In 2002, Mark Fishman walked into a glass building in Cambridge with an unusual assignment: to turn the Swiss pharmaceutical company, Novartis, into the world’s greatest therapeutics research firm. More unusually still, Fishman was — at least on paper — precisely the wrong man for the job.
The Harvard cardiologist had spent his career studying zebrafish hearts and teaching medical students. He had no pharmaceutical experience and no business training. And yet, Daniel Vasella — the physician-turned-CEO who had overseen the merger of Ciba-Geigy and Sandoz to form Novartis back in 1996 — had just handed Fishman billions of dollars to reignite the company’s internal drug discovery programs.
The timing was inauspicious. Fishman was recruited at a moment when pharmaceutical R&D productivity was halving every nine years. In the early 2000s, a dollar of research produced only a fraction of the drugs it generated in 1950. The pharmaceutical industry at large was adapting by acquiring innovative drugs, rather than discovering them in-house. Pfizer was purchasing companies left and right. Merck was cutting research budgets. Even Roche, with its legendary research heritage, was turning to external partnerships. The consensus was absolute: internal R&D was finished.
But Fishman didn’t see it that way.
What emerged from his unlikely hire over the next fourteen years would systematically violate many principles of modern pharmaceutical management. But the Novartis Institutes for Biomedical Research (NIBR) would achieve something the pharmaceutical industry had considered impossible: Under Fishman’s tenure, 65 percent of the company’s new drug approvals came from internal discovery. Many of these drugs would go on to earn the company tens of billions in revenue. And then, in 2016, Novartis began dismantling it.
This is the story of an academic cardiologist and a CEO who showed that curiosity‑driven research can rival the best work in pharma, and why even that success could not shield their institute from unforgiving market forces.
The Bronze Age Collapse of Pharma
When Daniel Vasella announced in 2001 that Novartis would create the largest corporate research organization in the industry, the timing couldn’t have been worse.
The late 1990s brought a crisis of confidence in pharmaceutical safety, effects that continued into the early 2000s. Twelve prescription drugs, or roughly 5 percent of all marketed medicines, vanished from pharmacy shelves between 1997 and 2001. Most were withdrawn due to safety concerns. The popular “fen-phen” weight-loss combo, for example, was found to damage heart valves, thus ending the first weight-loss drug craze.
Then, in September 1999, eighteen-year-old Jesse Gelsinger died during a gene therapy trial, the first person publicly identified to have died from an experimental gene treatment. His death shook regulators so much that the once-hyped gene therapy sector collapsed. The fallout continued for decades.
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