Shellfish poison has been a threat to humans for centuries and we have no way to stop it. ‘Red tide’ algal blooms found on the Pacific coast are deadly contributors, producing one of the most dangerous neurotoxins known: saxitoxin (STX). Eat the wrong shellfish, and you will get paralytic shellfish poisoning (PSP). There is no antidote. Or at least, it wasn’t until researchers at UC San Francisco found one hiding in a bullfrog. New research published in the journal Nature Communications shows that a protein found in some frogs can neutralize saxitoxin.
A frog protein that could save hundreds of lives
The neurotoxin STX was stockpiled as a chemical weapon in ‘red tide’ algae blooms during the Cold War, because there was no antidote. The UC San Francisco study may have changed that. Research led by Daniel Miner, PhD, a professor at UCSF’s Cardiovascular Research Institute, found that a frog protein called saxiphilin can neutralize saxitoxin in mice. This protein can also reverse otherwise fatal poisoning.This protein is found naturally in bullfrogs and many other frogs around the world. It essentially works like a molecular sponge, tightly binding saxitoxin in the bloodstream before it can reach nerve and muscle cells that normally attack it.Previous research on an antidote for STX has focused on disrupting the complex biological processes it uses to disable nerve cells or trying to trigger immune responses against it. Those efforts ended in disappointment.“This was a problem that needed a solution,” Miner said. “It turns out that all it takes to release this toxin is a naturally occurring protein.”As these algal blooms become more common around the world, this discovery could be an important step forward. Miner discovered the antidote in collaboration with Stanford chemist Justin Du Bois, Ph.D.
A poison ‘sponge’
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This new study builds on a 2021 paper in which Miner and colleagues showed that saxiphyllin binds strongly to saxitoxin. Frog protein absorbs the poison like a sponge and prevents its toxic properties. However, whether this interaction would work inside a living organism remains uncertain.In the new study, Miner and postdoctoral scholars Samantha Nixon, PhD, and Sandra Zakrzewska, PhD, tested saxiphyllin on rats exposed to lethal doses of STX. The researchers found that when the protein was given before or along with STX, it prevented the toxicity. It also cured almost all the rats exposed to the poison – closely mirroring what can happen if humans unknowingly eat poisonous shellfish.“We had this really big protein that needed to capture a small toxin molecule, which started working. We weren’t really sure it would work,” Miner said.The researchers observed that the protein not only improved survival but also reduced symptoms associated with severe toxicity, without any harmful side effects. They also found that saxiphyllin spreads throughout the body, reaching the brain, heart, and muscles, allowing it to stop the toxin wherever it travels.
Solving a century old puzzle
The origins of the discovery date back to the 1920s and 1930s, when UCSF physician-scientist Herman Sommer investigated outbreaks of shellfish poisoning off the California coast. He believed that the poison came not from the shellfish but from the microorganisms associated with them. Then it was called ‘muscle poison’. His observations laid the foundation for the eventual identification of saxitoxin. They also observed that some frogs appeared to be resistant to the poison. Nearly a century later, that observation has been proven correct.Scientists now know that STX is not a single toxin but a family of more than 50 variants with closely related structures. Miner’s previous studies found that saxiphyllin can bind a wide range of these types, making it a strong candidate for an antidote.Miner now hopes to determine whether smaller, engineered versions of saxiphyllin can work in the same way, or even better, protect against a range of STX variants. It may also provide information on improving shellfish safety. In California, the state testing laboratory in Richmond routinely tests shellfish for paralytic shellfish toxins.Miner concluded, “Nature has had to solve this problem many times. Therefore, there is resilience to toxins throughout the biological world.”