Drug Development: A Whole New Tack

What does a cardiologist who made his name studying zebra fish -- tiny, striped denizens of the aquarium -- know about the drug industry? Not that much. But that's one reason Novartis CEO Daniel Vasella chose the aptly named Dr. Mark C. Fishman, a 52-year-old Harvard Medical School professor, to head its brand-new, 750,000-square-foot research center in the biotech and academic hotbed of Cambridge, Mass. Vasella is counting on Fishman's impeccable credentials to lure some of the best scientific talent worldwide to work there. "The hiring of Fishman was a real coup for Novartis," says Eric S. Lander, director of the Whitehead-MIT Center for Genome Research in Cambridge.

Fishman has been presented with a make-or-break challenge -- to completely revamp the way Novartis creates new drugs. Traditionally, medicines are developed based on the symptoms of a particular illness, a process that involves a huge amount of trial and error. Fishman plans to use the wealth of information unlocked by the decoding of the human genome to design treatments that target the specific gene malfunction or abnormality that causes a disease. Although many companies are following a similar approach, Fishman believes that Novartis is a step ahead of the competition, thanks to hefty investments in new technologies, such as genomics. "To develop a drug that is both effective and well tolerated, you need to understand the molecular mechanism that causes a disease," he says.

That's where the zebra fish swim into the picture. When Fishman began to experiment on the tiny fish to gain a better understanding of cardiovascular disease in humans, his colleagues were skeptical. But, by introducing mutations into the fish's sperm, Fishman catalogued more than 100 genes related to cardiovascular development -- many of them similar to those found in humans. "His work on zebra fish will open up a multitude of new targets for drugs to treat heart disease," says Joerg Reinhardt, Novartis' head of global development. The Swiss drugmaker plans to boost the number of scientists working on cardiovascular research to more than 200, from 30.

Fishman also will try to develop drugs for diabetes, cancer, and infectious diseases such as hepatitis and AIDS, where there is still massive need. In all, Novartis is sinking $4 billion over 10 years into the Cambridge center, called the Novartis Institutes for Biomedical Research.

Novartis has more than money riding on the man and his research. "With the Cambridge center, Novartis is making a bet that over the next 10 to 20 years it will be possible to have a firm enough understanding of biology to double or triple the paltry success rate of drug development," says Lander. Still, there's a big risk that in the process of revamping its entire research program, Novartis could seriously stall the development of new drugs. Even Fishman is careful to temper his zeal with caution. "There's massive potential, but it won't be realized overnight," he says. In the meantime, he has already drawn up plans to outfit the new center with giant aquariums filled with -- what else? -- zebra fish.

By Kerry Capell in London

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