HavedoctorsbeenwrongabouthowtotreatAlzheimer’sdisease?医生们治疗阿尔兹海默症的方法是否一直存在谬误？AnewbookarguesthatdogmaandbadscienceledAlzheimer’sresearchastray一本新书揭露：教条主义与伪科学如何将阿尔兹海默研究引入歧途Alzheimer’sdiseaseaffectsmorethan30mpeopleworldwide,mostlytheelderly.Aftertheageof65,thechanceofdevelopingitdoubleseveryfiveyears.By85,theoddsareoneinthree. 阿尔兹海默症影响着全球超3000万人，患者多为老年人。65岁后罹患此病的风险每五年翻一番，85岁人群患病率高达三分之一。Itssymptoms,whichincludememoryloss,difficultywithbasictasksanddepression,progressivelyworsen.Asgloballifeexpectancyrises,sowillcasesofAlzheimer’s,makingitoneofthebigpublic-healthchallengesofanageingworld.其症状包括记忆衰退、基础行动困难与抑郁情绪，且会持续恶化。随着全球预期寿命延长，阿尔兹海默症病例将持续攀升，成为老龄化社会面临的重大公共卫生挑战。Thereisnocure.Between1995and2021,around$42bnwaspouredintomorethan1,000clinicaltrials.Yetonlyahandfulofdrugshasmadeittomarket.Eventhosemostlytreatthesymptomsofthedisease,ratherthanstopit.目前该病尚无根治之法。1995至2021年间，超420亿美元资金投入到1000多项临床试验，但仅有寥寥数款药物成功上市。即便获批药物也仅能缓解症状，无法阻止病程发展。TheleadingexplanationofAlzheimer’sisthe“amyloidhypothesis”,whichsuggeststhatdepositsofbeta-amyloid,atypeofprotein,accumulatebetweenneuronsanddisrupttheirfunction. 主流理论"淀粉样蛋白假说"认为，β-淀粉样蛋白在神经元间沉积导致功能紊乱。Butthetheoryremainscontroversial:allbrainswithAlzheimer’sshowbeta-amyloidplaques,yetnoteveryonewiththeseplaquesexperiencescognitivedecline.Whetheramyloidbuild-upcausesAlzheimer’s,orismerelyasymptom,remainsunresolved.但该理论始终存在争议：所有阿尔兹海默患者脑部均存在淀粉样斑块，但具有此类斑块者未必都会出现认知衰退。淀粉样蛋白堆积究竟致病还是仅为病症表现，至今未有定论。In“Doctored”CharlesPiller,asciencejournalist,detailshowgroupthinkanddishonestysteeredAlzheimer’sresearchoffcourse.In2006 aNaturepaper byresearchersattheUniversityofMinnesotaappearedtoprovideamajorbreakthrough.Thestudyclaimedthatasubtypeofbeta-amyloidcausedmemoryimpairment.Itquicklybecameoneofthemostcitedpapersandinspiredhundredsofmillionsofdollarsinpublic-researchgrants. 科学记者查尔斯·皮勒在《篡改的科学》一书中详述了群体思维与学术不端如何扭曲阿尔兹海默研究。2006年明尼苏达大学研究团队在《自然》发表的论文看似取得重大突破，声称某种β-淀粉样亚型会导致记忆损伤。这篇高被引论文催生了数亿美元公共研究经费。Anotherinfluentialpaperpublishedin2012byscientistsassociatedwithCassavaSciences,abiotechfirm, bolstered theamyloidtheorybylinkinginsulinresistancetoamyloidplaqueformation.ThefindingfuelledawaveofresearchintotheideaofAlzheimer’sbeinga“diabetesofthebrain”thatcouldbemanagedwithdrugs.Therewasjustoneproblem—bothstudieswerebasedon falsifieddata.2012年生物科技公司木薯科学关联科学家发表的另一重磅论文，通过论证胰岛素抵抗与淀粉样斑块形成的关联进一步巩固该假说，引发"脑部糖尿病"治疗理念的研究热潮。