NIH roadmap for medical research.

In May 2002, Elias Zerhouni became director of the NIH and promptly set out to enhance the agency's capacity to foster state-of-the-art science utilizing current technology. The NIH, Zerhouni reasoned, had to streamline the process by which emerging systems-level views of cells and disease could be applied to clinical care--in other words, shorten the distance from the laboratory bench to the bedside. An explosion in biology knowledge fueled by the growth of genomics and related fields was providing new means to link diseases through common biological pathways, and NIH research, Zerhouni wrote in the 3 October 2003 issue of Science, needed to reflect this new reality.

Today, this thinking is reflected in a far-reaching set of initiatives known collectively as the NIH Roadmap for Medical Research. The Roadmap was released after several months of meetings with biomedical and behavioral experts from academia, industry, the private sector, and health care, along with other stakeholders, and it identifies knowledge gaps and needs, providing a framework of priorities for NIH activities in the coming years.

NIEHS director Kenneth Olden is "excited and pleased" about the opportunities contained in the new scheme. "All the NIEHS's priorities are embedded in the Roadmap," he says. "It's a perfect fit for what this institute has to be about if it intends to be a player in the NIH."

Nuts and Bolts 

The path to the Roadmap began with a set of questions posed by the NIH to more than 300 biomedical leaders in late 2002. What are today's most pressing scientific challenges? What are the roadblocks to progress? What must be done to overcome these roadblocks? And what efforts are beyond the mandate of one of a few institutes, but rather are the responsibility of the whole NIH?

The answers to these questions were molded into three core themes that today form the Roadmap's foundations. Working under the first theme, known as New Pathways to Discovery, investigators will seek to better understand complex biological systems, in part by building new tools for biomedical research, such as imaging technologies and informatics databases. Within the Research Teams of the Future theme, scientists will explore new organizational models for interdisciplinary research and training, and investigate opportunities for high-risk studies that could produce extraordinary findings. And under the third theme, known as Re-engineering the Clinical Research Enterprise, NIH scientists will create integrated research networks and related informatics. This effort will entail new approaches to training the research workforce, facilitating translational research, and assessing patient-reported outcomes, among other activities.

The three Roadmap themes are further divided into nine separate "implementation groups" that collectively administer a total of 27 tangible research initiatives. According to Dushanka Kleinman, the assistant director for NIH Roadmap coordination, implementation of All 27 initiatives will begin in 2004. Kleinman says each initiative will be coordinated by a single lead institute that works closely with the designated implementation group to coordinate initiative activities and monitor progress. All of the fiscal year 2004 initiatives will draw monies from a collective funding pool fed by a combination of the NIH director's discretionary fund and contributions made by all the NIH institutes and centers, amounting to about one-third of a percent of each of their annual budgets. Currently valued at $128 million for fiscal year 2004, NIH officials expect the cumulative Roadmap for the years 2004-2009 to total $2.1 billion.

Specifics relating to the administration of the Roadmap are under development. A framework for operations of initiatives is now being drafted, Kleinman says, that will provide guidelines for both pre- and postaward management. The draft is expected sometime this spring. Moving forward, the Roadmap will strive to ameliorate what many experts see as deficiencies in the existing U.S. clinical research system: poor integration of regional networks, inadequate training for clinical investigators, inconsistent data standards, and a propensity for avoiding risky research in the NIH's approach to science.

Construction Ahead

Anne Sassaman, director of the NIEHS Division of Extramural Research and Training, points out two Roadmap initiatives that she believes will figure especially prominently on the NIEHS radar. One is Metabolomics Technology Development, which falls under the New Pathways to Discovery theme and is led by the National Institute of Diabetes and Digestive and Kidney Diseases. This initiative will develop tools to measure concentrations of carbohydrates, lipids, amino acids, and other metabolites within single cells. The resultant data will enable researchers to better understand the cellular metabolome--the collection of all metabolites and their activities, under both normal and diseased states.

Metabolomics is the ultimate step forward from gene expression, Sassaman explains, placing the field squarely in the context of gene-environment interactions, which are addressed at the NIEHS, in particular at the institute's National Center for Toxicogenomics, where scientists study how environmental pollutants and the genome interact to produce disease.

A second initiative, Interdisciplinary Research Centers, falls under the Research Teams of the Future theme and is led by the National Center for Research Resources. This initiative will create interdisciplinary programs that address significant and complex biomedical problems, particularly those that may resist more traditional research approaches. Because environmental health is largely interdisciplinary, combining toxicology, epidemiology, and other related specialties, the NIEHS will benefit from NIH efforts to promote cross-training among scientists with divergent backgrounds, Sassaman says.

But the NIEHS is by no means limited to these two initiatives. According to Allen Dearry, associate director for research coordination, planning, and translation at the NIEHS and the institute's Roadmap liaison, opportunities for the NIEHS exist within each of the 27 initiatives. "All Roadmap initiatives are relevant to the NIEHS extramural community," he says. "Furthermore, NIEHS staff contributed directly to many of these Roadmap initiatives, including those related to clinical research."

Finding New Direction

What the Roadmap does not explicitly provide, some experts say, are specific references to disease prevention. David Eaton, who is associate dean for research at the University of Washington School of Public Health and Community Medicine and director of the university's Center for Ecogenetics and Environmental Health, says this could be a problem for institutes (such as the National Cancer Institute and the NIEHS) that have focused substantial portions of their research portfolios on prevention-based strategies.

Although many Roadmap initiatives are relevant to the NIEHS, says Eaton, it is less clear where more traditional prevention-based research projects will fit into the plan. "Any institute that continues to pursue prevention-based research might have a harder time justifying their budgets if their activities aren't consistent with the Roadmap," he says. This is unfortunate, he adds, because "from a public health perspective, it can be more effective to prevent a disease from happening than to treat it after it's formed."

However, Eaton and other stakeholders do note that support for disease prevention is implied in many parts of the document. Dearry, for instance, points out that technologies developed as part of New Pathways to Discovery will enhance the creation of biomarkers and disease indicators, which he says apply to prevention research. "A lot of people are worried because they don't see words like 'prevention' or references to specific diseases like cancer in the Roadmap," Olden adds. "But nothing in the Roadmap is institute-specific, nor should it be. The focus is not on specific diseases but on an understanding of disease mechanisms. We want to understand how biological systems function; these principles will apply to all diseases."

Olden says the NIEHS is well positioned to take advantage of the Roadmap's emphasis on systems biology as well as interdisciplinary and translational research. Ongoing NIEHS research in toxicogenomics and bioinformatics applies in this context, he says. So do the existing interdisciplinary research centers on breast cancer and child health. "We will continue to do exactly what we've been doing," Olden says. "It's not so much about predicting the orientation of a new NIH director. It's about anticipating where science is going and making sure you're in the right place and hopefully ahead of the pack."

For more information on the NIH Roadmap for Medical Research, visit http://www.nihroadmap.nih.gov/