Spirals in Time: The Secret Life and Curious Afterlife of Seashells (33 page)

CHAPTER NINE

Bright Ideas

F
or hundreds and thousands of years people have used molluscs and their shells as symbols of sex and death, as gems and ornaments and food, musical instruments and money, a source of golden fibres and things to simply gather together and look at. Now people are pondering molluscs and finding new and powerful things to use them for. And of all the mollusc species on the planet, it’s the ones that do surprising things that are proving to be especially useful. There are molluscs that live in unlikely places, that are faster and stronger and more deadly than we might at first presume. Together they are giving rise to the next generation of mollusc-inspired ideas and discoveries. Some of the most ground-breaking innovations are coming from a group of slow, ponderous snails that hunt animals which should, by all rights, just swim off and leave them behind.

Unlocking the cone snails’ secrets

During the daytime cone snails don’t do much. They tuck themselves into crevices in coral reefs or bury themselves in sand, hiding away those intricate patterns drawn like memories across their shells. Only when dusk falls do these hunters emerge and begin their search for dinner.

There are approximately 700 species of cone snail, making
Conus
quite possibly the most diverse animal genus in the sea, and most of them have become specialist hunters that catch only one type of animal. Some hunt for worms, some for snails (including other cone snails) and some achieve the seemingly impossible: they eat fish.

After a cone snail has woken up, it will shuffle along, sweeping its proboscis through the water, probing for the scent of a sleeping fish. Silently, the predator picks up a trail and glides towards the oblivious target, then shoots out a hollow dart, loaded with venom. It impales the fish, paralysing it instantly. The snail then slowly draws in a thin cord attached to the dart and reels in its prey. Like a python swallowing an antelope, the snail distends its mouth to grotesque proportions, engulfing the fish and then settling down to digest its dinner. Several hours later the cone snail regurgitates a bundle of bones and scales.

Another tactic used by cone snails to catch fish involves doping them with puffs of sedatives that they release into the water. The snail will then unfurl its mouth into a huge net that draws in and smothers the snoozing prey, sometimes entire shoals of little fish at a time. Once they’re bundled up inside, the snail shoots each one in turn with poison darts to make sure they don’t try to escape.

The secret to the cone snails’ expert hunting skills lies in their darts. These weapons are fashioned from individual, hollowed-out radula teeth with fearsome, backward-pointing barbs that get firmly stuck in the prey’s skin. Each dart can be up to one centimetre long, and is only used once, like a disposable hypodermic needle. They are filled
with venom and then stored, like a quiver of arrows, waiting to be deployed. When prey comes into range, a poison tooth is shot out at ballistic speed from the end of the proboscis by the squeeze of a sac called the venom bulb (the contracting muscle is assisted by the same enzyme that allows scallops and squid to achieve frantic bursts of speed).

As well as hunting small fish, cone snails can also kill people. They don’t deliberately go after humans or consider us food; the deadly cones are simply defending themselves and will deploy their venomous darts if they feel threatened. Being picked up by an unwary fisherman or shell collector is enough to scare them, and because their bendy proboscis can reach around the entire body and shell there’s no safe place to hold a cone snail.

When Dutch naturalist Georg Eberhard Rumphius was working for the Dutch East India Company in the early eighteenth century, he wrote about an Indonesian girl picking up a shell, feeling a ‘tickling sensation’ in her hand and then dropping dead on the spot. Since then there have been around 30 recorded cases of death by cone snail, mostly due to heart attacks and suffocation from the diaphragm being paralysed. The severity of a cone snail’s sting depends on the species. Most won’t actually kill you but their stings are unpleasant nonetheless, causing numbness and partial paralysis that can last for weeks. But whatever you do, don’t mess with Geography Cone Snails: seven times out of ten, their sting is fatal to humans.

For such small animals to be loaded with enough venom to incapacitate a full-grown person is obviously quite over the top, and that is exactly why scientists became interested in them in the first place. For a long time, people have wanted to know why and how cone snails have become masters of chemistry and transformed themselves into such formidable killers.

The
why
part of that question is reasonably straightforward to answer. It all began with worm-eating cone snails, which
were the first to evolve around 50 million years ago. It is thought these ancestral cone snails caught worms using relatively mild toxins, as many of the living worm-hunters do today. Before too long, though, they began to face competition from fish that sneaked up and tried to steal their dinner. The snails’ response was to jab the intruders with painful stings to shoo them away. At first this was probably enough to deter the fish but it’s possible they became more aggressive, and as a result the snails evolved more potent toxins. Eventually, their stings became so effective against intruding fish that it allowed the snails to switch to a whole new diet. In order to feed on fish, the snails needed toxins that instantly knocked them down; if the toxin takes even a few seconds to act, that would be enough time for the fish to swim off and collapse somewhere the snail may never find it. These powerful toxins are clearly a highly advantageous hunting tool; reconstructions of the cone snail family tree show that fish-hunting has evolved on at least three separate occasions. Time and again, as their prey got faster, the snails’ venom became more toxic.

The bigger, more difficult question to answer about cone snails is precisely
how
their venom is so powerful. This is a conundrum that has kept researchers busy for decades. It was
Alan Kohn
at Yale University, back in 1956, who first saw cone snails hunting for fish and set out to understand how they detect their prey. He carefully put cones in aquarium tanks and watched as they buried themselves in the sand up to their eyes. Then he offered them various things to eat. A living fish dropped in the tank elicited an immediate hunting response; the cones would rise up out of the sand and start searching. In contrast, they totally ignored dead fish, but they were excited by a few drops of water from an aquarium in which living fish had been swimming; the snails set out hunting even though there was nothing for them to find. Through these experiments, Kohn had landed on the idea that cone snails sniff out prey. He went on to
become a professor at the University of Washington and a world authority on cone snails, the animals that almost bear his name.

