Volunteer for NIAID-funded clinical studies related to tuberculosis on ClinicalTrials.gov.
On the evening of March 24, 1882, before a skeptical audience of Germany's most prominent men of medicine, Robert Koch announced a discovery that awed his listeners and brought him worldwide acclaim. New laboratory techniques had helped scientists discover microbial causes of other infectious diseases, but TB remained a stubborn exception. Koch succeeded by staining the organism with not one but two dyes, and at last was able to bring the elusive microbe into view. "Under the microscope the structures of the animal tissues, such as the nucleus and its breakdown products are brown, while the tubercle bacteria are a beautiful blue," he wrote in the paper that followed his dramatic presentation that March evening.
Koch was the first to get colonies of TB bacteria to grow in the lab. The bacteria, he discovered, are extremely slow-growing, requiring two weeks before clumps of them could be seen with the naked eye. Further research by Koch revealed that TB was spread from person to person and, as such, potentially controllable. Also, the way TB spreads—carried on droplets expelled in an infected person's cough—became clear. An optimistic Koch wrote, "When the conviction that tuberculosis is an exquisite infectious disease has become firmly established among physicians, the question of an adequate campaign against tuberculosis will certainly come under discussion and it will develop by itself."
A key element in that campaign was a public health movement that isolated the sick—sometimes by force—from the well. This era of TB sanatoria actually began in 1849, well before the scientific proof of TB's contagious nature. A consumptive German doctor traveled to the Himalayas and returned cured. The doctor, Hermann Brehmer, became convinced that life at high elevation, continuous exposure to fresh air, sun, and cold, along with copious amounts of food, could turn TB from a death sentence into a curable disease. In the United States, less emphasis was placed on high elevation, but the basic outlines of sanatorium care and philosophy remained the same.
A young doctor named Edward Livingston Trudeau established the most famous sanatorium in the United States at Saranac Lake, in New York's Adirondack Mountains. Like Brehmer, Trudeau suffered from TB and was informed by his doctors that he would not live long. In 1882, Trudeau became aware of Koch's experiments with TB bacteria and of Brehmer's sanatorium. Although very weakened by his illness, Trudeau established a small laboratory in Saranac Lake and began an extraordinary series of experiments.
Five rabbits were inoculated with TB bacteria and set loose on a small island where they were provided with fresh vegetables in addition to the naturally occurring grasses. After 4 months, one rabbit died, but the others remained robustly healthy. Upon autopsy of the apparently healthy rabbits, no evidence could be found of the point of inoculation, reported Trudeau in an 1887 paper. Evidently, the rabbits' healthy life permitted them to fend off infection.
Believing his findings gave a strong empirical basis to the European-style sanatorium treatment regimens, Trudeau instituted many of those regimens in the "cure cottages" he established at Saranac Lake. Patients were under strict and constant supervision; every aspect of their lives was detailed in rule books issued to each invalid. Typically, a newcomer spent a minimum of three months on complete bedrest. The resident was exposed to fresh air for most of the day and was required to consume enormous amounts of food, including many servings of milk, each day.
A noticeable decline in the incidence of TB in the United States began around the turn of the century. Some of the decline was probably due to a natural waning of the epidemic, but some was also the product of quarantining the sick in sanatoria and of aggressive public health education campaigns. Publications aimed at children and adults admonished against spitting and recommended plenty of sleep, fresh air, and exercise for everyone.
In 1908, French scientists Albert Calmette and Camille Guérin developed a vaccine against TB. They began by isolating Mycobacterium bovis (which causes TB in cattle) from a dead cow. Every 3 weeks for the next 13 years, the scientists grew a new batch of bacteria in a solution of beef bile and potatoes. Each new generation of bacteria was weaker than the one before. Eventually the bacteria lost the power to cause disease, but could still provoke the immune system to protect a person from TB. The vaccine Bacille Calmette-Guérin (BCG) was first administered in 1921 to an infant whose mother had died of TB. Since then, more than a billion people have been inoculated with the cheap and safe BCG vaccine. The vaccine's efficacy, however, is unclear. The consensus is that while BCG vaccine can prevent TB infection in the brain among children, it is nearly useless in preventing adult pulmonary TB.
During the 1940s, TB vaccines took a back seat to advances in drug therapy. Dogged effort by the American scientist Selman Waksman produced streptomycin, a relatively non-toxic antibiotic derived from a soil fungus. On November 20, 1944, a critically ill TB patient received streptomycin. Within days, he began a near-miraculous recovery. A host of drugs followed on the heels of streptomycin and, when used in combination, they could usually cure TB without engendering drug-resistant bacteria. Some of the most important drugs introduced during the 1940s and '50s included isoniazid, rifampin, and ethambutol.
Effective drugs brought the sanatorium era to a close. Some research journals devoted to TB ceased publication, and organizations such as the American Lung Association (formerly known as The National Association for the Study and Prevention of Tuberculosis) redirected their efforts. Confidence arose that TB, like infectious diseases of previous centuries, could be completely conquered by drug therapy. Indeed, the United Nations predicted the worldwide elimination of TB by the year 2025. But this ancient enemy was not so easily routed.
back to top
Last Updated August 12, 2010