Fresh Start 2002: Roche's New Scientific Method

Leading the GO team was Juergen Hammer, a vivacious German-born genomics expert. He had been chafed by the fact that his department was producing all of this exciting data, but no one else at Roche was able to look at it. Now he had his chance. His mandate: to focus on colon cancer, a disease that was common and well understood on a molecular level, but that still was not being treated very effectively with existing drugs.

Hammer's approach involved a blizzard of GeneChip experiments that were designed to show which genes might be linked to colon cancer. "You let the data speak," he explains. "That's the genomics paradigm." The oncologists were intrigued -- but they were much more comfortable with a classic review of scientific literature and molecular structure, where they would try to identify targets with the best potential for effective drug interaction. "It was almost as if two different languages were being spoken by the geneticists and the oncologists," Goggin recalls. "We had to bridge the gap."

Gradually, team members found ways to make the most of one another's specialties. When data analysis grew numbingly complex, the GO team recruited James Rosinski, who joined the team and helped colleagues unravel the numbers. From the early GeneChip experiments, more than 100 genes were identified as being potentially associated with colon cancer. Some of those genes also turned out to be critical for normal heart or kidney function. They were rapidly discarded. All through 2001, the list of promising candidates grew steadily narrower.

Eventually, two targets, which were endorsed by senior management, were selected. Intriguingly, both of the first two selections had been among the 50 most promising prospects in those early GeneChip experiments. But neither had been among the top 10. By combining genomics and oncology techniques, researchers had isolated new drug targets that would have been overlooked by either set of specialists working alone.

Hire Young Researchers for a Young Field

Ask Holly Hilton about her PhD research before she joined Roche, and she offers a wry smile. "It took me six years to gather all the data," she says. "We were making our gels by hand back then. Now you could probably run all of my experiments in two months. And at the time, we thought that we were so cutting edge."

In most fields, you don't hear that kind of reminiscing until people are in their fifties or sixties. But everything associated with the human genome is moving at a breakneck pace. Research techniques that seemed breathtakingly sophisticated in the mid-1990s are now as quaint and outdated as computer punch cards or hand-cranked automobile engines. As a result, researchers who are in their mid-thirties, such as Hilton, aren't viewed as apprentices who must still finish their hands-on training. They are regarded as fully formed experts in their field.

"This is such a fast moving field," says Klaus Lindpaintner, Roche's worldwide head of genetics research. "We're doing molecular biology now with equipment that we couldn't have dreamed of having 10 years ago. I'm not sure that it really helps you to have started your career in the era when you had to distill your own compounds. A young researcher can be fully up to speed with the most modern stuff and be less distracted by all of the other things that 50-year-olds focus on."

In her own lab, Hilton supervises a 27-year-old scientist, Nishi Sinha; a 38-year-old colleague, Mark Walstead; and an assistant who is in her late twenties. The four of them swing into action immediately after GeneChip experiments, running what is known as a single-tissue expression profiling (STEP) lab. Their mission: to run fresh tests that help narrow down the GeneChip experiments' enormous list of candidates.

Each time a GeneChip researcher thinks that she has found something promising, Hilton and her team assess its behavior in as many as 200 different tissue samples. They check to see if that gene is especially active in a healthy liver, heart, pancreas, or in other organs. They investigate whether it behaves differently in cancerous cells -- and, if so, whether that behavior varies depending on the type or stage of cancer.

By the time they are done, it's a lot clearer whether a gene's impact is narrow or broad. That's a crucial distinction. Genes that are associated with cancer and little else can make promising targets for new pharmaceuticals. But if a gene touches many aspects of life, it almost certainly would be futile to try to disrupt its function with a new drug.

These days, Hilton's STEP lab is a precision machine, running just the way Roche wants it. Hilton has about 10 other researchers' projects that will be ready for her lab's attention soon, but they all have scheduled start dates, and no one is complaining about delays. New equipment added last year lets Hilton analyze 96 samples at a time, up from just a handful at a time when she started.