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Clad in their hiking gear, headlights punching through the shadows, Carolina Muñoz and her teammates slogged through the thick foliage of the Amazon jungle of Colombia, searching for slimy fluorescent treasure while trying to evade the thorns of chonta palms and rattan lianas, and the fangs of venomous snakes. When they finally spotted their quarry, she and her team all froze to avoid startling it. Then, they plucked the lime green and blue frog—an Orinoco lime treefrog—from the tree branch and plopped it into a fabric bag, where it would stay, swaddled in foliage and water mist, until it was ready for its new home.
It was just one of many amphibians the frog-hunting crew collected over a five year period, repeating this process in forests, mountains and wetlands, even urban areas, around the country. In all, they collected two frogs from 50 different species of interest. Each frog they captured held the promise of a cure hidden in its skin.
Back in the lab at the Universidad de las Andes in Bogotà, Muñoz and colleagues swabbed the frog bodies and collected the gooey mucus they secrete, to test for chemicals that might cure human diseases.
They had good reason to believe they would be successful. Frog skin is a marvel of nature. A mucous membrane, this outer layer is kept moist and is filled with a cocktail of chemicals that frogs have developed over millennia of evolution. It’s thin and delicate and highly permeable, which allows frogs to use it to breathe in oxygen when they’re submerged under water, and to spit out toxins that kill infections and poison predators when they’re under attack.
Read more: “Can Organoids Take Us into a New Era of Medicine?”
During her field work in the Amazon, in addition to the chubby green Orinoco lime treefrogs, Muñoz collected warty Boulenger’s backpack frogs and tiger-striped whistling frogs known as rã-assobiadora, among others. When she took them back to her lab, she found that the skins of all three species of frog are infused with new-to-science peptides—small protein snippets—that can help cells fight the yellow fever virus, a viral disease spread by mosquitoes in much of Africa and South America that presents with severe flu-like symptoms. Cells treated with the peptide saw their infection potency reduced by 35 percent.
Orinoco lime treefrogs, it turns out, ooze peptides known as frenatin and buforin II, which can jam up bacterial membranes and DNA. And her tests of the skin of 11 other frogs and toads from her field work revealed some molecules that can break down cancerous human leukemia cells.
Frog secretions may even help with wound healing.
Muñoz initially thought she would find the most potent antidotes to human maladies in frogs that live in the most remote areas of the jungle. But she soon realized that the ones living closer to human settlements—such as an Orinoco lime treefrog specimen she actually picked up from a playground in an Amazonian city—would be more likely to encounter the same pathogens as humans, and therefore develop toxins that could be useful to us. “Frogs that we captured near human activity have peptides that are 10 or more times more potent than the ones that are far from humans,” says Muñoz. Still, she has a lot more work to do: “We identified nearly 70 peptides, but only published reports about two or three,” she says.
Muñoz is not the only one who has looked to frog skin for anti-viral, anti-cancerous, and anti-bacterial remedies. Researchers from Emory University in Atlanta have also found that the slime produced by the skin of some frogs could act as an antidote for the influenza virus, and maybe even for COVID-19.
Elsewhere, scientists studying jaguar leaf frogs and Kuatun frogs have found peptides that act both as antimicrobials and anti-cancerous molecules, too. The jaguar leaf frog’s skin, for instance, is bathed in a peptide that, in a petri dish, corrodes the cells of human lung cancer, breast cancer, prostate cancer, and brain cancer. It also has these same effects, though less potent, in real-life mice without many toxic side effects.
Frog secretions may even help with wound healing, some researchers have found. A team in China analyzed the skin secretions of the Yunnan odorous frog, a stinky frog found in South Asia, and found a peptide that can boost human skin-cell reproduction in a petri dish and can accelerate wound closure in the skins of real-life mice. The skin secretions of the East Asian bullfrog—famed in Chinese traditional medicine—have also been shown to contain a peptide that can treat wounds, as has the goo from the skin of the Asian black-spined toad. Ideally, these organic molecules could be used to design creams, gels, and other topical drugs to help heal burns or chronic wounds, such as the kind that some people with diabetes develop.
