NYT: Tu Youyou

My note: I's taken by surprise with these two articles, reporting in details about Ms. Tu Youyou and her work - history, key steps, and her impact. Some I've never heard about in Chinese newspapers - Their angle of viewing is fascinating.check it out, below.

Tu Youyou in the 1980s. Dr. Tu, 84, on Monday became the first citizen of the People’s Republic of China to win a Nobel Prize in the sciences, for discovering artemisinin, a drug that is now part of standard therapy.

BEIJING — During the upheaval of China’s Cultural Revolution in the 1960s, when many of the country’s Western-trained scientists were shunned and persecuted, the government had an urgent scientific problem that needed attention.

North Vietnam, an important ally that was in the middle of war with the United States, had asked for a way to reduce the deaths of its soldiers from malaria, which had become resistant to the drug chloroquine. Malaria was also killing large numbers of people in southern China.

Mao Zedong set up a secret military project, Project 523 — named after its starting date, May 23, 1967 — to find a solution. But China’s top expert in the field of malaria research, like legions of other Chinese in this time of high political turmoil, had been labeled a “rightist” and shunted aside.

After making little headway on the problem, the government turned to the Academy of Traditional Chinese Medicine in Beijing, and to a little-known scientist, Tu Youyou, who had studied both Western and Chinese medicine — and who found the solution in traditional Chinese healing.

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Dr. Tu, 84, on Monday became the first citizen of the People’s Republic of China to win a Nobel Prize in the sciences, for discovering artemisinin, a drug that is now part of standard antimalarial regimens. She shared the Nobel for medicine or physiology with two scientists who also developed antiparasitic drugs.

Dr. Tu, through the Institute of Chinese Materia Medica at the Academy of Chinese Medical Sciences where she works, issued a statement about the value of artemisinin and traditional Chinese medicine.

“Artemisinin is a gift for the world’s people from traditional Chinese medicine,” the statement said.

Two Chinese-born scientists had previously been awarded the Nobel in physics, but only after making their careers in the United States and becoming American citizens. The Chinese government has long wanted a Nobel in the sciences for the sake of prestige and as a confirmation of the quality of its education system.

The Chinese government and state-run news media celebrated Dr. Tu’s prize as an acknowledgment of the rising strength of Chinese science as well as a vindication of the value of traditional Chinese medicine. But some scientists and commentators also said that until now, China’s scientific establishment had treated Dr. Tu somewhat dismissively.

Prime Minister Li Keqiang said that Dr. Tu’s Nobel “was an expression of the prosperity and progress of Chinese science, and of the huge contribution that Chinese traditional medicine and pharmacy has made to the health of humankind.”

But Dr. Tu had been denied a place as an academician in China’s highest honorary body for scientists, apparently because of her lack of foreign training and a doctoral degree, other commentators noted.

“I think that Tu Youyou’s prize should lead to deeper reflection about China’s scientific efforts,” Wang Yuanfeng, a professor in Beijing said in an online commentary. “There are many problems in the institutions and mechanisms of scientific work in China.”

At the start of her research for Project 523, Dr. Tu, then 39, was sent to Hainan Island, in the southernmost region of China, to see how the disease was affecting the population. Her husband had been purged during the Cultural Revolution, and she put her 4-year-old daughter into a nursery. Her visit to Hainan was the start of a decade of work, she told New Scientist in an interview in 2011.

She visited traditional medical practitioners across China, and from those conversations, compiled a notebook, “A Collection of Single Practical Prescriptions for Anti-Malaria.” Among 2,000 traditional Chinese recipes, she said, one compound was found to be effective: sweet wormwood, or Artemisia annua, which was used for “intermittent fevers,” a hallmark of malaria.

In the interview, Dr. Tu told New Scientist that she reread a particular recipe, written more than 1,600 years ago in a text titled “Emergency Prescriptions Kept Up One’s Sleeve.” The directions were to soak one bunch of wormwood in water and then drink the juice.

But Dr. Tu said she realized that her method of preparation — boiling the wormwood — probably damaged the active ingredient. So she made another preparation using an ether-based solvent, which boils at 35 degrees Celsius, or 95 degrees Fahrenheit. When tested on mice and monkeys, she said, it proved 100 percent effective.

