中国精准医学2035发展战略
  精准医学是科学研究的前沿,体现了医学科学发展趋势,代表了临床实践发展方向。精准医学理念和研究范式已在医学研究和临床中应用和实践。《中国精准医学 2035 发展战略》系统阐述了精准医学的科学意义与战略价值,分析了精准医学的发展规律与研究特点,对精准医学的发展现状与发展态势进行了研判,并在此基础上,围绕人民健康、经济和社会发展的重大需求,提出了面向 2035 年我国精准医学的发展战略,并提出了有针对性的资助机制与政策建议。
  本书适合高层次的战略和管理专家,相关领域的高等院校师生、研究机构的研究人员阅读,是科技工作者把握前沿领域和重点方向的重要指南,也是科技管理部门重要的决策参考,同时也是社会公众了解精准医学发展现状及趋势的权威读本。
编委会

总序

  党的二十大胜利召开,吹响了以中国式现代化全面推进中华民族伟大复兴的前进号角。习近平总书记强调“教育、科技、人才是全面建设社会主义现代化国家的基础性、战略性支撑”,明确要求到 2035 年要建成教育强国、科技强国、人才强国。新时代新征程对科技界提出了更高的要求。当前,世界科学技术发展日新月异,不断开辟新的认知疆域,并成为带动经济社会发展的核心变量,新一轮科技革命和产业变革正处于蓄势跃迁、快速迭代的关键阶段。开展面向 2035 年的中国学科及前沿领域发展战略研究,紧扣国家战略需求,研判科技发展大势,擘画战略、锚定方向,找准学科发展路径与方向,找准科技创新的主攻方向和突破口,对于实现全面建成社会主义现代化“两步走”战略目标具有重要意义。

  当前,应对全球性重大挑战和转变科学研究范式是当代科学的时代特征之一。为此,各国政府不断调整和完善科技创新战略与政策,强化战略科技力量部署,支持科技前沿态势研判,加强重点领域研发投入,并积极培育战略新兴产业,从而保证国际竞争实力。

  擘画战略、锚定方向是抢抓科技革命先机的必然之策。当前,新一轮科技革命蓬勃兴起,科学发展呈现相互渗透和重新会聚的趋势,在科学逐渐分化与系统持续整合的反复过程中,新的学科增长点不断产生,并且衍生出一系列新兴交叉学科和前沿领域。随着知识生产的不断积累和新兴交叉学科的相继涌现,学科体系和布局也在动态调整,构建符合知识体系逻辑结构并促进知识与应用融通的协调可持续发展的学科体系尤为重要。

  擘画战略、锚定方向是我国科技事业不断取得历史性成就的成功经验。科技创新一直是党和国家治国理政的核心内容。特别是党的十八大以来,以习近平同志为核心的党中央明确了我国建成世界科技强国的“三步走”路线图,实施了《国家创新驱动发展战略纲要》,持续加强原始创新,并将着力点放在解决关键核心技术背后的科学问题上。习近平总书记深刻指出:“基础研究是整个科学体系的源头。要瞄准世界科技前沿,抓住大趋势,下好‘先手棋’,打好基础、储备长远,甘于坐冷板凳,勇于做栽树人、挖井人,实现前瞻性基础研究、引领性原创成果重大突破,夯实世界科技强国建设的根基。”

  作为国家在科学技术方面最高咨询机构的中国科学院和国家支持基础研究主渠道的国家自然科学基金委员会(简称自然科学基金委),在夯实学科基础、加强学科建设、引领科学研究发展方面担负着重要的责任。早在新中国成立初期,中国科学院学部即组织全国有关专家研究编制了《1956—1967 年科学技术发展远景规划》。该规划的实施,实现了“两弹一星”研制等一系列重大突破,为新中国逐步形成科学技术研究体系奠定了基础。自然科学基金委自成立以来,通过学科发展战略研究,服务于科学基金的资助与管理,不断夯实国家知识基础,增进基础研究面向国家需求的能力。2009 年,自然科学基金委和中国科学院联合启动了“2011—2020 年中国学科发展战略研究”。2012 年,双方形成联合开展学科发展战略研究的常态化机制,持续研判科技发展态势,为我国科技创新领域的方向选择提供科学思想、路径选择和跨越的蓝图。

  联合开展“中国学科及前沿领域发展战略研究(2021—2035)”,是中国科学院和自然科学基金委落实新时代“两步走”战略的具体实践。我们面向 2035 年国家发展目标,结合科技发展新特征,进行了系统设计,从三个方面组织研究工作:一是总论研究,对面向2035 年的中国学科及前沿领域发展进行了概括和论述,内容包括学科的历史演进及其发展的驱动力、前沿领域的发展特征及其与社会的关联、学科与前沿领域的区别和联系、世界科学发展的整体态势,并汇总了各个学科及前沿领域的发展趋势、关键科学问题和重点方向;二是自然科学基础学科研究,主要针对科学基金资助体系中的重点学科开展战略研究,内容包括学科的科学意义与战略价值、发展规律与研究特点、发展现状与发展态势、发展思路与发展方向、资助机制与政策建议等;三是前沿领域研究,针对尚未形成学科规模、不具备明确学科属性的前沿交叉、新兴和关键核心技术领域开展战略研究,内容包括相关领域的战略价值、关键科学问题与核心技术问题、我国在相关领域的研究基础与条件、我国在相关领域的发展思路与政策建议等。

  三年多来,400 多位院士、3000 多位专家,围绕总论、数学等18 个学科和量子物质与应用等 19 个前沿领域问题,坚持突出前瞻布局、补齐发展短板、坚定创新自信、统筹分工协作的原则,开展了深入全面的战略研究工作,取得了一批重要成果,也形成了共识性结论。一是国家战略需求和技术要素成为当前学科及前沿领域发展的主要驱动力之一。有组织的科学研究及源于技术的广泛带动效应,实质化地推动了学科前沿的演进,夯实了科技发展的基础,促进了人才的培养,并衍生出更多新的学科生长点。二是学科及前沿领域的发展促进深层次交叉融通。学科及前沿领域的发展越来越呈现出多学科相互渗透的发展态势。某一类学科领域采用的研究策略和技术体系所产生的基础理论与方法论成果,可以作为共同的知识基础适用于不同学科领域的多个研究方向。三是科研范式正在经历深刻变革。解决系统性复杂问题成为当前科学发展的主要目标,导致相应的研究内容、方法和范畴等的改变,形成科学研究的多层次、多尺度、动态化的基本特征。数据驱动的科研模式有力地推动了新时代科研范式的变革。四是科学与社会的互动更加密切。发展学科及前沿领域愈加重要,与此同时,“互联网 +”正在改变科学交流生态,并且重塑了科学的边界,开放获取、开放科学、公众科学等都使得越来越多的非专业人士有机会参与到科学活动中来。

  “中国学科及前沿领域发展战略研究(2021—2035)”系列成果以“中国学科及前沿领域 2035 发展战略丛书”的形式出版,纳入“国家科学思想库 - 学术引领系列”陆续出版。希望本丛书的出版,能够为科技界、产业界的专家学者和技术人员提供研究指引,为科研管理部门提供决策参考,为科学基金深化改革、“十四五”发展规划实施、国家科学政策制定提供有力支撑。

