For centuries, shellfish poisoning has been a threat to humans, and we have had no way to stop it. The ‘red tide’ algal blooms found on the Pacific coast are deadly contributors, producing one of the most vicious neurotoxins known: saxitoxin (STX). Eat the wrong shellfish, and paralytic shellfish poisoning (PSP) follows. There is no antidote. Or at least, there wasn’t, until UC San Francisco researchers found one hiding in bullfrogs. New research published in the journal Nature Communications shows that a protein found in certain frogs may neutralise saxitoxin.
A frog protein that can save hundreds of lives
The neurotoxin STX in ‘red tide’ algal blooms was stockpiled as a chemical weapon during the Cold War, as there was no antidote. The UC San Francisco study may have changed that. The research, led by Daniel Minor, PhD, a professor in UCSF’s Cardiovascular Research Institute, found that a frog protein called saxiphilin can neutralise saxitoxin in mice. This protein can even reverse otherwise lethal poisoning.This protein occurs naturally in bullfrogs and many other frogs from around the world. It essentially acts like a molecular sponge, binding tightly to saxitoxin in the bloodstream before it can reach the nerve and muscle cells it normally attacks.Previous research on an antidote for STX has focused on interrupting the complex biological processes it uses to disable nerve cells or trying to trigger immune responses against it. Those attempts ended in disappointment.“This was a problem looking for a solution. It turns out that one naturally occurring protein is all that’s required to take this toxin out of commission,” Minor said.As these algal blooms become more common across the world, this discovery could be a crucial step forward. Minor discovered the antidote in collaboration with Stanford chemist Justin Du Bois, PhD.
A toxin ‘sponge’
Representative image
This new study is built on a 2021 paper in which Minor and colleagues showed that saxiphilin binds strongly to saxitoxin. The frog protein soaks up the toxin like a sponge and blocks its toxic properties. However, whether this interaction would work inside a living organism remained uncertain.In the new study, Minor and postdoctoral scholars Samantha Nixon, PhD, and Sandra Zakrzewska, PhD, tested saxiphilin on mice exposed to lethal doses of STX. The researchers found that when the protein was given before or alongside STX, it prevented poisoning. It also cured nearly all mice exposed to the toxin—closely mirroring what might happen if humans unknowingly consume poisoned shellfish.“We had this really big protein that needed to catch up with a tiny toxin molecule that has a running start on it. We really weren’t sure this was going to work,” Minor said.The researchers observed that the protein not only improved survival but also reduced symptoms linked to severe poisoning, with no harmful side effects. They also found that saxiphilin spread throughout the body, reaching the brain, heart and muscles, allowing it to intercept the toxin wherever it travelled.
Solving a century-old riddle
The discovery’s origins trace back to the 1920s and 1930s, when UCSF physician-scientist Hermann Sommer investigated shellfish poisoning outbreaks along the California coast. He recognised that the poison came not from the shellfish themselves but from microorganisms associated with them. It was then called ‘mussel poison’. His observations laid the foundation for the eventual identification of saxitoxin. He also observed that certain frogs appeared resistant to the toxin. Nearly a century later, that observation has been proved correct.Scientists now know that STX is not a single toxin but a family of over 50 variants with closely related structures. Minor’s previous studies found that saxiphilin can bind a wide range of these variants, making it a strong candidate for an antidote.Minor now hopes to determine whether smaller, engineered versions of saxiphilin can work in the same way, or even better, protecting against a range of STX variants. This may also provide insights into improving shellfish safety. In California, the state testing laboratory in Richmond routinely screens shellfish for paralytic shellfish toxins.“Nature has had to solve this problem multiple times. So, there is resilience to toxins all over the biological world,” Minor concluded.
