生物信息学包括可以解释重要蛋白质分子结构的自 Bioinformatics encompasses colculati( that can interpret the structure of important f 创新文化 美国的科技进步正在革新药物发现 A culture of innovatio TeChnoIogiCaI advances in the US are reVoIutioniSing drug discovery The science and technology of d rug discovery is ch{ _rapidly,New technologies and insights into the caU: I treatmentofdiseasea re revolutionising biopha rmace . r 治疗疾病的方法并给数百万患者带来希望。 54 PharmaTechnology・医药技术 维普资讯 http://www.cqvip.com
深入美国 Insidethe US :有时存在一些令人畏・惧的风险,但制药公司在新的研究开 的投入不断增加。2005年度美国药物研究和制造商协会 )的成员公司在新药研发上的总投资超过395 ̄7_,美元(3150亿 。pipeline are ta rgeting a growing list of previously intractable diseases and conditions.These medicines are improving how we treat disease and giving hope to millions of patients. 若合计 ̄PhRMA成员和其它私人及大学研究实验室的研究投 In spite of sometimes daunting risks.the investment of pha rmaceuticaI companies in new resea rch and development j生物制药研究的年投入则高达510亿美元(4070 ̄7_,人民币)。 :去的几年中,美国制药投资曾出现巨大的增长一1 980年新药 contiRues to g row.In 2005.member companies of the F发投入还只有20亿美元(16亿人民币)。私人投资仍然是新 Pha rmaceuticaI Resea rch and Manufactu rers of America j最重要的资金来源。美国投入资金用于基础科学研究。 【I hRMA)invested iust over USD 39.5bn(RMB 31 5bn)in 1286t7_,美金被分派给美国国立卫生研究院(NIH)用于其正常 resea rch and development of new medicines.When resea rch 是,其中相当一部分资金被用于正常运转和管理花销。 investments by non—PhRMA members and other private 『,约有超过2000种新药正处于研发阶段和进入美国药物审 and universitv resea rch Iaboratories a re taken fnto account. p。如果获得批准,这些药物将为癌症,高血压,心脏疾 annuaI US biopha rmaceuticaI resea rch investment topped l系统疾病和艾滋病带来更好的治疗方法。 USD 51bn fRMB 407bn). 可以带来重大的风险。研究表明,每10000个筛查具有药用 This is a massive increase on previOUS yea rs—in 1 980. E合物中,只有5个在最后研发阶段成为获得批准的药物。进 investment in research and development was iust USD 2bn 表明,一个获得批准的药物从实验室研究到出现在药房药 【RMB 1 6bn】.Private investment continues to be the most 有过程平均花费超出8tg美元(64亿人民币)。全过程可能 jmportant funding SOUrce for discoverjng new medjtines. 15年。 The US government invests in basic scientific resea rch. 嚏今为止的工业,风险已经惊人地全部还清。并且创新决不 USD 28.6bn“ MB 228bn)was allocated in 2005 to operate {。新工艺学,技术和进程正带来更多地发现和治疗方法。 the US NationaI Institute of HeaIth【NIH).However.a :保健的需求驱动药物的发现。作为一个社会,现在美国人 considerable portion of that funding is for operating and 口生活质量都好于历史上任何时期。这部分归功于药物的发 administration expenses. :率在降低,长期残疾比例在降低,人口预期寿命高于以 Currently,there are more than 2000 meditines in the ]正在不断攻克我们所面对的最为严重的疾病。当思考将来 research and development pipeline and advancing through 的发展方向时,有一件事是比较确定的:新型创新药物将 the US drug approval process.If approved.these medicines 代卫生健康质量的道路上承担越来越突出的作用。 w川resuIt in better treatments for cancer,hypertension.hea rt diseases.neurologicaI disease and AIDS. Investment brings siqnificant risks.Studies 正超越传统化学分析向开发靶向和遗传药物方面发展 1 in the US is advancing beyond traditional show that for every 1o.000 compounds lanalysis to develop targeted and genetic medicines examined as a potentiaI medicine.onIV five emerge as approved medicines at the end of the resea rch and development process.Further studies show that.on average.it costs in excess of USD 800m fRMB 6.4bn)to bring an approved d rug all the way from the laboratory to the pharmacy shelf,The process can take anything frOm 12 tO 15 years. Across the industry to date.the risks have paid—off impressively.And the innovations are far frOm over.New technologies.techniques and processes are bringing more discoveries and treatments to corne. Drug discovery s driven by healthca re needs.As a societv.Americans are Iiving Ionqer and better than at any time in history.In part. this is due to pharmaceuticaI advances.Death rates are down.Iong—term disabilitv is down,Iife expectancy is higherthan ever,and we‘re making progress against the most serious diseases we face.When considering the direction heaIth 医药技术・PharmaTechnology 维普资讯 http://www.cqvip.com
