Australian stinging trees inject scorpion-like venom. The pain lasts for days

Fig B Dexcelsa.

Irina Vetter, The University of Queensland; Edward Kalani Gilding, The University of Queensland, and Thomas Durek, The University of Queensland

Australia is home to some of the world’s most dangerous wildlife. Anyone who spends time outdoors in eastern Australia is wise to keep an eye out for snakes, spiders, swooping birds, crocodiles, deadly cone snails and tiny toxic jellyfish.

But what not everybody knows is that even some of the trees will get you.

Our research on the venom of Australian stinging trees, found in the country’s northeast, shows these dangerous plants can inject unwary wanderers with chemicals much like those found in the stings of scorpions, spiders and cone snails.

The stinging trees

In the forests of eastern Australia there are a handful of nettle trees so noxious that signs are commonly placed where humans trample through their habitat. These trees are called gympie-gympie in the language of the Indigenous Gubbi Gubbi people, and Dendrocnide in botanical Latin (meaning “tree stinger”).

A casual split-second touch on an arm by a leaf or stem is enough to induce pain for hours or days. In some cases the pain has been reported to last for weeks.

A gympie-gympie sting feels like fire at first, then subsides over hours to a pain reminiscent of having the affected body part caught in a slammed car door. A final stage called allodynia occurs for days after the sting, during which innocuous activities such as taking a shower or scratching the affected skin reignites the pain.

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Read more:
‘The worst kind of pain you can imagine’ – what it’s like to be stung by a stinging tree

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How do the trees cause pain?

Pain is an important sensation that tells us something is wrong or that something should be avoided. Pain also creates an enormous health burden with serious impacts on our quality of life and the economy, including secondary issues such as the opiate crisis.

To control pain better, we need to understand it better. One way is to study new ways to induce pain, which is what we wanted to accomplish by better defining the pain-causing mechanism of gympie-gympie trees.

How does these plants cause pain? It turns out they have quite a bit in common with venomous animals.

The plant is covered in hollow needle-like hairs called trichomes, which are strengthened with silica. Like common nettles, these hairs contain noxious substances, but they must have something extra to deliver so much pain.

Earlier research on the species Dendrocnide moroides identified a molecule called moroidin that was thought to cause pain. However, experiments to inject human subjects with moroidin failed to induce the distinct series of painful symptoms seen with a full Dendrocnide sting.

Finding the culprits

We studied the stinging hairs from the giant Australian stinging tree, Dendrocnide excelsa. Taking extracts from these hairs, we separated them out into their individual molecular constituents.

One of these isolated fractions caused significant pain responses when tested in the laboratory. We found it contains a small family of related mini-proteins significantly larger in size than moroidin.

We then analysed all the genes expressed in the gympie-gympie leaves to determine which gene could produce something with the size and fingerprint of our mystery toxin. As a result, we discovered molecules that can reproduce the pain response even when made synthetically in the lab and applied in isolation.

The genome of Dendrocnide moroides also turned out to contain similar genes encoding toxins. These Dendrocnide peptides have been christened gympietides.

The most toxic of the stinging trees, gympie-gympie or Dendrocnide moroides.
Edward Gilding, Author provided

Gympietides

The gympietides have an intricate three-dimensional structure that is kept stable by a network of links within the molecule that form a knotted shape. This makes it highly stable, meaning it likely stays intact for a long time once injected into the victim. Indeed, there are anecdotes reporting even 100-year-old stinging tree specimens kept in herbariums can still produce painful stings.

What was surprising was the 3D structure of these gympietides resembles the shape of well-studied toxins from spider and cone snail venom. This was a big clue as to how these toxins might be working, as similar venom peptides from scorpions, spiders, and cone snails are known to affect structures called ion channels in nerve cells, which are important mediators of pain.

Specifically, the gympietides interfere with an important pathway for conducting pain signals in the body, called voltage-gated sodium ion channels. In a cell affected by gympietides, these channels do not close normally, which means the cell has difficulty turning off the pain signal.

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Read more:
Explainer: what is pain and what is happening when we feel it?

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Better understanding may bring new treatments

The Australian stinging trees make a neurotoxin that resembles a venom in both its molecular structure and how it is deployed by injection. Taking these two things together, it would seem two very different evolutionary processes have converged on similar solutions to win the endgame of inflicting pain.

In the process, evolution has also presented us with an invaluable tool to understand how pain is caused. The precise mechanisms by which gympietides affect ion channels and nerve cells are currently under investigation. During that investigation, we may find new avenues to bring pain under control.