  在本丛书即将付梓之际,我们衷心感谢为学科及前沿领域发展战略研究付出心血的院士专家,感谢在咨询、审读和管理支撑服务方面付出辛劳的同志,感谢参与项目组织和管理工作的中国科学院学部的丁仲礼、秦大河、王恩哥、朱道本、陈宜瑜、傅伯杰、李树深、李婷、苏荣辉、石兵、李鹏飞、钱莹洁、薛淮、冯霞,自然科学基金委的王长锐、韩智勇、邹立尧、冯雪莲、黎明、张兆田、杨列勋、高阵雨。学科及前沿领域发展战略研究是一项长期、系统的工作,对学科及前沿领域发展趋势的研判,对关键科学问题的凝练,对发展思路及方向的把握,对战略布局的谋划等,都需要一个不断深化、积累、完善的过程。我们由衷地希望更多院士专家参与到未来的学科及前沿领域发展战略研究中来,汇聚专家智慧,不断提升凝练科学问题的能力,为推动科研范式变革,促进基础研究高质量发展,把科技的命脉牢牢掌握在自己手中,服务支撑我国高水平科技自立自强和建设世界科技强国夯实根基做出更大贡献。

“中国学科及前沿领域发展战略研究(2021—2035)”

联合领导小组            

2023 年 3 月            

前言
  精准医学是指针对疾病病因的复杂性,综合考虑个体生物特征、环境、生活方式存在的个体差异,制订有效健康干预和治疗策略的一种医疗模式。精准医学集合了诸多技术体系,是生物技术、信息技术、医学研究的交汇、融合与应用。精准医学既是科学研究的前沿,也体现了医学科学发展趋势,代表了临床实践发展方向。精准医学的发展将带动相关学科和技术加速发展,推动相关产业发展,孕育巨大市场空间。随着精准医学体系逐步成熟,发展路径全面推广,其科学与战略价值进一步凸显。
  2019年,国家自然科学基金委员会与中国科学院联合部署“中国学科及前沿领域发展战略研究(20121—2035)”项目,“中国精准医学研究布局与关键技术发展战略研究(2021—2035)”项目入选其中。项目由复旦大学、上海交通大学、中国科学院上海营养与健康研究所/上海生命科学信息中心协同推进,于2020年初启动。项目组汇聚了国内外精准医学领域的一批优秀科学家,包括研究人员、临床医生、科技管理人员,以及情报研究人员。项目进行了从技术与平台,到临床应用与推广,以及政策法规保障体系的多维度、全链条的研究设计,以制定满足我国需求的发展战略,提出我国发展精准医学的资助机制与政策建议。
  项目组通过资料调研、文献计量、实地调研、问卷调查、专家咨询相结合的方式完成了领域发展现状和趋势研判,以及我国现状分析与问题识别,为发展战略和政策建议奠定基础。项目组召开了10余次系列专题研讨会,参与研讨的专家500余位,研讨会围绕精准医学未来技术、精准医学产业化挑战与对策、精准医学临床应用与推广、中国精准医学发展战略与政策等中心议题进行了深入讨论。项目组还组织了“中国精准医学发展战略”香山科学会议和“中国精准医学发展战略高峰论坛”两次高层次的中国精准医学发展战略研讨会。通过反复的研讨,项目汇聚专家智慧、凝聚专家共识,制定了面向2035年我国精准医学的发展战略,并提出政策建议。
  本书首先明确了精准医学和个体化医疗的概念、科技内涵,分析了其科学意义、战略价值、发展规律与研究特点,以及二者之间的联系;研判了领域整体发展现状,预测未来发展趋势;通过对研究基础、现有设施、应用现状等进行实地调研和摸底,识别研究过程和临床实践中存在的问题,对组织模式、实施策略中的问题进行了分析;通过专家研讨,凝练了精准医学发展的核心技术与前沿方向,提出了发展战略与思路;最终为我国精准医学的发展提出了政策建议。
  在明确精准医学科技体系基础上,项目邀请来自不同领域的科学家对精准医学的关键技术和重点领域进行了思考和讨论,并进行专题撰写,形成了22个细分专题内容,主要包括基因组学、表观基因组学、蛋白质组学、代谢组学、队列研究、生物大数据、基因检测技术、分子影像、免疫疗法、个体化用药等关键技术和领域,精准医学在肿瘤、代谢性疾病、呼吸系统疾病、免疫性疾病、心血管疾病、脑血管疾病、儿童神经系统疾病、精神疾病、罕见病等不同疾病中的临床应用,以及精准医学发展涉及的卫生技术评估、公共卫生管理、伦理监管问题。每个专题基本按照领域发展状况、我国发展现状与趋势、我国发展战略与重点方向,以及资助机制与政策建议四部分进行分述。
  当前,我国正向第二个百年奋斗目标迈进,科技自立自强、“四个面向”是科技发展的指导方针。面向人民生命健康,发展精准医学是实现预防为主的健康策略的重要路径。我国前期布局也已夯实了精准医学研究的整体框架,初步形成了竞争优势,应紧抓发展机遇期、持续布局,保持与国际发展同步,甚至实现赶超发展。因此,建议我国持续加大研究投入、改革组织管理体制机制、建设研究平台和人才队伍、组建协同创新网络等,为构筑我国精准健康体系提供基础性支撑。项目组在研究期间,多次为科学技术部等相关管理部门提供一线数据,为政策制定提供支撑。希望本书能够为我国未来发展战略制定和实施提供“第一线”依据,为我国精准医学的前沿布局和战略规划提供决策参考。
  本书初稿于2021年7月完成,2021年9月23日在重庆召开的专家咨询会议上进行了认真的讨论,并根据专家意见进一步修改,形成了第二稿。2022年1月,书稿经中国科学院和国家自然科学基金委员会通讯评审通过,进入正式出版流程。由于认识局限,书中难免存在缺陷和不足,敬请读者批评指正。
  金 力   贺 林  陈国强
  《中国精准医学2035发展战略》战略研究组组长
  2023年3月
摘要
  一、精准医学的科学意义与战略价值
  精准医学是指针对疾病病因的复杂性,综合考虑个体生物特征、环境、生活方式存在的个体差异,制订有效健康干预和治疗策略的一种医疗模式。精准医学集合了诸多现代医学科技发展的知识与技术体系,是生物技术、信息技术、医学研究的交汇、融合与应用。精准医学既是科学研究的前沿,也体现了医学科学发展趋势,代表了临床实践发展方向。
  人民健康是最重要的社会民生问题,关乎国家经济发展和社会进步。随着工业化、城镇化、人口老龄化进程加快,以及个体生活方式的改变,我国卫生领域面临着多重疾病威胁并存、多种健康影响因素交织的复杂局面。当前全球医学研究目标已经从治疗为主转向预防为主。精准医学通过大型队列研究,长期持续监测群体中的个体健康状况、生活习惯等,从而发现疾病发生的风险因素,进而制订公共卫生干预措施,提高疾病预防和诊断水平,实现早发现、早预防。因此,精准医学是实现预防为主的健康策略的重要路径。精准医学充分考虑个体差异,形成个体化治疗方案,可以从根本上精准地优化诊疗效果,提高国民健康水平,避免医疗资源浪费,优化医疗资源配置。同时,发展精准医学可提升国家生物医药领域的创新能力,并带动相关产业的快速突破,推动经济发展。因此,随着精准医学体系逐步成熟,发展路径全面推广,其科学与战略价值进一步凸显,已成为科技竞争的焦点之一。
