外报阅读07.docx

外报阅读07.docx

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外报阅读07

Passage1:

Treatingcancerwithradioactivebacteria

Threewrongsmakearight

Asurprisingnewwaytokilltumours

Apr27th2013|Fromtheprintedition

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PANCREATICcancerisadreadfuldisease.Eveninrichcountries,onlyabout4%ofthosediagnosedwithitarestillaliveafterfiveyears.InAmericaitisthethird-most-commoncauseofcancerdeathsamongwomen,afterlungandbreastcancer;amongmenitisfourth,afterlung,prostateandcolorectalcancer.Dispiritingly,therehasbeenlittleprogressintreatingitformorethanaquarterofacentury.

Thereasonpancreaticcancerissodeadlyisthatitmetastasisesquickly.Thisspreadingofsecondarytumoursaroundthebodydamagesotherorgansandhasprovedimpossibletostop.ButagroupofresearchersledbyClaudiaGravekampoftheAlbertEinsteinCollegeofMedicine,inNewYork,haveanintriguingideaforchangingthat.AstheydescribeinapaperintheProceedingsoftheNationalAcademyofSciences,theyplantodoitbyinfectingpeoplewithradioactivebacteria.

DrGravekampcameupwiththeideafollowingherdiscoverythatweakenedbacteria（specifically,amodifiedformofListeriamonocytogenes）shewasusingforotherpurposesintumour-afflictedmice,andwhichwereclearedfrommostoftheanimal’sbodybyitsimmunesystemoverthecourseofafewdays,remainedinthetumours.Thiswasthankstotheabilitycancercellsevolvetosuppresstheimmunesystem’sactivitieswithintheirpurview.Withoutthattalent,cancersthemselveswouldfindtheywereunderfatalassaultfromtheimmunesystem.

DrGravekampandhercolleaguesthereforethoughtthattheirbacteriamightbeusedtodeliveranti-canceragentsspecificallytotumours.Atfirst,theyconsideredusingdrugs.ButontheadviceofEkaterinaDadachova,aradiologistandoneofthepaper’sauthors,theyeventuallyplumpedforattachingaradioactiveisotopeofrheniumtotheirbugs.

Radioactiverheniumiscommonlyusedinconventionalradiotherapy.DrGravekamp’shopewasthat,becausethebugsstickaroundinthecancer,theywouldprovideanovelwaytosolveradiotherapy’sbiggestproblem:

ensuringthatthetumouritselfiszappedhardwhileminimisingtheamountofradiationhittingsurroundinghealthytissue.

Andthat,moreorless,iswhathappened.Thebacteriatoleratedtheirradioactivepayloadswithlittlecomplaint.Inmicewithpancreaticcancer,acourseofseveraltreatmentswiththemkilledoffaround90%ofmetastasisedtumoursandmadeanotabledentintheoriginaltumouraswell.Admittedly,thetechnique’saimwasnotperfect.Theanimals’liversandkidneys,inparticular,receivedhighdosesofradiation—higher,infact,thanthoseenduredbythetumours.DrDadachovathinksthisisbecause,astheimmunesystemkilledtheListeria,theradioactiveremainsofthebacteriawereshippedtothelivertobebrokendownandrecycled,whileanythingunusablewascollectedbythekidneysforexcretion.

Fortunatelythismaynotmatter,forthehighdosesofradiationtheliverandkidneysreceiveddidnotseemtodothemmuchdamage.Thetumours,bycontrast,werefatallyafflicted.Thatdisparityisprobablybecauseofthewayinwhichradiationkills.ItsmaineffectistobreakDNAmolecules.Enoughofthesebreaksoverwhelmacell’sabilitytorepairitsDNA,causingittodie.Thefasteracellisdividing,themoresusceptibleitistothissortofdamage—andacancerisnothingmorethanamassofcellsthataredividingrapidlyanduncontrollably.

Asfarastheresearcherscoulddivine,theirproposedtreatmentcausesfewside-effects.Inclinicaltrialsinothercontexts,peopleexperimentallyinfectedwithanon-radioactiveformoftheweakenedListeriareportedonlymildandtransientflu-likesymptoms.DrDadachova’smice,whichgotthefull-strength,glow-in-the-darkversionofthebacteria,seemedsimilarlyunbothered.

Ofcourse,effectivenessinmiceisnotthesameaseffectivenessinpeople.Onequibbleisthatthenumberofmicegiveneachvariantofthetreatmentwassmall（justfive）,thoughtheresearchersarguethatthestrengthoftheeffecttheyobservedisenoughtoovercomeworriesaboutsuchsamplesizes.

DrGravekampandhercolleaguesarenowtryingtoimprovetheirtreatmentinmice,andareseekingsponsorsforatrialinpeople.Ifthatworks,thenthreenegatives（aninfectiousbacterium,aradioactiveisotopeandanastycancer）willhavecometogethertoproduceapositiveoutcome—apieceofmedicalalgebrathatdefiesconventionalmathematics.

Passage2:

Biotechnologypatents

Naturaljustice

America’sSupremeCourtistoruleonthepatentingofgenes

Apr20th2013|Fromtheprintedition

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Examiningthecase

THEninejusticesonAmerica’sSupremeCourtmustapplytheirmindstothethorniestoflegalquestions.OnApril15ththeywerepresentedwithaparticularlytestingpuzzler:

shouldthelawallowpeopletopatenthumangenes?

