Roguetheoryofsmellgetsaboost

1.Acontroversialtheoryofhowwesmell,whichclaimsthatourfinesenseofodourdependsonquantummechanics,hasbeengiventhethumbsupbyateamofphysicists.

2.CalculationsbyresearchersatUniversityCollegeLondon(UCL)showthattheideathatwesmellodourmoleculesbysensingtheirmolecularvibrationsmakessenseintermsofthephysicsinvolved.

3.That'sstillsomewayfromprovingthatthetheory,proposedinthemid-1990sbybiophysicistLucaTurin,iscorrect.Butitshouldmakeotherscientiststaketheideamoreseriously.

4."Thisisabigstepforward,"saysTurin,whohasnowsetuphisownperfumecompanyFlexitralinVirginia.Hesaysthatsincehepublishedhistheory,"ithasbeenignoredratherthancriticized."

5.Mostscientistshaveassumedthatoursenseofsmelldependsonreceptorsinthenosedetectingtheshapeofincomingmolecules,whichtriggersasignaltothebrain.Thismolecular'lockandkey'processisthoughttoliebehindawiderangeofthebody'sdetectionsystems:itishowsomepartsoftheimmunesystemrecogniseinvaders,forexample,andhowthetonguerecognizessometastes.

6.ButTurinarguedthatsmelldoesn'tseemtofitthispictureverywell.Moleculesthatlookalmostidenticalcansmellverydifferent—suchasalcohols,whichsmelllikespirits,andthiols,whichsmelllikerotteneggs.Andmoleculeswithverydifferentstructurescansmellsimilar.Moststrikingly,somemoleculescansmelldifferent—toanimals,ifnotnecessarilytohumans—simplybecausetheycontaindifferentisotopes(atomsthatarechemicallyidenticalbuthaveadifferentmass).

7.Turin'sexplanationforthesesmellyfactsinvokestheideathatthesmellsignalinolfactoryreceptorproteinsistriggerednotbyanodourmolecule'sshape,butbyitsvibrations,whichcanenourageanelectrontojumpbetweentwopartsofthereceptorinaquantum-mechanicalprocesscalledtunnelling.Thiselectronmovementcouldinitiatethesmellsignalbeingsenttothebrain.

8.Thiswouldexplainwhyisotopescansmelldifferent:theirvibrationfrequenciesarechangediftheatomsareheavier.Turin'smechanism,saysMarshallStonehamoftheUCLteam,ismorelikeswipe-cardidentificationthanakeyfittingalock.

9.Vibration-assistedelectrontunnellingcanundoubtedlyoccur—itisusedinanexperimentaltechniqueformeasuringmolecularvibrations."Thequestioniswhetherthisispossibleinthenose,"saysStoneham'scolleague,AndrewHorsfield.

10.StonehamsaysthatwhenhefirstheardaboutTurin'sidea,whileTurinwashimselfbasedatUCL,"Ididn'tbelieveit".But,headds,"becauseitwasaninterestingidea,IthoughtIshouldproveitcouldn'twork.Ididsomesimplecalculations,andonlythenbegantofeelLucacouldberight."NowStonehamandhisco-workershavedonethejobmorethoroughly,inapapersoontobepublishedinPhysicalReviewLetters.

11.TheUCLteamcalculatedtheratesofelectronhoppinginanosereceptorthathasanodorantmoleculeboundtoit.Thisratedependsonvariouspropertiesofthebiomolecularsystemthatarenotknown,buttheresearcherscouldestimatetheseparametersbasedontypicalvaluesformoleculesofthissort.

12.Thekeyissueiswhetherthehoppingratewiththeodorantinplaceissignificantlygreaterthanthatwithoutit.Thecalculationsshowthatitis—whichmeansthatodouridentification

newweapontofightcancer

1.Britishscientistsarepreparingtolaunchtrialsofaradicalnewwaytofightcancer,whichkillstumoursbyinfectingthemwithviruseslikethecommoncold.

2.Ifsuccessful,virustherapycouldeventuallyformathirdpillaralongsideradiotherapyandchemotherapyinthestandardarsenalagainstcancer,whileavoidingsomeofthedebilitatingside-effects.

3.LeonardSeymour,aprofessorofgenetherapyatOxfordUniversity,whohasbeenworkingonthevirustherapywithcolleaguesinLondonandtheUS,willleadthetrialslaterthisyear.CancerResearchUKsaidyesterdaythatitwasexcitedbythepotentialofProfSeymour’spioneeringtechniques.

4.Oneofthecountry’sleadinggeneticists,ProfSeymourhasbeenworkingwithvirusesthatkillcancercellsdirectly,whileavoidingharmtohealthytissue."Inprinciple,you’vegotsomethingwhichcouldbemanytimesmoreeffectivethanregularchemotherapy,"hesaid.

5.Cancer-killingvirusesexploitthefactthatcancercellssuppressthebody’slocalimmunesystem."Ifacancerdoesn’tdothat,theimmunesystemwipesitout.Ifyoucangetavirusintoatumour,virusesfindthemaverygoodplacetobebecausethere’snoimmunesystemtostopthemreplicating.Youcanregarditasthecancer’sAchilles’heel."

