The Modest Woman Who Beat Malaria for the World

By PhilMcKenna

 

1 Forty years ago a project inChina yielded one of the greatest drug discoveries in modern medicine.Artemisinin remains the most effective treatment for malaria today and hassaved millions of lives. Until recently, though, the drug’s origins were amystery.

 

2 “I was at a meeting in Shanghaiin 2005 with all of the Chinese malariologists and I asked who discoveredartemisinin,” says Louis Miller, a malaria researcher at the US NationalInstitutes of Health in Rockville, Maryland. “I was shocked that no one knew.”

 

3 Miller and his NIH colleagueXinzhuan Su began digging into the drug’s history. After reviewing letters,researchers’ original notebooks and transcripts from meetings, they concludedthe major credit should go to pharmacologist Tu Youyou. Two months ago Tureceived America’s top medical accolade, the Lasker award.

 

4 Now 80, Tu still runs a lab inBeijing where she continues to study artemisinin. Shortly before receiving theaward she met me at a hotel near New York’s Central Park. Tu is a diminutive figurewith short, jet black hair that curls in wisps around her ears. Reading glassesdangle from a chain around her neck. On responding to any kind of praise she issoftly spoken and painfully modest. Talking about her research, however, shespeaks with an urgency and passion undimmed by passing years.

 

5 Tu carried out her work in the1960s and 70s, when China had a pressing need to fight malaria, a diseaserampant in the country. The primary treatment was a drug called chloroquine,but the malaria parasite was rapidly evolving resistance.

 

6 China’s leader Mao Zedong setup a drug discovery project, known as 523, for the date it was launched: 23 May1967. Within a couple of years hundreds of scientists had tested thousands ofsynthetic compounds without success and it was common knowledge that a similarprogramme in the US had drawn a blank too.

 

7 With no synthetic drugsforthcoming, attention turned to China’s traditional medicines. The governmentasked the Academy of Traditional Chinese Medicine in Beijing to appoint one ofits researchers to scour China’s herb garden for a cure.

 

8 The academy chose Tu, amid-career scientist who had studied both Chinese and western medicine and knewenough about both to realise it would not be an easy job. “By the time Istarted my search over 240,000 compounds had been screened in the US and China withoutany positive results,” she says.

 

9 Soon after joining project 523,Tu was sent to Hainan province, a region in the far south long plagued bymalaria, to observe the effects of the disease firsthand. As Tu’s husband, anengineer, had been sent to the countryside at the time, she had to entrust her4-year-old daughter to the care of a local nursery.

 

10 On Tu’s return to Beijing sixmonths later, her daughter didn’t recognise her and hid from the “strangewoman”. But Tu seems to bear no bitterness. “The work was the top priority, soI was certainly willing to sacrifice my personal life,” she says. And her timein Hainan had made a big impression. “I saw a lot of children who were in thelatest stages of malaria,” Tu says. “Those kids died very quickly.”

 

11 She and three assistantsreviewed more than 2,000 recipes for traditional Chinese remedies in theacademy’s library. They made 380 herbal extracts and tested them on mice. Oneof the compounds did indeed reduce the number of malaria parasites in theblood. It was derived from sweet wormwood (Artemisia annua), a plant common throughoutChina, which was in a treatment for “intermittent fevers” — a hallmark ofmalaria.

 

12 The team carried out furthertests, only to be baffled when the compound’s powers seemed to melt away. Tureread the recipe, written more than 1,600 years ago in a text appositelytitled “Emergency Prescriptions Kept Up One’s Sleeve”. The directions were tosoak one bunch of wormwood in water and then drink the juice.

 

13 Tu realised that their methodof preparation, boiling up the wormwood, might have damaged the activeingredient. So she made another preparation using an ether solvent, which boilsat 35°C. When tested on mice and monkeys, it proved 100 per cent effective. “Wehad just cured drug-resistant malaria,” Tu says. “We were very excited.”

