1902, Secretin and Fischer: A Physician’s Read on the Birth of Peptide Science

Research Decodes
Written By Samasta Admin

By Andres Zuleta, MD · Physician's read

Episode 1 of The Peptide Breakthroughs goes back to the year the field got both its name and its first hormone. Two labs, two capitals, opposite ends of the same molecule class: Fischer building peptides in a flask in Berlin, and Bayliss and Starling catching the body using one in London. Here is my read on the discovery, the results, the limits and why it still matters at the bedside.

The 37-second version is on YouTube Shorts. For a patient and family version of this story, see the Thrive City Blog post.

The discovery

London, January 16, 1902. The question was how acid entering the duodenum triggers bicarbonate-rich pancreatic secretion. The Pavlov school held that only neural reflexes were involved. Bayliss and Starling denervated a loop of jejunum in an anesthetized dog, instilled acid, and the pancreas still secreted. A mucosal extract given intravenously reproduced the response, more strongly. Starling's reported reaction: "Then it must be a chemical reflex." They named the agent secretin and published in The Journal of Physiology that year (free full text, linked below).

Berlin, 1901 and 1902. Emil Fischer and Ernest Fourneau synthesized glycylglycine, the first free dipeptide, in 1901. On September 22, 1902, at the Karlsbad meeting of German scientists and physicians, Fischer introduced the term "peptides."

The results

  • A new control system. Secretin established humoral signaling as a physiological principle. Starling introduced the word "hormone" in 1905.

  • Replication by the skeptics. When Pavlov's lab repeated the work, Pavlov conceded: "Of course they are right."

  • Structure, 68 years later. Mutt, Jorpes and Magnusson reported the sequence of porcine secretin in 1970. Secretin is a 27-residue peptide; the first hormone was a peptide all along.

The limits

  • Priority is messier than the headline. Curtius made a protected dipeptide (benzoylglycylglycine) in 1882; Fischer's was the first free dipeptide. Fischer's 1902 Nobel Prize recognized sugars and purines.

  • Chemistry lagged physiology. Solution-phase peptide synthesis stayed slow for about five decades, until Merrifield's solid-phase method in 1963 made it rapid and automatable.

  • An extract is not a drug. Nothing in 1902 was close to a therapy, and the active agent was undefined.

  • Neural and hormonal control coexist. Starling himself later recognized that both regulate the pancreas; the 1902 framing as either/or was too simple.

Why it matters now

More than 80 peptide drugs have reached the market (Muttenthaler, Nat Rev Drug Discov 2021). Synthetic human secretin is still FDA-approved as a diagnostic aid for exocrine pancreatic dysfunction. And the GLP-1 receptor, target of today's incretin-based therapies, is a class B GPCR in the secretin receptor family. The hormone concept that started with one denervated loop of gut runs straight through insulin to the GLP-1 era.

What I tell patients about their own gut peptides

Endogenous gut peptides respond to how we eat. The evidence is small and short-term, so I frame it as support, not substitution:

  • Meal order. In 16 adults with type 2 diabetes (Shukla 2017), carbohydrate last vs carbohydrate first lowered glucose iAUC by 53% and raised GLP-1.

  • Protein and satiety. High-protein intake produced the greatest PYY release and fullness (Batterham 2006).

  • Movement. A meta-analysis of seven one-day crossover trials found light walking breaks during prolonged sitting lowered postprandial glucose and insulin (Buffey 2022).

Practical version: vegetables and protein first, bread last, and break up long sitting with short walks.

Next in the series: Leonard Thompson and the first insulin injection.

Be proactive. More at thrivemed.ai.

References

Educational only, not medical advice. The video uses an AI avatar sharing my script.

Samasta Admin
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