Those coming to see Tom Cruise's breakthrough film might have been disappointed, but it's safe to say most of the attendees at the jam-packed opening session of the NIH Research Festival had no confusion about the name and thoroughly enjoyed NIH's version of "Risky Business." Following on the heels of the first annual Pioneer Award Symposium highlighting the NIH Roadmap's high-risk, high-reward approach, the festival's Oct. 18 opening session demonstrated how NIH's intramural program has long incubated researchers pursuing such research. NIH director Dr. Elias Zerhouni followed four researchers' talks by discussing his perspective on the intramural research program, including its future direction.

Dr. Susan Buchanan

The first speaker, Dr. Susan Buchanan of NIDDK, detailed her investigations into the transport of molecules across bacterial outer membranes. She explained that outer membrane proteins may make good vaccine and drug targets since they are surface-accessible, antigenic and often unique to bacteria.

Dr. Shiv Grewal of NCI spoke about the hot topic of RNA interference and its role in gene regulation; recent work by his laboratory was named a "Breakthrough of the Year" by Science magazine.

Dr. Orna Cohen-Fix of NIDDK explained her studies of why the nucleus is round — a question that may seem simple on its surface but that requires an inventive approach to answer. She demonstrated that the shape of the nucleus is a function of the nuclear membrane itself, not the DNA within.

Finally, Dr. Mark Gladwin of NHLBI outlined new thinking about the role of nitrite in the regulation of vasodilation. He described tantalizing new evidence that nitrite, which is considerably less expensive than nitric oxide, may prove to be an effective therapeutic in itself for regulating vascular homeostasis in diseases like pulmonary hypertension and sickle cell disease.

NHLBI's Dr. Robert Balaban		2005 Research Festival co-chair Dr. Sheldon Miller of NEI

Zerhouni put the talks in context by giving his broad impressions of the IRP's past and future promise. He began by showing a slide representing scattered small islands of knowledge in a sea of information. "What is the strategy that works best to discover those islands of knowledge?" he asked.

His answer: "If you don't know what's out there, the best strategy is to send out explorers in multiple directions. That's been the approach of the IRP. The more you send out, the more likely one of them is to hit an island of knowledge." He added, "This has been the strength of the IRP."

Only in the IRP, Zerhouni noted, can you continue an inventive line of research for multiple years. Also unique to the IRP is the ability for researchers to change directions, as Cohen-Fix showed in freely moving from cell cycle studies to investigations into the shape of yeast nuclei.

	Dr. Ira Levin of NIDDK

Zerhouni pointed out that as we get to know more of those islands, different strategies are also needed. As more about a field of science becomes known, we can do a better job of predicting where the next discoveries will be, he said. Larger efforts in certain research directions — armadas, to stretch the analogy — start to become fruitful, whereas before they may have cast too many resources in the wrong direction.

Dr. Orna Cohen-Fix of NIDDK

Research is also becoming considerably more complex, Zerhouni noted. Researchers in disparate fields are now building bridges between islands that once seemed far apart. One of NIH's top priorities will be to take a leading role in removing barriers to collaboration to allow larger, more diverse research teams to work together productively.

	NIH director Dr. Elias Zerhouni opens Research Festival 2005

He described NIH's efforts to strengthen the transition from bench to bedside to make sure that we quickly take advantage of breakthroughs when they occur. He also mentioned the importance of helping investigators early in their careers.

As for the next scientific frontier, Zerhouni said that the first priority for NIH will be to help usher in an era of quantitative biological measurements. Rob Phillips, a Pioneer Award recipient, had spoken at the awards symposium about his hope for transforming an empirical understanding of biological events into a quantitative understanding. It is this vision that NIH needs to promote, argued Zerhouni.

Dr. Doug Lowy of NCI

But whatever changes come to NIH's research portfolio, Zerhouni stressed that the IRP is unique. It has a special family sense, he said, and we need to continue exploration in multiple directions. He said that as NIH formulated the Roadmap, the IRP was something of a model. The IRP gives researchers "incubator space" for the type of high-risk, high-impact research that NIH wants to encourage more of throughout its research portfolio.