Cone-snail depletion threatens medical research
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For personal use. Only reproduce with permission from The Lancet. THE LANCET Oncology Vol 4 December 2003 http://oncology.thelancet.com 714 Newsdesk Emanuele Sher (Lilly, Basingstoke, UK) is working on a conotoxin-based radioimmunoassay to detect early small-cell lung cancer, a tumour of neuroectodermal origin that expresses voltage-gated calcium channel proteins. Chivian and colleagues suggest that cone snails should be listed under the Convention on International Trade in Endangered Species, which would require trading countries to develop management plans to ensure that collection from the wild is sustainable. “Efforts to cultivate cone snails have so far failed”, says Roberts. “A surer way to sustain supplies is to invest in protecting wild stocks and their habitats. We urge companies seeking benefit from cone snail peptides to support this effort.” Dorothy Bonn The loss of marine snails from the Tropics could have devastating effects on the development of new cancer drugs, say scientists. Cone snails, prized by collectors, are a potentially rich source of powerful new medicines. But wild populations are being decimated by overfishing and by destruction of the coral reefs and mangroves they inhabit, says Eric Chivian (Harvard Medical School, Boston, MA, USA) and colleagues (Science 2003; 302: 391). About 500 species of cone snails are known, each producing a unique combination of toxins with which they paralyse their prey. Only about 100 of an estimated 50 000 conotoxins have been characterised so far, and only a few tested for pharmacological activity. “We will never know what drugs we might have discovered from species that have gone extinct”, says co-author Callum Roberts (University of York, UK). “The risk of extinction is greatest for species with a narrow geographical distribution, and one in five cone snails are in this category. Their marine habitats are disappearing as fast as the rainforests on land.” John Reynolds (University of East Anglia, Norwich, UK) comments: “Cone snails are particularly vulnerable, because they live in shallow water, where even the rarer ones are fairly easy to collect.” Conotoxins act on various recep- tors to block neural transmission at the neuromuscular junction. One of the attractions for researchers is their small size (10–30 aminoacids), which makes synthetic derivatives easy to manufac- ture. They are also very stable and selective in their receptor binding sites. Intrathecal ziconotide, a synthetic conotoxin that blocks a voltage-gated calcium channel in nerve terminals, is in phase III clinical trials for the relief of intractable pain, eg, in patients with cancer or AIDS. The data show that ziconotide is 1000 times more potent than morphine. Researchers at the University of Utah (Salt Lake City, UT, USA), who are beginning clinical trials for pain treatment with another cone-snail-derived peptide, are also building up a DNA library of natural conotoxins. Cone-snail depletion threatens medical research Formaldehyde link to cancer Investigators carrying out the largest extended follow-up of industrial workers to date have reported an increased risk of death from leukaemia (particularly myeloid leukaemia) in individuals exposed to formaldehyde. (J Natl Cancer Inst 2003; 95: 1615–23). Researchers compared mortality in 25 619 workers (producing formal- dehyde, molded plastics, photographic film, and plywood) exposed to varying amounts of formaldehyde, from back- ground concentrations of 0·1 ppm to high short-term exposures of more than 4·0 ppm. The average exposure was associated with an increase in lymphohaematopoietic cancers. “But the most interesting and extraordinary measure was peak expo- sure, which has not been studied in an industrial cohort of formaldehyde workers before”, says lead author Michael Hauptmann (National Can- cer Insititute, Bethesda, MD, USA). Peak exposure defined workers whose average exposure was exceeded by short bursts of high contact with for- maldehyde, for example, when loading mixing machines. Workers with peak exposures >4·0 ppm had a relative risk of 3·5 of myeloid leukaemia. However, another study published in the same issue of J Natl Cancer Inst (2003; 95: 1608–15) followed 14 014 British factory workers who produced or used formaldehyde and found a positive association with risk of lung cancer. Overall, the cohort showed no evidence of haematopoietic cancers. Lead author David Coggon (Medi- cal Research Council Environmental Epidemiology Unit, Southampton, UK) catagorised workers into four exposure categories with high expo- sure more than 2 ppm. “However, the factory with greatest exposures was located where lung cancer rates are higher than average”, explains Cog- gon. When adjusted for location, the excess was less but still significant. “These studies present different conclusions about leukaemia risk among formaldehyde workers”, com- ments James J Collins (Dow Chemical Company, MI, USA). “Because of the biological implausibility of this finding and the inconsistency across studies, formaldehyde is probably not a leukaemogen”, he states. “However, increased risk of leukaemia and other diseases such as pancreatic cancer have been observed among pathologists and may be due to better diagnosis or to occupational exposures other than formaldehyde in this profession.” Kathleen Nelson Cone snails need protecting. Callum Roberts
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Transcript of Cone-snail depletion threatens medical research
For personal use. Only reproduce with permission from The Lancet.
