Sometimes, when I’m camping, I dream about angry bears ripping through my tent and attacking me for that forgotten bit of food I left in my pack. A perfectly logical nightmare, all things considered, but far from my worst. In that one, I was SCUBA diving with my cat when she encountered a 6-inch long cone snail. In a sudden flash of activity, one of my best buds was murdered in a rush of sadness and a chorus of bubbly muffled screaming.
I must have been about 12 years old at the time I had the nightmare, and it keep recurring. These nightmares started the same night that I first learned about cone snails and their cat-murderingly lethal toxins from a Disvocery Channel documentary. Not once have I had a nightmare about a Badass Biology topic, let alone one that still rips at the psychological wounds 13 years later.
What about cone snails makes them so horrible? So memorable? Get comfortable, I have a lot to write.
The 6 reasons why cone snails deserve to invade my nightmares:
1) I’m convinced cone snails are heralds to the war of the end times.
Cone snails look pretty innocent. In fact, many of them, like the textile cone pictured below, have intricate colors and gorgeous patterns that would make them desirable for any unsuspecting shell-lover to snatch in an instant. Just look at this little guy here:
How cute, right? I think so. I’d hold him. However, what I wouldn’t expect is for that fleeting joy to be one of the last thoughts my brain could process before I’d rapidly be dead.
Unlike the garden variety of snail, cone snails are carnivorous marine snails. They’re common in Indo-Pacific waters, though they also inhabit the temperate waters around California, the Mediterranean, and South Africa among other habitats. The smaller varieties eat benthic invertebrates, though the larger ones must be quick and deadly to capture the small fish they feed upon. This selection pressure created one of the most badass weapons in the natural world.
To catch their quick prey, cone snails possess a small harpoon-shaped structure within the snail’s radula, a feeding structure that other snails use to scrape food from surfaces. In cone snails, the harpoon carries a toxic cocktail of sometimes hundreds of lethal compounds, all stored in a venom sac that supplies the harpoon with enough venom to apply to their next murder victim. This harpoon is used blindingly quickly, leaving little chance for their prey to escape. Then, after that, the cone snails engulf them whole with a mouth so horrifying that I cannot find the guts to post a picture here, thereby I suggest you just Google it.
2) Take a moment today to call your mother and let you know you love her.
Cone snails produce more toxins than any genus of organisms discovered by science. In fact, there are so many that an entire database has been developed to catalogue and characterize conotoxins, the potent toxic compounds present in cone snail venom. This database, called ConoServer, presently has 8482 chemical entries from no more than 215 species within the cone snail genus, a staggering number for a single organismal group.
But what are these toxic chemical compounds? Most are peptides, short strings of amino acids chained together with a special carbon-nitrogen bond. If these chains were considerably longer, portions of the string would begin interacting with other parts and fold itself into a protein, a type of molecule I’m sure you’ve heard of. Peptides, though shorter, are still useful molecules to manufacture, forming the surfactants that keep mammalian lung tissue from sticking to itself, adding nutritional value to milk, and in the case of our nightmarish cone snails, killing stuff really really quickly.
Conotoxin peptides are mostly used defensively. Most human stings are caused by a wayward foot delivered to a cone snail hiding in the sediment. However, roughly 10% or so of classified cone snail toxins have been found to be used in foraging and hunting, paralyzing their prey.
3) I am now hoarding Morton’s salt under my pillow in case one tries to break into my home.
All of the 600-700 species of cone snails are capable to stinging and injecting their toxins into humans. Not only are there a multitude of lethal toxins in a cone snail’s sting, but their lethality is nearly unparalleled. A useful way to measure how lethal a toxin can be is to measure what’s called a LD50, or the dosage expressed in mass/kg of body weight at which 50% of a population of test animals (usually rats) are killed. Arsenic, a well-known toxic substance, has an LD50 of around 15mg/kg, meaning it would take about half a teaspoon of crystallized arsenic compounds to kill a male human weighing 83.6kg, or around 181 lbs. The LD50 for some conotoxins can be as low as 0.005mg/kg, meaning you could very well be killed by conotoxin at a volume little larger than 10 medium grains of sand.
