PAIN BARRIER
Being stung by scorpions, spiders, bull ants and wasps is all part of Dr Samuel Robinson’s ground-breaking scientific research
The sting of the bark scorpion, says Dr Samuel Robinson with good authority, is not so bad, kind of like a brief encounter with a low-voltage barbed-wire fence. For a whiff of expired parmesan cheese just before the sensation of having a staple fired into your thumb, the assassin bug is the go-to critter. Touch an angry redheaded centipede and a hot, cramp-like ache will build and spread, like a plant taking root in your arm. And that plant is on fire.
But for a truly gripping and shockingly powerful sting, it’s hard to go past the Australian spider-hunting wasp, that hefty orange and black insect that paralyses huntsman spiders and drags them off to its lair to lay eggs on them, providing a ready meal for the newborns as they emerge.
“These wasps look really intimidating and they hurt like crazy,” says Robinson. “It’s this shooting pain, sort of like jamming your hand in a door but it’s got an electrical component to it.”
There’s footage of Robinson, 34, at home in Logan, holding the wasp in large tweezers and applying it to his pinky finger. He lets out an immediate gasp of pain, then a series of “oww-awws”. He squats and doubles over as he battles the pain. His finger beads with sweat. A photograph taken an hour later shows the pinky is swollen, with a reddish rash spreading across his palm.
Robinson has done this to himself about 180 times. He’s stuck his finger at bees, wasps, ants, scorpions and spiders, then rated and described the pain. He’s even got an Excel spreadsheet.
All in the name of science. The creepy, itchy, freaky world of stinging insects and plants that can fell a grown man fascinates Robinson, a research fellow at the University of Queensland’s Institute for Molecular Bioscience.
What clues do those stings give about the chemicals in the toxins? What do those toxins target in a human body? And how can that power be analysed, understood and harnessed to help overcome pain?
Humans have exploited the natural world in our search for medicines for millennia. Without willow bark, we wouldn’t have aspirin, for example.
But the complex molecular structure of the toxins of insects have only been able to be truly understood with the advent of new DNA technologies, driven by the Human Genome Project of the early 2000s. Scientists such as Robinson are using these technologies to unlock nature’s medicine cabinet – and the secrets of our nervous system – with the hope of producing drugs to alleviate pain, reduce chemotherapy side-effects or better control diabetes.
It’s highly skilled laboratory work that doesn’t really require getting stung. But when Robinson was setting up his research program to discover the molecular makeup of toxins in stings, he thumbed through first-hand reports about “strange and unusual” stings that were worth studying.
One of them was the sting of the gympiegympie, colloquially known as the “suicide tree” because the pain it causes is said to have driven people to kill themselves.
“As I was writing it up, I was like, ‘This seems a bit hypocritical; I’m using other people’s information’,” says Robinson.
So, one day on a walk in Main Range National Park near Warwick, he stuck his finger into “a nice big spine on the stem” of a gympie-gympie.
“And it was like, Tcchhoowww! This shooting pain, the kind you’d expect from an ant or a wasp, very intense and lasts a long time,” says Robinson.
Most people would call it quits after that. Not Robinson. “I thought, ‘Well, there’s no reason I can’t do this with a bunch of stuff’.”
The suburban Queensland backyard offers a cornucopia of stinging things. No need to head to a rainforest, says Robinson. He just sits out the back for an hour or two, with a net and container at hand, and waits for them to flutter or crawl by.
He’s been doing that since he was a kid. Granted, that was in New Zealand which just isn’t as “special” as Australia in terms of things that sting. But Robinson was the boy who always had a jar filled with insects and lizards, little critters that filled him with wonder.
At the University of Auckland, Robinson
planned to become a doctor but he just couldn’t stop taking electives in biology and before he knew it, he was way down the path of biomedical science. He joined a molecular neuroscience lab after graduating, then headed to Melbourne in 2011 to do a PHD at Monash University.
“I wanted to study toxins that can be used as tools (to understand how neurons work) and I’d seen this work on cone snails, sea snails that sting fish and paralyse them and I thought, ‘Those are really cool’.”
His discoveries in this emerging field were groundbreaking, leading to him being awarded the highly prized Mollie Hollman doctoral medal of excellence in 2015.
Robinson adapted a process using highthroughput DNA sequencing to determine every single toxin in a cone snail’s venom. “Those techniques have been applied all over the world now,” he says.
He also revealed two interesting elements of the toxins that continue to be investigated by other scientists. One was a peptide in one type of cone snail’s toxin that was an analgesic, a possible alternative to opioids.
“Opioids are great painkillers but you get dependent on them so there’s a big gap for new painkillers,” Robinsons says.
The other was the insulin molecule that a different cone snail uses to sedate fish. “This snail opens up its mouth like a net to swallow the fish but the fish needs to be dopey first, so the snail releases the insulin into the water and the fish becomes lethargic.” The effect on the fish was immediate.
Robinson points out that while insulin has been saving the lives of diabetics for years, it has a limitation: it takes about 15 minutes to work.
“Drug companies have been trying to reduce that time for 40 years, pumping millions into it and we just found it in this snail,” he says.
