Rick Lifton's brightly lit maze of laboratories and offices, arrayed along a gracefully curved corridor of Yale's Boyer Center for Molecular Medicine, is a deceptively low-key place. The few sounds—the delicate clink of glassware at lab benches, the clicking of computer keys, the subtle murmur of consultations over data—give little hint of the dynamic discoveries emerging from within.

Lifton is naturally proud of those accomplishments, but he's equally proud of the scientists he mentors here, most of them physicians with purely clinical backgrounds. These young scientists are mastering the full range of talents they'll need to see their own projects through from start to finish and to assume leadership roles in their fields. Given Lifton's holistic perspective, team members come away not only equipped to pin down a disease in the clinic but also capable of rigorously analyzing its genetics and then figuring out how a genetic mutation causes disease.

"Most of the people trained in his lab have been physicians who came here not even knowing how to run a gel and then left as really good scientists," says Murat Gunel, a neurosurgeon who joined the lab eight years ago and is now establishing his own research group. "They learned to ask the key questions that enable translation of basic research to answer clinical problems."

The need to master both the tools of the profession and the strategy of using them to attack scientific questions was a lesson Lifton learned early on. "I was fortunate to have some spectacular mentors who gave me extremely good training and insight into how to approach problems," he says, citing in particular Lawrence Kedes and David Hogness, with whom he worked at Stanford. Just as those scientists encouraged him to identify his own project and follow wherever it led, so Lifton does for the young scientists in his own laboratory.

"I realized that to be successful in science, one needs to be intellectually flexible and not just wedded to one set of tools," he says. "That's not going to give an individual a broad perspective on science or the confidence to start their own lab."

Many labs don't allow young researchers to identify a disease and take full responsibility for studying it, he admits. "I think there are a lot of laboratories that operate more as factories," he says. Among such labs, Lifton has observed two particular syndromes.

"One is where the lab is built around a particular technology, and that's it. It's like the old saying that to a child with a hammer, everything is a nail. This laboratory's leaders say, 'We won't think about doing problems that can't use this same hammer and the same nail,'" he explains.

"And secondly, there's the phenomenon of team science. In some areas, including genomics, it's relatively popular to develop, either within or across labs, big consortiums in which you divide up the problem. As a result, one person will only do, say, the analysis of linkage, and one person will only do the physical mapping, and one person will only do the gene identification and mutation detection."

Such an approach may seem efficient, but ultimately it does not produce fully capable scientists, Lifton contends. "I think in the long run it takes away a lot of the zest of doing science—which is driven by the fact that you've got an interesting problem. The reason you want to do science is that you're passionate about solving problems."

Researchers with holistic training are also prepared to adapt to changing scientific tools and to lead the way in developing them. "Anyone working today who thinks that 10 years from now they're going to be using the same tools is sadly mistaken," Lifton warns.

Ali Gharavi, a physician in the laboratory, relishes the environment Lifton has created. "There are no walls, no barriers, in this lab. I walked in and Rick said, 'Pick a project and you can work on it.' And having an M.D., I could identify certain problems that were important in my field and try to address them."

For Murat Gunel as well, Lifton's encouragement has been crucial.

"As I had to make the important choices, he helped me and guided me," Gunel says. "At those times when I felt I was only going to be a mediocre scientist, it was Rick who kept pushing me, supporting me."

—DM

Photo: Harold Shapiro

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Reprinted from the HHMI Bulletin,
May 2001, pages 22-27.
©2001 Howard Hughes Medical Institute