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On Orders From Mao, Researchers Set Off On Nobel-Winning Drug Work

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The Nobel Prize in medicine was awarded Monday to three scientists for their work on parasitic diseases.

William C. Campbell and Satoshi Omura were recognized for discovering a compound that effectively kills roundworm parasites. A Chinese scientist, Dr. Youyou Tu, won for her work in isolating a powerful drug in the 1970s to fight malaria.

For Tu, it all started in the 1960s, when Americans and North Vietnamese fighters were hurting — not just from jungle warfare with each other but also from a common enemy: drug-resistant malaria.

Scientists on both sides of the line scurried to develop a new drug that would keep troops malaria-free. American military scientists toiled in the laboratories of Walter Reed Army Institute of Research. Meanwhile, Mao Zedong ordered hundreds of Chinese scientists to develop a new drug. Tu led a team of researchers working on what was called "Project 523."

The research would eventually result in artemisinin, an extremely effective anti-malarial medication that has been credited with halving the number of malaria deaths worldwide. In addition to the Nobel Prize, Tu earlier this year won the Alpert Foundation Prize from Harvard and in 2011 the Lasker Prize for Clinical Medical Research.

In aiming to develop a new drug, her group combed the literature on traditional Chinese medicine, looking for plants that might hold promising ingredients for a malaria cure. Artemisia annua, also known as "sweet wormwood" or "qinghao," had been given as a tea to malaria patients for centuries, cited as an anti-fever medicine as early as the second century B.C., and as an anti-malarial by alchemist Ge Hong in the fourth century. When Tu's team brought it to the lab, they found that it killed the malaria parasites in mice. They eventually isolated the active ingredient — a chemical now known as artemisinin.

A fourth-century tea recipe involving the plant, the doctor wrote in the journal Nature Medicine, "gave me the idea that the heating involved in the conventional extraction step we had used might have destroyed the active components, and that extraction at a lower temperature might be necessary to preserve antimalarial activity."

The centuries-old manuscripts were right. By late 1971, they had isolated "a nontoxic, neutral extract that was 100 percent effective" against malaria in infected mice and monkeys. Tu wrote that she and her colleagues tested the new drug on themselves before starting human trials.

"This was during the Cultural Revolution, when Chinese scientists and other intellectuals were sent off to the countryside to do hard labor and be publicly humiliated," says Keith Arnold, who was researching malaria on the U.S. side at the time and would later work with the Chinese researchers. Back then, he says, they "often worked overnight and in the basement of buildings. And they were in fact harassed and treated very badly, until the word came down that these scientists were protected by Mao."

Arnold, the first Western scientist to write about artemisinin, learned about the secret national project when he met some of the scientists on a trip to China in the late 1970s. He says he looked at the data "and noticed that this was incredible. We had no compound comparable to this that would kill the parasite as quickly as this."

Despite comparative studies that showed that it far outshone the U.S. drug mefloquine, mutual distrust between East and West kept artemisinin off the international market.

"It was delayed far too long," Arnold says.

Just as Tu's work on artemisinin is being showered with recognition, malaria parasites in South East Asia have started to show resistance. Scientists are now searching for the next breakthrough drug. The world's deadliest animal remains the mosquito.

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