The "NIH Roadmap for Medical Research" released last week by NIH Director Elias A. Zerhouni contains several important physical sciences and interdisciplinary components. The plan will guide NIH's research during the 21ast century, and has three major themes: New Pathways to Discovery, Research Teams of the Future, and Re-engineering the Clinical Research Enterprise. Selections from the first two themes pertinent to physical sciences research are below. The entire plan may be viewed at http://nihroadmap.nih.gov
NEW PATHWAYS TO DISCOVERY:
"To fully capitalize on the recent completion of the human genome sequence and many recent discoveries in molecular and cell biology, the research community needs wide access to technologies, databases and other scientific resources that are more sensitive, more robust and more easily adaptable to researchers' individual needs. Among the resources to be established are libraries of chemical molecules that may provide: probes of biological networks; imaging probes for molecular and cellular events; improved computational infrastructure for biomedical research; nanotechnology devices capable of viewing and interacting with basic life processes; and potential targets for new therapies.
"These initiatives will provide a solid scientific foundation for new strategies for diagnosing, treating, and preventing disease. Implementation groups in this area are: Building Blocks, Biological Pathways, and Networks. Molecular Libraries & Molecular Imaging. Structural Biology. Bioinformatics and Computational Biology. Nanomedicine"
Molecular Libraries and Imaging:
"In these initiatives, NIH will support development of high-specificity/high-sensitivity probes with the goal of improving detection sensitivity 10- to 100-fold within five years. An existing NIH database of imaging probes relevant to cancer and brain function will be expanded to establish a single database that describes specificities, activities and applications of imaging probes for a wide range of diseases and biological functions.
"In addition, NIH will construct an Imaging Probe Development Center to provide a mechanism for producing significant quantities of probes for which there is no good commercial supplier, as well as to generate novel imaging probes for biomedical research and clinical applications. The development of these probes will be aided by discoveries that emerge from the screening of small molecules for their affinity for targets of interest. Once developed, these probes will in turn aid the development of effective therapeutic agents by monitoring their biological behavior.
"Molecular imaging holds great promise for early detection and treatment of numerous diseases, for providing researchers with detailed information about cellular physiology and function, and for facilitating the goal of personalized medicine. By significantly enhancing the support of this emerging field, the NIH will ensure that molecular imaging will become a powerful tool for biomedical research and will be a synergistic component of the overall research in molecular medicine that promises landmark improvements in clinical care."
" The NIH Roadmap's Structural Biology initiative is a strategic effort to create a gallery of molecular pictures of the shapes of all the different types of proteins in living things. This research investment will involve the development of rapid, efficient and dependable methods to produce protein samples that scientists can use to determine the three-dimensional structure, or shape, of a protein. The new effort will catalyze what is currently a hit-or-miss process into a streamlined routine, helping researchers clarify the role of protein shape in health and disease.
"What will it take to accomplish this task? NIH will begin by funding interdisciplinary groups of scientists to develop innovative methods for producing large quantities of membrane proteins, those proteins that are wedged tightly within the wrappings of our cells. Scientists currently find it extremely difficult to wrestle these proteins out of cells in a condition suitable for structure-mapping techniques.
"Project planners expect that the development of new, protein-producing methods will lead to the creation of specialized facilities that will be capable of quickly and efficiently manufacturing large quantities of research-grade membrane protein samples. Once scientists have access to sufficient quantities of proteins for their experiments, they can determine a protein's shape using standard methods involving X-rays or extremely powerful magnets."
Bioinformatics and Computational Biology:
"Biology has always been a haven for microscopes, test tubes and Petri dishes, but this conventional picture of the field is expanding rapidly. Sophisticated techniques borrowed from physics enable scientists to use computers and robots to separate molecules in solution, read genetic codes or paint pictures of the three-dimensional shapes of natural molecules like proteins. All of these techniques generate large amounts of data, and biology is changing fast into a science of information management."
"By embarking on the Bioinformatics and Computational Biology initiatives, the NIH Roadmap is paving a future ‘information superhighway' dedicated to advancing medical research. A central focus of the initiative will be a set of National Centers for Biomedical Computing, the first few of which will be funded next year.
"As the centers begin to generate the software and data management tools to serve as fundamental building blocks for 21st century medical research, individual scientists will be funded to work together with the centers. ‘Big science' and ‘small science' will work hand-in- hand to advance all of science. Through these efforts, researchers will be able to share data gathered from large experiments. The best minds will be able to work together more efficiently to tackle unsolved biomedical mysteries, such as the role of heredity in individuals' different responses to medicines and the complex interplay of genetic and environmental factors in common diseases such as heart disease, cancer and diabetes.
