近几年来，全球生物制药公司（注：此处生物制药公司包括传统制药公司、生物技术公司以及两者的混合型）不约而同的向美国波士顿 / 剑桥地区聚集，和此趋势相对应的是，波士顿 / 剑桥地区今年被多个媒体或网站评为生物制药或生命科学领域的冠军，其中影响最大的是 GEN 在今年３月份推出的“ Top 10 U.S. Biopharma Clusters ”， 波士顿 / 剑桥地区首次荣登冠军宝座，成功将加州三藩湾区 PK 掉。那么，这些生物制药公司在波士顿 / 剑桥地区到底是怎么扎堆？又是为何在该地区扎堆呢，本文试图解答这两个问题，也希望波士顿 / 剑桥地区的成功经验对我国众多的生物制药开发区建设有所启示。 首先在波士顿 / 剑桥地区（包括大波士顿地区）的众多生物制药公司不仅仅是美国本土的公司，而是来自世界各地，其中也包括中国的公司尤其是欧洲的公司。这些大公司以不同方式、不同地点和布局方式在波士顿地区存在着，大公司在剑桥市最为集中：如在剑桥扎根多年、总部也在此的百键 (Biogen) ；总部也在剑桥并在波士顿地区有多家分公司的健赞（ Genzyme, 现属法国的赛诺菲） ; 在剑桥经营多年瑞士的诺华和美国的辉瑞 (Pfizer, 包括此前收购的惠氏 ); 刚从 百特 (Baxter) 拆分出不久的 Baxalta （尽管百特的总部在伊利诺伊州）； 2018 年将在剑桥开始运营其研发中心的百时美施贵宝 (BMS) ；收购了千禧药业的日本武田 (Takeda) 。另外还有位于波士顿市的默沙东 (Merck), 波士顿近郊还有一些大公司通过收购成立的一些分公司（有些小型公司的名字已经不复存在了），如位于 Billerica 小城的 德国默克旗下的雪兰诺 (Merck Serono) ；位于 Bedford 的新基 (Celgene); 位于 Marlborough 的罗氏 (Roche); 位于 Waltham 的 GSK 和 BMS, 阿斯利康 (AZ) 在 Waltham 也有分公司 , 位于波士顿远郊 Worcester 的 艾伯伟（ AbbVie ，从雅培拆分后改名），尽管 Worcester 是整个新英格兰地区第三大城市。所以毫不夸张的说，世界 Top20 制药公司大多数不是已在波士顿地区，就是正在进军波士顿尤其是剑桥的路上。 当然除了这些大公司外，中小型生物制药公司就更多了，其中包括中国的至少两家公司：药明康德 ( 包括此前收购的 Nextcode 和今年新开张的办公室，不过药明已经算是大公司了 ) 和百济神州（也仅仅是办公室，新任 CFO 已在此走马上任）。美国大约占整个世界药物市场的一半，另外，美国的药物市场的监管也最为严格，被 FDA 批准上市的新药几乎可以被认为是免检产品，绝大多数都陆续在世界其它各国获批。所以毫不夸张地说，对于全球制药公司而言，得美国者得天下，而要想得美国，剑桥现在已经成为了首选之地，可以预见：剑桥将更是众多有志进军美国的世界生物制药公司的兵家必争之地。 众所周知，波士顿地区的房价已经很高，尤其是剑桥的实验室和办公室租金更是高的离谱，但是为何又有这么多制药公司不顾高企的成本，在该地区扎堆呢？本文主要侧重谈谈在剑桥扎堆的原因。限于笔者的眼界和知识面，本文意在抛砖引玉，期待能引起业内人士的对这两个问题的关注和讨论。 药企在剑桥扎堆的一个显而易见的原因是那两所世界顶级大学的存在，但是哈佛和 MIT 已经在剑桥存在 N 年，缘何近几年扎堆明显？！想必还有其它重要原因。笔者认为至少还有如下几个原因： 波士顿的世界顶级医疗资源：波士顿有三所医学院（哈佛、波士顿大学和 Tufts ）和两所药学院，尤其是哈佛医学院下属的三大综合性医院和波士顿儿童医院以及 Dana–Farber 癌症研究所最为出名，这些医院基本集中在波士顿市的 Longwood 医疗区。麻省总医院 (MGH) 虽不在这个医疗集中区，但在综合性医院中，根据最新权威排名它是全美第一名。尤其值得一提的是 波士顿儿童医院，多年来一直是美国最好的儿童医院。现在用于治疗罕见病的孤儿药越来越成为欧美制药公司研发和投资的重点，而大多数罕见病是遗传性的，会伴随终身，而有大约 30% 的罕见病儿童会在 5 岁前离开人世。因此儿童是罕见病的重要人群，而各种罕见病儿童病人全世界最为集中的地方恐怕就是波士顿儿童医院了，该医院的国际中心每年接诊来自全球 100 多个国家的儿童病人，所以，对于发愁病人入组困难的罕见病临床实验而言，波士顿儿童医院是很理想的地方。波士顿儿童医院也位于 Longwood 医疗区，但在该区的大药厂只有默沙东一家。大公司为何只对剑桥独有情钟呢？也许，波士顿超强的医疗资源并非根本原因。 近几年，由于多种原因（如不断攀升的药物研发成本、专利悬崖和有限的社会支付能力）导致整个制药行业利润率不断下降，这也使得大药厂原来遍地开花、全线作战的模式难以为继，迫使这些公司至少在两个方面压缩战线：分公司的地点和数量以及药物研发的治疗领域。不太重要或者位置不理想的分公司和自己公司不太擅长的治疗领域通过关、停、并、转得以整合，从而实现两个聚焦：研发中心地点的聚焦 / 集中和治疗领域的聚焦。在研发中心地点的选择上，在生物药日益重要的今天，剑桥地区显然是首选之地。另外，今天的大药厂更加依赖中小创新型公司来丰富、调整自己的研发管线（参见美中药源另一分析文章： 收购是比创新更有效的增长手段吗？ ） ，而剑桥拥有为数众多的创新型制药公司，而这一点也是笔者个人认为的大公司在剑桥扎堆最为重要的原因，为何这么说，下面稍微展开说说。 剑桥的创新型制药公司不但为数众多（至少上百家 , 主要集中在 Kendall 广场，名单参见文末附表），更重要的是这些公司的水平和质量之高更为惊人。水平高，不是笔者自己吹的，下面仅仅通过一组数据，以管窥豹。著名业内媒体 Fierce 每年都会从全球范围内评选出 15 家初创的创新型生物制药公司，即 Fierce 15, 这都是经过业内专业人士和管理人员选出来的精英公司，很大程度上代表了制药领域未来 5-10 年甚至更长时间的发展趋势和可能取得重大突破的方向。自开始评选的 十余 年来，剑桥地区的公司占比都相当惊人，仅以最近 3 年来的数据为例，波士顿地区的占比每年都超过了三分之一，如果只计算剑桥，这一数字则为 15 家（参见下面入选的公司英文名单，没有列地点的公司均位于剑桥市），也就是说，只有区区 10 万人的剑桥小城，在这个榜单中占了世界的三分之一，这个成绩全球没有其它任何一个城市可以出其右。 