ing research effort, summarize the current market for these scientists, and recommend specific changes in the NRSA program that may be effective in expanding the cadre of physician-scientists needed at this time.

ADVANCES IN CLINICAL SCIENCE

Advances in clinical science have been enormous and include, but are not limited, to the following:

  • Identification of the genetic defect in various genetic disorders, including cystic fibrosis. Cystic fibrosis is the most common genetic disorder in Caucasians, affecting 1 of every 2,000 children. The disease is characterized by pulmonary infections and pancreatic insufficiency and is due to a cellular defect in the development of secretions. The genetic defect associated with the disorder is found in chromosome 7. This discovery allows three major advances. First, it allows genetic counseling within families. Second, it has allowed a determination of the product of the gene. This information will provide a rational approach to developing drugs to correct the defect. Finally, it will allow studies that attempt to replace the defective gene with a normal one in tissues that are affected. Indeed, such somatic gene therapy has already begun.

  • Identification of the gene associated with bowel cancer. Very recently, two separate groups of investigators demonstrated a genetic defect localized to chromosome 2, which is associated with hereditary nonpolyposis colon cancer. The gene involved appears to control DNA repair, and a defective gene seen in patients with colon cancer leads to instability of cellular DNA. This research is a spectacular example of the different ways in which basic research can lead to clinical advances. In one laboratory the research developed from studies performed in yeast and bacteria that examined how these organisms repair DNA and the genetic defects associated with DNA instability. In another laboratory there is a long history of studies in humans examining genetic defects associated with a variety of colon cancer syndromes. In other words, this remarkable advance in our understanding of colon cancer came from distinct pathways, one originating from basic studies of normal mechanisms in bacteria and yeast and the other from more clinically oriented studies looking at abnormal growth and differentiation of colon cells. These studies will allow the development of reagents that can be used to screen for colon cancer.

  • Creation of an animal model for ankylosis spondylitis by using transgene methodology. Ankylosis spondylitis is a syndrome that predominantly affects joints of the spine. Approximately two decades ago it could be demonstrated that the disease was significantly associated with a specific HLA type, HLA-B27. Indeed, 90 percent of patients with ankylosis spondylitis had the HLA-B27 genotype. In an attempt to demonstrate the nature of the association between the gene and the disease, investigators established a rat model in which the human HLA-B27 gene was inserted by using transgene methodology. In some of the animals a disease developed that mimicked human ankylosis spondylitis. These animals not only provide a model for determining just how the gene influences the expression of the disease but also for deciding what other factors may be involved. They also provide a model for studying the effectiveness of various forms of therapy.

The importance of clinical research to advancing our understanding of clinical disorders is captured in a recent editorial in Science written by Editor-in-Chief Daniel E. Koshland Jr. (1993):

In the 1980s and 1990s NIH researchers, intramural and extramural, performed the first trial of gene therapy in humans, proved the effectiveness of methotrexate for treating rheumatoid arthritis, developed new methods for growing skin to repair burns, showed that control of glucose levels slows progression of diabetes, showed effectiveness of cholesterol reduction in the prevention of heart disease, demonstrated an effective treatment for spinal cord injury, found a new drug for Parkinson's disease, showed that aspirin and coumadin lower the risk of stroke, developed methods of hypertension control that have reduced heart attacks and strokes by more than 50 percent, and so on for many other discoveries. .... These followed many earlier discoveries, including the polio vaccine, the measles vaccine, hormone replacement therapy, fluoride to prevent tooth decay, to name a few. We are living longer, we are living with less pain, we are living with less cost to alleviate health deficiencies than any previous generation because of the findings of health researchers. .... In the not-so-distant past, smallpox epidemics killed 25 percent of the inhabitants of towns that were invaded by the virus. Today we are storing the last traces of the virum because that dread disease has been eradicated from the Earth.

Clearly, this partial list of clinically relevant discoveries supports the practical value of clinical research. The United States is the world leader in clinical research and we must make a renewed commitment to retain this leadership. The recommendations of this report should allow us to remain in this position of preeminence.

ASSESSMENT OF THE CURRENT MARKET FOR CLINICAL SCIENTISTS

Degree Production and Career Patterns

Clinical scientists work in a variety of settings but primarily in academic health centers. Between 1981 and 1991, the number of full-time faculty employed in clinical depart-



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