"The Bioinformatics and Computational Biology initiatives also will create a national software engineering system. Through a computer-based grid, biologists, chemists, physicists and computer scientists anywhere in the country will be able to share and analyze data using a common set of software tools. Developers of the project envision that the system will resemble that of the integrated software packages for office tools installed on most home computers today, in which information can be traded seamlessly between software such as spreadsheets, word processing and e-mail programs."
"Federally supported research in this area, conducted under the rubric of the National Nanotechnology Initiative, is ongoing with coordinated support from several agencies. The NIH Roadmap's Nanomedicine initiatives will build on these efforts, with its focus centering squarely on health-related nanotechnology applications."
"NIH will begin its effort by establishing a handful of Nanomedicine Centers, which will serve as the intellectual and technological centerpiece of the Nanomedicine initiatives. These centers will be staffed by a highly interdisciplinary scientific crew including biologists, physicians, mathematicians, engineers and computer scientists. Research conducted over the first few years will be spent gathering extensive information about how molecular machines are built. A key activity during this time will be the development of a new kind of vocabulary – lexicon – to define biological parts and processes in engineering terms.
"Once researchers have completely catalogued the interactions between and within molecules, they can begin to look for patterns and a higher order of connectedness than is possible to identify with current experimental methods. Mapping these networks and understanding how they change over time will be a crucial step toward helping scientists understand nature's rules of biological design. Understanding these rules will, in many years' time, enable researchers to use this information to address biological issues in unhealthy cells. The availability of innovative, body-friendly nanotools will help scientists figure out how to build synthetic biological devices, such as miniature, implantable pumps for drug delivery or tiny sensors to scan for the presence of infectious agents or metabolic imbalances that could spell trouble for the body."
RESEARCH TEAMS FOR THE FUTURE:
"The scale and complexity of today's biomedical research problems increasingly demands that scientists move beyond the confines of their own discipline and explore new organizational models for team science. For example, imaging research often requires radiologists, physicists, cell biologists, and computer programmers to work together on integrated teams. Many scientists will continue to pursue individual research projects; however, they will be encouraged to make changes in the way they approach the scientific enterprise. NIH wants to stimulate new ways of combining skills and disciplines in both the physical and biological sciences. The Director's Innovator Award will encourage investigators to take on creative, unexplored avenues of research that carry a relatively high potential for failure, but also possess a greater chance for truly groundbreaking discoveries. In addition, novel partnerships, such as those between the public and private sectors, will be encouraged to accelerate the movement of scientific discoveries from the bench to the bedside."
"Biomedical research traditionally has been organized much like a series of cottage industries, lumping researchers into broad areas of scientific interest and then grouping them into distinct, departmentally based specialties. But, as science has advanced over the past decade and the molecular secrets of life have become more accessible, two fundamental themes are apparent: the study of human biology and behavior is a wonderfully dynamic process, and the traditional divisions within biomedical research may in some instances impede the pace of scientific discovery.
"To lower these artificial organizational barriers and advance science, this set of NIH Roadmap initiatives will establish a series of awards that make it easier for scientists to conduct interdisciplinary research. These new awards include funding for: training of scientists in interdisciplinary strategies; creation of specialized centers to help scientists forge new and more advanced disciplines from existing ones; and initiation of forward-looking conferences to catalyze collaboration among the life and physical sciences, important areas of research that historically have had limited interaction.
"Interdisciplinary research integrates the analytical strengths of two or more often disparate scientific disciplines to solve a given biological problem. For instance, behavioral scientists, molecular biologists and mathematicians might combine their research tools, approaches and technologies to more powerfully solve the puzzles of complex health problems such as pain and obesity. By engaging seemingly unrelated disciplines, traditional gaps in terminology, approach and methodology also are gradually eliminated. With roadblocks to potential collaboration removed, a true meeting of minds can take place that broadens the scope of investigation into biomedical problems, yields fresh and possibly unexpected insights, and may even give birth to new hybrid disciplines that are more analytically sophisticated.
"By establishing new awards aimed at building interdisciplinary research teams, NIH hopes to help accelerate research on diseases of interest to all of its institutes, centers and offices with an eye toward improving the nation's public health. As currently planned, the first awards will be made in FY 2004 to establish 15 planning grants for interdisciplinary research centers. In addition, Request for Applications, or RFAs, will also be issued in FY 2004 to provide training to scientists in this emerging area of science.
"In developing these NIH Roadmap initiatives, organizers have taken great pains to lower several traditional barriers that have slowed interdisciplinary studies. For instance, the new awards will: grant principal investigator status to not one investigator, as is now the norm, but to all key members of the research team; provide indirect research costs to multiple institutions involved in the research; require integrated reviews of grants, which take into account the melding of the various disciplines to the problem at hand; and encourage the interdisciplinary team to evolve in both directed and serendipitous ways."
Information on grants and funding opportunities can be found at: http://nihroadmap.nih.gov/interdisciplinary/grants.asp