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Scientists Explore Evolution of Infectious Diseases

By Linda Joy

Which strain of flu virus will strike next year? Why is antibiotic resistance such a problem in hospitals? Could vaccines for pneumonia or dengue fever do more harm than good?

For medical researchers who study infectious diseases, these are important and complex questions. And increasingly, biomedical scientists are finding clues to these puzzles from an unexpected source — evolutionary biology.

To bring some of the puzzle pieces together, Dr. Irene Eckstrand of the NIGMS Division of Genetics and Developmental Biology organized a meeting on the "Evolution of Infectious Diseases" that was held recently. The meeting was co-sponsored by NIGMS and the Ellison Medical Foundation, a private, nonprofit organization that funds aging and global infectious disease research.

Evolutionary biology can contribute significantly to the understanding of disease-causing organisms, Eckstrand said. "Because evolution is a fundamental feature of all living systems, it must be built into the models," she explained. One goal of evolutionary biology is to build better models of how and why populations change over time. Another is to help identify which genes and blocks of genes are undergoing evolutionary changes, an important consideration in developing antimicrobial drugs and vaccines. A third goal is to build mathematical and computational models that give insight into biological processes.

Scientists (from l) Karen Day, University of Oxford; Daniel Hartl, Harvard University; and Dyann Wirth, Harvard School of Public Health, discuss differing models for dating the most recent common ancestor of the malaria parasite during a break at the "Evolution of Infectious Diseases" meeting held at the Natcher Conference Center recently.

The meeting was held to give researchers participating in an NIH funding initiative on the same topic the opportunity to look for common themes in the evolution of disease-causing organisms and to identify productive areas for future research. The initiative was started 2 years ago by NIGMS and NIAID. NIDCR and NIDDK have also participated. Its goal is to develop a predictive science of infectious disease by applying evolutionary biology methods to the study of disease emergence, prevention and treatment. To date, the initiative is funding 35 research projects.

The more than 100 attendees included NIH grantees, other leading evolutionary biologists, mathematicians, computer scientists and infectious disease experts from around the world. Participants were eager to share their own results and learn about the work of colleagues whose research covered diverse organisms such as Streptococcus bacteria, the malaria parasite, various plant pathogens, the Lyme disease organism and the dengue fever virus.

"We want to understand the basic principles of evolution. The fact that we're doing it with infectious diseases makes it more relevant and interesting," Eckstrand said. Evolutionary biologists have already helped biomedical researchers more accurately predict future flu strains and develop more effective drugs and vaccines.

Several of the scientists who attended the meeting have recently published articles in Science and other prominent journals, an indication of heightened interest in this field. "It's a very hot topic," said Eckstrand.

During the meeting, scientists presented recent findings on evolutionary processes in many different disease-causing organisms and the hosts they infect, and on related topics such as antibiotic resistance and vaccine development.

In one workshop devoted to the "Evolution of Virulence," Dr. Michael Hood of the University of Virginia presented evidence of a "host-shift" in a fungus that attacks particular flowers in the carnation family. The fungus causes anther smut disease in one species of flower, yet in field studies Hood observed it infecting a related species that it had previously never infected.

Understanding how and why this shift occurred could help biomedical researchers understand the ecological and genetic conditions that lead bacteria, viruses and fungi to shift species. Many microbes that cause human disease, including the AIDS and flu viruses, shifted to humans from other species.

In another talk, Dr. Marc Lipsitch of Harvard School of Public Health discussed a study that could help assess the potential effects of new vaccines for pneumonia. Although a vaccine could block a strain of Streptococcus bacteria known to cause pneumonia, it might also make way for other related — and potentially harmful — strains to colonize the respiratory tract.

Certain strains of Streptococcus colonize specific tissues within the body. Other strains are held in check by competition. Removing one strain through widespread vaccine use could release other strains from their competitive disadvantage. Sufficiently complex models of the ecological relationships between related strains are needed to help assess the potential effects of widespread use of a vaccine against one strain, he said.

In other talks, researchers challenged common notions about antibiotic resistance, discussed models for the evolution of malaria and covered the development of variation in a bacterium associated with stomach ulcers, Helicobacter pylori. Dr. Paul Keim of Northern Arizona University, an internationally known expert on DNA analysis of the bacterium that causes anthrax, delivered the keynote speech on "Evolutionary Biology and Bioterrorism."

Many attendees told Eckstrand that prior to the meeting, they only knew a small percentage of the other scientists attending. The meeting gave them the opportunity to meet many new colleagues and discuss new collaborations. Several scientists also told her that for that reason, the meeting was especially productive, Eckstrand said.

To learn more about the meeting, see http://pub.nigms.nih.gov/evolution.


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