屠呦呦團隊新發現:青蒿素對治療紅斑狼瘡也有獨特療效

雙氫青蒿素對治療具有高變異性的紅斑狼瘡效果獨特。Dihydroartemisinin had a positive effect on the treatment of highly variable lupus erythematosus.

在這世界上還有什麼比戰爭更可怕呢？答案是病毒——一顆在和平年代裡，隨時會爆炸的定時炸彈。在世界衛生組織2016年發布的關於瘧疾的十個事實中，有一點令人觸目驚心：全世界約一半人口處於罹患瘧疾的風險之中。2015年10月，一名叫屠呦呦的科學家因獲得諾貝爾醫學獎而走進了全世界的視野，她在瘧疾治療研究中取得了非凡成就。

What could be more horrible in this world than war? The answer is a virus — a time bomb ready to explode at any time, and in peacetime. Of the 10 facts about malaria published by the World Health Organization(WHO) in 2016, the one that shocks people most is that about half of the world's population is at risk of contracting malaria. In October 2015, a scientist named Tu Youyou came to the world's attention when she was awarded the Nobel Prize in Physiology and Medicine for her major contribution to the treatment of malaria, a disease which people have suffered from for centuries.

瘧疾：永動的生命收割機

Malaria：The Constant Live Taker

自瘧疾爆發之日，全世界都在尋找治療的方法。生活在熱帶、亞熱帶的土著最先發現了一種金雞納樹的樹皮能治瘧疾。後來的幾個世紀，經過科學家們的不斷研究，終於提取出了其中最有效的成分，這種藥物被命名為奎寧。

Since the very first outbreak of malaria, people have been seeking a cure. The bark of the Cinchona tree, first discovered by indigenous people living in the tropics and subtropics, was found to be effective in treating malaria. Following centuries of continuous study, scientists extracted the most effective pharmacological component from it, and developed a drug named quinine.

儘管可以使用奎寧防治，但瘧疾持續對世界各地人們的生活和健康造成毀滅性影響。僅在中國，瘧疾就已肆虐數百年之久，連清朝康熙皇帝都被這種疾病傳染過，後服用傳教士帶來的奎寧才得以痊癒。

Despite the availability of quinine, malaria continues to take a hefty toll on the health and lives of people around the world. In China alone, malaria raged for several centuries, even infecting Emperor Kangxi of the Qing Dynasty, who recovered only after taking quinine from missionaries.

時至今日，根據世界衛生組織《2018年世界瘧疾報告》最新數據，2017年全球共發生2.19億瘧疾病例（95%置信區間：2.03億至2.62億），與之相比，2010年瘧疾病例數是2.39億（95%置信區間：2.19億至2.85億），2016年是2.17億（95%置信區間：2.00億至2.59億）。2017年，全球有43.5萬人死於瘧疾。與之相比，2016年瘧疾死亡人數是45.1萬人，2010年是60.7萬人。

The latest information in theWorld Malaria Report 2018 published by the World Health Organization (WHO) shows that an estimated 219 million cases of malaria occurred worldwide in 2017 (95% confidence interval[CI]: 203-262 million), compared with 239 million cases in 2010 (95% CI: 219-285 million) and 217 million cases in 2016 (95% CI: 200-259 million). In 2017, there were an estimated 435,000 deaths from malaria globally, compared with 451,000 estimated deaths in 2016, and 607,000 in 2010.

世衛組織一直高度重視防治瘧疾，並於2015年出臺了《2016-2030年全球瘧疾技術戰略》。世衛組織總幹事陳馮富珍博士表示：「該戰略的目的是幫助各國減少這個世界上最致命的蚊媒疾病所導致的人類痛苦。通過推進這項戰略，各國將對落實2015年後可持續發展框架做出重大貢獻。大幅擴大瘧疾應對工作不僅將幫助各國實現2030年衛生相關目標，還將促進減貧工作和其它發展目標。」

The WHO, which attaches great importance to the prevention and cure of malaria, introduced theGLOBAL TECHNICAL STRATEGY FOR MALARIA 2016-2030 in 2015. This strategy has been developed with the aim of helping countries reduce the human suffering caused by the world’s deadliest mosquito-borne disease, noted Dr. Margaret Chan, former Director-General of the WHO. By taking this strategy forward, countries will be able to make a major contribution to implementing the post-2015 sustainable development framework. A major scale-up of malaria response will not only help countries reach health-related targets for 2030, but also contribute to poverty reduction and other development goals.

