‘I didn’t mean to hurt you’: new research shows funnel webs don’t set out to kill humans

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Bryan Fry, The University of Queensland and Volker Herzig, University of the Sunshine Coast

Funnel webs are considered one of Australia’s most fearsome spiders, but their ability to kill humans is by accident rather than design, our new research shows.

In findings published today, we reveal how the highly toxic and quick-acting venom of male funnel-web spiders is likely to have developed as a defence against predators.

When male funnel-web spiders are young, their venom is potent mainly to insects, which they eat. But once males start searching for a female mate, they must leave the safety of their burrows. That’s when their venom becomes potent to vertebrates such as reptiles and mammals – including humans.

So while humans can theoretically die from a funnel web bite, this is just an evolutionary coincidence – our research suggests the spiders aren’t specifically out to get us.

Funnel webs are among Australia’s most feared spiders.
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Why so deadly?

About 15% of all animals use venom for reasons such as to kill or immobilise prey, self-defence or to gain advantage over competitors, such as during breeding season. As an animal matures and its activities change, so too can its venom.

Australian funnel webs are among a small group of spiders whose venom can kill humans. However all 13 recorded deaths occurred before anti-venom was introduced in 1981.

Funnel web venom is lethal because it contains a type of neurotoxin called “delta-hexatoxin”. This toxin can kill humans by attacking the nervous system, keeping nerves “turned on” and firing over and over again. In severe cases the venom can cause muscles to go into spasm, blood pressure to drop dangerously, coma and organ failure, and ultimately death – sometimes within a few hours.

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Scientists have long been puzzled by why these toxins are so deadly to humans, when we and other primates have never been funnel web prey or predator. Scientists were also perplexed as to why male funnel webs appeared to have much deadlier venom than females, and caused most human deaths.

However we did know most funnel web bites in humans occur during the spiders’ summer mating season, when the male spiders rarely feed. This suggested the venom played a defensive role.

Venom from a male funnel web spider can kill vertebrates, including humans.
David Wilson

Spider sleuthing

We set out to solve this mystery, using molecular analysis of the venom. Although 35 species of Australian funnel-web spiders were officially recognised, only nine delta-hexatoxins from four species had previously been identified. Our analysis increased the number of known delta-hexatoxins to 22, from the venom of ten funnel-web species.

Having this extra data helped us paint a much clearer picture of the venom’s story. It all comes down to natural selection – the process where organisms best adapted to their environment survive and procreate. The genes responsible for this success are preserved and carry on to the next generations, driving the process of evolution

Our data revealed how natural selection triggered a change in the venom of adult male funnel webs. When males sexually mature, they leave the safety of their burrow and wander considerable distances to find a female. This puts male funnel web spiders in the path of vertebrate predators. These can include reptiles (such as lizards or geckos), marsupials (such as antechinus and dunnarts), mammals (such as rats) and birds.

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When funnel-web spiders evolved millions of years ago, toxins in its venom mainly targeted their natural prey: insects such as cockroaches and flies. We examined the genetic sequences of all delta-hexatoxins in funnel web venom. We found over time, the venom of adult males evolved to be potent to vertebrate predators. Unluckily for humans, who are vertebrate animals, we copped it in the process.

Female funnel webs stay safely in their burrows and let the males come to them. So the venom of females is thought to remain potent only against insects their entire lives.

Female funnel webs stay in their burrows, so are less likely to be eaten by predators.
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Take comfort

Now armed with a stronger understanding of how delta-hexatoxins evolved, we want to put that knowledge to use. The new genetic sequences we discovered will enable a better understanding of what funnel web spider venom does to the human body. This could be critical for improving existing anti-venoms, and for designing evidence-based treatment strategies for bite victims.

We’re not just looking at the venoms of sexually mature males. We’re also examining female funnel-web venom, hoping their insect-specific toxins will lead to new types of insecticides which are less harmful to non-target insects and the broader environment.

Funnel webs may be one of Australia’s most deadly spiders. But perhaps its some comfort to know their venom is not targeted against us, and the potential lethal effects are just a stroke of evolutionary bad luck.

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Bryan Fry, Associate Professor, School of Biological Sciences, The University of Queensland and Volker Herzig, Associate Professor, University of the Sunshine Coast

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

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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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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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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.

