T.B. Harlem: A Portrait of a Disease
In her 1940 painting “T.B. Harlem,” painter Alice Neel portrays a tuberculosis victim of Spanish Harlem. The subject – her lover’s brother Carlos, who actually lived near Neel – is shrouded in white, pointing plaintively to the bandage that covers his surgical wound. This incision, made to drain Carlos’ lung of fluid, warped his spine, producing the painfully contorted figure depicted in Neel’s portrait.2
It is significant that the artist connected the disease with its location in her title. In the remainder of this unit, students should think not just about the biological mechanisms of tuberculosis, but the social conditions that have made it such a threat.
Humanity’s Unwelcome Friend: A History of Tuberculosis and its Victims
We’ve been observing tuberculosis infections for almost as long as we’ve been recording history. Every step of human civilization, the bacterium has followed: perhaps it’s a bit ironic that modern medicine has been accompanied by the rise of multi-drug resistant TB, a similar “technological leap” on the part of our microbial nemeses. Here, then, is the story of mankind’s unwanted partner in history.
Ancient History:
Tuberculosis is a very old disease, with remains from Egyptian mummies showing evidence of decay from the illness3. It was also known to the ancient Greeks, as the term consumption was first used by Hippocrates in 460 BC to describe the way in which victims seemed to be consumed by the disease, rapidly growing thinner and wasting away3. Later, during the Roman Empire, a variety of bizarre cures were suggested for the disease, including eating wolf’s livers, drinking animal blood, or even bathing in urine3. However, Roman physicians were not entirely misguided when they recommended fresh air, a concept utilized hundreds of years later in the sanatoria of the 17th and 18th centuries3.
The White Plague:
Tuberculosis became an immense threat in Europe during the late 18th and early 19th centuries, overshadowing other illnesses such as cholera4. Due to limited medical technology, the disease was usually fatal, and may have accounted for as many as a third of all deaths in the 19th Century21. The list of authors claimed by the disease reads like a who’s who of the time, and consumption showed up frequently in their works as well. However, most at the time believed the illness was hereditary not infectious. The insight that it was caused by a small organism was supplied by English physician Benjamin Marten in 1720, and confirmed in 1865 by a series of experiments in which French doctor Jean-Antoine Villemin demonstrated the transmission of the bacteria between cows, rabbits, and humans5. However, he never observed the organisms responsible under a microscope – this would be Koch’s contribution (see below).
Vampirism in the Colonies:
Likely introduced from the West by Columbus and other explorers, TB took hold in the new world and was a scourge of the New England settlers in the 19th Century. While in Europe, the image of the consumption victim was often romanticized in art. In New England, however, it became the basis for vampire legends6. Colonists observing pale TB victims and the subsequent wasting away of the victim’s families believed they were witnessing a vampire preying upon its kin6.
A particularly famous case was that of Mercy Brown, a young girl who died of tuberculosis in 1891 in Rhode Island after her mother and older sister had already fallen to the disease7. When her brother Edwin also displayed symptoms of consumption, Mercy’s former neighbors believed this indicated that one deceased member of the Brown family must be a vampire preying on the boy7. Persuading her father to exhume his wife and two daughters, the townspeople of Exeter discovered that Mercy’s body was remarkably well-preserved in comparison to the others7. Taking this as a sign that she was rising as a vampire to feed on Edwin (instead of the remarkable ability of cold New England soil to preserve human bodies), Mercy’s father was persuaded to remove the corpse’s heart, burnt it, and give the ashes mixed with water to his ailing son7. Though this was meant to end the vampire’s feasting, the bacteria actually responsible for Edwin’s illness were not susceptible to such rituals, and the boy soon followed his other family members to the grave7.