Thecaseistheculminationofabattlethatbeganin2009.ItpitsAmerica’sAssociationforMolecularPathologyandvariousotherinterestedparties—representedbylawyersfromtheAmericanCivilLibertiesUnion—againstMyriadGenetics,abiotechnologyfirmthatholdspatentsontwohumangenes,calledBRCA1andBRCA2.ThatmakesMyriadthesoleproducerofteststodetectmutationsinthosegenes.Suchmutationsoftenincreaseawoman’sriskofdevelopingbreastorovariancancer.

Itisanemotionallychargedquestion.Patentofficesaroundtheworldhavebeengrantingpatentsongenes,humanandotherwise,fordecades,buttimehasdonelittletosoftenoppositiontotheidea.Laymenareoftenbaffledwhentheyfindoutthatitispossibletopatentpartsofthehumangenome.Anti-patentingcampaignersarguethattheideaofclaimingapatentoverthesharedgeneticheritageofthehumanraceisabsurd,immoralorboth.

Butthecourtisunlikelytobaseitsrulingonsuchairyethicalprinciples.Thelegaldebaterevolvesnotaroundthetwogenes’humanness,buttheirnaturalness—forthejudgesarebeingaskedtorulewhetherMyriad’sgenescountasa“productofnature”.Iftheydo,thenunderAmericanlawtheycannotbepatented.

Atfirstglance,itmayseemoddtoarguethatageneisanythingotherthanaproductofthenaturalworld.ButMyriad’spatentsdonotcoverthegenesastheyoccurinlivingcells.Rather,theycoverisolatedformsofthegenes,whichhavebeenidentified,snippedfromthegenomeandchemicallymodifiedtomakethemanalysableinalaboratory.Myriadarguesthatthesealterations,andthenewusetowhichtheresultinggeneisputaspartofadiagnostictest,maketheirproductsufficientlyinnovativetobeworthyofthelaw’sprotection.

Theplaintiffs（andthejudgewhofirstruledagainstMyriadin2010）saythisreasoningisspurious:

thechemicalchangesaretrivial,andtheresultingbitofDNAusefulonlybecauseitisidenticalineverymeaningfulwaytotheversionthatoccursinvivo.Doctors,patientsandbiotechnologycompaniesareinterestedintheinformationcontentofgenes,theargumentruns,nottheincidentaldetailsoftheirchemicalcomposition.Forawhile,thecourtfounditselfboggeddowninanalogieswiththepatent-eligibilityofchocolate-chipcookiesandbaseballbats.

ThereareothercriticismsofMyriad.Oneisthatitspatentsaretoobroad.Thefirm’stestslookforvariationsinBRCAgenes.Ratherthanpatentingeveryconceivablevariant,thecompanyclaimsjurisdictionoverisolatedDNAsequences,15basepairslong,thatmatchshortpartsofthegenes.（Thebasesinquestionarethechemical“letters”ofthegeneticcode.）AnanalysisbyJeffreyRosenfeldandChristopherMason,oftheSacklerInstituteforComparativeGenomicsandCornellUniversityrespectively,publishedinGenomeMedicine,foundthat689otherhumangenescontain15-base-pairstringsfoundinBRCA1,suggestingMyriad’spatentstechnicallycoverthoseunrelatedgenes,too.

Theeconomicsofgenomics

TheargumentsrangedbeyondthearcanaofhumangeneticsandAmericanpatentlaw.Thejudgeswerekeentoexploretheimpactofahypotheticalanti-Myriadrulingonthecountry’sthrivingbiotechnologyindustry,which,accordingtooneestimate,wasworth$92billionin2011.SeveralquestionedChristopherHansen,theplaintiffs’lawyer,onwhatincentivefirmswouldhavetoidentifyinterestinggenesiftherewerenopossibilityofwinningapatentonthem.Developingsuchtestsisnotcheap.AccordingtoMarkCapone,Myriad’spresident,thefirmspentaround$500mbeforeithadaproductitcouldbringtomarket.

Othersarguethatsuchpatentsholdbackbiotechnology,anindustrythatischangingfast.DonaldVerrilli,America’ssolicitorgeneral,whorepresentsthegovernment’sviewinthecase（itsupportsneitherside）,pointedoutthatcompetitorsneedthepatent-holder’spermissiontoisolatethegenestoseeiftheycandevelopabettertest,oreventoexaminethemforanyothereffectstheymayhave.

Someobserversthinkananti-Myriadrulingwouldhavelittlepracticaleffect.Thefirm’spatentsexpirein2015,andtechnologyhasmovedon.Thecostofgeneticsequencingisfallingfast,anditmaysoonbepossibleforpeopletohavetheirentiregenomessequencedforlessthantheroughly$4,000Myriadchargesforitstests.Anygenesofinterestcouldthusbeexaminedforworrisomemutations,probablywithoutinfringinganypatents.AndMrHansenconcededthatmuchworkinmodernbiotechconcernsrecombinantDNA,whichinvolvescuttingandpastingDNAfromdifferentsourcestomakesyntheticsequencesnotfoundinnature,somethingthattheplaintiffsagreeshouldbecoveredbypatentlaw.

Whateverconclusionthecourtcomesto,thejudgesseemedkeentoavoidanoverlybroadruling.Thatmay