中医药：一种命运未定的文化
英国《自然》2007.7.12
(方舟子译)
刘文龙(音)在北京的普通诊所看上去和大多数诊所没有什么不同。但是他不是个普通医生。刘从来没有要求做实验室检验，也从来不给病人开方做高科技影像诊断。他只依靠简单的观察，检查病人的脉搏、脸色和味道，询问病人的习惯和病史。他今年69岁，已从事中医43年，并坚信中医的好处。“人们总是回头再来的，因为它治好了他们，增进了他们的健康。”他说。
整个上午一个接一个进来让刘看病的患者，其病情从过敏到肺癌都有。有些是第一次来，显得紧张；其他的则是常客，对中医药充满了信心。黄女士是北京郊区的一名会计，困扰她多年的偏头痛在吃了三帖中药后消失了，她对此很高兴。“我以前一直靠止痛药，老是觉得疲惫，”她说，“现在我变成了完全不同的一个人。”
在这个正在热烈地拥抱现代化的国家，像刘这样采用数千年来一成不变的看病方法的诊所，看来很脆弱和过时。的确，对中医的不同态度已让这个国家分裂。去年，湖南长沙中南大学的张功耀在杂志上发表文章称中医是伪科学，应该退出公共医疗和研究。舆论为之大哗。今年早些时候，中国政府宣布一项雄心勃勃的计划，要让已有上千年历史的中医现代化。
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但是如此巨大的鸿沟应该架桥联通吗？现代西方医学一般是针对特定的疾病采取治疗措施，通常是根据疾病的生理因素。然而，中医却是注重症状，使用植物和动物产品，针灸和艾灼。但是，这些方法是否有效，有效的话其机理如何，却一直成为笑柄。最大的分歧在于检验方法。在西方，研究者用随机、有对照的临床试验检验一种药物的安全性和有效性。中医治疗则是根据病人的症状和性质，当场混合多种药物，采用的是代代相传的理论。
中国以及国外的医学界主流对中医理论一向持严厉批评的态度。中医的观念包括气(经络)，认为疾病是气脉阻塞引起的；阴阳，强调能量的平衡；和五行，把人的器官和健康状态根据它们的属性分类：火、木、水、土和金。
在过去的十年，医药公司对中药变得更有兴趣。但是他们采用的方法是西式的：分离出活性成分，挨个做检验。这种还原论的方法发现了一些源自中药的新药，获得批准，例如治疗疟疾的青蒿素和治疗急性早幼粒细胞白血病的砒霜。
, 百拇医药 但是鉴别活性成分并不容易。大多数中医药方都是复方，含有的草药能多达50种，包含成千上万种化学成分。要深入挖掘中医疗法，研究者认为他们也许应该看看混合成分是如何一起发挥作用的。
放宽管理
批准含草药成分的新药的标准现在开始放宽了，至少在美国是如此。在2004年6月，美国食品药品管理局(FDA)发布新规章，即使草药混合物的活性成分未知，但只要能证明其安全和有效，也能获得批准。去年10月，FDA根据新规章批准了第一种草药，德国MediGene公司从绿茶提取物研发出来的、用于治疗生殖器疣的混合药物Veregen。
这些新的规章促使医药业界对复杂药方重新产生兴趣。一个全新的西方领域也许能够被开发出来从中药的深层秘密中获利。系统生物学通过研究一个有机体各个组成部分的相互作用，试图了解其功能和行为。它被认为是用更有整体观的方法研究生物学，并被某些人视为是中医药的一个完美匹配。
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通过同时测量许多基因、蛋白质和代谢物，系统生物学可以为整个身体对草药的复杂混合物的反应提供一种测量方法。“如果有任何技术能够导致中医药研究的突破的话，那就是系统生物学，”荷兰莱顿大学生药学系主任Robert Verpoorte说。但是并非每个人都认同这个新技术是用来检验旧观念的。
上海交通大学系统生物医学研究中心的药理学家贾伟和中国科学院武汉物理与数学研究所的唐惠儒想要更完整地理解草药提取物是如何影响整个身体的。他们正与伦敦帝国学院生物分子医学系主任Jeremy Nicholson合作，采用核磁共振和质谱分析之类的技术分析一个人的尿液或血液中的代谢物——他们称该学科为代谢组学。
贾及其合作者发现，用二甲肼诱发结肠癌的大鼠的尿液中所含的代谢物成分与对照组的不同。给大鼠服用两种中药——中医广泛用来治疗胃病的黄连和吴茱萸——提取物的混合物之后，能够逆转这些代谢变化。他们的研究结果还未发表。但是研究人员说通过检察代谢物变化的细节，他们已确定了草药所影响的代谢途径。
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文化变化
荷兰宰斯特SU Biomedicine的Jan van der Greef及其同事王梅(音)也在用类似的方法。用一种代谢综合征——例如胰岛素抵抗和高血压等通常一起出现的症状的组合——的小鼠模型，他们及其团队观察一种中药秘方对脂质成分的影响。这些小鼠被喂以高脂肪饮食，使它们对胰岛素的抵抗增强。这些小鼠的脂质成分与那些喂以正常饮食的小鼠有显著的不同，而在服了中药之后，朝健康状态转变。
研究人员注意到，脂质成分的转变与治疗肥胖者的西药Rimonabant导致的相似，后者是通过作用于一种称为CB-1内源性大麻受体的蛋白质起作用的。van der Greef说，他们还未发表的细胞培育实验结果表明，草药提取物能够通过相同的受体影响脂质代谢。该团队现在在对该药方做临床试验。
虽然一种活性成分能像西药那样起作用，但是其他附加成分的不确定作用和活性成分的可变性会导致混乱。“可变性让人担忧。”Nicholson说。同一种植物生长在不同的地区，在不同的季节采摘，都能使其化学成分出现差异。对草药研究者来说，这向来是个让人苦恼的难题。
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在Nicholson实验室，唐及其同事分析了来自埃及、斯洛伐克、匈牙利的黄春菊的分子成分，能够很容易地区分它们。用类似的方法，武汉物理与数学研究所的团队发现不同公司生产的同一种草药，甚至是同一家公司生产的同一种草药的不同批次，也有显著的差异。“中国想要让其草药在世界市场上占更大的份额，必须解决这个问题，”唐说。
对许多自诩的系统生物学家来说，需要采用几种研究方法才能构建一个活的有机体的完整图像，并理解中药的作用。不过，系统生物学很显然是一个难以定义的领域。许多人很宽松地使用这个术语，而该领域的先驱者认为，技术手段还未精致到足以被用于做这些研究。
