Mastering venom

Venom was one of the first weapons to develop in animals through evolution, preceding speed, stealth and cunning by millions of years.

It has evolved independently several times and is now present in 25% of all animal groups, from scorpions to sedentary sea anemones.

Opportunistic humans were quick to find ways to use this natural phenomenon to their advantage - against predators, prey and even human competitors. Venom can be considered a weapon in one of the early forms of biological warfare.

Snakes on a plain

Humans using venom as a weapon can be traced back to antiquity.

One of its first uses was as coating for arrow tips, used to slow or kill enemies.

Scythian warriors used this tactic two thousand years ago - although venom was not the only thing coating the arrows. The soldiers are believed to have concocted a horrifying mixture of viper venom, human blood and animal faeces. They left this to putrefy underground before liberally applying it to arrow and spear tips.

Famous Cathaginian Hannibal Barca (247-181 BCE), considered one of the greatest military commanders in history, once commanded his crew to throw snake-filled pots onto enemy ships. Given the close confines, this unexpected method proved effective in both the element of surprise and delivering life-threatening bites.

A similar tactic was employed in 198 during the siege of the Hatra, an ancient fortress city in present-day Iraq, against future Roman emperor Septimius Severus. The inhabitants of Hatra rained venomous arthropods down on the attacking Roman army as they ascended the walls.

The insects may have included desert scorpions and assassin bugs, which were common in the area and known to deliver a nasty bite.

Severus abandoned the siege of Hatra after 20 days.

Medieval fascination

Dr Kathleen Walker-Meikle of King's College London collaborated on research for the exhibition Venom: Killer and cure. An expert on medieval medicine, she also (literally) wrote the book on medieval pet-keeping.

Her studies of domestic animals and rabid dogs led her to uncover what she describes as an 'almost excessive' interest in venomous snakes in medieval medical literature.

Medieval medical texts, particularly on herbals and poison, are full of descriptions of venomous creatures from far-off lands.

It is unlikely that Western medical practitioners would have ever encountered the vast array of snakes detailed in these texts (such as basilisks or 'the snake that makes blood pour out of all pores'), but medical volumes devote swathes of description to them all the same.

'The attention they pay to describing and identifying animals is very interesting and highly detailed,' Kathleen says.

'Authors pay great attention to the shape, size and number of puncture wounds, detailing all the gory symptoms and sometimes even the including geographical location and behaviour of the animals.'

'Authors might mention frogs or toads with poisonous skin and caterpillars with poisonous hairs, but it is venomous animals and their bite that they seem most interested in,' she says.

'In medieval times there was this biblical idea that humans are supposed to be on top and that the animals exist to serve them. Then there are all these animals behaving badly, going against the natural order of things by biting or eating you. 

'I do think they are slightly obsessed with snakes, and it could be for the same reason as we today are preoccupied with great white sharks,' Kathleen adds. 'Fear might a big part in the amount of priority and attention that are given to venomous creatures.'

Cure-alls and snake oils

Treatments for venomous snakebites changed relatively little over the centuries.

The medical texts of Avicenna, a Persian physician born around 980, remained integral to Western medicine until the seventeenth century, though some treatments still appear in popular culture today.

'The classic one of finding a willing party to suck venom out the wound we now know is really not the best thing to do if somebody has been bitten by a snake, but there are a great many accounts of this,' says Kathleen.

Theriac, a widespread historical concoction, has its origins in the ancient world. A universal cure for all kinds of ailments, it was considered a particularly effective treatment for venomous bites.

Although the recipe varied by physician and ailment, a number of key ingredients appeared frequently.

To make the famous Great Theriac, physicians would combine ground-up snakes with opium, herbs and spices, and other precious materials. Mummy powder (from real Egyptian mummies) was also sometimes added to the mix. Other varieties of theriac might include walnuts or rue (a herb noted for its application to heal snakebites).

'Theriac was hugely popular in the medieval and early modern periods and there is evidence of its use as late as the eighteenth century. 

'The term "snake oil" comes along a little later, but the idea that snakes boiled in oil were beneficial for all sorts of ailments has been around for a very long history,' Kathleen says.

'There are also some beauty remedies where you used bits of snakes and applied them to your face or drank them as a potion to make you look more fabulous,' she quips.

'Looking at history it's important not to get stuck on the question of whether a particular cure worked or not. It's about whether it worked for the people of the time and their understanding of the world.

'There is a tendency to look back at the history of medicine or science and prevailing theories of the time and think, "They are so backwards and we are so superior," but it's also an important reminder that the prevailing theories and approaches of any time are just that,' she says.

The first antivenom

Dr Léon Charles Albert Calmette (1863-1933) was a French biologist and immunologist.

Appointed director of the new Saigon (present-day Ho Chi Minh City in Vietnam) branch of the Pasteur Institute in 1891 by famed chemist Louis Pasteur himself, Calmette began studying bee and snake venoms.

That same year, heavy rains drove numerous cobras to take refuge in villagers' huts near Bac-Lieu in southern Vietnam. Four people died from snakebites.

Calmette began developping a serum to neutralise the cobra venom after 19 of the displaced snakes were delivered to him at the Institute.

He injected a number of animals with small amounts of the venom. The animals' natural immune systems fought the injected substance, releasing venom counteracting antibodies into the blood.

From the blood Calmette isolated a serum containing these toxin-fighting proteins, which would become the world's first snake antivenom.

The method was very similar to that used by Pasteur to create the rabies vaccine.

No universal cure

Over a century later, scientists are using a similar method for creating antivenom.

Museum venom expert Ronald Jenner says, 'Today antivenoms are made by injecting small amounts of a toxin into an animal. We collect the antibodies that bind to the toxins and prevent them from reaching their target.

'You then purify the antibodies and that's what you inject into a human - that's the antivenom.'

But antivenoms are created to target specific toxins.

'If you were bitten by a viper but given cobra antivenom, it wouldn't work, because antivenom has to be made from the species whose venom you want to neutralise.'

The complex chemical structure of an individual species's venom is part of why a universal cure remains for now a scientific pipe-dream.

A neglected disease

Currently it is not possible for scientists to formulate cures to the venoms of all species of toxic animal, nor would it be financially viable for manufacturers to produce them.

There are over 200,000 known venomous animal species on Earth. Bites from venomous snakes alone kill over 100,000 people each year.

The majority of envenomations occur across Africa, Asia and Latin America, affecting mostly agricultural workers and children.

Low production of vital antivenoms has resulted in a dramatic price climb over the last 20 years, putting life-saving treatments out of reach of the majority of those who need it most. A number of factors, including lack of clarity on the number and types of bites, as well as deficient distribution policies, mean that some manufacturers have ceased the production of vital cures.

In June 2017 the World Health Organization designated envenomation by snakebite a neglected tropical disease.