2014 Fierce 15 （ 6 ） DimensionTherapeutics Editas Medicine Navitor Pharmaceuticals Seres Health Spero Therapeutics Voyager Therapeutics 2013Fierce 15 （ 6 ） Acetylon Pharmaceuticals (Boston) Jounce Therapeutics Kala Pharmaceuticals ( Waltham , MA ) Moderna Therapeutics Nimbus Discovery Visterra 2012Fierce15 （ 7 ） Alkeus Pharmaceuticals Bluebird Bio Enanta Pharmaceuticals ( Watertown , MA ) EnVivo Pharmaceuticals( Watertown , MA ) Foundation Medicine Mersana Therapeutics Seaside Therapeutics 在这些小公司中，基本都有自己的绝活，有不少已经成为各自领域的明星企业，如入选 2012 年度的蓝鸟 (Bluebird), 是现在风头正劲的基因治疗领域的领军公司，也是美国 5 家已经上市的基因治疗公司中市值最高的，很多人都预测这只蓝鸟会飞的更高（参见 : 飞翔的蓝鸟： BluebirdBio 镰刀状细胞贫血基因疗法 LengiGlobin 在第一例病人显示疗效 ） 。另外还有基于 mRNA 技术的 Moderna Therapeutics ，以及基因编辑技术的 Editas Medicine( 参见： 英雄配宝马：比尔盖茨投资 Editas ) 等。 尽管小型创新制药公司在剑桥不断涌现，这些小公司的存在也是大公司在剑桥扎堆的重要原因，但 Kendall 广场不断快速增长的房租使小公司不堪重负，这最终也可能使得小公司无法在剑桥生存，小公司不存在了，而大公司也就失去了存在的土壤，这也是寸土寸金的剑桥被人诟病的重要一点。 当然生物制药在波士顿／剑桥地区的扎堆的原因当然不仅仅是上面罗列的这些，而更在于在该地区形成的 生物科技创新生态系统。这个系统就如同根深叶茂的梧桐树，在不断的吸引金凤凰来此筑巢。药明康德的首席运营官杨青博士曾在两年前从宏观角度详细分析了一个健全有活力的生物科技创新生态系统的几个要素： “ 结构丰富互补，价值链完整开放，人才多样相关联，资金充足并能承担风险，政策稳定透明。 ” 这五大要素 波士顿／剑桥地区都具备而且表现突出（尤其是人才和风投资金方面），在人才方面：波士顿被人半开玩笑地称为 “ 博士屯 ” ，不是浪得虚名，本地不但有 H M 等名校源源不断培养高素质的毕业生，更有成千上万的有经验的科研人员，华人是其中的中坚力量，在生物制药领域波士顿地区就活跃着两个华人协会： 美中医药开发协会纽英伦分会 (SAPA-NE) 和美中生物医药协会 (CABA) 。 在风险投资方面，文末附表也包括了几家风险投资公司其中包括著名的 Fidelity Biosciences 。 附录：美国麻州剑桥市的生物医学机构（ Biomedical organizations at Cambridge, MA ） # Name Category 1 Acceleron Pharma, Inc. Drug Development 2 Addgene, Inc. Non-Profit Organization 3 Aegerion Pharmaceuticals, Inc Drug Development 4 Agilis Biotherapeutics Drug Development 5 Agios Pharmaceuticals Drug Development 6 Aileron Therapeutics, Inc. Drug Development 7 Akebia Therapeutics, Inc. Drug Development 8 Alantos Pharmaceuticals, Inc. Drug Development 9 Alexion Pharmaceuticals Drug Development 11 Alnylam Pharmaceuticals, Inc. Drug Development 12 ALS Therapy Development Institute Disease Foundation 13 Amgen, Inc. Drug Development 14 Anutva Services Inc. Drug Development 15 Apeiron-Synthesis, Inc. Contract Research Manufacturing 16 ARIAD Pharmaceuticals, Inc. Drug Development 17 Ariana Data Intelligence, Inc. Bioinformatics 18 Astrocyte Pharmaceuticals, Inc. Drug Development 19 Aura Biosciences Drug Development 20 AuxoCell Research Products Instrumentation 21 Avastus Preclinical Services Contract Research Manufacturing 22 Aveo Oncology Drug Development 23 Axios Biosciences Drug Development 24 Baxalta Incorporated Drug Development 25 BIND Therapeutics Drug Development 26 BioAnalytix Inc. Agricultural / Industrial Biotechnology 27 BioAxone BioSciences Inc. Drug Development 28 Biogen Drug Development 29 Bio-Pact Drug Development 30 bluebird bio Drug Development 31 Blueprint Medicines Drug Development 32 Boston Biochem, Inc. Research Products Instrumentation 33 Boston Biomedical Inc. Drug Development 34 Broad Institute of MIT Harvard Non-Profit Research Institute 35 Cambridge BioLabs Drug Development 36 Cambridge Community Development Government 37 Cancer Research Technology Inc. Disease Foundation 38 Catabasis Pharmaceuticals Drug Development 39 Celexion LLC Drug Development 40 Cellay Inc Medical Device 41 Cerulean Pharma Inc. Drug Development 42 Compass Therapeutics LLC Drug Development 43 Constellation Pharmaceuticals Inc. Drug Development 44 CRISPR Therapeutics, Inc. Drug Development 45 Cydan Development, Inc. Drug Development 46 Cytel