揭開中藥的面紗
記者：Richard Stone美國《科學》2008年2月8日(翻譯：方舟子)
大連，中國——基因組學、蛋白質組學、代謝組學……本草組學？做為揭開大自然的生物化學秘密的最近一次進攻，位于這個海濱城市的一個中國團隊正開始一項15年計劃，試圖鑒定出在中國用了數(shù)百年的草藥藥方的成分。
本草物質組計劃是最新的——也是最雄心勃勃的——試圖讓中藥現(xiàn)代化的一次嘗試。這些古老的藥方——多達40萬個方劑、用了1萬種草藥和動物酊劑——是中國許多人選擇的治療方法，常常是唯一的方法。在1970年代，在中藥的啟發(fā)下研究人員從青蒿中發(fā)現(xiàn)了青蒿素做為抗瘧疾的良藥。但是中藥的名聲由于其不可靠的療效和嚴重的副作用而大受損害，導致批評者抨擊它是過時的民間醫(yī)術�！爸兴幉皇墙⒃诳茖W，而是建立在玄學、巫術和傳聞的基礎之上，”生物化學學者方是民說，他以方舟子為筆名自任中國科學警察。他認為本草物質組計劃只是“浪費科研經(jīng)費”。
, 百拇醫(yī)藥
為了反擊中藥的批評者，本草物質組計劃將采用高通量篩選、毒性檢驗和臨床試驗以鑒定出常用藥方中的活性成分和毒性污染物�！拔覀冃枰_保中藥是安全的，并且顯示它不止是青蒿素，”在上海藥物所負責中醫(yī)藥現(xiàn)代化項目但未參與本草物質組計劃的果德安說。最初的目標是癌癥，肝臟和腎臟疾病，以及用西藥難以治療的其他疾病，例如糖尿病和抑郁癥。
中國科學院最大和科研資金最充足的研究所之一——大連化學物理研究所獲得了一筆5百萬美元的啟動基金用以研發(fā)純化方法；科技部正在審核這個計劃，打算把它劃入自2010年開始的下個5年計劃的一項7千5百萬美元的創(chuàng)新規(guī)劃中。今年春天北京香山會議——相當于中國的戈登學術會議——將為此舉行一個規(guī)劃會議。
中藥界的幾名權勢人物已支持這項規(guī)劃�！伴_始這個項目正是時候，”上海中醫(yī)藥大學校長、化學家陳凱先說。上海中藥創(chuàng)新研究中心理事長惠永正說，制藥公司應該會對本草物質組計劃感興趣，因為它能夠鑒定出許多候選藥物。
, 百拇醫(yī)藥
在世界上許多地方，傳統(tǒng)醫(yī)學藥方是通過口述代代相傳的。但是在中國，2千多年前的醫(yī)生已開始編寫藥典。雖然在大城市西醫(yī)已大體上取代了中醫(yī)，但是許多中國人仍然相信中醫(yī)藥做為預防藥物和治療慢性病很有效，而在鄉(xiāng)村的中國人還在依賴它�！拔覀兇蠖鄶�(shù)人在感到身體不適時，就吃中藥，”大連化學物理研究所的梁鑫淼說。
自從毛澤東時代以來，中國政府就在強烈支持中醫(yī)藥，部分原因是因為沒錢向大眾提供西醫(yī)藥。中國媒體至今還忌諱把中醫(yī)稱為偽科學�！皩υS多中國人來說，批評中醫(yī)藥是無法想像的，幾乎就像是犯了叛國罪，”方舟子說。
支持者堅持認為中醫(yī)藥可以提供很多東西。但是伴隨著每一項中藥成功的宣稱，都有不良反應的報告，有的來自天然毒性成分，有的來自殺蟲劑之類的污染物。中藥劑量也難以確定，因為藥方的效力根據(jù)草藥產地和采集時間而發(fā)生變化。不同的廠家和不同的批次的藥物質量能夠出現(xiàn)差異。“這就是為什么許多人不信任中藥，”果德安說。在中藥現(xiàn)代化進程時，質量控制是一個首要關注的問題。
, 百拇醫(yī)藥
本草物質組計劃打算把現(xiàn)代化帶到一個全新的水平。這項計劃是梁鑫淼首先提出的，他相信許多中藥是有效的。“問題是我們不知道它為什么有效，”他說。主要的障礙是藥方很復雜。做為一個例子，梁鑫淼展示了一種用以外涂消除肌肉疼痛的藥方“紅花油”的色譜圖。梁鑫淼說，在化學家處理的許多樣品中，一個峰通常代表一種化合物。但是對紅花油來說，一個峰是許多化合物，將之分餾產生了更多的多化合物峰，就像俄羅斯套偶。梁鑫淼說，紅花油至少由1萬種化合物組成：“我們只知道100種。”
面對這種復雜性，“我們必須發(fā)明新的方法學，”梁鑫淼說。“這是本草物質組計劃的戰(zhàn)場。”首先，他在大連化學物理研究所的45人團隊正在研發(fā)新的分離介質。草藥將被分解成“多組分”：相似的成分為一組。為了確定哪種物質是有益的或有毒性的，他的研究組計劃設計本草組芯片，其中的化合物將根據(jù)它們與關鍵多肽的結合能力進行篩選。擴大后的本草物質組計劃將會有國內外許多研究機構的人員參與。
本草物質組計劃有隱藏的危險性。其中之一是擔心西方制藥公司會通過改造該計劃鑒定出的化合物研發(fā)出銷量巨大的藥物，掠走戰(zhàn)利品。為了對抗這種可能性，果德安說：“我們鼓勵科學家不要急于發(fā)表論文，并先(對鑒定出的候選藥物)做結構改造�！比缓髨F隊會對一組相似結構的化合物申請專利。
, 百拇醫(yī)藥
并不是所有的中醫(yī)業(yè)者都接受對中醫(yī)藥去神秘化�！坝行┤藫膫鹘y(tǒng)會喪失掉，”陳凱先說。但是惠永正說“為了調和西醫(yī)知識導向的演繹法和中醫(yī)經(jīng)驗導向的歸納法”，現(xiàn)代化是必要的。方舟子另有看法：“你能夠結合占星術和天文學，煉金術和化學嗎？它從來就行不通�！�
