Fresh Start 2002: Roche's New Scientific Method

When Hilton joined Roche in 1998, the STEP lab didn't exist in any form, and building it was a matter of constant improvisation. "No one was an expert in genomics then," she recalls. In early 2002, Hilton almost certainly will upgrade her neatly constructed STEP lab with more-advanced equipment that can handle 384 samples at a time. That's progress.

"You need people who have the agility to handle change," Hilton observes. "I haven't been doing this for 20 years. By the traditional definition, I'm not an expert. But I'm very comfortable being a team player. I'm not wedded to the idea that we have to do things the way we've always done them. I'm willing to try something new. And that's important."

Fail Fast, so You Can Succeed Sooner

One of the biggest challenges in drug research -- or in any field -- is letting go of a once-promising idea that just isn't working anymore. Without strict cutoff rules, months and even years can slip away as everyone labors to keep a doomed project from dying. Meanwhile, much brighter prospects sit dormant, with no one able to give them any attention.

Roche went outside its ranks to hire Lee Babiss as the new head of preclinical research at Nutley headquarters. Babiss arrived from arch rival Glaxo with a simple message: Fail fast. Babiss wanted successes as much as anyone. But he also knew that the best hope of finding the right new drugs involved cutting down the time spent looking at the wrong alternatives.

Four years later, Babiss's doctrine of failing fast has spread throughout Roche's U.S. labs. "It's a numbers game," explains Philip Familletti, a Roche research manager. "To identify 2 targets as clinical candidates that deserve further development, you need 18 to go in for review. The further you go with development, the more it costs. And once you start clinical trials with patients, the cost is outrageous."

This sifting process has become more vital than ever, now that Roche's genomics teams are finding a flurry of unexpected new drug targets. A few of those targets will turn out to be breakthroughs, if Roche can come up with a molecule that will jump into a specific target and change biological pathways in a manner that will help patients. Many others will turn out to be dead ends, where there just won't be any way to get a potential drug locked into that target -- or where the only molecules that will fit will ultimately be harmful to patients.

The only way to know for sure about these targets is to start screening molecules, one by one. At most big drug companies, that means working through a "library" of 500,000 to more than 1 million possible compounds. The only way to know if compound 337,194 might work is to try it. If that's a dud, it's time to move on to compound 337,195.

At one point, Familletti delicately explains, "screening was becoming a bottleneck for us." But not anymore. At locations around the world, including Nutley, Roche has installed an ultra-high-throughput screening system made by Carl Zeiss of Germany. It is an enormous four-part robot with conveyor belts and work stations where trays jammed with 1,536 samples apiece are analyzed. The cost: more than $1 million.

"We can test 100,000 compounds a day," says Larnie Myer, the technical robotics expert who keeps the Zeiss system at Roche running. Nearly all of those compounds will turn out to be useless for the mission at hand. But that's fine. If his team can get the losers out of consideration for that trial in a hurry and identify a handful of "hits" within a few weeks of testing, that speeds Roche's overall efforts.

What's more, the Zeiss machine represents the gradual retooling of Roche's overall research efforts. Thanks to advances in genomics and molecular biology, the beginning of the research cycle is packed with an enormous outpouring of possibilities. That surge is starting to flow through everything else that Roche does. Processes farther down the pipeline must be upgraded and reworked in order to handle much greater volume. That is hard and disruptive work -- but it is vital.

Change Everything -- One Piece at a Time

Peek into almost any aspect of Roche's business, and you will find someone who is excited about the ways that genomics could change things. In Palo Alto, researcher Gary Peltz has built a computerized model of the mouse genome that allows him to simulate classical lab studies in a matter of minutes.

In Iceland, Roche is teaming with a company called Decode, which researches genealogical records from the Icelandic population. That data has helped Decode identify and locate genes that are associated with stroke as well as schizophrenia and other diseases, giving Roche new research leads that otherwise might never have surfaced with such clarity.