Nobel Prize for Chinese traditional medicine expert who developed malaria cure

Developed for Communist troops fighting in the Vietnam War, Tu Youyou's treatment was major breakthrough in global fight against malaria

Tu Youyou, right, working with Prof Lou Zhicen in the 1950s (Xinhua via AP)

A Chinese scientist who pioneered a malaria treatment for Communist troops fighting America 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.

Pharmacologist Tu Youyou attends an award ceremony in Beijing in 2011 (Reuters)

The other two winners are Irish-born William Campbell and Japan's Satoshi Omura, who developed avermectin, derivatives of which are used to treat river blindness and elephantiasis.

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“The two discoveries have provided humankind with powerful new means to combat these debilitating diseases that affect hundreds of millions of people annually,” the Nobel committee said. “The consequences in terms of improved human health and reduced suffering are immeasurable.” Ms Tu's work created the drug artemisinin, which now forms part of the mainstay of malaria treatment in Africa. Used in tandem with insecticide-impregnated bednets, it is credited with helping to halve malaria mortality rates worldwide in the last 15 years.

Yet for decades, its exact origins remained unknown - as did the remarkable story of its creator, which could easily form the script for a Hollywood movie.

It begins in 1969, when Ms Tu - then a mid-career scientist - was recruited to Chairman Mao’s top-secret Project 523. Its task was to investigate cures for malaria, which in the 1960s was developing resistance to existing drugs such as chloroquine.

An illustration describing Ms Tu's work displayed during the press conference announcing the winners of the Nobel Medicine Prize (AFP)

It was also taking a heavy toll on the armies of China's communist ally, North Vietnam, who were losing more soldiers to malaria in their jungle warfare against US troops than they were to American bombs or bullets.

At the time, the quest for an effective alternative to chloroquine had baffled the world's scientific community, which had tested some 240,000 different compounds without success.

It was then that Ms Tu, who had studied both Chinese and Western medicines, began reviewing some 2,000 ancient herbal recipes from the Academy of Traditional Chinese Medicine in Beijing.

One of them, written in a 1,600 year old text called "Emergency Prescriptions Kept Up One’s Sleeve”, recommended soaking sweet wormwood in water and then drinking the resulting juice.

Tried out first on mice and monkeys, it proved highly effective, although it then had to be tested to see if was harmful of humans. As head of the research group, Ms Tu volunteered to be the first test subject herself. Subsequent trials on labourers who had caught malaria while working in dense forests proved that it could banish malarial parasites from the bloodstream within just over a day.

While such a discovery might have won Ms Tu considerable fame in the West, in Maoist-era China, she gained no kudos at all. At the time, scientist and intellectuals were viewed with suspicion at best, with Ms Tu’s husband having been banished to the countryside, and the idea of an individual scientist claiming credit for a breakthrough sat uneasily with Maoist notions of collective endeavour. Tu was not even allowed to publish her findings until 1977, a year after Mao's death, and even then, her contribution remained anonymous.

News of her work only emerged in the West when Louis Miller, an American research scientist, met Chinese scientists in 2005 and chanced to ask who had discovered artemisinin. Intrigued at the blank stares that his question produced, he began investigatingin detail.

An illustration describing the research on roundworm infections by Nobel Medicine Prize winners (AFP)

Various official paperwork - much of it once secret - revealed it to be Ms Tu, who by then was living in a shabby apartment block in Beijing. At the time, she was known by colleagues as "The Professor of the Three Nos", since she had no post-graduate degree, was not a member of any national academy, and had no foreign research experience.

While Ms Tu received America’s top medical accolade, the Lasker award, in 2011, this is the first time that any expert in Chinese traditional medicine has been awarded a Nobel.

"This is indeed a glorious moment," said Li Chenjian, a vice provost at Peking University. "This also is an acknowledgement to the traditional Chinese medicine, for the work began with herbal medicine."

Artemisinin-based drugs are now routinely used by pharmaceuticals giants like Sanofi and Novartis in the fight against malaria, which still kills half a million people a year.

It is not yet clear whether the ageing Ms Tu will attend the Nobel annual award ceremony, which takes place on December 10. Each winner will also get a diploma and a gold medal.

