Dangerous History: The Genetic Secrets of a Savvy Killer

By Sohn, Emily | Science News, May 26, 2007 | Go to article overview

Dangerous History: The Genetic Secrets of a Savvy Killer


Sohn, Emily, Science News


Throughout recorded time, tuberculosis has wrought death among the people infected and frustration among those trying to tame it. As recently as the 1950s, prescribed treatment included little more than rest, sunlight, and fresh air. Today, patients take powerful drug cocktails for months. Even so, tuberculosis kills more people each year than any infectious disease other than AIDS.

And it is still unclear exactly how Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB) in people, does its damage. Other mysteries include why only some people get sick after being infected and why some outbreaks have managed so effectively to dodge vaccines and to resist antibiotic treatment.

In recent years, DNA analyses and fossil finds have revealed a surprising diversity in the genetic makeup of M. tuberculosis. Among its 4,000 genes, small but important differences appear to separate thousands of M. tuberculosis strains into distinct families, each with its own pattern of infection. A scientific community that long assumed TB had one genetic profile is now adapting to the idea that tens of thousands of years of evolution have sustained a pathogen that foiled human defenses by constantly changing.

As researchers piece together the M. tuberculosis family tree, they are finding tantalizing clues about why the pathogen has been so hard to get rid of and why new and virulent strains have repeatedly appeared in various places throughout history and are still showing up in Africa, Eastern Europe, and Asia today. The new information may eventually lead to better vaccines and treatments that target individual strains.

"It's been the default assumption for years that it's not really worth looking at the differences [among M. tuberculosis strains] because those differences must be so small," says David Sherman, a molecular geneticist at the Seattle Biomedical Research Institute. "It has become clear in the very recent past that there are differences that are clearly relevant, and we are only just scratching the surface" in understanding what those differences mean.

One-third of the world's population has TB, and a new person becomes infected every second, according to the World Health Organization. Most of those people show no symptoms of the disease until their immune systems become compromised by infection with the AIDS virus (HIV), by age, or by other factors.

When it does become active, TB usually strikes the lungs, though it can affect other organs such as the kidneys, liver, and bones. Nearly 2 million people die of the disease annually, and the death rate shows no sign of slowing. Many of those deaths are the work of new strains that resist most anti-TB drugs.

As the death toll continues to mount, scientists are scouring M. tuberculosis for weak spots. The work has been slow going, however; mostly because the bacterium takes its time, says Richard Chaisson, director of the Johns Hopkins Center for Tuberculosis Research Laboratory in Baltimore. Infectious bacteria such as Escherichia coli and Streptococcus species grow quickly in the lab and respond in minutes to tests with antibiotics or other drugs. But M. tuberculosis takes 24 hours to replicate, making lab experiments frustratingly slow. A trial of a new drug in animals, can take a year to complete because it takes that long to know whether all the bacteria in a given animal have been destroyed.

The bacterium is likewise hard to eradicate from an infected person, Chaisson says. A patient must take at least four drugs, for a period of 6 months or more. And if the patient stops treatment too soon, an all-too-common occurrence in developing countries, bacteria that develop drug resistance can survive.

DIVERSITY LURKS For years, most TB research rested on the assumption that all cases of M. tuberculosis were the same, because the DNA sequences of different strains of the bacterium show much less diversity than the genomes of other bacteria do. …

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