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Leo
10-16-2003, 04:27 PM
[ Back to EurekAlert! ] Public release date: 16-Oct-2003
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Contact: Kathleen Frith
kfrith@hms.harvard.edu
617-384-8591
Harvard Medical School
New medicines at risk from biodiversity loss
Science study reveals that habitat loss imperil one of the world's most promising source of new drugs
In a letter published in the October 17th issue of Science, three scientists warn that biodiversity loss could have devastating consequences for drug discovery and the development of new medicines. "Tropical cone snails may contain the largest and most clinically important pharmacopoeia of any genus in Nature" says lead author of the study, Eric Chivian from the Harvard Medical School, "but wild populations are being decimated by habitat destruction and overexploitation. To lose these species would be a self-destructive act of unparalleled folly."

Approximately 500 species of cone snails inhabit shallow tropical seas. They defend themselves and paralyze their prey � worms, fish, and other molluscs � by injecting a cocktail of toxins through a hollow, harpoon-like tooth. Each species has its own distinct set of around 100 'conotoxins', which like a gourmet chef it mixes in constantly changing proportions, thereby preventing evolution of resistance in their prey. Co-researcher Aaron Bernstein, also of Harvard, says "To date, only about 100 of the estimated 50,000 cone snail toxins have been characterized, and only a handful tested for pharmacologic activity. The results have extraordinary promise for the development of powerful new drugs."

With more than 2600 studies published in the last 20 years, there is much excitement about conotoxins in biomedicine. "Most conotoxins are a succinct ten to forty amino acids in length and are exquisitely selective about their receptor binding sites. This makes them powerful tools for understanding how cells work and a rich source for discovery of new medicines", said Bernstein. Among many discoveries, conotoxins that block key neurological pathways have been effective in the early detection and may also help treat small-cell lung cancer, one of the most devastating human cancers. A compound now in clinical trials has powerful anti-epileptic activity. Experiments suggest that conotoxins could treat muscle spasticity following spinal cord injury. They could prevent cell death when there is inadequate circulation, such as during strokes, head injuries or coronary bypass surgery. They could also be used to treat clinical depression, heart arrhythmias and urinary incontinence.

Conotoxin research has advanced farthest in treatment of pain. The synthetic drug Prialt is in extended Stage III clinical trials for the treatment of intractable pain (unremitting, severe, and essentially untreatable pain) and could soon be on the market. "Prialt may be 1000 times more potent than morphine. More importantly, it does not seem to lead to addiction or tolerance, where increasing doses are required to achieve the same effect" said Chivian. These problems have greatly limited the long-term effectiveness of the current mainstays of severe pain therapy, morphine and other opiates. Many millions of people suffer from intractable pain and have developed tolerance to opiates, so a potent painkiller like Prialt could represent an enormous therapeutic breakthrough.

Just as we are appreciating the remarkable potential of cone snails as a source of new medicines, they are coming under intense pressure in the wild. Their shallow tropical habitats are rapidly being destroyed and snails are being collected at alarming rates from the wild to supply the ornamental shell trade as well as for biomedical research.

Cone snails are exquisitely beautiful and have been coveted by collectors since at least the 16th Century. A rare cone snail shell was sold at an Amsterdam auction in 1796 for more than a Vermeer painting! Collectors still cherish these shells, and rates of capture from the wild are escalating rapidly. "Millions of cone snails are now sold annually for as little as a few cents each in shops all over the world. But we could not find any country that monitors this trade" said co-author Callum Roberts, of the University of York, "Nobody is looking out for them."

Alongside overexploitation, cone snail habitats are being degraded and destroyed by coastal development, overfishing, pollution, disease and global climate change. A quarter of the planet's coral reefs have already been seriously damaged or destroyed and half of the world's mangroves cleared. The risk of global extinction is highest for species with narrow geographic distributions. The study found that one in five cone snail species had global ranges encompassing less than 3500km2 of reef, equivalent to a single medium sized atoll. For example, eight species are unique to the Philippines, the hub of the world's ornamental shell trade. People threaten 97% of Philippine coral reefs and extinctions are inevitable if impacts are not alleviated soon.