How do these toxins kill at such small dosages? If you’re an avid reader of mine, you may remember textrodotoxin, a neurotoxin in blowfish that kills by interfering with ion channels in neurons. Ion channels allow neurons to fire, and conotoxins bind to these channels with startling specificity, prohibiting their ability to function. Conotoxins kill humans in much the same way, and like tetrodotoxin, most human deaths from conotoxins are related to the asphyxia caused by the diaphragm being unable to contract. There is no anti-venom, and in some species like the geography cone, a sting is 70% fatal.
4) I strongly suggest we flee for the mountaintops.
Diabetic or not, you’ve heard of insulin. Insulin too is a peptide, and in humans it acts a hormone to help mediate the amount of glucose present in the bloodstream. Cone snails have now added another use for insulin in the natural world.
In January of this year, researchers published a study characterizing two species of cone snails that possess the first and only recorded case of weaponized insulin in the history of the planet.
That’s right. Weaponized insulin. Used as a predatory tactic, cone snails release insulin into the surrounding water when prey are nearby. It then passes through the gills of prey fish, enters the bloodstream, and drops the blood sugar enough to prevent the fish from having enough energy to flee the encounter, all in a matter of seconds.
5) Oh dear God, there’s more?!
Conotoxins are so potent that there are serious efforts dedicated to determine whether they can be weaponized and used on mass numbers of victims by terrorists groups. In a paper published in the Journal of Bioterrorism and Biodefense, scientists outline the probability of a terrorist attack in the form of aerosolized conotoxins or contamination of food or water. Their verdict is surprisingly reassuring, citing the difficulty to extract most conotoxins from living animals and the difficulties synthesizing conotoxins in a usable and deliverable form. However, not all varieties of conotoxins face these same issues, and the risk of three broad biochemical classifications of conotoxins are candidates for bioterrorism should those few key technical hurdles be overcome.
6) Oh hey, a fact that’s not actually all that terrible.
Remember when I mentioned ConoServer, the online database that combines efforts of dozens of biochemists seeking to catalogue the vast variety of Conotoxins? Why spend the time to catalogue them if terrorists could simply learn to replicate these peptides in vitro?
Many of today’s most common and effective pain-killers carry powerful negative consequences. For example, the narcotic pain medications like the opioids hydrocodone (Vicodin), morphine, oxycodone (Percoset), and codeine are highly addictive and can leave patients with withdrawal symptoms after their course is complete. The hunt is on for a powerful non-habit forming pain killers with few side effects that can be cheap, easy to deliver, and easy to scale up.
Conotoxins may provide the solution. Much like snake venom, most research efforts on conotoxins are geared toward repurposing the toxins to serve as pain killers. Perhaps a single toxin or a cocktail of a few or several toxins could serve as potent yet non-costly painkillers, and collaborative research efforts like ConoServer could rapidly speed progress towards a revolution in patient care and pain management.
One promising conotoxin pain drug is ziconitide, a synthetic drug identical to a toxin produced by the cone snail Conus magus. Ziconitide has been FDA-approved for treating intractable pain and has shown some promise in its effectiveness. However, the drug degrades rapidly and cannot be delivered orally. Instead, ziconitide must be injected directly to the spinal cord via a surgically-implanted pump. Not terribly convenient if you ask me, but it seems to be a good start nonetheless.
Progress is being made to develop oral conotoxins-derived pain medications. In 2014, Dr. David Craik from the University of Queensland presented new evidence at the 2014 meeting of the American Chemical Society. Craik and colleagues looped peptide chains, amplifying their stability over the long-term while preserving their potency as analgesics. The prototype drug was given orally to test animals and showed nearly a 100-fold increase in effectiveness in comparison to the common painkillers morphine and gabapentin.
Overall, I find it pretty badass that such an effective killer lurks in the oceans. It delivers death in seconds to its prey and in minutes to a fully-grown human, and with no anti-venom, its effects are second to none. Hell, these guys even weaponized insulin. On top of that, they may gift humanity with a revolution in pain management. That’s pretty badass.
Want to suggest a future topic? Write it down in the comments below. Do it. Do it do it do it doitdoitdoitdotidoit.
For further reading:
http://www.conoserver.org/?page=about_conotoxins&bpage=keyrefs (list of current review papers on conotoxins as pain killers and the difficulties faced with their use)
http://www.theconesnail.com/ (lab website of the Olivera lab group at the University of Utah)