From Insulin to Now: A Century of Peptide Discovery

In 1921, a young surgeon with no research funding and a half-formed idea walked into a university laboratory and changed medicine forever.

A century of peptide discovery, told through its turning points. OP Labs · Research

His name was Frederick Banting. He was not a biochemist, he had no track record in research, and his idea was, by his own account, scribbled down in the middle of a sleepless night. What followed is one of the defining stories of twentieth-century science — and the beginning of the modern history of peptides.

That history is worth telling, because the molecules now studied in laboratories around the world exist in a direct line of descent from a handful of remarkable discoveries.

How did insulin change everything?

Banting’s idea concerned the pancreas. Researchers suspected the organ produced something that governed blood sugar, but extracting it had defeated everyone — the pancreas’s own digestive enzymes destroyed the substance before it could be isolated.

Working in the Toronto laboratory of John Macleod, with the medical student Charles Best as his assistant, Banting found a way around the problem. By 1922, with crucial purification work by the biochemist James Collip, the team had isolated a usable pancreatic extract. The active substance was insulin — a peptide hormone (Banting & Best, 1922).

The impact is hard to overstate. Before this work, a diagnosis of what we now call type 1 diabetes carried a grim outlook. Insulin transformed that prognosis. The 1923 Nobel Prize followed almost immediately.

For our purposes, the key point is what insulin is. It is a peptide — a chain of amino acids — and its discovery proved that these small molecules sit at the very centre of how the body regulates itself. If the word peptide is still unfamiliar, our explainer on what peptides are sets out the basics.

How did we learn what a peptide is made of?

There was a missing piece between isolating insulin and doing anything further with it. Researchers had the molecule, but they did not know its sequence — the precise order of amino acids along the chain. Without that, a peptide was a black box.

Solving it fell to Frederick Sanger, working in Cambridge through the late 1940s and early 1950s. Sanger devised chemical methods to chip away at insulin from its ends, identifying one amino acid at a time, and slowly reconstructed the full order (Sanger & Tuppy, 1951).

By 1955 he had the complete sequence of insulin — the first time the exact amino acid order of any protein or peptide had been determined. It earned him the 1958 Nobel Prize in Chemistry, the first of two he would win.

Who first built a peptide from scratch?

Isolating a peptide from living tissue is one achievement. Knowing its sequence is a second. Building one from individual amino acids is a third — and for decades that third step seemed nearly impossible.

The breakthrough came in 1953, in the laboratory of the American biochemist Vincent du Vigneaud. His target was oxytocin, a small peptide hormone released by the brain. Du Vigneaud and his colleagues determined its sequence and then synthesised it — assembling the molecule, amino acid by amino acid, from scratch (du Vigneaud et al., 1953).

It was the first time a peptide hormone had been chemically synthesised, and the achievement earned du Vigneaud the 1955 Nobel Prize in Chemistry. The significance was conceptual as much as practical. It proved that a biologically active peptide was not some irreducible product of life — it was a defined chemical structure that could, in principle, be reproduced.

But du Vigneaud’s method was painstaking, carried out step by step in solution, with every intermediate needing its own purification. Synthesising a molecule as small as oxytocin — nine amino acids — was a feat. Anything longer was barely conceivable.

What made peptide synthesis practical?

That idea arrived in 1963, and it came from Robert Bruce Merrifield at the Rockefeller Institute in New York.

Merrifield’s insight was deceptively simple. Instead of building a peptide in solution, anchor the first amino acid to a small, insoluble resin bead. Then add each subsequent amino acid in turn, washing away the excess reagents after every step. Because the growing chain stays fixed to the bead, purification becomes a matter of rinsing (Merrifield, 1963).

This was solid-phase peptide synthesis, or SPPS. It turned a slow, expert craft into a repetitive, reliable cycle — one that could eventually be automated and run by machine. Merrifield received the 1984 Nobel Prize in Chemistry for it.

SPPS is the quiet foundation of nearly all peptide research today. It is the reason a scientist can specify a sequence and receive precisely that molecule, verified for purity. The story of how those molecules are sourced and made — from natural origins to the synthesis bench — continues in where do peptides come from.

How was GHK-Cu discovered?

Not every important peptide arrived with a Nobel Prize. Some emerged quietly, from researchers simply following an unexpected observation.

In the early 1970s, the researcher Loren Pickart was studying human blood plasma. He noticed that a particular small fraction of it had a striking effect on liver cells in culture, and he set about identifying the molecule responsible. It turned out to be a tripeptide — a chain of just three amino acids — that bound copper. It became known as GHK-Cu (Pickart & Thaler, 1973).

What made GHK-Cu notable was that it occurs naturally in human plasma. It was not a foreign compound but a native one, and Pickart spent much of his subsequent career studying its role in tissue signalling, drawing on laboratory and animal research.

It is important to be precise here: the early work was preclinical, and much of the GHK-Cu literature still rests on in vitro and animal models rather than large human trials. We examine that evidence carefully — and the limits of it — in our dedicated guide to understanding GHK-Cu.

What does modern peptide research look like?

The decades after Merrifield brought a quieter but profound shift. In the late 1970s, researchers used the new tools of genetic engineering to produce human insulin in bacteria, rather than extracting it from animal pancreases (Goeddel et al., 1979).

That moment widened the field. Peptides and small proteins could now be produced by two complementary routes — chemical synthesis for defined sequences, and biological production for larger or more complex molecules. The analytical side advanced in step, with mass spectrometry and chromatography making it routine to confirm exactly what had been made.

Modern peptide research is, as a result, less about heroic single discoveries and more about systematic exploration: cataloguing the body’s own peptides, mapping how they interact with receptors, and probing why some are stable and others fleeting. To understand that interaction at the molecular level, see how peptides work.

There was a quieter middle period worth noting. For a stretch of the late twentieth century, peptides fell somewhat out of fashion as drug candidates — they were seen as too unstable, too quickly broken down, too hard to deliver. Attention shifted to conventional small molecules. Peptide research never stopped, but it was no longer the centre of attention.

What revived it was partly better chemistry and partly better tools. Improved synthesis, a deeper understanding of why peptides degrade, and the analytical power to characterise them precisely all combined to make the category attractive again. The past two decades have seen a marked resurgence of interest, and peptides are once more among the most actively studied molecules in bioscience.

What researchers are asking next

The open questions echo the history. Synthesis, for all Merrifield’s brilliance, still struggles with very long or chemically awkward sequences, and chemists continue to extend what is possible.

The peptidome — the full catalogue of peptides the human body produces — remains incomplete, with many entries still lacking a confirmed function. And the translational gap that a century of research keeps revealing is itself a subject of study: why does so much promising preclinical work fail to carry over to humans?

Peptide research also increasingly intersects with the wider biology of ageing and cellular energy — territory occupied by molecules such as NAD+, which we explore in NAD+ and cellular energy.

If there is a lesson in this timeline, it is one of patient accumulation. Insulin, oxytocin, SPPS, GHK-Cu — each was a step, and each took years of careful work to establish. The same standard applies to everything being studied now.