但问题在于——两项研究均基于伪造数据。“Doctored”followsMrPiller’sinvestigationintothedeception.Centraltothestoryisagroupofimage sleuths,withasharpeyeformanipulatedpixelsofWesternblots(alabtechniqueusedtostudyproteins,whichwere doctoredinthestudies). 《篡改的科学》记录了皮勒对学术造假的调查历程。故事核心是一群图像侦探，他们以专业眼光识别蛋白质印迹实验（研究中遭篡改的蛋白质检测技术）的像素篡改痕迹。Somechaptersreadlikeascientific whodunnit.Inone,MrPillerhastoworkhardtoearnthetrustofa reluctantwhistleblower.Inanother,hetravelstoPragueforaprivatemeetingwithagroupofimagedetectiveswithcrypticpseudonyms.部分章节犹如科学探案：皮勒需费尽周折赢得泄密者信任；又专程赴布拉格与化名神秘的图像分析专家秘密会面。Despiteclearevidenceofmanipulatedresearchresults,journalsandregulatorswereslowtoact.MrPillerblamespowerfulbackersoftheamyloidhypothesiswhoignoredredflags. 尽管篡改证据确凿，期刊与监管机构却反应迟缓。皮勒指责淀粉样假说的权势支持者刻意忽视危险信号。ItwasonlyinJune2024—twoyearsafterallegationsfirstsurfaced—thattheNaturepaperwasretractedbyitsauthors.CassavaSciences,whiledenyingwrongdoing,stoppedtrialsofitsAlzheimer’sdrug,Simufilam,inNovemberafteritfailedtoshowclinicalbenefits.首起学术不端指控浮现两年后，《自然》论文才于2024年6月被作者撤回。木薯科学虽否认过失，其药物Simufilam因缺乏临床疗效已于去年11月终止试验。Thesepapers’consequencesgobeyondthelab.Forpatientsandtheirfamilies,experimentaltreatmentsoftenrepresentafinallifeline.Encouragingpeopletopintheirhopesonmedicinesthatareineffective,orevenunsafe,isa betrayal.Fixationonatheoryofferinglimitedsuccessinhumantrialsmayalsohavedivertedresourcesfromothermorepromisingtherapies.这些论文的影响远超实验室范畴。对患者家庭而言，实验性疗法常是最后希望。诱导人们寄望于无效甚至危险的药物实属背叛。执着于临床试验屡屡受挫的理论，可能已挤占其他更具前景疗法的研发资源。Since2023theFoodandDrugAdministration,America’sdrugregulator,hasapprovedtwonewmedicinesthatmodestlyslowedcognitivedeclinebyattackingtheamyloidplaques. 2023年以来，美国食药监局批准了两款通过清除淀粉样斑块延缓认知衰退的新药。但部分患者出现脑肿胀、脑出血等严重副作用。Theyalsocomewithdangerousside-effectsforsome,whichincludebrainswellingandbleeding.MrPillerremainsscepticalofthesetreatments.Sowillmanyofhisreaders,afterhisgrippingstoryofmedicalgroupthinkand warped incentives.皮勒对这些疗法持怀疑态度。随着这部揭露医学界群体思维与扭曲激励机制的作品问世，相信众多读者也将产生同样疑虑。（红色标注词为重难点词汇）重难点词汇：bolster [ˈboʊlstər]n. 长枕；支持物 v. 支持；增强；巩固sleuth [sluːθ]n. 侦探；私家侦探 v. 像侦探般调查；搜寻whodunnit [ˈhuːdʌnɪt]n. 侦探小说；推理小说reluctant [rɪˈlʌktənt]adj. 不情愿的；勉强的whistleblower [ˈwɪslbloʊər]n. 告密者；检举者；揭发者betrayal [bɪˈtreɪəl]n. 背叛；出卖；辜负warp [wɔːrp]n. 弯曲；变形 v. 弯曲；变形；歪曲（事实等）
