"In some ways," said Niko Canner, a consultant with Katzenbach Partners, "Big Pharma is a victim of its own success. There was a tremendous period when they were coming up with drugs for chronic diseases that affected lots of people. There is now a lot of very good generic product on the market. And while there have been significant innovations, there hasn't been a big wave like the last one."

And there's more: the science of drug discovery is changing in ways that favor small, nimble biotech companies. The new discoveries tend to be in areas like cancer, where companies can charge very high prices for small populations - and where the sales force needs to be steeped in the science of the drug. Mr. Cutler believes that drugs are eventually going to be customized for individuals - and the kind of broadly available drugs Big Pharma has been so good at producing, requiring huge clinical trials, simply won't make sense anymore.

Mr. McKinnell, Pfizer's former chief executive, was wedded to the blockbuster model; in retrospect, it seems obvious that that is part of the reason he no longer has his job. (He also had very little credibility on Wall Street, and wasn't well liked within the company.) In his announcement this week, Mr. Kindler talked about needing to make the sales force operate differently, about turning its managed care customers into partners instead of foes, and about getting as good at developing $500 million drugs as in coming up with new blockbusters.

He was speaking in code, but if you were attuned to it, the message was clear. He wants to wean Pfizer from its blockbuster culture. But even with 10,000 fewer employees, Pfizer is still a very big company, and very set in its ways. It had a great deal of success doing things one way. And however much its people may say they want to change and thrive, Mr. Kindler is about to discover the same thing executives in the newspaper and auto industries already know. It's hard to teach an old dog new tricks.