Habitat loss and escalating, uncontrolled exploitation make a lethal combination that today threatens with extinction cone snails and many other species of biomedical interest. "International markets can develop rapidly in the modern world, which means that wild populations can be decimated before regulatory agencies see any need to protect them." said Roberts. "For this reason, we believe all internationally traded organisms (whether alive or dead) must be monitored, regardless of whether they are currently listed as threatened. This would allow countries to identify emerging markets and act early enough to prevent depletion." This could be achieved, say the authors, by extending CITES (The Convention on International Trade in Endangered Species) to cover all wild-caught species. Meanwhile, at the earliest opportunity cone snails should be added to Appendix II of CITES, so requiring countries to monitor trade and prevent overexploitation.

"Wild nature has been the template for most of the medicines we use today but we have barely even begun to tap its potential", said Chivian, "If we fail to protect cone snails, the loss to future generations would be incalculable."

###

For More Information Contact:

Kathleen Frith, Director of Communications, HMS Center for Health and the Global Environment, Harvard Medical School, Boston, USA. Tel: 617-384-8591, kfrith@hms.harvard.edu

"All you have to decide is what to do with the time that is given you."
Gandolf the Gray

Max
10-17-2003, 10:34 AM
Poisoned potential

JOHN INNES


POISONOUS shellfish that live on coral reefs could provide a wealth of new medicines.

Yet just as scientists are beginning to discover the potential of cone snails, they are coming under threat.

Scientists yesterday appealed for action to protect the brightly-coloured creatures which are coveted by shell collectors. Dr Eric Chivian, from Harvard Medical School, in Boston, in the United States, said: "Tropical cone snails may contain the largest and most clinically important pharmacopoeia of any genus in nature, but wild populations are being decimated by habitat destruction and overexploitation. To lose these species would be a self-destructive act of unparalleled folly."

About 500 species of cone snails inhabit shallow tropical seas. They defend themselves and paralyse their prey - worms, fish, and other molluscs - by injecting a cocktail of toxins through a hollow, harpoon-like tooth.

Each species has its own distinct set of around 100 "conotoxins". Like a gourmet chef, they mix them in constantly changing proportions to prevent the evolution of resistance in their prey.

To date, only about 100 of the estimated 50,000 cone snail toxins have been characterised, and a mere handful tested for their medical potential.

Those investigated so far have already yielded enormous potential for biomedicine, Dr Chivian and a team of US and British experts wrote in the journal Science. More than 2,600 conotoxin studies had been published in 20 years.

Conotoxins that blocked key neurological pathways were shown to be effective in the diagnosis and possibly treatment of small-cell lung cancer, one of the biggest cancer killers. A conotoxin-based compound now in clinical trials also had a powerful anti-epileptic effect.

Other research suggested conotoxins could treat muscle spasticity following spinal cord injury, prevent cell death after strokes, head injuries or heart bypass surgery, and treat clinical depression, erratic heartbeats and urinary incontinence.

Pain treatment was the area where conotoxin research had advanced furthest. It had produced the synthetic drug Prialt which was undergoing extended phase III clinical trials for tackling severe, unremitting pain.

"Prialt may be 1,000 times more potent than morphine," said Dr Chivian. "More importantly, it does not seem to lead to addiction or tolerance."

The snails have been cherished by collectors since at least the 16th century - and one rare cone snail shell was sold at an Amsterdam auction in 1796 for more than a Vermeer painting.

Max
10-18-2003, 01:16 PM
"Wonder Drug" Snails Face Threats, Experts Warn

John Pickrell in England
for National Geographic News
October 16, 2003


A new report warns that a group of tropical sea snails, famous for yielding new wonder drugs to treat chronic pain, cancer, and many other afflictions, could rapidly become extinct if measures are not taken to protect them.

Read the full story >>






Cone snails have long been cherished for their beauty and some fetch high prices with collectors, but the toxins these animals produce could produce medicines of immeasurable value.

