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英國《自然》: 中醫藥:一種命運未定的文化
送交者: 好文欣賞 2009年06月03日12:14:19 於 [健康生活] 發送悄悄話
中醫藥:一種命運未定的文化 英國《自然》2007.7.12 (方舟子譯)   劉文龍(音)在北京的普通診所看上去和大多數診所沒有什麼不同。但是他 不是個普通醫生。劉從來沒有要求做實驗室檢驗,也從來不給病人開方做高科技 影像診斷。他只依靠簡單的觀察,檢查病人的脈搏、臉色和味道,詢問病人的習 慣和病史。他今年69歲,已從事中醫43年,並堅信中醫的好處。“人們總是回頭 再來的,因為它治好了他們,增進了他們的健康。”他說。   整個上午一個接一個進來讓劉看病的患者,其病情從過敏到肺癌都有。有些 是第一次來,顯得緊張;其他的則是常客,對中醫藥充滿了信心。黃女士是北京 郊區的一名會計,困擾她多年的偏頭痛在吃了三帖中藥後消失了,她對此很高興。 “我以前一直靠止痛藥,老是覺得疲憊,”她說,“現在我變成了完全不同的一 個人。”   在這個正在熱烈地擁抱現代化的國家,像劉這樣採用數千年來一成不變的看 病方法的診所,看來很脆弱和過時。的確,對中醫的不同態度已讓這個國家分裂。 去年,湖南長沙中南大學的張功耀在雜誌上發表文章稱中醫是偽科學,應該退出 公共醫療和研究。輿論為之大嘩。今年早些時候,中國政府宣布一項雄心勃勃的 計劃,要讓已有上千年歷史的中醫現代化。   但是如此巨大的鴻溝應該架橋聯通嗎?現代西方醫學一般是針對特定的疾病 採取治療措施,通常是根據疾病的生理因素。然而,中醫卻是注重症狀,使用植 物和動物產品,針灸和艾灼。但是,這些方法是否有效,有效的話其機理如何, 卻一直成為笑柄。最大的分歧在於檢驗方法。在西方,研究者用隨機、有對照的 臨床試驗檢驗一種藥物的安全性和有效性。中醫治療則是根據病人的症狀和性質, 當場混合多種藥物,採用的是代代相傳的理論。   中國以及國外的醫學界主流對中醫理論一向持嚴厲批評的態度。中醫的觀念 包括氣(經絡),認為疾病是氣脈阻塞引起的;陰陽,強調能量的平衡;和五行, 把人的器官和健康狀態根據它們的屬性分類:火、木、水、土和金。   在過去的十年,醫藥公司對中藥變得更有興趣。但是他們採用的方法是西式 的:分離出活性成分,挨個做檢驗。這種還原論的方法發現了一些源自中藥的新 藥,獲得批准,例如治療瘧疾的青蒿素和治療急性早幼粒細胞白血病的砒霜。   但是鑑別活性成分並不容易。大多數中醫藥方都是複方,含有的草藥能多達 50種,包含成千上萬種化學成分。要深入挖掘中醫療法,研究者認為他們也許應 該看看混合成分是如何一起發揮作用的。   放寬管理   批准含草藥成分的新藥的標準現在開始放寬了,至少在美國是如此。在2004 年6月,美國食品藥品管理局(FDA)發布新規章,即使草藥混合物的活性成分未 知,但只要能證明其安全和有效,也能獲得批准。去年10月,FDA根據新規章批 准了第一種草藥,德國MediGene公司從綠茶提取物研發出來的、用於治療生殖器 疣的混合藥物Veregen。   這些新的規章促使醫藥業界對複雜藥方重新產生興趣。一個全新的西方領域 也許能夠被開發出來從中藥的深層秘密中獲利。系統生物學通過研究一個有機體 各個組成部分的相互作用,試圖了解其功能和行為。它被認為是用更有整體觀的 方法研究生物學,並被某些人視為是中醫藥的一個完美匹配。   通過同時測量許多基因、蛋白質和代謝物,系統生物學可以為整個身體對草 藥的複雜混合物的反應提供一種測量方法。“如果有任何技術能夠導致中醫藥研 究的突破的話,那就是系統生物學,”荷蘭萊頓大學生藥學系主任Robert Verpoorte說。但是並非每個人都認同這個新技術是用來檢驗舊觀念的。   上海交通大學系統生物醫學研究中心的藥理學家賈偉和中國科學院武 漢物理與數學研究所的唐惠儒想要更完整地理解草藥提取物是如何影響整 個身體的。他們正與倫敦帝國學院生物分子醫學系主任Jeremy Nicholson合作, 採用核磁共振和質譜分析之類的技術分析一個人的尿液或血液中的代謝物——他 們稱該學科為代謝組學。   賈及其合作者發現,用二甲肼誘髮結腸癌的大鼠的尿液中所含的代謝物成分 與對照組的不同。給大鼠服用兩種中藥——中醫廣泛用來治療胃病的黃連和吳茱 萸——提取物的混合物之後,能夠逆轉這些代謝變化。他們的研究結果還未發表。 但是研究人員說通過檢察代謝物變化的細節,他們已確定了草藥所影響的代謝途 徑。   