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Living and Writing in the Natural World

Pick Your Poison

the mu Conotoxin

If you’re a writer of murder mysteries, you’ve got to love poisons. And if, in your day job, you’re a biologist, then you’re doubly blessed, because nothing tells us more about life than the many bizarre ways creatures have devised to end it. In my (current) two mysteries and a thriller, my villains employ maculotoxin from the blue-ringed octopus, the plant alkaloid aconitine (from monkshood), conotoxin (from cone shells), and tetrodotoxin (from puffer fish).

All these deadly poisons affect the transmission of ions across the electrically-charged cell membranes of nerves and muscles. If you want to reliably and quickly end the life of a victim, either in a murder mystery or in real-life defense against predators, you’re well-advised to strike at the delicate polarity of the cell membrane, because that’s where life is most vulnerable.

Take tetrodotoxin (TTX). This neurotoxin, 100 times more deadly than cyanide, blocks sodium ion channels through the nerve cell membrane, thus preventing transmission of signals from nerve to muscle tissue. The result is paralysis, loss of vagus-nerve regulation of heart rate (causing it to increase dramatically), and loss of sensation, among other affects, which frequently lead to death of the recipient creature.

Captain James Cook was among the first Westerner to notice TTX. He had netted a slew of puffer fish in the Pacific on September 7, 1774, and fed it to his crew (and the scraps to some pigs aboard the Endeavor). Within hours the crew was struck with shortness of breath and numbness. All the pigs died the next day. The dose of TTX is relatively low in the fish flesh the crew ate, but high in the organs, such as the liver, distributed to the pigs.

Highly trained Japanese chefs are permitted to prepare puffer fish, which, correctly done, gives the adventuresome diner an interesting mixture of numbness and tingle in the mouth and tongue, even as their heart races pleasantly. Incorrectly done—well, that’s another story, and deaths from eating puffer fish are amply documented.

But the most interesting thing about TTX is that it is found not just in puffer fish, but also in several kinds of sea stars, a polyclad flatworm, several species of arrow worms (Chaetognatha), several nemertean ribbon worms, and several species of xanthid (or “rubble”) crabs. How could all these diverse marine creatures have independently come up with the TTX poison?

It gets more bizarre. Biochemists discovered in 1964 that tarichatoxin, the deadly poison found in rough-skinned newts of the genus Taricha, was identical to TTX—is TTX! And in 1978 it was discovered that maculotoxin, the neurotoxin of the blue-ringed octopus (Hapalochlaena lunulata) is also TTX.

To a biologist, it’s inconceivable that things as unrelated as octopus, newts, puffer fish, crabs, and “worms” from three phyla could all stumble upon the same molecule to mess up sodium ion transmission channels, whether to disable prey (octopus) or to deter predators (the rest). Recently, the mystery has apparently been solved: bacteria are the poison-producers.

It’s been established that the bacteria Vibrio alginolyticus, which lives symbiotically within the blue-ringed octopus, produces TTX and hands it off to the octopus, which injects it into its prey. Symbiotic colonies of V. alginolyticus are also found in the puffer fish, and the arrow worms and ribbon worms, where it is now assumed they produce the TTX and pass it along to the hosts. Though research has yet to find Vibrio symbionts in the newt, sea stars, Xanthid crabs, or flatworm, it seems likely that they exist and produce the TTX for those creatures as well.

It has also been established that other bacteria (in the genera Pseudomonas and Pseudoalteromonas) also produce TTX. Perhaps it is these bacteria that are symbionts of the newt, sea stars, Xanthid crabs, and flatworms. Research continues in this area, and to be fair not all researchers are confident that the mystery of the source of TTX, in the diverse range of creatures in which it occurs, has been completely resolved.

In a further bizarre twist, in 1983 the Harvard ethnobotanist Wade Davis in his book The Serpent and the Rainbow suggested that the “zombies” produced in Haitian voodoo magic were produced by the administration of sub-lethal doses of TTX from puffer fish, perhaps in conjunction with various alkaloids from the skin of cane toads on the island. The issue has proved difficult to resolve, and not surprisingly most scientists are skeptical.

Another rich source of poisons disrupting ion channels across cell membranes are the “poison dart frogs” of Central and South America, whose neurotoxic secretions have long been applied to their arrows or darts by native-Americans in those regions, to paralyze prey. These neurotoxins are alkaloids, a class of organic molecules containing nitrogen and often alkaline (basic) in pH. The frogs’ skin contains a witches brew of these alkaloids, 500 types in some 28 structural classes, to deter predators. The best-studied are the various pumiliotoxins (which affect sodium ion channels) and batrachotoxin (BTX).

BTX also affects sodium ion channels, as does TTX, but in the opposite manner. That is, rather than blocking the channels and preventing transmission of signals from nerve to muscle, it dramatically increases the permeability of the channel to sodium ions, to the point where the nerve cannot re-polarize after it “fires”. Thus BTX permanently depolarizes the nerve membrane, which has the same affect of disabling transmission of signals from the nerve to the muscles.

BTX is found not just in the poison dart frog Phyllobates terribilis (nice name, eh?), but strangely enough also in Melyrid beetles, particularly the genus Choresine. Then, in 1990, an ornithologist was extricating a Hooded Pitohui songbird from a mist-net in New Guinea, handling its glossy orange and black feathers admiringly. Very soon his fingers began to burn. “And if you put your finger in your mouth after handling a Pitohui, your mouth begins to tingle. It’s a lot like tasting hot chili peppers or touching a 9-volt battery.” Yep—he had discovered a bird with BTX in its feathers. Soon another New Guinea songbird (genus Ifrita) was added to the list.

As with TTX in its wide array of marine creatures, this presence of the poison is a range of unrelated (terrestrial) creatures suggests that BTX is being produced by some other creature common to the BTX possessors. In this case, increasing evidence supports the diet-toxicity hypothesis, which suggests that ants in the cosmopolitan (worldwide) Formicine group may be the key link. Frogs eat these ants, as do Melyrid beetles. The New Guinea birds presumably eat the beetles, who are also cosmopolitan, and thus come to possess the BTX.

These complicated dietary links between BTX creatures are extremely difficult to study and pin down, in part because the BTX levels in the ants, the frogs, and the beetles vary both geographically and seasonally. It has even been suggested that the BTX presence in the ants (and possibly the beetles) may be due to—you guessed it, bacterial symbionts within the ants or their colonies!

The moral of all this poison-study, for me, is that it highlights how deliciously devious and complicated are the interactions among living creatures. “No man is an island,” John Donne told us three centuries ago. Nor is a puffer fish, a blue-ringed octopus, a New Guinea bird, or a poison-dart frog an island. All of us are interconnected to the bacteria living on and within us, to the molecules in the food we eat. All connected, with bizarre, unexpected, and un-imaginable bonds. Indeed, we are inextricably linked to the earth and our fellow creatures. We’d better get used to it. We’d better celebrate it.

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