“可以设想系统生物学能够被用于刷选中草药的成分，但是现在还只是非常早期的，”华盛顿州西雅图系统生物学研究所所长、被视为系统生物学之父的Leroy Hood说。“在当前这会是个巨大的挑战。”
根据Hood的说法，系统生物学在模型动物上有所成功，但是在人体研究上的成功则小得多。在研究者能够开始考虑如何对付像中药这么复杂的问题之前，还有许多障碍需要克服。例如，需要有更好的检测系统来精确地测量血液中的代谢物，特别是蛋白质，以及需要用更强大的计算和统计工具，它们对处理大量和复杂的数据是至关重要的。“这些技术还只处于成熟早期，”Hood说。
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对中医的支持者和反对者来说，中医药现代化好都有更大的问题值得关注。有些人对把中药从中医理论分离开来加以研究、开发的做法感到不满。“中医不仅是一个医学体系，也是做为中国文化的重要组成部分的哲学和治疗艺术的一个分支，”北京中国中医科学院的退休研究员、中医古籍出版社社长傅景华说。“脱离了其文化内涵，它就会成为无根之树。”
崇高理想
但是张功耀，以及主持以打击中国的伪科学和学术不端行为著称的新语丝社、美国训练的生物化学学者方舟子说，应该被抛弃的恰恰是那些中医理论。类似阴阳、五行和气这些观念“是对人体模糊的描述，近乎臆想”，方舟子说。
文化因素会是联通东西方鸿沟的不可避免的最大障碍。“中医领域臭名昭著地不能容忍任何批评，”中国医学科学院的医学哲学家袁钟说，“如果人们不能被允许表示不同意见，任何学科都没有希望会有进步。”
, 百拇医药 虽然对中医药未来走向的争论处于白炽化，刘文龙还照常行医。他对中医和西医的结合感到乐观，但是采取的是一种实用态度。“不管是中医还是西医，我们的共同目标都是增进人类健康。只要有效，什么都行。”他评论说。但是刘说他还没看到这两种哲学的结合有任何真正的进展，在那之前，他的诊所和他经验——以及中医看来神秘的理论和方法——对他及其病人都凑合。
《自然》社论：
难以下咽：有没有可能评判中药的真实潜力？
全世界的研究者、从业者和医药公司在翩翩起舞，想要找到挖掘中药的未知潜力的最佳方式。科学界和医药业界都倾向于对“传统”疗法嗤之以鼻；但是有一种强烈的感觉认为，在中国延续千年的医疗实践——它的大部分缺乏记录——有可能至少产生某些有效的疗法。
可以理解，医药公司渴望进入中国市场，波士顿顾问集团估计这个市场去年价值130亿美元，并正在快速增长。但是最刺激他们的是这样一种可能前景：该国的传统医药中也许含有许多可能赢利的化合物，隐藏在一堆神秘的药剂和草药混合物之中的某处。
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要发现这些隐藏的宝物，通常采用的是还原论的方法，即研究者去寻找也许会对治疗特定的疾病起作用的单个化合物。这种方法有时能获得成功：例如，目前用来治疗疟疾最有效的药物青蒿素就是从一种用来治疗发烧的草药中提取出来的。但是这种成功的故事非常稀少。
那么，如果中医药是那么伟大的话，为什么对其结果的定性研究没有为众多治疗打开方便之门呢？最明显的答案是，它实际上没有多少可提供的：它基本上不过是伪科学，它的大多数疗法没有合理的机制。中医拥护者反驳说，研究者没有掌握其奥妙，特别是传统疗法中不同成分之间的相互作用。
不过，医药产业在现在并没有充斥着有希望的新药。也许由于这个原因，全世界的管理机构对传统的方法越来越接受。例如，在2004年，美国食品药品管理局发布有关草药的新规章，如果一种草药以前被用过的话，就很容易让其提取物进入临床试验，而且无需鉴定提取物中的所有成分。
同时，中国和其他地方的一些研究者正在提倡系统生物学——研究蛋白质、基因、代谢物和细胞或有机体其他组分的相互关系的学科——做为评定传统医药的用途的一种方法。我们欢迎那些建设性的方法用以预测传统传统疗法的可能用途。但是，要把一种基本上还未经过临床检验的全新技术，用来检验充斥着伪科学的中医药的准确性，看来是很成问题的。而且，对那些依据一个模糊不清的知识体系所做出的宣称，应该按惯例抱着怀疑态度，这对科学和医学来说都是基本原则。
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News Feature
Nature 448, 126-128 (12 July 2007) | doi:10.1038/448126a; Published online 11 July 2007
Traditional medicine: A culture in the balance
Jane Qiu1
1. Jane Qiu writes for Nature from Beijing.
Traditional Chinese medicine and Western science face almost irreconcilable differences. Can systems biology bring them together? Jane Qiu reports.
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Liu Wen-long's modest Beijing practice looks no different from most clinics. But he is no ordinary doctor. Liu never orders lab tests, nor does he prescribe high-tech imaging diagnostics. He relies on simple observations, checking a patient's pulse, complexion and odour, and asking about habits and medical history. At 69 years old, he has been practising traditional Chinese medicine for 43 years and he is resolute about its benefits. "People keep coming back because it cures them and improves their well-being," he says.