Irina Vetter, Australian Research Council Future Fellow, The University of Queensland; Edward Kalani Gilding, Postdoctoral Research Officer, The University of Queensland, and Thomas Durek, Senior Research Fellow, The University of Queensland

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Animals and Pain

Suffering for science: why I have insects sting me to create a pain index

Justin Schmidt, University of Arizona

Over the past 40 years (but in reality since I was five years old), I’ve been fascinated with insects and their ability to sting and cause pain. In graduate school, I became interested in why they sting and why stings from such tiny animals hurt so much.

To answer these questions, we first needed a way to measure pain – so, I invented the insect pain scale. The scale is based on a thousand or so personal stings from over 80 insect groups, plus ratings by various colleagues.

Insects sting to improve their lives and increase their opportunities. The stings provide protection, thereby opening doors to more food resources, expanded territories, and social life within colonies. By studying stinging insects, we gain insight into our own lives and the societies we live in.

Why sting?

To say that insects sting “because they can” isn’t all that helpful. The real question is why insects evolved a stinger in the first place. Obviously, it had some value, otherwise it would have never evolved – or, if initially present, it would have been lost through natural selection.

Stingers have two major uses: to get food and to avoid becoming food for some other animal. Examples of the stinger used for sustenance include parasitic wasps that sting and paralyse caterpillars that become food for the wasp young, and bulldog ants that sting difficult prey insects to subdue them.

More importantly, the stinger is a major breakthrough in defence against large predators. Imagine, for a moment, that you’re an average-sized insect being attacked by a predator a million times larger than you. What chance would you have?

Honeybees face this problem with honey-loving bears. Biting, scratching or kicking won’t work. But a stinger with painful venom often does.

In this sense, the stinging insect has found a way to overcome its small size. The stinger is an “insect gun” of sorts – it neutralises the size difference between assailant and victim.

The insect sting pain index

This is where the insect sting pain index comes in. Unless we have numbers to compare and analyse, sting observations are just anecdotes and stories. With numbers, we can compare the effectiveness of one stinging insect’s painful defence against others and test hypotheses.

One hypothesis is that painful stings provide a way for small insects to defend themselves and their young against large mammalian, bird, reptile or amphibian predators. The greater the pain, the better the defence.

Greater defence allows insects to form groups and become complex societies as we see in ants and social wasps and bees. The greater the pain, the larger the society can become. And larger societies have advantages not enjoyed by solitary individuals or smaller societies.

Human and insect societies

Human sociality allows individuals to specialise and do a particular task better than most others. Examples of human specialists include plumbers, chefs, doctors, farmers, teachers, lawyers, soldiers, rugby players and even politicians (a profession sometimes viewed dubiously, but required for society to function).

Social insect societies also have specialists. They forage for food, tend to young, defend the colony, reproduce and even serve as undertakers removing the dead. Another advantage of societies is the ability to recruit others to exploit a large food source, or for the common defence, or to have additional helpers for difficult tasks.

Sociality also has a more subtle advantage: it reduces conflict between individuals within a species. Individuals not living in social groups tend to fight when they come in contact. But to live in a group, conflict must be reduced.

In many social animals, conflict is reduced by establishing a pecking order. Often, if the dominant individual in the pecking order is removed, violent battles erupt.

In human societies, conflict is also reduced via pecking order, but more importantly through laws, police to enforce laws, and gossip and societal teachings to instil co-operative behaviour. In insect societies, conflict is reduced by establishing pecking orders and pheromones, chemical odours that identify individuals and their place in society.

Why do we love pain?

The insect sting pain index also provides a window into human psychology and emotion. Put simply: humans are fascinated by stinging insects. We delight in telling stories of being stung, harrowing near-misses, or even our fear of stinging insects.

Why? Because we have a genetically innate fear of animals that attack us, be they leopards, bears, snakes, spiders or stinging insects.

People lacking such fear stand a greater chance of being eaten or dying of envenomation and not passing on their genetic lineage than those who are more fearful.

Stinging insects cause us fear because they produce pain. And pain is our body’s way of telling us that bodily damage is occurring, has occurred, or is about to occur. Damage is bad and harms our lives and ability to reproduce.

In other words, our emotional fear and infatuation with painful stinging insects enhances our long-term survival. Yet, we have little emotional fear of cigarettes or sugary, fatty foods, both of which kill many more people than painfully stinging insects. Fear of those killers is not in our genes.

