Tuberculosis: The Disease That Changed World History

Almost forgotten today, tuberculosis (TB) is still one of the deadliest infectious diseases in the world. In an interview with Coliquio, Ronald D. Gerste, MD, PhD, an ophthalmologist and historian, looked back on this disease's eventful history, which encompasses outstanding discoveries and catastrophic failures in diagnosis and treatment from the Middle Ages to the present day.

Under different names, TB has affected mankind for millennia. One of these names was the "aesthetic disease," because it led to weight loss and pallor in the younger patients that it often affected. This was considered the ideal of beauty in the Victorian era. Many celebrities suffered from the disease, including poets and artists such as Friedrich Schiller, Lord Byron, and the Bronte family. As recently as the early 1990s, the disease almost changed world history, because Nelson Mandela became ill before the negotiations that led to the end of apartheid in South Africa.

Today, the global community is still not on track to meet its self-imposed targets for controlling the infectious disease, as reported by the World Health Organization (WHO) on World TB Day in late March. Children and young people are the leading victims. In 2020 alone, 1.1 million children and adolescents under age 15 years were infected with TB, and 226,000 died of the disease, according to the WHO.

Coliquio: Nelson Mandela was ill with tuberculosis during his imprisonment. How did the disease manifest itself in the future Nobel Peace Prize winner, and what is known about the treatment?

Ronald D. Gerste: Nelson Mandela contracted tuberculosis in 1988. At that time, he was 70 years old and had been in prison for 26 years. The disease presented in him with the almost classic symptom: he was coughing up blood and was also increasingly fatigued and losing weight. After doctors initially suspected a viral infection, but then TB was proven, he was treated with medication, and fluid was also drained from his lungs. Mandela was hospitalized for six weeks at Tygerberg Hospital in Cape Town, the second largest hospital in South Africa. The therapy worked well, but Mandela's lungs remained damaged. He was subsequently prone to pneumonia and was repeatedly hospitalized for pneumonia in 2012 and 2013.

Mandela was lucky that the treatment worked for him. A few years later, the first antibiotic-resistant pathogen strains developed. How did medical research respond to this development?

Gerste: The emergence of multidrug resistant (MDR) strains of the pathogen prompted the WHO to declare a "global health emergency" in 1993. Three years later, World TB Day was proclaimed to raise awareness of the threat posed by this disease, which has been known since ancient times. It always takes place on March 24, the day in 1882 when Robert Koch gave his famous lecture in Berlin in which he announced the discovery of the pathogen Mycobacterium tuberculosis.

Medical research has introduced new drugs into TB therapy, such as bedaquiline and delamanid. But MDR tuberculosis therapy remains a global challenge and has diminished hopes of eradicating tuberculosis, as we did with smallpox some 40 years ago. Today, only 56% of all MDR-TB patients worldwide are successfully treated.

As already mentioned, the TB pathogen was discovered by Robert Koch. How did this come about?

Gerste: Along with cholera, TB was a great epidemic of the 19th century. For an ambitious researcher like Robert Koch, who had made a name for himself with the discovery of anthrax in 1876, there was no more rewarding goal than to find the cause of this infectious disease, which claimed the lives of many famous people such as Kafka, Dostoevsky, and Schiller, as well as many whose names are forgotten today.

Koch worked with his cultures for several years; the method of staining with methylene blue that was developed by the young Paul Ehrlich represented a breakthrough. To this method, Koch added a second, brownish dye. After countless experiments, this allowed slightly curved bacilli to be identified in tuberculous material under the microscope.

On the evening of March 24, 1882, Koch gave a lecture at the Institute of Physiology in Berlin with the title "Etiology of TB," which sounded less than sensational on the invitations. One or two dozen participants had been expected, but more than one hundred came; numerous listeners had to make do with standing room behind the rows of chairs in the lecture hall. After a rather dry presentation (Koch was not a great orator nor a self-promoter), he presented his results to those present.

His assistants had set up a series of microscopes in the lecture hall through which everyone could get a glimpse of this enemy of humanity: the tubercle bacillus. When Koch had finished his remarks, there was silence in the hall. There was no burst of applause; the audience was too deeply aware that they had witnessed a historic moment. Paul Ehrlich later said that this evening had been the most significant scientific experience of his life. Over the next few weeks, the newspapers made a national hero out of Robert Koch, and the Emperor appointed him a Privy Councilor of the Government. The country doctor from Pomerania was now the figurehead of science in the young German Empire.

