Etiology

The etiology, pathogenesis and treatment of this syndrome are not well studied but appear primarily to trace to a mismatch between the number of independent investigators and the funds available for sustaining a healthy steady state. The latter remains dominated by NIH extramural funding, especially R01 funding.

To be sure, the NIH and NSF are not the sole causes of the toxic professor syndrome. When NIH funds increased many years ago, there was a clear expansion at many universities. More faculty members were hired, leading to an increase in the number of grant applications. Additionally, universities required investigators to obtain increasing portions of their salaries from their direct funds. In effect, and unwittingly, the NIH has emerged as the key supporter of biomedical research as well as faculty salaries. As such, academic medicine and its administrative leaders have become increasingly dependent on the NIH for basic operation. The price has been a highly leveraged financial system, leading to stress and contributing to what is effectively unfunded or underfunded faculty.

Pathogenesis

The pathogenesis of this disorder can be understood by analogy to simple metabolic pathways with a rate-limiting initial step, subsequent reactions that advance precursors/products on a metabolic pathway, and simple feedback mechanisms (Fig. 1). As flux through the pathway slows at key junctures, there is an accumulation of toxic intermediates and byproducts, primarily the unfunded investigators. This profoundly influences the operation of the system. Not only are those faculty members unable to conduct the research to which they have already committed lifetimes of study and preparation, but they become financial burdens on their departments and colleges. The professors send negative feedback signals to earlier steps in the pathway, alerting junior faculty, postdoctoral fellows, graduate students and even undergraduate students to the overflow in the system, thus discouraging students from pursuing training and careers in academic research.

Treatment

So what is the cure? The solution will entail devising a rational approach for the growth and sustainability of biomedical research as we move into the 21st century. We cannot offer specific solutions, but we do suggest some areas of study and further investigation.

One approach will require action by the NIH, preferably in conjunction with academic societies and college administrators (e.g., AAMC). From an experimental point of view, these toxic academic pathways are amenable to modeling approaches and economic analyses. For example, one could predict a reasonable steady-state number of investigators who can be supported by the system (the NIH, universities and other funding sources) and the natural turnover of those investigators, allowing the determination of a healthy rate of influx into the system. The NIH can help control the influx by awarding a predetermined number of R01s to beginning and early career investigators. The current policy of inflating this number simply backfires; it increases the flow through the assistant professor level and creates a bottleneck that spills into the unfunded investigator pathway (Fig. 1).

Academic institutions, individually or collectively (e.g., through AAMC), also could help. Lessening the salary burden on individual proposals would enhance the ability of an investigator to conduct research with a reduced number of awards. Analysis should also extend to defining the necessary size of the workforce and supplemental components as well as approaches that incentivize academic institutions to participate in defining sustainability.

There are additional examples of efforts to alleviate, if not cure, this syndrome. The American Society for Biochemistry and Molecular Biology Public Affairs Advisory Committee has outlined a series of recommendations for providing a healthier environment. These essentially involve refocusing NIH priorities toward individual-investigator, RO1-driven research.