How we used CRISPR to narrow in on a possible antidote to box jellyfish venom

Venom from box jellyfish causes extreme pain and tissue damage. Massive exposure can cause death.
from www.shutterstock.com

Greg Neely, University of Sydney

Warm Australian waters are home to the box jellyfish (Chironex fleckeri), which is considered to be one of the most venomous animals on the planet.

Box jellyfish stings lead to excruciating pain lasting days, tissue death and scarring at the site of the sting, and with significant exposure, death within minutes. While most jellyfish stings do not lead to death, pain and scarring is quite common.

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Despite its potent ability to cause pain and death, to date we’ve had very little understanding of how this deadly venom works. This makes it very difficult to understand how it can cause so much pain – and how to develop medicines to block venom actions.

Published today, our new research has uncovered a potential antidote for box jellyfish venom. By working with humans cells and the gene-editing tool CRISPR, we identified a common, cheap drug that is already on the market and which could be a candidate for treating box jellyfish stings.

Flipping all the switches

This work began in 2012, when we set out to determine what it was about box jellyfish venom molecules that made them so effective in causing pain and damage.

The venom didn’t seem to work through the known pathways that cause cell death. So we used CRISPR genome editing technologies in human cells grown in the laboratory. This let us systematically turn off each gene in the human genome, and test to see which of these is needed for the jellyfish venom to kill the cells.

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It’s kind of like flipping all the switches in a house, trying to figure out which one turns off the kitchen lights, but at the whole genome level. We actually didn’t even know if it would be possible to find single genes that when turned off could block the venom action.

But luckily, we were successful. While normal human cells exposed to venom die in the laboratory within five minutes, we identified gene-edited cells that could last for two weeks continually exposed to venom.

Putting the evidence together

Then using new DNA sequencing technologies (that allow us to identify CRISPR guide RNAs targeting specific genes), we identified which human genes had been switched off in our genome editing experiments.

By putting the evidence together, we worked out which genes the box jellyfish venom needs to target in order to kill human cells in the lab.

One we identified is a calcium transporter molecule called ATP2B1, and is present on the surface of cells.

We tested a drug that we know targets this gene. If we added the drug before the venom, we could block cell death, but if we added the drug after the venom, it didn’t have any effect.

So this helped us understand more about how the venom works – and maybe even how it causes pain. We are still looking at this particular pathway in more detail, but at the moment it doesn’t seem promising for a therapy.

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Stopping cell death

Next we looked at the pathways involved in how box jellyfish venom kills cells.

We found four of the top ten genes required for venom action were all part of a pathway that makes cholesterol in cells.

Since cholesterol has been heavily studied over the last 30 years, there are already drugs available that target lots of different steps in cholesterol regulation. We focused on drugs that could bind to cholesterol and remove it quickly, basically acting like a cholesterol sponge.

We found these drugs could completely block the box jelly fish venom’s ability to kill human cells in the lab if added before venom exposure. We also found there is a 15-minute window after venom exposure where if we add this cholesterol sponge, it still blocks venom action.

This was exciting, as the capacity to have effect after the venom means the drug could work as a treatment in the case of being stung by a box jellyfish.

So far our additional studies show that these same drugs can block pain, tissue death and scarring associated with a mouse model of box jellyfish stings.

Moving towards a human treatment

The really cool thing about this work is that the potential box jellyfish antidote we found is in a family of drugs called cyclodextrins. These are known to be safe for us in humans, and are cheap and stable.

So now we are trying to work with the state or national government, or first responders, to see if we can move this venom antidote forward for human use.

As well as developing a topical application at the site of a sting, we also aim to develop this idea as a potential treatment for cardiac injection in the emergency room in the case of very severe box jellyfish sting cases.

Greg Neely, Associate Professor , University of Sydney

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

Snake venom can vary in a single species — and it’s not just about adaptation to their prey

Wolfgang Wüster, Bangor University and Giulia Zancolli, Université de Lausanne

Few sights and sounds are as emblematic of the North American southwest as a defensive rattlesnake, reared up, buzzing, and ready to strike. The message is loud and clear, “Back off! If you don’t hurt me, I won’t hurt you.” Any intruders who fail to heed the warning can expect to fall victim to a venomous bite.

But the consequences of that bite are surprisingly unpredictable. Snake venoms are complex cocktails made up of dozens of individual toxins that attack different parts of the target’s body. The composition of these cocktails is highly variable, even within single species. Biologists have come to assume that most of this variation reflects adaptation to what prey the snakes eat in the wild. But our study of the Mohave rattlesnake (Crotalus scutulatus, also known as the Mojave rattlesnake) has uncovered an intriguing exception to this rule.