Photograph courtesy Callum Roberts





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More than 2,600 scientific studies over the last 20 years testify to the important contribution toxins extracted from cone snails have made to medicine and cellular biology. To date only 100 out of a potential 50,000 toxins have been extracted and analyzed. Despite this, few measures have been put in place to regulate exploitation or trade in these species, 69 percent of which live within regions where coral reefs are threatened by human activity.

The 500 known "tropical cone snails may contain the largest and most clinically important pharmacopoeia of any genus in nature," said medical scientist and study author Eric Chivian of Harvard University in Cambridge, Massachusetts. "But wild populations are being decimated by habitat destruction and overexploitation. To lose these species would be a self-destructive act of unparalleled folly."

The study is detailed in a letter to appear tomorrow in the research journal Science.

Pretty Dangerous

Beautiful yet deadly, cone snails mostly inhabit the shallow tropical waters of coral reefs or mangrove swamps. They harpoon other invertebrate prey with a concealed hollow tooth, through which they inject conotoxin venom. The venom is a mixture of different toxic protein molecules, of which each species might possess 100 varieties. Constantly revising that recipe makes it more difficult for prey to evolve resistance.

Cone snail shells come in a dazzling array of colors and patterns, said the letter's co-author, ecologist Callum Roberts at the University of York in England. "But as swimmers who made the mistake of tucking an attractive shell into their costume have found out, they produce a powerful venom." That poison is strong enough to paralyze or kill a person.

The snails' toxin molecules work by disrupting communication between cells, and this activity has made them very useful for understanding how cells work. However, the area in which conotoxin research shows the most promise is in clinical medicine. Treatments are under development for neurological auto-immune diseases, cancer, and chronic pain. One new synthetic drug developed from a conotoxin may be a thousand times more potent than morphine without any of the addictive properties. Conotoxins also have the potential to treat epilepsy and clinical depression.

Degradation and Exploitation

So far, as few as 100 venom molecules have been studied, with 95 percent of research carried out on just three of the 500 known species of cone snails, said Roberts. However, concurrent with the increase in interest in these species, they are facing threats in the wild as never before.

Although there has been little documented evidence of cone snail extinctions, "the reason we're very worried is that we know all the prerequisites for species to go extinct are in place," said Roberts. Many species live in narrow ranges, a fact that combined with wide-scale habitat destruction and exploitation for trade is a "lethal cocktail," he said.

The study reports 88 percent of Southeast Asia coral reefs are threatened by human activities. The region is home to 56 percent of cone snail species. Worryingly, nearly 70 percent of species face habitat loss in more than half of their current geographic ranges.

Habitat loss is exacerbated by direct exploitation. The attractive shells are collected in their millions from Mexico, Indonesia, Fiji, and elsewhere, and sold in seaside resort towns worldwide, said Roberts. It's not just the tourist industry though, he added. One unnamed U.S. research institute recently imported the venom glands from 10,000 snails collected in China.

"The recent increase in bioprospecting provides levels of harvesting which may well accelerate the current rates of decline," commented Mary Seddon, World Conservation Union (IUCN) mollusk specialist and biodiversity scientist at the National Museums and Galleries of Wales in Cardiff. Bioprospecting is the process of searching for new medicines, and otherwise useful compounds in nature.

Damage Limitation

Despite these threats, very few mollusk species enjoy international protection. "There are only five species of [cone snails] listed on the IUCN red list of globally threatened species," said Seddon. "This is not a true reflection of the potential threats of extinction for the rare and narrowly localized species."

The Convention on International Trade in Endangered Species (CITES), which serves to legally protect threatened animals, should be extended to cover cone snails, argues the Science letter. Earlier this month, additional protection was given under this convention to the queen conch mollusk, a popular food item famous for its enormous pink shell.

If the cone snail genus was added to a part of the CITES agreement known as Appendix II, their trade would be allowed to continue, said Roberts, but countries would be obliged to both monitor trade and limit exploitation.



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