6.Onlyasmallamountofthevirusneedstogettothecancer."Theyreplicate,yougetamillioncopiesineachcellandthecellburstsandtheyinfectthetumourcellsadjacentandrepeattheprocess,"saidProfSeymour.

7.Preliminaryresearchonmiceshowsthatthevirusesworkwellontumoursresistanttostandardcancerdrugs."It’saninterestingpossibilitythattheymayhaveanadvantageinkillingdrug-resistanttumours,whichcouldbequitedifferenttoanythingwe’vehadbefore."

8.Researchershaveknownforsometimethatvirusescankilltumourcellsandsomeaspectsoftheworkhavealreadybeenpublishedinscientificjournals.Americanscientistshavepreviouslyinjectedvirusesdirectlyintotumoursbutthistechniquewillnotworkifthecancerisinaccessibleorhasspreadthroughoutthebody.

9.ProfSeymour’sinnovativesolutionistomaskthevirusfromthebody’simmunesystem,effectivelyallowingthevirusestodowhatchemotherapydrugsdo-spreadthroughthebloodandreachtumourswherevertheyare.Thebighurdlehasalwaysbeentofindawaytodelivervirusestotumoursviathebloodstreamwithoutthebody’simmunesystemdestroyingthemontheway.

10."Whatwe’vedoneismakechemicalmodificationstothevirustoputapolymercoataroundit-it’sastealthviruswhenyouinjectit,"hesaid.

11.Afterthestealthvirusinfectsthetumour,itreplicates,butthecopiesdonothavethechemicalmodifications.Iftheyescapefromthetumour,thecopieswillbequicklyrecognisedandmoppedupbythebody’simmunesystem.

12.Thetherapywouldbeespeciallyusefulforsecondarycancers,calledmetastases,whichsometimesspreadaroundthebodyafterthefirsttumourappears."There’sanawfulstatisticofpatientsinthewest...withmalignantcancers;75%ofthemgoontodiefrommetastases,"saidProfSeymour.

13.Twovirusesarelikelytobeexaminedinthefirstclinicaltrials:adenovirus,whichnormallycausesacold-likeillness,andvaccinia,whichcausescowpoxandisalsousedinthevaccineagainstsmallpox.Forsafetyreasons,bothwillbedisabledtomakethe

Don'twashthosefossils!

StandardmuseumpracticecanwashawayDNA.

1.Washing,brushingandvarnishingfossils—allstandardconservationtreatmentsusedbymanyfossilhuntersandmuseumcuratorsalike—vastlyreducesthechancesofrecoveringancientDNA.

2.Instead,excavatorsshouldbehandlingatleastsomeoftheirbountywithgloves,andfreezingsamplesastheyarefound,dirtandall,concludesapaperintheProceedingsoftheNationalAcademyofSciencestoday.

3.AlthoughmanypalaeontologistsknowanecdotallythatthisisthebestwaytouptheoddsofextractinggoodDNA,Eva-MariaGeigloftheJacquesMonodInstituteinParis,France,andhercolleagueshavenowshownjusthowimportantconservationpracticescanbe.Thisinformation,theysay,needstobehammeredhomeamongthepeoplewhoareactuallyoutinthefielddiggingupbones.

4.Geiglandhercolleagueslookedat3,200-year-oldfossilbonesbelongingtoasingleindividualofanextinctcattlespecies,calledanaurochs.ThefossilsweredugupatasiteinFranceattwodifferenttimes—eitherin1947,andstoredinamuseumcollection,orin2004,andconservedinsterileconditionsat-20oC.

5.Theteam'sattemptstoextractDNAfromthe1947bonesallfailed.Thenewlyexcavatedfossils,however,allyieldedDNA.

6.Becausetheboneshadbeenburiedforthesameamountoftime,andinthesameconditions,theconservationmethodhadtobetoblamesaysGeigl."AsmuchDNAwasdegradedinthese57yearsasinthe3,200yearsbefore,"shesays.

Washin,washout

7.Becausemanypalaeontologistsbasetheirworkontheshapeoffossilsalone,theirmethodsofconservationarenotdesignedtopreserveDNA,Geiglexplains.

8.Thebiggestproblemishowtheyarecleaned.Fossilsareoftenwashedtogetheron-siteinalargebath,whichcanallowwater—andcontaminantsintheformofcontemporaryDNA—topermeateintotheporousbones."NotonlyistheauthenticDNAgettingwashedout,butcontaminationisgettingwashedin,"saysGeigl.

9.MostancientDNAspecialistsknowthisalready,saysHendrikPoinar,anevolutionarygeneticistatMcMasterUniversityinOntario,Canada.Butthatdoesn'tmeanthatbestpracticehasbecomewidespreadamongthosewhoactuallyfindthefossils.

10.GettingholdoffossilsthathavebeenpreservedwiththeirDNAinmindreliesoncloserelationshipsbetweenlab-basedgeneticistsandtheexcavators,sayspalaeogeneticistSvantePbooftheMaxPlanckInstituteforEvolutionaryAnthropologyinLeipzig,Germany.Andthatonlyoccursinexceptionalcases,hesays.