, 百拇医药
Indeed, patients trickle in to see Liu all morning for conditions ranging from allergies to lung cancer. Some are nervous first-timers, others are regulars, confident in what traditional Chinese medicine has to offer. Ms Huang, an accountant from the outskirts of Beijing, is delighted that her migraines, which haunted her for years, disappeared after three herbal regimens. "I used to live on painkillers and felt tired all the time," she says. "I am now a totally different person."
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In a country that is fiercely embracing modernity, clinics such as Liu's, which have been operating the same way for thousands of years, seem vulnerable and out of place. Indeed, attitudes on traditional Chinese medicine have divided the country. Last year, Zhang Gong-yao, from the Central South University in Changsha, Hunan, published an article in a Chinese journal calling traditional Chinese medicine a pseudoscience that should be banished from public healthcare and research1. The article caused uproar in the country, and earlier this year the government announced an ambitious plan to modernize the millennia-old practice2.
, 百拇医药
But should such a formidable gap be bridged? Modern Western medicine generally prescribes treatments for specific diseases, often on the basis of their physiological cause. Traditional Chinese medicine, however, focuses on symptoms, and uses plant and animal products, minerals, acupuncture and moxibustion — the burning of the mugwort herb (Artemisia vulgaris) on or near the skin. But whether these methods are effective and, if they are, how they work remain a source of some derision. The greatest divide is in the testing. In the West, researchers test a drug's safety and efficacy in randomized, controlled trials. Traditional Chinese treatments are mixtures of ingredients, concocted on the spot on the basis of a patient's symptoms and characteristics and using theories passed down through generations.
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The mainstream medical community, in China and abroad, has been highly critical of the underlying theories. Traditional Chinese medicine is based on ideas such as qi (meridian), in which illness is caused by blocked energy channels; yin and yang, which emphasizes the balance of energy; and wuxing (five elements), in which people's organs and health status are categorized according to their 'elemental characteristics': fire, wood, water, earth and metal.
Pharmaceutical companies have become more interested in traditional Chinese medicines over the past decade. But their approach has been characteristically Western: isolate the active ingredients and test them one at a time. This reductionist approach has led to the approval of drugs such as artemisinin for malaria, which is used to treat fever in traditional Chinese medicine, and arsenic trioxide, which has been carried over from Chinese medicine for treatment of acute promyelocytic leukaemia.
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But identifying the active ingredients isn't easy. Most remedies in traditional Chinese medicine, as it turns out, are compound formulae — or fufang — that contain as many as 50 species of herbs, and thousands of chemicals therein (see 'Knowledge mining'). To tap into the deeper well of traditional Chinese treatments, researchers think they may need to look at how the mixtures of ingredients act in concert.Relaxed regulation
The criteria for approval of herbal mixtures as medicines are now starting to relax, at least in the United States. In June 2004, the US Food and Drug Administration (FDA) issued new guidelines that permit the approval of herbal mixtures if they can be shown to be safe and effective, even if the active constituents are not known. Last October, the FDA approved the first such botanical drug under the new rules, a proprietary mixture of green-tea extracts called Veregen developed by the German company MediGene for treating genital warts.
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These new regulations have helped to renew industry's interest in the complex formulae. And a buzzing new Western field could be poised to capitalize on the deeper secrets of traditional Chinese medicine. Systems biology attempts to understand the function and behaviour of an organism by studying the interactions between its components. It has been called a more holistic approach to biology and is seen by some as a perfect match for traditional Chinese medicine.
, http://www.100md.com By measuring many genes, proteins and metabolites at the same time, systems biology may provide a measure of the entire body's response to a complex mixture of herbs. "If there is any technology that could lead to a breakthrough in traditional Chinese medicine, it will be systems biology," says Robert Verpoorte, head of the pharmacognosy department at the University of Leiden in the Netherlands. But not everyone agrees that the new technology is equipped to test old ideas.
, 百拇医药
Jia Wei, a pharmacologist at the Shanghai Centre for Systems Biomedicine at Jiao Tong University, and Tang Hui-ru at the Wuhan Institute of Physics and Mathematics, part of the Chinese Academy of Sciences, want to understand more fully how herbal extracts affect the whole body. They are collaborating with Jeremy Nicholson, head of the department of biomolecular medicine at Imperial College London, and using technologies such as nuclear magnetic resonance spectroscopy and mass spectrometry to profile the metabolites in a person's urine or blood — a discipline they call metabonomics.
, 百拇医药
Jia and his colleagues found that rats given the compound 1,2-dimethylhydrazine to induce tumours in their colons had different metabolic profiles in their urine from those in the control group. And by feeding the rats a combination of two herbal extracts — Coptidis rhizoma and Evodia rutaecarpa, which are widely used in traditional Chinese medicine to treat gastric conditions — the researchers were able to reverse these changes in metabolism. Their results have not yet been published, but the researchers say that by looking at the changes in metabolites in detail, they have pinpointed the metabolic pathways that the herbs affect.Culture shift
, 百拇医药
Jan van der Greef from SU Biomedicine in Zeist, the Netherlands, and his colleague Wang Mei are using a similar approach. In a mouse model of metabolic syndrome — a cluster of conditions such as insulin resistance and high blood pressure that often occur together — they and their team looked at the effect of an undisclosed formula used in traditional Chinese medicine on lipid profiles. When these mice are fed a high-fat diet, they become more resistant to insulin. The lipid profiles of these mice were clearly distinguishable from those of mice fed a normal diet, and they shifted towards the healthy state when the mice were given traditional Chinese medicine3.
, 百拇医药
The researchers noticed that the profile shift resembled that caused by the Western obesity drug Rimonabant, which acts on proteins called CB-1 endocannabinoid receptors. And their unpublished work with cell culture suggests that herbal extracts can affect lipid metabolism through the same receptor, says van der Greef. The team is now testing the formula in clinical trials.
Although one active ingredient may act as the Western drug, the uncertain role of additional ingredients and the variability of active ingredients confounds Western sensibilities. "Variations worry people," Nicholson says. The same plant species grown in different regions and harvested in different seasons could have distinct chemical compositions. This has always been a vexing issue for herbal-medicine researchers.