THE LANCET Oncology Vol 4 December 2003 http://oncology.thelancet.com714
Newsdesk
Emanuele Sher (Lilly, Basingstoke,UK) is working on a conotoxin-basedradioimmunoassay to detect early
small-cell lung cancer, a tumour ofneuroectodermal origin that expressesvoltage-gated calcium channelproteins.
Chivian and colleagues suggest thatcone snails should be listed under theConvention on International Trade inEndangered Species, which wouldrequire trading countries to developmanagement plans to ensure thatcollection from the wild is sustainable.“Efforts to cultivate cone snails have sofar failed”, says Roberts. “A surer wayto sustain supplies is to invest inprotecting wild stocks and theirhabitats. We urge companies seekingbenefit from cone snail peptides tosupport this effort.”Dorothy Bonn
The loss of marine snails from theTropics could have devastating effectson the development of new cancerdrugs, say scientists. Cone snails, prizedby collectors, are a potentially richsource of powerful new medicines. Butwild populations are being decimatedby overfishing and by destruction of thecoral reefs and mangroves they inhabit,says Eric Chivian (Harvard MedicalSchool, Boston, MA, USA) andcolleagues (Science 2003; 302: 391).
About 500 species of cone snailsare known, each producing a uniquecombination of toxins with which theyparalyse their prey. Only about 100 ofan estimated 50 000 conotoxins havebeen characterised so far, and only afew tested for pharmacologicalactivity. “We will never know whatdrugs we might have discovered fromspecies that have gone extinct”, saysco-author Callum Roberts (Universityof York, UK). “The risk of extinction isgreatest for species with a narrowgeographical distribution, and one infive cone snails are in this category.Their marine habitats are disappearingas fast as the rainforests on land.” JohnReynolds (University of East Anglia,Norwich, UK) comments: “Conesnails are particularly vulnerable,because they live in shallow water,where even the rarer ones are fairlyeasy to collect.”
Conotoxins act on various recep-tors to block neural transmission at theneuromuscular junction. One of theattractions for researchers is their smallsize (10–30 aminoacids), which makessynthetic derivatives easy to manufac-ture. They are also very stable andselective in their receptor binding sites.
Intrathecal ziconotide, a syntheticconotoxin that blocks a voltage-gatedcalcium channel in nerve terminals, isin phase III clinical trials for the relief ofintractable pain, eg, in patients withcancer or AIDS. The data show thatziconotide is 1000 times more potentthan morphine. Researchers at theUniversity of Utah (Salt Lake City, UT, USA), who are beginning clinicaltrials for pain treatment with anothercone-snail-derived peptide, are alsobuilding up a DNA library of naturalconotoxins.
Cone-snail depletion threatens medical research
Formaldehyde link to cancerInvestigators carrying out the largestextended follow-up of industrialworkers to date have reported anincreased risk of death from leukaemia(particularly myeloid leukaemia) inindividuals exposed to formaldehyde.(J Natl Cancer Inst 2003; 95: 1615–23).
Researchers compared mortality in25 619 workers (producing formal-dehyde, molded plastics, photographicfilm, and plywood) exposed to varyingamounts of formaldehyde, from back-ground concentrations of 0·1 ppm tohigh short-term exposures of morethan 4·0 ppm. The average exposurewas associated with an increase inlymphohaematopoietic cancers.
“But the most interesting andextraordinary measure was peak expo-sure, which has not been studied in an industrial cohort of formaldehydeworkers before”, says lead authorMichael Hauptmann (National Can-cer Insititute, Bethesda, MD, USA).Peak exposure defined workers whoseaverage exposure was exceeded byshort bursts of high contact with for-maldehyde, for example, when loadingmixing machines. Workers with peakexposures >4·0 ppm had a relative riskof 3·5 of myeloid leukaemia.
However, another study publishedin the same issue of J Natl Cancer Inst
(2003; 95: 1608–15) followed 14 014British factory workers who producedor used formaldehyde and found apositive association with risk of lungcancer. Overall, the cohort showed noevidence of haematopoietic cancers.
Lead author David Coggon (Medi-cal Research Council EnvironmentalEpidemiology Unit, Southampton,UK) catagorised workers into fourexposure categories with high expo-sure more than 2 ppm. “However, thefactory with greatest exposures waslocated where lung cancer rates arehigher than average”, explains Cog-gon. When adjusted for location, theexcess was less but still significant.
“These studies present differentconclusions about leukaemia riskamong formaldehyde workers”, com-ments James J Collins (Dow ChemicalCompany, MI, USA). “Because of thebiological implausibility of this findingand the inconsistency across studies,formaldehyde is probably not aleukaemogen”, he states. “However,increased risk of leukaemia and otherdiseases such as pancreatic cancer havebeen observed among pathologists andmay be due to better diagnosis or tooccupational exposures other thanformaldehyde in this profession.” Kathleen Nelson
Cone snails need protecting.
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