11.Pbo'steam,whichhasbeensequencingNeanderthalDNA,continuallyfacestheseproblems."WhenyouwanttostudyancienthumanandNeanderthalremains,there'sabigissueofcontaminationwithcontemporaryhumanDNA,"hesays.

12.Thisdoesn'tmeanthatallmuseumspecimensarefatallyflawed,notesPbo.TheNeanderthalfossilsthatwererecentlysequencedinhisownlab,forexample,hadbeenpartofamuseumcollectiontreatedinthetraditionalway.ButPboiskeentoseesamplesoffossilsfromeverymajorfindpreservedinlinewithGeigl'srecommendations—justincase.

Warmandwet

13.Geiglherselfbelievesthat,withcooperationbetweenbenchandfieldresearchers,preservingfossilsproperlycouldopenupavenuesofdiscoverythathavelongbeenassumedcl

1.Thefailureofahigh-profilecholesteroldrughasthrownaspotlightonthecomplicatedmachinerythatregulatescholesterollevels.Butmanyresearchersremainconfidentthatdrugstoboostlevelsof'good'cholesterolarestilloneofthemostpromisingmeanstocombatspirallingheartdisease.

2.DrugcompanyPfizerannouncedon2Decemberthatitwascancellingallclinicaltrialsoftorcetrapib，adrugdesignedtoraiseheart-protectivehigh-densitylipoproteins(HDLs).Inatrialof15000patients，asafetyboardfoundthatmorepeoplediedorsufferedcardiovascularproblemsaftertakingthedrugplusacholesterol-loweringstatinthanthoseinacontrolgroupwhotookthestatinalone.

3.Thenewscameasakickintheteethtomanycardiologistsbecauseearliertestsinanimalsandpeoplesuggesteditwouldlowerratesofcardiovasculardisease."Therehavebeennoredflagstomyknowledge,"saysJohnChapman，aspecialistinlipoproteinsandatherosclerosisattheNationalInstituteforHealthandMedicalResearch(INSERM)inPariswhohasalsostudiedtorcetrapib."Thiscancellationcameasacompleteshock."

4.TorcetrapibisoneofthemostadvancedofanewbreedofdrugsdesignedtoraiselevelsofHDLs，whichferrycholesteroloutofartery-cloggingplaquestotheliverforremovalfromthebody.Specifically，torcetrapibblocksaproteincalledcholesterolestertransferprotein(CETP)，whichnormallytransfersthecholesterolfromhigh-densitylipoproteinstolowdensity，plaque-promotingones.Statins，incontrast，mainlyworkbyloweringthe'bad'low-densitylipoproteins.

Underpressure

5.Researchersarenowtryingtoworkoutwhyandhowthedrugbackfired，somethingthatwillnotbecomeclearuntiltheclinicaldetailsarereleasedbyPfizer.Onehintliesinevidencefromearliertrialsthatitslightlyraisesbloodpressureinsomepatients.Itwasthoughtthatthismildproblemwouldbeoffsetbytheheartbenefitsofthedrug.Butitispossiblethatitactuallyprovedfatalinsomepatientswhoalreadysufferedhighbloodpressure.Ifbloodpressureistheexplanation，itwouldactuallybegoodnewsfordrugdevelopersbecauseitsuggeststhattheproblemsarespecifictothiscompound.OtherprototypedrugsthatarebeingdevelopedtoblockCETPworkinaslightlydifferentwayandmightnotsufferthesamedownfall.

6.ButitisalsopossiblethatthewholeideaofblockingCETPisflawed，saysMotiKashyap，whodirectsatherosclerosisresearchattheVAMedicalCenterinLongBeach，California.WhenHDLsexcretecholesterolintheliver，theyactuallyrelyonLDLsforpartofthisprocess.SoinhibitingCETP，whichpreventsthetransferofcholesterolfromHDLtoLDL，mightactuallycauseanabnormalandirreversibleaccumulationofcholesterolinthebody."You'reblockingaphysiologicmechanismtoeliminatecholesterolandeffectivelyconstipatingthepathway,"saysKashyap.Goingup

7.Mostresearchersremainconfidentthatelevatinghighdensitylipoproteinslevelsbyonemeansoranotherisoneofthebestroutesforhelpingheartdiseasepatients.ButHDLsarecomplexandnotentirelyunderstood.Oneapproveddrug，calledniacin，isknowntobothraiseHDLandreducecardiovascularriskbutalsocausesanunpleasantsensationofheatandtingling.Researchersareexploringwhethertheycanbypassthissideeffectandwhetherniacincanlowerdiseaseriskmorethanstatinsalone.Scientistsarealsoworkingonseveralothermeanstobumpuphigh-densitylipoproteinsby，forexample，introducingsyntheticHDLs."Theonlythingw

Moreandmorecompaniesareallowingemployeestoworkathome.Doyouthinkthisisapositiveornegativedevelopment?