A Chinese scientist who pioneered a malaria treatment for Chinese troops fighting in the Vietnam War has won the Nobel Prize for Medicine.
Tu Youyou spearheaded a secret programme set up by Chairman Mao to see if traditional Chinese herbal cures could reduce the number of North Vietnamese troops dying to malaria.
After sifting through thousands of different folk remedies, she finally unearthed a 1,600-year-old recipe using sweet wormwood that formed the basis for one of the most effective treatments ever discovered.
Under Mao's Cultural Revolution, which saw academics as part of the despised bourgeoisie, her name was kept anonymous for decades, and until recently, even colleagues had never heard of her.
Now, though, at the age of 84, she has finally taken her rightful place in world medical history, with the Nobel judges announcing on Monday that she would be a joint winner of this year's $960,000 award.
But her extraordinary tale, which began during the Vietnam war, also shows traditional medicine’s limitations.
In the war, the North Vietnamese were not just fighting American-supported forces but also failing to fight malaria. The parasite that caused the disease had developed resistance against chloroquine, which was commonly used as treatment. So, in desperation, they turned to China’s leader, Mao Zedong, for help.
Mao’s answer was to make searching for a new malaria drug a military project. Soon, more than 500 scientists were involved. One group screened some 40,000 known chemicals to find a malaria drug. The other turned to traditional medicine literature and sent for finding “secret cures” in Chinese villages.
Those looking at traditional medicine literature succeeded, but not easily.
We investigated more than 2,000 Chinese herb preparations and identified 640 hits that had possible antimalarial activities. More than 380 extracts obtained from 200 Chinese herbs were evaluated against a mouse model of malaria. However, progress was not smooth, and no significant results emerged easily.
The first taste of success came when an ancient text revealed a method of using qinghao—the Chinese name for sweet wormwood—to extract artemisinin. After five years, in 1972, Tu had found a method to successfully extract the drug from the plant. But such were the days of China’s Cultural Revolution that clinical trials could not be performed.
In the question-and-answer session after the announcement at the Karolinska Institute, which awards the Nobels, one of the panelists emphasized not just the quality of Tu’s scientific research, but also the value of recorded empirical experience in the past.
The antifebrile effect of the Chinese herb Artemisia annua (qinghaosu 青蒿素), or sweet wormwood, was known 1,700 years ago, he noted. Tu was the first to extract the biologically active component of the herb – called Artemisinin – and clarify how it worked. The result was a paradigm shift in the medical field that allowed for Artemisinin to be both clinically studied and produced on a large scale.
Tu’s team volunteered to be the first patients to deem the drug’s safety, and only then could they go out to do proper trials. But soon after, when the war in Vietnam ended, the project that found the drug was disbanded. Even though Tu had managed to publish her results widely by the 1980s, the development of the drug languished.
It took nearly 30 years for the World Health Organization to endorse the drug. The reasons for the delays are not clear, but were perhaps caused by a combination of political instability, lack of patents that could spur pharma companies to invest in the development, and malaria afflicting mostly the poor.
Though it took time, Tu’s method showed other Chinese researchers how to capitalize on the ancient knowledge hidden in scrolls and passed down through word of mouth. China’s success is extraordinary in the light of India’s failed efforts to turn its much-treasured traditional medicine into widely-useful therapies. While chemicals sourced from Chinese herbs such as huperzine A (treats memory dysfunction) and paeoniflorin (treats cardiovascular disease) have successfully undergone rigorous clinical trials and are set to find wider use soon, none of India’s Ayurvedic medicines have reached that stage.
The plant- and animal-based treatments of traditional medicine contain hundreds of chemicals, which can vary hugely in their amounts from one batch to another. If it works, there is no understanding why it worked or whether it will work again. The rigor of clinical trials, which allows for development of replicable results, forces researchers to find the active ingredient from a natural source that shows the most promise. The story of artemisinin is one where Tu and her colleagues managed to marry the knowledge of Chinese traditional medicine with the rigors of modern medicine.
Traditional ingredients, modern drugs
Just because a compound has natural roots and has long been used in traditional medicine is no reason to take it lightly.
You might remember that in 2004, the FDA actually banned ephedra-containing dietary and performance-enhancing supplements. They’d been the cause not only of serious side effects but also several deaths. The ban remains in effect in the US despite a court challenge from ephedra manufacturers. Related drug ephedrine, however, is used to treat low blood pressure and is a common ingredient in over-the-counter asthma medicines.
As for Realgar, its toxicity was well-known in both ancient Greece and Chinese antiquity. In Chinese medical thought, though, skillfully administered toxins may also be powerful antidotes for other toxins. Realgar thus continues to be used in Chinese medicine as a drug that relieves toxicity and kills parasites. Applied topically, it treats scabies, ringworm and rashes on the skin’s surface; taken internally, it expels intestinal parasites, particularly roundworms.
Although biomedicine does not currently use Realgar or its related mineral arsenicals in treatments, Chinese researchers have been studying their anticancer properties for some time now. In 2011, a Chinese researcher at Johns Hopkins University, Jun Liu (with other colleagues), also discovered that the Chinese medicinal plant Tripterygium wilfordii Hook F (lei gong teng 雷公藤 “Thunder God Vine”) is effective against cancer, arthritis and skin graft rejection.
Tu’s groundbreaking work on artemisinin, in fact, can be seen as the tip of the iceberg of the extensive and global scientific study of pharmacologically active Chinese medicinals, including another successful antimalarial Dichroa febrifuga (changshan 常山) that has roots in the new scientific research on Chinese medicinals in 1940s mainland China.
It was validation of this traditional drug as an antimalarial in the 1940s, in fact, that set the foundation for Chinese leader Mao Tse Tung’s directive two decades later in the late 1960s to find a cure for malaria. Indeed, Tu’s research is best understood within the complex politics and history of top-down support from the Chinese government of Chinese medicine in mainland China during the long durée of the 20th century, and not just in the Maoist period.
Even outside mainland China, though, such research has yielded results. In the 1970s, for example, US and Japanese researchers developed the statin drugs used to lower cholesterol from studying the mold Monascus purpureus that makes red yeast rice, well, “red.”
Empirical evidence of the medical efficacy in the rich Chinese medical archive from centuries earlier similarly influenced the initial direction of this research.
So is this Nobel Prize for Tu’s discovery a signal that Western science has changed how it perceives alternative systems of medicine? Perhaps, but only slightly.
One of the Karolinska Institute panelists acknowledged that there are many sources from which scientists draw inspiration to develop drugs. Among them, we should not ignore the long history of experiences from the past. As he clarified, such sources may be inspirational, but the old herbs found there cannot be used just as they are. Don’t underestimate the sophisticated methods Tu used to extract the active Artemisinin compound from Artemesia annua, another one of the panelists concluded.
So the Nobel Prize is not only acknowledging this complete transformation of a Chinese herb through modern biomedical science into something powerfully efficacious, but also the millions of lives saved because of its successful application worldwide, particularly in the developing world.
But there’s something else that marks Tu as extraordinary vis-à-vis both her two fellow Nobel Laureates for medicine, William C Campbell and Satoshi Ōmura, and her more Western medically oriented colleagues in pharmacology. She embodies, in both her history and her research, what I call medical bilingualism – the ability not only to read in two different medical languages but to understand their different histories, conceptual differences, and, most importantly for this unexpected news, potential value for therapeutic interventions in the present.
This medical bilingualism is a quality that current researchers mining the same fine line between the empirical knowledge of traditional medical traditions and the highest level of modern biomedical science would be lucky to share with Nobel Laureate Youyou Tu.