In the 1960’s, the world was plagued with malaria, and drug resistance was rising. Tu Youyou, a pharmacologist in China, was put on a top secret task force to find a new cure. Her weapon of choice? A collection of ancient Chinese medicinal texts, including Ge Hong’s 2,000-year-old A Handbook of Prescriptions for Emergencies.
It was a dark time in her country’s history. Her husband had been sent to a reeducation camp because like her, he was an academic. That meant he was trained in Western ideas that threatened the current regime. Perhaps Tu was even more dangerous to the state – not only did she get a Western education in pharmaceutical chemistry, but also one in traditional Chinese medicine. The new government wanted to eradicate both. But rather than send her to a reeducation camp, she was recruited to lead a top secret government research project. They wanted her to use that unique interdisciplinary skillset to find a new treatment for drug-resistant malaria.
This mission came with diverse challenges. Tu’s new job required her full attention. With her husband sent away, how would their daughters be cared for? They sent their youngest to Tu’s mother, and the oldest to a boarding school. When Tu reunited with them years later, they wouldn’t recognize her. Another challenge was the hazards of the era: the infamous Cultural Revolution meant less resource manufacturing, so Tu would have to extract chemicals in toxic conditions. She was convinced, however, that this was a task so important that nothing else mattered.
“As a young scientist early in her career life,” Tu stated in her Nobel lecture, “I felt overwhelmed by the trust and responsibility received for such a challenging and critically important task. I had no choice but to fully devote myself to accomplishing my duties.”
During this time, the Chinese government became interested in malaria for political reasons. Mao Zedong wanted to show his support for North Vietnam in the war that plagued the 1960’s, and mosquitoes were spreading the disease like wildfire in the humid jungles. Treatments for malaria had already been identified, but drug resistance was on the rise. Could China provide a novel cure? Perhaps, but the political motivations meant Zedong wanted the project kept top secret. Tu, with her knowledge of modern and ancient Chinese medicine, was the top choice. And she was ready to devote everything to the task – one that reached far beyond the current cultural moment and could impact the world for the better.
Tu began by gleaning ancient Chinese literature. She looked for remedies used to treat anything with malaria-like symptoms. The survey resulted in the discovery of 2,000 potential treatments, which she narrowed down to 640. One of the plants that came up often was qinghao – sweet wormwood.
Tu and her team ran many tests on the various wormwood species native to China. The ancient books didn’t differentiate between species and subspecies like we do today, and they would eventually discover that only one of them was effective. When they did settle on qinghao, the extractions they tested were unpredictable. In the rare case that an extract showed antimalarial activity, it was not a strong enough effect to be medically helpful. Tu returned to her books.
That’s when she noticed a passage in Hong’s book that read: “A handful of qinghao immersed with 2 liters of water, wring out the juice and drink it all.”
Tu realized that their chemical extraction methods always involved heat. But this ancient text said nothing about boiling or cooking. Perhaps temperature damaged the active ingredient.
She designed various extraction methods at lower temperatures. It wasn’t until they tested extract No. 191 that they received exciting results. It showed 100% effectiveness against malaria in rodents. Then in monkeys, it again worked perfectly.
Would it work in people? In order to get large enough quantities to run in human trials, they had to extract the herbs using household vats, without any ventilation typical of chemistry labs. The researchers got sick from the fumes, including Tu. Then, a debate erupted from confusing data: would it be safe enough for people? Eager to avoid any further delays, Tu and a couple other colleagues volunteered to take the extract under close hospital examination. She explained, “During the Cultural Revolution, there were no practical ways to perform clinical trials. So, in order to help patients with malaria, my colleagues and I bravely volunteered to be the first people to take the extract.”
No side effects were observed. Three more offered to take it. Everyone was fine.
This daring effort led to the extract’s use in a trial with actual malaria patients. All of them recovered, and there wasn’t a trace of the parasite left in them. Tu was successful.
The active ingredient was eventually identified as artemisinin, a kind of terpenoid. Terpenoids are a class of chemicals found ubiquitously in nature, contributing to everything from a tomato’s blush to the scent of earth after a rain. This wasn’t the first time a terpenoid was shown to have medicinal properties – and it wasn’t the last.
Artemisinin has now become the world favorite for treating malaria, and artemisinin derivatives have proven even more potent in fighting this disease. It is the strongest antimalarial drug we have, and, based partly on the “combination therapy” strategy that pairs artemisinin with other drugs, resistance is not common. Though it’s been dubbed a “miracle drug,” it wasn’t until 1991 that scientists found out how it actually worked! As it turns out, artemisinin is also harmless to the parasite itself. But red blood cells are full of hemin, a molecule used by the oxygen-carrying proteins in our blood. Malaria preys on red blood cells, so they rapidly obtain more hemin than anything else around them. Turns out, when hemin and artemisinin mix, they produce a deadly compound. This makes artemisinin kill malaria selectively, leaving the patient unscathed.
Tu Youyou received the Nobel Prize in 2015 and is the first ever Chinese Nobel laureate in Physiology or Medicine. She remains passionate about both science and her beloved culture, stating, “It is my dream that Chinese medicine will help us conquer life-threatening diseases worldwide and that people across the globe will enjoy its benefits for health promotion.” She concluded her Nobel Lecture with another treasure from ancient Chinese literature – a poem:
The sun along the mountain bows;
The Yellow River seaward flows;
You will enjoy a grander sight;
By climbing to a greater height.
–On the Stork Tower by Wang Zhihuan
Tu believes that there is even more that traditional Chinese medicine has to offer the world. Perhaps other cultures hold life-saving secrets in their medical histories as well. Most modern drugs were first discovered in nature. All it takes are scientists as passionate and persistent as Tu Youyou to discover them.
By Hannah Edstrom
References
108 Poems from ShiJing. Translated by Sen Du & Chen Zhong.
Leung, Julie. 2019. Who Did It First? 50 Scientists, Artists, and Mathematicians who Revolutionized the World (A. Hart, Ed.). Henry Holt & Co.
Tu, Youyou. 2016. Artemisinin – A Gift from Traditional Chinese Medicine to the World (Nobel Lecture). Angewadte Chemie, 128(35):10366-10382.
Tu, Youyou. 2011. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nature Medicine, 17(10):1217-1220.Meshnick, Steven R., et al. 1991. Artemisinin (qinghaosu): the role of intracellular hemin in its mechanism of antimalarial action. Molecular and Biochemical Parasitology, 49:181-190.
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