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While at Nicholson's lab, Tang and his colleagues analysed the molecular components in chamomile plants from Egypt, Slovakia, and Hungary, and could classify them easily4. Using similar approaches, the team from the Wuhan Institute of Physics and Mathematics found significant variations in the same herbal medicines produced by different companies and even between different batches produced by the same company. "This is an issue China must tackle for its herbal medicines to raise their game in the world market," says Tang.
, 百拇医药
To many self-purported systems biologists, several approaches are needed to build a complete picture of a living organism and to understand the effect of traditional Chinese medicine. Nevertheless, systems biology has been a conspicuously hard field to define. Many have used the term loosely, and pioneers in the field contend that the technologies haven't been honed to the point that they could be used for these approaches.
"It's conceivable that systems biology could find applications in trying to sort out components in Chinese herbal medicine, but it's very early days," says Leroy Hood, president of the Institute for Systems Biology in Seattle, Washington, and regarded as the field's founding father. "It would be an enormous challenge at this point and time."
, 百拇医药
Systems biology has been successful in model organisms, according to Hood, but is much less so in human studies. Many hurdles need to be overcome before researchers could even begin to contemplate how to deal with subjects as complex as traditional Chinese medicine. For example, better detection systems are needed to measure metabolites, especially proteins, accurately in the blood, and more powerful computational and statistical tools are crucial for dealing with large and complex data sets. "Those technologies are at early stages of maturation," Hood says.
, 百拇医药
There are also broader concerns about the modernization of traditional Chinese medicine, from both advocates and sceptics of the practice. Some are uncomfortable with separating the study and development of Chinese herbal medicines from the theories that underlie its normal practice. "Traditional Chinese medicine is not just a medical system, but a branch of philosophy and healing art that is an important part of Chinese culture," says Fu Jing-hua, a retired researcher at the Chinese Academy of Chinese Medicine Sciences in Beijing and president of the Chinese Ancient Books Publishing House in Beijing. "Devoid of that cultural context, it would become a tree without roots."Lofty ideals
, 百拇医药
But Zhang and Fang Shi-min, a US-trained biochemist who now runs a society called New Threads that is known for fighting pseudoscience and research misconduct in China say that it is exactly those traditional Chinese medicine theories that should be abolished. Conceits such as yin and yang, wuxing and qi "are inaccurate descriptions of the human body that verge on imagination", he says.
Inevitably, cultural factors may be the biggest obstacle in bridging the East–West gap. "The field of traditional Chinese medicine is notorious for being averse to criticism," says Yuan Zhong, a philosopher of medicine at the Chinese Academy of Medical Sciences. "If people are not allowed to disagree or voice their opinions, there would be no hope of progress for any discipline."
, 百拇医药
But although heated exchanges are boiling over in debates on the future of traditional Chinese medicine, it's business as usual in Liu's practice. He is sanguine about the convergence between traditional Chinese medicine and Western medicine, but has a pragmatic attitude towards it. "Whether from the East or the West, we share the same goal of improving human health. As long as it works, anything goes," he remarks. But Liu says that he is yet to see any real progress in the merging of the two philosophies and, until then, his intuition and experience — as well as traditional Chinese medicine's seemingly arcane theory and practice — will serve him and his patients just fine.
, 百拇医药
See Editorial, page 106.
References
1. Zhang, G.-Y. Med. Phil. 27, 14–17 (2006). 2. Qiu, J. Nature 446, 590–591 (2007). | Article | 3. Wang, M. et al. Phytother. Res. 19, 173–182 (2005). | Article | PubMed | ChemPort | 4. Wang, Y. et al. Planta Med. 70, 250–255 (2004).
Editorial
Nature 448, 105-106 (12 July 2007) | doi:10.1038/448106a; Published online 11 July 2007
, http://www.100md.com
Hard to swallowIs it possible to gauge the true potential of traditional Chinese medicine?
Researchers, practitioners and drug companies around the world are engaged in a complex, tentative dance over the best way to tap into the unknown potential of traditional Chinese medicine. The scientific community and the drug industry both tend to be sniffy about 'traditional' cures; yet there is a strong sense that millennia of practice in China — much of it barely documented — is likely to have yielded at least some treatments that work.
, 百拇医药
Pharmaceutical companies are understandably eager to enter a Chinese domestic market that was estimated by the Boston Consulting Group to be worth US$13 billion last year, and growing fast. But they are tantalized by one opportunity above all: the prospect that the nation's traditional medicine might contain a number of potentially profitable compounds hidden somewhere in its arcane array of potions and herbal mixtures.
The task of finding these elusive gems has been approached in a typically reductionist manner, with researchers seeking single compounds that might have a role in treating specific diseases. Sometimes this has been successful: artemisinin, for example, which is currently the most effective treatment for malaria, was fished out of a herbal treatment for fevers. But such success stories have been few and far between.
, 百拇医药
So if traditional Chinese medicine is so great, why hasn't the qualitative study of its outcomes opened the door to a flood of cures? The most obvious answer is that it actually has little to offer: it is largely just pseudoscience, with no rational mechanism of action for most of its therapies. Advocates respond by claiming that researchers are missing aspects of the art, notably the interactions between different ingredients in traditional therapies.
Nevertheless, the drug industry is not exactly awash with promising new medicines at the moment. Perhaps as a result, the global regulatory process has become increasingly receptive to traditional approaches. In 2004, for example, the US Food and Drug Administration issued new guidelines on botanical drugs that made it much easier to get extracts into clinical trials if there was some history of prior use, and that obviated the need to characterize all compounds in an extract.
