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          On the trail of ancient cures

          By NICHOLAS ZAMISKA (WSJ)
          Updated: 2006-11-15 12:35

          http://online.wsj.com/public/article/SB116354914377323235-NnLFTPz5b_zTWYbbnant_Wwm788_20061121.html?mod=regionallinks

          SHANGHAI -- On an afternoon in Xinjiang province in China's remote and mountainous west, botanist Shen Jingui was searching for a snow lotus, a grayish-white flower used for centuries in Chinese medicine to alleviate the symptoms of premenstrual syndrome. He spotted the plant on a rock ledge and shimmied across to pick it. He slipped and plunged some 30 yards, slamming into rocks on the way down.

          When he regained consciousness, local farmers were putting him on a horse to take him to the nearest health clinic, several hours away. "I was very scared," he recalls of the incident, "but I was happy to collect the material."

          Mr. Shen, head botanist for the Shanghai Institute of Materia Medica, a government-funded laboratory, has spent three decades trekking across China and going to great lengths to ferret out rare plants and herbs traditionally used in treatments for ailments ranging from aches and pains to cancer.

          His bag of plants has captured the interest of Swiss drug giant Novartis AG, which since 2000 has invested several million dollars in a venture with SIMM. Last month, Novartis struck a similar deal with the Kunming Institute of Botany, an organization that works with traditional remedies in the country's southwestern Yunnan province. Earlier this month, Novartis announced it will invest about $100 million in its own pharmaceutical research-and-development center in Shanghai.

          Facing soaring costs in developing new drugs and a limited pipeline of promising candidates, Novartis hopes that traditional Chinese medicines will hold the secrets for a new generation of blockbusters to fight diseases such as Alzheimer's. While Novartis isn't the only multinational drug company seeking to tap traditional Chinese cures -- French drug maker Servier also has a collaboration with SIMM -- Rachel Lee, a senior manager at Boston Consulting Group in Shanghai, says "no other major pharma has gone further than Novartis" in this area.

          The collaboration between East and West on drug development is in many ways an unlikely one. Chinese and Western specialists approach pharmacology from very different angles. For centuries, Chinese doctors have tinkered with different mixtures of medicines, guided in part by trial and error, to see which ones are most effective. Working with that body of knowledge, they operate on the assumption that the traditional remedies work, even if by Western scientific standards it's not completely clear why. Chinese doctors "know it will cure people, but they don't know what target it hits," says Shen Jingkang, a professor at SIMM.

          In contrast, researchers at Western pharmaceutical companies often begin the search for a drug by identifying a target, and then look for a chemical compound that has the desired effect. If they do find a drug that works, they usually understand the mechanism behind it. That helps in refining the compound to make it more effective and in convincing regulatory authorities such as the U.S. Food and Drug Administration that the medicine is safe and effective.

          Novartis hopes to isolate the particular compounds active in the Chinese traditional medicines by testing the raw extracts from plants collected by Mr. Shen and fellow botanists.

          "There are so many compounds in nature, from the seas to the jungles, it's very difficult to know where to start," says Paul Herrling, the head of corporate research at Novartis. "China has thousands of years' experience of using plants in Chinese traditional medicines. The idea was, why not use the Chinese experience as a kind of filter?"

          Novartis has experienced the potential of Chinese traditional medicines firsthand. The company's malaria drug Coartem stems from a traditional Chinese cure for fever. Mention of the plant, Artemisia annua L. or sweet wormwood, was found in a Chinese medicine book written on silk, unearthed from a tomb of the West Han Dynasty, which began around 200 B.C. Chinese military scientists developed the drug from the plant in the 1970s to treat Chinese soldiers suffering from malaria in Vietnam. In the early 1990s, Novartis struck a deal with the Chinese to purchase the rights to Coartem, a combination of a derivative of the plant and another antimalarial treatment, paying a few million dollars up front and royalties on future sales. Novartis declined to reveal the revenue it makes on the drug, most of which it sells to developing countries at $1 per treatment.

          Since the venture began, Novartis says SIMM has provided around 1,000 natural products to the Swiss drug company's laboratories in Basel. In return, Novartis has agreed to pay SIMM royalties and fees if certain plants yield marketable pharmaceuticals.

          So far, nine of the compounds have shown particular promise against specific disease targets, and two have been selected for further study, according to Dr. Herrling. While those numbers may seem small, the search for drugs using conventional methods is far less fruitful, he says. The investment is also small when stacked up against Novartis's typical research-and-development outlays.

          In this particular project, it all goes back to a small group of botanists led by Mr. Shen -- before any research can begin in the lab, they must venture out in the field and find the plant.

          On a recent afternoon at the laboratory in Shanghai, Mr. Shen dried lily bulbs and snow pine branches in small, neat piles on the floor of a sun-soaked hallway. He says he decided on this line of work when, as a student at a Shanghai university, he saw a film about the life of a Chinese botanist. The movie had a sad ending: The botanist dies after an accident collecting plants in a remote area and is carried home on the back of a horse. Nevertheless, Mr. Shen found the story inspiring.

          "I love this career," says Mr. Shen, whose forearms and legs are covered with scars from his arduous trips to collect rare plants.

          One of his most memorable finds was in spring 1999. Shortly after the snows melted, he set out on a weeklong journey to western China's remote Qinghai plateau. He was searching for a certain type of Aweto, an exceedingly rare fungus that Chinese-medicine doctors believe helps strengthen the immune system and fend off cancers. When dried, it looks like a small light-brown caterpillar.

          Mr. Shen hired a guide and set off on horseback into the mountains, armed with descriptions from old Chinese texts. Deep in the forest, he spotted something, and got off his horse for a closer look.

          "We won! We finally got it!" he recalls shouting as he jumped up and down. "I was screaming, 'I found it -- I found it!'" Gathering hundreds of bunches, he put them in his bag for the journey back to Shanghai.



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