Inc. Drug Development 47 DecImmune Therapeutics Drug Development 48 Deciphera Pharmaceuticals, LLC Drug Development 49 Diagnostics For All, Inc. Human Diagnostic Development 50 Dicerna Pharmaceuticals Drug Development 51 Dimension Therapeutics, Inc. Drug Development 52 Edimer Pharmaceuticals Drug Development 53 Editas Medicine Drug Development 54 Eleven Biotherapeutics Drug Development 55 Emulate, Inc. Research Products Instrumentation 56 Ensemble Therapeutics Corporation Drug Development 57 Enumeral Biomedical Holdings Inc Human Diagnostic Development 58 Epiva Therapeutics Human Diagnostic Development 59 Epizyme, Inc. Drug Development 60 Era7 Bioinformatics Inc Bioinformatics 61 Eutropics Pharmaceuticals Inc. Drug Development 62 Evelo Therapeutics Drug Development 63 Exosome Diagnostics Human Diagnostic Development 64 Feinstein Kean Healthcare Marketing / Communication 65 Fidelity Biosciences Investment Capital Firms 66 Flagship Ventures Investment Capital Firms 67 Foundation Medicine Human Diagnostic Development 68 Fuld Co. Business Financial Consulting 69 Gen9, Inc. Research Products Instrumentation 70 Genocea Biosciences, Inc. Drug Development 71 Genometry Inc Contract Research Manufacturing 72 Genosco Drug Development 73 Genzyme Corporation Drug Development 74 GNS Healthcare Bioinformatics 75 Good Start Genetics Human Diagnostic Development 76 H3 Biomedicine Inc Drug Development 77 H4 Boston Marketing / Communication 78 HiFiBiO Inc Drug Development 79 HireMinds LLC Staffing Solutions 80 Horizon CombinatoRx Contract Research Manufacturing 81 Hybrigenics Corp Research Products Instrumentation 82 Hydra Biosciences, Inc. Drug Development 83 Idera Pharmaceuticals Drug Development 84 iGEM Foundation Non-Profit Organization 85 Immuneering Corporation Bioinformatics 86 ImmusanT, Inc. Drug Development 87 Infinity Pharmaceuticals, Inc. Drug Development 88 Intellia Therapeutics Drug Development 89 InVivo Therapeutics Corporation Medical Device 90 Ipsen Bioscience, Inc. Drug Development 91 Ironwood Pharmaceuticals, Inc. Drug Development 92 Jounce Therapeutics, Inc. Drug Development 93 Kanyos Bio Drug Development 94 Kendall Square Association Non-Profit Organization 95 KEW Group Inc. Human Diagnostic Development 96 LabCentral Incubator 97 Locust Walk Partners, LLC Business Financial Consulting 98 Lysosomal Therapeutics Inc Drug Development 99 MediSapiens Inc. Bioinformatics 100 Merrimack Pharmaceuticals, Inc. Drug Development 101 Mersana Therapeutics, Inc. Drug Development 102 Metamark Genetics, Inc. Human Diagnostic Development 103 Millennium: The Takeda Oncology Company Drug Development 104 Mitobridge, Inc. Drug Development 105 Moderna Therapeutics Drug Development 106 Momenta Pharmaceuticals, Inc. Drug Development 107 MPM Capital Investment Capital Firms 108 Nanobiotix Drug Development 109 Navitor Pharmaceuticals, Inc. Drug Development 110 NEHI Non-Profit Organization 111 NeoScientific Contract Research Manufacturing 112 NeuroPhage Pharmaceuticals Drug Development 113 Nimbus Discovery Drug Development 114 Novartis