The funnel-web spider is one of the most venomous spiders in the world. Just one bite causes confusion, convulsions, extreme pain and, if left untreated, death. The spider’s size and speed just adds to its menacing reputation.
Yet to Professor Glenn King, Atrax robustus isn’t just a spider. It’s a chemical treasure house whose venom contains riches beyond measure: everything from environmentally friendly insecticides to treatments for neurological diseases to new and more targeted forms of pain relief.
And his love affair with the funnel-web began with a dozen glass pipettes with some freeze-dried spider venom at the bottom. “Sent by regular mail,” King told The Brilliant. “You couldn’t do that today.”
The insecticide breakthrough
King is a professor at the Institute for Molecular Bioscience at The University of Queensland, and a world-renowned expert in the biochemistry of venom. It’s a long way from the days when he used nuclear magnetic resonance (NMR) imaging to study cancer-causing proteins. He set up an NMR lab at the University of Sydney and “cancer was my thing,” he says.
In 1996 he was contacted by toxicologist Dr Merlin Howden, who asked him to identify the structure and mode of action of a molecule found in funnel-web venom. “He was interested in it because it was insecticidal,” says King.
King quickly solved the three-dimension structure of the molecule. Curious to know more, he teamed up with a pharmacology colleague, and they discovered the venom molecule acts on insect ion channels; ion channels are the doors that open and close to let an ion carrying an electric charge into or out of a cell. When the channels are disrupted, the cells can’t function.
“I thought, well this is fun stuff,” says King. Dr Howden sent him more samples by mail, and King got to work. “I thought that venom would be pretty simple secretions,” he said.
Using a technique known as High Performance Liquid Chromatography (HPLC), King separated the venom’s components. “There were literally hundreds of molecules in the venom,” he says. “I was blown away by the complexity.”
What began as a side project began to absorb him.
I thought, wow, this is surely a goldmine for insecticidal molecules,” he says. “And so, over the next few years, we started taking all the individual components to inject them into a range of insects.” He was looking for a molecule that targeted insects, but not bees or vertebrates. “You don’t want it to kill birds. You don’t want it to kill the farmer’s dog. You don’t want to kill the farmer.”
And then he found it.
To commercialisation
Convinced that industry would leap at the chance to produce environmentally friendly insecticides, King talked to agrichemical companies. “Their eyes glazed over,” he says.
In 2005, King founded Vestaron, a USA based company, which engineered the genes coding for the spider toxins into yeasts. As the yeasts ferment, they produce insecticides.
“The thing that’s really convenient for farmers is that with a lot of chemical insecticides, once you spray, you can’t harvest for a while because of the toxicity. These are things you can spray in the morning and harvest in the afternoon,” says King, “and they are also safe for bees”.
The USA’s Environmental Protection Authority recognised the breakthrough in 2020, bestowing Vestaron a Green Chemistry Award.
Both poison and cure
While his research on insecticides continues, King says 80 percent of the work he now does is on “using venoms as a source of therapeutics”. Today, the IMB’s venom library has expanded to include secretions from about 500 venomous creatures.
“We work on what I broadly refer to as ‘nervous system disorders’, where the cause of the disorder is an ion channel,” says King, adding that most anti-epileptic and many analgesic drugs modify the activity of ion channels. “We’re after molecules that target ion channels and virtually all invertebrate venomous animals have venoms that target ion channels in the nervous systems of their prey.”
King says that once his lab has a sample of venom, it can obtain a full chemical profile in about two weeks. The next step is to use HPLC to break the venom into its constituent parts. “This molecule that we found in the venom of the Fraser Island funnel-web spider looks pretty exciting. We think it could potentially change the way we manage stroke.”
According to the Stroke Foundation, the economic cost of strokes in Australia alone is devastating; $6.2 billion in direct costs and another $26 billion in premature mortality and disability. At a personal level, a stroke can be a devastating event, because it guarantees brain damage. There are two types of stroke: haemorrhagic stroke, which is a brain bleed, and ischaemic stroke from a clot which blocks blood vessels. Clot-busting medication can’t be given to stroke patients until the type of stroke has been confirmed by hospital imaging, as it will worsen a haemorrhagic stroke. But every minute a stroke isn’t treated means more brain damage, because two million neurons a minute are lost forever.
King says funnel-web venom contains a peptide called Hi1a, which can block the ion channels causing much of the destruction.
This venom-derived peptide has the potential to completely change the management of stroke and not only save lives but transform quality of life for survivors.”
The hardest part
Given the potential of King’s research, it’s easy to imagine that people are beating a path to his door, wanting to donate or invest. But he says the hardest part of his research isn’t the search or the testing, but raising money. “It’s very, very difficult,” he says.
Yet it’s hard to overstate the promise held out by venomous creatures. Inside their toxin sacs lie environmentally friendly insecticides, alongside cures for seemingly intractable diseases. And despite the potency of their toxins, King says that most venomous creatures are harmless to humans.
“It’s really important to note that a loss of these venomous animals could be the loss of an important drug,” he says.
Far from being a terrifying menace, the funnel-web spider is a national treasure – as are all the other venomous creatures. Thanks to King, they’re finally getting the respect they deserve.
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Article by Felicity Carter
Photo Credit: Photo supplied