深入美国 Inside the US care will take in the future.one thing iS certain:new and innovative medieines will assume an increasingly prominent role fn the way we improve the quailty of care for futu re generations. One eritieal role of new medicines wilI be the prevention.treatment, and management of many diseases suffered by the aging ‘’baby boomer”generation.born during the population explosion that oeeu rred after the Second World War.1n the year 2000.there were roughly 35.6 mfIlion Americans aged 65 and olde ̄ By 2030.this number is pr ̄eeted to more than double.to an estimated 71.5 m…ion. Diseases like diabetes and Alzheimer‘S represent a growing threat.not onlY to patients but also to healthea re eeonomies.Lifestvrles and healtheare systems must be improved to avoid an enormous disease burden on patients.their families,employers. and federal and state governments. New pharmaeeutiealS are a vital Da rt of the SOlution to thiS rapidly intensifying problem. AIzheimer。S disease poses a signiifcant challenge to aging baby boomers on the verge of retirement. A recent report by the US Alzheimer。S Association川ustrates how meditines present an important solution to this ehallenqe.as well as underlining the importanee of finding new health solutions.As the elderly population grows.the number of people over 65 with AIzheimer。S iS expected to g row frOm 4.5 million in 2000 tO 6.5 milIion in 2025 and 1 3.4 m…ion in 防,治疗和管理年老的“婴儿 2050.Without new solutions.health insurance spending on 人口激增时期出生的一代人的多 Alzheimer。S will triple by 201 5. 及以上的人口约达 ̄356o万。到 Better treatments that delay the onset of the disease and ,估计约为715O万。 slow its prog ression could have a dramatic effect.not only on 病代表着一种正在不断增长的威patients lives but on spending for the disease.According to the f医疗卫生经济学的。生活方式和 report.medieal research breakthroughs eould result in nea rly 免众多疾病对患者及其家属,雇th ree million fewer Americans with Alzheimer。S and savings of 。新药是解决这一快速加剧问题 USD 1 50bn(RMB 1.200bn)in savings to government programs like Medieare and Medieaid by 2025. 医药技术・PharmaTechnology 57 维普资讯 http://www.cqvip.com
阿尔茨海默氏病对即将退休的老年“婴儿潮”一代提出了强烈 的挑战。最近一份美国阿尔茨海默氏病协会的报告阐述了药物做为 性。随着年老人群的增长,超过65岁并患有阿尔茨海默氏病的人数 预计将从2000年的450万增长YU2025年650万,及2050年1 340万。如 果没有新的解决办法, ̄U2015年花费在阿尔茨海默氏病上的健康保 险将会增加至目前的三倍之多。 更好的延迟疾病发生和延缓疾病进展的治疗方法不仅对患者 Spendinq on research t0d: sayings to the Medica re progr 解决这一挑战的重要・陛,并强调了寻找新的医疗解决手段的重要 each dolla r(RMB 8】invested in yield USD 10(RMB 80】in savir 200lin savings by 2025. Scientiic advances are n frange of conditions and prey( quality of Iire.patients familie n biopha rmaceuticaI and mc 的生活,同时也对疾病治疗的花费都有惊人的影响。据报道,到 i2025年医学研究的突破可能会导致美国阿尔茨海默氏病患者减少近 increasingly pointing toward t{ 300万及节约了如联邦医疗照顾(Medica re)和医疗补助(Medicaid) 这样的项目资金15OOE美元(11200E人民币)。 目前研究项目上的投入预计会大量节省Medica re项目的资金。 