The deadly poison lurking in a frog the size of your fingernail

Brachycephalus verrucosus: packing some punch. Marcio Pie, CC BY-NC-SA

The unexplored regions of the world continue to shrink. Satellites are able to give us previews of places humans have never been and fewer and fewer native tribes remain uncontacted.

It’s not just undiscovered humans, though; seven new species of tiny frogs – the size of your fingernails – were recently discovered on seven different mountains in south-eastern Brazil. The cloud forests on each mountain are cut off from their neighbours by climatic barriers which allow species on each mountain to develop independently of their neighbours.

One of the most interesting features of many of these frogs is their orange skin colour, warning predators of the poisonous molecule they contain for their defence against bigger foes. The poisonous molecule they contain is well known and goes by the name of tetrodotoxin.

The lethal dose to a human is a fraction of a milligram – it’s many times more poisonous than cyanide. It works by blocking channels in the membrane of nerve cells. These channels permit sodium ions to move through the membranes to allow the transmission or nerve impulses. You soon know about it – tingling feelings are followed by numbness and incontinence, and you soon stop breathing because of muscular paralysis.

Fugu looking at? Tim Sheerman-Chase

Tetrodotoxin is found in a number of animals, but the best known is the pufferfish. These slow-moving fish have several defence mechanisms – their spines, their ability to dramatically inflate themselves in size and, last but not least, tetrodotoxin. The meat of the fish is a delicacy in many parts of the Far East, such as Japan, where it is known as fugu. But before it can be eaten, a specially trained chef has to cut out certain tetrodotoxin-rich parts, such as the liver. Even so, there are numerous casualties and fatalities each year (though it will never be the Emperor of Japan as he’s not allowed the delicacy).

The first celebrity victim was Captain James Cook, the explorer. In September 1774 he and his crew were off Polynesia when he had a pufferfish supper, before the remains were fed to a pig on board the ship. Cook was distinctly unwell, but recovered – the pig wasn’t so lucky.

Well I won’t be eating that again. National Maritime Museum

As the captain wrote in his diary:

About three to four o’clock in the morning, we were seized with most extraordinary weakness in all our limbs attended with numbness of sensation like to that caused by exposing one’s hands and feet to a fire after having been pinched much by frost. I had almost lost the sense of feeling nor could I distinguish between light and heavy objects, a quart pot full of water and a feather was the same in my hand. We each took a vomit and after that a sweat which gave great relief. In the morning one of the pigs which had eaten the entrails was found dead.

The reason that the pufferfish does not poison itself is that a single amino acid mutation has caused them to have a modified sodium channel that cannot bind to tetrodotoxin. The fish does not make its own tetrodotoxin, but gets it from its diet, which comprises other tetrodotoxin-containing organisms. Tetrodotoxin is quite widespread in nature, as it is made by certain symbiotic bacteria.

You’ve seen tetrodotoxin at work in James Bond films. At the end of From Russia With Love, Rosa Klebb kicks James Bond on the shin with a steel blade hidden in her shoe.

Klebb foot. Insomniacpuppy

This blade was coated with tetrodotoxin; Bond survives through the literary device of an antidote. However, there is no known antidote to tetrodotoxin. Another tetrodoxtoxin-laced animal pops up in Octopussy, in the form of the blue-ringed octopus.

The rough-skinned newt, found in parts of America, protects itself with tetrodoxtoxin. In 1979, a man in Oregon swallowed one of these newts for a dare; it killed him.

If people get a near-lethal dose of tetrodotoxin they do not die but spend several days in a state of conscious paralysis before recovering. At one time it was believed that people with such a paralysis could be buried alive and subsequently “rise from the grave”, giving rise to stories of zombies, notably in Haiti. This idea was popularised by the ethnobotanist Wade Davis in the book The Serpent and the Rainbow. The idea is generally discredited but makes great movies.

Oophaga pumilio, one of the many ‘poison dart frogs’. Jay Iwasaki, CC BY

The South American rainforests give shelter to even more brightly coloured frogs containing even more toxic molecules – the Dendrobatidae family. Often used by the local Indians in hunting, they are popularly known as “poison dart frogs”. Then there are the Aromobatidae.

Scientists have identified these lethal molecules, which go by names that include batrachotoxin and epibatidine.
Epibatidine in particular has been studied as a lead molecule for new painkillers, though no viable medicine has yet emerged. So study of the natural sources of many animals’ chemical defences is providing new insights into nature’s medicine chest.

These forests are an untapped resource, especially of molecules that could be new medicines. No better argument is needed for their conservation.

Read more here about the seven new species of miniature frogs discovered in the threatened Brazilian cloud forest.