Youyou Tu

In 2015, pharmacologist Youyou Tu (born 1930) became the first Chinese researcher to earn a Nobel Prize in a scientific discipline for studies carried out in China. Tu discovered artemisinin and perfected ways to extract this substance from the sweet wormwood plant. Her accomplishment led to the development of a new drug to treat malaria, drastically reducing mortality rates across the globe for those infected with the mosquito-borne illness.

Chinese pharmacologist Youyou Tu won the Nobel Prize in Physiology/Medicine, sharing the honor with researchers William Campbell and Satoshi Ōmura, who uncovered a new drug to treat roundworm infections. The drugs discovered by both camps revolutionized treatment against parasitic infections. “This is one of those Nobel Prizes for drugs that have truly impacted hundreds of millions of people, no exaggeration,” U.S. immunologist Anthony Fauci told Science News shortly after the Nobel announcement.




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Studied Chinese, Western Medicine

Tu was born December 30, 1930, in Ningbo, Zhejiang, China. Of five children in the family, Tu was the only girl, and she was named “Youyou” in reference to an ancient Confucian Chinese text in The Book of Songs that mentions the “you-you” mew of baby deer. Tu's family valued education and sent her to distinguished private schools. At age 16, she contracted tuberculosis and spent two years out of the classroom recuperating. Prompted by the experience, she decided to pursue medical research. Following high school, Tu earned admittance to the pharmacy department at Peking University's medical school; during her time there, the medical school split from Peking University and became known as Beijing Medical University. At the school, Tu received training with a solid foundation in Western theory. Some of her instructors had trained in Western medicine.

After graduating from Beijing Medical University in 1955, Tu remained in the city and found work at the Academy of Traditional Chinese Medicine (now known as the China Academy of Chinese Medical Sciences). Her first project involved an investigation of Lobelia chinensis. Also known as creeping lobelia, the plant was used to treat a parasitic flatworm that caused schistosomiasis, or “snail fever,” a disease most common in developing areas of Africa, Asia, and South America. Based on this investigation, Tu published her first professional research paper in 1958, sharing co-author credits with her supervising professor, Lou Zhicen.

From 1959 to 1962, Tu took part in a Ministry of Health–sponsored training program aimed at teaching Chinese medical practitioners the art of blending Western medicine with Traditional Chinese Medicine (TCM). At the time, medical advances were lagging in China and the nation had more TCM practitioners than Westerntrained physicians. The goal of the program was to provide cross-training so that medical staffers and researchers would better understand and utilize the two approaches as complementary practices. Traditional Chinese Medicine has its roots in ancient China and has developed over thousands of years. Practitioners of TCM treat health issues with herbal medicines and mind-body practices like tai chi and acupuncture. As Tu learned more about Chinese medicine, she came to understand that the processing of the herbal compounds used in TCM was very important because improper processing could alter the properties and potency of the medicine.

Headed Malaria Research Team

During the late 1960s, malaria was a prevalent problem in tropical areas of the world. An infectious disease spread by mosquitos, malaria's symptoms include headache, vomiting and fatigue and periods of shiver-inducing chills followed by fever. Left untreated, it can cause neurological issues, seizures, and death. For decades, malaria was treated with quinine (derived from cinchona bark) and synthetic quinolones. By the 1960s, however, many malaria parasites had become resistant to those anti-malarial drugs.

The Chinese government had a vested interest in finding a cure. At the time, the country was an ally of North Vietnam, a country that was locked in battle against South Vietnam and its ally, the United States. North Vietnam was losing more soldiers to malaria than to combat. To deal with the situation, the country's leader, Ho Chi Minh, persuaded the Chinese government to launch an investigation into finding a cure for malaria. U.S. soldiers also suffered from malaria infections during the Vietnam war, and during the mid-1960s, researchers at the Walter Reed Army Institute of Research in Washington, D.C., started an investigation into malaria treatment. By 1972, U.S. researchers had screened thousands of compounds but had found no solutions to the problem.

The Chinese government began its malaria research in the 1960s. Chinese leader Mao Tse-tung launched the topsecret program, calling it “Project 523”—which was the date the program started: May 23, 1967. The Chinese government established the National 523 Office to coordinate research. By 1969, Chinese researchers had tested several thousand synthetic compounds but found no cure. At this point, researchers decided to look at Traditional Chinese Medicine to find a remedy.

Tu sent her one-year-old daughter to live with her parents in Ningbo, and her four-year-old daughter went to live with her nursery school teacher. When Tu returned to collect her daughters, the younger one could not recognize her and the older one hid behind her teacher. For Tu, it was just part of the job, part of her duty to her country. “The work was the top priority, so I was certainly willing to sacrifice my personal life,” she recalled to Phil McKenna in New Scientist. “I saw a lot of children who were in the latest stages of malaria. Those kids died very quickly.” The devastation Tu witnessed propelled her forward in her research.

