Deadly Snails Kill Pain
Bruce - What I've been doing is exploring the potential of animals that live in the great barrier reef for production of novel painkillers.
Chris - Specifically what are you been looking at?
Bruce - Well we've been looking at venomous cone shells. These creatures developed just after the death of the dinosaurs and in the 500 million years since, they've developed a very sophisticated venom apparatus. They go out each night and they hunt down their prey. They do this by injecting them with a cocktail of very small molecules called peptides that make up the venom. One of those peptides is of particular importance to us, because its a very potent analgesic and we hope the develop this for the treatment of some very painful conditions, like neuropathic pain. That's the kind of pain you would have if you were to lose a limb-you may have heard of phantom limb syndrome? Where people have had an accident, lost a a limb, can't get to sleep at night because of the pain in their so-called phantom limb, which is very real to them. Another really painful condition, which happens mainly in older people, is shingles. Once again a very painful condition and a large unmet need with existing medicines not being very good at curing the pain.
Chris - How does the cone shell actually use this? Why does it actually want to use a painkiller to kill something?
Bruce - Well I think it perhaps doesn't need the painkiller, but it uses something like 200 other components in the venom. It uses these components to put its animal to sleep. That means the animal is not going to thrash around and they can eat it quite quietly without it feeling apprehensive, and maybe thats where the painkiller come in.
Chris - What do these shells actually look like then and how do they catch things?
Bruce - Well they're very pretty. There are over 500 different varieties of cone shell and they've been collectors pieces for hundreds of years. In fact, everybody in the 1600's who had a curiosity cabinet where they kept biological specimens wanted a cone shell. They were highly prized because they came mainly from the Indo-Pacific region and that meant they were quite expensive to buy. In fact, some of these cone shells sold at auction in the Hague for more than a Vermeer painting. These day, you can still pay up to $1000 for a very rare cone shell, but mostly you can get a very good collection, such as the one I have behind me, for 5 to 10 dollars a piece.
Chris - But how do they actually catch stuff? How do they use this amazing example of overkill, these toxins, to catch things?
Bruce - It's amazing that they need this overkill. I mean one of the toxins would probably serve the purpose well. I think the variety of toxins is there because their prey changes and they have to adapt their venom to the prey. So they make thus suite of toxins in the hope that one of them will kill their prey. Cone shells are marine snails, so like a garden snail, they're pretty slow moving and they need some benefits. What they do is they lay and wait, then put this long tongue out of their mouth, called a proboscis, and on the end of the tongue they've loaded it up with a modified, hollow, tooth, called a Radula. That tooth is stuffed full of venom, and they actually make a whole quiver of these arrows, harpoons if you like, they make the in one of the sacs in their internal digestive system, and they move them into an adjacent sac. They put their tongue back and pick up, with the muscular end of the tongue, they pick up one of these arrows stuffed full of venom and then they impale their victim with this. Now the victim, it depends on the kind of cone snail involved, but there are basically three kinds of victim. There are 'fish', some of these cone snails hunt fish, and they're the ones that are dangerous to us. There are 'others', the majority of them hunt marine worms, and then there's still another group that hunt other molluscs.
Chris - Say I was to go near one and it stuck one of these things in my foot, what would I notice then?
Bruce - Well if it was the kind that hunt fish, you could be in trouble. There have been thirty deaths from cone shell in envenomation worldwide and there's no antidote to it. The first hint that you would have would be that you would have blurred vision, and then your respiration starts to slow and then you would die from asphyxia up to 7-9 hours later. The things that interested us was, in the descriptions of such envenomations, that they said the patient dies a painless death. So I thought, I know what kills the person, but what is component there that acts as an analgesic? We went out on purpose to look for the analgesic component.
Chris - Have you tracked it down?
Bruce - Yeah, there are actually a number of different components but the one that we tracked down we got from a cone shell from Broome, in Western Australia. Conus Victorii its name is. Named after Queen Victoria but in fact its not in the state of Victoria, its in western Australia. This component is a small peptide of 16 amino acids and that acts as a very potent analgesic between 1000 and 10,000 more portent than morphine.
Chris - How do you know its going to work in us?
Bruce - We don't. We know that it works in animal models of pain and we're current in phase 2 clinical trials, testing it on people who have painful sciatica. The results of those studies will be known mid-year. At this stage everything is coded, so the patients don't know if they're receiving a placebo or the real drug. And the results will be analysed and well the results will tell us if it's going to be an effective medicine or not. We've got out fingers crossed, as you can see I've got both fingers crossed and my legs crossed. We're hoping for a good result because there's really a big unmet need of patients for whom conventional analgesics are not working and they need something else. We hope that the cone shell has the solution to their problems.