 

14 But would it work in humans —and was it safe? Tu volunteered to be the first test subject. “As the head ofthis research group, I had the responsibility,” she says. After suffering noill effects, Tu began clinical trials with labourers who had contracted malariain the forest. Within 30 hours their fevers had subsided and parasites were gonefrom their blood.

 

15 Tu’s work wasn’t publisheduntil 1977. As was customary, the authors remained anonymous; in such anegalitarian society the group was considered more important than theindividual.

 

16 The discovery of artemisininremains a point of pride for China, and some argue it shows the worth ofscouring herbal lore for other buried botanical gems. The drug now helps tensof millions of people a year, and it is still obtained from sweet wormwood,grown in China, Vietnam and East Africa. Research is ongoing to breed strainswith higher yields of the active compound.

 

17 In the past decade the firstresistance to artemisinin has emerged, in Cambodia. The drug still works but ittakes longer, typically four days instead of two. To stop resistance fromspreading further doctors now only use artemisinin in combination with anotherantimalarial; it is harder for the parasite to evolve resistance to two drugs simultaneously.

 

18 As Tu says, malariaresearchers have to remain vigilant. “It is scientists’ responsibility tocontinue fighting for the healthcare of all humans.” And despite the importanceof her work, she is modest. “What I have done was what I should have done as a return for the educationprovided by my country,” she says.

 

19 She expressed gratitude at theLasker award ceremony, with her husband, daughter and granddaughter at herside. But that was just the icing on the cake: “I feel more reward when I seeso many patients cured.”

 

Update: Tu Youyou has beenawarded a share of the 2015 Nobel Prize for medicine or physiology for herdiscovery of artemisinin. She is the first Chinese scientist to receive ascientific Nobel Prize for research done in China, and the first Chinese womanever.

 

为世界战胜疟疾的谦虚女性

菲尔·麦肯纳

 

1 40年前，中国的一个科研项目带来了现代医学上最伟大的药物发现之一。如今青蒿素仍然是治疗疟疾最有效的药物，已经拯救了数百万人的生命。直到最近，这个药物的缘起还是一个谜。

2 “2005年，我在上海跟中国的疟疾专家一起参加一个会议时，我问他们是谁发现了青蒿素，”在马里兰州罗克维尔市的美国国家卫生研究院工作的疟疾研究员路易斯·米勒说。“与会者谁都答不上来，这让我大吃一惊。”

3 米勒和他在美国国家卫生研究院的同事苏新专开始钻研这款药物的历史。在审阅了书信、研究员们的原始笔记本和会议记录后，他们得出结论，认为头号功臣应该是药理学家屠呦呦。两个月前，屠呦呦获得了美国医学最高荣誉——拉斯克奖。

4 今年80岁的屠呦呦还在北京管理着一间实验室，继续从事青蒿素研究。就在接受拉斯克奖前不久，她同我在纽约中央公园附近的一家酒店见面。屠呦呦身材娇小，短发漆黑，两耳边的头发打着卷。脖子上的链子挂着一副老花眼镜。每当听到任何赞美之辞时，她总是轻声回应，谦虚不已。不过，一谈到她的研究，她的语调里就带着一种不因时光流逝而黯淡的紧迫感和激情。

5 上世纪六七十年代屠呦呦开展青蒿素研究，那时，中国迫切需要找到对抗蔓延全国各地的疟疾的治疗方法。当时主要采用的治疗药物是氯奎，但疟原虫很快对它产生了耐药性。

6 中国领导人毛泽东建立了一个药物发现计划，被称为“523项目”，因为它是1967年5月23日建立的。几年间，成百上千的科学家测试了数千种合成化合物，但均未取得突破。而且大家都知道美国的一个类似研究项目也一无所获。

7 既然合成药物没有突破，科学家们就把眼光转向了中国传统医药。政府要求坐落在北京的中国中医研究院任命一位研究人员从中草药中寻找治疗方法。

8 中国中医研究院选定了屠呦呦。她当时处于事业中期，对中西医学都有研究，这两方面的知识，使她意识到这不会是件轻松的任务。“我开始研究的时候，美中两国已经筛查了24万多种化合物，但都没有取得积极成效，”她说。