Looked to Ancient Chinese Texts

At the start of her investigation, Tu read through all of the ancient TCM texts she could find. There were several volumes, dating back thousands of years. She scoured the books, looking for references to malaria and remedies used on the disease. Tu found malaria mentioned in a book called Zhou Li, which was written between 1046 and 256 B.C.E. Malaria was also mentioned in The Synopsis of Prescriptions of the Golden Chamber, written between 206 B.C.E. and 220 C.E. She even found a volume titled The Malignant Malaria Guide, published during the Quing dynasty (between 1644 and 1911). Tu also traveled across China to interview TCM practitioners and collect their folkremedy recipes. Within a few months’ time, she had gathered more than 2,000 possible remedies for testing: herbal, animal, and mineral. She compiled these in a 1969 report titled, “Antimalarial Collections of Recipes and Prescriptions,” which highlighted 640 of the options, and sent the publication to other research groups across China to aid in their investigations.

From May 1969 to June 1971, Tu oversaw rodent testing of many of the extracts mentioned in the texts. Nothing worked well. After reviewing the ancient texts once more, she decided to focus on Qinghao, a plant in the Artemisia family that is best known as sweet wormwood. The plant's name references the color green— “qing” in Chinese—because of the dark green leaves of the plant. Tu's research team isolated different compounds in the wormwood and found artemisinin to be effective against malaria. Tests revealed initial promise but results varied.

Once again, Tu went back to the ancient texts and reread different recipes utilizing wormwood. She discovered that Ge Hong's A Handbook of Prescriptions for Emergencies mentioned a cold-temperature method for preparing the wormwood tincture. Ge Hong lived around 300 A.D. His method suggested immersing a handful of the plant in two liters of water, then squeezing out the juice for consumption. Tu's team had been boiling the herb in water to extract the active ingredient, a common preparation in TCM. At this point, it occurred to Tu that heating the wormwood might destroy the curative properties of the plant. She designed new experiments to extract the artemisinin at lower temperatures. She also devised tests to utilize the stems and leaves separately to see which portion of the plant held the densest concentration of the active ingredient. Besides water, Tu designed techniques that used ethanol and ethyl ether to extract the artemisinin.

In October 1971, Tu's team discovered that the Qinghao ethyl ether extract seemed to be most effective in eradicating malaria in rodents. After the drug was tested on monkeys with positive results, Tu's research laboratory got busy producing mass amounts of Qinghao extracts for clinical study. They worked long hours, seven days a week, extracting the active ingredient using household vats. Meanwhile, clinical animal studies continued. In July of 1972, Tu took the medicine herself to check for safety. She and two other researchers ingested the artemisinin in a hospital, where they were monitored for a week. There were no ill effects.

From August to October 1972, Tu's team conducted a study of artemisinin in treating malaria patients in Hainan province. The extract was given to 21 malaria sufferers, although they received different dosing regimens. During treatment, blood samples were draw to keep track of the number of parasites roaming the blood. Each patient recovered. In 1973, researchers conducted another trial, this one using artemisinin tablets, which proved ineffective. Further study revealed that the tablets were too hard and failed to dissolve properly.

A study using artemisinin capsules proved effective. Later studies conducted by Tu focused on the use of dihydroartemisinin, which was found to be more potent than artemisinin. In 1986, the China Ministry of Health issued a drug certificate for artemisinin, and a certificate for dihydroartemisinin was issued in 1992. After the discovery, Tu continued her research, searching for the best species of wormwood to use for the medicine and locating the best regions and growing seasons for the plant.

Received Recognition for Discovery

With China isolated from the Western world, the benefits of artemisinin spread slowly. The World Health Organization approved its use in 2000 and dubbed it an “essential medicine.” As use of the drug spread, so did Tu's fame. In 2011, she and her husband traveled to the United States so she could accept an Albert Lasker Award in recognition of the impact her discovery had on public health. Given annually, Lasker Awards recognize individuals for contributions to medical science. Many recipients go on to win the Nobel Prize—just as Tu did, becoming the first Chinese woman to do so.

Periodicals

Chinese American Forum, October–December 2015.

New Scientist, November 12, 2011, Phil McKenna “Malaria's Nemesis.”

New York Times, October 7, 2015, Jane Perlez, “Answering an Appeal by Mao Led Tu Youyou … to a Nobel Prize.”

Science News, October 31, 2015.

Time, May 2, 2016.

Online

Guardian online (London, England), https://www.theguardian.com/science/ (October 5, 2015), “Tu Youyou: How Mao's Challenge to Malaria Pioneer Led to Nobel Prize.”

Nobel Prize website, http://www.nobelprize.org/ (December 7, 2015), “Artemisinin—A Gift from Traditional Chinese Medicine to the World”(lecture).❑

(MLA 8th Edition)