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Some researchers in China and elsewhere, meanwhile, are advocating systems biology — the study of the interactions between proteins, genes, metabolites and components of cells or organisms — as a way to assess the usefulness of traditional medicines (see page 126). Constructive approaches to divining the potential usefulness of traditional therapies are to be welcomed. But it seems problematic to apply a brand new technique, largely untested in the clinic, to test the veracity of traditional Chinese medicine, when the field is so fraught with pseudoscience. In the meantime, claims made on behalf of an uncharted body of knowledge should be treated with the customary scepticism that is the bedrock of both science and medicine., http://www.100md.com
(方舟子译)
刘文龙(音)在北京的普通诊所看上去和大多数诊所没有什么不同。但是他不是个普通医生。刘从来没有要求做实验室检验，也从来不给病人开方做高科技影像诊断。他只依靠简单的观察，检查病人的脉搏、脸色和味道，询问病人的习惯和病史。他今年69岁，已从事中医43年，并坚信中医的好处。“人们总是回头再来的，因为它治好了他们，增进了他们的健康。”他说。
整个上午一个接一个进来让刘看病的患者，其病情从过敏到肺癌都有。有些是第一次来，显得紧张；其他的则是常客，对中医药充满了信心。黄女士是北京郊区的一名会计，困扰她多年的偏头痛在吃了三帖中药后消失了，她对此很高兴。“我以前一直靠止痛药，老是觉得疲惫，”她说，“现在我变成了完全不同的一个人。”
在这个正在热烈地拥抱现代化的国家，像刘这样采用数千年来一成不变的看病方法的诊所，看来很脆弱和过时。的确，对中医的不同态度已让这个国家分裂。去年，湖南长沙中南大学的张功耀在杂志上发表文章称中医是伪科学，应该退出公共医疗和研究。舆论为之大哗。今年早些时候，中国政府宣布一项雄心勃勃的计划，要让已有上千年历史的中医现代化。
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但是如此巨大的鸿沟应该架桥联通吗？现代西方医学一般是针对特定的疾病采取治疗措施，通常是根据疾病的生理因素。然而，中医却是注重症状，使用植物和动物产品，针灸和艾灼。但是，这些方法是否有效，有效的话其机理如何，却一直成为笑柄。最大的分歧在于检验方法。在西方，研究者用随机、有对照的临床试验检验一种药物的安全性和有效性。中医治疗则是根据病人的症状和性质，当场混合多种药物，采用的是代代相传的理论。
中国以及国外的医学界主流对中医理论一向持严厉批评的态度。中医的观念包括气(经络)，认为疾病是气脉阻塞引起的；阴阳，强调能量的平衡；和五行，把人的器官和健康状态根据它们的属性分类：火、木、水、土和金。
在过去的十年，医药公司对中药变得更有兴趣。但是他们采用的方法是西式的：分离出活性成分，挨个做检验。这种还原论的方法发现了一些源自中药的新药，获得批准，例如治疗疟疾的青蒿素和治疗急性早幼粒细胞白血病的砒霜。
, 百拇医药 但是鉴别活性成分并不容易。大多数中医药方都是复方，含有的草药能多达50种，包含成千上万种化学成分。要深入挖掘中医疗法，研究者认为他们也许应该看看混合成分是如何一起发挥作用的。
放宽管理
批准含草药成分的新药的标准现在开始放宽了，至少在美国是如此。在2004年6月，美国食品药品管理局(FDA)发布新规章，即使草药混合物的活性成分未知，但只要能证明其安全和有效，也能获得批准。去年10月，FDA根据新规章批准了第一种草药，德国MediGene公司从绿茶提取物研发出来的、用于治疗生殖器疣的混合药物Veregen。
这些新的规章促使医药业界对复杂药方重新产生兴趣。一个全新的西方领域也许能够被开发出来从中药的深层秘密中获利。系统生物学通过研究一个有机体各个组成部分的相互作用，试图了解其功能和行为。它被认为是用更有整体观的方法研究生物学，并被某些人视为是中医药的一个完美匹配。
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通过同时测量许多基因、蛋白质和代谢物，系统生物学可以为整个身体对草药的复杂混合物的反应提供一种测量方法。“如果有任何技术能够导致中医药研究的突破的话，那就是系统生物学，”荷兰莱顿大学生药学系主任Robert Verpoorte说。但是并非每个人都认同这个新技术是用来检验旧观念的。
上海交通大学系统生物医学研究中心的药理学家贾伟和中国科学院武汉物理与数学研究所的唐惠儒想要更完整地理解草药提取物是如何影响整个身体的。他们正与伦敦帝国学院生物分子医学系主任Jeremy Nicholson合作，采用核磁共振和质谱分析之类的技术分析一个人的尿液或血液中的代谢物——他们称该学科为代谢组学。
贾及其合作者发现，用二甲肼诱发结肠癌的大鼠的尿液中所含的代谢物成分与对照组的不同。给大鼠服用两种中药——中医广泛用来治疗胃病的黄连和吴茱萸——提取物的混合物之后，能够逆转这些代谢变化。他们的研究结果还未发表。但是研究人员说通过检察代谢物变化的细节，他们已确定了草药所影响的代谢途径。
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文化变化
荷兰宰斯特SU Biomedicine的Jan van der Greef及其同事王梅(音)也在用类似的方法。用一种代谢综合征——例如胰岛素抵抗和高血压等通常一起出现的症状的组合——的小鼠模型，他们及其团队观察一种中药秘方对脂质成分的影响。这些小鼠被喂以高脂肪饮食，使它们对胰岛素的抵抗增强。这些小鼠的脂质成分与那些喂以正常饮食的小鼠有显著的不同，而在服了中药之后，朝健康状态转变。
研究人员注意到，脂质成分的转变与治疗肥胖者的西药Rimonabant导致的相似，后者是通过作用于一种称为CB-1内源性大麻受体的蛋白质起作用的。van der Greef说，他们还未发表的细胞培育实验结果表明，草药提取物能够通过相同的受体影响脂质代谢。该团队现在在对该药方做临床试验。
虽然一种活性成分能像西药那样起作用，但是其他附加成分的不确定作用和活性成分的可变性会导致混乱。“可变性让人担忧。”Nicholson说。同一种植物生长在不同的地区，在不同的季节采摘，都能使其化学成分出现差异。对草药研究者来说，这向来是个让人苦恼的难题。
