Collins describes road map for medicine's future

Buoyed by the completion of the historic effort to decode the human genome, Dr. Elias Zerhouni, the first radiologist director of the National Institutes of Health, has laid out an ambitious plan to revolutionize medicine.

Zerhouni's road map -- announced in September -- focuses the combined energy of the NIH's 27 institutes and centers, according to Dr. Francis S. Collins, director of the National Human Genome Research Institute.

Collins substituted for Zerhouni on Monday in the presentation of the RSNA's annual Pendergrass New Horizons lecture. Zerhouni flew to Africa over the weekend to join members of the administration for the launch of a new international AIDS initiative.

Radiology and the emerging field of molecular imaging play prominent roles in the road map, Collins said. They factor into each of three major initiatives: new pathways to disease, interdisciplinary research teams of the future, and reengineering of the research enterprise.

All of the road map's goals were derived at least in part from discoveries by the Human Genome Project, the massive campaign that produced a catalog of three billion genetic sequences. These sequences make up the building blocks for discoveries of genetic pathways and networks responsible for disease, according to Collins.

"Although we have the sequences in front of us, we cannot precisely say which is and is not a gene, what the protein products of those genes actually do, and how they interact with one another," he said.

The road map calls for the creation of a computer model of cell biology to simulate and predict the cell's behavior in any circumstance. Structural biology will provide 3D images of proteins and other structures. Nanomedicine will lead to interesting medical applications, Collins said.

The creation of a molecular library represents a paradigm shift for the NIH, according to Collins. By discovering genes and their byproducts, the HGP helped identify tens of thousands of potential genetic pathways and molecular targets that will ultimately result in new therapies. So many promising targets exist that their potential will not be realized unless academic centers are empowered to conduct research.

Combinatorial chemistry and the availability of large libraries of chemical compounds make it possible to set up high-throughput screening laboratories to assess promising assays and devise a short list of compounds representing antagonists and agonists for specific molecular targets, he said.

The first of these laboratories will be established on the NIH campus before the end of the year. Five additional labs will be funded at various universities over the next two years.

The assays that attract the most attention will have a direct connection to molecular imaging, according to Collins. Imaging agents will be attached to compounds that target specific structures.

The NIH is planning to substantially increase funding for molecular imaging research, Collins said. The underlying goal is to find binding elements for specific targets, coupled with a universal linking element connected to a detector element. Gadolinium nanoparticles capable of detecting nascent vascular thrombus are an example.

Program goals include:

• enabling preclinical disease detection for a long list of conditions
• creating personalized, targeted therapies for molecular profiling of cell and tissue function
• delineating cell physiology and functional data for personalized treatment and computational modeling

"These are ambitious but obtainable goals in the current climate," Collins said.

To realize these goals, however, imaging researchers will have to overcome problems with resolution. Imaging will have to become much more sensitive if some molecular imaging applications are to find a place in clinical practice. More research chemists are needed, and the synthesis capabilities of laboratories must be expanded, he said.

As a consequence of the road map, academic radiologists will soon receive requests for proposals for initiatives to solve these problems, Collins said. The new Director's Innovation Awards, $500,000 five-year grants, will be issued to individual researchers who have shown promise in making discoveries relevant to the NIH's goals for molecular imaging.

Although the aims of the road map may appear futuristic, Collins predicted that molecular imaging will influence medical practice by 2010, and individualized preventive medicine will be a reality in the next six years. Predictive genetic tests for at least 12 diseases will be in general use, and molecular imaging will be used extensively for early disease detection.

"We crossed the threshold this year from not knowing our own instruction book to knowing it. The most critical database for the human species is now in hand," Collins said. "We need to be bold, and the road map attempts to achieve that."