惠永正堅持認為中醫(yī)能與西醫(yī)共處。梁鑫淼希望他的本草物質組計劃將會證明惠永正是對的。
Science 8 February 2008:Vol. 319. no. 5864, pp. 709 - 710DOI: 10.1126/science.319.5864.709
BIOCHEMISTRY:Lifting the Veil on Traditional Chinese MedicineRichard 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.
, 百拇醫(yī)藥
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."
, 百拇醫(yī)藥
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.
, 百拇醫(yī)藥
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.
, 百拇醫(yī)藥
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.
, 百拇醫(yī)藥
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.
, http://www.www.srpcoatings.com
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."
, http://www.www.srpcoatings.com
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.
, http://www.www.srpcoatings.com
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., 百拇醫(yī)藥
大連，中國——基因組學、蛋白質組學、代謝組學……本草組學？做為揭開大自然的生物化學秘密的最近一次進攻，位于這個海濱城市的一個中國團隊正開始一項15年計劃，試圖鑒定出在中國用了數(shù)百年的草藥藥方的成分。
本草物質組計劃是最新的——也是最雄心勃勃的——試圖讓中藥現(xiàn)代化的一次嘗試。這些古老的藥方——多達40萬個方劑、用了1萬種草藥和動物酊劑——是中國許多人選擇的治療方法，常常是唯一的方法。在1970年代，在中藥的啟發(fā)下研究人員從青蒿中發(fā)現(xiàn)了青蒿素做為抗瘧疾的良藥。但是中藥的名聲由于其不可靠的療效和嚴重的副作用而大受損害，導致批評者抨擊它是過時的民間醫(yī)術�！爸兴幉皇墙⒃诳茖W，而是建立在玄學、巫術和傳聞的基礎之上，”生物化學學者方是民說，他以方舟子為筆名自任中國科學警察。他認為本草物質組計劃只是“浪費科研經(jīng)費”。
, 百拇醫(yī)藥
為了反擊中藥的批評者，本草物質組計劃將采用高通量篩選、毒性檢驗和臨床試驗以鑒定出常用藥方中的活性成分和毒性污染物�！拔覀冃枰_保中藥是安全的，并且顯示它不止是青蒿素，”在上海藥物所負責中醫(yī)藥現(xiàn)代化項目但未參與本草物質組計劃的果德安說。最初的目標是癌癥，肝臟和腎臟疾病，以及用西藥難以治療的其他疾病，例如糖尿病和抑郁癥。
中國科學院最大和科研資金最充足的研究所之一——大連化學物理研究所獲得了一筆5百萬美元的啟動基金用以研發(fā)純化方法；科技部正在審核這個計劃，打算把它劃入自2010年開始的下個5年計劃的一項7千5百萬美元的創(chuàng)新規(guī)劃中。今年春天北京香山會議——相當于中國的戈登學術會議——將為此舉行一個規(guī)劃會議。
中藥界的幾名權勢人物已支持這項規(guī)劃�！伴_始這個項目正是時候，”上海中醫(yī)藥大學校長、化學家陳凱先說。上海中藥創(chuàng)新研究中心理事長惠永正說，制藥公司應該會對本草物質組計劃感興趣，因為它能夠鑒定出許多候選藥物。
, 百拇醫(yī)藥
在世界上許多地方，傳統(tǒng)醫(yī)學藥方是通過口述代代相傳的。但是在中國，2千多年前的醫(yī)生已開始編寫藥典。雖然在大城市西醫(yī)已大體上取代了中醫(yī)，但是許多中國人仍然相信中醫(yī)藥做為預防藥物和治療慢性病很有效，而在鄉(xiāng)村的中國人還在依賴它�！拔覀兇蠖鄶�(shù)人在感到身體不適時，就吃中藥，”大連化學物理研究所的梁鑫淼說。
自從毛澤東時代以來，中國政府就在強烈支持中醫(yī)藥，部分原因是因為沒錢向大眾提供西醫(yī)藥。中國媒體至今還忌諱把中醫(yī)稱為偽科學�！皩υS多中國人來說，批評中醫(yī)藥是無法想像的，幾乎就像是犯了叛國罪，”方舟子說。
