Diving into myths for facts

We scientists don’t have much patience for myths, science fiction or pseudo-science. Postcards of jackalopes irritate our rational sensibilities. But sometimes it is really fun to dive into myths and such and try to discover a factual basis for these wild tales. Ask me about jackalopes, in fact, next time you see me! With this in mind, and zeroing in on one particular molecule, called tetrodotoxin, we can weave together a fascinating narrative of cultures, fads, ceremonies, word-choice, and basic natural history.  C’mon, follow me!

Tetrodotoxin (TTX) is an extraordinarily powerful toxin that binds to sodium channels in the nerves of animals. These sodium channels cyclically pump sodium ions into and out of the muscle cell, causing contraction and relaxation of the cell. Muscle cells blocked by TTX are an immediate and serious problem for any unlucky animal who somehow managed to ingest the stuff because they become paralyzed. Paralysis of key muscles, such as your diaphragm or heart, means death. This stuff is thousands of times more toxic than cyanide. TTX is biochemically produced by some forms of bacteria, and these bacteria can be found living in certain animals, including newts, pufferfish, blue-ringed octopus, certain worms, and many more. So, we have an assemblage of very unrelated animal species that share the unique distinction of having TTX in their tissues. 

In other words, these unassuming creatures are deadly toxic! TTX affects human cultures in a number of ways. Scuba divers around Australia know to stay away from the small, but fatal, blue-ringed octopus. The rough-skinned newt (Taricha granulosa) is one of the most abundant animals in the Pacific Northwest. Hikers see them marching by the hundreds to ponds and streams for breeding, but most are unaware that they may be lethally poisonous. Ancient Asian cultures learned, presumably the hard way, that eating pufferfish is a death warrant. But, through brave (reckless?) experimentation, those cultures learned which tissues, such as the liver, in the pufferfish contained the most TTX (though the molecule had not yet been discovered). This tradition led to the modern-day culture of eating fugu in Japan, in which carefully trained chefs create raw dishes of the low-TTX muscle tissues mixed with tiny amounts of the high-TTX liver. They joyous (reckless?) diner is then treated to a delightful round of tingling low-level paralysis of the mouth and face, and some certain “euphoric” disruption of brain function. No thanks. An even more remarkable feat of table-top chemistry has been mastered by Voudou priests, especially in Haiti, who prepare a powder derived from parts and carcasses of several animals, including pufferfish. Very careful manipulation of the dosage will render a person paralyzed and just on the edge of death. Motionless and with barely detectable heartbeat and breathing, these people appear to be dead. They often can recover, however, leading to the—evidently very convincing—spectacle of a dead person coming back to life and, in the process, stumbling around incoherent and lethargic. There we have a pretty interesting “zombie” origin story.

On the biological side of things, TTX features in some extraordinary examples of evolution and co-evolution. In a career-length investigation into the TTX in rough-skinned newts, Dr. Edmund D. Brodie, Jr., and his son Dr. E. D. Brodie III, discovered that not all populations of newts were lethally toxic. Some certainly are so, yet others are not. But the newts are indistinguishable in appearance. Over their decades of work on the subject, they also discovered that some populations of the common garter snake (Thamnophis sirtalis) are resistant to TTX and regularly eat newts bearing enough TTX to kill a dozen adult humans. Among the snake populations, they found snakes that will die from eating a newt, others that become zombies and recover eventually, and others that are entirely resistant to the toxic effects. Careful field work and biochemical prospecting led them to discover a fantastically complex patchwork of so-called “hot spots” and “cold spots.” In the hot spots, the local newts and snakes are engaged in a co-evolutionary arms-race in which resistance in snakes encourages survival of the more toxic newts, which leads to survival of the more resistant snakes. In the cold-spots we find newts of low toxicity and snakes of low, or zero, resistance. Returning again to the dichotomy of venomous vs. poisonous (see Research Blog March 8, 2017), as you can imagine, the story gets weird with TTX.  The Brodies also discovered that these super-resistant garter snakes were capable of storing some of the TTX from their decidedly poisonous newt prey. With wallops of TTX stored in their livers, these individual snakes become toxic for a matter of months. In other words, we now have an example of a truly poisonous (but not venomous) snake! 

In closing, please don’t try fugu, and don’t eat newts.  Stay safe, my friends!

Here is a wonderful PBS documentary about the father-and-son team Brodie, and their innovative work on snake–newt co-evolution:

https://www.pbs.org/wgbh/evolution/library/01/3/l_013_07.html

Here is a great blog on the topic that goes into more detail, by my friend Dr. Andrew Durso:

http://snakesarelong.blogspot.com/2014/07/tetrodotoxin-resistant-snakes.html

Joseph Mendelson, PhD
Director of Research