Drug Development 115 NovoBiotic Pharmaceuticals Drug Development 116 Novogy, Inc. Agricultural / Industrial Biotechnology 117 OvaScience Research Products Instrumentation 118 Pfizer, Inc. Drug Development 119 Planet Nutshell Marketing / Communication 120 Potenza Therapeutics Drug Development 121 Preceres LLC Agricultural / Industrial Biotechnology 122 PROMETRIKA, LLC Contract Research Manufacturing 123 Pronutria Biosciences, Inc. Drug Development 124 Propel Careers Human Resources Operations Consulting 125 Proteostasis Therapeutics, Inc. Drug Development 126 Q-State Biosciences Inc. Human Diagnostic Development 127 Quest Diagnostics Other 128 RaNA Therapeutics Drug Development 129 Ra Pharmaceuticals Drug Development 130 Retrophin, Inc. Drug Development 131 Rubius Therapeutics Drug Development 132 SAGE Therapeutics Drug Development 133 Sanofi Drug Development 134 Sarepta Therapeutics Drug Development 135 Scholar Rock Drug Development 136 SciFluor Life Sciences, LLC Drug Development 137 SeLux Diagnostics Research Products Instrumentation 138 Selventa Drug Development 139 Semma Therapeutics Drug Development 140 Semprus Biosciences Corporation Medical Device 141 Seres Health Agricultural / Industrial Biotechnology 142 Seventh Sense Biosystems, Inc. Human Diagnostic Development 143 Solid Biosciences Drug Development 144 Stemgent Inc. Research Products Instrumentation 145 Strategic Science Technologies Drug Development 146 Summit Therapeutics Drug Development 147 Surface Oncology Drug Development 148 Symbiota, Inc, Agricultural / Industrial Biotechnology 149 SynDevRx, Inc. Drug Development 150 Syros Pharmaceuticals, Inc. Drug Development 151 TargAnox, Inc. Human Diagnostic Development 152 Tetragenetics, Inc. Drug Development 153 The Forsyth Institute Non-Profit Research Institute 154 TissueVision Research Products Instrumentation 155 Tokai Pharmaceuticals, Inc. Drug Development 156 UK Trade Investment Foreign Agencies 157 Unum Therapeutics Drug Development 158 VBI Vaccines Inc Drug Development 159 Vedantra Pharmaceuticals, Inc Drug Development 160 Vericel Corporation Drug Development 161 Visterra, Inc. Drug Development 162 VL32 Human Diagnostic Development 163 Voisin Consulting, Inc. Business Financial Consulting 164 Voyager Therapeutics, Inc. Drug Development 165 Warp Drive Bio LLC Drug Development 166 Whitehead Institute Non-Profit Research Institute 167 WuXi AppTec Sales Contract Research Manufacturing 168 WuXi NextCODE Bioinformatics 169 XRpro Corporation Drug Development 170 Zalicus Drug Development 171 Zimmer Etex Medical Device 表格内容主要信息来源： http://www.massbio.org 美中药源原创文章，转载注明出处并添加超链接，商业用途需经 书面授权 。 ★ 更多深度解析访问 《美中药源》 ~
2012年5月10日，在MIT举办的“美国制造业的未来”（ The Future of Manufacturing in the U.S.）会议中，制药企业巨头诺华公司的CEO Joseph Jimenez报告称其公司的制药工艺将有巨大改变，一种新型的药片生产方法能够极大地减少时间，增加税收并改进质量。 通常化学药物是分批生产的，一批化工制造车间的工人先投放一定的原材料将之转化成为活性药物配料，然后再通过船运转移到另一个地点，另一批工人再赋型制备成药片。而诺华，或者还有其他公司，将来将以完全不同的方式生产药剂。诺华与MIT合作五年开发了一种连续制备药剂的系统。此连续工艺可使生产商使用不同的化学反应来代替传统的方法。 Jimenez的报告声称合作非常成功，例如，制备相同量的药剂Diovan（诺华公司一种治疗高血压和心脏病的药物）， 传统分批工艺会耗时12个月，而 连续的生产工艺制备仅需6小时。 Jimenez说：”这种工艺将改变全世界制药的方式“ 诺华公司计划到2015年以前建成一个商业规模的连续生产设施。 英文原文链接http://www.technologyreview.com/blog/editors/27839/
