When Roche's management acquired a $2.1 billion stake in Genentech in 1990, it eyed not only a deep pipeline of drugs, but also a team of dedicated, independent scientists. At the same time, Roche executives also saw a financial market buzzed about Genentech stock. So the Swiss company bought a majority stake, with an option to buy up the rest later, and left Genentech as a stand-alone unit.

In 1999, the Basel-based pharma exercised that option, taking Genentech off the market for a few brief months before placing it back on the New York Stock Exchange in another public offering, taking advantage of the bullish environment. Roche then reduced its ownership by selling off shares twice more, bringing in nearly $8 billion for the three offerings (each public sale at a higher per-share price) and Roche got to keep the majority of product revenue every year, as a primary stakeholder.

By all accounts, this relationship was mutually beneficial. The pharma's stake in Genentech was essentially a gift that kept on giving. For its part, Genentech retained product marketing rights inside the United States and was able to foster its science in a 'small company' culture free from interference by its Swiss partner.

But Roche couldn't resist taking the final bite: in March last year the pharma acquired the remaining 44% stake it didn't already own in a $46.8 billion deal. Analysts fretted that the entrepreneurial culture would yield to a staid Swiss lockstep. Even Roche chairman Franz Humer, who drove the deal, had previously said that a buyout would “never work, because if we owned all of Genentech we would kill it.”

In market share alone, Roche-Genentech is now the seventh largest US pharmaceutical company, projected to generate $17 billion in revenue yearly. In the months since the merger, Roche pulled out of the Washington, DC, lobbying group Pharmaceutical Research and Manufacturers of America, saying it would work instead through the biotech equivalent, the Washington, DC–based Biotechnology Industry Organization. And the June American Society of Clinical Oncology meeting was chock-full of rosy reports from Roche-Genentech's growing oncology portfolio, with ten new molecular entities in clinical development. In August, the US Food and Drug Administration approved Avastin (bevacizumab) for kidney cancer. New uses for established drugs, such as Tarceva (erlotinib), Lucentis (ranibizumab) and Avastin, are also moving through confirmatory trials.

The union produced its share of changes in senior management. CEO Arthur Levinson moved up to the board of directors and the president of product development, Susan Desmond-Hellmann, departed. Sandra Horning, a longtime Stanford academic with no pharma experience, took over as senior vice president, global head, clinical development, hematology/oncology. Executive vice president, research, Richard Scheller, and his top lieutenants stayed. Time will tell whether the new structure can sustain the track record of the independent biotech, but even before the buyout, Genentech's business had become more reliant on extensions of its existing product franchise (similar to any other big company) rather than production of new therapeutic entities.

Few pharma-biotech relationships look anything like the Roche-Genentech courtship. Consider Johnson & Johnson (J&J) of New Brunswick, New Jersey, locking up Centocor for $4.9 billion in 1999. Centocor was another biotech with an early blockbuster and good science to back it up. But J&J treated it like any other merger; though it left the biotech as a stand-alone unit, the latter was not public and had no scientific autonomy. In 2008, J&J merged Centocor with Ortho Biotech, slashed 400 jobs at Ortho and deployed the remaining resources to support Centocor's high-selling anti-tumor necrosis factor alpha compound Remicade (infliximab). Today, J&J partially owes its standing as a leading drug maker to Remicade: in 2008, it had worldwide revenue of $5.3 billion. That's a big hitter in J&J's lineup, but it has made Centocor look an awful lot like a one-trick pony. Genentech, it was not.

More diversifying was Basel-based Novartis' purchase of Emeryville, California–based Chiron for $5.1 billion in 2006. Here again, unlike Roche's hands-off approach with Genentech, the acquisition immediately sent executives from the biotech packing and put scientists and their projects on the bubble. That year, Novartis launched a three-year reorganization plan, and Chiron went inside Novartis' vaccine and diagnostics division, which last year accounted for just 4% of its $42.6 billion in sales. Though Chiron's vaccine expertise has been important in developing chicken egg–free flu vaccine production methods, Novartis did not buy Chiron to play parent; it bought it to hoard the valuables.

Is there another young Genentech and nurturing pharma parent still out there? Staring across today's biotech landscape (economic downturn or not), the answer seems to be no. Another Genentech would need not only to have a promising and established pipeline, but also to be surrounded by a free-wheeling scientific culture. That is awfully hard to find these days, in part because biotech companies are no longer built with flexible business plans designed to chase big questions down dark alleys, as Genentech was.

Firms are designed for a quick and total buyout and a return on venture money. Any burgeoning Genentech wannabe would be cherry-picked long before its first product launch. What's more, once consummated, big mergers today tend to isolate resources for the probable winning compounds, leaving the rest of the science to wither on the vine. The priorities for today's top management are more myopic: how does an acquisition and its compounds affect the balance sheet; science is secondary.

One final reason that Genentech-Roche is a once-in-a-lifetime relationship: luck. Though Genentech was a clear biotech leader in 1990, and its vaunted pipeline has long been discussed as one of the industry's best, the business of making drugs is scored by failure and serendipity alike. It took the financial stability of Roche, the genius of Genentech's scientists, an inspiring intellectual culture and providence to spin out product after product. But lightning does not strike twice.