Scientists closer to beating TB

THE COMPLETE DNA fingerprint of the biggest serial killer in history has been uncovered. A group of scientists announced yesterday that it had unravelled the 4,000 genes making up the entire genetic sequence of tuberculosis (TB), the bacterium responsible for millions of deaths throughout human history.

Using the information revealed by the genes, medical teams are now racing to develop vaccines against TB, to replace antibiotics which are rapidly losing out to drug- resistant strains of the bacterium. If successful, they might even wipe out TB in the same way that smallpox was eradicated in the 1980s.

"Despite the availability of short-course chemotherapy and the BCG vaccine, TB continues to claim more lives than any other infectious agent," said Dr Bart Barrell of the Sanger Centre in Hinxton, Cambridge, which co-operated with teams in France, the United States and Denmark to sequence the TB genome.

More than 3 million people die every year from TB, which infects the lungs. Strains resistant to antibiotics are on the rise, particularly in the industrialised world, where over-prescription of antibiotics, linked to high healthcare costs, has meant people have helped to breed bacteria that can survive attack by those drugs.

In March, the World Health Organisation said that TB - whose re-emergence it described in 1993 as a "global emergency" - could infect a billion more by 2020, and kill 70 million if control is not strengthened. It already kills more than malaria and Aids combined.

However, the new work, published today in the science journal Nature, offers a blueprint for future therapies that could defeat the disease.

"It lays the foundation for a lot of research in the next five to 10 years," said Douglas Young, of the Department of Infectious Disease at Imperial College, London.

He was not involved in the work but applauded its results: "It was technically very difficult because of the characteristics of the TB DNA, which contains high amounts of two base pairs, guanine and cytosine, that make it hard to sequence."

The TB genome is the largest disease bacterium ever sequenced, and took two years to complete. Even so, it pales against the Human Genome Project, which aims to sequence the estimated 100,000 genes in human DNA.

Being able to look at the entire genome of the bacterium means scientists can pick weak spots in its defences.

One approach is to target proteins - antigens - which appear on its cell wall. A vaccine that contains these could sensitise the human body against anything with those proteins.

Dr Young said such techniques would have the advantage that it should make it more difficult for resistant mutations to arise.

"Drugs generally attack just one target antigen, and the bacterium mutates away from that," he said. "But I think a vaccine based on this system would target two or more. To evade that, the bacterium would need multiple mutations, and that's not so likely."

The idea that TB could, like smallpox, eventually be driven from the face of the Earth, to a last resting place in laboratories, seemed more likely now, he added: "In theory, in the long term we could think about really doing that."