  二、精准医学的研究特点、发展规律
  精准医学是人类在医学发展至不同时期从不同角度对现代医学的探索和思考,是学科融合和技术交汇的产物。医学技术和生物技术的快速发展,尤其是生命组学和生物大数据技术的快速发展,催生并推动了精准医学的发展。
  1.精准医学的内涵不断发展和明确
  精准医学理念最早由美国哈佛大学商业战略专家Clayton Christensen提出,用以表述通过分子检测等方法直接获得明确的诊断结果,使医生不再依赖直觉和经验进行诊治,但当时该表述并未引起关注。直到2011年,美国国家研究理事会(National Research Council,NRC)发布报告《迈向精准医学:构建生物医学研究知识网络和新的疾病分类体系》(Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease),正式提出精准医学并对其主要任务进行了描述:为每一个体建立一个整合各种相关信息的疾病知识网络。此后,精准医学的理念受到重视,相关技术不断发展成熟,精准医学体系逐渐形成。2013年,我国贺林院士作为共同主席主持自然遗传学大会——从全基因组关联分析到精准医学(Nature Genetics Conference—From GWAS to Precision Medicine);同年作为东亚人类遗传学联盟主席,出席了以“精准医学”为主题的第十三届东亚人类遗传学联盟学术年会。
  2015年初,美国国情咨文提出“精准医学计划”(Precision Medicine Initiative,PMI),核心目标是要实现“在合适的时间,给合适的患者,以合适的疗法”,并在重点布局的“百万自然人群队列”项目的规划“精准医学计划队列项目——为21世纪医学研究奠定基础”(The Precision Medicine Initiative Cohort Program — Building a Research Foundation for 21st Century Medicine)中,将精准医学的内涵阐述为:根据人群基因特征、社会环境以及生活方式的个体差异,寻求疾病治疗和预防效果最大化的新手段。
  我国国家重点研发计划“精准医学研究”重点专项在2015年初开始设计实施方案,2016年初正式启动。该专项中对精准医学实施路径的描述更加丰富和完善,即在大样本研究获得疾病发病的分子机制的知识体系基础上,以生命组学数据为依据,根据患者个体在基因型、表型、环境和生活方式等各方面的特异性,应用现代遗传学、分子影像学、生物信息学和临床医学等方法与手段,发现相关变异与疾病发生发展的关系,进而对疾病进行精准分型、制订精准防诊治方案,最终实现个体化治疗。个体化医疗是临床实践的最终目标,精准医学为个体化医疗提供具体实施路径。
  2.精准医学理念体现了系统生物学的思想
  系统生物学是研究生物系统中所有组成成分的构成,以及在特定条件下这些组分间的相互关系的学科。系统生物学是以整体性研究为特征的一种大科学,其基础是信息,核心是整合。精准医学恰是系统生物学思想的集中体现。2011年,美国国家研究理事会发布报告《迈向精准医学:构建生物医学研究知识网络和新的疾病分类体系》,将精准医学描述为整合个体的基因组、蛋白质组和代谢组等分子数据与临床信息、社会行为和环境等不同层级、不同维度的数据,构建人类疾病知识数据库,进而支持精准诊断和个体化治疗的一种医学模式,其主要任务是为个体建立一个整合各种相关信息的疾病知识网络。我国“精准医学研究”重点专项的实施路径和美国“精准医学计划”的“百万自然人群队列”建设项目,都体现了精准医学的系统思想。
  3.精准医学研究体现了数据密集型科研范式,是大科学、大数据、大平台、大发现的典型代表
  精准医学的形成与发展得益于大数据技术的发展:通过大规模人群队列研究,并结合生命组学技术获取健康和疾病人群的海量数据,利用大数据技术进行分析,并进一步应用现代遗传学、分子影像学、生物信息学和临床医学等方法与手段,发现相关变异与疾病发生发展的关系,进而对疾病进行精准分型、制订精准防诊治方案,最终实现个体化治疗。因此,精准医学整合分析大规模人群的个体信息的研究范式是典型的数据密集型科研范式,也是典型的大科学组织范式。
  4.精准医学研究体系覆盖了从基础研究到临床应用的全创新链条
  要实现精准医学的总体目标,需要进行多层次信息数据基础、前沿技术支持和临床转化应用方案的全面研究。第一,精准医学研究的开展要通过大规模人群队列和特定疾病专病队列研究获取健康和疾病过程信息,开展疾病患病风险因素等分析,形成人群健康与疾病状态的数据;第二,需要通过生命组学研究,对疾病进行精准分型,获得多层次、组合生物标志物及生物标志物谱,以奠定对疾病进行精准防诊治的知识基础和数据基础。第三,需要搭建生物大数据平台,研发大数据分析和人工智能技术,对海量数据进行标准规范的收集、存储、质控、整合、挖掘和分析,从而获取更多的知识发现,为精准预防、精准诊断和精准治疗提供数据和新知识。最后,在应用方面需要与临床研究、检测与诊断技术研发、个体化治疗技术开发等结合,且需要对个体化治疗方案进行临床应用和示范推广,并要考虑卫生经济学、普惠性质和效益优化,实现精准医学研究成果的最终应用。由此可见,精准医学覆盖了从基础研究的知识发现到临床应用的诊疗方案的创新全链条,其实施需要多类型创新主体的协同,需要“举国体制”式的管理模式。
  三、全球精准医学发展趋势
  1.精准医学体系逐渐成熟走向应用,其理念和研究范式已在医学研究和临床中应用和实践
  精准医学理念和研究范式已在癌症、糖尿病、罕见病等疾病的基础研究和临床诊治中逐步得到应用和实践。2018年,美国糖尿病协会和欧洲糖尿病研究协会启动“糖尿病精准医学计划”(Precision Medicine in Diabetes Initiative,PMDI),并于2020年发布了第一阶段共识报告,分析了糖尿病精准医学发展现状与面临的挑战,提出了实现路径和关键领域,绘制了发展路线图。精准医学的核心领域大型队列和数据平台持续建设,基于组学特征谱的疾病精准分型研究不断突破,为药物研发提供新机制、新靶点。乳腺癌、卵巢癌、肺癌、胃癌、胰腺癌和结直肠癌等癌症的分子分型已用于指导临床治疗;多项基因检测、液体活检、分子影像等技术与产品获批进入临床应用,提高了疾病精准诊断和早诊早筛水平;靶向治疗、免疫治疗、基因治疗、RNA疗法等精准治疗药物和方法陆续进入临床应用,大幅度提高了疾病治疗水平。2018年11月,靶向基因突变特征而非肿瘤组织类型的“广谱”抗癌药拉罗替尼(Vitrakvi)获美国食品与药品监督管理局(FDA)批准上市,标志着药物开发思路与审批依据向精准医学模式的转变。