The insect sting pain index is more than just fun (which it is too). It provides a window into understanding ourselves, how we evolved to where we are, and what we might expect in the future.

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This article is the final part of our series Deadly Australia. You can see the whole series here.

Justin Schmidt, Entomologist, Southwest Biological Institute, University of Arizona

This article was originally published on The Conversation. Read the original article.

Animal venoms don’t just cause pain, they may soon be a cure for it too

Richard Lewis, The University of Queensland

Bites or stings from venomous animals or insects can be dangerous; they lead to numerous fatalities globally each year despite the development of antivenoms that can neutralise many of their worst effects.

But research into their molecular components shows venoms aren’t all bad. Many contain bioactive components (mini-proteins or peptides) that are so stable to the body’s enzymes and selective of their biological target that they’re increasingly being used as new research tools.

They’re even being used as lead molecules in drug development efforts around the world.

Because of their often unique mode of action and exquisite selectivity, many of these peptides have the potential to identify new targets and approaches to treating diseases, especially where traditional approaches have failed.

Indeed, the fact that many venomous animals have evolved not just hundreds but often thousands of unique peptides makes venoms a largely untapped chemical treasure chest.

Blood clotting and pain killing

Two clinical areas where animal venom peptides have been particularly successful are in blood clotting and pain.

Snakes have evolved a range of toxins that either enhance or inhibit the rate at which blood clots.
F Delventhal/Flickr, CC BY

Snakes, in particular, have evolved a range of toxins that either enhance or inhibit the rate at which blood clots. Given most snake venom has evolved to prey on small mammals, it’s not surprising they also work on human blood.

When purified, these components can be developed into therapeutics to be used at the right dose and clinical setting, such as stopping bleeding during surgery.

Perhaps more surprising are the analgesic or pain-killing effects of venom peptides. Here, the most promising leads for developing drugs come from venomous invertebrates such as cone snails, spiders and scorpions that don’t prey on mammals.

Cone snail secrets

It seems some groups of animals have evolved venom components specifically for defence against vertebrate threats and not for predation. This was initially discovered in cone snails, which are marine molluscs that live mostly in warmer waters.

Cone snails are marine molluscs that live mostly in warmer waters.
Richard Ling/Flickr, CC BY-NC-ND

These snails have evolved different venoms in different sections of their venom duct. Amazingly, these venoms can be separately deployed, depending on whether the cone snail has identified a threat or prey. Analgesic peptides are concentrated in the venom they use to defend against larger invertebrate threats, such as octopus, and even fish.

Cone snail venoms contain relatively small and highly structured peptides, and the first marine drug found to be a painkiller – ω-conotoxin MVIIA or Prialt – comes from this venom. Another class of cone snail venom peptide called χ-conotoxins – originally discovered in Australia – also holds promise as a new class of analgesic.

There’s much untapped potential to find and validate new therapeutic targets and even to find leads to important new classes of drugs from venoms. This promise, coupled with our ability to apply technology that can help deliver peptides into the central nervous system, is expected to drive the expansion of venom peptide discovery efforts into the clinic.

This article is part of our series Deadly Australia. Stay tuned for more pieces on the topic in the coming days.

Richard Lewis, Professor & Director, Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland

This article was originally published on The Conversation. Read the original article.

Don’t go in the water: a world of pain awaits in Australia’s deep blue seas

Lisa-ann Gershwin, CSIRO

Australia’s reputation for deadly creatures of all kinds is known the world over. Tourists worry about it, and comedians have a field day with it. Here’s what Bill Bryson says in his book In a Sunburned Country:

[Australia] has more things that will kill you than anywhere else. Of the world’s ten most poisonous snakes, all are Australian. Five of its creatures – the funnel web spider, box jellyfish, blue-ringed octopus, paralysis tick and stonefish – are the most lethal of their type in the world.

Bryson certainly has a way with words. But, to be honest, he forgot a few things.

The long list

Australia has at least nine species of Irukandjis, a group of jellyfish so nasty that their drop-for-drop toxicity leaves the box jellyfish in the dust.

Impressive, considering the box jelly has long been considered the world’s most venomous animal. A massive sting from a box jelly kills in as little as two minutes; for other victims, it’s generally painful with some scarring, but that’s about it.

Irukandji, in contrast, with just an imperceptible brush of venom leaves almost no mark. But after about a half hour you develop Irukandji syndrome, a debilitating mix of nausea, vomiting, severe pain, difficulty breathing, drenching sweating and sense of impending doom. You get so sick that your biggest worry is that you’re not going to die!