在《西西河 · 淘客熙熙》网站上看到如下留言： 弗莱明因此没有独享诺奖 于 :2011-09-20 02:40:43 由于 “ 弗莱明既没有提纯，也没有做人体实验 ” ，而是由 Chain 和 Florey 完成的，因此总共三人得奖。 屠的 “ 青蒿素 ” 在临床试验差点因为心脏毒性被毙 , 是山东和云南救了这个药。 ( 这个问题造成了后来山东和云南对屠 “ 首先发现青蒿素 ” 持异议 ) 。看看中药常山，是中医最常用的抗疟药，因为毒性一直无法使用。 Lasker 奖颁给屠是对她贡献的肯定，不过更多在她光环背后的人的故事一样精彩。 事实上， 2009 年的 Lasker 临床奖就做得很好，有关 GLEEVEC 的科学研究，药厂研发和临床试验的代表，一个不拉。 最后于 2011-09-20 05:18:35 改 , 共 1 次 ; http://www.talkcc.com/thread/3560881/3#C3567681 这个提示非常好，因为格列卫和复方蒿甲醚都是瑞士诺华公司开发的药品， 2009 年两个药品的专利发明人 Jürg Zimmermann 和周义清等同时获得欧洲发明人奖，对此比较了解。进而由此留言思考：为什么 2009 年的抗癌药格列卫可以三个人获得拉斯克临床医学奖，而 2011 年的抗疟药青蒿素就只能是一个获奖人？ 首先考虑的是先对比 2009 年和 2011 年获奖项目的介绍，为了让读者了解原文和方便按时间历程进行对比，故只摘录原文，先不翻译，原文比较更加准确。 从写法上看有什么不同？读者由此能得出什么结论，对此的看法又是什么？欢迎探讨。 其实， Lasker 奖的推荐人和委员会更应该给予解释。 格列卫 Gleevec 青蒿素 Artemisinin (Coartem) Lasker~DeBakey Clinical Medical Research Award Brian Druker, Nicholas Lydon, and Charles Sawyers For the development of molecularly-targeted treatments for chronic myeloid leukemia, converting a fatal cancer into a manageable chronic condition. Lasker~DeBakey Clinical Medical Research Award Tu Youyou For the discovery of artemisinin, a drug therapy for malaria that has saved millions of lives across the globe, especially in the developing world. Award Description Award Description 1. In 1960, Peter Nowell and the late David Hungerford, working in Philadelphia, noticed an abnormally small chromosome in cells from patients with CML. 2. Several world-class molecular biology groups then figured out that the Philadelphia chromosome generates an enzyme that promotes aberrant cell division. Although the idea held enormous appeal, many scientists thought it would not work. 3. As these results emerged in the mid 1980s, Druker, who was training to be an oncologist at the Dana-Farber Cancer Institute, and Lydon, a biochemist at Ciba-Geigy (now Novartis) realized that blocking BCR-ABL might obliterate a CML cell's ability to stir trouble. 4. By the early 1980s, the field of oncogenes had implicated unruly kinases in cancer, and Ciba-Geigy had begun to explore these proteins as potential drug targets. Lydon set up the company's tyrosine kinase inhibitor program in 1986, under the direction of Alex Matter. Their team , which included cell biologist Elizabeth Buchdunger and chemist Jürg Zimmermann, was screening large chemical collections for compounds that hamper tyrosine kinases in test tubes and inside cells. 5. They then chemically tweaked promising compounds, hoping to improve potency and selectivity. Along the way, Lydon began using a molecular tool that Druker made while studying kinases in the laboratory of Thomas Roberts (Dana-Farber Cancer Institute). 