July 21, 2024

The devil arrived at Andrew Walker’s laboratory in a cardboard box. Its fluorescent green body, covered in a thicket of menacing spikes, was adorned on both sides with a pair of black horns.

For residents of the north-east Queenslandthis devil – scientific name Come on monomorpha – is known as the electric caterpillar. Its sting, typically received while tending to lily pads in the garden, is particularly painful.

The venom causes a nasty stain and a significant rash that can last for a week. It is so bad that some victims have spent a night in an emergency department. Health professionals who treated afflicted people saw swelling, blood-filled boils and ulcers – but they could find nothing to relieve the pain.

According to one poster to a Townsville community group on Facebook, it “feels like the seven rings of hell”.

Glenn King holds the discarded shell of a tarantula spider. Photo: David Kelly/The Guardian

But where unhappy gardeners see an enemy, Walker sees a potential ally. “Caterpillars are my favorite venomous animal at the moment,” he says.

Walker, a molecular entomologist at the University of Queensland’s Institute of Molecular Bioscience, has characterized the venoms of some of the world’s least-studied venomous animals, including centipedes, assassin bugs and various caterpillars.

Together with Glenn King, a friendly biochemist who leads the Institute’s “bugs and drugs” group, and a former colleague, Volker Herzig, the group collected venom from more than 500 species and built up an unparalleled collection of animal toxins.

Red tiger assassin bugs, common in Brisbane’s bushland. Photo: David Kelly/The Guardian

“It’s by far the largest invertebrate venom library in the world—probably the largest venom library in the world,” King says.

As it includes venoms from Australian tarantulas, a Brazilian caterpillar and the deadly funnel web spider, it could even be considered the deadliest library in the world. But researchers like King and Walker aren’t interested in poisons’ ability to kill.

They want to use it to heal.

Qenom is, in the simplest terms, a toxin delivered by one animal into another. But that definition diminishes toxins’ complexity – they are composed of rich cocktails of molecules. More than 200,000 species on Earth are venomous and each has developed its own set of biological weapons to help it kill prey or, as with the caterpillar, defend against it.

By studying the molecules that make up venom, scientists have been able to develop compounds that can relieve chronic pain, treat diabetes and create eco-friendly insecticides. So far, six venom-derived therapeutics have been approved for use in humans.

Many toxins are adept at a piece of mammalian cellular machinery known as a ion channel. These channels are used for everything from breathing to muscle contraction and neural signaling.

Andy Walker in the cold room, where freezers set at -80C house precious biological samples, including 500 different toxins. Photo: David Kelly/The Guardian

Scientists like King and Walker use that quirk of nature to their advantage: By identifying key molecules in venom that interact with ion channels, they hope to uncover molecules that can target those channels, ultimately leading to the creation of targeted therapeutics.

A toxin library supercharges 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 disorder where we think an ion channel may be involved in the disease,” says King.

ohOn a hot Brisbane morning in early April, Walker leads me through double locked doors to the institute’s insect. There are signs on the walls outside about the dangers that may lurk within; chief among the threats is the funnel web.

Inside, the space is not much bigger than an apartment bedroom. The sterile white and windowless laboratory is characterized by three large gray cabinets – the kind you might find at a large hardware store. Walker opens one, picks out a plastic lunch box and lifts the lid.

It’s not a funnel web, to my relief. This is Hector, the institute’s “media-trained” rainforest scorpion. Walker places it in my hands.

skip past newsletter promotion

From top: a tarantula is anesthetized with dry ice before venom is extracted; spider specimens at the Institute for Molecular Bioscience Photo: David Kelly/The Guardian

To date, snakes have provided the most useful venoms for human drugs and therapies. Scorpions, such as Hector, and spiders – belonging to the same class of animals – have long provided useful insights into venom, although no therapeutic compounds have been developed from them. The bugs and drugs group hopes to change that.

Using the venom library, the University of Queensland team, together with scientists from Monash University, characterized the venom of a subspecies of funnel web spider and discovered a peptide with powerful physiological effects. Known as Hi1a, the small protein blocks a signaling pathway that tells cells to die when there is a shortage of oxygen. When given to patients who have had a heart attack or stroke, Hi1a can protect against extensive, lasting damage.

In animal models, studies have suggested that the molecule may have protective effects against heart attack. It is planned for preliminary human clinical trials in 2025.

As Hector rests peacefully in my palm, Walker explains how his research has moved him from neuroscience to studying silk proteins, now looking beyond scorpions and spiders.

“My idea was that, if you went to another group of animals that had evolved venom independently, you would start to see many 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 milk yield of a spider can be measured in microliters. Venom yield in caterpillars is measured in nanoliters – amounts barely detectable in a test tube.

King says it would have been impossible to study this amount of venom just 20 years ago, but technological advances have enabled researchers to identify peptides from minuscule volumes. This resulted in a few surprises.

Dani Rojas-Azofeifa, Andy Walker and Glenn King examine a live scorpion in their University of Queensland laboratory. Photo: David Kelly/The Guardian

For one, caterpillar venoms have been predicted to contain simple peptides and proteins – much like bee venom – because they are used purely for defense. But Walker’s studies have shown that the molecules produced in caterpillar venoms are much more complex than expected.

In the case of the aspen caterpillar, a moth larva that looks like a toupee, Walker evidence found that it may have acquired its toxic abilities through gene transfer with bacteria many millions of years ago. In research yet to be published, he suggests that the electric caterpillar may have undergone a similar process.

Both species contain toxins rich in molecules capable of punching holes in a cell membrane, causing an attacking animal to feel pain.

A funnel web spider. Photo: David Kelly/The Guardian

These proteins provide a possible route to new insecticides and therapeutics. 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 stresses, but there are immediate benefits to understanding what its venom is made of – especially if you’re a north-east Queensland resident.

Electric caterpillar envenomation has been notoriously difficult to treat. Ice packs don’t seem to work. An insect bite gel? Forget about 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 at the university cafe to talk about caterpillars, they are devising a potential 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 may be the best course of action for suffering patients.

Walker didn’t seem entirely convinced, but decided to email a health professional in north-east Queensland who was looking for answers. Maybe he finally found one.

Source link

Leave a Reply

Your email address will not be published. Required fields are marked *