After the successful animal tests, Dr. Tu volunteered to be the first human subject, along with two colleagues. Satisfied that she had suffered no ill effects, she conducted clinical trials with patients.

“We had just cured drug-resistant malaria,” Dr. Tu told New Scientist. “We were very excited.”

Ten years after Mao founded Project 523, her work was published, though anonymously.

Western aid agencies did not take advantage of artemisinin for decades, even after its effectiveness was established. Older drugs were cheaper, but resistance to them was growing and some experts said the delay endangered lives.

The Nobel is not the first recognition for Dr. Tu’s work. In 2011, when she won the Lasker Award for clinical medical research, which named her the discoverer of artemisinin, some Chinese and Western malaria experts protested. China Network/Reuters

The Nobel is not the first recognition for Dr. Tu’s work. In 2011, when she won the $250,000 Lasker Award for clinical medical research, which named her the discoverer of artemisinin, some Chinese and Western malaria experts protested.

Dr. Nicholas J. White, a prominent malaria researcher at Oxford, said that others involved in the research equally deserved the honor. He suggested that the clinical trial leader, Dr. Li Guoqiao, and a chemist, Li Ying, had contributed just as much. A malaria researcher from Hong Kong, Dr. Keith Arnold, agreed.

But Dr. Tu said in an interview that she had done the decisive work. As the leader of a small team within the large Project 523, she was the first to isolate the active ingredient, and the one who had thought of using ether to extract it rather than the boiling method, she said.

The Lasker citation had noted that the research under Project 523 was collaborative. In 1978, she was singled out to accept an award from the Chinese government to Project 523.

By all accounts, Dr. Tu, who was born in Ningbo, a port city in the province of Zhejiang, is modest and shuns the limelight. She was born in 1930, the only daughter among five children, and was admitted to the Beijing Academy of Medical Sciences. She said she was “very lucky” to go to university as a woman, according to a blog post by Songshuhui, a nongovernmental organization focused on writing about science.

New Scientist described Dr. Tu as diminutive, with wisps of black curls, and passionate about her work. In 2008, a Phoenix television reporter described meeting her in her office in central Beijing, where there was an old couch and barely any heating. A phone and a refrigerator for storing medicines were the only modern touches, the reporter said.

Some analysts have said that Chinese scientists have not had the stability and long-term funding needed to establish a tradition of excellence in research. The lack of a Nobel Prize for science has been particularly galling in recent years, as the government has tried to emphasize that China can be as innovative as the West in the technology and medical sectors.

Liu Xiaobo, the Chinese writer, dissident and literary critic, was awarded the Nobel Peace Prize in 2010, the first Nobel of any kind to be given to a citizen of China. Mr. Liu was serving an 11-year prison sentence for “subversion of state power” at the time of the designation, and he remains in prison. The Chinese novelist Mo Yan won the Nobel for literature in 2012.

Despite her age, and some health problems associated with osteoporosis, Dr. Tu has continued to work, said her son-in-law, Lei Mao, who works at a pharmaceutical company in North Carolina. He said Dr. Tu lives quietly in Beijing with her husband, an engineer, and works on scientific projects on a part-time basis.

MADE TO ORDER Mao Zedong, center, demanded that Chinese scientists act when a malaria strain felled North Vietnamese troops. Agence France-Presse — Getty Images

The Chinese drug artemisinin has been hailed as one of the greatest advances in fighting malaria, the scourge of the tropics, since the discovery of quinine centuries ago.

Artemisinin’s discovery is being talked about as a candidate for a Nobel Prize in Medicine. Millions of American taxpayer dollars are spent on it for Africa every year.

But few people realize that in one of the paradoxes of history, the drug was discovered thanks to Mao Zedong, who was acting to help the North Vietnamese in their jungle war against the Americans. Or that it languished for 30 years thanks to China’s isolation and the indifference of Western donors, health agencies and drug companies.

