How peptides are changing medicine
Peptide drugs are a century old and are having their biggest decade yet. What that does, and doesn’t, say about the research-peptide market that grew up beside them.
A peptide is a short chain of amino acids, the same building blocks that make up proteins. Where a protein might run to hundreds or thousands of amino acids, a peptide is usually somewhere between two and fifty. The body makes thousands of them and uses them as messengers: hormones, signals, the instructions that tell one organ what another is doing. That is why peptides have interested medicine for a century, and also why they were so hard to turn into drugs for most of it.
This piece is about peptides as medicines: how they got here, why they are suddenly everywhere, and where the field appears to be going. It ends with something the Foundation cares about more directly. The research-peptide market sells many of the same molecules and almost none of the rest of what makes a medicine a medicine, and seeing the pharmaceutical side clearly is the best way to see what the other side is missing.
A century of peptide drugs
The first peptide drug was insulin. It was isolated in 1921 and given to a patient in early 1922, and within a few years a diagnosis of type 1 diabetes had gone from fatal to manageable. For sixty years it was extracted from the pancreases of cattle and pigs. In 1982 it became the first medicine produced with recombinant DNA, made by engineered bacteria, and the modern biotechnology industry more or less began there.
Progress in between was slow, for reasons worth understanding. Peptides are fragile. Enzymes in the gut and the blood break them down within minutes, so most can't be swallowed and don't last long in the body. They are large enough to struggle crossing cell membranes and small enough to be cleared quickly by the kidneys. And until the 1960s, making one in a laboratory meant months of chemistry for a few milligrams. Solid-phase synthesis, invented in 1963, changed that last part, and it is still how most peptides are made today. Even so, by the end of the twentieth century only a few dozen peptide drugs had reached patients, most of them versions of hormones the body already made.
Why the last decade has been different
Two things changed.
Chemists learned how to make peptides last. A fatty-acid chain attached to the molecule lets it bind to albumin in the blood and stay in circulation for days rather than minutes. Swapping or modifying individual amino acids protects it from the enzymes that would otherwise cut it apart. And formulations now exist that get some peptides absorbed from the stomach. A molecule that once needed several injections a day can now be given once a week, or in a few cases as a tablet.
And one class of them became the most talked-about drugs in the world. GLP-1 receptor agonists mimic a gut hormone that signals to the pancreas and the brain after a meal. The first was approved in 2005 for type 2 diabetes, and was derived, improbably, from a peptide in the venom of the Gila monster. Longer-acting successors followed and were later approved for chronic weight management as well. By the middle of this decade they were among the best-selling medicines ever made, prescribed to millions of people, and the subject of trials in conditions well beyond the ones they were first approved for.
The count tells the story. Roughly a hundred peptide drugs are now approved somewhere in the world, well over a hundred more are in clinical trials, and the pipeline is fuller than it has ever been.
Where the field appears to be going
Nobody knows the future of a drug class, and anyone who claims to should be read with care. But the direction of the current research is visible.
Longer-acting and oral peptides, so that more of them can be taken without injections. Multi-agonists: single molecules built to act on two or three hormone receptors at once. Peptide conjugates, in which the peptide is a delivery vehicle carrying a payload, a radioactive isotope for instance, to cells that carry a particular receptor; some cancer therapies already work this way. And design by computation. The tools that recently transformed protein structure prediction are now being used to design peptides that don't exist in nature, which would have been science fiction ten years ago.
Where all of this lands is not something we're in a position to predict. What can be said is that peptides have gone from a difficult corner of pharmacology to one of its main streets, and that will keep drawing money, talent and attention for a long time.
A molecule is not a medicine
Here is the part that matters for the Foundation's work.
Demand for the new peptide drugs outran supply for years. When people couldn't get a medicine, some went looking for the molecule, and they found it: the same or similar sequences, sold by online resellers, labeled for research use only. The research-peptide market existed before that, mostly around compounds that had never completed clinical development, but the shortage made it far larger, and the end of the shortage has not made it small again.
It's easy to look at a research vial and an approved drug and see the same thing. They may well contain the same molecule. But an approved medicine is the molecule plus everything around it: a manufacturing process that is inspected and controlled; identity, strength, purity and sterility tested against a published standard on every batch; years of clinical evidence about what it does, to whom, and with what side effects; a label that says how it is to be used; and a system for catching problems after it reaches the market. Approval is a property of a product and a process, not of a sequence of amino acids. The same sequence can be a medicine coming out of one process and an unregulated research chemical coming out of another.
Products labeled for research use only have the molecule, sometimes, and none of the rest. That isn't a criticism of the market. It is a description of it, and it is the description the label itself gives.
The Foundation takes no position on whether any compound is good, safe or worth taking. What we do think is that most of the gap between a research vial and a medicine can't be closed from outside, and one part of it can: what is actually in the vial, measured by someone with nothing to gain from the answer, and published whether or not anyone likes the result. That is the part we work on. The other half of the gap, the evidence, is the subject of research peptides, without the research.