What’s in those glands? It depends where you are!
W. Wüster

A 20-minute drive can take you from a population of this rattlesnake species with a highly lethal neurotoxic venom, causing paralysis and shock, to one with a haemotoxic venom, causing swelling, bruising, blistering and bleeding. The neurotoxic venom (known as venom A) can be more than ten times as lethal as the haemotoxic venom (venom B), at least to lab mice.

The Mohave rattlesnake is not alone in having different venoms like this – several other rattlesnake species display the same variation. But why do we see these differences? Snake venom evolved to subdue and kill prey. One venom may be better at killing one prey species, while another may be more toxic to different prey. Natural selection should favour different venoms in snakes eating different prey – it’s a classic example of evolution through natural selection.

This idea that snake venom varies due to adaptation to eating different prey has become widely accepted among herpetologists and toxinologists. Some have found correlations between venom and prey. Others have shown prey-specific lethality of venoms, or identified toxins fine-tuned for killing the snakes’ natural prey. The venom of some snakes even changes along with their diet as they grow.

We expected the Mohave rattlesnake to be a prime example of this phenomenon. The extreme differences in venom composition, toxicity and mode of action (whether it is neurotoxic or haemotoxic) seem an obvious target for natural selection for different prey. And yet, when we correlated differences in venom composition with regional diet, we were shocked to find there is no link.

Variable venoms

In the absence of adaptation to local diet, we expected to see a connection between gene flow (transfer of genetic material between populations) and venom composition. Populations with ample gene flow would be expected to have more similar venoms than populations that are genetically less connected. But once again, we drew a blank – there is no link between gene flow and venom. This finding, together with the geographic segregation of the two populations with different venoms, suggests that instead there is strong local selection for venom type.

Mohave rattlesnake feeding on a kangaroo rat, one of its most common prey items.
W. Wüster

The next step in our research was to test for links between venom and the physical environment. Finally, we found some associations. The haemotoxic venom is found in rattlesnakes which live in an area which experiences warmer temperatures and more consistently low rainfall compared to where the rattlesnakes with the neurotoxic venom are found. But even this finding is deeply puzzling.

It has been suggested that, as well as killing prey, venom may also help digestion. Rattlesnakes eat large prey in one piece, and then have to digest it in a race against decay. A venom that starts predigesting the prey from the inside could help, especially in cooler climates where digestion is more difficult.

But the rattlesnakes with haemotoxic venom B, which better aids digestion, are found in warmer places, while snakes from cooler upland deserts invariably produce the non-digestive, neurotoxic venom A. Yet again, none of the conventional explanations make sense.

Clearly, the selective forces behind the extreme venom variation in the Mohave rattlesnake are complex and subtle. A link to diet may yet be found, perhaps through different kinds of venom resistance in key prey species, or prey dynamics affected by local climate. In any case, our results reopen the discussion on the drivers of venom composition, and caution against the simplistic assumption that all venom variation is driven by the species composition of regional diets.

From a human perspective, variation in venom composition is the bane of anyone working on snakebite treatments, or antidote development. It can lead to unexpected symptoms, and antivenoms may not work against some populations of a species they supposedly cover. Anyone living within the range of the Mohave rattlesnake can rest easy though – the available antivenoms cover both main venom types.

Globally, however, our study underlines the unpredictability of venom variation, and shows again that there are no shortcuts to understanding it. Those developing antivenoms need to identify regional venom variants and carry out extensive testing to ensure that their products are effective against all intended venoms.

Wolfgang Wüster, Senior Lecturer in Zoology, Bangor University and Giulia Zancolli, Associate Research Scientist, Université de Lausanne

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

Like alchemists with killer precision, brown snakes make different venoms across their lifetime

Timothy N. W. Jackson, University of Melbourne

It’s spring in Australia and that means reptiles are starting to move about again. Including snakes.

The venom of the eastern brown snake (Pseudonaja textilis) is, drop for drop, one of the most potent of any venoms tested on laboratory mice.

Venoms work by targeting the bitten animal with deadly chemicals. And our recent research shows toxins in the venom of eastern brown snakes change as the snakes grow from juveniles to adults. It’s the first example of a significant age-related change in venom from an Australian snake.

