The History of Peptide Therapy: From Insulin to Longevity
The History of Peptide Therapy: From Insulin to Longevity
The story of peptide therapy begins with desperation. Before 1922, a diagnosis of Type 1 diabetes was a death sentence. Children would waste away over months, their bodies unable to use the sugar in their blood for energy. The best treatment available was a starvation diet that might extend life by a year or two.
Then, in January 1922, a 14-year-old boy named Leonard Thompson became the first human to receive an injection of insulin. Within days, his blood sugar normalised. He would live another 13 years, eventually dying of pneumonia rather than diabetes. The peptide revolution had begun.
The Discovery of Insulin
The insulin story illustrates both the promise and complexity of peptide therapeutics. Frederick Banting and Charles Best, working at the University of Toronto, had extracted a substance from dog pancreases that could lower blood sugar in diabetic animals. But getting from animal extracts to a treatment suitable for humans required solving significant problems.
The early extracts were impure and caused severe reactions. James Collip, a biochemist who joined the team, developed purification methods that made the substance safe for human use. Even then, producing consistent, high-quality insulin was challenging. The team had to figure out large-scale production, standardisation, and quality control.
These challenges would echo throughout the history of peptide therapeutics. Peptides are delicate molecules that can be difficult to produce, purify, and stabilise. Each new peptide therapeutic has had to overcome similar hurdles.
The Hormone Era
Insulin's success sparked interest in other peptide hormones. Throughout the mid-20th century, researchers identified and characterised the body's hormonal messengers.
Adrenocorticotropic hormone (ACTH) was isolated in the 1940s and became available for treating inflammatory conditions. Growth hormone was isolated from human pituitary glands in 1956 and eventually used to treat growth hormone deficiency in children, though supply was limited by the need for human sources.
Oxytocin and vasopressin, peptides produced in the hypothalamus, were synthesised in 1953 by Vincent du Vigneaud, who received the Nobel Prize for this work. These were the first peptide hormones to be synthesised chemically, proving that peptides could be manufactured rather than extracted.
Calcitonin, a peptide regulating calcium metabolism, was discovered in 1962 and eventually developed as a treatment for bone diseases.
Each discovery expanded understanding of how peptides regulate physiology and suggested therapeutic possibilities.
The Synthesis Revolution
Early peptide therapeutics came from natural sources, primarily animal tissues. This limited supply, raised concerns about contamination, and made production expensive. The development of synthetic peptide chemistry changed everything.
Bruce Merrifield's invention of solid-phase peptide synthesis in 1963 was transformative. This technique allowed peptides to be built amino acid by amino acid on a solid support, dramatically simplifying production. Merrifield received the Nobel Prize in 1984 for this work.
Solid-phase synthesis made it possible to produce peptides in large quantities with consistent quality. It also enabled the creation of modified peptides, analogues that might have improved properties compared to natural versions.
The first synthetic peptide drug, the LHRH agonist leuprolide, was approved in 1985 for prostate cancer. It represented a new paradigm: a synthetic peptide designed to modulate a specific hormonal pathway. Many peptide drugs would follow this model.
Growth Hormone and Its Secretagogues
The growth hormone story illustrates the evolution of peptide therapeutic strategies. Early growth hormone therapy used hormone extracted from human pituitary glands. Supply was extremely limited, and the treatment was reserved for children with severe deficiency.
Then came disaster. In 1985, several patients who had received pituitary-derived growth hormone developed Creutzfeldt-Jakob disease, a fatal brain disorder transmitted by contaminated tissue. The human-derived product was withdrawn from the market.
Fortunately, recombinant DNA technology offered an alternative. Genentech had already developed methods to produce human growth hormone in bacteria, and their product, Protropin, was approved in 1985. For the first time, a human peptide hormone could be produced in unlimited quantities without contamination risk.
Recombinant growth hormone enabled broader use, eventually including adults with growth hormone deficiency and other conditions. But direct growth hormone administration had limitations, including the need for daily injections and concerns about non-physiological hormone patterns.
This led to interest in growth hormone secretagogues, compounds that stimulate the body's own growth hormone release. The discovery of GHRH (growth hormone-releasing hormone) in 1982 opened one pathway. The discovery of ghrelin and its synthetic analogues (growth hormone-releasing peptides) opened another.
Peptides like CJC-1295 and Ipamorelin represent the current generation of this approach: synthetic compounds that enhance natural growth hormone release rather than replacing it.
The Research Peptide Era
While pharmaceutical development of peptides followed formal regulatory pathways, another stream of peptide research developed somewhat separately.