文化變化   荷蘭宰斯特SU Biomedicine的Jan van der Greef及其同事王梅(音)也在 用類似的方法。用一種代謝綜合徵——例如胰島素抵抗和高血壓等通常一起出現 的症狀的組合——的小鼠模型,他們及其團隊觀察一種中藥秘方對脂質成分的影 響。這些小鼠被餵以高脂肪飲食,使它們對胰島素的抵抗增強。這些小鼠的脂質 成分與那些餵以正常飲食的小鼠有顯著的不同,而在服了中藥之後,朝健康狀態 轉變。   研究人員注意到,脂質成分的轉變與治療肥胖者的西藥Rimonabant導致的相 似,後者是通過作用於一種稱為CB-1內源性大麻受體的蛋白質起作用的。van der Greef說,他們還未發表的細胞培育實驗結果表明,草藥提取物能夠通過相 同的受體影響脂質代謝。該團隊現在在對該藥方做臨床試驗。   雖然一種活性成分能像西藥那樣起作用,但是其他附加成分的不確定作用和 活性成分的可變性會導致混亂。“可變性讓人擔憂。”Nicholson說。同一種植 物生長在不同的地區,在不同的季節採摘,都能使其化學成分出現差異。對草藥 研究者來說,這向來是個讓人苦惱的難題。   在Nicholson實驗室,唐及其同事分析了來自埃及、斯洛伐克、匈牙利的黃 春菊的分子成分,能夠很容易地區分它們。用類似的方法,武漢物理與數學研究 所的團隊發現不同公司生產的同一種草藥,甚至是同一家公司生產的同一種草藥 的不同批次,也有顯著的差異。“中國想要讓其草藥在世界市場上占更大的份額, 必須解決這個問題,”唐說。   對許多自詡的系統生物學家來說,需要採用幾種研究方法才能構建一個活的 有機體的完整圖像,並理解中藥的作用。不過,系統生物學很顯然是一個難以定 義的領域。許多人很寬鬆地使用這個術語,而該領域的先驅者認為,技術手段還 未精緻到足以被用於做這些研究。   “可以設想系統生物學能夠被用於刷選中草藥的成分,但是現在還只是非常 早期的,”華盛頓州西雅圖系統生物學研究所所長、被視為系統生物學之父的 Leroy Hood說。“在當前這會是個巨大的挑戰。”   根據Hood的說法,系統生物學在模型動物上有所成功,但是在人體研究上的 成功則小得多。在研究者能夠開始考慮如何對付像中藥這麼複雜的問題之前,還 有許多障礙需要克服。例如,需要有更好的檢測系統來精確地測量血液中的代謝 物,特別是蛋白質,以及需要用更強大的計算和統計工具,它們對處理大量和復 雜的數據是至關重要的。“這些技術還只處於成熟早期,”Hood說。   對中醫的支持者和反對者來說,中醫藥現代化好都有更大的問題值得關注。 有些人對把中藥從中醫理論分離開來加以研究、開發的做法感到不滿。“中醫不 僅是一個醫學體系,也是做為中國文化的重要組成部分的哲學和治療藝術的一個 分支,”北京中國中醫科學院的退休研究員、中醫古籍出版社社長傅景華說。 “脫離了其文化內涵,它就會成為無根之樹。”   崇高理想   但是張功耀,以及主持以打擊中國的偽科學和學術不端行為著稱的新語絲社、 美國訓練的生物化學學者方舟子說,應該被拋棄的恰恰是那些中醫理論。類似陰 陽、五行和氣這些觀念“是對人體模糊的描述,近乎臆想”,方舟子說。   文化因素會是聯通東西方鴻溝的不可避免的最大障礙。“中醫領域臭名昭著 地不能容忍任何批評,”中國醫學科學院的醫學哲學家袁鍾說,“如果人們不能 被允許表示不同意見,任何學科都沒有希望會有進步。”   雖然對中醫藥未來走向的爭論處於白熾化,劉文龍還照常行醫。他對中醫和 西醫的結合感到樂觀,但是採取的是一種實用態度。“不管是中醫還是西醫,我 們的共同目標都是增進人類健康。只要有效,什麼都行。”他評論說。但是劉說 他還沒看到這兩種哲學的結合有任何真正的進展,在那之前,他的診所和他經驗 ——以及中醫看來神秘的理論和方法——對他及其病人都湊合。   《自然》社論:   難以下咽:有沒有可能評判中藥的真實潛力?   全世界的研究者、從業者和醫藥公司在翩翩起舞,想要找到挖掘中藥的未知 潛力的最佳方式。科學界和醫藥業界都傾向於對“傳統”療法嗤之以鼻;但是有 一種強烈的感覺認為,在中國延續千年的醫療實踐——它的大部分缺乏記錄—— 有可能至少產生某些有效的療法。   可以理解,醫藥公司渴望進入中國市場,波士頓顧問集團估計這個市場去年 價值130億美元,並正在快速增長。但是最刺激他們的是這樣一種可能前景:該 國的傳統醫藥中也許含有許多可能贏利的化合物,隱藏在一堆神秘的藥劑和草藥 混合物之中的某處。   要發現這些隱藏的寶物,通常採用的是還原論的方法,即研究者去尋找也許 會對治療特定的疾病起作用的單個化合物。