It’s a beautiful example of evolutionary adaption, in which the chemistry of the snake’s venom appears to change in parallel with its diet.

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What is snake venom?

Venoms are typically a mixture of different toxins, each of which attacks the system of a potential prey animal or predator in a different way.

Sometimes toxins work together, each making the other more powerful, and sometimes they work completely independently, engaging in chemical warfare on multiple fronts.

Brown snake venom contains many toxins, but there is one toxin above all others that is responsible for the life-threatening effects of bites to humans. This toxin is a “haemotoxin”, which means it attacks the blood.

The haemotoxin starts clotting the blood at an extremely elevated rate, using up all of the coagulation factors, which clot the blood under normal circumstances. When all these are used up, the victim is at risk of bleeding to death.

In the worst case scenario this toxin, perhaps working with others, gives the system such a shock that people collapse within a short period of time following the bite. In this situation, immediate CPR can be the difference between life and death.

Why venom evolved

Venom is a tool that has evolved in snakes to help them secure a meal: it gives them a chance of overpowering animals that would otherwise be very difficult for them to subdue. Venom and its toxins are therefore “designed” (by evolution) to mess up the normal operations of a prey animal’s body.

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The best toxins for this purpose may differ according to the specific type of prey animal (e.g. mammal or reptile), or the condition of that prey animal (e.g. whether it is active or inactive) when the snake finds it. As a result, we often find snakes that feed upon different types of animals have different toxins in their venoms.

This starts to get really interesting when you consider brown snakes, because adult brown snakes seem to have quite different diets from baby brown snakes.

Testing a venom hypothesis

Age-related shifts in venom chemistry have already been demonstrated for the venoms of a few species of pit vipers from the Americas, but not for anything even remotely related to Australian brown snakes.

This wasn’t because people hadn’t looked – several species of Australian snake had been investigated, but no evidence of a significant age-related change in venom had been found for any of them. This made sense to me, because none of those snakes dramatically change their diets throughout their lives.

Brown snakes are special – as far as we know the juveniles eat lizards almost exclusively, whereas the adults are generalists that eat a lot of mammals.

Baby snake venom is different

When we compared venom in adult and baby brown snakes, we did indeed find them to be different. Baby brown snake venom seems to entirely lack haemotoxins: instead, it’s almost exclusively composed of neurotoxins – toxins that attack nerve junctions.

What this suggests is that the haemotoxins that are so dangerous to humans (and lab mice) aren’t very effective against the lizards that baby brown snakes eat. We can make this dietary link with a degree of confidence because many other Australian snakes that feed exclusively on lizards have similar venom – no haemotoxins, only neurotoxins.

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We don’t yet know what this means from a clinical perspective. It may be that baby brown snake venom is less dangerous to humans than adult brown snake venom, but the opposite might also be true – brown snake antivenom might be less effective against the venom of the babies.

There has been at least one fatal bite from a very small brown snake in Australia, so they must be treated with respect at any age.

As always, the best policy for snakes is to leave them alone and let them go about their business, and to teach children to do the same – snakes want no more to do with us than we want with them.

Timothy N. W. Jackson, Postdoctoral Research Fellow, Australian Venom Research Unit, University of Melbourne

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.

Mortal poison: the story of how venom works

Ken Winkel, University of Melbourne

Centuries ago it was thought that snakes caused their deadly effects because of “a mortal poison that lurked in the bile”. It wasn’t until the 17th century that Italian doctor Francesco Redi (1626-1697) conclusively located the poison as being in the yellow liquid from glands attached to the two front teeth of venomous snakes.

Shortly afterwards, English physician Richard Mead (1673-1754) went one step further and personally drank, without ill effect, viper venom to show that it must be injected into the body to cause harm.

The study of venom has progressed so that we now have a detailed understanding of what’s in venom and how the constituent toxins work. The major ways that venom can be a “mortal poison” are explained below.

Neurotoxins

Perhaps the most common type of poison in animal venoms is the nerve toxin. This group can acts in diverse ways to block or over-stimulate the nervous system – rarely a good thing.

The most dangerous of these are the ones that block nerve signalling, causing paralysis of the muscles required for breathing. Depending on the toxin, such paralysis may be very rapid (blue-ringed octopus venom can act within minutes) or take many hours (neurotoxins of the taipan snake typically progress over five to ten hours).