青蒿素：為人類帶來生的希望

Artemisinin: Bringing Hope to Mankind

屠呦呦自小對中醫治療耳濡目染，工作後從事中藥和中西藥結合研究。1969年，在瘧疾瘋狂肆虐的大背景下，中國中醫研究院接受抗瘧藥研究任務，屠呦呦領導課題組從系統收集整理歷代醫籍、本草、民間方藥入手，在收集2000餘方藥基礎上，編寫了640種藥物為主的《抗瘧單驗方集》，對其中的200多種中藥開展實驗研究，歷經380多次失敗，利用現代醫學和方法進行分析研究、不斷改進提取方法，終於在1971年成功使用青蒿抗瘧。由此，從1980年到1990年，中國的年瘧疾病例從兩百萬例下降到九十萬例。

Tu Youyou, imperceptibly influenced by what she saw and heard regarding traditional Chinese medicine since an early age, has been committed to studying the integration of traditional Chinese medicine and Western medicine. In 1969, against the backdrop of rampant malaria, the China Academy of Traditional Chinese Medicine began to develop antimalarial drugs. Later on, a book titled 640 Folk Prescriptions was compiled by Tu's team, based on more than 2,000 prescriptions following a systematical collection of medical books, herbs and folk prescriptions from past dynasties. In addition, they had lab tests on over 200 kinds of traditional Chinese medicines, and experienced more than 380 failures, using modern medicine technology and methods for analysis and research to constantly improve the extraction of drugs. Finally, artemisia annua was successfully used to fight malaria in 1971, contributing to a sharp decrease in malaria cases in China from 2 million in 1980 to 900,000 in 1990.

▲ 1950年代，屠呦呦與老師樓之岑一起研究中藥。

In the 1950s, Tu studied traditional Chinese medicine with her teacher Lou zhicen.

中科院遺傳學博士李雷認為，青蒿素的發現解決了奎寧存在的普遍抗藥性問題，使得因抗藥性而無法進行治療的病患可以被醫治，挽救了數以萬計的生命。而且作為一種便於獲得的原材料，青蒿的普及也將為非洲貧困地區的患者帶來更實惠、療效更好的藥物。

Dr Li Lei, a geneticist at the Chinese Academy of Sciences, said the discovery of artemisinin solves the problem of quinine resistance in malaria, allowing patients whose treatment was discontinued due to quinine's ineffectiveness to be treated once again, saving tens of thousands of lives. As a readily available raw material, artemisia annua will become the more affordable, better drug for the victims of malaria in poor areas of Africa.

奎寧因使用時間長而出現了抗藥性，那麼難道青蒿素在後期使用中就不會出現這個問題嗎？其實青蒿素也面臨著同樣的困境，由於青蒿素最早在東南亞地區被廣泛使用，所以該地區最先出現了抗藥性問題。世衛組織和東南亞國家的多項研究表明，在柬埔寨、泰國、緬甸、越南等大湄公河次區域國家，對瘧疾感染者採用青蒿素聯合療法的三天周期治療過程中，瘧原蟲清除速度出現緩慢跡象，並產生對青蒿素的抗藥性。

If plasmodium develops resistance to quinine, could that not also happen to artemisinin used for later treatment? In fact, the first evidence of malaria's resistance to artemisinin has already been found in Southeast Asia, where artemisinin was first widely used. Studies by the WHO and countries in Southeast Asia have found that in countries of the Greater Mekong Subregion, such as Cambodia, Thailand, Myanmar and Vietnam, signs have been observed including the slow elimination of plasmodium and drug resistance to artemisinin over a three-day period during which people infected with malaria were treated with artemisinin-based combination therapy.

