Tuberculosis Treatments Past and Present

Throughout tuberculosis’ long history with humanity, our understanding of how to treat this disease has evolved considerably. Attempting to defeat this deadly disease, we’ve tried strange potions, mystical and occult solutions, and questionable scientific procedures. For much of human history, tuberculosis wasn’t so much treated as contained or at best battled to a draw. 

As an extremely widespread disease, tuberculosis often created an opportunity for fraud and moneymaking. As the playwright George Bernard Shaw famously wrote, the treatment of tuberculosis during his time was a “commercial system of quackery and poison.” Superstition and religion also played large roles in the confusion surrounding tuberculosis and how to combat it, leading to some semi-effective techniques and many ineffective or even harmful ones. For much of human history, tuberculosis wasn’t so much treated as contained or at best battled to a draw. The advent of modern medicine changed this, but overall tuberculosis’ incidence and mortality rates have gone thorough peaks and troughs influenced as much by environmental factors as treatment strategies. 

For centuries curing tuberculosis cases was considered a way for doctors to make their name, spurring many zany proposals for how to address the disease. Pliny the Elder prescribed eating the liver of a wolf boiled in wine, while others later in history suggested inhaling smoldering cow dung or drinking noxious potions made of various animals and plants. Monarchs were even thought to have god-given powers that would allow them to cure various diseases. Different rulers specialized in different ailments; the English and French kings were known for curing tuberculosis (at times called the “King’s Evil”).

One longstanding treatment for tuberculosis was a combination of clean air, rest, and posture. Before the advent of more advanced medicine, these were very sensible treatment options. Clean air meant that patients’ lungs were not irritated by dirty city conditions, rest offered the opportunity to recover and let lesions in the lungs heal, and certain postures could help stimulate healing by letting pulmonary cavities close. The goal with this treatment regimen was to support patient’s natural immune response and push the disease into remission while also containing infected persons. 

A number of surgeries, most involving some way of restricting respiration, were also contrived to help treat tuberculosis. This served two purposes: first to allow cavities created in the lungs to close and heal, and second to decrease the amount of extracellular bacteria expelled by an infected person’s coughing and breathing. While primitive, collapsing the lung of the infected patient was a fairly ingenious treatment. Tuberculosis breeds in the space inside the lung, thus less lung volume produces fewer bacteria.

The turning point in tuberculosis treatment was the discovery of the bacterium that causes tuberculosis by Robert Koch, unveiled in 1882. In addition to being a blueprint for scientific procedure to better understand diseases, he isolated the organism that causes tuberculosis. This supported the development of medicine targeted toward the actual characteristics of the disease, rather than simply expressed symptoms. 

Antimicrobial chemotherapy is the term used to describe drug treatment aimed at reducing the population of a particular microbe (in this case Mycobacterium tuberculosis). Today, chemotherapy is the colloquially used to refer to the regimen of treatment applied to cancer patients, but it is a technically accurate term for any type of treatment regimen featuring chemicals. After the discovery of penicillin, there was a huge push to discover other antibacterial and antimicrobial compounds to fight diseases like tuberculosis. The era of effective treatment of tuberculosis was thought to begin in 1946, with the use of streptomycin. This came after the testing of many compounds, most of which proved to be too toxic for use despite their potential to effectively handle the disease. Considering that there was no chemical compound effective at treating tuberculosis prior to streptomycin, this was a huge breakthrough in fighting the disease.

Tuberculosis created a number of difficulties for antimicrobial chemotherapy treatments. First, its capability to lie dormant at low metabolic activity levels means that antibiotics can fail to eliminate the presence of the disease. Second, the bacterium can be located deep in pulmonary cavities or inside solid material that makes antibiotic penetration difficult. Third, tuberculosis bacterium takes advantage of a variety of environments inside the body, meaning that antibiotics must be used that address multiple types of infections and infected areas. These challenges led to the current approach, using three to four drug treatments with different drugs targeting extracellular bacteria in sputum, inside necrotic tissue, and persistent strains. Of course the risk in multi-drug treatment is creating a bacterium that is resistant to multiple antibiotics. Interestingly, spontaneous resistance has been shown to be unlikely to develop, meaning that resistance is largely a product of dosage variance and irregularity in taking doses. The number one priority for treating tuberculosis is to ensure that patients have access to the right drugs and take them on schedule. 

Today, there are a number of methods for treating tuberculosis, including potential new vaccines on the horizon. This is a massive improvement considering the paucity of options available for much of human history. However, new challenges have developed with growing incidences of drug resistant tuberculosis, including MDR (multiple drug resistant) and XDR (extensively drug resistant) strains. XDR strains are a serious threat, especially for immunodeficient patients who are significantly less likely to recover without the assistance of effective drugs. Luckily, there is a global effort to control and eventually eradicate tuberculosis.  As part of this effort, Intellectual Ventures Laboratory is working to improve the quality of tuberculosis diagnostics in developing countries. Some of our work includes developing microscope stains for identifying drug resistance, faster methods of bacterial culture, and research into new tuberculosis biomarkers.