It is hard to discuss the world of medical research without mentioning the National Institutes of Health. With a budget exceeding $27 billion and a staff of nearly 20,000, the 27 Institutes and Centers that comprise NIH make up one of the world's premier medical research centers. One might think that it is only by miracles that such a complex bureaucracy can manage the tens of thousands of annual grant applications which flow into NIH. But as I learned from Brent Stanfield, Acting Director of the Center for Scientific Review, and Anthony Demsey, Senior Policy Advisor for the Office of Extramural Research, it is not by miracle but through thoughtful, creative leadership and remarkable contributions from clinical researchers around the country - no small feats indeed - that NIH remains able to set the standard in medical research.

"The state of biomedical research in the world is in large part due to the state of biomedical research in the United States," said Stanfield, "and the state of biomedical research in the United States is in large part due to the success of the NIH system." What is that system? How does NIH do research?

Three times a year, NIH receives about 16,000 grant proposals to be evaluated for possible funding. The evaluation is administered centrally by a system of peer review organized through the Center for Scientific Review (CSR). Through CSR, NIH assesses the merits of individual proposals and communicates their scores to the researchers and to the individual Institutes or Centers of NIH (such as the National Institute of Mental Health or the National Cancer Institute) which would potentially fund the research. Each of these Institutes or Centers funds projects independently.

To evaluate the proposals, NIH convenes Integrated Review Groups, panels of research scientists with the expertise to assess each proposal. It is here that the magic of the CSR review process occurs, as clinical researchers come from around the country to evaluate and comment on new research in their respective fields. As Demsey put it, "It's a very energizing atmosphere to be sitting around the table with 20 of your peers and evaluating some of the hottest, newest stuff that's coming out."

"It's amazing that people are willing to do this," said Stanfield, "but the reason they are willing to do this is because they realize how important it is to NIH."

Indeed, peer reviewers prioritize their work with NIH. Before actually attending the sessions, the reviewers must individually research and prepare to discuss the proposals they will be seeing as a group. And even in extenuating circumstances, they work to make sure they get to NIH. Stanfield described the review sessions that took place in October 2001, as the country was still recovering from the terrorist attacks and air traffic was still much reduced. He remembers a conversation with one reviewer who told him that despite canceling all other winter flying, he still traveled to his NIH peer review because the work was so important. Such a sense of community and worth among the reviewers helps contribute to a fair and well-informed NIH review process.

Yet, as the perceptive Stanfield and Demsey were quick to point out, the challenges - and rewards - of a peer review system have been changing rapidly in the past decade. Specifically, research has become increasingly multi-disciplinary. "Ten or fifteen years ago you could pick up an application and say, 'this is a cardiophysiology application,'" said Stanfield. "That's not the case anymore. More and more researchers put together an application that involves a whole different perspective." Demsey agreed: "There's a lot more collaborations these days, looking at a problem from many different aspects. Now you're getting biologists working with biophysicists working with chemists, and that causes a more complex kind of science."

Although a more complex science may produce added challenges for NIH and reviewers as they determine how to classify and evaluate a proposal, the benefits can be impressive. "All of us, we get into tracks," said Stanfield. "It's good to have someone who's really fresh and who says 'have you ever thought of looking at it this way?'" The NIH leaders appeared welcoming to these fresh methods and ideas.

One might wonder how NIH can keep its medical priorities insulated from political pressures. After all, as part of the Department of Health and Human Services, NIH falls under the jurisdiction of the Executive Branch, and as its budget must be appropriated and approved by Congress, there is some reason to fear improper political influence. And the mainstream press has occasionally highlighted public disputes between NIH leaders and Congress. Is there this great tension between the politics of Congress and the medicine of NIH?

For the most part, said Stanfield and Demsey, it doesn't work that way.

"I think that the Congress has been very good about understanding that it's best not to tell NIH exactly what they want done," said Stanfield. "They consult with NIH and there have been some wise individuals in Congress that make sure that they don't compel Congress to spend money that wouldn't be good. They receive a huge amount of pressure from interests groups but they are good about not funding pet projects - they understand that many things would not be quickly solved just because you throw more money at it."

Serving public health, of course, requires engaging with those who constitute "the public." "It's very important for NIH to nurture relationships with Congress because often you have to balance public health needs with scientific opportunity," said Stanfield. "If the opportunity isn't available, we need to understand that funding something is not really worth it."

And despite the occasional debate in the mainstream press between NIH and Congress, it's clear that NIH has succeeded in building its credibility with the legislative branch. "It's not as politicized as you think we might be," Demsey told me, "and that's in large part because we've been very successful saying that what we fund is funded after being reviewed by the best experts in the country."