  2.精准医学的科学和社会价值日益凸显,各国加大布局,提供持续稳定的资金保障
  美国自2015年提出“精准医学计划”后,通过多个资助渠道为其提供发展资金,并通过《21世纪治愈法案》,确保对其进行持续
  10年的稳定支持。美国国立卫生研究院(NIH)在新一轮发展战略(2021~2025财年)中,仍然将精准医学作为重点领域进行布局。美国“精准医学计划”布局的重点是国家“百万自然人群队列”项目,在队列建设中保障人群多样性和广覆盖,采集资源类型全面、丰富、精细,注重数据的关联性,保持长期随访,以夯实精准医学研究的基础平台建设。截至2021年,美国政府已经向“百万自然人群队列”项目投入22亿美元。未来,美国“精准医学计划”将持续建设百万自然人群队列,并重点发展表型组学研究、常规化临床用基因组技术等。
  英国持续加码布局精准医学的重点领域、夯实精准医学研究基础。英国持续扩大基因组测序规模,继“十万人基因组计划”完成后,在2018年又通过《产业战略:生命科学行业协约》提出了100万人全基因组测序计划、500万人规模的大型队列计划,并已于2021年启动。英国还支持50万人规模的国家级队列英国生物样本库(UK Biobank)的迭代升级,扩大队列规模,丰富队列数据类型,引入多组学研究等新技术,不断提高人群队列数据质量和精细度。在大数据平台方面,英国已经通过英国健康数据研究所(HDR UK)对医疗健康大数据进行一体化管理与应用。这些举措为英国精准医学发展搭建了完善的发展平台。事实上,英国已经将英国生物样本库、“十万人基因组计划”和“500万人基因组计划”(又名Our Future Health)视为英国对疾病预防和早期诊断开展的大规模基础设施建设的三个关键。
  此外,欧洲主要国家与日本、韩国等国家,以及一些发展中国家也已持续推出相关发展计划,作为精准医学发展关键的国家级大型队列建设也已在全球铺开。
  四、我国精准医学发展现状
  我国前瞻部署了“精准医学研究”重点专项,为我国精准医学的超越发展奠定了基础,初步搭建了精准医学体系框架,精准医学的理念与路径在临床实践中快速推广。
  “十三五”时期,科学技术部抢抓精准医学起步的时间窗口,系统设计、前瞻布局了国家重点研发计划“精准医学研究”重点专项。该专项于2015年编制实施方案,2016年初正式启动,与美国“精准医学计划”同步规划,为赶超发展提供了政策与经费支持。该专项设计了生命组学技术、大规模人群队列、大数据平台、疾病精准防诊治方案、临床应用示范推广体系五大任务,设计系统、前瞻、完整,覆盖从基础研究到临床应用的完整链条,充分考虑了国情,既设计了旨在解决仪器与技术短板问题的研究,也设计了临床示范,以保障精准医学研究成果尽快落地,实现惠民目标。经过5年多的实施,专项成效显著,部分成果达到国际领先水平,建设了126万人的自然人群队列和125万人的专病队列,以及4万人的罕见病队列,搭建了精准医学研究的国家级队列框架;建成了精准医学大数据平台,推进了数据的标准规范管理和共享应用,开发了精准医学知识库,降低了对国外精准医学知识库的依赖度;建立了精准医疗示范网络,部分自主研发的精准医学防诊治方案开始应用,普惠人民群众。该专项集聚全国9000余名骨干科研人员参与,承担单位覆盖了27个省(自治区、直辖市)的500余家科研机构,将零散的研究体系初步集成为国家精准医学研究网络,体现了举国体制的优势。
  虽然在“精准医学研究”重点专项的支持下,我国已初步搭建精准医学框架体系,为超越发展奠定了基础,但是我国在精准医学体系建设和发展的支持机制中还存在不足,超越发展面临巨大挑战。
  1.我国精准医学体系建设中存在的问题
  我国精准医学体系建设中存在的问题主要有以下六个方面。
  (1)队列建设质量与利用效能不足。我国大规模队列建设刚刚起步,缺乏国家级队列,现有队列的标准化、规范化和系统化水平亟待提高,各队列的有效规模、科学管理、质量控制和利用率亟待加强,队列之间的联合运行和共享机制亟待完善,大型队列的随访、可持续发展等问题亟待解决。
  (2)精准医学大数据平台持续建设能力不足,数据质量和标准化、规范化不足,共享机制不完善,“数据孤岛”问题尚未有效解决,数据使用效能严重被制约。
  (3)临床研究开展的数量和质量不足,尤其是前瞻性、多中心规范的临床研究能力不足;临床上使用的疾病诊断标准、临床治疗指南缺乏,95%以上是参考国外;合作机制尚未畅通,基础研究和临床研究之间仍存在鸿沟。
  (4)生命组学核心技术、设备和配套试剂的原研能力弱,严重依赖进口,仅有少数机构在开展相关的研发工作,其产品的性能远未达到国际上主流产品的水平,国产设备使用的产业生态也仍未建立。
  (5)精准医学临床诊疗技术与原创药物开发不足。国内高精尖诊断用试剂、高端药物依赖进口,国内市场仍被跨国企业占据,也间接导致了“吃进口药、看病贵”的问题。
  (6)精准医学防诊治方案的临床推广体系建设不足。
  2.管理机制与精准医学创新特点的协同性不足
  管理机制与精准医学创新特点的协同性不足体现在以下四个方面。
  (1)精准医学是“大科学、大数据、大平台、大发现”的典型代表,需要整体设计、统筹部署、举国体制和长期稳定持续支持。“十三五”时期,我国对“精准医学研究”重点专项给予了五年期的支持;“十四五”阶段,精准医学的部分内容被纳入“生物与信息技术合”(BT&IT融合)、“前沿生物技术”、“常见多发病防治”等“十四五”国家重点研发计划重点专项中,没有对精准医学持续给予整体资助。这与精准医学的创新特点不匹配,将使我国“十三五”超前布局支持取得赶超发展的优势丧失;“十三五”时期建设的人群队列、数据平台得不到持续支持,有可能导致我国失去精准医学领域系统前瞻布局形成领先局面的“先手棋”,更有可能导致我国在医疗技术、诊断产品、原创药物等方面出现新的“卡脖子”问题。
  (2)投入经费严重不足,尤其是数据、队列等基础支撑平台建设投入不足。
  (3)资助和管理制度与全链条设计的协同性不够。数据、平台、队列的国家统一建设尚未实现。数据、平台、队列衔接不够,无法真正建立完整的精准医学体系。
  (4)精准医学的数据共享政策、监管与审批制度、伦理监管与规范等配套政策与法规尚不健全。基因检测等技术仍无明确的监管法规和定价机制,导致无法合理使用,乱象丛生。
  五、我国精准医学发展战略(2021~2035年)
  1.精准医学关键科学问题
  高质量大型队列、大数据、疾病精准防诊治方案研发是未来精准医学实施的关键。精准医学的实施需要大型队列结合生命组学,对健康状态和疾病的发生发展开展系统研究,形成精准防诊治方案。因此,高质量大型队列是未来精准医学实施的关键,其建设需要满足人群的多样性和覆盖度、参与者完整健康数据的收集,以及整合多组学、环境、表型信息进行归因分析,并确保参与者能够长期随访。在队列研究中,标准统一、互联互通、开放共享、数据的关联整合研究是关键。精准防诊治方案的研发是精准医学临床应用的关键,阐释疾病的发生发展机制,对疾病进行精准分型,并发现生物标志物,进行防诊治方案研发,从而实现个体化治疗。
