A century of peptides — from one hormone to engineered combinations

1922Banting, Best, Macleod & Collip — insulin

In Toronto, Frederick Banting and Charles Best, working in John Macleod's laboratory with biochemist James Collip, isolate insulin and achieve the first successful treatment of a diabetic patient — the first peptide therapeutic, and the proof that a peptide can be a medicine. The 1923 Nobel Prize goes to Banting and Macleod, who share their awards with Best and Collip.

1953du Vigneaud — a peptide made, not extracted

Vincent du Vigneaud's team synthesises oxytocin — the first peptide hormone built in a laboratory rather than purified from tissue. Sequence becomes something chemists can write, not just read. Nobel Prize in Chemistry, 1955.

1963Merrifield — peptides on a solid phase

Robert Bruce Merrifield at Rockefeller University invents solid-phase peptide synthesis: anchor the first amino acid to a resin bead, then add each next one in a repeatable cycle. Synthesis becomes engineering — chains long and exotic enough to design, not merely copy. Nobel Prize in Chemistry, 1984.

2018Lau & Dunn tally the renaissance

Jerry Lau and Michael Dunn review the therapeutic-peptide landscape: dozens of marketed peptides, hundreds in development, and a field transformed by synthesis, half-life engineering and delivery science. Their framing — historical perspective, current trends, future directions — becomes a standard map of the peptide renaissance.

Lau J.L., Dunn M.K., Bioorganic & Medicinal Chemistry 26, 2700 (2018) — doi:10.1016/j.bmc.2017.08.052

2021Muttenthaler and colleagues — the engineered era

Markus Muttenthaler, Glenn King, David Adams and Paul Alewood survey peptide drug discovery in Nature Reviews Drug Discovery: the pipeline's centre of gravity has moved from natural sequences to engineered, multifunctional design — constrained peptides, conjugates, and molecules built to address more than one target.

Muttenthaler M., King G.F., Adams D.J., Alewood P.F., Nature Reviews Drug Discovery 20, 309 (2021) — doi:10.1038/s41573-020-00135-8

2022–The multi-target era goes public

Eli Lilly's tirzepatide — one engineered peptide acting on both GIP and GLP-1 receptors — receives FDA authorization for type 2 diabetes in 2022, and its successor retatrutide pushes the same logic to three targets in clinical trials. Whatever one thinks of any single product, the field's verdict is in: engineered combination outperforms single-target design in this class. The remaining question is architectural — one fused chain, or a system of chains engineered together?