The History Of Peptides — A Slow Unfolding Of Discovery
Peptides began as an idea before the word even existed. They are small chains of amino acids, linked to each other in what we today refer to as the peptide bond. Yet throughout much of the 19th Century, no one had sufficient language and tools to characterise them. They were concealed within the greater enigma of the proteins. And even proteins — important, opaque, and ubiquitous — had been recognisable only insofar as a sticky, nitrogenous substance. They were observed, touched, and incinerated by chemists who, however, did not comprehend them.
What comes next is not a straight-line narrative, but a winding path of conjectures, false leads and long gaps between the little wins. Each generation added a fragment until the whole picture began to form.
During the early 1800s, Jons Jakob Berzelius suggested that such nitrogen compounds should be a special type of organic matter. Henri Braconnot, who tried to prepare gelatin and sulfuric acid together around 1820, isolated a crystalline compound which he called glycine. It was the initial amino acid to be discovered. He was, however, ignorant that it belonged to a chain — it was not similar to anything he had previously drawn out of organic tissue.
More research followed. Through the middle decades of the century, chemists identified leucine, tyrosine, and tryptophan — names that would later become central to biology. They could separate these substances but not explain how they connected. Proteins remained black boxes.
Late in the century Emil Fischer changed that. He suspected that amino acids were linked together by a specific chemical bridge. He named it ‘the peptide bond’ and spent years proving it. Fischer not only theorised; he built short chains himself, stringing amino acids one after another by hand. In doing so he created the first synthetic peptides and gave the discipline its foundation. He believed that one day scientists would synthesise whole proteins. That belief drove the next hundred years of work.
Fischer’s generation left the concept; later generations built the tools. Progress through the early 20th Century moved carefully, sometimes painfully slowly. Instruments were primitive and techniques uncertain. Still, the idea that proteins could be broken into pieces and rebuilt stayed alive.
By 1953 Vincent du Vigneaud had succeeded where Fischer could only imagine. He synthesised oxytocin — a small hormone that controls uterine contractions and milk ejection. It was the first time a biologically active peptide had been created artificially. That one success proved that nature’s work could be repeated in glassware.
From there the field expanded. Dozens of natural peptides were isolated, described, and measured. Scientists began to see them not as curiosities but as a separate language inside biology—one used for signalling, defence, and repair.
But the real moment of the peptide came many decades before that as, in 1921, Frederick Banting and Charles Best isolated insulin in animal pancreas. This was a peptide hormone that would transform an otherwise terminal disease into a treatable one. The discovery not only saved lives, but demonstrated what peptides could do.
Through the 1920s and 1930s researchers tried to understand what insulin looked like on the molecular level. They could identify which amino acids were present but not the exact order. The technology simply did not exist. Still, each experiment refined the picture.
In 1935, Adolf Butenandt and his subordinates identified two further peptide hormones, once more oxytocin, and vasopressin, in the pituitary gland. These molecules controlled reproduction and water balance proving that small chains of amino acids were able to govern enormous physiological processes. By the eve of the Second World War, peptides were recognised as the body’s most precise instruments.
The 1950s brought tools powerful enough to turn guesswork into structure.
The impossible happened when Frederick Sanger successfully made the full sequence of insulin. Years of chemical decomposition and analysis later, he unlocked the exact sequence of amino acids and demonstrated that there were two peptide chains attached to insulin. That work not only won him the 1958 Nobel Prize, but it also demonstrated that all proteins are a known sequence, and not a globular piece of tissue. Biology could now be read like code.
Only a few years later Robert Bruce Merrifield in New York introduced solid-phase peptide synthesis (SPPS). Instead of mixing amino acids in solution, he anchored the first one to a solid resin and added the rest step by step. When the chain was complete he detached it, pure and intact. The simplicity of the method hid its power. SPPS turned peptide synthesis into a routine operation. In 1984 Merrifield received his own Nobel Prize, closing a circle that had begun with Fischer’s dream.
Together Sanger and Merrifield gave scientists the two halves they needed: the ability to read peptides and the ability to build them.
Once it became possible to synthesise peptides on demand, the labs started to study them as medications and as a tool. A fully synthetic hormone, gonadotropin-releasing hormone (GnRH), was used in its initial clinical application in the 1970s. Variations were made, and they assist in the treatment of infertility and cancers that are hormone sensitive.