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在Nicholson实验室，唐及其同事分析了来自埃及、斯洛伐克、匈牙利的黄春菊的分子成分，能够很容易地区分它们。用类似的方法，武汉物理与数学研究所的团队发现不同公司生产的同一种草药，甚至是同一家公司生产的同一种草药的不同批次，也有显著的差异。“中国想要让其草药在世界市场上占更大的份额，必须解决这个问题，”唐说。
对许多自诩的系统生物学家来说，需要采用几种研究方法才能构建一个活的有机体的完整图像，并理解中药的作用。不过，系统生物学很显然是一个难以定义的领域。许多人很宽松地使用这个术语，而该领域的先驱者认为，技术手段还未精致到足以被用于做这些研究。
“可以设想系统生物学能够被用于刷选中草药的成分，但是现在还只是非常早期的，”华盛顿州西雅图系统生物学研究所所长、被视为系统生物学之父的Leroy Hood说。“在当前这会是个巨大的挑战。”
根据Hood的说法，系统生物学在模型动物上有所成功，但是在人体研究上的成功则小得多。在研究者能够开始考虑如何对付像中药这么复杂的问题之前，还有许多障碍需要克服。例如，需要有更好的检测系统来精确地测量血液中的代谢物，特别是蛋白质，以及需要用更强大的计算和统计工具，它们对处理大量和复杂的数据是至关重要的。“这些技术还只处于成熟早期，”Hood说。
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对中医的支持者和反对者来说，中医药现代化好都有更大的问题值得关注。有些人对把中药从中医理论分离开来加以研究、开发的做法感到不满。“中医不仅是一个医学体系，也是做为中国文化的重要组成部分的哲学和治疗艺术的一个分支，”北京中国中医科学院的退休研究员、中医古籍出版社社长傅景华说。“脱离了其文化内涵，它就会成为无根之树。”
崇高理想
但是张功耀，以及主持以打击中国的伪科学和学术不端行为著称的新语丝社、美国训练的生物化学学者方舟子说，应该被抛弃的恰恰是那些中医理论。类似阴阳、五行和气这些观念“是对人体模糊的描述，近乎臆想”，方舟子说。
文化因素会是联通东西方鸿沟的不可避免的最大障碍。“中医领域臭名昭著地不能容忍任何批评，”中国医学科学院的医学哲学家袁钟说，“如果人们不能被允许表示不同意见，任何学科都没有希望会有进步。”
, 百拇医药 虽然对中医药未来走向的争论处于白炽化，刘文龙还照常行医。他对中医和西医的结合感到乐观，但是采取的是一种实用态度。“不管是中医还是西医，我们的共同目标都是增进人类健康。只要有效，什么都行。”他评论说。但是刘说他还没看到这两种哲学的结合有任何真正的进展，在那之前，他的诊所和他经验——以及中医看来神秘的理论和方法——对他及其病人都凑合。
《自然》社论：
难以下咽：有没有可能评判中药的真实潜力？
全世界的研究者、从业者和医药公司在翩翩起舞，想要找到挖掘中药的未知潜力的最佳方式。科学界和医药业界都倾向于对“传统”疗法嗤之以鼻；但是有一种强烈的感觉认为，在中国延续千年的医疗实践——它的大部分缺乏记录——有可能至少产生某些有效的疗法。
可以理解，医药公司渴望进入中国市场，波士顿顾问集团估计这个市场去年价值130亿美元，并正在快速增长。但是最刺激他们的是这样一种可能前景：该国的传统医药中也许含有许多可能赢利的化合物，隐藏在一堆神秘的药剂和草药混合物之中的某处。
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要发现这些隐藏的宝物，通常采用的是还原论的方法，即研究者去寻找也许会对治疗特定的疾病起作用的单个化合物。这种方法有时能获得成功：例如，目前用来治疗疟疾最有效的药物青蒿素就是从一种用来治疗发烧的草药中提取出来的。但是这种成功的故事非常稀少。
那么，如果中医药是那么伟大的话，为什么对其结果的定性研究没有为众多治疗打开方便之门呢？最明显的答案是，它实际上没有多少可提供的：它基本上不过是伪科学，它的大多数疗法没有合理的机制。中医拥护者反驳说，研究者没有掌握其奥妙，特别是传统疗法中不同成分之间的相互作用。
不过，医药产业在现在并没有充斥着有希望的新药。也许由于这个原因，全世界的管理机构对传统的方法越来越接受。例如，在2004年，美国食品药品管理局发布有关草药的新规章，如果一种草药以前被用过的话，就很容易让其提取物进入临床试验，而且无需鉴定提取物中的所有成分。
同时，中国和其他地方的一些研究者正在提倡系统生物学——研究蛋白质、基因、代谢物和细胞或有机体其他组分的相互关系的学科——做为评定传统医药的用途的一种方法。我们欢迎那些建设性的方法用以预测传统传统疗法的可能用途。但是，要把一种基本上还未经过临床检验的全新技术，用来检验充斥着伪科学的中医药的准确性，看来是很成问题的。而且，对那些依据一个模糊不清的知识体系所做出的宣称，应该按惯例抱着怀疑态度，这对科学和医学来说都是基本原则。
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News Feature
Nature 448, 126-128 (12 July 2007) | doi:10.1038/448126a; Published online 11 July 2007
Traditional medicine: A culture in the balance
Jane Qiu1
1. Jane Qiu writes for Nature from Beijing.
Traditional Chinese medicine and Western science face almost irreconcilable differences. Can systems biology bring them together? Jane Qiu reports.
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Liu Wen-long's modest Beijing practice looks no different from most clinics. But he is no ordinary doctor. Liu never orders lab tests, nor does he prescribe high-tech imaging diagnostics. He relies on simple observations, checking a patient's pulse, complexion and odour, and asking about habits and medical history. At 69 years old, he has been practising traditional Chinese medicine for 43 years and he is resolute about its benefits. "People keep coming back because it cures them and improves their well-being," he says.
