The Thrill of Defeat

Yet for all that, if the previous occupants of this patch of shoreline had designed and built submarines the way its current denizens develop and test new drugs, whole fleets would have slipped to the bottom without a trace. To help her team deal with the daunting odds that face them every day, Hutson has forged a community of people with a common sense of mission. "You can see how people react to her when she walks the halls," says Richard Leider, Hutson's executive coach. "People love her. This is her family, and she treats them that way."

Pfizer's future may well depend on how well Hutson's "family" manages disappointment. A year ago, the company said it would bring an unprecedented 20 medicines to market by the end of 2006. Pfizer chief Hank McKinnell has staked the company's performance--and mostly likely his career--on the ability of the drug giant's scientists to produce new therapies for treating an array of ills, from epilepsy to nicotine addiction to high cholesterol.

Of the thousands of drug-development programs at Pfizer that have ultimately floundered, one quest exemplifies both the tantalizing promise and the daunting odds of those efforts: the 32-year attempt to develop a medicine to treat the devastating complications of diabetes. It is the longest drug-discovery odyssey in Pfizer's 155-year history; it might well be one of the most futile pursuits in the annals of modern drug development. It is also the effort that taught a young Nancy Hutson how to survive a broken heart.

To Make One Life Better

When Hutson arrived at Groton Labs some 23 years ago, Pfizer was a third-tier drug company, and the campus consisted of three buildings. After studying biochemistry at Vanderbilt University and completing a postdoctoral stint at the University of Oxford, Hutson could have spent her career in academe. Instead, she surprised her fellow academics by opting for the hurly-burly of experimental drug discovery. "I wanted to make a difference in people's lives," she says, "and the only way for me to do that was to apply my science in the U.S. pharmaceutical industry, where 99% of the world's drugs are discovered and developed."

When Hutson joined Pfizer in 1981, its pursuit of a drug to treat diabetic complications was already nearly a decade old. The company had predicted what has now come to pass: that diabetes would become a global epidemic. Currently, there are an estimated 151 million diabetics worldwide; that number is expected to increase by 46% within the next six years. So Pfizer's diabetes program long ago passed the first hurdle for any major drug-development effort: the certainty of a huge and growing market. The program also had a particular personal appeal to Hutson: Her husband, Ian Williams, a fellow postdoc whom she met at Oxford and who was hired along with her at Pfizer, has had type 1 diabetes since he was 11 years old. "It was almost my fate to work in diabetes," Hutson says.

Pfizer's research into diabetic complications began in 1972, after university scientists and investigators at the National Institutes of Health identified an enzyme, aldose reductase, that seemed to play a critical role in the slow destruction of diabetics' nerves, eyes, and kidneys. Pfizer scientists scanned the company's library of new molecular entities against the enzyme. They eventually found a molecule that blocks aldose reductase. Other companies were soon trying to develop their own compounds. But within four years, Pfizer synthesized sorbinil, the chemical name for the first orally active aldose-reductase inhibitor.

When Hutson arrived at Pfizer, sorbinil was just entering large-scale human trials. "Those were enormously heady times," she says. "There was a woman in the sorbinil trial who suffered from diabetic neuropathy--the nerves in her feet were so damaged, she couldn't tell whether she was standing on carpet or a tiled floor. But after she tried sorbinil, she regained sensation in her feet. Once I heard that story, I was hooked. To make one life better--that's the most exciting occupation that anyone could have. You have to be indefatigably optimistic to survive in this business. And we were."

It's a refrain you often hear when you probe Pfizer scientists about what enables them to persist. There's a quality of unabashed idealism to what they do, and the hope that a successful project may ultimately save or improve lives can be so awe-inspiring that repeated setbacks seem somehow less significant.

Peter Oates, an expert in glucose metabolism, has harnessed that hope to sustain him through 19 years of work on Pfizer's diabetes project. His mantra: The patients are waiting. "If you have ever massaged cream into the stumps of a diabetic's legs, as I have, or known someone who's died from diabetic renal failure, as many of us have, this is not an empty slogan," says Oates, whose uncle lost both legs to diabetes. "They're not only waiting, they're counting on us."