In the last decades of the 20th century, a basic paradigm emerged for biomedical research: to more effectively battle disease, science would seek to understand it at its most basic levels. With this approach, scientists and physicians have made remarkable progress in fighting--and in some cases, eliminating--disease. But, according to National Institutes of Health (NIH) Director Elias Zerhouni, that momentum is in danger of floundering. And he has a plan to restore it: the NIH Roadmap.

When first announced to the public at a 30 September 2003 press conference at the National Press Club in Washington D.C., the Roadmap was little more than an ambitious set of vague objectives. But within the past few months, the NIH has announced enough Roadmap-related new initiatives (via requests for applications or RFAs) that the map began to take concrete form. Using the map, NIH has started to build a road.

Laying the foundation

Long before the Bush administration adopted the terms for its Middle East peace initiative, surveying for NIH's Roadmap was under way. The historic doubling of the NIH budget in an unprecedented 5 years was coming to an end. The biomedical research community had made incredible progress, typified by the complete sequencing of the genomes of several complete species, including human beings.

To maintain that progress--in a fiscal environment that would be neither as generous nor as supportive--the NIH Office of the Director (OD), working with the Directors of NIH's 27 Institutes and Centers (ICs), began discussions with some 300 experts in government, academia, and industry. They were given a simple task: to identify the roadblocks that were impeding the nation's progress in meeting its health needs, and to devise strategies and plans to clear them. Led by IC directors, 16 working groups spent a year investigating and debating the issues. A draft proposal was presented to the Advisory Committee to the Director on 30 June 2003; this proposal was refined and presented to the public in September.

The initiatives

In a Policy Forum in the 3 October 2003 issue of Science, Zerhouni laid out the Roadmap's three themes:

  • New Pathways to Discovery, a set of proposals that will create and develop new tools and technologies for bench scientists

     

  • Research Teams of the Future, a set of initiatives to promote public-private partnerships and to train investigators to work in interdisciplinary and multidisciplinary teams

     

  • Reengineering the Clinical Research Enterprise, a complete re-organization, expansion, and streamlining of clinical research in the United States.

Zerhouni's article, as well as background information on these proposals, NIH documents, and funding announcements (even if the ink is still wet, the Roadmap has already yielded 13 new RFAs) can be found at: nihroadmap.nih.gov

Roadmap winners

This being Washington, D.C., analysts are eager to identify who wins--and who loses--under any new proposal. With an estimated 5-year cost of $2.1 billion, the stakes are high. In my view, the biggest beneficiaries of the Roadmap (apart from the tremendous strides in advancing science and improving the nation's health) are likely to be young scientists, including students, postdocs, and junior faculty.

Recognizing that research is increasingly collaborative, the Research Teams of the Future initiative seeks to train young scientists in interdisciplinary and multidisciplinary research. Many laboratories currently engage in multidisciplinary research, where individuals trained in different fields work together on a single problem. In contrast, in NIH parlance, interdisciplinary research results when collaboration creates completely new and separate disciplines, such as biophysics and bioinformatics. NIH will fund programs to train new investigators in how to conduct these sorts of studies. Such training will give young scientists an advantage over their more discipline-based senior colleagues in the new scientific world that Zerhouni envisions. This initiative also seeks to build stronger collaborations among industry, academia, and government.

Clinical research is tightly regulated in the United States. This is a good thing, generally, but those same regulations are stifling interest in training investigators in clinical research and even in undertaking such projects. The Roadmap seeks to reverse these trends and reinvigorate clinical research, in several ways. The NIH will work with other federal agencies to streamline regulatory requirements. New clinical researchers will be trained, and neighborhood networks of care providers and patients will be built throughout the United States. These networks will be supported by regional clinical research centers providing a full suite of core support services. Finally, investments will be made in training and infrastructure.

Taken as a whole, the Roadmap is a comprehensive strategy to reorganize and reinvigorate research in the United States--an attempt, as Zerhouni put it, to "turbocharge the NIH." "Turbocharge" seems an apt word choice: NIH is often criticized for being too conservative and unwieldy. Coming as they do after only a year and a half of research, consultation, and design, the first Roadmap requests for applications (all of which can be accessed at nihroadmap.nih.gov) indicate that NIH, despite its tractor-trailer reputation, can sometimes handle like a sports car.

New Training Programs

Four of the new RFAs are directed at training scientists. One of these, Curriculum Development Award in Interdisciplinary Research, provides about $1.5 million in fiscal year 2004 (FY2004) to develop "courses or curricula at the undergraduate, graduate, or postdoctoral levels that integrate the principles and conceptual approaches of multiple, diverse disciplines in emerging areas of biomedical research."

Another RFA, Short Programs for Interdisciplinary Research Training, will support nine to 12 grants in FY2004 and FY2005 to develop 8- to 10-week training programs that combine lectures with lab experience. These short courses are targeted not only at trainees, but also at "senior scientists" seeking to develop interdisciplinary research programs. NIH is opening this program up to the scientific community of the entire planet: Applications from domestic, foreign, and U.S. government laboratories are all welcome, in stark contrast to almost all of NIH's other training programs.

