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How a secret Chinese military drug based on an ancient herb won the Nobel Prize

The Nobel Prize for Medicine was awarded to William C. Campbell, Satoshi Ōmura and Youyou Tu for their work on parasitic infections. (Video: Twitter/Nobel Prize)

Nearly 50 years ago, Tu Youyou began working on a classified Communist military project using clues from ancient Chinese medicine in search of new cures for malaria.

Monday, Tu shared the Nobel Prize for Medicine in recognition of her work, which has led to one of the world’s final and most potent defenses against a tropical disease that kills over half a million people each year.

The prize caps off a remarkable journey for Tu, a researcher without a Ph.D. who did much of her seminal work in secret, at a time when China was executing its own scientists en masse in revolutionary fervor. For years, Tu’s discovery of a cutting-edge drug developed from an ancient Chinese folk remedy was hardly known beyond the country’s borders.

[American among trio of Nobel winners for work on parasitic diseases]

The development of qinghaosu — or artemisinin — is one of modern China’s proudest accomplishments, but it’s also a story about Communism, Chairman Mao, and China’s return to the world economy.

Humanity has been at odds with malaria for millennia, long enough for the struggle to be written into our genes. The most famous remedy for malaria began with Native Americans near Peru, who had been using the bark from the cinchona tree to reduce fevers. In colonial times, Western explorers discovered that the bark was particularly effective at treating malaria. French scientists in 1820 identified quinine as the active ingredient in cinchona bark, and this extract became the standard treatment for malaria.

Today, malaria is known mostly as a public health problem in developing nations, but a hundred years ago, it was a wartime headache for generals fighting tropical campaigns. Most of the world’s cinchona at the time came from Indonesian farms controlled by the Dutch, who were Allied sympathizers. The lack of supply during World War I prompted German scientists to research synthetic versions of quinine that could be manufactured in the lab.

One of those drugs, chloroquine, became the preferred treatment for malaria in the 1940s and 1950s, for its efficacy as well as its mild side effects. But the use of chloroquine became so widespread that resistant strains of malaria quickly began to emerge. By the 1960s, when the United States started sending troops into the jungles of Vietnam, chloroquine-resistant malaria was a scourge that had no good remedy.

In response, the American military started a massive drug screening effort run out of Walter Reed Army Institute of Research. The aim was to find a replacement for chloroquine. What they didn’t know at the time was that China, at the request of its ally North Vietnam, was working toward the same goal.

On May 23, 1967, Chinese scientists commenced Project 523, a secret effort that enlisted hundreds of researchers to discover a new malaria drug. The project launched at the height of Mao Zedong’s Cultural Revolution, a brutal time during which academics and intellectuals were murdered, imprisoned, or sent to “reeducation camps” in mass purges.

For doctors and chemists. Project 523 was a lifeline, according to Professor Zhou Yiqing of the Chinese Academy of Military Medical Sciences, himself a malaria researcher. “By the time Project 523 had got under way, the Cultural Revolution had started and the research provided shelter for scientists facing political persecution,” he said in a 2009 interview with the World Health Organization.

By Zhou’s account, the project had two branches. Some teams searched for synthetic chemicals in the lab. Other teams, including one eventually led by Tu Youyou, sought inspiration from ancient Chinese medical textbooks.

Tu, who was born in 1930, had an unusual background. She studied pharmacy in college, and then spent a few years training in traditional Chinese medicine. At the time there was intense interest in folk medicine, which fed a political narrative: China as a proud, wise nation with a distinguished history of discovery.

Tu’s research project sought to find modern logic in ancient ways, much as the French researchers identified quinine from the bark of the cinchona tree. According to Tu, she and her team screened over 2,000 different Chinese herbs described in old texts, of which about 200 were good enough to test in mice. That’s when they hit upon a plant called Artemisia annua: annual wormwood, or qinghao in Chinese.

They found a reference in a third-century text from Chinese physician Ge Hong. To cure “intermittent fevers,” the recipe called for soaking the qinghao plant in water, wringing it out, and drinking the juice — as opposed to boiling it in a tea.

As Tu writes, there had been some trouble making a useful extract from the qinghao plant. She credits Ge Hong’s recipe for the idea to use lower temperatures in processing the qinghao plant.

This worked exceedingly well. They tested the extract in rats, and it cured nearly every one. They tested it on themselves to make sure it wasn’t toxic. Then they tested it on human patients, and showed that it worked far more aggressively than the existing standard treatment, chloroquine.

By in the early 1970s, Tu wrote, her team had isolated the active compound in the extract, which they called qinghaosu, or “essence of qinghao.”

At the time, all of this work remained a Chinese military secret; some of the results were published in Chinese-language journals, but it would be well after the death of Mao Zedong until China would reveal that it had discovered a surprisingly potent new weapon against malaria.

In the late 1970s, Mao’s successor Deng Xiaoping began opening up the country, reforming the economy and building diplomatic ties. These efforts led famously to a trip to the Carter White House in 1979. That same year, word had begun to trickle out about a new Chinese malaria drug. In 1981, Chinese researchers presented data on qinghaosu at a World Health Organization meeting. Tu gave the initial presentation.

Yet, the international community would be slow to pick up on qinghaosu, or artemisinin, as it's known outside of China.

The Vietnam War was long over, and many of the most afflicted countries couldn’t afford to pay for expensive new treatments. (The American military research effort had also been somewhat successful, resulting in the toxic but often effective drug mefloquine.) And China was still getting the hang of its new market-based economy. In the 1990s, Western pharmaceutical companies began partnering with Chinese firms to produce drugs based on artemisinin, but in relatively small quantities.

Demand quickly grew. Drugs that contain artemisinin or its sister compounds are special not only because they wipe out malaria quickly, but also because they attack the parasite in a new, unique way. By the early 2000s, multi-drug resistant strains of malaria were spreading in several regions of the world. Artemisinin became the one of last lines of defense, and the World Health Organization ramped up efforts to provide the drug.

Today, the WHO recommends a combination of artemisinin and another anti-malarial as the standard treatment for malaria. It's fast, effective, and taking the different drugs in together helps reduce the risk of resistance.

This has all been a source of immense pride for many Chinese. Artemisinin was the first major pharmaceutical discovery to come out of China, and its roots in traditional Chinese medicine heighten its mythology.

The lion’s share of the credit rightly goes to Tu Youyou and the countless other Chinese scientists who worked on Project 523. But Oxford anthropologist Elisabeth Hsu suggests that the political climate at the time also deserves recognition. Qinghaosu might never have been discovered had it not been for Maoist China’s nationalist infatuation with Chinese folk medicine.

“It was thus a feature specific to institutions of the People’s Republic of China that scientists, who themselves had learnt ways of appreciating traditional knowledge, worked side by side with historians of traditional medicine, who had textual learning,” she argues. “This was crucial for the ‘discovery’ of qinghao.”

Tu Youyou, trained in both worlds, would be the one to put the pieces together.