TB's Lethal Blueprint Laid Bare

LONDON--Researchers have unraveled the complete genetic sequence of one of the world's worst scourges: the tuberculosis bacterium. The achievement, announced here last week, could usher in new diagnostic tests and drugs against a bug that kills some 3 million people in the world each year.

TB is the latest in a line of microbes, including Escherichia coli and brewer's yeast, to have its genome completely sequenced. With 4.41 million base pairs, Mycobacterium tuberculosis's genome isn't enormous, but its chemical composition made it one of the most challenging yet to sequence. The genome is packed with stretches rich in cytosine and guanine, nucleotides that tend to stick together, turning a DNA strand into a nasty knot. To solve the structure, a team headed by Bart Barrell at the Wellcome Trust's Sanger Centre near Cambridge, working with a group led by Stewart Cole at the Pasteur Institute in Paris, chopped the genome into tiny stretches that could be decoded and then painstakingly patched together to form the whole sequence. The project took little more than a year to complete.

"We have been waiting for a long time for a major advance in tackling this disease," says epidemiologist Paul Fine of the London School of Hygiene and Tropical Medicine. One problem has been distinguishing lethal TB strains from innocuous cousins. "I hope one of the earliest outcomes of the genome project will be the development of more sensitive diagnostic tools which can distinguish between" tuberculosis and its relatives, he says. Drug companies are also thrilled with the new data. "We now know the sequence of every potential drug target," says Ken Duncan of the drug giant Glaxo Wellcome's TB unit in Stevenage, United Kingdom. "Having the sequence is enormously beneficial" for trying to design new drugs to hit those targets.