Blue-ringed octopuses are among the deadliest animals in the sea. Throughout their range in Australia and the eastern Indo-Pacific, several humans suffer bites each year. Unfortunately, some of these are fatal. In Australia where blue-rings occur in shallow coastal waters and can be relatively common in areas frequented by beach-goers, there have been dozens of reported bites and several deaths. Typically, the victim is unaware of the danger and either picks up the innocuous looking octopus or inadvertently contacts it. The bite is slight and produces at most only a small laceration with no more than a tiny drop of blood and little or no discoloration. Bites are usually reported as being painless. Often the victim doesn’t even know that he had been bitten. This can make it difficult for emergency and medical personnel to determine the cause of a patient’s distress. In fact, there is some question as to whether the octopus even needs to bite to envenomate a human. In cases with prolonged contact, the venom might pass directly through the skin. While most severe envenomations appear to involve bites, I can report developing mild local neurological symptoms after immersing my hand in sea water in which a large blue-ring had been shipped.
Depending on how much venom has been transferred into the wound, the onset of symptoms can be quite rapid. Within five to ten minutes, the victim begins to experience parasthesias and numbness, progressive muscular weakness and difficulty breathing and swallowing. Nausea and vomiting, visual disturbances and difficulty speaking may also occur. In severe cases, this is followed by flaccid paralysis and respiratory failure, leading to unconsciousness and death due to cerebral anoxia. Interestingly, the victim’s heart continues to beat until extreme asphyxia sets in. Some victims report being conscious, but unable to speak or move. They may even appear clinically dead with pupils fixed and dilated. Not all bites result in the transfer of venom. The severity of symptoms is dose-dependent. Smaller adults and especially children are most at risk.
The venom of blue-ringed octopuses is contained in their saliva. In the late 1960s, the primary active toxin was extracted from the greatly enlarged posterior salivary glands of an Australian species of blue-ringed octopus, Hapalochlaena maculosa. These globular shaped glands are situated in the anterior body cavity behind the brain. Ducts from each gland join to form a common duct that passes down through the brain and opens into the mouth cavity. The toxin was characterized as a low molecular weight, non-protein molecule and was named maculotoxin. It was recognized to be similar to tetrodotoxin (TTX), the extremely deadly toxin found in pufferfishes. Experiments with rabbits showed that a single adult blue-ringed octopus weighing just 25 g possessed enough venom to fatally paralyze 10 large humans.
Subsequent work demonstrated that the maculotoxin is in fact TTX. TTX is found not only in blue-rings and many fishes in the family Tetraodontidae (hence the name tetrodotoxin), but also in several other groups of animals including California newts (genus Taricha), central American harlequin frogs (genus Atelopus),as well as a scattering of invertebrates including a South American tunicate (sea squirt), a sea star, several snails, some xanthid crabs, a horseshoe crab, two ribbon worms, some arrow worms, and a flatworm. It was a mystery why such a diversity of unrelated organisms would all evolve the same toxin, until it was recently discovered that bacteria associated with many of these animals actually produce TTX. This is the case in blue-ringed octopuses. Their salivary glands harbor dense colonies of TTX-producing bacteria. The blue-rings have evolved a symbiotic relationship with the bacteria, providing them ideal living conditions while using the toxin they produce to subdue prey and as part of their highly advertised defense.
TTX is a potent neurotoxin that blocks the movement of sodium (Na+) ions across neural membranes by attaching to a Na+ channel receptor and capping the Na+ channel. TTX is particularly effective blocking the propagation of nervous impulses in mammalian myelinated peripheral nerves which produces flaccid voluntary muscle paralysis. This interferes with the muscles of the diaphragm and chest wall and leads to respiratory failure. There is little or no direct effect of TTX on the heart or brain (because it does not cross the blood-brain barrier) until a lack of oxygen causes these organs to fail. One milligram of TTX can kill a person, making it one of the most potent natural toxins known. There is no antidote to TTX. Treatment consists of life-supportive measures including artificial ventilation. This is why researchers in my laboratory studying blue-ringed octopus are required to work in pairs and must be trained in CPR. Patients who survive 24 hours typically make a full recovery, unless lack of oxygen to the brain has caused permanent damage. Interestingly, blue-ringed octopuses are not affected by TTX, probably because they have evolved a slightly different sodium channel receptor that does not interact with the TTX molecule.
As an aside, TTX plays interesting roles in various human rituals. Fugu, the Japanese delicacy, is prepared from pufferfish that contain lethal doses of TTX. It is estimated that each year close to a hundred people die from eating fugu that has not been properly prepared. TTX is also claimed to be an active ingredient used by some Haitian voodoo sorcerers to create “zombies”. It is known that the toxic powder used is often prepared from, among other things, porcupine and pufferfishes that contain TTX.