据报道,目前投入到阿尔茨海默氏病研究的资金平均1美元(8人民 (200人民币)。 of“personaIised medicine。: ThiS approach means thal medicines wiII increasingIY be fr0m genetic and other molec 币) ̄U2025年会节约10美元(80人民币), ̄U2o25年会节约25美元 these tests WiII revea1 whether a weIIto a drug—or avoidtoxic si, mediCiRe at the right time. There a re 1 2 such treatme 科学进步对于处理大范围内的情况和控制医疗保健,生活治 to treatment can ensu re that e 疗,患者家庭,及经济的不断损失是极有必要的。美国生物制药和 医学研究的发展趋势越来越指向靶向治疗和创立“个性化用药”。 S field iS rapidly expandin(j 这种趋势意味着,新药的临床使用越来越受到遗传学和其它分 thi子水平检测的预测性证据的指导。预期这些检测可以反应不同个体 tests can reveaI a patient。S SI 58 PharmaTechnology・医药技术 维普资讯 http://www.cqvip.com
墨 差垦 Inside the US 是否对药物反应良好或是避免产生毒副作用。靶向治疗方法可以 can also guide preventive treatment before symptoms a rise.The eme rgence of personaIised medicine wiII shift the focus of medicaI ca re from”disease treatment”to “healthca re management.” SimuItaneously,America S biODharmaceuticaI resea rch companies a re exploring a wide range of new technologies and tools in the effort to create new treatments.1he process of d rug discovery relies heavily on innovation.insight and a Iot of ha rd work.But in the past decade.a new industriaI revolution 保证每名患者在正确的时间使用正确的药物。 目前已有1 2种此类治疗方法在临床使用,并且此领域的发展十 分迅速。因为分子水平的诊断检测可以反应患者对疾病的易感性, 所以这些检测也可以用于指导无症状表现前的预防性治疗。个性化 用药的出现将医疗保健从“疾病治疗”转换为“医疗保健管理”。 美国的生物制药研究公司同时也在广泛地探索新技术和新工具 以创建新的治疗方法。新药发现的过程很大程度上依赖于创新,洞 察力和大量辛苦的劳动。但在刚过去的十年里,一种新型的工业革 新技术已经进入了实验室。 has entered the laboratory. The jntroduction of automation and robotics into the resea rch and development process is greatly enhancing 自动化技术和机器人技术引入研究和开发过程极大提高了科学 家探知和鉴定候选新药的能力。自动化技术和机器人技术的进步意 昧着,数百万化合物可以在大约几周的时间内合成。 the ability of scientists to explore and identify new drug candidates.Advanees in automation and robotics mean miIlions of themieaI tompounds can now be manufaetu red 使用液体,化学试剂和样品板,机器人就可以检测数千个化合 物对生物样品的潜在治疗活性。通过混合和比对这些化合物的近似 选新药的最佳药物分子结构组合。 生物信息学是另一项为研究提供极大成效的相对较新的领域。 药物发现的过程会产生大量对发现新药十分重要的信息。生物信息 学可以使用不同系统和数学模型以推进对生物系统的了解。 of weeks. 的分子结构单元,参与研究的生物药学家就可以确定日后可成为候 in a matterUsing liquids.chemicals and sample plates.robots can run tests on thousands of these tompounds on biological sampies for potential therapeutic activity.By mixing and matching these tompounds like buiIding blocks.resea rch bio—pharmacists can 维普资讯 http://www.cqvip.com
从最简单的水平而言,生物信息学包括创建和维护生物数据 determine the best combination that mi0ht one day become a new drug candidate. Bioinformatics iS another relatively new field that has greatly enhanced the performance of research.The d rug discovery process produces vast amounts of information that may be important in discovering new medicines.Bioinformatics uses systems and mathematicaI models to advance the science 库,如DNA序列。此外,生物信息学还包括破解疾病分子通路,探寻 基因对药物反应的方式,解释重要蛋白分子的三维结构和帮助结算 机辅助设计新药的计算工具。 每种疾病在人体内都有一种分子水平的“生物标记物”,如表 达开闭的基因,或释放入血的蛋白质分子。其它的样品能告诉我们 自己身体的状态和我们对治疗会产生怎样的反应。生物标记物代表 了一种可以在疾病最早期状态和症状出现前,即通常是疾病最容易 治疗的时间,辅助诊断某些疾病的强有力的新型工具。 生物标记物还可以辅助指导医生开具最为有效的药物处方以最 Of Understandin0 Iivinq systems. At its SimPIest IeveI.bi0info rmatiCS invoIyes the creati0n and maintenance of bi0IoqicaI databases.SUch as DNA seaUences.Bi0info rmat CS aISO encompasses caICUIati0n tooIS that can deciPhe r the moIecuIa r pathways of disease.find patte rns in the way genes respond to d rugS.inte rp ret the th ree dimensionaI st ructu re of impo rtant P roteins and benefit the COmpute r—assisted desiqn of new d ruqS. 