The National Institute of Mental Health (NIMH) is sponsoring an initiative that seeks to train scientists to integrate behavior, environment, and biology into a single discipline. The RFA states that mental illness will be studied "by approaches that integrate neuroscience, genetics, behavioral science, computational science/modeling, and clinical sciences, using both animal models of these disorders and human populations." This program will spend $2.1 million in FY2004 to fund four to five postdocs in six to eight new training programs using the NIH's T32 Ruth L. Kirschstein Institutional Training Grants National Research Service Award (NRSA) mechanism. That's a total of 24 to 40 new positions in a field that is at the forefront of research. Applicants for these programs must be U.S. citizens or permanent residents, and recipients of this prestigious award will be encouraged to apply for the even more prestigious individual NRSA, the F32.

Finally, organizations funded by this proposal are required to track the careers of their trainees, even after they leave the program, and to solicit advice from those trainees on the successes and failures of the program. This is the sort of information--heretofore lacking--that many analyses have cited as central to the development of work force- related policies.

These programs will train new scientists, complement the training of others, and mandate the collection of career information on trainees--important, evolutionary changes. But just 2 weeks ago, the NIH announced that it wanted to make revolutionary changes as well.

"Training for a New Interdisciplinary Research Workforce" uses a new funding mechanism, the T90, that seeks to "develop a cadre of interdisciplinary research scientists by capitalizing on the infrastructure of existing multidisciplinary and interdisciplinary research programs." This new mechanism, which combines aspects of research grants and NRSAs into a single mechanism, includes $6 million in 2004 to fund 10 to 12 new training programs. Just about all organizations, foreign and domestic, can submit applications for this program; trainees can be at any level, from undergraduate to postdoc, and do not need to be U.S. citizens or permanent residents. If widely implemented, the T90 may be the most exciting of the Roadmap initiatives when it comes to the training new scientists. We'll provide more information on the T90 mechanism in a future article.

As previously described, the training of scientists and clinicians gets a strong boost under the Roadmap.

The Roadmap places a heavy emphasis on interdisciplinary and multidisciplinary research. Young scientists are most likely to have been trained--formally or otherwise--in this approach and thus may field more competitive grants.

The tool-building programs of the Roadmap will be invaluable to all investigators, including young ones. Some of these resources, such as libraries of small molecules, are currently available only to pharmaceutical companies. Other technologies are simply too expensive to be adopted and used by most young scientists, who are disproportionately underfunded. By making these and other tools available to all scientists, the NIH is "leveling the playing field" and allowing small labs with limited funds to compete with larger, better-funded groups.

Bench scientists will also benefit from the renewed support for clinical research. Congress and the American taxpayer have funded the NIH generously for the past 50 years because the NIH promised to improve the health of the nation. Many prognosticators have proposed a new paradigm to crack complex diseases, such as heart disease, depression, and schizophrenia: Use human genetics to gain insight into one or two key genes. Understanding what those genes do--and with what they interact--will allow scientists to trace out complete pathways, ultimately yielding new targets for treatment. This approach requires close coordination between clinics and researchers. Well-funded labs already do this, but the Roadmap will organize and pay for new networks of patients, clinics, and labs--another boon to the young investigator.

Over the next few years, the NIH budget isn't likely to grow by more than 5% per year. The NIH will spend $130 million on the Roadmap in FY2004 and about $2.1 billion over the next 5 years--very likely, more than 1% of NIH's budget for the period. So where's the money going to come from?

Congress allocated $45 million early in the FY2004 budget cycle for the Roadmap. The balance will come from the various institutes, which will make contributions in proportion to their budgets--a sort of tax on NIH institutes. But that "tax" has to be paid from some fund; reporters at the 30 September news conference expressed concern that research in other areas would have to be reduced to fund the Roadmap initiatives. In principle, the impact on young investigators, who do not already have large grant portfolios, ought to be smaller than on their more established colleagues, who already have more of the existing pie. But this remains to be seen.

Summary

Although the specific goals of the Roadmap themes are numerous, taken together they can be seen as an ambitious, desperately needed attempt to renew the commitment of NIH to the support for young investigators. Observers outside government may not appreciate the scale and speed with which the Roadmap was created and is being implemented. The Roadmap--and the speed and scale of its early implementation--can be seen, in part, as a meaningful expression of NIH's very real concern that young scientists are receiving smaller and smaller pieces of the research pie. By making new "Roadmap" resources available to young investigators, NIH has an opportunity to clear a path to the future for students, postdocs, and tenure-track scientists. Whether they will succeed depends on the courage and will by administrators at the various institutes to invest resources from the investigators of today to those of the future.

Peter J. Kozel is a postdoctoral fellow at the NIH and a member of the National Postdoctoral Association (NPA). The opinions expressed are his own and do not represent those of the NIH, the U.S. Government, or the NPA.