Robert Koch and Tuberculosis

Robert Koch, a German physician and scientist, presented his discovery of Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), on the evening of March 24, 1882. He began by reminding the audience of terrifying statistics: "If the importance of a disease for mankind is measured by the number of fatalities it causes, then tuberculosis must be considered much more important than those most feared infectious diseases, plague, cholera and the like. One in seven of all human beings dies from tuberculosis. If one only considers the productive middle-age groups, tuberculosis carries away one-third, and often more."

Koch's lecture, considered by many to be the most important in medical history, was so innovative, inspirational and thorough that it set the stage for the scientific procedures of the twentieth century. He described how he had invented a new staining method and demonstrated it for the audience. Koch brought his entire laboratory to the lecture room: microscopes, test tubes with cultures, glass slides with stained bacteria, dyes, reagents, glass jars with tissue samples, etc. He wanted the audience to check his findings for themselves. Koch showed tissue dissections from guinea pigs which were infected with tuberculous material from the lungs of infected apes, from the brains and lungs of humans who had died from blood-borne tuberculosis, from the cheesy masses in lungs of chronically infected patients and from the abdominal cavities of cattle infected with TB. In all cases, the disease which had developed in the experimentally infected guinea pigs was the same, and the cultures of bacteria taken from the infected guinea pigs were identical. One important scientist in the audience was Paul Ehrlich (Nobel Laureate in Physiology or Medicine in 1908) who later confessed, "I hold that evening to be the most important experience of my scientific life." When Koch ended his lecture there was complete silence. No questions, no congratulations, no applause. The audience was stunned. Slowly people got up and started looking into the microscopes to see the TB bacteria with their own eyes.

News of Koch's discovery spread rapidly. The results were published in a German medical journal on April 10, in England after a rapid translation in The Times on April 22, and in the US in The New York Times on May 3, 1882. Robert Koch was now a famous scientist and became known as "The Father of Bacteriology." He was presented with the Nobel Prize in Physiology or Medicine in 1905 "for his investigations and discoveries in relation to tuberculosis."

Today, more than a century after Koch discovered Mycobacterium tuberculosis, there are still many infected individuals and around two million deaths annually resulting from the disease.

Tuberculosis is a global disease which is not only specific to humans. There are variants of the TB bacterium that infect cattle (milk was known to transmit the disease from cattle to humans before heat treatment - pasteurization - efficiently removed the risk), birds, fish, turtles and frogs.

In humans, symptoms of active TB often include coughing, fever, nightly sweats and wasting of the body. TB usually affects the lungs, but it can also affect the brain, the kidneys or the skeleton. The symptoms of TB of the lungs include persistent coughing, chest pain and coughing up blood. Symptoms involving other areas of the body vary, depending on the affected organ.

Tuberculosis is spread from person to person through the air, in tiny microscopic droplets. When a person with TB in the lungs coughs or sneezes, the bacteria can be inhaled by persons nearby, often family members or co-workers.

Usually, persons infected with tuberculosis harbor the bacteria without developing symptoms. This condition is called "latent TB infection." In this state, the bacteria are inactive, kept in check by the body's immune defense system. The person does not feel sick. However, the disease may become active in the future. It is estimated that one-third of all living beings are latently infected.

People with HIV/AIDS are particularly vulnerable to reactivation of latent TB infection to active disease. This is because the HIV-infected individual has a weakened immune system. About one-third of the more than 40 million HIV/AIDS patients are co-infected with TB bacteria. TB is actually the cause of death in many HIV-infected individuals. In fact, anything which weakens the body's immune defense system can cause latent TB infection to become active disease.

Even after the identification of the TB bacterium and the establishment of tuberculosis as an infectious disease, the standard medical therapy for decades to come was based on rest, the sanatorium, and a good climate with lots of fresh cold air. Why? Because it took a long time before antibacterial drugs were developed.

After Koch's discovery, many attempts were made over the years to find a compound that could stop the growth of TB bacteria. In 1910, a German scientist named Paul Ehrlich discovered a chemical that could kill the microorganism that causes another disease, syphilis, and effectively treat that disease. This initiated the search for other chemical substances which could destroy disease-causing microorganisms.

In 1935, another German scientist named Gerhard Domagk published a report on the use of "Prontosil," an organic compound containing sulfur (sulfanilamide), for treatment of bacterial infections. Domagk was awarded The Nobel Prize in Physiology or Medicine for his discovery in 1939. Prontosil, and derivatives of it, had some effect on TB bacteria in laboratory studies, but only in concentrations that would be poisonous to humans.

Other ideas were pursued independently. Scientists observed that pathogenic (disease-causing) bacteria do not survive for long in enriched soil. It was found that fungi living in the soil were able to suppress their growth. In 1943, an American named Selman Waksman, together with his co-workers, discovered that a fungus called Streptomyces griseus produced an antibiotic substance which they named "streptomycin." After successful animal tests, the first tuberculosis patient was treated in 1944, and she was cured of her life-threatening disease! Further trials confirmed that streptomycin was indeed effective in the treatment of tuberculosis. Selman Waksman was awarded the Nobel Prize in Physiology or Medicine in 1952 for his discovery of streptomycin.

Unfortunately, early in the studies, it became evident that the TB bacteria were becoming resistant to streptomycin. This severely reduced the usefulness of the drug for treating tuberculosis.

In 1943, another drug called para-aminosalicylic acid (PAS) was developed. When this drug was used together with streptomycin it prevented the TB bacteria from becoming resistant. However, the patient had to use the drugs for periods of months in order to be cured.

Another drug called "isoniazid," a derivative of a compound researched earlier by Domagk, was developed in 1952. It also found its place in TB therapy.

Thus, in the decade between 1944 and 1954, largely due to the work of Nobel Laureates, three drugs - streptomycin, PAS and isoniazid – became available. When taken in combination, and for a sufficient length of time, the prognosis for a patient with TB disease changed from dismal to the expectation of cure.

Today, the cornerstone for any treatment of tuberculosis is still multidrug therapy. At least two drugs are given at the same time to prevent the emergence of drug resistance. Sometimes patients are treated with up to four different antibacterial drugs, and for periods of a minumum of 6 to 24 months.

Tuberculosis, once called "consumption" and "white plague," is an ancient disease that may have always been with us. Evidence of tubercular decay found in the skulls and spines of Egyptian mummies, tell us that TB has been plaguing humans for at least 4,000 years. Hippocrates, the ancient Greek physician, noted that "phthisis" (consumption) was the most widespread and fatal disease of his time.

It has been estimated that in the two centuries from 1700 to 1900, tuberculosis was responsible for the deaths of approximately one billion (one thousand million) human beings. The annual death rate from TB when Koch made his discovery, was seven million people. Although the disease has not been eradicated, there is no doubt that Robert Koch's discovery of the tubercle bacillus, subsequent inventions for curing infected and sick individuals as well as the application of measures to prevent the spread of TB, has had a profound impact on human history and has saved many lives.

First published 9 December 2003