PLANNING FOR CHANGE IN BIOMEDICAL RESEARCH

Michael Gottesman

Running the NIH has been described as equivalent to steering an aircraft carrier—you cannot turn on a dime and you have to think way ahead to keep from running aground. Biomedical research is entering an era of enormous change, and we all need to start thinking about how these changes will affect how we will do research in the future. Scientists are by nature conservative–"If it ain’t broke, don’t fix it!" is a favorite phrase of many bench scientists in describing their experimental approaches. But even the most conservative of us realize that the future will not look like the present. What should the intramural program at NIH be doing to stay one step ahead of new developments in biomedical research?

We will undoubtedly need to deal with the enormous quantities of data currently being loaded into central databases: genome sequences; microarray gene expression analyses as a function of development, disease, tissue type, etc.; complete medical records, including radiological and pathological images; and the entire world’s literature at our fingertips. We need networks that allow quick and easy access to this information, software that predigests information or displays it in ways that are meaningful to us, and appropriate computer terminals for all scientists at NIH. The leadership of NIH has been working with Al Graeff, the director of the Center for Information Technology, and with IT staff in the Institutes and Centers to be sure that the most flexible infrastructure exists to support these scientific demands. The Clinical Center has taken the lead in developing a state-of-the-art Clinical Research Information System (CRIS) to replace our outmoded Medical Information System (MIS). This development takes money and talented individuals, and we are making good progress on both fronts.

The scale of many of our laboratory activities is also undergoing great change. For example, in the 1940s and 1950s, we were content to purify an enzyme and demonstrate an activity; in the 1960s and 1970s, we wanted to clone and sequence the enzyme; in the 1980s and 1990s, we expected to do all of these and also crystallize it to determine structure, map the gene, and create a genetic model lacking or mutating the enzyme to determine its function. In the new millennium, no one is satisfied with one enzyme—we want to characterize the complete family of such enzymes, its whole evolutionary tree, and perhaps the entire pathway in which the enzyme resides.

In the not too distant future, we will be combining physiological and molecular information to gain insight into how cells actually work, how they integrate into tissues and organs, and how these organs produce organisms that interact with their environments.

To satisfy these scientific imperatives, we need resources to allow creation of new animal models—housing transgenic mice alone is a major resource commitment—and the requirements for zebrafish and large animal models will be substantial. We are currently planning a new central vivarium on campus that will provide the space and flexibility to support these models and resources for histopathology, genetic manipulation, behavioral analysis, and special surgery.

We will also need resources to support high-resolution structural studies. Currently, the NIH intramural program supports a dedicated X-ray beam line at Brookhaven and one at Argonne for our crystallographers. We have also upgraded our high-resolution electron microscope facilities, which will be housed in Building 50, and we are planning for larger and larger magnets for high-resolution NMR studies of molecular structure. For clinical imaging research, we have a shared in vivo NMR center, and the new animal imaging facility will open in 2001. These facilities will put intramural NIH at the forefront of the technology needed to support our research.

The design of our new laboratory buildings reflects the changing nature of biomedical research. Each of the new buildings on campus has a basic interstitial design, which means that all of the support utilities for the labs are on floors layered between the lab floors. This will make it easy in the future to change and maintain plumbing, electrical, and air supplies to the labs without disrupting the laboratories themselves. Other elements of new lab design include computer networking, electrical supply that meets the high energy needs of current equipment, and more efficient heating and cooling systems. And all of the new buildings bring natural light and more space to our researchers. The NIH Master Planning process has provided a mechanism for rational growth and renovation of our campus, and we are currently considering other ways to meet our burgeoning space needs.

Finally, the vast power that these new research tools give us also brings new responsibilities. Current ethical concerns about clinical research are a direct result of our increasing ability to restructure human genes and human bodies. Our planning for the future must include oversight systems to reassure both ourselves and the public that we are taking the right approaches and continuing to serve humanity.

—Michael Gottesman
Deputy Director for Intramural Research

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