這種方法有時能獲得成功:例如,目 前用來治療瘧疾最有效的藥物青蒿素就是從一種用來治療發燒的草藥中提取出來 的。但是這種成功的故事非常稀少。   那麼,如果中醫藥是那麼偉大的話,為什麼對其結果的定性研究沒有為眾多 治療打開方便之門呢?最明顯的答案是,它實際上沒有多少可提供的:它基本上 不過是偽科學,它的大多數療法沒有合理的機制。中醫擁護者反駁說,研究者沒 有掌握其奧妙,特別是傳統療法中不同成分之間的相互作用。   不過,醫藥產業在現在並沒有充斥着有希望的新藥。也許由於這個原因,全 世界的管理機構對傳統的方法越來越接受。例如,在2004年,美國食品藥品管理 局發布有關草藥的新規章,如果一種草藥以前被用過的話,就很容易讓其提取物 進入臨床試驗,而且無需鑑定提取物中的所有成分。   同時,中國和其他地方的一些研究者正在提倡系統生物學——研究蛋白質、 基因、代謝物和細胞或有機體其他組分的相互關係的學科——做為評定傳統醫藥 的用途的一種方法。我們歡迎那些建設性的方法用以預測傳統傳統療法的可能用 途。但是,要把一種基本上還未經過臨床檢驗的全新技術,用來檢驗充斥着偽科 學的中醫藥的準確性,看來是很成問題的。而且,對那些依據一個模糊不清的知 識體系所做出的宣稱,應該按慣例抱着懷疑態度,這對科學和醫學來說都是基本 原則。 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. 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. 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." 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. 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. 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. 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. 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. 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. 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. 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 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. 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. 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. 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." 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. 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 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." 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. 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 Hard to swallow Is 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. 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. 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. 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.
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