin production shifts to yeast (Saccharomyces cerevisiae) and other hosts for many products.
Background
The insulin project was, in retrospect, an ideal first application of recombinant DNA technology. Insulin had a known sequence (from Sanger), well-established clinical importance, and a relatively small molecule size (two chains of 21 and 30 amino acids joined by disulfide bonds). Animal-derived insulin was a proven therapy with a known market, making regulatory approval of a human-sequence version more tractable than for a novel drug.
Still, the engineering challenges were substantial. The two chains had to be expressed in bacteria, purified, and combined correctly to form the native disulfide pattern. An alternative later approach expressed proinsulin in yeast with subsequent enzymatic conversion to mature insulin, improving yield and purity.
Modern Relevance
Essentially all insulin used today is recombinant. The original Humulin remains on the market and is joined by a family of insulin analogs — lispro, aspart, glulisine, glargine, detemir, degludec — all produced by recombinant expression and all designed with specific pharmacokinetic goals in mind.
Beyond insulin, recombinant production is now standard for growth hormone, erythropoietin, clotting factors, monoclonal antibodies, and many other biological drugs. Humulin's approval in 1982 opened this era. For closely related history, see banting-best-insulin and insulin-structure-solved.
Related Compounds
Related entries
- Banting and Best: The Discovery of Insulin— How Frederick Banting, Charles Best, J.J.R. Macleod, and James Collip isolated insulin in 1921 at the University of Toronto.
- The First Peptide Drug— The first peptide drug is generally considered to be animal-derived insulin, introduced in 1923, followed by synthetic peptide hormones in the 1950s and 1960s.
- Solving the Structure of Insulin— The amino acid sequence of insulin was solved by Sanger in 1955, and its three-dimensional structure by Dorothy Hodgkin in 1969.