支持者堅持認為中醫(yī)藥可以提供很多東西。但是伴隨著每一項中藥成功的宣稱，都有不良反應的報告，有的來自天然毒性成分，有的來自殺蟲劑之類的污染物。中藥劑量也難以確定，因為藥方的效力根據(jù)草藥產地和采集時間而發(fā)生變化。不同的廠家和不同的批次的藥物質量能夠出現(xiàn)差異。“這就是為什么許多人不信任中藥，”果德安說。在中藥現(xiàn)代化進程時，質量控制是一個首要關注的問題。
, 百拇醫(yī)藥
本草物質組計劃打算把現(xiàn)代化帶到一個全新的水平。這項計劃是梁鑫淼首先提出的，他相信許多中藥是有效的。“問題是我們不知道它為什么有效，”他說。主要的障礙是藥方很復雜。做為一個例子，梁鑫淼展示了一種用以外涂消除肌肉疼痛的藥方“紅花油”的色譜圖。梁鑫淼說，在化學家處理的許多樣品中，一個峰通常代表一種化合物。但是對紅花油來說，一個峰是許多化合物，將之分餾產生了更多的多化合物峰，就像俄羅斯套偶。梁鑫淼說，紅花油至少由1萬種化合物組成：“我們只知道100種。”
面對這種復雜性，“我們必須發(fā)明新的方法學，”梁鑫淼說。“這是本草物質組計劃的戰(zhàn)場。”首先，他在大連化學物理研究所的45人團隊正在研發(fā)新的分離介質。草藥將被分解成“多組分”：相似的成分為一組。為了確定哪種物質是有益的或有毒性的，他的研究組計劃設計本草組芯片，其中的化合物將根據(jù)它們與關鍵多肽的結合能力進行篩選。擴大后的本草物質組計劃將會有國內外許多研究機構的人員參與。
本草物質組計劃有隱藏的危險性。其中之一是擔心西方制藥公司會通過改造該計劃鑒定出的化合物研發(fā)出銷量巨大的藥物，掠走戰(zhàn)利品。為了對抗這種可能性，果德安說：“我們鼓勵科學家不要急于發(fā)表論文，并先(對鑒定出的候選藥物)做結構改造�！比缓髨F隊會對一組相似結構的化合物申請專利。
, 百拇醫(yī)藥
并不是所有的中醫(yī)業(yè)者都接受對中醫(yī)藥去神秘化�！坝行┤藫膫鹘y(tǒng)會喪失掉，”陳凱先說。但是惠永正說“為了調和西醫(yī)知識導向的演繹法和中醫(yī)經(jīng)驗導向的歸納法”，現(xiàn)代化是必要的。方舟子另有看法：“你能夠結合占星術和天文學，煉金術和化學嗎？它從來就行不通�！�
惠永正堅持認為中醫(yī)能與西醫(yī)共處。梁鑫淼希望他的本草物質組計劃將會證明惠永正是對的。
Science 8 February 2008:Vol. 319. no. 5864, pp. 709 - 710DOI: 10.1126/science.319.5864.709
BIOCHEMISTRY:Lifting the Veil on Traditional Chinese MedicineRichard 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.
, 百拇醫(yī)藥
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."
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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.
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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.
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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.
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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.
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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."
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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.
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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., 百拇醫(yī)藥
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