At the same time new insulin analogues improved diabetic care. Naturally-derived peptide antibiotics such as gramicidin and polymyxin joined hospital formularies. The biomedical world discovered that peptides could be probes, enzyme substrates, antigens, and carriers. They became the experimental currency of molecular biology.
Parallel to chemistry, genetics was rewriting the script of how life makes peptides on its own. The discovery of messenger RNA, and later the cracking of the genetic code, explained the connection between DNA and peptide chains. Ribosomes were revealed as the actual machines linking amino acids. The chemistry of peptides and the biology of genes merged into one continuous process.
Instrumentation was prevalent in the last years of the 20th Century. Mass spectrometry was developed to a level of accuracy that defined peptides concealed in complicated tissues. The accuracy led to the emergence of proteomics, the examination of all proteins and their fragments simultaneously. It transformed how disease was investigated. Peptides became clues, like fingerprints of cellular behaviour.
By the 2020s the pharmaceutical catalogue of approved therapeutic peptides had passed 80. Hundreds more were in various stages of testing. Some names became familiar beyond the lab:
Researchers appreciated peptides due to their specificity, which is very targeted and often has less side effects compared to small-molecule medications. There were still limitations, however, including short half-lives, instability in the bloodstream, and the inability to deliver orally. To beat them, chemists generated more robust ones, conjugated peptides with pharmaceutical molecules, and encircled them in nanoparticles.
Peptide engineering now allows scientists to add non-natural amino acids, create cyclic structures that resist enzymes, and design peptidomimetics—synthetic shapes that behave like natural peptides but last longer. The result is a field that crosses chemistry, medicine, and materials science all at once.
Looking backward, the story feels inevitable but it wasn’t. Every step depended on the last. Braconnot found glycine; Fischer imagined a link; Sanger decoded insulin; Merrifield gave a method; du Vigneaud proved synthesis could copy life. Each of them worked largely in isolation, and yet their discoveries interlocked perfectly.
Peptides turned out to be the common language between disciplines. They described protein construction, cell communication, and precision in designing medications. Since the 19th Century chemical benches to the nanotechnology of today, they have pursued one single thread, the peptide bond itself — a narrow connection between two amino acids that somehow holds together the larger world of science.
More than 100 years after Fischer first started his experiments, the field continues to grow. Peptides are in an intermediate position: not large enough to qualify as proteins, but too complicated to be simple molecules. The innovation flourishes in that in-between place.
Proteomics continues to map thousands of new peptide fragments. Engineers adapt peptide frameworks for sensors, for tissue scaffolds, for targeted cancer therapy. Even artificial intelligence in medication discovery relies on peptide data to model folding and binding. The bond that Fischer guessed at has become one of the most studied interactions in all of chemistry.
What’s striking, reading through old papers, is how slowly certainty arrived. It took decades to move from the idea of ‘nitrogenous material’ to the exact sequence of insulin. It took another 50 years before chemists could reproduce the process with precision. Science rarely rushes; peptides remind us of that. Each advance rested on stubborn patience, small experiments, and repeated failures.
Peptides link more than amino acids. They link generations of inquiry. They brought 19th Century chemistry to 20th Century biology and 21st Century biotechnology. It is this bond that surprised Fischer, that is the stronghold of targeted medication, molecular diagnostics, and the third-generation biomaterials.
The history is long but not finished. Each year brings another branch — new delivery systems, synthetic backbones, hybrid materials. The questions are different now but the method is the same: find the connection, test it, build it again.
When people speak of peptides today, they often mean powders or injections or supplements. But behind every vial stands 200 years of work, a trail beginning with boiled gelatin and ending with programmable chemistry. It is, at its core, the story of how human curiosity moved from observing life to constructing it.
Peptides have moved quietly through every scientific century since their discovery. They began as a chemical curiosity and ended up as the bridge between disciplines. In their structure one can see the whole rhythm of research — observation, deduction, synthesis, application.
From Braconnot’s crude acid pot to Merrifield’s resin beads and the spectrometers of proteomics labs, the chain keeps growing. The peptide bond itself, small and ordinary under a microscope, has held together not just molecules but the effort of generations trying to understand what life is made of.
And that bond, still, continues to teach.