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Rubin's Risky Business

Oct. 16, 2006 | Gerry Rubin's successful partnership with Craig Venter to sequence the Drosophila genome in 1999 was a stunning dress rehearsal for Celera's assembly of the human genome. But for Rubin, it was an end in itself, the culmination of the UC Berkeley geneticist's decade-long dream to sequence the genome of his favorite model fruit fly.

In 2000, seeking a fresh challenge, Rubin joined Nobel laureate Tom Cech as the new leadership team at HHMI, ushering in a new era of "risky" research and encouraging - nee insisting that - the nation's smartest scientists use the institute's lavish resources to conduct bolder, more imaginative lines of research.

But Janelia Farm represents an even bolder vision - a new interdisciplinary research campus modeled on Bell Labs to foster new technologies and areas of research. "We started with the premise that we'd try to do things that aren't done well elsewhere," a relaxed Rubin told me. "There's not been good funding for developing new tools and new methods."

Rubin wanted to avoid high-profile areas such as genomic medicine, where "smart people will get money from the NIH." Instead, HHMI looked for problems that would benefit from an interdisciplinary environment, ideally with a technological component. Following a set of scientific workshops, two major goals/criteria were identified.

Says Rubin: "One was the goal of understanding how information is stored and interpreted in the nervous system. It starts with the premise - which I hold strongly - of evolutionary conservation. We believe that there are fundamental mechanisms underlying how information is processed in all animals and we can discover these mechanisms in genetically tractable organisms, such as fruit flies, mice, worms."

Rubin commends the NIH for pouring money into research on Alzheimer's, Parkinson's, and other neurological disorders, but there is little left for basic research. "This may be medically relevant in 30-40 years," says Rubin. "That's fine, that's soon enough."

The other goal for Janelia Farm is to develop methods and techniques to image neural activity. "NIH spends lots of money on imaging, but its nearly all human diagnostics," Rubin explains. "We want to study the nervous system and improve imaging methods, build better microscopes, and [develop] computational analysis."

As for his own research, Rubin has scoped out his own project "to identify all the enhancers and promoters in the Drosophila genome that are directed to subsets of cells in the adult brain." The project involves making thousands of transgenic animals, using his extensive high-throughput genomics experience. The end result will be a valuable tool for the community.

Misfits and Molecules
What particularly pleases Rubin is the preponderance of physicists arriving at Janelia Farm. "We have more people with physics undergraduate degrees than biology degrees: We have mathematicians, computational scientists, physicists, biologists, they're all beginning to interact."

One of the early arrivers is Gene Myers, former chief of informatics at Celera. "The type of people working at Celera in its heyday are exactly the type of people we want working here," says Rubin. "We wanted to be different. We didn't want to be competitive with Harvard Medical School or the Whitehead Institute.... We wanted to do things here that attract "misfits" - people that don't fit into conventional academic institutions."

Breaking these boundaries is paramount for HHMI's bold experiment to succeed. The research facility contains 147,000 square feet of Belgian glass, one of the largest installations in the US, providing open visibility into every laboratory. Compressed lunch hours encourage communal dining; and there is a pub named "Bob's" after HHMI's resident architect, Bob McGee, which Rubin says serves a "nice cappuccino" and another communal venue in the evenings.

Janelia Farm has its skeptics, but that's fine with Rubin. "Half of people think this is just crazy. Only ten percent people say this is for them, this is where I want to be. My goal going in was for Janelia to be different enough that only ten percent of scientists would be enthusiastic." -- K.D.

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