EP 081:39

Insulin: one chain, cut in two

The body makes insulin as one long chain and cuts out the middle. The story of the 1922 patient, the Nobel Prize, and why the FDA now calls insulin a protein.

Transcript and sources
  1. In January nineteen twenty-two, a fourteen-year-old boy in Toronto got an injection of insulin. The first try did little. The second, with a purer extract, brought immediate improvement.
  2. Insulin is a hormone made of fifty-one amino acids, in two chains: one of twenty-one, and one of thirty.
  3. Three sulfur bridges hold the chains together: two link them, and one loops inside the short chain.
  4. But the body doesn't make two chains. It makes one, called proinsulin, eighty-six amino acids long.
  5. Then enzymes cut out a thirty-one-amino-acid middle piece, the C-peptide, and what's left is insulin.
  6. In nineteen twenty-three, Banting and Macleod won the Nobel Prize for the discovery of insulin, and Banting, Best and Collip sold their patent to the University of Toronto for one dollar each.
  7. In the nineteen fifties, Frederick Sanger worked out insulin's full sequence, the first protein ever mapped. He won a Nobel Prize for it in nineteen fifty-eight.
  8. In nineteen eighty-two, the FDA approved Humulin, human insulin made by bacteria: the first approved medicine made with recombinant DNA.
  9. Then, in twenty twenty, the FDA moved insulin from drugs to biologics. Why? U.S. rules call a chain longer than forty amino acids a protein, and insulin's two chains count together: fifty-one.
  10. So by the FDA's own ruler, insulin is a protein, though the medicine itself hasn't changed. See where every peptide sits, at peplexicon.com.

Sources

  1. UniProt P01308, Insulin (human, INS); entry v284, annotation updated 2 Sep 2026
  2. Steiner DF. The proinsulin C-peptide: a multirole model. Exp Diabesity Res. 2004
  3. Steiner DF, Oyer PE. The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma. PNAS. Feb 1967
  4. Nobel Prize in Physiology or Medicine 1923, summary
  5. Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. Pancreatic extracts in the treatment of diabetes mellitus: preliminary report. CMAJ. Mar 1922;12:141–6
  6. Lewis GF, Brubaker PL. The discovery of insulin revisited: lessons for the modern era. J Clin Invest. 2021
  7. US Patent 1,469,994 (Banting, Best, Collip), granted 9 Oct 1923
  8. FDA History Office. 100 Years of Insulin (content current 8 Jun 2022)
  9. Nobel Prize in Chemistry 1958, summary
  10. Sanger F. The chemistry of insulin. Nobel Lecture, 11 Dec 1958
  11. Ryle AP, Sanger F, Smith LF, Kitai R. The disulphide bonds of insulin. Biochem J. 1955
  12. Adams MJ, Blundell TL, Dodson EJ, Dodson GG, Vijayan M, Baker EN, Harding MM, Hodgkin DC, et al. Structure of rhombohedral 2 zinc insulin crystals. Nature. 1969;224:491–5
  13. Drugs@FDA, BLA 018780 (Humulin R)
  14. FDA. "Deemed to be a License" Provision of the BPCI Act (content current 9 Feb 2024)
  15. FDA. Definition of the Term "Biological Product", final rule. 85 FR 10057–10063, 21 Feb 2020
  16. FDA. List of Approved NDAs for Biological Products That Were Deemed to be BLAs on March 23, 2020 (corrected 2 Apr 2020)
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