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Basic Biology

Of all these efforts, perhaps none is being watched as closely as Novartis’s. Vonderscher, an Alsatian-born biochemist who trained in Lyon and has been with Novartis (or one of its predecessors, Ciba-Geigy) for nearly 25 years, has a craggy, bearded, Gallic face that seems to be animated by a permanent, if controlled, sense of urgency. What Novartis and other pharmaceutical companies are trying to do right now, he explained, is take a hard look at biotechnology and selectively adopt those technologies “that will help us in boosting our pipeline and our drug discovery processes.” It’s not a simple task, he said, “because, especially five years ago, there were a lot of interesting things, but there was a lot of crap in the biotech world at the same time.” Despite his skepticism about the lack of discipline in the less mature biotech industry, however, Vonderscher stressed that it has much to offer the pharmaceutical industry. “We need the risk-taking of biotechs,” he said.

Indeed, in shifting the heart of its R&D efforts from Basel, Switzerland, to Cambridge, Novartis is in effect abandoning technology roots that stretch back several centuries through its predecessor companies, Sandoz and Ciba-Geigy. The hope is that the multibillion-dollar gamble in making the move will pay off in an approach that will, in Vonderscher’s words, allow researchers to be “more clever”-that is, allow the company to identify problems (and possibilities) and make shrewder decisions earlier in the drug discovery process. Part of that added cleverness derives from new technologies based on an increased understanding of biology, and part from a change in corporate culture.

The culture of drug discovery at Novartis began to change in 2002, when the company hired Mark C. Fishman, head of cardiology at Massachusetts General Hospital and a professor at Harvard Medical School, to lead all of its research and development efforts. Fishman is a respected cardiologist who also brings blue-ribbon credentials as a basic researcher studying the genetic and molecular mechanisms of cardiac development. He immediately instilled the ethic that a more academic-style understanding of biological processes and pathways could speed up the drug discovery process-even though basic research is often viewed as slow, tedious, and curiosity-driven rather than market-driven.

Key to Novartis’s new enterprise is a shift from focusing on particular molecules as targets to looking at biological pathways-interconnected sequences of biological events that together affect the course of a disease. Teasing apart biological pathways used to be a purely academic pursuit, and it can be a laborious and time-consuming process, but Novartis believes that the new molecular-biology tools will sharpen the understanding of the pathways and increase the odds of making unexpected discoveries. “I call it guided serendipity,” said Vonderscher.

Novartis has paid a great deal of attention to creating an infrastructure for this guided serendipity, and has done so very rapidly. “This was an empty shell in the summer of 2002,” Vonderscher said, walking through the lobby of the new research headquarters in Cambridge. Although there was a hectic, unsettled feel to the place-Vonderscher’s office still had boxes waiting to be unpacked, and many labs remained vacant-the research and development staffs were rapidly ramping up; every other Monday morning, management circulated a list of another ten or so new employees. The facility is slated to house a total of about 400 researchers by the end of the year.

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Tagged: Biomedicine

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