image: The antimalarial drug artemisinin (Qinghaosu) was discovered by Youyou Tu and her colleagues from Artemisia annua L., a plant used in traditional Chinese medicine. view more
Credit: ©Science China Press
The discovery of artemisinin and its derivatives dramatically changes the landscape to combat malaria, and approximately 22% of the 663 million averted clinical cases were due to the use of artemisinin combination therapies (ACTs), according to a recent estimate. Artemisinin leads to two paradigm shifts in antimalarial research and therapy: one is the change from quinoline-based antimalarial drugs to artemisinin-based therapies, and the other is the change of research direction in antimalarial drug development.
Artemisinin was discovered during the Chinese "Cultural Revolution" in the 1970s, and results from ongoing projects such as the 523 Project were not published. In January 1969, Professor Tu was brought into the project and designated as a team leader to search for Chinese herb recipes having antimalarial activities. After searching more than 2,000 recipes and compiling 640 recipes, prof. Tu's team discovered that an extract from a plant called 'Qinghao' or Artemisia annua had inhibition activity towards a rodent malaria parasite Plasmodium berghei, but the activity was not stable. Getting inspirations from recipes written by Hong Ge ~1700 years ago, prof. Tu optimized the methods of A. annua extraction, obtained samples that could inhibit rodent malaria (October, 1971) and monkey malaria with 100% activity in December, 1971, and led a clinical trial team to Hainan Island and tested her extracts on 21 patients, achieving 95%-100% efficacy. After her report in a meeting held on November 17, 1972, a large-scale, countrywide effort was made to produce large quantities of the pure ingredient (or arteimisinin crystal) to determine its structure and to chemically synthesize artemisinin involving scientists from many institutions.
Professor Tu played a critical role in the discovery of artemisinin. Her major contributions are: Bringing the plant into the 523 Project, the discovey of a method to extract active ingredient, conducting the first clinical trial of Artemisia extract in human patients, isolation of active ingredient for structural studies, and the discovery of dihydroartemisinin that greatly improved water solubility. Because of her critical contributions and achievements, Professor Tu received numerous awards from the Chinese government and private organizations worldwide. Interviews with prof. Tu's peers also support her key role in the discovery.
There have been many controversial issues associated with credits and contributions to the 523 Project and the discovery of artemisinin. Although it is a fact that a large number of people took part in and contributed to the 523 project, all later work was based on her initial demonstration of active ingredient from the Qinghao plant. Often when multiple people are involved in an important research development, The Nobel Prize Committee recognizes only the individual who made the seminal discovery that led to the development. There is no doubt that Professor Tu is the first person who brought the A. annua into the 523 Project, the first person who obtained the active ingredient (extract and crystal), and the first person who demonstrated antimalarial activity in humans. The impact of artemisinin on public health is immediate and tremendous. There are few scientific discoveries that have the same scale and instant impacts on public health, human productivity, and scientific research as artemisinin has!
Drs Su and Miller also pointed out a serious issue related to artimisinin in treating malaria: After years of the large-scale use of artemisinin, P. falciparum parasites that are potentially resistant (or more tolerant) to the drug have been reported in countries in Southeast Asia. Prof. Tu has also been trying to raise public awareness of this serious issue for years.
###
This work was supported by the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases (NIAID).
See the article:
This article was published online in the Science China Life Sciences, by Science China Press and Springer-Verlag Berlin Heidelberg.
http://link.springer.com/article/10.1007%2Fs11427-015-4948-7 http://life.scichina.com:8082/sciCe/EN/abstract/abstract518841.shtml
Science China Press
http://www.scichina.com/
Journal
Science China Life Sciences