, 百拇医药
Indeed, patients trickle in to see Liu all morning for conditions ranging from allergies to lung cancer. Some are nervous first-timers, others are regulars, confident in what traditional Chinese medicine has to offer. Ms Huang, an accountant from the outskirts of Beijing, is delighted that her migraines, which haunted her for years, disappeared after three herbal regimens. "I used to live on painkillers and felt tired all the time," she says. "I am now a totally different person."
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In a country that is fiercely embracing modernity, clinics such as Liu's, which have been operating the same way for thousands of years, seem vulnerable and out of place. Indeed, attitudes on traditional Chinese medicine have divided the country. Last year, Zhang Gong-yao, from the Central South University in Changsha, Hunan, published an article in a Chinese journal calling traditional Chinese medicine a pseudoscience that should be banished from public healthcare and research1. The article caused uproar in the country, and earlier this year the government announced an ambitious plan to modernize the millennia-old practice2.
, 百拇医药
But should such a formidable gap be bridged? Modern Western medicine generally prescribes treatments for specific diseases, often on the basis of their physiological cause. Traditional Chinese medicine, however, focuses on symptoms, and uses plant and animal products, minerals, acupuncture and moxibustion — the burning of the mugwort herb (Artemisia vulgaris) on or near the skin. But whether these methods are effective and, if they are, how they work remain a source of some derision. The greatest divide is in the testing. In the West, researchers test a drug's safety and efficacy in randomized, controlled trials. Traditional Chinese treatments are mixtures of ingredients, concocted on the spot on the basis of a patient's symptoms and characteristics and using theories passed down through generations.
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The mainstream medical community, in China and abroad, has been highly critical of the underlying theories. Traditional Chinese medicine is based on ideas such as qi (meridian), in which illness is caused by blocked energy channels; yin and yang, which emphasizes the balance of energy; and wuxing (five elements), in which people's organs and health status are categorized according to their 'elemental characteristics': fire, wood, water, earth and metal.
Pharmaceutical companies have become more interested in traditional Chinese medicines over the past decade. But their approach has been characteristically Western: isolate the active ingredients and test them one at a time. This reductionist approach has led to the approval of drugs such as artemisinin for malaria, which is used to treat fever in traditional Chinese medicine, and arsenic trioxide, which has been carried over from Chinese medicine for treatment of acute promyelocytic leukaemia.
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But identifying the active ingredients isn't easy. Most remedies in traditional Chinese medicine, as it turns out, are compound formulae — or fufang — that contain as many as 50 species of herbs, and thousands of chemicals therein (see 'Knowledge mining'). To tap into the deeper well of traditional Chinese treatments, researchers think they may need to look at how the mixtures of ingredients act in concert.Relaxed regulation
The criteria for approval of herbal mixtures as medicines are now starting to relax, at least in the United States. In June 2004, the US Food and Drug Administration (FDA) issued new guidelines that permit the approval of herbal mixtures if they can be shown to be safe and effective, even if the active constituents are not known. Last October, the FDA approved the first such botanical drug under the new rules, a proprietary mixture of green-tea extracts called Veregen developed by the German company MediGene for treating genital warts.
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These new regulations have helped to renew industry's interest in the complex formulae. And a buzzing new Western field could be poised to capitalize on the deeper secrets of traditional Chinese medicine. Systems biology attempts to understand the function and behaviour of an organism by studying the interactions between its components. It has been called a more holistic approach to biology and is seen by some as a perfect match for traditional Chinese medicine.
, http://www.100md.com By measuring many genes, proteins and metabolites at the same time, systems biology may provide a measure of the entire body's response to a complex mixture of herbs. "If there is any technology that could lead to a breakthrough in traditional Chinese medicine, it will be systems biology," says Robert Verpoorte, head of the pharmacognosy department at the University of Leiden in the Netherlands. But not everyone agrees that the new technology is equipped to test old ideas.
, 百拇医药
Jia Wei, a pharmacologist at the Shanghai Centre for Systems Biomedicine at Jiao Tong University, and Tang Hui-ru at the Wuhan Institute of Physics and Mathematics, part of the Chinese Academy of Sciences, want to understand more fully how herbal extracts affect the whole body. They are collaborating with Jeremy Nicholson, head of the department of biomolecular medicine at Imperial College London, and using technologies such as nuclear magnetic resonance spectroscopy and mass spectrometry to profile the metabolites in a person's urine or blood — a discipline they call metabonomics.
, 百拇医药
Jia and his colleagues found that rats given the compound 1,2-dimethylhydrazine to induce tumours in their colons had different metabolic profiles in their urine from those in the control group. And by feeding the rats a combination of two herbal extracts — Coptidis rhizoma and Evodia rutaecarpa, which are widely used in traditional Chinese medicine to treat gastric conditions — the researchers were able to reverse these changes in metabolism. Their results have not yet been published, but the researchers say that by looking at the changes in metabolites in detail, they have pinpointed the metabolic pathways that the herbs affect.Culture shift
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Jan van der Greef from SU Biomedicine in Zeist, the Netherlands, and his colleague Wang Mei are using a similar approach. In a mouse model of metabolic syndrome — a cluster of conditions such as insulin resistance and high blood pressure that often occur together — they and their team looked at the effect of an undisclosed formula used in traditional Chinese medicine on lipid profiles. When these mice are fed a high-fat diet, they become more resistant to insulin. The lipid profiles of these mice were clearly distinguishable from those of mice fed a normal diet, and they shifted towards the healthy state when the mice were given traditional Chinese medicine3.
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The researchers noticed that the profile shift resembled that caused by the Western obesity drug Rimonabant, which acts on proteins called CB-1 endocannabinoid receptors. And their unpublished work with cell culture suggests that herbal extracts can affect lipid metabolism through the same receptor, says van der Greef. The team is now testing the formula in clinical trials.
Although one active ingredient may act as the Western drug, the uncertain role of additional ingredients and the variability of active ingredients confounds Western sensibilities. "Variations worry people," Nicholson says. The same plant species grown in different regions and harvested in different seasons could have distinct chemical compositions. This has always been a vexing issue for herbal-medicine researchers.