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Now that story is coming out. But as happens so often in science, versions vary, and multiple contributors are fighting over the laurels. That became particularly clear in September, when one of the Lasker Awards — sometimes called the “American Nobels” — went to a single one of the hundreds of Chinese scientists once engaged in the development of the drug.

LATE BLOOMER Sweet wormwood provides artemisinin, discovered decades ago in China. Luigi Rignanese

Mao’s role was simple.

In the 1960s, he got an appeal from North Vietnam: Its fighters were dying because local malaria had become resistant to all known drugs. He ordered his top scientists to help.

But it wasn’t easy. The Cultural Revolution was reeling out of control, and intellectuals, including scientists, were being publicly humiliated, forced to labor on collective farms or even driven to suicide. However, because the order came from Mao himself and he put the army in charge, the project was sheltered. Over the next 14 years, 500 scientists from 60 military and civilian institutes flocked to it.

Meanwhile, thousands of American soldiers in Vietnam were also getting malaria, and the Walter Reed Army Institute of Research began its own drug hunt. That effort ultimately produced mefloquine, later sold under the brand name Lariam.

While powerful, mefloquine has serious drawbacks, including nightmares and paranoia. In 2003, dozens of American Marines in Liberia got malaria after refusing to take pills because of military scuttlebutt that several Special Forces soldiers who killed their wives after returning home from Afghanistan in 2002 had been driven insane by the drug.

China’s effort formally began at a meeting on May 23, 1967, and was code-named Project 523, for the date.

Researchers pursued two paths. One group screened 40,000 known chemicals. The second searched the traditional medicine literature and sent envoys into rural villages to ask herbal healers for their secret fever cures.

One herb, qinghao, was mentioned on tomb carvings as far back as 168 B.C. and praised on medical scrolls through the centuries, up to the 1798 Book of Seasonal Fevers. Rural healers identified qinghao as what the West calls Artemisia annua, or sweet wormwood, a spiky-leafed weed with yellow flowers.

In the 1950s, officials in parts of rural China had fought malaria outbreaks with qinghao tea, but investigating it scientifically was new. It also had at least nine rivals from traditional medicine with some anti-malarial effects, including a pepper.

In the lab, qinghao extracts killed malaria parasites in mice. Researchers tried to find exactly which chemical worked, which plants had the most, whether it could cross the blood-brain barrier to fight cerebral malaria, and whether it worked in oral, intravenous and suppository forms.

Outmoded equipment slowed research. But by the 1970s it was known that the lethal chemical, first called qinghaosu and now artemisinin, had a structure never seen before in nature: In chemical terms, it is a sesquiterpene lactone with a peroxide bridge. Trials in 2,000 patients showed that it killed parasites remarkably rapidly.

However, the body eliminated it so fast that any parasites it missed made a comeback. So scientists began mixing it with slower but more persistent drugs, creating what is now called artemisinin combination therapy. (One new combination includes mefloquine.)

A 2006 history of the project by Zhang Jianfang, its former deputy director, contains some gripping details: petty disputes between rivals, Cultural Revolution street fighting that forced one laboratory into a basement, project doctors’ living on brown rice and vegetables as they did clinical trials in remote villages in China’s tropical southern mountains, and other doctors’ hiking the Ho Chi Minh Trail with the Vietcong.

Mao died in 1976; Project 523 was officially disbanded in 1981, though clinical work continued.

In 1979, Dr. Keith Arnold, a malaria researcher in Hong Kong who had helped the Army develop mefloquine, wangled his way into China, hoping to test his drug there. He met Dr. Li Guoqiao, who was testing artemisinin variants. They decided to try head-to-head trials, and the Chinese mystery drug beat his, Dr. Arnold said.

Soon, World Health Organization scientists asked for articles from China’s medical journals, the first of which had been published in 1977, in response to reports that a Yugoslav chemist was experimenting with wormwood.

In 1982, The Lancet had an article by Chinese researchers. It won a prize, but the check, in British pounds, could not be cashed in China.

