Mon. Oct. 16, 2006. | Updated at 01:52 PM

 

 

 

A picture and a thousand words

Oct. 15, 2006. 01:00 AM

PETER CALAMAI

 

UNIVERTSITY OF MELBOURNE - PHOTO BY DAVID PAUL AND BRUCE LIVETT

A Textile Cone is in an aquarium. The living animal protrudes from the lip of the shell, built up from calcium-carbonate excretions.

 

 

In the year 40, the emperor Caligula marched his Roman legions across Gaul, now France, and down to the sea as if embarking on an invasion of Britain. There he ordered his soldiers to gather seashells, calling them “the spoils of a conquered ocean.”

It was the first recorded large-scale shell-collecting field trip. By then, however, people had already been picking up and treasuring these compellingly beautiful objects for centuries.

I started my collecting a mere 50 years ago, on a visit to grandparents in Florida. A fascination with the internal structure of snails and other gastropods led to a science-fair exhibit; pursuit of the rarer varieties of the cowry family has taken me from the wild coasts of Namibia to Heron Island in Australia’s Great Barrier Reef.

One attraction of shells is that they’re marvels of evolution: tens of thousands of species adapted to location, climate and food source. Yet a visit with Bruce Livett at the University of Melbourne earlier this year made clear how much shells are also marvels of biochemical engineering.

Livett is a biochemical pharmacologist who has been spearheading a research effort in Australia to transform the specialized killing apparatus found in cone shells into a major boon to humanity — a new type of pain-killer thousands of times more potent than morphine, but not addictive and without debilitating side-effects.

This painkiller holds out the promise of defeating neuropathic pain, that intractable variety associated with diabetic leg ulcers, shingles, some cancers, and also the phantom-limb syndrome after amputations.

This new analgesic would be a clone of one of the scores of compounds in the toxic witch’s brew that carnivorous cone shells use to first stun and then kill their prey, which ranges from marine worms to other molluscs and even small fish. This toxin is delivered by hollow, harpoon-like barbs thrust from the cone’s extendable, nose-like proboscis.

You’ve probably seen a cone shell, in a picture if not in someone’s vacation haul. The more than 500 species of these elegantly marked conical shells have been a favourites with collectors for centuries (although Caligula’s legionnaires wouldn’t have picked up any since cone shells inhabit the tropical waters of the Indian and Pacific Oceans).

So most people in Canada haven’t had much opportunity to see a live cone like the Conus textile in our photograph. More fanciful, but typical of the unquenchable romanticism of conchologists (shell collectors) is its sobriquet, Blanket of Gold Cone.

This Textile Cone is in an aquarium. The living animal protrudes from the lip of the shell, built up from calcium-carbonate excretions. That fleshy flap on the bottom is the foot with which the cone shell can drag itself laboriously along the ocean bottom. Sticking out to the top right above are the two short white eye stalks and a long black-and-white banded tube with a deep red tip, which is the siphon for water and waste.

The only exterior evidence of the cone’s remarkable killing apparatus is that Pinocchio-like pink proboscis arrayed between the siphon above and the eye stalks below. Hidden away inside, however, is a death-dealing biological apparatus so cleverly honed that Livett says nothing better could be designed.

An internal venom duct continually produces poisonous toxins made up of between 50 and 100 different biologically active compounds. These toxins travel down the coiled duct, up to 30 centimetres long, to the rear end of the proboscis.

In another internal sac, the animal is crafting hollow and barbed harpoons, a specialized adaptation of the radulae or teeth found in many shells. The venom fills the hollow harpoons stored in the sac like arrows in a quiver, and the animal loads them one at a time onto the end of its proboscis.

Thus armed, the cone shell hunts, burying itself in the sand until only the pink tip of its proboscis is showing, acting as a worm-like lure. When prey comes within range, the harpoons are launched. A fine thread is attached so the harpoon’s victim can be hauled back to the cone shell’s mouth. In a day, a Textile Cone can ingest a small guppy and spit out the bones.

Livett’s scientific interest was initially aroused by an observation that cropped up in reports about the rare human fatalities from a cone shell, usually Conus geographus but also C. textile. The victims were described as expiring in a “painless death.” To a pharmacologist this strongly suggested an analgesic intended to put prey to sleep so they didn’t struggle.

More than eight years of research and experimentation by Livett and colleagues have led to a candidate analgesic, called ACV1, synthesized to match a compound isolated with great effort from the venom of the Conus victoriae (named after Queen Victoria) gathered from a remote location in western Australia.

Chemically, the process is like the development of aspirin after salicylic acid was identified as the fever-defeating compound in willow bark. But the Australian researchers were dealing with something much more complex, requiring the entire armoury of modern molecular biology to identify the key analgesic compound in the cone shell’s toxin.

That natural analgesic, and its synthetic clone ACV1, are a kind of small protein known as peptides. These appear to work by blocking a cell receptor and thus inhibiting the charged ions that trigger pain transmittal through nerve fibres.

At least eight more years of clinical trials and regulatory hurdles lie ahead before ACV1 might be on the market. There’s also a rival analgesic derived from a different cone shell toxin by another research group.

Such competition is nothing new in the world of cone shells. In the 18th and 19th centuries, wealthy private collectors and museums vied to buy specimens of Conus gloriamaris, or Glory of the Sea, of which only a handful had been found. As recently as 1957, a collector paid $2,500 for one. But in 1969 scuba divers discovered a mother lode off Guadalcanal Island. Prices plunged and today a fine Glory of the Sea can cost less than $150.

Which is good, since gloriamaris, like all other cone shells, will have unique venom harbouring who knows what biomedical surprises.

Bruce Livett’s home page is a grimwade.biochem.unimelb.edu.au/cone

Additional articles by Peter Calamai