AT A GLANCE

Nobel Prizes 2015

Pic: AP/Fernando Vergara

Nobel Prize for Medicine

Awarded jointly for discoveries that assisted the treatment of infections caused by roundworm parasites, and Malaria

• William C Campbell & Satoshi Omura
• Youyou Tu

Nobel Prize in Physics

Awarded jointly "for the discovery of neutrino oscillations, which shows that neutrinos have mass"

• Takaaki Kajita and Arthur B. McDonald

Nobel Prize in Chemistry

Awarded jointly to three people for "mechanistic studies of DNA repair"

• Tomas Lindahl, Paul Modrich and Aziz Sancar

Nobel Peace Prize

• To be announced 9 October

Prize for Economics Science

• To be announced 12 October

Nobel Prize in Literature

• Awarded to the Belarusian author Svetlana Alexievich

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Discovery of DNA Repair Methods Nails 2015 Chemistry Nobel Prize

Three scientists who found ways that cells fix damaged DNA—staving off cancer and other diseases—have won this year's prize There ...

Discovery of DNA Repair Methods Nails 2015 Chemistry Nobel Prize

Three scientists who found ways that cells fix damaged DNA—staving off cancer and other diseases—have won this year's prize

There are three reasons we are not constantly riddled with cancer, and today the scientists who discovered those reasons—three ways that cells repair damaged DNA that can ruin bodies--won the 2015 Nobel Prize for Chemistry.

This morning The Royal Swedish Academy of Sciences announced the coveted prize is going to Tomas Lindahl from the Francis Crick Institute and Clare Hall Laboratory in Hertfordshire, England; Paul Modrich from the Howard Hughes Medical Institute and Duke University School of Medicine in North Carolina in the United States; and Aziz Sancar from the University of North Carolina in Chapel Hill, also in the U.S. “I know, over the years, that I’d been mentioned for the prize,” Lindahl said in a telephone call to the academy. “But hundreds of people get considered every year so I feel very lucky.”

He and the other two researchers, working independently over the last 40 years, described three different mechanisms that create errors in DNA—the molecule that controls cell behavior—and the different ways that chemical and biological processes fix many of these problems.

“All forms of cancer start with DNA damage,” said biochemist Claes Gustafsson, one member of the Nobel chemistry committee. “If you do not have DNA repair, we would have a lot more cancer. That’s how important this is.” He added that the repair techniques let us understand how cigarette smoke, sunlight, and even mundane substances like water can damage DNA and point to ways that the damage can be rectified.

It is not just about cancer, Diane Grob Schmidt, president of the American Chemical Society, told Scientific American in an interview. “The understanding that we have of these mechanisms help us design drugs to repair all sorts of DNA errors,” she said. There are also several genetic diseases caused by the inability of cells to fix DNA properly, for instance, and work on the repair methods aids understanding of these ailments and how to treat them.

The discoveries illustrate the crucial and central role of chemistry, Schmidt added. “These mechanisms are fundamentally about the making and breaking of chemical bonds,” she said.

Scientists used to believe that DNA molecules were extremely stable. After all, they had to reliably transmit genetic information from generation down to generation. Then in the 1970s Lindahl demonstrated that the neat double helix and its components constantly decays. Every day, hundreds of those components, the DNA building block chemicals abbreviated as A, T, C, and G, get knocked out of their places. If the process continued unabated, the development of life on Earth would have been impossible. This insight led Lindahl to discover a series of enzymes and reactions, called base excision repair, which constantly works to fight this decay. The C building block, for instance, is repeatedly broken down into another molecule that should not be in DNA. The enzymes Lindahl found identify that broken molecule and rebuild it into a C.

Sancar found that cells use another technique to repair damage to DNA caused by ultraviolet light, the same thing that gives you a sunburn. This DNA fix is called nucleotide excision repair. People born with defects in this repair system will develop skin cancer if they are exposed to sunlight. Excision enzymes cut out the DNA lesions. The cell also uses this repair system to correct DNA damage people get after they are born, when they encounter mutagenic substances

Finally, Modrich found out how a cell corrects errors that occur during a vital biological process: Cell division, when DNA is replicated. This copying process is supposed to produce identical strands of DNA but often there are stretches of the new stand that do not match up. The set of cellular chemicals that Modrich found, a complex called mismatch repair, scans the strands and fixes them, reducing the error frequency during replication by about a thousand times during each replication cycle. (Modrich co-authored a Scientific American article on genetic engineering.)

“Without all of these repair mechanisms.” Lindahl said, “we would not be long-lived.” For finding them, he and the two other scientists will split $1 million dollars in three equal shares.
- By Josh Fischman | Scientific American







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