National Institute of
General Medical Sciences

In 1998, the National Institute of General Medical Sciences (NIGMS) initiated a grants program on the Evolution of Infectious Diseases. As of mid-2002, NIGMS has funded 27 research grants in this field; other NIH institutes have funded an additional 8 grants. The program encourages development of a predictive science by applying the perspectives, theories, and methods from many scientific disciplines to important issues of disease emergence, transmission, prevention, and the consequences of treatment. Each research grant explicitly involves interdisciplinary collaborations.

On August 28-29, 2002, NIGMS and the Ellison Medical Foundation invited all grantees, as well as their collaborators and students, to discuss their current work and the next big questions facing the field. Over the two-day meeting, 109 participants heard presentations and discussions on the following topics:

• molecular epidemiology of pathogens
• mathematical and experimental models of evolutionary dynamics
• prevention and treatment of infectious diseases
• evolution of virulence
• evolutionary ecology
• living in place: plant models of resistance to infectious diseases
• untested assumptions of models of infectious disease
• evolutionary biology and bioterrorism

Several themes emerged from the meeting.

• Many parasites that cause diseases such as anthrax, plague, malaria, and tuberculosis are monomorphic; that is, there are very few genetic or protein variants in these pathogens. However, the few specific genes that do show variation are likely the targets of intense selection. (In malaria, the variation appears to be concentrated in membrane proteins.) These pathogens have complex life cycles involving several host species and must evolve mechanisms for evading the defenses of all of these hosts. It may be worth considering strategies for designing drugs that target proteins under selection, which could be identified using evolutionary tools.
   
• By contrast, commensal microbes, such as Escherichia coli, Helicobacter pylori, and Streptococcus, tend to be highly polymorphic. They live for generations within a host and find tissue-specific or ecological niches within the body. Genetic variants compete with one another for niches and are held in check by competition. If a common strain is eliminated by antibiotic therapy, for example, a rare strain may be released from its competitive disadvantage and become common. This poses a challenge to medicine because treatment may eliminate the major population of pathogens, but if small populations of microbes remain behind, the disease can re-emerge.
   
• Population models have been developed with Drosophila or E. coli in mind. While these models give us many useful insights, they may not work well for organisms under extreme selection, such as parasites. A challenge for population and evolutionary biology is to develop new mathematical models to explain the dynamics of infectious disease systems.

Participants agreed that the meeting was very useful in stimulating new lines of research and new collaborations. For the future, it will be important to focus on improving the mathematical analyses of infectious disease systems and on integrating data across many disciplines.

Additional Info:
Web Site  / NIH Record Story (no longer available)