▲ 在中國最大的青蒿素生產基地裡，培育著在瓶裡生長的青蒿苗。

At China's largest artemisinin production base, artemisinin seedlings are grown in bottles.

中科大學化學博士袁嵐峰在2018年就曾提及過，惡性瘧原蟲出現對於青蒿素的抗藥性，其實是進化論的必然後果，因為藥物是相當於對病原體的一種自然選擇。微生物的生命周期很短，進化得很快，因此這是一場對於人類長遠而言幾乎註定要輸掉的鬥爭。

Dr Yuan Lanfeng, a chemist at the university of science and technology of China, said in 2018 that the emergence of plasmodium falciparum resistance to artemisinin was a corollary of evolutionary theory, since it is the result from pathogens undergoing natural selection under the circumstance of drugs. Microbes have a short life cycle and are evolving rapidly, so this is a long-run battle that humans are likely to lose.

然而在今年的4月26日，也就是第12個世界防治瘧疾日，國際權威期刊《新英格蘭醫學雜誌》發表了屠呦呦團隊的最新研究成果。屠呦呦團隊針對青蒿素產生的抗藥性問題提出了新的治療方案：一是適當延長用藥時間，由三天療法增至五天或七天療法；二是更換青蒿素聯合療法中已產生抗藥性的輔助藥物。

On April 26, 2019, the 12th World Malaria Day, the latest research findings from Tu's team were published by The New England Journal of Medicine. The team proposed new treatments for artemisinin resistance: an extension of the treatment period from three days to five or seven days, as well as the replacement of adjuvant drugs to which the drug resistance has developed in artemisinin-based combination therapy.

屠呦呦認為，解決「青蒿素抗藥性」難題意義重大：一是堅定了全球青蒿素研發方向，即在未來很長一段時間內，青蒿素依然是人類抗瘧首選高效藥物；二是因青蒿素抗瘧藥價格低廉，每個療程僅需幾美元，適用於疫區集中的非洲廣大貧困地區人群，更有助於實現全球消滅瘧疾的目標。

Tu Youyou believes that resolving artemisinin resistance is of great significance. On the one hand, Tu and her team remain committed to artemisinin research in alignment with global vision, because, for a long period into the future, artemisinin is set to remain the most effective anti-malaria drug. On the other hand, because of the low cost of artemisinin antimalarials, each course of treatment costs only a few dollars, making it affordable for the vast number of people in poor areas of Africa where the epidemic is concentrated. This brings humans closer to the goal of achieving the goal of global elimination of malaria.

▲ 2019年6月14日，「青蒿素與全球瘧疾防控和消除：歷史與未來」研討會現場，世衛組織全球瘧疾項目主任佩德羅·阿隆索做題為「全球消除瘧疾的形勢和挑戰」主旨演講。（圖片/新華社）

June 14, 2019. at the "Artemisinin and Global Prevention and Elimination of Malaria: The Past and the Future" seminar, Pedro Alonso, director of the WHO Global Malaria Program, delivered a keynote address entitled "The Situation and challenges of Global Malaria Elimination". (Photo/Xinhua)

「截至目前，青蒿素聯合療法治癒的瘧疾病患已達數十億例。屠呦呦團隊開展的抗瘧科研工作具有卓越性，貢獻不可估量。」世衛組織全球瘧疾項目主任佩德羅·阿隆索對屠呦呦團隊表達了高度讚譽。

Pedro Alonso, director of the WHO Global Malaria Program, noted that the artemisinin-based combination therapy has cured billions of victims of malaria. Alonso praised Tu's team for its great contribution to anti-malaria research.

雖然我們在與病毒的賽跑中搶先了一步，但正如科學家們擔憂的那樣，這不可能是一勞永逸的勝利。不過，為人類在這場戰爭中贏得更多的時間，本身就是一項偉大的成就。藥學家們的存在，正如哲學家加繆在《西西弗的神話》中所說：「他超出了他自己的命運。他比他搬動的巨石還要堅硬……」

Although humans have taken one step ahead in the race against virus, there remains a long way to go. However, it bought more time for mankind in this fight against malaria, which is a great achievement. The great pharmacists, just like the person described by philosopher Albert Camus in his work called The Myth of Sisyphus, stands 「beyond his own destiny. He is harder than the boulder he moved."

