Mortal poison: the story of how venom works

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).

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.

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.

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 receives funding from the NH&MRC.