And that’s just the beginning: up to a third of victims require life support and a quarter have ongoing complications, including permanent heart damage or neurological damage.

Bryson also forgot the blue bottles that sting some 25,000 to 45,000 people each year in Australia, at least one species of which causes Irukandji syndrome.

And he forgot the bullrout, which is kind of a brackish-water version of the stonefish – caution, they hang out at boat ramps and these suckers hurt.

And stingrays, which combine stabbing and venom into the one injury. And the cone snail, which looks mild-mannered, but can imperil your life with one stab of its lightning-fast barb.

Then there are sea urchins and stinging hydroids and venomous sponges, which will put you in a world of hurt. But nobody ever thinks to include them.

And the sea snakes: if you get one in your fishing net, or your dive equipment, or your hair, remember the old adage “don’t grab a snake by its tail”. Well, I’m not sure if that’s an adage or not, but it should be. In fact, “don’t grab a snake” would be better.

Bryson also forgot the world’s only venomous mammal, the platypus: males have a venomous spur on the back legs, and they seriously hurt. And my new favourite, the arrow worm. Yes, the arrow worm.

Granted, there aren’t any reported deaths from arrow worms, but they deserve respect. They look like a beansprout with fish fins, with a fish tail at one end and rows of big scary spines at the other, which they use to grasp their food. And they “bite” with tetrodotoxin – the same venom that makes fugu (the pufferfish delicacy) and blue ring octopus so lethal.

And swans. Bryson forgot swans. At least three people have reportedly been killed by swans. I’m just sayin’. (Good news: these are not the native Australian black swans).

But why?

Okay, venomous beansprouts, swans and fear of not dying aside, what is it with Australia’s dangerous creatures? The typical explanation for powerful venoms is subduing dinner or dealing quickly with danger, especially for delicate creatures or those that aren’t able to track prey for long distances.

But certainly the box jellyfish’s venom is overkill, while the Irukandji takes too long. What’s more, fish don’t appear to get Irukandji syndrome … although I’ve never been sure how to tell if a fish is sweating.

Similarly, the dinner-or-danger hypothesis doesn’t seem to hold true for stabbing fish wounds, such as those delivered by stonefish, bullrouts and stingrays. Certainly, the stabbing must be far more effective than all but the most instant venom effects.

But one must keep in mind that these creatures evolved their toxins long before Homo sapiens fossicked the tide pools or snorkelled the reefs. So although their venoms can harm us, this may just be coincidental.

A question that often arises is what effect climate change will have on these creatures or their venoms. Well, the answer is we really don’t know yet.

With regard to species, there will be winners and losers. Many of the venomous sea creatures are tropical, and many tropical species are expanding southward. To what extent this may put the more populated southerly areas at higher risk is still unclear.

One group, however, seems particularly poised to benefit: the jellyfishes. As warmer water stimulates their metabolism, they grow faster, eat more, breed more and live longer. Irukandjis and box jellyfish become more toxic as they mature, so getting there faster and staying there longer could have undesirable outcomes for sea users.

How, then, can we possibly navigate these dangers when curious sea snakes want to swim with us, duckbilled platypus, stones and beansprouts must be viewed with suspicion, blue is sounding like the new warning colour, invisible jellyfish will lay us flat, and even the swans, a symbol of romance, are scary?

Four tips for keeping safe

Rule 1: First and foremost, try to make it a rule never to touch an animal that isn’t a personal friend. This will prevent the vast majority of bite and sting injuries, and not just from sea creatures.

Rule 2: Do the stingray shuffle when moving in sandy water: drag your feet in such a way that you’re continuously kicking sand in front to where you’re about to step. This will scare most creatures away so that you don’t step on them.

Rule 3: Wear protective clothing (a full-body lycra suit, for instance) when swimming in areas where box jellyfish or Irukandjis may appear. If stung by box jellyfish or Irukandjis or unknown jellyfish in the tropics, douse with vinegar to neutralise undischarged stinging cells.

Rule 4: Don’t try to make friends with swans.

Finally, read the Australian Resuscitation Council website for the latest on prevention and first aid for bites and stings.

This article is part of our series Deadly Australia. Stay tuned for more pieces on the topic in the coming days.

Lisa-ann Gershwin, Research scientist, CSIRO

This article was originally published on The Conversation. Read the original article.