BPC-157, studied extensively by researchers in Zagreb starting in the 1990s, showed remarkable healing properties in animal studies but never completed the pharmaceutical approval process. Thymosin Beta-4 (TB-500) was characterised in the 1980s and showed promise for tissue repair, with some clinical development but no widespread approval.
These peptides accumulated substantial research evidence without becoming conventional pharmaceuticals. They existed in a grey zone: too well-studied to dismiss, but lacking the regulatory validation of approved drugs.
The internet and global commerce eventually made these research peptides accessible. What had been laboratory curiosities became available to practitioners and individuals willing to use them based on available evidence rather than regulatory approval.
This created both opportunity and risk. The opportunity was access to potentially beneficial compounds that might never complete the expensive journey to formal approval. The risk was using compounds without the safety validation that the approval process provides.
The Longevity Revolution
The past two decades have seen peptides incorporated into longevity medicine and optimisation approaches. This represents a shift from treating disease to maintaining function and preventing decline.
The logic is straightforward: many peptides that decline with age might be worth replacing. Growth hormone production falls by roughly half between age 20 and 60. Thymic peptides decline as the thymus involutes. Various regenerative signals diminish. If these declines contribute to ageing, might restoring them slow the process?
This framing has driven interest in peptides like Ipamorelin and CJC-1295 (for growth hormone optimisation), Thymosin Alpha-1 (for immune function), GHK-Cu (for tissue quality), and MOTS-c (for metabolic function). These aren't treatments for disease so much as support for systems that naturally deteriorate.
The evidence base for longevity applications is inevitably weaker than for disease treatment. You can't easily run a clinical trial for "ageing slower." Instead, the rationale rests on understanding mechanisms, observing surrogate markers, and accumulating clinical experience.
Recent Discoveries
Peptide science continues to advance. Several recent developments are particularly noteworthy.
Mitochondrial-derived peptides were discovered starting in 2015. These small peptides, encoded in mitochondrial DNA, include MOTS-c and humanin. They represent a newly recognised class of signalling molecules with significant metabolic and protective effects.
Improved understanding of peptide mechanisms has refined how they're used. We know more about receptor pharmacology, signalling cascades, and how different peptides interact. This knowledge enables more rational protocol design.
Better production methods continue to improve peptide quality and accessibility. Advances in synthetic chemistry, purification techniques, and analytical methods have made high-quality peptides more available.
Lessons from History
The history of peptide therapy offers several lessons.
Peptides work because they tap into the body's existing regulatory systems. From insulin onwards, successful peptide therapeutics have worked by providing or modulating signals the body already uses. This is fundamentally different from small-molecule drugs that often work through non-physiological mechanisms.
Technical challenges matter. Production, purification, stability, and delivery have constrained peptide therapeutics throughout their history. Solving these practical problems has been as important as understanding the science.
The path from discovery to use isn't always through traditional pharmaceutical development. Many valuable peptides exist outside the approval process, used based on research evidence and clinical experience. This creates both opportunities and responsibilities.
The field continues to evolve. New peptides are discovered, mechanisms are elucidated, and applications expand. What's possible with peptides today exceeds what was imaginable even two decades ago, and the trajectory continues.
Where We Are Today
Peptide therapy today spans a spectrum from formally approved medications to research compounds used off-label to emerging options still being characterised.
At one end are the established peptide drugs: various insulins, growth hormone, GLP-1 agonists for diabetes and obesity, and dozens of others with full regulatory approval.
In the middle are peptides with substantial evidence and clinical use but limited regulatory validation. Many of the peptides discussed elsewhere on this site, including BPC-157, TB-500, various growth hormone secretagogues, and others, fall into this category.
At the emerging edge are newly identified peptides with promising preclinical data but limited human experience. These represent the frontier, where potential is high but uncertainty is also significant.
Navigating this landscape requires understanding both the science and the limitations of available evidence. The history of peptide therapy suggests optimism about what peptides can do, tempered by recognition that not every promising compound fulfils its early promise.
Conclusion
From Leonard Thompson's first insulin injection in 1922 to today's sophisticated peptide protocols, the field has transformed. What began as crude extracts from animal tissues has evolved into precisely designed synthetic compounds that can modulate specific physiological pathways.
The fundamental insight has remained constant: the body uses peptides to regulate its functions, and providing or modulating these peptides externally can influence health and function. The tools and understanding have improved dramatically, but the basic principle holds.
For those exploring peptide therapy today, this history provides context. You're participating in a tradition that spans a century, one that has saved countless lives and continues to offer new possibilities for health and longevity.
This article is for educational purposes and does not constitute medical advice. If you're interested in exploring whether peptide therapy might be appropriate for your situation, we encourage you to book a consultation to discuss your individual circumstances with our clinical team.