大程度降低患者的副反应。生物标记物代表了医学的未来,即疾病 的诊断,治疗,监控和预防都要在我们的分子性状的连续指示分子 指导下完成。 分子靶向技术是美国制药工业发展的前沿方向。分子靶向技术 的基本想法是设计药物可以特异性攻击致病的分子通路,但不影响 我们细胞和组织的正常功能。采用此种方法开发的药物与目前的药 物相比毒性更低,药效更好。 靶向药物已经在抑制或清除一些癌细胞导致的肿瘤中表现出了 超强的药效。此种治疗方法可以使患者维持生活质量不受化疗的副 作用影响。 Every disease Ieaves a signatu re of molecular“biomarkers”in the human body,such as genes that tu rn on and off,or proteins released into the bloodstream.Other samples can tell US the state of our heaIth and how we might respond to treatment. WWW.i d is p h a rm a.co m/c h i n a MANAGlNG woRLD MEDlClNEs l甍 维普资讯 http://www.cqvip.com
深入美国 insIdethe us Bioma rkers represent a powerful new tooI that can help detect certain diseases in their ea rliest state and before symptoms appear—at the time when disease iS often at its most treatable. Biomarkers can also help guide physicians to prescribe more effective medicines that W…minimise side—effects f0r the patients.Biomarkers represent the futu re of medicine.a futu re in which disease diagnosis,treatment.monitoring and prevention will be guided by a continuaI indicator of OU r moleeuIar make—u0. Moleeular ta rqeting iS at the forefront of advances in the US d rugs industry.The idea behind moleeuIa r ta rgeting iS to design drugs that speciifcally attack the moleeuIa r pathways that cause disease. without disrupting the normaI functions in ou r cells and tissues.Drugs developed USinq thiS approach can be Iess toxic and more effective than cu rrent medicines. Ta rgeted d rugs have aI ready demonstrated SUperior effectiveness in reducinqoreIiminatingtumoursfrom some types of cancer.Such treatments aflow patients to maintain their quaIitv Of Iife without the side effects of chemotheraPY. The development of targeted drugs iS cornplex.1t requi res a better Understanding of molecuIar pathways.viewing them as if they were pa rt of a network or ci rcuit Of interactions.If the network can be Understood,than a d rug can be developed that shuts down one of the criticaf pathways facilitating the disease.without disturbing others. 纳米技术需要先进的生物信息学工具 NanOfechnOlOgy requires advanced informatics tools NanOtechnOIOgy S the science of building microscopic devices at the molecuIa r and atomic Ievels.In mediciRe. 靶向药物的开发是比较复杂的。它需要深入了解疾病发生的分 nanotechnology WiII be used to diaqnose as weII as treat disease. 子通路,将他们视为相互作用的网络或回路中的成员。如果网络得 Tinv gold—coated”nanoshellS”a re being developed to act Iike 以深入了解,则药物可以开发用于关闭促进疾病发生的某条重要通 smart bombs.closing in on a tumou r,entering cancer cells 路,却不影响其它通路。 and Iyinq in wait UntiI an infra red beam or radio wave signaIS 纳米技术是在分子和原子水平构建显微装置的学科。在医学 the pa rticles to release an intense.deadly dose of energy that 中,纳米技术可以用于疾病诊断和治疗。微小的金包被“纳米球壳 destroys the ca ncer cells. 微粒”设计得象聪明的,包围肿瘤组织,进入并潜伏癌细胞 Cancer patients often Underq0 radiation o r 内,直至红外线或无线电波激发后释放出强烈的致命剂量的能量杀 themotheraPY treatments to kilJ cancer celJs.BUt in 死癌细胞。 the process.normaI ceIIS a re aIso kiIIed.weakening the 医药技术・PharmaTechnology 61 维普资讯 http://www.cqvip.com