9 加入523项目后不久，屠呦呦就被派到海南省去第一手观察疟疾造成的影响。该省地处中国最南端，长期遭受疟疾的肆虐。当时，屠呦呦身为工程师的丈夫已经下放到农村，所以她不得不将4岁的女儿托付给北京当地一个托儿所照顾。

10 6个月之后，屠呦呦回到北京。她女儿没认出她来，想躲开这个“陌生女人”。不过屠呦呦似乎并没有怨艾。“工作第一，我当然愿意牺牲个人生活，”她说。而且海南的日日夜夜给她留下了深刻的印象。“我看到许多疟疾晚期的孩子，”屠呦呦说。“这些孩子很快就死去了。”

11 她和3名助手查阅了中国中医研究院图书馆所藏的2,000多张中药处方，提取了380种草本植物的成分，在小鼠身上做了实验。其中一种复合物果然能减少血液中的疟原虫数量。它是从青蒿（拉丁名Artemisia annua）中提取的。青蒿是中国常见植物，用来治疗“间歇热”——而间歇性发热是疟疾的明显特征。

12 研究团队进行了更多实验。令他们费解的是，该复合物的药效似乎消失了。屠呦呦重新研读了药方。该药方记载于1,600多年前的古籍，书名起得颇为贴切，叫《肘后备急方》。药方说明须将一把青蒿浸在水里，然后服用浸渍出来的汁。

13 屠呦呦意识到他们原先的制备方法，也就是煎熬青蒿，可能破坏了活性成分。于是她改用沸点为35°C的乙醚溶剂来制备。这个制剂用在小鼠和猴子身上百分之一百有效。“我们治愈了耐药性疟疾，”屠呦呦说。“我们很激动。”

14 然而，这个制剂用在人身上会有效吗——还有，安全吗？屠呦呦第一个自愿试药。“作为研究组的组长，我有责任，”她说。结果她没有经受任何不良反应。于是屠呦呦开始在从森林中感染疟疾的劳动者身上进行临床试验。30小时之后，他们退烧了，血液中不再检测到疟原虫。

15 屠呦呦的研究成果直到1977年才发表。按照当时中国的惯例，论文作者们的姓名被隐去；在这样一个平等主义的社会里，集体被视为比个人更重要。

16 青蒿素的发现令中国自豪至今。有些人坚持认为，这说明有必要对本草学进行仔细研究，以便找到其他被埋没的草药瑰宝。目前，该药物每年帮助数千万人，而且依然从生长在中国、越南和东非的青蒿中提取。目前正在培植活性成分含量更高的青蒿品种。

17 过去10年间，柬埔寨报告了第一例耐青蒿素的疟疾病例。青蒿素仍能起效，但起效时间拉长，一般需要4天，而不是以往的两天。为了防止耐药性的进一步扩展，目前医生们在使用青蒿素的同时还会联合使用另一种抗疟疾药；疟原虫对两种药物同时产生耐药性比较难。

18 正如屠呦呦所言，疟疾研究人员们应时时保持警惕。“持续保护人类健康是科学家们的天职。”虽然她的工作很重要，她还是很谦虚。“我所做的一切都是应该的。祖国给我受教育的机会，我就该报效祖国。”她说。

19 屠呦呦在丈夫、女儿和外孙女的陪伴下出席了拉斯克奖颁奖典礼。她对获奖表示感谢。不过，得奖只是锦上添花：“看到这么多病人得以痊愈对我来说是更高的奖赏。”

最新消息：屠呦呦因为发现青蒿素和其他几位科学家共同获得了2015年诺贝尔生理学或医学奖。她是首位因在中国完成研究而获得科学类诺贝尔奖的中国科学家，也是首位获得诺贝尔奖的中国女性。