  2.我国精准医学的总体目标
  精准医学既是科学技术的前沿,也体现了医学科学发展趋势,代表了临床实践发展方向。随着研究的深入,精准医学的科学价值和社会价值日益凸显,美国、英国等国家将精准医学作为重要领域进行长期布局,科技竞争进一步加剧。我国在“十三五”时期,已经抢抓精准医学刚刚起步的时间窗口,布局了“精准医学研究”重点专项,这为赶超发展创造了良好机遇,奠定了发展基础,并已初步形成竞争优势。
  当前,我国正向第二个百年奋斗目标迈进,更需要持续和深化精准医学研究,充分利用我国人群疾病资源丰富和举国体制的优势,以建设国家级队列和精准医学大数据平台为抓手,解决“原创弱、研发散、推广难”的瓶颈问题,开展基于国家级队列、符合我国人群特征的疾病精准防诊治方案的研发与推广,系统解决医疗技术、诊断产品、原创药物等方面存在的“卡脖子”问题,最终构筑我国精准健康体系,满足人民生命健康需求,实现科技自立自强,整量级提升我国生命健康基础研究水平、医药健康产业的创新策源能力,助力我国经济高质量发展。
  3.我国精准医学至2035年的发展思路和战略
  面向精准医学发展前沿,立足我国人民健康需求,在已经搭建的精准医学体系框架基础上,实施三步走战略:第一步,夯实基础,建成国家级队列和精准医学数据平台,进一步推广精准防诊治方案(2021~2025年);第二步,深化发展,实现关键技术与产品自主可控全面推广精准防诊治方案(2026~2030年);第三步,全面建成精准健康体系,实现国际引领,产业具有国际竞争力(2031~2035年)。
  4.我国精准医学重点任务和研究方向
  1)重点任务
  以“建平台、促研究、惠民生、兴产业”作为指导方针,明确我国精准医学发展的三大重点任务:一是建设国家级队列和精准医学大数据平台。建成全球领先的高质量、高精度、多维度国家级队列和标准化、可共享、可持续的精准医学大数据平台,全面加强高精度表型测量、多维纵向大数据融合等核心共性技术研发,支撑我国医学研究范式转变,为原创超越和引领发展奠定基础。二是基于国家级队列,系统研发疾病精准防诊治方案。建立符合中国人群遗传背景与疾病特征的精准预防、精准诊断和精准治疗方案,持续产出重大疾病和罕见病精准防诊治的“中国标准”、“中国指南”和“中国方案”。三是提升基层专科能力,全面建设疾病临床精准防诊治方案的应用示范推广体系。采取边建设、边研究、边应用、边推广的模式,加快精准医学研究成果在全国的应用推广。结合智慧医疗和远程医疗体系,将疾病精准防诊治方案和规范快速推广到基层,提升基层专科能力,惠及民众。
  2)优先发展领域
  (1)开发具有自主知识产权的生命组学技术。紧抓第三代基因测序技术初步发展的窗口期,大力发展具自主知识产权的基因测序技术。研发先进的定性、定量蛋白质组学技术,突破技术瓶颈;发展超灵敏、高覆盖代谢组定量分析技术,推动其进入医疗健康领域。紧抓影像数据集成优势,发展高通量影像组技术,实现技术引领。
  (2)建设标准化、规范化、系统化的高精度国家级大型队列。成立国家人群队列管理和资助中心,赋予该中心布局、管理、定向和持续资助队列的体制机制。进一步建设标准化、规范化、系统化的国家级大型人群队列,提升国家级队列资源的维度、精细化程度和支撑能力,加强队列的科学管理、质量控制,完善队列间的联合运行和共享机制,为精准医学的研究和临床应用奠定基础。
  (3)搭建标准化、共享的国家精准医学大数据中心。发挥举国体制优势,建立国家精准医学大数据中心。明确建立健康医疗数据管理机制,促进数据采集和管理的标准化、结构化、规范化,保障数据质量和数据安全;促进数据开放共享,推动健康医疗大数据资源的高效整合利用,为精准医学发展奠定基础。
  (4)开发用于医疗领域的先进人工智能技术与辅助诊疗系统。紧抓全球科技和产业变革的大趋势,基于我国人工智能技术研发与医疗应用的基础,集成大数据分析技术与人工智能技术,开发多种辅助诊疗系统,大幅提高核心技术原创能力,实现疾病预警、治疗、评估、康复等各环节的个体化精准服务。聚焦数字医学影像设备和先进影像辅助决策系统研发,形成以重点企业为龙头、关键技术与试剂配套的高端医疗创新链和产业链,为早期诊断、精准诊断和精准治疗提供支撑。
  (5)聚焦先进靶向药物、免疫疗法、基因疗法的快速产业化。加大研发投入,支持原创性、具自主知识产权的靶向药物、免疫疗法、基因疗法等先进疗法的开发。搭建功能性平台,解决关键技术问题,打破技术壁垒,完善精准医学产业链,推动精准医学领域的最新科研成果与企业的对接转化,形成一批中国制造、国民用得起的精准医学先进药物与疗法。鼓励企业开展精准医学相关产品的国际认证,推动精准治疗产品进入国际主流市场,提高我国在医药健康领域的国际竞争力,抢占精准医学先进领域的制高点。
  (6)针对可精准治疗的疾病开展应用示范与推广。以边研究、边应用、边推广为指导原则,依托已建立的国家临床医学研究中心协同创新网络,聚焦已初步实现精准化防治的肺癌和乳腺癌先期开展临床应用示范,形成一批中国制定、国际认可的疾病预防和临床诊疗指南,并针对恶性肿瘤、心脑血管疾病、代谢性疾病、罕见病等疾病进行全创新链布局,整合多个创新主体,集成攻关,提高疾病的精准防诊治水平,不断扩大“临床可精准化的疾病”范畴。同时,通过临床示范基地和精准医学体系建设、大数据平台和智慧医疗、远程医疗设施建设,完善精准医学服务体系及相关保险制度,实现已精准化防治方案在全国的全面推广。
  5.我国精准医学发展的资助机制及政策建议
  当前,生命科学已进入大科学、大数据、大平台、大发现的阶段,处在这一发展趋势下,科学研究的组织更需要“举国体制”。精准医学是这一趋势的典型代表,为推动我国精准医学发展,建议我国建立长期持续资助机制、建设研究平台和人才队伍、组建协同创新网络,为构筑我国精准健康体系提供制度举措保障。
  具体建议包括:①制定长期发展战略,在“十三五”期间已取得成效的基础上,在“十四五”阶段甚至更长时间内对精准医学进行持续稳定支持;②充分发挥举国体制,在已经初步建设精准医学队列和大数据平台的基础上,系统设计和一体化建设国家级队列与数据平台;③以专病为抓手,研讨专病的精准预防、诊断及治疗策略和路径,加速专病精准医学防诊治研究和临床应用;④完善政策法规与伦理体系,保障精准医学全面有序发展;⑤建立政产学研经协同网络,构建新型可持续组织模式,统筹各类市场主体协同推进;⑥支持产业基地和集群建设,推动精准医学产业快速发展;⑦健全多层次人才培养体系,加大复合型人才培养和引进力度。
 