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While at Nicholson's lab, Tang and his colleagues analysed the molecular components in chamomile plants from Egypt, Slovakia, and Hungary, and could classify them easily4. Using similar approaches, the team from the Wuhan Institute of Physics and Mathematics found significant variations in the same herbal medicines produced by different companies and even between different batches produced by the same company. "This is an issue China must tackle for its herbal medicines to raise their game in the world market," says Tang.
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To many self-purported systems biologists, several approaches are needed to build a complete picture of a living organism and to understand the effect of traditional Chinese medicine. Nevertheless, systems biology has been a conspicuously hard field to define. Many have used the term loosely, and pioneers in the field contend that the technologies haven't been honed to the point that they could be used for these approaches.
"It's conceivable that systems biology could find applications in trying to sort out components in Chinese herbal medicine, but it's very early days," says Leroy Hood, president of the Institute for Systems Biology in Seattle, Washington, and regarded as the field's founding father. "It would be an enormous challenge at this point and time."
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Systems biology has been successful in model organisms, according to Hood, but is much less so in human studies. Many hurdles need to be overcome before researchers could even begin to contemplate how to deal with subjects as complex as traditional Chinese medicine. For example, better detection systems are needed to measure metabolites, especially proteins, accurately in the blood, and more powerful computational and statistical tools are crucial for dealing with large and complex data sets. "Those technologies are at early stages of maturation," Hood says.
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There are also broader concerns about the modernization of traditional Chinese medicine, from both advocates and sceptics of the practice. Some are uncomfortable with separating the study and development of Chinese herbal medicines from the theories that underlie its normal practice. "Traditional Chinese medicine is not just a medical system, but a branch of philosophy and healing art that is an important part of Chinese culture," says Fu Jing-hua, a retired researcher at the Chinese Academy of Chinese Medicine Sciences in Beijing and president of the Chinese Ancient Books Publishing House in Beijing. "Devoid of that cultural context, it would become a tree without roots."Lofty ideals
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But Zhang and Fang Shi-min, a US-trained biochemist who now runs a society called New Threads that is known for fighting pseudoscience and research misconduct in China say that it is exactly those traditional Chinese medicine theories that should be abolished. Conceits such as yin and yang, wuxing and qi "are inaccurate descriptions of the human body that verge on imagination", he says.
Inevitably, cultural factors may be the biggest obstacle in bridging the East–West gap. "The field of traditional Chinese medicine is notorious for being averse to criticism," says Yuan Zhong, a philosopher of medicine at the Chinese Academy of Medical Sciences. "If people are not allowed to disagree or voice their opinions, there would be no hope of progress for any discipline."
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But although heated exchanges are boiling over in debates on the future of traditional Chinese medicine, it's business as usual in Liu's practice. He is sanguine about the convergence between traditional Chinese medicine and Western medicine, but has a pragmatic attitude towards it. "Whether from the East or the West, we share the same goal of improving human health. As long as it works, anything goes," he remarks. But Liu says that he is yet to see any real progress in the merging of the two philosophies and, until then, his intuition and experience — as well as traditional Chinese medicine's seemingly arcane theory and practice — will serve him and his patients just fine.
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See Editorial, page 106.
References
1. Zhang, G.-Y. Med. Phil. 27, 14–17 (2006). 2. Qiu, J. Nature 446, 590–591 (2007). | Article | 3. Wang, M. et al. Phytother. Res. 19, 173–182 (2005). | Article | PubMed | ChemPort | 4. Wang, Y. et al. Planta Med. 70, 250–255 (2004).
Editorial
Nature 448, 105-106 (12 July 2007) | doi:10.1038/448106a; Published online 11 July 2007
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Hard to swallowIs it possible to gauge the true potential of traditional Chinese medicine?
Researchers, practitioners and drug companies around the world are engaged in a complex, tentative dance over the best way to tap into the unknown potential of traditional Chinese medicine. The scientific community and the drug industry both tend to be sniffy about 'traditional' cures; yet there is a strong sense that millennia of practice in China — much of it barely documented — is likely to have yielded at least some treatments that work.
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Pharmaceutical companies are understandably eager to enter a Chinese domestic market that was estimated by the Boston Consulting Group to be worth US$13 billion last year, and growing fast. But they are tantalized by one opportunity above all: the prospect that the nation's traditional medicine might contain a number of potentially profitable compounds hidden somewhere in its arcane array of potions and herbal mixtures.
The task of finding these elusive gems has been approached in a typically reductionist manner, with researchers seeking single compounds that might have a role in treating specific diseases. Sometimes this has been successful: artemisinin, for example, which is currently the most effective treatment for malaria, was fished out of a herbal treatment for fevers. But such success stories have been few and far between.
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So if traditional Chinese medicine is so great, why hasn't the qualitative study of its outcomes opened the door to a flood of cures? The most obvious answer is that it actually has little to offer: it is largely just pseudoscience, with no rational mechanism of action for most of its therapies. Advocates respond by claiming that researchers are missing aspects of the art, notably the interactions between different ingredients in traditional therapies.
Nevertheless, the drug industry is not exactly awash with promising new medicines at the moment. Perhaps as a result, the global regulatory process has become increasingly receptive to traditional approaches. In 2004, for example, the US Food and Drug Administration issued new guidelines on botanical drugs that made it much easier to get extracts into clinical trials if there was some history of prior use, and that obviated the need to characterize all compounds in an extract.
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Some researchers in China and elsewhere, meanwhile, are advocating systems biology — the study of the interactions between proteins, genes, metabolites and components of cells or organisms — as a way to assess the usefulness of traditional medicines (see page 126). Constructive approaches to divining the potential usefulness of traditional therapies are to be welcomed. But it seems problematic to apply a brand new technique, largely untested in the clinic, to test the veracity of traditional Chinese medicine, when the field is so fraught with pseudoscience. In the meantime, claims made on behalf of an uncharted body of knowledge should be treated with the customary scepticism that is the bedrock of both science and medicine., http://www.100md.com