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Artemisinin’s Rocky Road to Globalization: Part I

by Yanzhong Huang
February 27, 2015

A Thai Public Heath Ministry official places a thermometer into a child's mouth at a malaria clinic in Sai Yoke district, Kanchanaburi Province October 26,2012. The child, who lives on the Thai-Myanmar border, came to the clinic to get tested for malaria. Globally, 3.3 billion people are at risk of malaria infection. While Africa has the highest malaria burden, most the 46,000 deaths outside Africa occurred in Asia Pacific. There are also concerns over a growing parasite resistance. Studies and research show artemisinin-based therapies - currently the most effective treatment against malaria - are taking longer to cure some of the patients. REUTERS/Sukree Sukplang (THAILAND - Tags: POLITICS HEALTH) A Thai Public Heath Ministry official places a thermometer into a child's mouth at a malaria clinic in Sai Yoke district, Kanchanaburi Province, on October 26, 2012 (Sukree Sukplang/Courtesy of Reuters).

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Artemisinin, or Qinghaosu, is isolated from Artemisia annua L., a plant native to China but now naturalized in many other countries. Today, the artemisinin group of drugs is considered the most efficacious and fast-acting antimalarial known to the humankind. In 2011, Dr. Tu Youyou, a Chinese medical scientist, won the Lasker Award in Clinical Medicine—one of the most respected science prizes in the world—for discovering the antimalarial treatment that has saved millions of lives worldwide, especially in the developing countries.

The discovery of artemisinin-based therapies can be traced to the 1960s, during the Vietnam War, when the malaria parasite Plasmodium falciparum started to develop widespread resistance to existing antimalarial drugs such as chloroquine. Given malaria’s devastating effect on an army’s fighting capabilities, it became imperative to develop a new antimalarial drug. This led the U.S. military to develop mefloquine in the 1970s; the North Vietnamese, meanwhile, looked for help from their northern neighbor. In 1967, China launched a top secret mission called Project 523, which mobilized more than sixty research organizations and about five hundred scientists to develop an antimalarial medicine. After screening a list of herbs and folk remedies, Tu Youyou and her team in the early 1970s noted artemisinin’s healing power for malaria and were the first to develop a novel extraction process to maximize yield and efficacy. Based on the information and extraction methods of Tu’s team, another two teams of Chinese scientists were able to obtain crystals from A. annua L. that were active against malaria infection. History is full of ironies: while Project 523 aimed to develop an effective antimalarial drug for the Vietnamese, the artemisinin-based antimalarial drugs were first used by the People’s Liberation Army (PLA) when it invaded Vietnam in 1979.

Project 523 was officially discontinued in 1981. But Chinese scientists continued their search for effective antimalarial drugs. In the early 1980s, based on clinical studies comparing artemisinin and mefloquine, they were among the first to recommend the use of combination therapy to reduce the risk of recurrence and development of resistance. In 1985, they combined artemether and lumefantrine into a single tablet, thereby creating the first artemisinin combination therapies (ACT). It was registered as a new drug in China in 1992, with the Institute of Microbiology of the Chinese Academy of Military Medical Science (IME/AMMS) being the original patent holder. In 1987, Guilin Pharmaceutical also developed intravenous (IV) artesunate for patients with severe malaria. The liquid form of the drug was the first drug ever developed entirely by a domestic Chinese company.

These discoveries, however groundbreaking, unfortunately occurred during the Cold War, when China’s participation in international health cooperation was limited. The lack of international scientific exchange meant that artemisinin-based therapies did not make a timely contribution to global health. Indeed, it was not until December 1979 that scientists outside China learned about the discovery via a paper published in the Chinese Medical Journal. It would take another two decades before ACTs were officially adopted by the World Health Organization (WHO) as frontline drugs in the global fight against malaria.  Paradoxically, even today artemisinin-based drugs made in China only accounts for 1 percent of the international market share. Why? This will be the subject of my next blog post.

 

Correction: A previous version of this blog stated that in 1987, Guilin Pharmaceutical also developed artesunate, a semi-synthetic derivative of artemisinin.

Post a Comment 5 Comments

  • Posted by Vivian Jardim

    I’m interest in your next post about why this drug has not been made widely available since it seems to be affordable and effective in the treatment of these diseases.

  • Posted by NL

    I believe there is a factual error in the following statement:
    “In 1987, Guilin Pharmaceutical also developed artesunate, a semi-synthetic derivative of artemisinin.”

    Semi-synthetic artemisinin is an alternative pathway of synthesizing artemisinin in a lab using genetically modified yeast. What I believe your referring to in the statement is that Guilin synthesized artemisinin into the active pharmaceutical ingredient (API) artesunate which has a greater bio-availability in the blood than artemisinin.

  • Posted by YHuang

    Hi Vivian,
    Thank you for your interest in the forthcoming part two of this blog series. Stay tuned!
    Best,
    Yanzhong Huang

  • Posted by YHuang

    Hi NL,
    Thank you for your interest in the piece. For your reference, I used the definition from the following article http://www.ncbi.nlm.nih.gov/pubmed/25074847. I do think you are correct that the Guilin method is different from the alternative method of synthesizing artemisinin in a lab using genetically modified yeast. Please see my correction in the blog, above.
    Best,
    Yanzhong Huang

  • Posted by John

    awesome epistomology on the discovery qinghaosu. A very well derserved noble prize.

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