The History of Peptides: From Insulin to the Modern Era
TL;DR: Peptide science traces a documented arc from Frederick Banting and Charles Best's 1921 isolation of insulin — the first peptide used in human medicine — through R. Bruce Merrifield's Nobel-winning 1963 invention of solid-phase peptide synthesis, to the discovery of GLP-1 and the modern proliferation of peptide research compounds. Today, peptides represent one of the most active areas in biomedical research, with more than 100 approved therapeutics on record and hundreds more under investigation. This article documents that journey and explains why a calibrated, evidence-graded reference remains essential.
What Are Peptides? A Working Definition for Researchers
Peptides are short chains of amino acids linked by peptide bonds, typically defined as containing between 2 and 50 amino acid residues. They are chemically distinct from proteins (which are longer and more structurally complex) and from small-molecule drugs (which are synthesized from non-amino acid building blocks). Because they closely mimic the body's own signaling molecules, peptides have attracted sustained interest across pharmacology, biochemistry, and biomedical research for more than a century.
The documented history of peptide science is, in large part, a history of discovery: identifying what these molecules do in biological systems, developing methods to synthesize them reliably, and progressively mapping the landscape of compounds worthy of further investigation. Understanding that arc matters for any researcher working with peptide compounds today — context clarifies why evidence tiers, synthesis purity, and rigorous sourcing are not incidental concerns, but the direct inheritance of a century of scientific effort.
The Insulin Era: Peptide Science Is Born (1900–1930)
Before Banting: The Long Search for the Pancreatic Hormone
The symptoms of diabetes mellitus had been recognized since antiquity, but the existence of a pancreatic regulatory hormone remained contested through the late 19th century. Multiple European investigators attempted to produce active pancreatic extracts in the decades before 1920, with limited reproducibility. According to a 2022 historical review in Biologie Aujourd'hui, the breakthrough required the right institutional setting: the University of Toronto, where physiologist John Macleod provided laboratory space to a young surgeon named Frederick Banting (doi: 10.1051/jbio/2022006).
Banting, Best, and the 1921 Discovery
In 1921, Frederick Banting and his assistant Charles Best successfully isolated a pancreatic extract from dogs that reversed diabetic symptoms — the compound that would be named insulin. A 2024 review in Cureus documents Banting's trajectory and the work with Best and biochemist James Collip that produced a purified extract sufficient for the first human administration in January 1922 (doi: 10.7759/cureus.73806).
The Nobel Prize in Physiology or Medicine was awarded to Banting and Macleod in 1923 — among the fastest Nobel recognitions in history. The contested priority claims, including the parallel work of Romanian scientist Nicolae Paulescu, remain part of the historical record and have been examined in scholarly literature as recently as 2023 (doi: 10.1007/s00592-023-02136-6). Insulin's significance for peptide science extends well beyond its clinical application: it established the category — a small, biologically active molecule composed of amino acids, capable of mediating complex physiological responses.
Sequencing and the Structural Revolution (1950s)
Sanger's Sequencing of Insulin
If Banting and Best proved peptide hormones existed and could be isolated, Frederick Sanger proved they had a defined, reproducible chemical structure. Between 1949 and 1955, Sanger's laboratory at Cambridge determined the complete amino acid sequence of bovine insulin — 51 amino acids in two chains. This was the first time the complete sequence of any protein had been determined, earning Sanger the Nobel Prize in Chemistry in 1958.
Du Vigneaud and the First Synthetic Peptide Hormones
In 1953, Vincent du Vigneaud and colleagues at Cornell achieved the first total chemical synthesis of a polypeptide hormone: oxytocin (nine amino acids), followed by vasopressin. Du Vigneaud was awarded the Nobel Prize in Chemistry in 1955 for the first synthesis of a polypeptide hormone — demonstrating that peptide hormones were not only isolable and sequenceable but synthetically reproducible.
The Merrifield Revolution: Solid-Phase Peptide Synthesis (1963)
The Problem Merrifield Solved
Through the 1950s, synthesizing even modest peptide sequences required months or years of painstaking solution-phase chemistry. Each step demanded isolation of intermediates, removal of protecting groups, purification, and verification. This bottleneck severely limited the pace of peptide research.
