Hidden costs of biodefense research.

Infectious diseases have threatened human civilization for more than 2000 yr. Hippocrates seems to have been the first observer to record an influenza pandemic in 412 B.C. (UW-Madison 2004). In addition, a major plague epidemic likely occurred in Egypt in 540, and then spread to Europe and Asia in the 14th century (Smith 1996-1997). The latter, known as the “Black Death,” devastated the peoples of the Old World on multiple occasions and is an oft-cited example of infectious disease. More insidious and equally profound in contemporary times has been the steady increase of human immunodeficiency virus, which now infects 38 million people, with 5 million new cases per year worldwide, and has caused 20 million deaths since its first diagnosis (UN AIDS 2004). Malaria afflicts 300 million people globally, with 1 to 1.5 million deaths annually (WHO 2004). Yet these statistics pale in comparison with tuberculosis, from which one third of the world population is infected, with 2 to 3 million deaths annually, and antibiotic-resistant tuberculosis is on the increase (WHO 2004). The influenza pandemic of 1918 occurred on a global scale and resulted in 40 million deaths. It was the most devastating epidemic in world history, and the origin of the 1918 virus remains undetermined. What is known is that epidemics of influenza occur annually, and the likelihood of another pandemic is certain (Reid and Taubenberger 2003). Recent outbreaks of severe acute respiratory syndrome (SARS) elicit concern that a similar event might occur with this newly emergent zoonotic coronavirus. Of the last 12 emerging infectious diseases, 11 have been zoonotic, or transmitted from animals to people (F. A. Murphy, University of California-Davis, personal communication, 2004). Increasing populations, poverty, politics, religious zealotry, despair, travel, environmental degradation, intensive farming, and many other factors are creating a virtual “witches brew” of opportunity for emerging and re-emerging pathogens. Iatrogenic introduction (a.k.a. bioterrorism) is simply another means of transmission and spread of infectious agents, which, in the current political climate, evokes considerable fear among the populace. Through the dark side of the human condition, pathogens can now be elegantly engineered genetically, although in many cases, this process is not necessary because relatively primitive means can be used to utilize them for malicious intent. Bioterrorism, which was on the agenda of the cold war for decades, has taken on totally new dimensions with the realization that the geopolitics of detente between super powers can no longer contain the possibility of a bioterrorist event from happening. The US anthrax scare showed us that a simple anonymous postal envelope can serve as a fomite of terror. Remarkably, 22 cases and five deaths from anthrax, which are certainly not trivial, have effectively terrorized the politics of research in the United States, and in many ways have overshadowed the much more sobering but paradoxically accepted terror of AIDs, tuberculosis, malaria, influenza, and emerging and re-emerging infectious diseases. The National Institutes of Health (NIH), which was established in 1949, has been an American success story. It fostered innovative research and individual initiative within the scientific community, which in turn created a vital biomedical research infrastructure for academia, including robust scientific environments for training the next generation of scientists in hypothesis-driven research. The system allowed funding of a broad range of subjects, with peer review and funding based on merit and relatively unencumbered by politics. This broad base of science fostered interdisciplinary discovery as research results were openly published in peer-reviewed journals. Advances in one field often fostered advances in others. Congress recognized the enormous impact of NIH-funded research on both the economy and the health of the nation, with unprecedented bipartisan support that resulted in doubling of the NIH budget over the last 5 yr. This investment has ended, and the modest increases that are projected for the NIH budget cannot keep pace with increasing costs of performing science, sustaining excellence, and solving complex diseases that require basic research. Those days are indeed over, and they ended even more abruptly after September 11, 2001. Almost immediately, $1.7 billion became available for biodefense research. The Stephen W. Barthold, D.V.M., Ph.D., is a Professor in the Department of Comparative Medicine, University of California, Davis, and a member of the Institute of Medicine.