The Development of Sanatoria
To cope with the TB epidemic, some European physicians decided that fresh air was the best treatment and set about institutionalizing this approach. The first such treatment facility, which came to be known as sanatoria, was opened in Germany in 18548. They were introduced to the US in 1885 with an isolated facility in the Adirondacks of New York State9. Sanatoria soon became popular across the US, and even if they did not directly cure TB, they may have ultimately aided its treatment. Indeed, Koch mentions in his Nobel lecture that his observations in the sanatoria helped guide his research: the hygienic procedures in these facilities led him to speculate about the transmission of the disease which was much more prevalent in close quarters10.
Keats, Physician and Poet:
‘Beauty is truth, truth beauty,’ – that is all
Ye know on earth, and all ye need to know.
-“Ode on a Grecian Urn”
One of the more famous victims of tuberculosis was John Keats, the English poet whose mournful verses are a hallmark of Romantic Era. Interestingly, he studied as a surgeon before forsaking medicine for poetry11. Perhaps he might have lived longer if he had stuck with the former, for, when he sought relief from his tuberculosis in Italy in 1820, his physician did not believe he had the disease, and ordered vigorous exercise that probably hastened Keats to his grave at the young age of 2511,12.
Koch’s Revelation:
On March 24, 1882, German Physician Robert Koch presented his discovery of the tuberculosis-causing bacteria to a room of stunned onlookers13. This address, considered one of the most important lectures in the history of medicine, laid out the germ basis of disease that would come to define modern medical research13. By demonstrating how these microorganisms could cause infection in a pool of laboratory guinea pigs, Koch gave inscrutable evidence that tuberculosis really was an infectious malady13. No wonder one of the audience members described the talk as “the most important experience of my scientific life”. For his seminal contribution, Koch would be awarded the Nobel Prize in 190513.
Koch’s Postulates
Though he worked specifically on TB, Koch conceived a number of general rules through this research related to bacterial transmission of disease that are known collectively as “Koch’s Postulates.” By these rules, a disease is caused by a particular species of bacteria if:
1. The bacteria are found in any given case of the disease.
2. The bacteria can also be isolated from the infected host and grown in pure culture.
3. A healthy host will develop the disease if injected with this pure culture of bacteria. The bacteria must also be able to be isolated from this second, experimentally infected host.
TB Returns: “Ebola on Wings”14
With the discovery of streptomycin and other antibiotics that effectively treated tuberculosis, it seemed in the middle years of the 20th century that TB would soon become a thing of the past. However, that optimistic vision has been shattered in recent years by the emergence of Multi-Drug Resistant Tuberculosis (MDR-TB), which is strictly defined by the World Health Organization as a strain of M. tuberculosis that is resistant to both isoniazid and rifampin, two commonly prescribed antibiotics for TB15. However, sometimes the infection is resistant to any drug, and certain strains resistant to any single antibiotic have been found16. One of the worst things about this particular epidemic is that it might have been prevented decades ago when tuberculosis was almost eliminated. Even though US government was warned in the 1970s about the necessity for TB funding during the crucial years when the disease was almost eliminated domestically, no action was taken to combat remaining hot spots in areas like Harlem, New York. Ultimately the necessary funding for the final step in eliminating TB never materialized.
Mixing Maladies:
Early signs of trouble visited Harlem Hospital in 1981 when doctors began to observe a proliferation of unusual TB cases14. Usually the disease is confined to the lungs, but it was appearing in brain abscesses, wrists, spines, and other peculiar internal organs14. While all the patients were immune-compromised, AIDS had not yet been definitively described nor had the interaction between AIDS and TB fathomed. The first indication of the true magnitude of the reinvigorated tuberculosis threat came in 1991, when 12 inmates and a guard at a Syracuse, NY prison died of what turned out to be a drug-resistant strain of the mycobacterium14. The guard was undergoing chemotherapy; the inmates were HIV-positive14. Both immunosuppressed conditions made the victims more susceptive to tuberculosis. In the coming weeks, more cases were reported across the US.
