Nobel Prize in Medicine 2015, Part 1: Tu Youyou and the Discovery of Artemisinin
Nobel Prize season has began, and with that will be a series of posts detailing the chemistry-related prizes that are awarded! Today’s post will be about one half of the Physiology/Medicine prize, awarded to Chinese pharmacologist Tu Youyou for the discovery of the antimalarial drug artemisinin. This is the first natural science Nobel Prize awarded to a native mainland Chinese scientist. (Other awards have been given to scientists of Chinese descent that did their work in other countries.)
Tu Youyou (屠呦呦) was born in Ningbo, Zhejiang, China, in 1930 and graduated from the Department of Pharmaceutical Sciences at Peking University Medical School in 1955, and worked as a researcher at the China Academy of Chinese Medical Sciences afterwards. She participated in a secret government research program, Project 523, that aimed to discover new antimalarial drugs in an effort to aid North Vietnam in the Vietnam War.
The discovery process was guided by traditional Chinese herbal remedies found in ancient medical texts. One particularly effective remedy was found in “The Handbook of Precriptions for Emergency Treatments” (肘後救卒方), a medical text written in the 4th century: “take one bunch of qinghao [Artemisia annua], soak in two sheng [~400 mL] of water, wring it out to obtain the juice, and ingest it in its entirety.” In 1971, Tu was able to extract the active compound from the herb, artemisinin (also known as qinghaosu, 青蒿素, after the Chinese name for the herb). Tu and her colleagues later determined the chemical structure in 1979, and published their findings anonymously.
Artemisinin and its related derivatives are one of the most effective remedies for malaria. The structure of artemisinin includes an unusual peroxo bridge that is crucial to its antiparasitic activity. Upon ingestion, the ester carbonyl is hydrogenated to form dihydroartemisinin, which is the biologically active metabolite. The mechanism through which dihydroartemisinin kills parasites is unknown, but likely involves radical formation from the peroxo bridge, causing oxidative damage to the parasite.
References:
(1) https://en.wikipedia.org/wiki/Tu_Youyou
(2) http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/
(2) Miller, L. H; Su, X. Cell. 2011, 146 (6), 855-858.
(3) Cumming, J. N.; Ploypradith, P.; Posner, G. H. Adv. Pharmacol. 1996, 37, 253-297
quicksilverink 