News in Science

Box jelly venom under the microscope

Deadly poison Australian box jellyfish can cause deadly cardiac arrest within minutes by punching holes in red blood cells and causing potassium to leak out of them, Hawaiian researchers have found.

But, say the researchers, writing today in the journal PLoS ONE, a zinc-based compound could one day be used as a treatment.

"The box jellyfish is the most venomous animal in the world," says lead author, Dr Angel Yanagihara, of the University of Hawaii's Department of Tropical Medicine.

The Australian box jellyfish (Chironex fleckeri) inhabits coastal waters from Australia to Vietnam.

The creature is the size of a basketball and has 60 two-metre long tentacles covered in stinging cells. Apart from causing unsuspecting swimmers excrutiatingly pain and other symptoms, being stung also occasionally leads to rapid death from cardiac arrest.

"The fastest deaths have been within 2 to 5 minutes," says Yanagihara.

Venom study

For many years scientists have been trying to pin down how the box jellyfish's venom works so fast and to find effective treatments.

Antivenom is the only treatment available to neutralise venom, but some people still die despite its administration.

Now, Yanagihara and colleague Dr Ralph Shohet say they have found out exactly how the venom causes such rapid cardiac arrest.

The researchers extracted venom from the jellyfish's stinger cells, separated it into its different components and then tested its effects in vitro and on mice.

Yanagihara and Shohet found the fasting-acting agent was a molecule called porin, which creates tiny 'pores' in red blood cells, allowing potassium to leak out.

"The leakage of massive amounts of potassium from red blood cells is one of the worst things that could happen in the body," says Yanagihara.

"When the plasma potassium gets too high there's no more electromotive force and the heart cannot beat."

Yanagihara says administering zinc gluconate prevented the release of potassium and was effective in extending the life of envenomated mice, while CSL's antivenom was not.

She says studies are currently under way to find out how zinc gluconate disrupts porins.

Yanagihara now wants to test her findings in pigs, which are more human-like than mice. This will include an infusion of the zinc gluconate.

Meanwhile, her work is the subject of multiple US and international patents and has been licensed to a commercial company.

Important experiments

CSL, the company which produces the box jellyfish antivenom, states that antivenom has a role in treating "all degrees of envenoming, not just the rare life threatening cases", but welcomes the new research.

"The findings by Yanagihara and Shohet are interesting and if confirmed by other researchers may allow development of more effective treatment of severe life-threatening box jellyfish stings, which may involve a combination of therapies," a spokesperson said in a statement.

Dr Ken Winkel, director of the Australian Venom Research Unit at the University of Melbourne, says while pore-forming toxins have been identified in box jellyfish before, this is the first time their action has been studied in such great detail.

"I think it's a very important set of experiments to implicate potassium release which has been hitherto relatively overlooked," he says.

But, he says, while the model used suggests the zinc compound was clearly more effective than antivenom at preventing death, Winkel would like to see future tests combining the two.

"They may be complementary," he says.

Beachside treatment

Winkel says about 30 people were hospitalised in Australia between 2002 and 2005 with box jellyfish stings.

By contrast cardiac arrest following box jellyfish stings leads to only around 1 death every two or three years.

Winkel says deaths occur most commonly in children and on the beach, before people get taken to hospital.

"Typically it's a remote location in Northern Australia where you can't get an ambulance full of drugs to the scene," he says.

Due to the speed at which cardiac arrest can occur, Winkel says whatever treatments eventuate from the latest research, will have to be given at the beachside if they are to be effective.

He says regardless of drug treatments, prevention of deaths via resuscitation at the time of cardiac arrest seems to be crucial in people surviving box jellyfish stings.