Investigations into the active ingredients of fish-hunting venoms began in the 1970s at the University of Queensland, where Bob Endean and co-workers had the Great Barrier Reef and a ready supply of cone snails on their doorstep. They were the first to figure out that the venoms are mixtures of several compounds. However, back then, no one yet suspected quite how elaborate the cone snail’s toxins truly are.

The next major research efforts looking at cone snail venoms – which came to be known generally as conotoxins – took place in the 1980s in labs run by Baldomero Olivera. Originally from the Philippines, Olivera studied in the United States where he specialised in DNA and enzymes, and on returning to his home country found himself at a university with very little equipment to continue his molecular research. As a child he collected shells and knew very well the deadly reputation of cone snails, so he decided to test their venom on laboratory mice, a technique that didn’t require much kit.

Olivera started with a simple experimental set-up that involved persuading mice to cling upside down to a horizontal wire screen, then injecting them with different extracts of cone snail venom (he split the venom into fractions of different-sized molecules). He then timed how long it took for each extract to take effect. When mice were paralysed, they would let go of the screen and fall off: this was the ‘falling time’. Early studies like this showed that mice were paralysed by some venom extracts – but not all of them. Olivera’s next goal was to see if the non-paralytic parts of the venom had any other effects.

A breakthrough took place back in the US, in Olivera’s new lab at the University of Utah, where he enlisted the help of some smart undergraduates. One of them, Craig
Clark, came up with the idea of injecting venom extracts directly into the nervous systems of mice. Olivera admits that at the time he wasn’t convinced this would work, but Clark carried on regardless. A succession of students perfected the technique and, before their eyes, mice started behaving very strangely. Depending on which venom extract was injected, the mice would tremble or scratch themselves uncontrollably; others would fall into a hypnotic trance for 24 hours then snap right out of it; and some would frantically run around their cages and climb up the walls.

It became clear that conotoxins affected different parts of the nervous system in very different ways. By the 1990s research groups around the world had caught on to the idea that cone snails and their venom held great potential for studying nerves and brains, and perhaps for developing new pharmaceuticals. Soon these snails became some of the most intimately studied animals from the oceans.

An enormous amount is now known about cone snails and their complex venoms. We know that conotoxins are composed of a mixture of peptides. Most are made of between 10 and 30 amino acids with lots of disulphide bonds that sculpt them into small, stiff shapes. We know that each cone snail species has its own signature mix of between 50 and 200 peptides, which they blend in their venom ducts. Along the length of the venom duct there are genes that are switched on and off, resulting in a tailored cocktail of peptides that trickles along the tube before being loaded into the hollow darts at the end. The cones can even adjust the recipe depending on whether they are hunting or stinging in defence.

It’s not known exactly how many conotoxins there are. Each of the 700 known cone snail species produces its own unique blend of toxins, so it follows that there could easily be tens or even hundreds of thousands of conotoxins. No
wonder there’s no cone snail anti-venom, because it would need to counteract each individual peptide. Only a minute fraction of them have so far been identified and studied, but those that have are revealing the intricate molecular secrets of the cone snail’s chemical armoury.

In general, conotoxins disrupt the passage of nerve impulses around the body by blocking or jamming neural signals. Normally, nerves fire when ions pass in and out of them to generate or dissipate electrical charges. The ions that carry these charges are sodium, calcium, chloride and potassium. Nerve membranes are densely dotted with channels made of protein that open and close to control the movement of each particular ion. These ion channels come in many varieties. The two most common types are those controlled by chemicals and those that respond to electrical charge itself, so as to either amplify or dampen ongoing activity. For a chemical to control an ion channel it must bind to a receptor on the channel and instruct it to open or close, much like a key in a lock. These chemicals include neurotransmitters that pass signals between nerve cells, allowing the brain to process information and communicate with the rest of the body. Together, all these ions, ion channels, receptors and signalling molecules govern the transmission of nerve impulses around the body, and many other complex cellular processes. When conotoxins come along they mess up this finely tuned symphony of ions by acting like signalling molecules, binding to ion channels and waywardly telling them to either open or close.

Based on their effects, different conotoxins have been sorted into groups that Baldomero Olivera and colleagues have nicknamed toxin cabals. Like secret societies plotting to overthrow a government, conotoxins gang up to overthrow the cone snail’s prey. The toxin cabals were first uncovered in the Purple Cone Snail, a species which launches a two-pronged attack on fish. First they unleash the ‘lightning strike cabal’. This makes nerves fire uncontrollably, essentially giving
the victim a massive electric shock. It happens because of the combined effects of a conotoxin that jams open channels, causing an influx of sodium ions together with another that blocks potassium channels, preventing these ions from leaving. The upshot is a very still, very stiff fish.

This gives time for a second toxin cabal to kick into action. The ‘motor cabal’ blocks signals that pass between nerves and muscles; this takes slightly longer than the ‘lightning strike cabal’, because the conotoxins have to reach the ends of nerve fibres. Once the ‘motor cabal’ gets going it causes total and irreversible paralysis. Acting synergistically like this, the two conspiring cabals have everything covered, leaving little hope for a fish harpooned and reeled in by a Purple Cone.