6. In 1993, Druker set up his own laboratory with a single goal in mind: Find a company that had a BCR-ABL kinase inhibitor and develop it for clinical use in CML patients. He contacted Lydon, who sent several compounds for Druker to test. 7. In 1996, Druker and Lydon reported that one of these substances, imatinib (now widely known as Gleevec), killed cultured cells that required BCR-ABL activity to survive, but did not affect a cell line that depended on a different tyrosine kinase, v-SRC. 8. Ciba-Geigy and Druker assembled a team to design the clinical trials. A key member was Charles Sawyers, who was studying BCR-ABL at the University of California, Los Angeles. To perform the first clinical trials, they enlisted the collaboration of Moshe Talpaz, an oncologist at MD Anderson Cancer Center. 9. But before they could conduct the study, the enterprise hit some bumps. Ciba-Geigy merged with Sandoz to form Novartis, and Lydon left the company soon afterward. Toxicity concerns arose, although Druker thought they could easily be handled in the clinic. Passionate in his belief that Gleevec showed tremendous promise and eager to offer patients a potentially life-saving therapy, he lobbied Novartis to move the project forward. 10. Druker, Sawyers, and Talpaz finally got the go ahead to begin a clinical trial, which started in June 1998. The first study aimed primarily to assess Gleevec's safety in chronic-phase CML patients who had not responded to interferon-based therapy or could not tolerate its side effects. These results were astonishing for a cancer drug. Typically, researchers hoped that about 10-20 percent of patients would respond in a clinical trial; in this study, 98 percent of the patients showed dramatic improvements. 11. In May of 2001, less than three years after the beginning of the first clinical study, the US Food and Drug Administration (FDA) approved the drug. 12. During the 2006 study, the scientists realized that Gleevec, as remarkable as it was, did not "cure" patients in the strictest sense. 13. But another challenge was simmering. Some patients were developing resistance to the drug and Sawyers wanted to figure out why. Initial analysis of the BCR-ABL gene revealed a sequence alteration that caused one amino acid to replace another at a particular spot in the protein. John Kuriyan (University of California, Berkeley) had recently deduced the structure of the BCR-ABL enzyme bound to Gleevec using X-ray crystallography, and the picture he produced explained what Sawyers observed. 14. Sawyers proposed to find agents that block the resistant enzyme's activity by fastening to BCR-ABL's active form, yet barring it from performing its reaction. Sprycel progressed rapidly through clinical trials and is FDA approved for patients with resistance to Gleevec. Scientists are exploring the possibility of treating people with combinations of Gleevec and second-generation medications such as Sprycel, with the hope of delaying or preventing the emergence of drug resistance. 15. Approximately 120,000 CML patients and 28,000 GIST patients are currently being treated with Gleevec worldwide. 16. Druker, Lydon, and Sawyers seized upon the known molecular defect that underlies CML, formulated the idea of tackling this root cause of the disease, crafted a specific kinase inhibitor, and designed a second-generation inhibitor when drug resistance developed. Druker, Lydon, and Sawyers have provided a stunningly successful treatment for CML and a new paradigm for cancer therapy. 