  Abstract
  I. Scientific significance and strategic value of precision medicine
  Precision medicine is an approach that takes full consideration of individual differences in the biological traits, environment, and lifestyle exposure to tailor effective health interventions and treatment strategies due to the complexity of etiologies. Precision medicine integrates various knowledge and technological systems of sciences and technological development in modern medicine, is the confuence, fusion and application of biotechnology, information technology, and medical research. Precision medicine represents the frontier of scientifc research, reflects the development trend of medical sciences, and heralds the direction of development of clinical practice.
  People’s health is the most important issue of the well-being of the society and people, and critical to the economic development and social progress of the nation. With the acceleration of industrialization, urbanization and aging and changes in individual lifestyle, the health feld of China is facing a complicated situation with the simultaneous presence of multiple diseases and multiple interwoven factors impacting on health. Currently, the goal of global medical research has moved towards being prevention-oriented from being treatment-oriented. Meanwhile, precisionmedicine may achieve early discovery and prevention by continuously monitoring the long-term status of individual health and life habits to identify the risk of disease occurrence through large cohort studies and implement public health intervention measures to enhance the levels of disease prevention and diagnosis. Therefore, precision medicine offers an important pathway to prevention-oriented health strategies. Precision medicine takes into full account of individual diferences and formulates personalized treatment plans and may precisely and fundamentally optimize the results of diagnosis and treatment, raise the health levels of citizens, avoid waste of healthcare resources, and optimize the allocation of healthcare resources. Meanwhile, development of precision medicine could elevate the nation’s innovativeness in the biomedical field, drive the rapid breakthrough of related-industries, and promote economic development. Therefore, with the gradual maturation of the precision medicine system and comprehensive promotion of development pathways, its scientifc and strategic values become even more prominent and have become one of the focuses of scientific and technological competition.
  II. Characteristics and rules of development of precision medicine research
  Development of precision medicine is the exploration and contemplation of modern medicine from a different perspective at a diferent stage of the development of medical sciences, and the product of disciplinary fusion and technical interchange. Rapid development of medical technology and biotechnology, especially rapid development of life omics and biological big data technology has ushered in and promoted the development of precision medicine.
  The connotation of precision medicine keeps developing and being defined. The concept of precision medicine, first proposed by Harvard University business strategist Clayton Christensen, was used to describe the explicit diagnostic results of molecular detection and other methods, allowing physicians to make a diagnosis and carry out treatment by no longer relying on intuition and experience. However, it did not attract any attention then. Until 2011, the USA National Research Council (NRC) published a report Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease and offered a formal description of “precision medicine”, with its main task being building a knowledge network integrating various related information about an individual. Thereafter, the concept gained momentum, and related technologies kept developing and becoming mature, and a precision medicine system gradually emerged. In 2013, academician Lin He co-chaired Nature Genetics Conference— From GWAS to Precision Medicine, and in the same year, as the chairman of the East Asian Union of Human Genetics , he hosted the 13th academic forum with the theme of precision medicine.
  At the beginning of 2015, US State of the Union address put forward the Precision Medicine Initiative (PMI), with the key goal of providing appropriate treatment at the appropriate time for the appropriate patient, with a key layout on the Million Person Precision Medicine Initiative Cohort Program “The Precision Medicine Initiative Cohort Program — Building a Research Foundation for 21st Century Medicine”, which defnes precision medicine as a new approach to maximize the efects of treatment and prevention of diseases based on individual diferences in population gene traits, social environment, and lifestyle.
  The implantation plan of special key “precision medicine study” programs in China was designed at the beginning of 2015 and initiated at the beginning of 2016. In the special key programs, the implementation pathways of precision medicine are elucidated in greater details and more refined, that is, on the basis of the network of knowledge of molecular mechanisms of pathogenesis acquired from studies using large samples, with evidence based on data from life omics, based on the specifcities of genotype, phenotype, environment and lifestyle of individual patients, the relationship between the related variations and the onset and development of diseases is identified using modern genetics, molecular imaging, bioinformatics and clinical medicine and other methods and approaches so that diseases can be precisely categorized and precise prevention,diagnosis and treatment plans can be made, eventually achieving personalized treatment. Personalized healthcare is the ultimate goal of clinical practice and precision medicine offers specific implementation pathways for personalized healthcare. 
  The concept of precision medicine reflects the thinking of systemic biology. Systemic biology is a science that investigates each component of a biological system (genes, mRNA, and proteins, etc.) and the relationship among the components under specifc conditions. Systemic biology is a mega-science that is characterized by integrative research; its basis is information, and its core is integration. Precision medicine happens to be the epitomization of systemic biology thinking. In 2011, a report “Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease” was published and described “precision medicine” as a medical model that integrates the molecular data of genomics, proteomics and metabolomics and clinical information, social behaviors and environment of individuals at different levels and different dimensions to build a knowledge bank of human diseases, thereby providing support for precise diagnosis and personalized treatment. Its main task is to establish a knowledge network that integrates all relevant information of individuals. The implementation pathways of the special key programs of precision medicine in China and the USAprecision medicine million-person cohort initiative both refect the systemic thinking of precision medicine. 
  Precision medicine research reflects the data intensive scientific research paradigm, and is representative of mega-science, big data, big platform, and big discovery. The formation and development of precision medicine benefit from the development of big data, acquire massive data of healthy subjects and patients through large cohort studies and by combining life omics technology, analyze the data using big data technology, and further utilize modern genetics, molecular imaging, bioinformatics and clinical medicine and other methods and approaches to discover the relationship between the related variation and the onset and development so that diseases can be precisely categorized and precise prevention and treatment plans can be made, eventually achieving personalized treatment. Therefore, the research paradigm of personalized medicine in integrating and analyzing the data of a massive number of individuals is a typical data intensive scientifc research paradigm and is also a typical mega-science paradigm.
  The scientifc research system of precision medicine covers the entire innovation chain from basic research to clinical applications. Achieving the overall goal of precision medicine requires a basis of information at multiple levels, support with frontier technology and thorough investigation of application protocols for clinical translation. First, to conduct research in precision medicine, large cohort studies are needed to acquire data on health and disease process, and analyze the risk of disease development to generate data on the health and disease status of populations in China. Meanwhile, precise classification of diseases is being undertaken through research on life omics to acquire combinatorial biomarkers and spectrum of biomarkers at multiple levels to lay the foundation of data and knowledge for precise prevention, diagnosis, and treatment of diseases. Second, it is necessary to build big data platforms, conduct big data analysis, and develop artifcial intelligence technology for the standardized collection, storage, quality control, integration, mining, and analysis of massive data to discover more knowledge, so as to provide data and new knowledge for precise prevention, diagnosis and treatment. Third, in the area of application, there is a need for clinical study, the development of detection and diagnostic technology, and personalized treatment technology; in addition, personalized treatment plans should have clinical applications and be promoted, taking into consideration of health economics, inclusiveness and beneft optimization to achieve the ultimate application of the research results of precision medicine. Therefore, precision medicine covers the entire innovation chain from knowledge discovery through basic research to diagnosis and treatment plans for clinical applications and requires the coordination of numerous types of innovating entities and a “whole country” management approach.
  III. Global trend of precision medicine development
  The system of precision medicine gradually matures towards being applied, and the concept and research paradigm of precision medicine have been applied in medical research and clinical practice. The concept and research paradigm of precision medicine have been gradually applied in medical research and clinical practice in cancer, diabetes, and rare diseases. The diabetes associations of the USAand Europe put forward the precision medicine diabetes initiative (PMDI) and published a consensus report on the first phase of the initiative in 2020. The report analyzed the current state and challenge of diabetes precision medicine, formulated the implementation pathways and key areas, and delineated the roadmap of development. Large cohort studies in the key areas of precision medicine and continuous building of data platforms, research breakthroughs in disease precise classifcation based on the spectrum of omics traits could provide novel mechanisms and new targets for drug development and have been used to guide clinical treatment of breast cancer, ovarian cancer, lung cancer, gastric cancer, pancreatic cancer and colorectal cancer. Numerous technologies and products of gene detection, liquid biopsy, molecular imaging and others have been approved and entered into clinical applications, enhanced the levels of precise and early diagnosis and early screening of disease. Precise treatment drugs for targeted therapy, immune therapy, gene therapy and RNA therapy, etc. have gradually entered into clinical applications, greatly raising the levels of treatment of diseases. Meanwhile, drugs targeting the mutational characteristics of target genes rather than “broad- spectrum anticancer drugs” were approved by FDA, marking the thinking of drug development and a shift to the precision medicine model in drug approval.
