Secrets of stonefish venom revealed

Researchers have done a “deep dive” into the most venomous fish species on Earth and revealed “surprising” new insights that might lead to better treatment for stings, and could be used to treat diseases such as cancer.

The estuarine (Synanceia horrida) and reef (Synanceia verrucosa) stonefish are found throughout the warm waters of the Indo-Pacific and in the Persian Gulf and the Red Sea.

People unlucky enough to step on a stationary stonefish will suffer excruciating pain and may also develop more serious symptoms, such as weakness, fast heart rate, fluid in the lungs, convulsions, respiratory and cardiac failure and, rarely, death.

Stonefish are one of the very few species that are both venomous and poisonous, Dr Silvia Saggiomo, who conducted the research at the Australian Institute of Tropical Health and Medicine (AITHM) at James Cook University (JCU), told Cosmos.

“Apart from the venom they have on their dorsal spines, which poses a significant threat to public health … they also have a toxin that they secrete onto their skin, but we don’t know much about its function.

“They are one of the very few fish species that can withstand long periods outside of the water, being found stuck in the sand and rocky shores or in tidal pools, once the tide recedes.

“They are also incredibly sluggish and somewhat averse to swimming, which is counterintuitive when you think of a fish! They prefer, instead, to sit and wait being ambush predators.”

Saggiomo, who is now at QIMR Berghofer Medical Research Institute in Australia, says that treatment for these stings is not straightforward.

“There is a lack of a protocol that clinicians and first-aiders could apply to effectively treat people,” she says.

“Sometimes immersing the affected limb in hot water improves symptoms, but this is not likely to stop the venom from causing further damage. More often than not, people are treated based on which symptoms they present at the time.”

When researching venoms, scientists mainly focus on the peptides, proteins, and enzymes, as they are usually associated with the medical pathologies seen in envenomated victims.

“It makes sense to focus on them, as [by] understanding their mechanisms (or how these molecules work) we can understand how to stop or ameliorate symptoms and pathologies,” says Saggiomo.

However, it also means that further investigation of the venom’s composition is often overlooked when a way to stop people from experiencing the worst symptoms of a sting has been found.

“In the case of stonefish, it becomes clear when you read the literature that there are many molecules – small and big – that have not been identified,” says Saggiomo.

“In my case, I’m interested in investigating possible molecules to use in venom-derived compounds that could aid in the treatment of other diseases, such as cancer, inflammation-related diseases, etc.

“Small molecules are the best candidates for the job. They are much easier to work with, given the smaller size, if you want to synthetise them in the laboratory.”

Saggiomo’s team tested the venom collected from stonefish housed at JCU Aquarium to isolate the small molecules for the first time.

“Professor Jamie Seymour has been milking these animals for years, extracting the venom for the production of antivenom, so he helped me obtain the venom.

“The process is simple, quick, and it does not hurt the animals, so it’s a sustainable practice.”

They discovered the presence of 3 molecules new to stonefish venom: gamma-aminobutyric acid (GABA); choline; and 0-acetylcholine.

These molecules have been previously found in other dangerous species, such as hornets and spiders. But according to Saggiomo, finding GABA was quite surprising.

“Not many species have this neuromodulator present – this is the first time GABA has been found in a fish or in any other truly aquatic animal for the matter,” says Saggiomo.

Neuromodulators are chemical messengers in the nervous system.

“We are still trying to understand how these neuromodulators affect envenomation mechanisms,” says Saggiomo.

The findings also highlight that the venoms of the 2 species, while sharing many molecules in common, have distinct molecular makeups.

“I believe that, depending on the molecular makeup of the venom, stings from different species of stonefish have a different symptomology associated with it,” says Saggiomo.

“The case studies (or medical cases) published in the literature would suggest that stings from S. verrucosa, the reef stonefish, are more dangerous and cause the highest amount of accidental envenomation around the world – in fact, the only truly well-documented case of a death caused by a stonefish sting identified the culprit as the reef stonefish.”

If Saggiomo’s theory is correct, this could improve treatments for the sometimes-deadly stings of these unique fishes.

The research is published in the journal FEBS Open Bio.