1. The first known medical description of Qinghao lies in a 2000-year-old document called "52 Prescriptions" (168 BCE) that had been unearthed from a Mawangdui Han Dynasty tomb. 2. The covert operation, named Project 523 for the day it was announced—May 23, 1967—set out to battle chloroquine-resistant malaria. 3. In early 1969, Tu was appointed head of the Project 523 research group at her institute, where practitioners of traditional medicine worked side by side with modern chemists, pharmacologists, and other scientists. 4. By 1971, her team had made 380 extracts from 200 herbs. 5. At a March 1972 meeting of the Project 523 group's key participants, she reported that the neutral plant extract —number 191—obliterated Plasmodia in the blood of mice and monkeys. Later that year, Tu and her team tested the substance on 21 people with malaria in the Hainan Province, an island off the southern coast of China. 6. On November 8, 1972, she and her colleagues obtained the pure substance. They named it Qinghaosu. Tu and her colleagues subsequently determined that it had an unusual structure. 7. Subsequent clinical trials on 529 malaria cases confirmed that the crystal they had isolated delivers the antimalarial blow. Many scientists from other institutes then joined efforts to improve the extraction procedures and conduct clinical trials. 8. In October 1981, the scientific working group on the chemotherapy of malaria, sponsored by the WHO, the World Bank, and United Nations Development Business, invited Tu to present her findings at its fourth meeting. 9. In 1973, as part of her structural studies, Tu had modified artemisinin to generate a compound called dihydroartemisinin. 10. Starting in the mid 1970s, Guoqiao Li (Guangzhou College of Traditional Chinese Medicine) performed clinical trials with artemisinin and these substances. 11. In 1980, Keith Arnold (Roche Far East Research Foundation, Hong Kong) joined Li's enterprise and two years later, they published the first high-profile clinical trial of artemisinin in a peer-reviewed, western journal. 12. In 2001, the WHO signed an agreement with Novartis, the manufacturer of one of these drug combinations, Coartem; it consists of artemether and lumefantrine, another antimalarial agent, which was originally synthesized by the Academy of Military Medical Sciences in Beijing. The company is supplying the drug at no profit to public health systems of countries where the disease is endemic. To date, Novartis has provided more than 400 million Coartem treatments. by Evelyn Strauss, Ph.D. by Evelyn Strauss, Ph.D. http://www.laskerfoundation.org/awards/2009_c_description.htm http://www.laskerfoundation.org/awards/2011_c_description.htm 请读者再参考 博文《拉斯克奖没有按WHO治疗疟疾规范办事》 http://blog.sciencenet.cn/home.php?mod=spaceuid=396469do=blogid=492494 中信出版社图书《神奇的抗癌药丸》
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