Soviet Collapse: TB in the Gulag
Meanwhile, the Soviet Union fell, causing an economic downturn that would send tuberculosis cases soaring in the troubled region17. Here, as was the case in Harlem in 1970s, social conditions helped the disease flourish. As the economy soured, more of the Russian citizenry became malnourished. They consequently contracted the disease more easily and spread it among members of crowded urban living environments. Similarly, these economic troubles led to greater petty crime and more imprisonments. Over time, the Russian penal system proved an immense harbor for the spread of tuberculosis, with almost 1 in 10 inmates infected with the mycobacteria14. In a crowded prison cell, the disease transmits easily between inmates, and every year the release of inmates from incarceration unleashes tuberculosis onto the rest of the population (in addition to the prison staff carrying the bacteria with them when they leave work).14
Besides crime, Russia’s economic problems have also correlated with increased incidence of prostitution and intravenous drug use – consequently, HIV/AIDS is also on the rise in the former Soviet Union, further boosting the spread of tuberculosis. Given all this, it seems no wonder that the average age of the Russian population is falling precipitously.
Improving Treatments:
How exactly did tuberculosis go from being almost exterminated to proliferating in resistant forms? Much of the problem has to do with how doctors prescribe treatments and see patients through the necessary process of recovery. As we will see in this unit, tuberculosis usually exists in a latent stage. Because of this, it is possible for a patient to take antibiotics and relieve their symptoms by destroying most of the bacteria making them sick18. However, a small portion will be left over, encased in a tubercule behind a wall of macrophages. These remaining bacteria are more resistant to the antibiotic treatment and, further, can spontaneously evolve drug-resistant mutations while they remain in the patient’s body19. In addition, there is evidence that many antibiotics are more effective against actively replicating bacteria than the slow-dividing cells in a tubercule, leading to a situation of slow and continual exposure to the antibiotic: this situation also favors the development of drug resistance20. These hardier bacteria will not cause immediate symptoms because they are trapped in the tubercule in a period of latency, but months or years after the patient has ceased their treatment, they can overwhelm the body’s immune system, resulting in a new case of tuberculosis that is more resistant to the antibiotic treatments used to treat the original infection.
In the U.S., this scenario played out frequently in large urban hospitals in New York in the 1980s, where tuberculosis patients would leave, not finish their prescribed medicines after feeling better, and ultimately spread their disease to others. If they survived, they might arrive back at the hospital months later bearing a resistant strain of M. tuberculosis. Similarly, much of the current epidemic in Russia is the result of the poor medical system in the nation’s prisons. Prisoners infected with TB are given few and insufficient medications, which cures their symptoms but does not destroy the entire bacterial population in their bodies. Thus, like the economically disadvantaged citizens of New York City, the closely packed inmates of the Russian gulag harbor resistant bacteria that then spreads quickly among their cellmates; the result is the same.<sup14
There have been advances, though, in combating this new threat. During the early 1990s in New York City, when the threat of MDR-TB epidemic loomed fearsomely, Directly Observed Treatment (DOT) became the new standard of tuberculosis therapy, in which physicians followed up with their patients and tried to ensure that those taking antibiotics for tuberculosis finished their full regimen of drugs14. While this kind of therapy has not been so effectively instituted in Russia, a modified version has been proposed in which prisoners are observed and their treatment is tailored to the specific strain of MDR-TB from which they are suffering16. The cost of the current crisis is immense, in both lives and money – it has been estimated that a single case of MDR-TB can cost almost $1.3 million to treat.21
Though the threat of tuberculosis appears larger than ever, there is hope: new methods of rapid diagnosis using sophisticated genetic screens coupled with drug development based on the TB genome will increase the effectiveness of anti-drug resistance strategies22. DNA chip technology – where the genetic material from a sputum sample could be analyzed for a number of bacterial drug resistance genes – could significantly accelerate diagnosis of particular strains of M. tuberculosis. Further knowledge of the mycobacterium’s unique genome should help identify novel drug targets, eventually increasing the number of antibiotics in the anti-tuberculosis arsenal.
