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“Yet the captain of all these men of death that came against him to take him away was consumption, for it was that that brought him down to the grave.”

— The life and death of Mr. Badman,

John Bunyan, 1680

Tuberculosis is an ancient disease which has been an integral part of the medical history, folklore, writings, and art of virtually every human civilization. The existence of Mycobacterium tuberculosis predates recorded history, and clinical descriptions and physical evidence of TB have been documented in the ancient civilizations of Egypt, India, and China. Potts deformities have been found in Egyptian and Andean mummies. DNA dating analyses on ancient specimens have documented evidence of the organism worldwide and in ancient civilizations, having been found in ancient Greece and Rome and in America before the time of Columbus. “Consumption” features prominently in countless works of art (see, for example, Keats, Dickens, Dostoyevsky, Dumas, Puccini, and Munch to name but a few).

The term “phthisis” (meaning to waste away, or consumption) first appeared in Greek literature, identified by Hippocrates as the most widespread disease of the time. While Aristotle considered it to be a contagious disease, most Greek authors believed it was inherited, and linked to an individual's mental and moral weakness. Roman physicians recommended therapies such as bathing in urine, eating wolf livers, and drinking elephant blood; medieval authorities believed that the physical touch of English and French royalty had the power to cure “King's evil” or scrofula. Throughout time and across countries, affected individuals were alternately urged to exercise or rest, eat or fast, travel to the mountains or live underground as cures for their consumption.

More modern scientific study began in 17^th century Amsterdam and England, while the 200 year epidemic of tuberculosis in Europe was underway. At this time, more precise anatomic and pathologic descriptions appeared, such as the characterization of the tubercle as a consistent finding in the lungs and other organs. In 1839 the famous German professor of medicine Johann Lukas Schönlein suggested the name ‘tuberculosis' to describe diseases with tubercles, but along with Drs. Morgagni and Virchow he considered scrofula and phthisis to be separate entities. Their contemporaries, the Parisian physician René Laënnec and the Viennese physician Karl von Rokitansky thought these diseases had a common origin.

It was not until the end of the 19^th century that Robert Koch demonstrated that these diseases were in fact both caused by a single microorganism, simultaneously introducing his famous postulates of infectious disease. Several years later, Koch reported on a compound that inhibited the growth of tubercle bacilli in guinea pigs. The compound, called “tuberculin”, was prepared from glycerol extracts of liquid cultures of tubercle bacilli. Although the compound ultimately failed as a treatment, it was soon demonstrated to be a valuable agent in the diagnosis of TB. Koch provided the first description of the partially purified derivative of tuberculin (PPD), which is used to this day in the Mantoux test.

For over 100 years, the diagnosis of tuberculosis has depended on the combination of centuries-old clinical descriptions and on the diagnostic methods established by Dr. Koch and the other giants of late 19^th and early 20^th century medicine. However, the age-old pathogen that has challenged humanity, infiltrating its tissues and organs as well as its art and literature, is challenging us once again: multiple drug resistance threatens the efficacy of therapeutic regimens, and co-infection with HIV limits the accuracy of our diagnostic methods. In response to these challenges, and due to recent advances in the application of modern immunology to diagnostic methods, we stand at the threshold of a new era in the diagnosis and management of tuberculosis infection and disease. In this month's issue, Drs. Lighter and Rigaud provide us with a thorough and forward-looking review of traditional and novel clinical and laboratory methods for diagnosing tuberculosis, including a critical look at the feasibility of adapting these methods to the resource-limited regions of our world. I had a strong sense of optimism in reading this article that translational science has the ability to provide effective responses to the new challenges posed by the age-old threat of tuberculosis. See what you think.

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