EARLY CURE An illustration from the 1941 Bulletin of the History of Medicine depicted the idea that quinine’s source, the cinchona tree, was named for a countess in Peru

Shortly thereafter, Dr. Arnold said, Walter Reed scientists found wormwood growing on the banks of the Potomac and extracted artemisinin. Nonetheless, the drug languished. The W.H.O. did not endorse it until 2000, and it was not widely available until 2006.

The reasons for that delay are disputed. China was in political disarray. Different labs in and outside China were working on derivatives. Patent law had vanished under communism, and China never took out Western patents, so there was no way a major drug company could get a monopoly and make big profits. Malaria was a disease of the poor, and today’s big donor funds did not exist.

Aid agencies could not buy drugs that were not W.H.O.-approved. For years, Dr. Arnold said, he tried to get permission for his Chinese collaborators to do clinical trials in Thailand and Vietnam, but the W.H.O. stalled. (As a United Nations agency, it is rarely bold, but the 1990s were a decade of particularly low morale and constant infighting.)

As nearly one million African children a year died, Dr. Arnold denounced its indecisiveness as “genocidal.”

The American military stuck with mefloquine, despite its expense. As late as 2002, as Doctors Without Borders clamored for artemisinin, an adviser to the United States Agency for International Development dismissed it in an interview with The New York Times as “not ready for prime time” and defended chloroquine and other old, cheap drugs even though resistance to them was widespread.

A Swiss company, Novartis, finally broke the logjam. It bought a new Chinese patent on a mix of artemether, an artemisinin derivative, and lumefantrine, another Chinese drug, and took out Western patents, planning to sell it under the name Riamet at high prices to tourists and militaries; in 2001, it agreed to sell it nearly at cost to the W.H.O. under the name Coartem.

The money to buy the drug on a large scale became available with the creation of the Global Fund to Fight AIDS, Tuberculosis and Malaria in 2002 and the Bush administration’s introduction of the President’s Malaria Initiative in 2005. Now, about 150 million doses of several combinations are bought for poor countries each year.

With that victory, surviving Project 523 scientists and some outsiders began vying for credit. In 1996, a Hong Kong science foundation recognized 10 team leaders. In 2009, Zhou Yiqing got the European Patent Office’s “Inventors of the Year” award for Coartem.

In September, the $250,000 Lasker Award for clinical medical research was given to Dr. Tu Youyou, former chief of the Institute of Chinese Materia Medica in Beijing. The Lasker committee named her “the discoverer of artemisinin.”

Some Chinese and Western malariologists were outraged.

Dr. Nicholas J. White, a prominent Oxford malaria researcher, said it was “not fair to credit this discovery to one individual”; he named others he considered equally deserving, including the clinical trial leader, Dr. Li, and a chemist, Li Ying.

Dr. Arnold, whose work with Dr. Li was mentioned in the Lasker citation, agreed. Richard K. Haynes, a malaria researcher and historian at the University of Science and Technology in Hong Kong, called naming one inventor “a travesty.”

The Lasker Foundation declined to comment, other than to note that Dr. Tu’s citation mentioned that Project 523 was a large collaborative effort.

In an interview before the ceremony, Dr. Tu, 81, argued that she deserved it because her team had been the first to isolate qinghao’s active ingredient while other teams worked on the wrong plants.

Also, after rereading a manuscript by Ge Hong, a fourth-century healer, prescribing qinghao steeped in cold water for fever, she realized that boiling, the typical extraction method, was destroying the active ingredient. She switched to ether, and qinghao became the first plant extract 100 percent effective at killing malaria in mice.

And before human testing began, Dr. Tu said, she and two colleagues took it themselves to make sure it was not toxic.

Before the West even heard of the drug, she said, she was one of the four anonymous authors of the

initial 1977 paper, and in 1978, she was chosen to accept the Chinese government’s overall award to Project 523.

However difficult winnowing the field would prove, the Nobel Prize committee would be forced to do it anyway. The Nobel rules specify no more than three winners. And no posthumous prizes, either — meaning Mao would be out of the question.

A version of this article appears in print on January 17, 2012, on page D1 of the New York edition with the headline: For Intrigue, Malaria Drug Gets the Prize. Order Reprints|Today's Paper|Subscribe

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