Insects, drugs and electric poison: is this the deadliest library in the world?
The devil arrived at Andrew Walker’s laboratory in a cardboard box. Its fluorescent green body, covered in a thicket of menacing spines, was adorned at either end with a pair of black horns.
For residents of North East Queensland, this is a devilish scientific name Comana monomorpha – is known as the electric caterpillar. The sting, which is usually received while tending lily pads in the garden, is exceptionally painful.
The poison causes a nasty welt and a significant rash that can last for a week. It’s so bad that some victims spent a night in the emergency department. Health workers treating the affected people saw swelling, blood-filled boils and welts – but they couldn’t find anything to ease the pain.
According to a poster from a Townsville community group on Facebook, this feels “like the seven rings of hell”.
But where hapless gardeners see an enemy, Walker sees a potential ally. “Caterpillars are my favorite poisonous animal right now,” he says.
Walker, a molecular entomologist at the University of Queensland’s Institute for Molecular Bioscience, has characterized the venom of some of the world’s least studied venomous animals, including centipedes, assassin bugs and various caterpillars.
Together with Glenn King, a sympathetic biochemist who heads the Institute’s “bugs and drugs” group, and a former colleague, Volker Herzig, the group has collected venom from more than 500 species, creating an unprecedented collection of animal toxins built up.
“This is by far the largest invertebrate venom library in the world – probably the largest venom library in the world,” says King.
In fact, considering it contains venom from Australian tarantulas, a Brazilian caterpillar and the deadly funnel-web spider, it could be considered the most deadly library in the world. But researchers like King and Walker aren’t interested in poison’s ability to kill.
They want to use it to heal.
Venom is, in the simplest terms, a poison delivered by one animal to another. But that definition reduces the complexity of toxins; they are composed of rich cocktails of molecules. More than 200,000 species on Earth are venomous, and each has evolved its own biological weapons to help them kill prey or, as with the caterpillar, defend against it.
By studying the molecules that make up poison, scientists have managed to develop compounds can relieve chronic complaints pain, treat diabetes and create environmentally friendly insecticides. To date, six venom-derived therapies have been approved for use in humans.
Many venoms are adept at disrupting a part of the mammalian cellular machinery, known as a ion channel. These channels are used for everything from breathing to muscle contraction and neural signaling.
Scientists like King and Walker are using that quirk of nature to their advantage: By identifying key molecules in venom that interact with ion channels, they hope to discover molecules that can target those channels, ultimately leading to the creation of targeted therapies.
A venom library augments this process, allowing researchers to screen hundreds of toxins simultaneously and quickly identify promising candidate molecules.
“We can apply (the library) to virtually any human condition where we think an ion channel may be involved in the disease,” says King.
OOn a warm Brisbane morning in early April, Walker leads me through double-locked doors to the institute’s insect room. Outside, there are signs on the walls about the dangers that may lurk inside; The main threat is the funnel web.
Inside, the space is not much larger than a bedroom in an apartment. The sterile windowless white laboratory is punctuated by three large gray cabinets – the kind you might find in a major hardware store. Walker opens one, takes out a plastic lunchbox and lifts the lid.
To my relief, it’s not a funnel web. It’s Hector, the institute’s ‘media-trained’ rainforest scorpion. Walker puts it in my hands.
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To date, snakes have provided the most useful venom for human medicine and therapies. Scorpions, like Hector, and spiders – which belong to the same class of animals – have long provided useful insights into venom, although no therapeutic compounds based on them have been developed. The bugs and drugs group hopes to change that.
Using the venom library, the University of Queensland team, along with scientists from Monash University, characterized the venom of a subspecies of funnel-web spider, discovering a peptide with powerful physiological effects. Known as Hi1athe small protein blocks a signaling pathway that tells cells to die when there is a lack of oxygen. When given to patients who have had a heart attack or stroke, Hi1a could protect against extensive, permanent damage.
In animal models, studies have suggested that this molecule could be protective effects against heart attack. It is scheduled for preliminary human clinical trials in 2025.
As Hector rests calmly in my palm, Walker explains how his research has taken him from neuroscience to studying silk proteins, and now looks beyond just scorpions and spiders.
“My idea was that if you went to another group of animals that had developed venom independently, you would see very different types of molecules,” he says.
Walker’s work with caterpillars is at a much earlier stage than the group’s funnel-web studies. Spiders are generally much larger than caterpillars and produce much more venom. The typical yield after milking a spider can be measured in microliters. Toxin yield in caterpillars is measured in nanoliters – amounts that are barely noticeable in a test tube.
King says it would have been impossible to study this amount of venom 20 years ago, but technological advances have allowed researchers to identify peptides from minuscule volumes. This has led to some surprises.
First, caterpillar venom was predicted to contain simple peptides and proteins – just like bee venom – because they are used purely for defense. But Walker’s studies have shown that the molecules produced in caterpillar toxins are much more complex than expected.
In the case of the asp caterpillar, a moth larva that resembles a toupee, Walker evidence found that it may have acquired its toxic properties many millions of years ago through gene transfer with bacteria. In yet-to-be-published research, he suggests that the electric caterpillar may have undergone a similar process.
Both species contain venom rich in molecules that can punch holes in a cell membrane, causing an attacking animal to feel pain.
These proteins represent a potential path to new insecticides and therapies. Similar molecules have been used to protect crops from pests and some are being developed as a way to deliver drugs into cells. The electric caterpillar is unlikely to have such an impact, Walker points out, but there are immediate benefits to understanding what the venom consists of – especially if you live in north-east Queensland.
Electrical caterpillar poisoning is notoriously difficult to treat. Ice packs don’t seem to work. An insect bite gel? Forget it. Vinegar does nothing. Aspirin and paracetamol do not relieve the pain.
Later in the afternoon of my visit, when I meet King and Walker in the university cafe to talk about caterpillars, they come up with a possible solution in real time. King notes that pain from jellyfish stings can be relieved by heat, and Walker’s work has shown that peptides in asp caterpillar venom break down at higher temperatures. The electric caterpillar is similar, so they reason that a heat pack might be the best course of action for affected patients.
Walker doesn’t seem entirely convinced, but decides to email a health worker in northeast Queensland who is looking for answers. Maybe he’s finally found one.