美国《科学》报道：揭开中药的面纱

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记者：Richard Stone
美国《科学》2008年2月8日
（翻译：方舟子） 　　大连，中国——基因组学、蛋白质组学、代谢组学……本草组学？做为揭开大自然的生物化学秘密的最近一次进攻，位于这个海滨城市的一个中国团队正开始一项15年计划，试图鉴定出在中国用了数百年的草药药方的成分。
　　本草物质组计划是最新的——也是最雄心勃勃的——试图让中药现代化的一次尝试。这些古老的药方——多达40万个方剂、用了1万种草药和动物酊剂——是中国许多人选择的治疗方法，常常是唯一的方法。在1970年代，在中药的启发下研究人员从青蒿中发现了青蒿素做为抗疟疾的良药。但是中药的名声由于其不可靠的疗效和严重的副作用而大受损害，导致批评者抨击它是过时的民间医术。“中药不是建立在科学，而是建立在玄学、巫术和传闻的基础之上，”生物化学学者方是民说，他以方舟子为笔名自任中国科学警察。他认为本草物质组计划只是“浪费科研经费”。
　　为了反击中药的批评者，本草物质组计划将采用高通量筛选、毒性检验和临床试验以鉴定出常用药方中的活性成分和毒性污染物。“我们需要确保中药是安全的，并且显示它不止是青蒿素，”在上海药物所负责中医药现代化项目但未参与本草物质组计划的果德安说。最初的目标是癌症，肝脏和肾脏疾病，以及用西药难以治疗的其他疾病，例如糖尿病和抑郁症。
中国科学院最大和科研资金最充足的研究所之一——大连化学物理研究所获得了一笔5百万美元的启动基金用以研发纯化方法；科技部正在审核这个计划，打算把它划入自2010年开始的下个5年计划的一项7千5百万美元的创新规划中。今年春天北京香山会议——相当于中国的戈登学术会议——将为此举行一个规划会议。
　　中药界的几名权势人物已支持这项规划。“开始这个项目正是时候，”上海中医药大学校长、化学家陈凯先说。上海中药创新研究中心理事长惠永正说，制药公司应该会对本草物质组计划感兴趣，因为它能够鉴定出许多候选药物。
　　在世界上许多地方，传统医学药方是通过口述代代相传的。但是在中国，2千多年前的医生已开始编写药典。虽然在大城市西医已大体上取代了中医，但是许多中国人仍然相信中医药做为预防药物和治疗慢性病很有效，而在乡村的中国人还在依赖它。“我们大多数人在感到身体不适时，就吃中药，”大连化学物理研究所的梁鑫淼说。
　　自从毛泽东时代以来，中国政府就在强烈支持中医药，部分原因是因为没钱向大众提供西医药。中国媒体至今还忌讳把中医称为伪科学。“对许多中国人来说，批评中医药是无法想像的，几乎就像是犯了叛国罪，”方舟子说。
支持者坚持认为中医药可以提供很多东西。但是伴随着每一项中药成功的宣称，都有不良反应的报告，有的来自天然毒性成分，有的来自杀虫剂之类的污染物。中药剂量也难以确定，因为药方的效力根据草药产地和采集时间而发生变化。不同的厂家和不同的批次的药物质量能够出现差异。“这就是为什么许多人不信任中药，”果德安说。在中药现代化进程时，质量控制是一个首要关注的问题。
　　本草物质组计划打算把现代化带到一个全新的水平。这项计划是梁鑫淼首先提出的，他相信许多中药是有效的。“问题是我们不知道它为什么有效，”他说。主要的障碍是药方很复杂。做为一个例子，梁鑫淼展示了一种用以外涂消除肌肉疼痛的药方“红花油”的色谱图。梁鑫淼说，在化学家处理的许多样品中，一个峰通常代表一种化合物。但是对红花油来说，一个峰是许多化合物，将之分馏产生了更多的多化合物峰，就像俄罗斯套偶。梁鑫淼说，红花油至少由1万种化合物组成：“我们只知道100种。”
面对这种复杂性，“我们必须发明新的方法学，”梁鑫淼说。“这是本草物质组计划的战场。”首先，他在大连化学物理研究所的45人团队正在研发新的分离介质。草药将被分解成“多组分”：相似的成分为一组。为了确定哪种物质是有益的或有毒性的，他的研究组计划设计本草组芯片，其中的化合物将根据它们与关键多肽的结合能力进行筛选。扩大后的本草物质组计划将会有国内外许多研究机构的人员参与。
　　本草物质组计划有隐藏的危险性。其中之一是担心西方制药公司会通过改造该计划鉴定出的化合物研发出销量巨大的药物，掠走战利品。为了对抗这种可能性，果德安说：“我们鼓励科学家不要急于发表论文，并先（对鉴定出的候选药物）做结构改造。”然后团队会对一组相似结构的化合物申请专利。
　　并不是所有的中医业者都接受对中医药去神秘化。“有些人担心传统会丧失掉，”陈凯先说。但是惠永正说“为了调和西医知识导向的演绎法和中医经验导向的归纳法”，现代化是必要的。方舟子另有看法：“你能够结合占星术和天文学，炼金术和化学吗？它从来就行不通。”
　　惠永正坚持认为中医能与西医共处。梁鑫淼希望他的本草物质组计划将会证明惠永正是对的。