Frog skin is “an extraordinarily fertile source for drug development,” says Michael Zasloff, the first scientist to describe antimicrobial peptides in a frog’s skin in the late 1980s. He has studied the evolution of frog skin peptides throughout the world.
But it’s one thing to get a molecule to fend off bacteria or cancer in cell culture, and quite another to get it to work in the human body. Almost all of the above-mentioned studies were carried out in the laboratory in petri dishes: the very first step for drug development. “When a peptide is put into the bloodstream, it’s now looking at membranes everywhere,” says Zasloff. “It has to be sufficiently selective so that it disregards all these membranes,” and zooms in on its target: the disease-causing molecule floating around a live organism’s blood.
The few tests being done on mice are also hard to extrapolate to humans, Zazloff adds. “One has to advance from mouse to humans. That’s really the issue, isn’t it?”
The excitement surrounding these discoveries, though, isn’t just about what the peptides do—but rather how they do it.
Frog skin is “an extraordinarily fertile source for drug development.”
Many of the peptides found in frog skin are positively charged, whereas bacterial cell membranes are composed of negatively charged lipids. As a result, these peptides are drawn by electrostatic charge to the bacterial membranes, and when they bump into the membrane, they destroy it. (Don’t worry, these peptides are not as violently drawn to cell membranes in animals and plants, which are mostly neutrally charged, instead.) The buforin II and frenatin peptides found in the Orinoco lime treefrog skin, for instance, kill bacteria by piercing into the bacterial cell’s membranes and scrambling their genetics, binding to the DNA and RNA. This is true for many of the peptides found in the jaguar leaf frog and the Chinese frogs, too, among many others.
“That’s marvelous and exciting for me,” says Muñoz, who also penned a paper about these types of peptides in Nature in 2024.
With antibiotic resistance rising, scientists have been racing to find new therapeutic compounds, and the ones hiding on a frog’s back might have unique advantage. Antibiotics conventionally target the enzymes in bacteria, and enzymes can mutate and adapt over time, reducing their vulnerability—but the bacteria themselves don’t have the same shapeshifting abilities, so they cannot adapt to membrane-scrambling antidotes. Similarly, these peptides act through multiple mechanisms at once; they don’t just disrupt the bacterial membrane but also penetrate the cell and bind to its genetic material, which is why bacteria find it much harder to develop resistance.
“Unlike traditional antibiotics that target a single pathway, these peptides attack from several fronts,” says Muñoz.
Most importantly, while antimicrobial peptides are much more gentle on human cell membranes than they are on those of bacteria—because human cell membranes are neutrally charged—they can still penetrate those membranes too, entering the cell without destroying it. This selective interaction is what makes them so promising as tools for delivering genes or drugs to the inside of a human cell. The peptides act like keys that unlock the cell membrane and guide or direct the therapeutic cargo to its destination, says Muñoz, as if the peptide started the engine of a truck full of medicine, allowing the delivery system to enter the cell and drive the treatment precisely to where it needs to go.
“These molecules can help to ensure the cargo is delivered in the right position in the nucleus,” says Muñoz.
This special power gives the frog skin molecules a whole new biotech application, says Muñoz, which is what she has been focusing most of her efforts on of late. Having recently moved on from her time plucking frogs from jungle tree branches, Muñoz now works on using artificial intelligence to help predict which of those molecules might have the best fighting chances against ailments in massive numbers, and studying and designing pathways for them to break into human cells in clever and effective ways.
Despite the challenges of bringing these compounds from the laboratory to the drugstore, it seems like the world of frog peptides still has a lot more to share. In a way, Muñoz has traded the jungle canopy for a digital one—using AI to predict which frog-made molecules could one day leap from petri dishes to patients. 
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Lead image: reptiles4all / Shutterstock
