1960-1970 - Need for new Medicine"Malaria was traditionally treated by chloroquine or quinine, but with declining success. By the late 1960s, efforts to eradicate Malaria had failed and the disease was on the rise. At that time, Youyou Tu in China turned to traditional herbal medicine to tackle the challenge of developing novel Malaria therapies. From a large-scale screen of herbal remedies in Malaria-infected animals, an extract from the plant Artemisia annua emerged as an interesting candidate. However, the results were inconsistent, so Tu revisited the ancient literature and discovered clues that guided her in her quest to successfully extract the active component from Artemisia annua. Tu was the first to show that this component, later called Artemisinin, was highly effective against the Malaria parasite, both in infected animals and in humans. Artemisinin represents a new class of antimalarial agents that rapidly kills the Malaria parasites at an early stage of their development, which explains its unprecedented potency in the treatment of severe Malaria."
Tu started working on the malaria antidote when the Chinese government along with Vietnam initiated a secret project (Project 523) to find a cure for malaria which was causing the death of more soldiers than the war. From 1930, chloroquine have been used as the antidote against malaria but it was facing increased resistance from the parasite lately. At the time when Tu started her work, around 240,000 compounds http://www.achaten-suisse.com/ had been screened in the US and China without any positive results. This triggered the interest in Chinese government to look for possible solution in the traditional Chinese medicines. Tu was apt for the research since she had studied both Chinese and Western medicine.
Tu and her team referred ancient text books and remedies in Chinese traditional medicine and analysed more than 2000 recipes from 640 herbs to make 380 extracts, which was then clinically tested on mice. One of the extracts from Artemisia annua (sweet wormwood) showed very good effect and it dramatically inhibited the malaria parasites growth in blood.
The 52 PrescriptionsThe first known medical description of Qinghao lies in a 2000-year-old document called "52 Prescriptions" (168 BCE) that had been unearthed from a Mawangdui Han Dynasty tomb. It details the herb's use for soothing hemorrhoids. Later texts also mention the plant's curative powers. Tu discovered a passage in the Handbook of Prescriptions for Emergencies (340 CE) by Ge Hong that referenced Qinghao's malaria-healing capacity. It said "Take a handful of Qinghao, soak in two liters of water, strain the liquid, and drink." She realized that the standard procedure of boiling and high-temperature extraction could destroy the active ingredient.
Clinical trials and TestingThis led Tu to redesign the extraction process, performing it at low temperatures with ether as the solvent. She also removed a harmful acidic portion of the extract that did not contribute to antimalarial activity, tracked the material to the leaves rather than other parts of the plant, and figured out when to harvest the herb to maximize yields. These innovations boosted potency and slashed toxicity. The clinical trial on mice and monkeys showed that it was completely effective against the infection.
Furthermore, Tu volunteered to be the first human subject. "As head of this research group, I had the responsibility" she said. It was safe, so she conducted successful clinical trials with human patients. Her work was published anonymously in 1977. In 1981, she presented the findings relating to artemisinin at a meeting with the World Health Organization.
Artemisinin, the present situationIn the past decade the first resistance to artemisinin has emerged, in Cambodia. The drug still works but it takes longer, typically four days instead of two. To stop resistance from spreading further doctors now only use artemisinin in combination with another antimalarial drug; it is harder for the parasite to evolve resistance to two drugs simultaneously.
Tu's achievement shows how our ancient science and traditional methods can speed up the process of drug discovery by shedding light into the intermediate process and potential candidates. We hope her work and achievements motivates a lot of people to continue work in this field and produce more ground breaking inventions.
- Nobelprice.org: Youyou Tu - Facts
- Nobelprice.org: Press Release (2015-10-05)
- Wikipedia: Artemisia annua
- Wikipedia: To Youyou
- JCI: From branch to bedside: Youyou Tu is awarded the 2011 Lasker~DeBakey Clinical Medical Research Award for discovering artemisinin as a treatment for malaria, Ushma S. Neil
- New Scientist: Nobel Prize goes to modest woman who beat malaria for China
- Wikipedia: Artemisinin