Science 8 February 2008:
Vol. 319. no. 5864, pp. 709 - 710
DOI: 10.1126/science.319.5864.709
BIOCHEMISTRY:
Lifting the Veil on Traditional Chinese Medicine
Richard Stone*
DALIAN, CHINA--Genome, proteome, metabolome … herbalome? In the latest industrial assault on nature's biochemical secrets, a Chinese team in this seaside city is about to embark on a 15-year effort to identify the constituents of herbal preparations used as medications for centuries in China.
The Herbalome Project is the latest--and most ambitious--attempt to modernize t raditional Chinese medicine (TCM). The venerable concoctions--as many as 400,000 preparations using 10,000 herbs and animal tinctures--are the treatment of choice and often the only recourse for many in China. In the 1970s, TCM tipped off researchers to qinghaosu, a compound in sweet wormwood whose derivatives are potent antimalaria drugs. But TCM's reputation has been blackened by uneven efficacy and harsh side effects, prompting critics to assail it as outmoded folklore. "TCM is not based on science but based on mysticism, magic, and anecdote," asserts biochemist Fang Shi-min, who as China's self-appointed science cop goes by the name Fang Zhouzi. He calls the Herbalome Project "a waste of research funds."
Hoping to rebut TCM critics, Herbalome will use high-throughput screening, toxicity testing, and clinical trials to identify active compounds and toxic contaminants in popular recipes. "We need to ensure that TCM is safe and also show that it is not just qinghaosu," says Guo De-an, who leads TCM modernization efforts at the Shanghai Institute of Materia Medica and is not involved in Herbalome. Initial targets are cancer, liver and kidney diseases, and illnesses that are difficult for Western medicine to treat, such as diabetes and depression.
The Dalian Institute of Chemical Physics (DICP), one of the biggest and best-funded institutes of the Chinese Academy of Sciences, won a $5 million start-up grant to develop purification methods; the Ministry of Science and Technology is reviewing the project with a view to including it as a $70 million initiative in the next 5-year plan to start in 2010. A planning meeting will be held at a Xiangshan Science Conference--China's equivalent of a Gordon Research Conference--in Beijing this spring.
Several TCM power players have thrown their weight behind the initiative. "It's the right time to start this project," says chemist Chen Kai-xian, president of the Shanghai University of Traditional Chinese Medicine. Herbalome should appeal to pharmaceutical firms, as it could identify scores of drug candidates, says Hui Yongzheng, chair of the Shanghai Innovative Research Center of Traditional Chinese Medicine.
In many parts of the world, traditional medicine recipes are handed down orally from one generation to the next. But in China, practitioners more than 2000 years ago began to compile formulations in compendia. Although in major cities Western medicine has largely supplanted TCM, many Chinese still believe in TCM's power as preventive medicine and as a cure for chronic ailments, and rural Chinese depend on it. "For most of us, when we feel unwell, we want to take TCM," says chemist Liang Xinmiao of DICP.
Since the Mao Zedong era, the government has strongly supported TCM, in part because it was too expensive to offer Western medicine to the masses. It remains taboo for Chinese media to label TCM as pseudoscience. "Criticizing TCM is unthinkable to many Chinese and almost like committing a traitorous act," says Fang.
Proponents insist that TCM has much to offer. But for every claimed TCM success, there are reports of adverse effects from natural toxins and contaminants such as pesticides. Dosages are hard to pin down, as preparations vary in potency according to where and when herbs are harvested. Quality can vary from manufacturer to manufacturer and from batch to batch. "That's why many people don't trust TCM," says Guo. In the modernization drive, quality control is a paramount concern.
Herbalome intends to take modernization to a whole new level. The initiative is the brainchild of Liang, who believes many TCM recipes are effective. "The problem is, we don't know why it works," he says. The main hurdle is the complexity of the preparations. As an example, Liang shows a chromatograph of Hong Hua, or "red flower," a preparation applied externally for muscle pain. In many samples chemists deal with, one peak usually represents one compound, Liang says. But for Hong Hua, each peak is many compounds, and fractionating these yields more multicompound peaks like nested matryoshka dolls. Hong Hua is composed of at least 10,000 compounds, says Liang: "We know only 100."
Faced with such complexity, "we must invent new methodologies," says Liang. "This is the battleground of the Herbalome project." For starters, his 45-person team at DICP is developing new separation media. Herbs will be parsed into "multi-components": groups of similar constituents. To determine which substances are beneficial or toxic, his group plans to devise Herbalome chips in which arrays of compounds are screened for their binding to key peptides. The expanded Herbalome project would involve researchers at many institutes in China and abroad.
Herbalome has potential pitfalls. One is a concern that Western companies will develop blockbuster drugs--and walk away with the spoils--by modifying compounds identified by the project. To counter this possibility, says Guo, "we're encouraging scientists not to rush to publish and do structure modifications [to identify drug candidates] first." Teams would then apply for patents on groups of similar structures.
Not all practitioners embrace TCM's demystification. "Some are afraid that the traditions will be lost," says Chen. But Hui says that modernization is necessary "to reconcile the knowledge-oriented, deductive process of Western medicine with the experience-oriented, inductive process of TCM." Fang has a different take: "Can you marry astrology and astronomy, alchemy and chemistry? It never works."
Hui insists that TCM can coexist wi th Western medicine. Liang hopes his Herbalome project will prove Hui right.
With reporting by Li Jiao in Beijing.

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据说中药不伤身