肿瘤患者经常进行放疗或化疗以杀死癌细胞。但是在治疗过程中, 正常细胞也会被杀死.导致患者免疫系统能力降低。纳米颗粒可以靶向 patient's immune system.Nanopa rtides can ta rget cance r cells.deIive ring the radiation o r d rugs to only these cells. Ieavina no rmaI cells untouched. Quantum dots a re minUSCUIe fIorescent signaIs that can Iiaht uP tumou rs and lymPh nodes.This enabIes su rgeons 癌细胞,只将放射性或药物传递给这些细胞,不影响正常细胞。 量子点是可以照亮肿瘤和淋巴结的微小荧光信号。这可以帮助 外科医生在手术中完全清除肿瘤或淋巴结。使用不同颜色标记的量 子点,科学家可以有效地创建快速分类肿瘤类型的条形码。 其它构建于微芯片上的细小装置使用纳米技术读取单链DNA,就 像自动收报机纸条一样。虽然此项技术仍处于未成熟阶段,但其可 行性是很大的。 一旦研究者完成人类基因组测序,他们就可以以DNA形式绘制出 人类基因图谱。这一崭新的遗传知识已经开启了根据个体特定基因 序列开发靶向治疗的可能性。这些信息还帮助医生从已知药物中选 择最适合不同个体基因型和环境差异的药物。 研究者也正在开发可以鉴别患者是否易感于某种类型癌症,动 脉粥样硬化,中风,骨质疏松,视力和听力降低甚至丧失的遗传检 测。患者和医生可以使用这些信息建立包括监督生活方式,营养或 预防性药物治疗在内的健康管理程序。 美国目前的医疗保健体系意味着,新药和新型医疗技术的风险 投资在市场上仍然受到鼓励。这种形式与全球各国强制的政 策,如附加的价格,阻碍革新的趋势形成鲜明对比。 新药不断从研发生产线中踊跃而出。例如,2005年28种新药经 美国食品药物管理局(FDA)批准可以供患者使用并进入美国药品市 场。这其中包括18种新型分子结构药物,2种新型治疗用生物制剂和 8种其它生物制剂。2004年38种新型生物药品获得批准。 美国生物制药厂家和全球生物制药工业的挑战是维持一个不断 前进和鼓励创新的环境。如果我们在这场持续的竞争中获胜,那 么目前使用的创新性技术将会为美国和全球的患者带来性的 医学奇迹。 本文由美国药物研究和生产商协会供稿 由于药物变得越来越靶向化,所以显微工具正变得更加先进 As medicine become s inc reo singly to rgefed microscopy fools are becoming more advanced tO remave the comPIete tumou r o r node du rina su rge ry. By using the diffe rently coIou red dots.scientist can effectively create a ba rcode that instantly cIassifies the type of tumou r found. Other tiny devices buiIt onto microchips use nanotechnology to read singIe strands of DNA.much Iike a ticke r tape.The technology is stilI in its infancy,but its possibiIities a re enormous. Once resea rchers campleted sequencing the human genome.they had a maP of the human genes in DNA.This new genetic knowledge has opened up the possibilitv of developing ta rgeted therapies for people with speciifc gene sequences. The information can also heIP physicians choose from among existing medicines the treatment that best meets the individual s genetic Iifestyle.and envi ronmentaI differences. Resea rchers a re aIso developing qenetic tests that can tel1 whether a patient may be susceptible to certain tvpes of cancer,atherosclerosis.stroke.osteoporosis.vision and hea ring IOSS or even cavities.The patient and physician can use this information to estabIish a prog ram of heaIth management incIuding monitoring as well as Iifestyle.nutrition or protective d rug therapy. The heaIthca re system that exists in the US means that risky investments in new medicines and new heaIthca re technologies may still be rewa rded in the ma rketplace.This situation contrasts favou rably with trends a round the aIobe where rigid government policies.such as government—imposed price controls.can discou rage innovation. New medicines continue to emerge from the resea rch and development pipeline.In 2005.for example.28 new medicines were approved for patient use by the US Food and Drug Administration(FDA)and added to the US medicine chest.These included 1 8 new molecula r entities.two new therapeutic biologics and eight other biologics.In 2004.38 new biopha rmaceuticaI medicines were approved. The challenge for American biODha rmaceuticaI manufactu rers and the globaI biopha rmaceuticaI industrv is to maintain an environment that promotes and rewa rds innovation.If we a re successful in this on-going struggle.than the innovative technologies now being used may welI deliver truly revolutiona ry medicaI miracles for patients in America and a round the gIobe.■ This article was contributed by the Pha rmaceutical Research and Manufacturers of America
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