The 1963 Breakthrough
R. Bruce Merrifield of Rockefeller University published his landmark paper on solid-phase peptide synthesis (SPPS) in 1963. The innovation: anchor the first amino acid to an insoluble polymer resin bead, then add each subsequent amino acid sequentially, washing away byproducts after each step — no intermediate isolation required. A 2013 review in Molecules notes that "since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially" (doi: 10.3390/molecules18044373). A 2005 review notes the method "has spawned the concept of combinatorial chemistry" (doi: 10.5483/bmbrep.2005.38.5.517).
Merrifield was awarded the Nobel Prize in Chemistry in 1984; the Royal Swedish Academy characterized his method as having "brought about a revolution in peptide and protein chemistry," transforming what had required years of labor into days and enabling full automation (NobelPrize.org).
What SPPS Made Possible
The consequences reshaped the research landscape. Peptide libraries of thousands of sequences could be screened systematically. Compounds present in the body in vanishingly small quantities could be synthesized at research scale. Modifications — truncations, substitutions, cyclizations — could be tested iteratively. The pace of peptide science accelerated and has not slowed since.
The Expansion of Peptide Science (1970s–1990s)
Neuropeptides and the Endorphin Era
The 1970s produced a wave of discoveries. The identification of enkephalins and endorphins — endogenous opioid peptides produced by the brain — demonstrated that the nervous system used peptides as signaling molecules on a scale researchers were only beginning to appreciate, opening neuropeptide pharmacology as a distinct discipline.
Growth Hormone Peptides and Secretagogues
Parallel endocrinology work characterized the hypothalamic peptides that regulate pituitary function: growth hormone-releasing hormone (GHRH) and somatostatin were both characterized in the 1970s, establishing the mechanistic basis for a later generation of synthetic research compounds designed to interact with the same receptor systems.
The Peptide Drug Pipeline Matures
By the 1990s, a substantial number of synthetic peptide drugs had reached clinical use — cyclosporine, leuprolide, and others across cardiovascular and metabolic areas. In parallel, recombinant DNA technology produced recombinant human insulin by 1982, demonstrating that biological manufacturing could complement chemical synthesis for peptide production.
The Incretin Discovery and the GLP-1 Story
From Gut Hormone to Research Cornerstone
The discovery of glucagon-like peptide-1 (GLP-1) represents one of the most consequential chapters in modern peptide research. GLP-1 is a 30-amino acid incretin hormone secreted by intestinal L-cells in response to food intake. The 2024 Lasker–DeBakey Clinical Medical Research Award was given to Joel Habener and Svetlana Mojsov for discovering GLP-1(7-37), and to Lotte Knudsen for developing sustained-acting analogues — an arc documented in PNAS in 2024 (doi: 10.1073/pnas.2415550121).
GLP-1 Analogues as a Research Model
The development of GLP-1 analogues illustrates the full modern pipeline: characterizing the native peptide's structure and receptor interactions, engineering modifications to extend its biological half-life (native GLP-1 is degraded by DPP-4 within minutes), and systematic preclinical and clinical evaluation. A 2025 review in Pharmaceutics documents how fatty-acid conjugation extended circulating half-life from minutes to days (doi: 10.3390/pharmaceutics17060768). The first GLP-1-based drug approved by the FDA reached patients in 2005 — roughly 20 years after the foundational molecular discovery, a timeline typical of how the field translates a biological observation into a well-characterized compound.
The Modern Research Peptide Landscape
Scale and Scope: Over 100 Approved Peptide Therapeutics
A 2024 analysis of FDA approvals in Molecules documented five peptide approvals in 2023 alone, describing it as "a spectacular year" for the TIDES category, and noted the broader multi-year trend (doi: 10.3390/molecules29030585). Across the full post-insulin history, the documented total of approved peptide therapeutics exceeds 100, spanning metabolic, cardiovascular, endocrine, oncology, and anti-infective areas.