“So that’s being developed now as a faster acting insulin.”
A couple of years at the University of Utah followed, where he became adept at experiments that screen hundreds of toxins to identify if any target particular components of neurons that are the focus of a scientist’s work, in the hope of developing drugs. Such methods have led to important discoveries in areas such as stroke and epilepsy.
But when Robinson returned to Australia in 2017, he wanted to turn that on its head. He wanted to start with the insect.
“Because I was more interested in the biology, I wanted to know what the toxin was actually doing for that animal, not what we wanted it to do,” he says. “When I do that experiment, it’s not a needle in a haystack. I find the toxin that causes pain.”
Pain is a curious thing. You hit your finger, it hurts. But the pain is not actually in your finger. It’s happening in your brain. The nerve ending sends a signal all the way to your spinal cord, which sends another signal to your brain which says “ouch”.
Once Robinson finds the make-up of the toxin, he can synthetically create it and “do all sorts of stuff to it” to figure out how it causes pain in humans.
“Some animals are using really interesting molecules to cause pain; molecules that are targeting things on our nerves that we don’t even know are on our nerves.”
These discoveries can help “rewrite the textbook” on how pain signalling works.
“You can figure out how all those individual components in your nerves are involved in pain signalling,” Robinson says. From there, other scientists at IMB or elsewhere can apply that knowledge.
“It can tell us that a particular ion channel receptor component of your nerve is important in a particular type of pain, therefore you can go and design a drug – or screen drugs – to target that component and you’ve got a new painkiller.”
Already, Robinson’s work on the toxins of the bull ant, green ant and the gympie-gympie have given exciting leads.
He found a molecule in the bull ant toxin that sensitises the neurons of mammals, making the nerve easier to activate.
There was anecdotal evidence of this, with reports of subsequent stings by bull ants hurting more than the first. It’s useful for the bull ant: if an echidna finds an ant nest but the pain from a defensive bull ant’s bite gets worse every bite, it might decide to find a feed elsewhere.
(AUSTRALIAN SPIDER-HUNTING) WASPS LOOK REALLY INTIMIDATING AND THEY HURT LIKE CRAZY. IT’S THIS SHOOTING PAIN, SORT OF LIKE JAMMING YOUR HAND IN A DOOR BUT IT’S GOT AN ELECTRICAL COMPONENT TO IT
Robinson has shown that the molecule targets the EGF receptor, which is associated with some cancers but “something we didn’t know was having a role in pain or that its role was to sensitise neurons”.
“We’ve provided that evidence that it causes hypersensitivity if it’s activated and we learned that from the humble bull ant,” says Robinson.
“So now we know that’s a druggable target in the context of long-term pain, imagine a scenario where a person has a certain type
of pain that involves hypersensitivity … targeting that receptor and blocking it might be a solution.”
He’s also figured out the toxin in the green ant sting that causes pain.
“That pain just builds and builds and builds,” he says. “It’s targeting something in your nerves, the sodium channel, that’s important for sending a signal … so it hits that target and it over-activates it, like your nerve is constantly detecting this painful stimulus.
“That tells us something new about the sodium channel, and possibly a way of precisely targeting that to affect other types of pain.”
And then there’s his first documented stinger, the gympie-gympie. After Robinson was stung, he experienced what others have reported; a return of pain when the sting spot hits cold.
“You might jump into a swimming pool or put a cold drink on it and the pain comes straight back,” says Robinson.
“It’s quite amazing and it will do that months afterwards.”
It’s a reaction known as cold allodynia, a debilitating condition that some chemotherapy drugs can cause.
“No one knows why it is, there’s no treatment,” says Robinson. For some patients, the pain caused by cold is so excruciating, they stop taking the medication.
Now, the toxin of the gympie-gympie is being studied by Dr Irina Vetter at IMB.
“The toxin might tell us what the molecular mechanism is behind that side effect,” says Robinson, “and we may be able to come up with a way of preventing that pain.”
There’s a world of stinging, itching, tingling
stuff out there and Robinson has only scratched the surface. One of the insects he’s keen to let loose on his skin is the bullet ant of Central and South America, known in the Indigenous language as “one who wounds deeply”.
The “King of Stings”, US entomologist Dr Justin Schmidt, considers it the most painful insect sting, “like walking over flaming charcoal with a three-inch nail embedded in your heel”.
Schmidt, 74, created the Schmidt pain index in the 1980s and has documented his experience of the pain of various stings.
The index goes from 1 to 4, calibrated by the familiar honey bee sting at 2. He gave the bullet ant a 4+.
Robinson is now good friends with Schmidt and uses the index for his work; the Australian spider-hunting wasp, for example, came in at 4. But Schmidt’s interest is from an insect evolution view point. Robinson has the molecular biology skills to turn those stings into knowledge that could unlock the mysteries of how pain is activated within the human body. And how to treat it.
So if you see a lanky bloke creeping up on a bug with his little butterfly net like a wide-eyed kid, don’t scoff: it could be Dr Sam Robinson, pursuing his dream of putting an end to pain.