Feature

National Institutes of Health (NIH) Director Elias A. Zerhouni, MD, has set his sights on increasing the pace of medical progress. So, with help from a team of 300 scientists, industry leaders, government officials and the public, he has mapped out a path of scientific discovery with the goal of giving scientists in the public sphere new tools for doing molecular-level research and translating discoveries into clinical applications.

The plan, first introduced in 2003 and known as the NIH Roadmap, provides an outline of 28 cross-institutional projects. Its details are still being fleshed out, but through it, Zerhouni seeks to bring together scientists from different disciplines to tackle obesity and other such knotty public health problems that result from multiple interacting factors, including behavioral ones.

For example, the roadmap calls for the creation of molecular libraries--publicly available repositories of information on small organic compounds and the proteins they bond with--that can aid the investigation of cellular-level molecular functioning. Meanwhile, other roadmap projects, such as a database of clinical research results--the National Electronic Clinical Trials and Research System (NECTAR)--are intended to speed those findings from the lab to medical application.

To achieve such goals, roadmap designers will need the help of behavioral scientists, says psychologist Alan Leshner, PhD, chief executive officer of the American Association for the Advancement of Science.

"Psychologists do all kinds of research, all the way from the molecular level to the whole person and up to group interactions," he says. "All of this research informs our understanding of how disease processes work."

According to Leshner and other roadmap observers, certain project initiatives may provide particular opportunities for psychologists to contribute.

Molecular libraries

By cataloging millions of small organic compounds and how they interact with proteins found in the body, NIH plans to create a powerful toolbox for scientists, including neuroscientists who do behavioral research at the molecular or cellular level, says psychologist Steve Foote, PhD, director of the division of neuroscience and basic behavioral science at the National Institute of Mental Health (NIMH).

These small molecules then can be used as probes, which when injected into the body of a rat, for instance, will turn on or off certain proteins. Then, psychologists can observe that protein's role in animal brain function and behavior--and infer the role of the genes that control that protein's production, Foote explains.

Additionally, says Bryan Roth, MD, PhD, a psychiatry and biochemistry professor at Case Western Reserve University Medical School, scientists can also employ small molecules as imaging probes. On introduction into the body, some molecules will bind to specific receptor sites in the brain and elsewhere in the body. A positron-emission tomography scan could then locate the molecules and, by association, the targeted receptors. This would allow scientists to investigate abnormalities in the relative abundance and placement of receptors in people with particular disorders, such as schizophrenia, or look for changes after an intervention, such as therapy.

But first, millions of such molecules must be compiled, catalogued and tested to determine how they interact with proteins. "It's a brute force process, and it isn't interesting to watch," says Roth.

Luckily, the mechanics of the process have been largely automated, with robots and computers able to screen the molecules at a breakneck pace, adds Foote. And the NIH is already vetting proposals to get started.

Clinical research database

The NIH Roadmap will also create NECTAR, a publicly available repository of clinical trials results. Data sharing is critical to medical and therapeutic advances because testing medical interventions is costly and time-consuming, explains Lawrence Friedman, MD, acting deputy director of the National Heart, Lung and Blood Institute, and a member of the NECTAR implementation group. NECTAR's intent, he says, is to save time and money--and reduce duplication among researchers studying medical and therapeutic interventions--with its infrastructure through which researchers can collect and share research results.

To do this, researchers will have to agree upon common standards for diseases and outcome measures, Friedman notes; otherwise the results of different studies cannot be compared with one another. For example, two studies of heart disease may measure the incidence of a death without warning, termed "sudden death." However, one might define a death as sudden if it occurs within one hour of the onset of symptoms, and the other may include deaths that occur within 24 hours of symptom onset.

And while finding common standards is difficult in medical research, it can be even more challenging in the behavioral sciences, says Bruce E. Wampold, PhD, a professor of counseling psychology at the University of Wisconsin-Madison.

"Psychologists have a hundred measures for the same thing, and often they are highly correlated," Wampold notes.

But because psychological testing has become a lucrative industry, many people have a vested interest in the use of any particular measure, Wampold says.

And while a database of clinical trials--including tests of the efficacy of certain therapies--would benefit psychologists, they must be cautious when applying the medical model of clinical trials to therapy because the same treatment provided by two different practitioners can result in different effects, he notes.

"Much of the variance can be traced back to the provider, not the treatment," Wampold explains.

NECTAR's creators will consider such challenges as they build the database, says Friedman. "Like all of the roadmap, this isn't going to be easy--and it will take a while," Friedman adds. "But we think it will be worth it."

Interdisciplinary research grants

Drafters of the roadmap also hope to encourage collaboration by funding more joint research.

"The disciplines are heavily entrenched in department silos at universities, but the problems we are grappling with do not fit into those silos any longer," says Richard Suzman, PhD, associate director of the National Institute on Aging and a member of the interdisciplinary research implementation group.

For example, says Suzman, while a few diseases may be entirely genetic in origin, most originate from a range of factors that are genetic, environmental, bacterial, viral and behavioral. Scientists from all of these areas must work together, he says. However, terminology, methodology and philosophical differences may make communication difficult among scientists from different fields, says Ken Pugh, PhD, a psychologist at the Yale University-affiliated Haskins Laboratories and a pioneer of interdisciplinary research.

To break down the silo walls, NIH will provide grants to groups of multidisciplinary investigators to plan future research, says Michael Huerta, PhD, also a member of the interdisciplinary research implementation group. During these discussions, researchers will compare notes and perhaps bring some new life to old problems, Huerta says.

With the first grant deadline just recently passed, which disciplines will be represented in these initial discussions is currently unknown, he notes.

"But I can tell you that behavioral sciences were very well represented in the applications," Huerta says.

Further Reading

Researchers interested in learning more about new roadmap grants can visit the NIH Roadmap Web site at http://nihroadmap.nih.gov.