  The scientific and social value of precision medicine has become increasingly prominent. Each country has increased efforts to lay out plans and provide stable funding for precision medicine. Since the USA Precision Medicine Initiative was put forward in 2015, funding for development has been provided through multiple channels and stable long-term funding over ten years is secured through the 21st Century Cures Act. In the new round of USANIH development strategy (2021-2025), precision medicine remains the key area for layout. The key project of the USA Precision Medicine Initiative is the Million-Person Precision Medicine Initiative Cohort Program, assuring the diversity and wide coverage of population in building the cohort. Data resources are comprehensive, abundant, and refned. Attention should be paid to the correlation among the data. Long-term follow-up should be undertaken in order to lay a solid foundation for building the platform for precision medicine research. By 2021, the USA government has provided 2.2 billion dollars for the “Million-Person Precision Medicine Initiative Cohort Program”. In the future, USA precision medicine will continue to build the Million-Person Precision Medicine Initiative Cohort Program, with a focus on phenotypic omics studies and regular clinical use of genomic technology. The UK has been continuously increasing layout in the key areas of precision medicine to build a solid foundation for precision medicine research. First, to continue the expansion of the scale of genomic sequencing following the completion of the “Million-Person Precision Medicine Initiative Cohort Program” (2012-2018), the UK passed the Industrial Strategy: Life Sciences Sector Deal in 2018, put forward the Million-Person Whole Genome Sequencing Initiative and started the initiative in 2021. Second, the UK also supported the upgrade of the National 500,000-Person Cohort UK Biobank and expanded the scale of the cohort and enriched the data types of the cohort by introducing multi-omics studies and other new technologies to improve the data quality and precision of the cohort. With regards to big data platform, the UK has passed HDR UK for integrated management and application of big health data. These measures built a perfect development platform for UK precision medicine development. In fact, the UK has regarded the UK Biobank, Million-Person Precision Medicine Initiative Cohort Program and Five Million-Person Genomics Initiative (also known as Our Future Health) as the three pillars for large scale construction of infrastructure for disease prevention and early diagnosis. In addition, major European countries, Japan, Republic of Korea, and other countries and some developing countries have put forward relevant development plans one after another. National large-scale cohorts key to precision medicine development have been built around the globe.
  IV.The current state of precision medicine development in China
  China has prospectively laid out key precision medicine projects and laid a foundation for transcending and development. It has preliminarily set up a framework for precision medicine system, and the concept of precision medicine and pathways have rapidly promoted the clinical practice.
  In the “13th five-year plan” period, the Ministry of Science and Technology seized the time window of the beginning stage of precision medicine, systemically designed and prospectively laid out key “precision medicine research” projects. The project formulated implementation plans in 2015 and was launched in March 2016, and was planned step in step with the USA, providing policy and funding support for transcending and development. The specific key projects have five important tasks including life omics technology, large cohort studies, big data platform, protocols for precise disease prevention, diagnosis and treatment, and promotion of clinical application paradigms. The plan is systemic, forward-looking, comprehensive, covering the entire innovation chain from basic research to clinical applications by taking into full consideration of the specific conditions of China. It has not only addressed the issue of instrument and technological deficiencies, but has also designed clinical paradigms, aiming at the implementation of results of precision medicine and achieving the goal of benefting the entire population. The specific key projects have achieved remarkable outcomes five years after implementation. Some results are at the internationally advanced level. A1,260,000-person natural person cohort and a 40,000-person rare disease cohort have been built and a national cohort framework of precision medicine has been established, and a big data platform of precision medicine has been constructed, promoting standardized data management and shared applications. A precision medicine knowledge bank has also been built to reduce dependency on precision medicine knowledge banks of other countries. Precision medicine treatment demonstration networks have been set up and protocols of precision medicine prevention, diagnosis and treatment that have been established by partially independent research and development, for the beneft of the entire population. The specifc projects have attracted nearly 9000 researchers, the participating institutions approach more than 500 scientifc research institutions in 27 provinces, autonomous regions, municipalities directly under the Central Government, preliminarily forming a national precision medicine research network, showing the advantage of a national system.
  Nevertheless, supported by the specific projects, China has preliminarily built a framework of precision medicine system, laying the foundation for development. However, there are still inadequacies in the construction of the precision medicine system and development support mechanism in China, and there are daunting challenges in development.
  In the construction of the precision medicine system, 1) the quality of cohort construction and the efciency of cohort utilization are inadequate. The building of large cohorts is just beginning in China and national cohorts are lacking. The level of standardization and systemization need to be increased and the effective scale, scientific management, quality control and utilization of each cohort should be strengthened. The combined operation and sharing mechanisms of cohorts should be improved. The follow up of large cohorts and sustainable development and other issues need to be solved urgently. 2) The ability for sustained construction of big data platform of precision medicine, data quality and data standardization are still inadequate and sharing mechanisms are still not perfect. The issue of “data island” is yet to be solved, and the efciency of data utilization is severely constrained. 3) The quantity and quality of clinical studies are inadequate. The quantity and quality of studies, especially prospective, multicenter clinical studies, are inadequate, and there is a lack of diagnosis standards and treatment guidelines for diseases, with over 95% of them referring to those in other countries. The cooperation mechanisms are still not smooth, and there is a huge gap between basic and clinical studies. 4) The original research ability for core technology, instrument and reagents in life omics is weak and depends heavily on imports and only a few institutions are engaging in related research and development, and their performance is far from the mainstream products. The industry ecology of domestic equipment has not been established. 5) Precision medicine-based clinical diagnosis and treatment technology and new drug development are still inadequate. Sophisticated diagnostic reagents and high-end drugs depend on imports in China and the domestic market is dominated by multinational corporations, indirectly leading to the issue of “taking imported drugs and expensive to see a doctor”. 6) The construction of the clinical promotion system for precision medicine prevention, diagnosis and treatment protocols is inadequate.
  Insufficient synergy of the management mechanism and the innovative traits of precision medicine. 1) Precision medicine is a typical representation of “mega-science, big data, big platform, and big discovery”, requiring overall design, overall planning, a national system and long-term stable and continuous support. During “the 13th Five-Year Plan” period, the specifc key projects are provided support for 5 years, and during “the 14th Five-Year Plan” period, part of the contents were listed in BT&IT, frontier biotechnology, prevention and treatment of common diseases and other specifc key projects in “the 14th Five-Year Plan”. No continuous, comprehensive financial support was provided, which does not match the traits of precision medicine, which will cost the advantage of advanced layout for development in “the 13th Five-Year Plan” period. The cohorts and data platform built during “the 13th FiveYear plan” period do not receive continuous support, losing the frst player advantage from forward-looking, systemic layout in the field of precision medicine, and likely becoming a bottleneck issue in the areas of new medical technology, new diagnostic products, and new drug development. 2) Funding is severely inadequate, especially funding for building data platform and cohorts. 3) The coordination among funding, management system and design of the entire chain is poor. Unifed national construction of data, platform, and cohorts has not been achieved. The cohesion among data, platform, and cohort is inadequate, and an integral precision medicine system cannot be truly established. 4) Supporting policy and statutes are incomplete for precision medicine data sharing policy, regulatory and approval systems, ethics regulation and standardization. There are no explicit regulations and pricing mechanism for gene detection and other technologies, making it impossible for their rational use and chaotic.
  V. The precision medicine development strategy in China (2021-2035)
  1. The key scientifc question in precision medicine
  The research and development of high-quality big cohort, big data, and precise prevention, diagnosis and treatment protocols are key to future implementation of precision medicine. The implementation of precision medicine pathways requires big cohort in combination with life omics, systemic investigation of health and the onset and development of disease, formulating protocols for precise prevention, diagnosis and treatment. Therefore, high-quality, big cohorts are key to future implementation of precision medicine, and their construction needs to satisfy the requirement for the diversity and coverage of populations, collection of complete health data of the participants, and integrating multi-omics, environment, and regression analysis of phenotypic information, and insure the long-term follow-up. In cohort studies, standardization, connection and openness, open and sharing, and data coupling and integration are key to research. The research and development of precise prevention, diagnosis and treatment protocols are key to clinical applications of precision medicine, elucidation of the mechanisms of disease occurrence and development, precise disease classification, discovery of biomarkers, research and development of prevention, diagnosis and treatment protocols, thereby achieving personalized treatment.
  2. Ideas and overall goals of precision medicine development in China
  Precision medicine is the frontier of science and technology, refects the development trend of medical sciences, and represents the direction of clinical practice development. With the deepening of research, the scientifc and social value of precision medicine has become increasingly prominent. The USA, the UK and other countries have made long term layout in the key areas of precision medicine, and scientific and technological competition becomes further intensifed. During the “13th five-year plan” period, China seized the time window of the beginning stage of precision medicine, systemically designed and prospectively laid out key “precision medicine research” projects, which provided a good opportunity for transcending other countries and development and had laid a foundation for development, gaining an competitive edge.
