Magainin-2 Antimicrobial
Peptide

Before 1987

A World Running Out of Antibiotics

The Invisible Crisis

By the 1980s, doctors were starting to worry. The antibiotics that had saved millions of lives since World War II were losing their power. Bacteria were learning to resist them. New superbugs appeared in hospitals. Drug companies were running out of new ideas.

Meanwhile, a quiet puzzle was hiding in plain sight. Scientists had been performing surgery on African clawed frogs for decades. These frogs were used in everything from pregnancy tests to genetics research. After surgery, they were placed back into tanks filled with murky, bacteria-laden water.

By all logic, these frogs should have been dying of infections. Their surgical wounds were open doors for germs. But the frogs healed perfectly. Every single time. Nobody stopped to ask why.

The Breakthrough

The Question Nobody Asked

A Surgeon Stops to Wonder

Michael Zasloff had performed surgery on thousands of frogs during his career at the NIH. One day in 1986, as he watched a frog heal perfectly in its dirty tank, he stopped mid-step. A question hit him like a lightning bolt: Why don't these frogs ever get infected?

He did something brilliantly simple. He took pieces of frog skin, ground them up, and tested the mixture against bacteria. The bacteria died almost instantly.

Zasloff spent months purifying the active ingredients. He filtered, separated, and tested hundreds of fractions. Finally, he isolated two short peptides — tiny chains of just 23 amino acids. He named them magainins, from the Hebrew word 'magain,' meaning 'shield.'

In August 1987, he published his findings. The paper was a bombshell. Frog skin contained its own natural antibiotics — and they worked against bacteria, fungi, and even some viruses.

The Trials

The Shield Goes to War

From Frog Skin to Medicine Cabinet

Zasloff's discovery sparked intense excitement. If frogs made their own antibiotics, could we use them as drugs?

A company called Magainin Pharmaceuticals was founded to turn the discovery into medicine. Scientists created pexiganan (also called MSI-78) — a synthetic version of magainin-2 that was even more powerful than the natural version. It killed bacteria faster and at lower doses.

The target was diabetic foot ulcers. Millions of people with diabetes develop sores on their feet that get infected. When antibiotics fail, doctors sometimes have to amputate. Pexiganan could be applied directly to these wounds as a cream.

Phase III clinical trials enrolled thousands of patients. The medical world held its breath. This was the first antimicrobial peptide to make it this far in drug development. If it worked, it would prove that nature's ancient weapons could become modern medicine.

The Crisis

The Rejection

When the Shield Wasn't Enough

In 1999, the results came in. And they were devastating.

Pexiganan worked. It killed bacteria in wounds. But it didn't work significantly better than existing antibiotic creams. The FDA advisory panel voted against approval. The dream was over.

For the entire field of antimicrobial peptide research, this was a crushing blow. Billions of dollars had been invested. Thousands of scientists had worked toward this moment. And the first peptide antibiotic to reach the FDA's door had been turned away.

Critics said antimicrobial peptides were too expensive, too fragile, and too similar to existing treatments to justify approval. Some scientists wondered if the whole field had been overhyped.

A second attempt at FDA approval was made in 2017 by a different company. It also faced challenges. Magainin-2's journey from frog skin to pharmacy shelf remained incomplete.

The Legacy

The Revolution That Mattered More

One Failure Launched a Thousand Breakthroughs

Here's what nobody predicted: the clinical failure didn't kill the field. It supercharged it.

Zasloff's 1987 frog skin paper became one of the most cited discoveries in immunology. Scientists around the world began searching for antimicrobial peptides everywhere — in human skin, in breast milk, in insects, in fish, in plants. Today, over 3,000 antimicrobial peptides have been discovered and studied.

Magainin-2 proved something far more important than any single drug. It proved that nature has been fighting bacteria with peptide weapons for over 500 million years. And those weapons still work — because bacteria struggle to develop resistance to them.

New peptide drugs based on magainin's principles are now in clinical trials for wound infections, superbugs, and even cancer. The field that started with one surgeon's curiosity about frog surgery has grown into a global research enterprise.

Michael Zasloff's question — 'Why don't these frogs get infected?' — turned out to be one of the most important questions in modern medicine.