Shortly after his discovery, Koch advertised a vaccination against TB with the active ingredient tuberculin. Was he able to convince with that too?

Gerste: No, this was the big flop, almost the disaster of a remarkable scientific career. The preparation of attenuated tubercle bacilli with water and glycerin not only did not prevent infection at all, it proved fatal for numerous users. However, tuberculin has survived in a modified form: as a tuberculin test, in which a characteristic skin rash indicates that a tested person has already had contact with the Mycobacterium.

How have diagnostic options and treatment of the disease evolved since Robert Koch's lifetime?

Gerste: A very decisive advance was made in diagnostics. With the rather accidental discovery of the rays soon named after him by Wilhelm Conrad Röntgen in the last days of 1895, it became possible to visualize the lung changes that tuberculosis caused in an unexpected way on living patients; the serial examinations for TB by X-rays were the logical consequence. Both scientists received Nobel Prizes, which were still new at the time, within a few years of each other: Röntgen in 1901 for physics, and Koch in 1905 for medicine and physiology.

Effective drugs were practically unavailable toward the end of the 19th century. For those who could afford it, however, a whole new world of (hoped-for or perceived) healing from "consumption" opened up: the sanatorium, located high in the mountains, surrounded by "fresh air." The most famous of these climatic health resorts is probably Davos. It is no disrespect to the Swiss Confederation, which I hold in high esteem, to point out that Switzerland owes its high status as a tourist destination and thus its prosperity in part to TB.

Things were quite different in earlier times. Until 250 years ago, the hopes of many patients rested on the medieval healing method of the "royal touch." What's that all about?

Gerste: In the Middle Ages, a "healing method" emerged from which not only lepers and other seriously ill people, but also those suffering from consumption expected to be saved: the "royal touch," which was first described by the Frankish king Clovis in 496. This ceremony was based on the idea that the king or queen, anointed by God, could improve or even cure the ailment of a sick person through a brief touch.

With the transition from the Middle Ages to the early modern period, this act, during which thousands often gathered in front of the ruler's residence, was practiced on a large scale. The sufferers passed by the anointed ruler as if in a procession and were briefly touched by him or her. The extremely few "successes" were of course exploited by royal propaganda to proclaim the blessing that the reign of the king or queen meant for the country. But on those who nevertheless fell victim to TB or another ailment, the chroniclers remained silent.

Charles II of England, who ruled from 1660 to 1685 during the Restoration after the English Civil War, is said to have touched 92,102 sick people during this period, according to contemporary counts. The record for a single day's performance is probably held by Louis XVI of France, who is said to have touched a total of 2400 sufferers on June 14, 1775. Some of them may have stood and cheered in the Paris crowd 18 years later as the king climbed the steps to the guillotine.

Another invention associated with TB diagnosis is the stethoscope. How did it come about?

Gerste: A young physician named René-Théophile-Hyacinthe Laënnec had already experienced the importance of diagnosing TB in his student years. His teacher in Paris was Xavier Bichat, considered the founder of histology, who died of TB in Laennec's second year at the age of only 30. Laennec was a devotee of auscultation and made it work with a massively overweight patient by rolling up a sheet of paper, then placing this on the woman's thorax to listen to her heart sounds. He developed the idea further and built a hollow wooden tube with a metal earpiece. In 1818, he presented the device at the meeting of the Academy of Sciences in Paris; he called it a stethoscope. He used his new instrument primarily to auscultate the lungs of patients with TB and distinguished the sounds of TB cavities from those of other lung diseases such as pneumonia and emphysema.

Back to the present day: The WHO wants to eradicate TB once and for all. What are the hopes and fears in the fight against this disease?

Gerste: There is no doubt that we are currently taking a step backwards in these efforts, and this is not only due to multiresistant pathogens. Especially in poorer countries particularly affected by TB, treatment and screening programs have been disrupted by lockdown measures targeting COVID-19. The WHO suspects that in the first pandemic year, 2020, about half a million additional people may have died from TB because they never received a diagnosis.

This article was translated from Coliquio.

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Cite this: Tuberculosis: The Disease That Changed World History - Medscape - May 16, 2022.