Tuberculosis — or TB for short — is as old as humanity itself. It is caused by Mycobacterium tuberculosis, an exclusive human pathogen. According to the World Health Organization, in 2013, 9 million people fell ill with TB and 1.5 million died from the disease worldwide.
Although it is difficult to estimate the number of deaths caused by TB throughout history, we know that M. tuberculosis has been an ever-present scourge for humanity, and may have killed more people than any other microbial pathogen. Indeed, TB has been given many unpleasant names. From Hippocrates through to the 18th century, it was known as phthisis and consumption. During the 19th century, TB was called the white death and the great white plague. Other “historical” TB names aptly evoke images of despair and horror — the robber of youth, the captain of all these men of death, the graveyard cough, and the king’s evil.
The long-standing relationship between M. tuberculosis and humans has been present not just for a few thousands of years, but for much longer. In 2013, researchers “found evidence that TB hitched its cart to the human evolutionary horse more than 70,000 years ago, before our ancestors migrated out of Africa.” They published their findings in the scientific journal Nature Genetics. Sebastien Gagneux, an infectious diseases specialist at the Swiss Tropical and Public Health Institute in Basel and senior author of the study, said: “The old, traditional view was that tuberculosis emerged during the Neolithic transition when people started to domesticate animals and develop agriculture, which started about 10,000 years ago. Our work suggest that TB is really much older.” The researchers explained in their paper that different strains of M. tuberculosis accompanied migrations of modern humans out of Africa, and expanded as a consequence of increases in human population density during the Neolithic period.
Between the 17th and the 19th century, TB caused about 20% of all human deaths in the United States and in Europe. Until the early 20th century, people infected with tuberculosis were isolated from society and placed in sanatoriums — self-contained communities that, not surprisingly, became known as “waiting rooms for death.” Now, a new study published in the journal Nature Communications, reveals how TB took hold in 18th century Europe. The researchers analyzed samples from mummies found in a Hungarian crypt, and found evidence of multiple tuberculosis strains derived from a single Roman ancestor that circulated in the 18th-century. Mark Pallen, senior author of the study, said in a press release: “Microbiological analyses of samples from contemporary TB patients usually report a single strain of tuberculosis per patient. By contrast, five of the eight bodies in our study yielded more than one type of tuberculosis — remarkably from one individual we obtained evidence of three distinct strains.”
The samples originates from a crypt, re-discovered in 1994, located in the Dominican church of Vác in Hungary. It contained the remains — which had undergone natural mummification — of over 200 individuals, mostly affluent Catholics from the eighteenth and early nineteenth centuries.
The researchers used a technique called “metagenomics” to identify TB DNA in the historical specimens — the technique draws on the remarkable throughput and ease of use of modern DNA sequencing technologies, and allows sequencing of DNA directly from samples, without the need of growing bacteria or deliberately fishing out TB DNA. The researchers found that the samples carried the genetic signature of M. tuberculosis Lineage 4, a strain that today accounts for more than a million TB cases every year in Europe and the Americas.
Pallen said: “By showing that historical strains can be accurately mapped to contemporary lineages, we have ruled out, for early modern Europe, the kind of scenario recently proposed for the Americas — that is, replacement of one major lineage by another — and have confirmed the genotypic continuity of an infection that has ravaged the heart of Europe since prehistoric times.” He added that the struggle to contain TB is far from over, and concluded: “We have shown that metagenomic approaches can document past infections. However, we have also recently shown that metagenomics can identify and characterize pathogens in contemporary samples, so such approaches might soon also inform current and future infectious disease diagnosis and control.”