Francesco Redi worked out where the poison of venomous snakes is stored.
Public domain via Wikimedia Commons

The blue-ringed octopus shares a common toxin type with the puffer or fugu fish – most famous as Japan’s deadly delicacy. Both contain a very powerful nerve blocker called tetrodotoxin.

Typically, tetrodotoxin poisoning initially causes a tingling around the mouth. If the dose is high enough, this will be followed by progressive difficulty in breathing. And, if untreated, it may be fatal.

Snake venoms, by contrast, start their paralysing effects on the muscles around the eyes (typically manifest as fixed dilated pupils, reduced eye movements and droopy eyelids). If not treated with antivenom, these early signs will eventually be followed by increasing difficulty talking, swallowing and, ultimately, breathing.

The Australian paralysis tick also has neurotoxins but, unlike snakes, these toxins take many days to cause paralysis. It usually starts by causing weakness in the legs.

Many paralysing venoms contain a cocktail of molecules that act together but in different ways to interfere with the transmission of nerve impulses.

The most dangerous paralysing toxins destroy the nerves themselves. Some Australian snake venoms, such as the mainland tiger snake, contain both receptor blocking and nerve destructive types of neurotoxins. Once this latter type of damage occurs, it may take weeks for the nerves to repair and during this time you may not be able to breathe without external support.

Some venomous marine snails have tens of different types of neurotoxins in their venom and can control the mix of toxin types depending on whether they’re protecting themselves from attack or hunting prey.

Impact on blood and heart

Another potentially lethal effect of snakebite, rarely seen with other types of venoms, is altered blood clotting. Most of Australia’s dangerous snakes have toxins in their venom that cause the body to destroy factors that help clot blood.

As well as being extremely painful, a brush with a box jellyfish can kill you in minutes.
Jellyfish image from http://www.shutterstock.com

The eastern brown snake, for example, can cause a very severe clotting disturbance. This type of venom can cause the sudden death of some people bitten by these snakes.

Arguably the most dangerous venom in the world is that of the box jellyfish, Chironex fleckeri, because of its ability to kill a healthy adult human in minutes. This remarkable lethality is attributed to powerful toxins that are injected into the skin through millions of tiny venom-filled harpoon-like weapons on the jellyfish tentacles.

Once in the circulation, these toxins seem to home in on, and punch holes in, the outer membrane of heart muscle cells. These holes disturb the smoothly co-ordinated contraction of the heart muscles.

Unsurprisingly, left untreated, this form of venom toxicity can cause death soon after you’ve been stung.

Muscle destruction and pain

A more insidious effect, particularly of snake venoms, is muscle destruction known as myotoxicity. While not as quick as the effect on blood clotting, heart function or nerve signalling, myotoxicity can also be lethal.

Typically, snake venom toxins dissolve the membrane of muscle cells. Not only is this a painful experience, it also causes the muscle protein, known as myoglobin, to leak into the urine, potentially poisoning the kidneys in the process.

English physician Richard Mead (1673-1754) drank viper venom to show it must be injected into the body to cause harm.
Mezzotint by R. Houston after A. Ramsay via Wikimedia Commons, CC BY-SA

People bitten by tiger snakes occasionally require kidney dialysis because of this. In some Asian countries, such as Myanmar, snakebite is a leading cause of renal failure.

Myotoxicity can also lead to massive increases in blood potassium levels, leached from the injured muscle cells. This effect can itself cause fatal damage to the normal rhythm of the heart.

Although many venoms have evolved to rapidly paralyse and digest prey, another important venom action is defence.

Venomous bees, wasps and ants are well known to most of us because of the characteristic pain that’s produced by their stings. Stinging fish and most venomous jellyfish are also conspicuous by their more prolonged painful stings.

Aside from the physical trauma to the skin from a bite or a sting, these venoms frequently contain toxins that act in various ways to injure cells, trigger inflammation and even kill skin cells. All of this can cause severe pain. The stonefish and box jellyfish are examples of this potent venom effect.

However, least you think the news about venoms is all bad, it is worth recalling the words of Claude Bernard, 19th century father of experimental medical science. Concerning the wide utility of venoms as scientific tools he wrote: “Poisons are veritable reagents of life, extremely delicate instruments which dissect vital units”.

Indeed such “reagents” have aided in many past Nobel Prizes . But that’s another story…

Learn more about the story of venom at the Medical History Museum’s online exhibition.

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

Ken Winkel, Toxinologist; Senior Research Fellow, Australian Venom Research Unit, University of Melbourne

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