Saturday, July 07, 2007

A few more thoughts on TB

When Robert Koch made the TB bacterium visible to the Physiological Society of Berlin in 1882, his audience knew they were participating in an historic moment. The 17th-century writer John Bunyan had called tuberculosis "the captain of all the men of death." The disease wreaked its terrible toll throughout the ages, at least as far back as the Neolithic, among all peoples, on all continents. In the late 19th century, it was feared that tuberculosis might destroy European civilization.

Koch's discovery of the cause of the disease was the first step in a long and ultimately successful search for a cure. By the early 1950's, two drugs, streptomycin and para-aminosalicylic acid (PAS), had proved their ability in combination to knock out the disease.

But the victory wasn't consolidated. Today, the tuberculosis bacterium -- Mycobacterium tuberculosis -- continues to take more victims than any other infectious agent. It has evolved new drug-resistant form, and it has forged a deadly alliance with the HIV virus, which weakens the body's natural defenses against the tuberculosis bacilli.

The genome of the Mycobacterium tuberculosis was sequenced in 1998, one of the earliest organisms to have its genome completely revealed -- 4.4 million chemical base pairs along its DNA double helix. The genome was displayed in the journal Nature as a five-foot-long fold-out map, beautifully colored, with a different hue for the genes of each functional category of proteins: metabolism, respiration, cell wall, virulence, and so on. It seemed to me then that the map resembled nothing so much as the score of a great symphony -- the symphony of life. What we saw in the foldout was not the face of evil -- the captain of all the men of death -- but the exquisite chemical dynamic that all life shares.

"Beauty is nothing but the beginning of terror," wrote the poet Rainer Maria Rilke. In the imagination of romantic poets, composers and writers, tuberculosis conferred a kind a spiritual beauty on its victims: Mimi in La Boheme, Alphonsine Plessis in La Traviata, Little Blossom in David Copperfield. A character in Thomas Mann's Magic Mountain says with somber conviction that the disease is "only love transformed" -- a thought that is unlikely to console a victim.

And yet, and yet -- in Nicholas Nickleby, Charles Dickens described tuberculosis as a "disease in which death and life are so strangely blended, that death takes the glow and hue of life." The same might be said for the genome of Mycobacterium tuberculosis as it was displayed in the fold-out pages of Nature -- a beautiful and terrible lesson in the inescapable and amoral dynamic of evolution.