May 2004, Issue 2

Infectious Agents of Zoonotic Diseases - Is Genetically Identical Truly Biologically Identical?

Sam R. Telford III, ScD, joined the Tufts School of Veterinary Medicine in September 2002 as an associate professor. Trained in tropical infections, Telford is an ecologist who brings a new perspective to the study of infectious disease. Rather than looking at one agent for one disease, as is taught in many clinical settings, Telford investigates the entire microbial assemblage that is present at the site of infection. "The old tropical medicine textbooks say, essentially, that the first thing you see is not the cause," Telford comments. He wants to understand the life cycle of an infectious organism, and those of the whole caravan of organisms that tend to travel with it, in order to discover weak points in its defenses that can then be exploited and used against the organism in disease prevention and treatment. A broader goal of his research is to understand the evolution of infectious agents.

After receiving his BA in ecology and evolution from the Johns Hopkins University, Telford went to Harvard to begin a long and fruitful relationship. He received his MS in tropical public health in 1987 and his ScD in parasitology in 1990. He did research and lectured at Harvard School of Public Health for the next ten plus years before coming to Tufts. His initial interest in the ecology of Lyme disease has broadened to include that of other tick-borne infections, such as babesiosis, ehrlichiosis, deer tick virus, and tularemia.

Often called upon by local and state governments to figure out ways to reduce risk once an infectious outbreak occurs, Telford starts by taking in the big picture. He tries to put the puzzle together with the who, what, when, where, and how of the outbreak. He recently became involved in an outbreak of tularemia on Martha's Vineyard. Francisella tularensis, a highly dangerous tick-borne bacterium, is Number 4 on the list of infectious agents of serious concern to the US government. Tularemia is preceded only by smallpox, plague, and anthrax. While tularemia has been around for a long time, the disease is presenting in an unusual manner on Martha's Vineyard, taking a rare but potentially deadly pneumonic form in more cases than would be expected. Martha's Vineyard is the only place in the US to have witnessed two outbreaks of tularemic pneumonic disease.

The pneumonic form is presumably acquired by inhaling bacteria. Preliminary evidence of antibody levels in inhabitants of Martha's Vineyard suggests that landscapers have had more exposure to F. tularensis than others on the island. "So the perception is that there's something in the soil," Telford says.

Telford has a two-year exploratory NIH grant to look into tularemia infections on Martha's Vineyard. He wonders if the microbes that are on the Vineyard are slightly different biologically from those found elsewhere, making the Vineyard microbe more apt to cause infection. He also needs to find out how people are getting infected. To find the answers, Telford's group has been collecting potentially infectious materials from various sites on the island and testing them for F. tularensis. Telford's lab diagnoses tularemia by fluorescent antibody, PCR, mouse inoculation, and cultivation. He also plans to compare the Martha's Vineyard F. tularensis with F. tularensis from other areas to see if they are identical.

Being identical is beginning to take on a whole new meaning for microbiologists. The standard test for determining whether two bacteria are "genetically identical" depends on a specific piece of ribosomal DNA. If the two ribosomal DNAs are identical, the bacteria are considered identical. But that standard has been called into question by startling evidence Telford received recently about another bacterium, Babesia divergens.

In Europe Babesia divergens has been known for half a century to cause disease in cattle and humans. It causes a severe infection that is almost always fatal in humans with compromised immune systems. So when B. divergens showed up in the Eastern US in rabbits on Nantucket Island, there was cause for concern. But although the ribosomal DNA of the Nantucket B. divergens was genetically identical to that of the European B. divergens, when injected into gerbils, the Nantucket B. divergens did not cause infection or disease. So, are the two identical or not? Is genetic evidence sufficient to warrant a definition of identity?

"This is a bigger debate in the biology of microorganisms," Telford says. "If gerbils don't get infected, and if our pending cattle inoculation experiments fail to produce typical bovine redwater disease, it's probably not Babesia divergens, and therefore the molecular data is lying — or rather not lying, but we overinterpreted the molecular data." Telford reasons that molecular data in isolation from biological data may not be sufficient to define a microbe. "We have to start rethinking how we look at the relatedness of organisms. A lot of people hoped that all you'd need was the DNA and it would tell you everything, when in fact you also need elements of the life cycle."

Telford will be focusing on tularemia in the near future, but he hopes to work on mosquito-transmitted viruses, such as West Nile virus and the virus that causes Eastern equine encephalitis, as well as that for tick-borne encephalitis, when time allows. "One of the things that attracted me here [to Tufts] is the tremendous expertise with veterinary medicine, actually working with the animals in terms of pathology and such," Telford says. He is excited about the potential for new collaborations available throughout Tufts. Telford has been working with Stephen Rich, PhD, a fellow TUSVM faculty member, for many years on the evolution of ticks and spirochetes. He also has active collaborations with Henry Wortis, MD, Department of Pathology at the Medical School, Edouard Vannier, PhD, Tufts-NEMC, and Linden Hu, MD, Tufts-NEMC.

Besides his busy research schedule, Telford has considerable teaching and administrative duties. He is involved in setting up and teaching courses for the new PhD program begun at the vet school this year, and is serving as the school's coordinator for the combined DVM/MPH program. He recently submitted an NIH training grant to expand that program to include specific training in biodefense issues, an area where he has considerable expertise.

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