Research Peptides: The Pre-Clinical Investigation Layer
Alongside approved therapeutics, a large and growing body of literature documents compounds under active preclinical investigation — peptides that have demonstrated measurable biological activity in cell culture or animal models, but whose full profile remains under study. It is important to note what the literature documents about this category: research compounds are not approved drugs. Their safety, tolerability, and efficacy in humans have not been established through the clinical trial process. The scientific interest is genuine, but the gap between preclinical findings and clinical validation is real and documented.
Why Evidence Tiers Matter: Lessons from a Century of Peptide Science
The history of peptide science is partly a history of premature claims. Compounds that appeared highly active in rodent models have repeatedly shown different profiles in human studies. This is not a failure of the science — it is how rigorous science works. But it means that treating any single study, or any single evidence tier, as definitive misrepresents how the field actually progresses. A calibrated reference that systematically distinguishes human clinical data, animal model data, and in vitro findings does not diminish the interest of preclinical compounds — it accurately represents where each compound sits in the investigational pipeline.
Where Peptide Science Stands in 2026
Peptide chemistry in the mid-2020s is characterized by several converging trends researchers should understand:
- Half-life engineering: Research into fatty-acid conjugation, PEGylation, and cyclic structures — descended from the GLP-1 analogue work — is now applied across compound classes.
- Delivery route diversification: Oral peptide formulation research, documented in multiple active clinical programs, represents a significant area of current investigation.
- Multi-target peptides: Dual-agonist and tri-agonist compounds acting on multiple receptor systems are among the most actively studied categories in current metabolic research.
- Peptide-polymer conjugates: Conjugation strategies that improve pharmacokinetic profiles while maintaining target selectivity represent an active research frontier.
The Case for a Calibrated Research Reference
A century of documented peptide science has produced a field of extraordinary depth and genuine complexity. The primary literature is the authoritative source. But for researchers who need a synthesized, evidence-graded starting point rather than hundreds of individual papers, a well-built reference that explicitly labels evidence tiers, cites primary sources, and distinguishes research-context findings from clinical conclusions is the minimum standard for responsible engagement with the field.
Research-Use Disclaimer: This article is for educational and historical reference purposes only. The compounds discussed in peptide research literature are research chemicals, not approved drugs. Nothing here constitutes medical advice, and no dosing, administration, or treatment guidance is intended or implied. The documented history describes what researchers have studied — it does not constitute a recommendation for any human use. For adults 18+ engaged in scientific reference research only.
Frequently Asked Questions
What was the first peptide ever used as a medicine in humans?
Insulin is documented as the first peptide used therapeutically in humans. Banting, Best, and colleagues at the University of Toronto isolated it in 1921; the first human administration occurred in January 1922, and the Nobel Prize followed in 1923 (doi: 10.7759/cureus.73806).
Who invented solid-phase peptide synthesis and why does it matter?
R. Bruce Merrifield invented SPPS, first described in 1963. The method builds a peptide chain on a polymer resin bead step by step, reducing synthesis from years to days. Merrifield won the 1984 Nobel Prize in Chemistry; reviews in Molecules (2013) and J. Biochem. Mol. Biol. (2005) document its transformative impact (doi: 10.3390/molecules18044373).
What is GLP-1 and how was it discovered?
GLP-1 is an incretin hormone produced in the gut after food intake. Its discovery is credited to Joel Habener and Svetlana Mojsov, recognized with the 2024 Lasker–DeBakey Award alongside Lotte Knudsen for long-acting analogues (doi: 10.1073/pnas.2415550121).
How many peptide drugs have been approved by the FDA?
A 2024 review in Molecules noted five peptide approvals in 2023 alone; across the post-insulin period, the documented total exceeds 100 approved peptide therapeutics (doi: 10.3390/molecules29030585).
Go deeper: This compound is one of 48 documented in the Legendary Labz Peptide Research Guide — a 224-page, evidence-tiered reference with primary citations throughout. Read a free compound profile.
Research use only. Not intended for human use. Not FDA approved. This article documents published scientific literature and history for educational purposes and is not medical advice; nothing here recommends human use of any compound. All citations link to primary sources. Must be 18+.