在「青蒿素抗藥性」研究出現新進展的同時，屠呦呦團隊還發現，雙氫青蒿素對治療具有高變異性的紅斑狼瘡效果獨特。目前參與臨床試驗的首批志願者並沒有發生非預期不良事件。臨床試驗一般共三期，二、三期試驗樣本量更大，至少還需7到8年。若試驗順利，預計新雙氫青蒿素片劑或最快於2026年前後獲批上市。屠呦呦說：「青蒿素對治療紅斑狼瘡存在有效性趨勢，我們對試驗成功持謹慎的樂觀。」

In the midst of new developments in drug resistance in artemisinin, Tu's team found that dihydroartemisinin had a positive effect on the treatment of highly variable lupus erythematosus. No unexpected adverse events occurred in the first group of volunteers currently involved in the clinical trial. Clinical trials typically include three phases, with more samples needed in Phase II and III, so the process will take at least seven to eight more years. If the trial goes well, it is expected that the new dihydroartemisinin tablets may be available on the market as soon as around 2026. "There are currently signs indicating that artemisinin is effective in treating lupus erythematosus and this is cause for cautious optimism, "Tu said.

屠呦呦及其團隊不但為飽受瘧疾和其他疾病困擾的人類帶來了新生的希望，同時也為中西醫的融合做出了巨大貢獻。中國中醫科學院表示，由屠呦呦團隊成員撰寫的青蒿素等傳統中醫藥科研論著，有望首次納入即將再版的國際權威醫學教科書《牛津醫學教科書(第六版)》。業界認為，這將成為中醫文化「走出去」的重要實踐成果。

Tu Youyou and her team have not only brought new hope to victims of malaria and other diseases, but also made a great contribution to the integration of Chinese and Western medicine. The Chinese Academy of Traditional Chinese Medicine has noted that the works on artemisinin and other traditional Chinese medicines, written by members of Tu's team, are expected to be included for the first time in the forthcoming sixth edition of the Oxford Textbook of Medicine, a globally authoritative textbook of medicine. Industry insiders believe that this will be considered one of the most significant outcomes of Chinese medicine in its efforts to "go global".

《牛津醫學教科書》主編考克斯教授說，他對傳統中醫藥論著即將納入該教科書感到高興。「中醫藥章節既重要又具深度。這一切都是中國科學家傑出努力的結果。」

Professor Timothy M. Cox, Editor in Chief of the Oxford Textbook of Medicine, said he is glad that traditional Chinese medicine is set to be included. "The chapter on traditional Chinese medicine is both important and profound, a credit to the efforts of Chinese scientists, "he said.

2018年12月6日，國務院發表《中國的中醫藥》白皮書。白皮書指出，中醫藥發展上升為國家戰略，中醫藥事業進入新的歷史發展時期。

On December 6, 2018, a white paper on Chinese medicine was published by the State Council. It points out that the program of traditional Chinese medicine has become a national strategy and has entered a new historical development period.

屠呦呦團隊在傳統醫學和現代醫學之間架起一座橋梁，讓中醫療法不僅在中國廣泛應用，而且因有效治療被越來越多的國家認可。青蒿素的研發過程及其成就讓世界認識到中醫是醫學進程中不可或缺的一部分，中醫不再是中國神秘的奇聞怪術，相信中西醫的結合將給出全球衛生治理一個「中國答案」！

Tu's team builds a bridge between traditional and modern medicine, allowing traditional Chinese medicine therapy not only to be widely used in China, but also approved by more and more countries for its effective treatment. The development of artemisinin and the contribution made by Tu's team have led the world to realize that traditional Chinese medicine is an integral part of international medical development, and is no longer seen as a mysterious or black art of China. We hope that the combination of Chinese and Western medicine in global health governance will show the significance of traditional Chinese medicine!

採訪、撰稿 / 董翎依

圖片 / 網絡

美編 / 高銘