for the following reasons: specialized veterinary care, which for all species is usually distributed in a species-nonspecific fashion, as are administrative and staff costs; the increased personnel efforts that are required to meet regulatory-compliance needs; and Office of Management and Budget (OMB) indirect-cost allotments.

For example, one US biomedical institution switched from non-species-specific allocation of costs to species-specific allocations (using an independent accounting firm) and lowered mouse charges by 30-40% (Stanford Medical School, 1998). Its former assessed charges exceeded by a factor of 2-5 the actual costs at institutions that use only mice for their research. The high mouse charges are common in the United States, but most laboratories in Europe and Japan are costed more directly or are subsidized. If this trend continues, many US researchers will have great difficulty in financially supporting mouse facilities.

Actions by major funding agencies could relieve much of the burden: First, all costs and resulting charges could be strictly species-specific. Second, cost-accounting for simple husbandry could be separated from that for veterinary-intensive care. Third, efforts to simplify (and, when appropriate, eliminate) regulatory-compliance requirements could be undertaken. Fourth, the A-21 set of guidelines from OMB regarding indirect cost charges for federally-funded research could be reevaluated as to whether animal facilities can be removed from the special-services category, so that indirect costs could be lowered.

4.2 Increased Competition from Europe and Other Countries

In many countries, there appears to be a trend away from the customary hierarchical systems of funding, research, and employment of scientists toward the US system of competitive peer review. There also appears to be a trend toward better funding from government and private agencies and an increasing emergence of the biotechnology industry in many European countries. Together, those factors will enhance the quality of non-US immunology and make it more competitive.

4.3 Clinical Immunology and the Shift Toward HMOs

The clinical impact of immunology has long been limited by clinical subspecialization. For example, although the clinical practice of allergy is separate from other aspects of clinical immunology (such as rheumatology), basic and clinical research in the two fields overlap extensively. Until recently, clinical immunology barely existed as a definable field. Although the situation had shown signs of improving, reports (May et al. 1997; Campbell et al. 1997) indicate that the increasing dominance of HMOs in funding medical care in the United States potentially has an increasingly adverse effect on clinical research in general and clinical immunology in particular. This are several reasons. For example, HMOs compete for patients with academic clinicians, and this means that fewer patients are available for academic clinical trials; this poses a loss of a source of income that has traditionally been a source of funding for academic clinical research and a concurrent loss of jobs and opportunities for training of clinical immunologists.

Figure 4.1 shows the number of US citizens and permanent resident PhD students in immunology, and Table 4.1 and Figure 4.2 show the degree to which they are supported by NIH. As shown in Figure 4.1, the number of PhD students in immunology research has roughly doubled over the last 20 years. The percentage of these students supported by NIH

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