  Currently, China is moving towards the second centenary goal, requiring continuous and more in-depth precision medicine research by fully utilizing the abundant resources of disease in the population and the advantage of a national system on the basis of building a national cohort and a big data platform of precision medicine. We should solve the issues of “weakness in original research, lack of concerted efforts in research and development, and difficulty in promotion”, and undertake research and development of disease precise prevention, diagnosis and treatmen protocols that suit the population characteristics of the population based on the national cohort, and systemically solve the bottleneck in new medical technology, new diagnostic products, and new drugs, ultimately building China’s precision health system, fulfilling the health needs of the people, realizing scientifc and technological independence and self-reliance, and enhance the levels of basic research on health in China, the epicenter of novelty in medical, pharmaceutical and health industry, thereby facilitating high-quality economic development in China.
  Development ideas:
  The development idea and strategy of precision medicine in China from now to 2035: Facing the frontier of precision medicine development and considering the health needs of our people and based on the framework of the precision medicine system, a three-step strategy in China is implemented. The first step is laying a solid foundation, building a national cohort and precision medicine data platform, and further promoting precision prevention, diagnosis and treatment protocols (2021-2025). The second step is furthering development, achieving self-reliance of key technology and products, and comprehensively promoting precision prevention, diagnosis and treatment protocols (2026-2030). The third step is completion of the precision health system in an all-round way, achieving international leadership and industry competitiveness (2021-2035).
  3. The key tasks and research direction of precision medicine in China
  The guiding principle of “building the platform, promoting research, benefting the livelihood, and invigorating the industry” is used to defne the three big research tasks of precision medicine development in our country. The frst is building the national cohort and the big data platform of precision medicine. The tasks include building an internationally advanced high-quality, high-precision, and multidimensional national cohort and a standardized, sharable, and sustainable precision medicine big data platform, strengthening high-precision phenotypic determination, research and development of multidimensional longitudinal fusion of big data and other core common technologies, providing support for paradigm change in medical research in China, and laying a foundation for transcending other countries in originality and leading development. The second is systemic research and development of precision prevention, diagnosis and treatment protocols based on the national cohorts. Building precision prevention, precision diagnosis and precision treatment protocols compatible with the genetic background and disease traits of Chinese population, continuously providing “China standards” “China guidelines” and “China protocols” for precision prevention, diagnosis and treatment of significant diseases and rare diseases. The third is directing at the grass-roots level and improving specialist capabilities by comprehensive promotion of application paradigms of precision prevention, diagnosis, and treatment protocols. The model of simultaneous construction, research, application, and promotion is used to accelerate the promotion of the application of the research results of precision medicine. In combination with intelligent healthcare and telemedicine systems, disease precision prevention, diagnosis and treatment protocols and regulations are rapidly promoted to the grass roots level, improve specialist capabilities, and bring benefts to the entire population.
  Priority areas:
  (1) Development of life omics technology with independent knowledge property rights.
  By seizing the time window of early development of the third generation gene sequencing technology, we should focus on developing knowledge gene sequencing technology with independent knowledge property rights. We should develop qualitative and quantitative proteomics technology, break the bottleneck of technology, develop ultrasensitive and high coverage metabomics quantitative analysis technology, and promote entry into the healthcare feld. We should realize technological leadership by taking full advantage of our strength in image data integration, high-throughput imageomics technology development.
  (2) Building standardized, conventionalized and systemic high precision national big cohort. 
  A national cohort management and funding center should be built; the center should be endowed with a system of laying out, manamging, directing and continous funding of the cohort. Furthermore, a standardized, conventionalized, and systemic national big cohort should be constructed to increase the dimension, degree of refineness and support capacity of national cohort resources. Scientific management, quality control, joint operation and sharing mechanism of cohorts should be strengthened in order to lay the foundation for precision medicine research and clinical applications.
  (3) Building a standardized and shared national precision medicine big data center. 
  Taking the full advantage of a national system, we should build a national precision medicine big data center. A definite healthcare data management mechanism should be established to promote the standardization, structuring and conventionalization of data collection and management to assure data quality and data safety. Data openness and sharing should be encouraged, and highly efficient and integral utilization of healthcare big data resources should be promoted in order to lay a foundation for precision medicine development.
  (4) Developing an advanced artificial intelligence technology and assisted diagnosis and treatment system in the medical feld.
  We should closely follow the big trend of change in global scientifc and technological development and industry, and on the basis of research and devleopment and medical application of artificial intelligence technology, we can integrate big data analysis technology and artificial intelligence technology and develop multiple assisted diagnosis and treatment systems, remarkably increase the originality of core technology, realize personalized precision service at each link including early disease warning, treatment, evaluation, and rehabilitation. We should focus on the development of digital medical imaging equipment and advanced imaging assisted decision making systems, develop a high-end medical innovation chain and industry chain with key technology and matching reagents with key enterprises as the leader, to proivde support for early diagnosis, precision diagnosis and precision treatment. We should also focus on rapid industrialization of targeted drugs, immune therapy, and gene therapy.
  (5) Focusing on rapid industrialization of targeted medicine immuno-therapy and gene therapy.
  We should increase investment in research and devleopment, support originality and develop targeted drugs with independent knowledge property, immune therapy, gene therapy and other advanced therapies. We also need to build functional platforms, solve key technological issues, break down technological barriers, improve the precision medicine industry chain, and promote the translation of the most recent research results into precision medicine by the industry, creating a batch of China-made afordable advanced precision medicine drugs and therapy therapy. Enterprises should be encouraged to obtain international certification of precision medicine-related products to promote the introduction of precision treatment products into international mainstream markets, and to enhance the country’s international competitiveness in the health care feld by seizing the high ground in the advanced areas of precision medicine.
  (6) Demonstration and promotion of application of precision treatment of disease.
  Under the guiding principle of simultaneous research, application, and promotion, and relying on the coordination of innovation network of the established national clinical medical research center, we can focus on achieving preliminary precision prevention and treatment of lung cancer and breast cancer, and carry out early demonstration of clinical applications, thus creating a group of China-made and internationally recognized guidelines for disease prevention and clinical diagnosis and treatment. Meanwhile, we can lay out the entire innovation chain in malignancies, cardiocerebrovascular diseases, metabolic diseases, rare diseases, and multiple innovation entities can be integrated to focus on overcoming the main obstacle and increase the level of precision prevention, diagnosis and treatment of disease, and expanding the category of diseases that fall within precision medicine. Meanwhile, through the construction of clinical demonstration bases and precision medicine systems, big data platform and intelligent healthcare, and construction of telemedicine facilities, we can improve the precision medicine service system, and the related insurance regulation, and achieve the nationwide promotion of precision medicine-based prevention and treatment protocols.
  4. Funding mechanisms of precision medicine development in China and policy considerations 
  Currently, life sciences have entered the development period of mega-science, big data, big platform, and big discovery. Under this development trend, scientific and technological organizations more particularly need a “national system”. Precision medicine is a typical representative of this trend. To promote precision medicine development in China, we recommend that a long-term continuous funding mechanism be established, and a research platform and a team of talented professionals be set up, and a coordinating innovation network be constructed, so that system support can be provided for a national precision health system. The specific recommendations are as follows: 1) Develop a long-term development strategy in China, and on the basis of achievements during the “13th fve-year plan” period, provide a longer term and stable support in the “14th fve -year plan” period. 2) Establish a systemically designed and unified national cohort and data platform by taking full advantage of the national system and on the basis of the preliminary precision medicine cohort and big data platform. 3) Study and discuss precision prevention, diagnosis, treatment strategies and pathways for specialized diseases using specialized diseases as a basis, and accelerate research and clinical applications of precision medicine prevention, diagnosis and treatment of specialized diseases. 4) Improve the policy, regulation and ethical system to ensure the comprehensive and orderly development of precision medicine. 5) Establish a collaborative network of government, industry, academia, research and economics, build a new sustainable organizational model, and coordinate the coordinated promotion of various market players. 6) Support industry base and cluster construction, and promote the rapid development of precision medicine industry. 7) Improve the multi-level talent training system, and increase the eforts of composite talent training and recruitment eforts.
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