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On the Prehistory of Tuberculosis

Written by Nathan Lee, Edited by Nikhil Chakravarty

Introduction: The Captain of All These Men of Death

Tuberculosis has followed humanity in its shadows for as long as recorded history has been kept. Currently, tuberculosis holds the Guinness World Record for the oldest documented human infectious disease in the world, and in addition to possibly being the oldest, it has consistently been one of the deadliest. German microbiologist Robert Koch, who first isolated Mycobacterium tuberculosis, wrote in his 1882 book Die Atiologie der Tuberculose, “if the importance of a disease for mankind is measured from the number of fatalities which are due to it, then tuberculosis must be considered much more important than those most feared infectious diseases, plague, cholera, and the like.” Historical estimates have suggested that during the 19th century, tuberculosis was responsible for as many as one in four human deaths in Europe. Even in the modern day, it is the leading cause of death from a single infectious agent, and kills approximately 1.2 million people annually (World Health Organization, 2020). 

But more than just being a leading agent of mortality, tuberculosis had just as significant a role in shaping human history, and rather than being just a historic killer, recent evidence suggests that tuberculosis may be a prehistoric one. This literature review examines recent advances in paleopathology that support the presence of tuberculosis in prehistoric hominids, reshaping our understanding of the disease’s antiquity and its relationship with humanity, as one of our longest-standing biological nemeses. 


A Modern Look at the White Plague

Tuberculosis is an airborne disease that primarily infects the lungs but can spread to other organs, such as the kidneys, spine, and brain. It spreads primarily via coughs and sneezes, and if left untreated, has a mortality rate of about 50%. Its causative agent, M. tuberculosis, is a slow-growing obligate pathogen with a unique cell wall composed of mycolic acid lipids, unlike the majority of bacteria, which lack this feature entirely. This unusual cell wall is an important virulence factor, as it protects the bacteria from antibiotics and the host’s immune system, and also plays a key role in its identification in paleopathology through lipid biomarkers.

A defining feature of tuberculosis infection is the formation of granulomas - clusters of immune cells meant to contain the bacteria when the immune system is unable to directly destroy them. Tuberculosis is able to persist in a latent, non-transmissible state – something that about 25% of the world’s population has – before showing any symptoms, which can include persistent blood or sputum-filled coughs, chest pains, severe weight loss, and drenching night sweats (Sakamoto, 2012). 

In some cases, chronic infection can lead to skeletal deformities, particularly in the spine, known as Pott's disease (tuberculous spondylitis). One reason tuberculosis has such a clear historical record is that, unlike many other infectious diseases, it can leave lesions in bones (Dutour, 2023), specifically osteolytic lesions where the bone is eaten away. These biological features make tuberculosis especially significant in the study of ancient diseases, as both its chronic nature and distinctive biomarkers increase the likelihood of preservation in the archaeological record. 


Prehistoric Evidence of Tuberculosis in Hominids (and Other Species)

Part 1: Physical and Biomolecular Evidence

Although this literature review is primarily about tuberculosis in hominids, evidence of a similar disease may date back even to before the earliest primates. A 245-million-year-old fossil of Proneusticosaurus – a Triassic non-dinosaurian reptile – was found with lesions on its ribs that have only been identified in humans with tuberculosis. While M. tuberculosis itself has only evolved relatively recently and primarily only affects humans and a few other mammals, this discovery suggests that tuberculosis-like infections, and possibly the broader Mycobacterium genus, are far older than was previously thought; this is also consistent with several bacteria’s ability to infect reptiles within the genus (Surmik et al., 2018). 

One of the oldest confirmed cases of tuberculosis in ancient hominins comes from 2 Neanderthal individuals – an approximately 25-35-year-old woman and a 3-4-year-old child – discovered in a cave in North-Eastern Hungary and dated to roughly 39,000-35,000 years ago. Both individuals exhibited bone lesions consistent with tuberculosis, but a more definitive diagnosis was made through biomolecular analysis, detecting tuberculosis-specific DNA fragments and mycolic acid, a feature exclusive to Mycobacterium that provides strong evidence of infection (Lee et al., 2023). 


Part 2: Genetic Evidence

Genetic evidence has also reshaped our understanding of tuberculosis’s origin. Earlier models proposed that tuberculosis originated from zoonotic transmission, similar to other infections such as smallpox or plague. However, after completely sequencing M. tuberculosis’s genome, it was suggested that animal tuberculosis likely originated from an ancestral human pathogen, rather than the reverse. Tuberculosis in humans is so ancient and has co-evolved so well alongside our species that genetic studies of the Mycobacterium tuberculosis Complex (MTBC) have been used to trace the expansion of human populations. 

A genomic study of 259 strains confirms that the human strain of an M. tuberculosis ancestor emerged in Africa around 70,000 years ago, and followed human migrations out of Africa in multiple waves to South Asia, Europe, and East Asia. However, the modern lineage of M. tuberculosis, defined by a deletion in the TbD1 gene, dates back only to around 40,000-35,000 years ago and may have even caused an evolutionary bottleneck by selecting for genetic resistance to the disease (Dutour, 2023). 


Part 3: But What Does it Mean? Implications and Limitations

Taken altogether, this skeletal, biomolecular, and genetic evidence suggests that tuberculosis existed in multiple hominid populations, predating modern humans as we know them. Indeed, the findings suggest that tuberculosis has been associated with human populations since their earliest dispersal, possibly even shaping the course of human evolution. It should be further noted that, according to modern data, only about 1-5% of patients with pulmonary tuberculosis, the most common kind, develop skeletal lesions; thus, detection of tuberculosis in paleopathology is almost certainly massively underestimated. 

At the same time, however, discovery of tuberculosis-like infections isn’t always conclusive proof of tuberculosis, especially regarding skeletal evidence. A Homo erectus fossil in Turkey, dated 500,000 years ago, was diagnosed with cranial tuberculosis based on lesions on the skull, but this interpretation was strongly questioned by other scientists (Buzic & Giuffra, 2020). 


Conclusion: Consumption and You

The growing body of paleopathological evidence demonstrates tuberculosis as not only an old disease, but one that has accompanied humans and even our common ancestors for tens of thousands of years. It is a sickness that has shaped human history as much as we have shaped it. Today, many people believe that tuberculosis is simply another disease of the past that we have conquered, but understanding tuberculosis’s past proves that our relationship with it isn’t just a simple matter of host and pathogen. Rather, this disease is deeply intertwined with human evolution and humanity as a whole; it has shaped, and will likely continue to shape, our biology, society, and history. While other diseases such as plague, Ebola, and anthrax may cause greater scares, tuberculosis was, and still is, a constant smoldering fire that continues to gnaw at us as a species.

References

  1. Dawid Surmik, Tomasz Szczygielski, Katarzyna Janiszewska, Bruce M. Rothschild; Tuberculosis-like respiratory infection in 245-million-year-old marine reptile suggested by bone pathologies. R Soc Open Sci. 1 June 2018; 5 (6): 180225. https://doi.org/10.1098/rsos.180225 

  2. Buzic, I., & Giuffra, V. (2020). The paleopathological evidence on the origins of human tuberculosis: a review. Journal of preventive medicine and hygiene, 61(1 Suppl 1), E3–E8. https://doi.org/10.15167/2421-4248/jpmh2020.61.1s1.1379 

  3. Olivier Dutour, (2023). The paleopathology and paleoepidemiology of Upper paleolithic tuberculosis: Review of evidence and hypotheses, Tuberculosis, Volume 143, Supplement, 102348, ISSN 1472-9792, https://doi.org/10.1016/j.tube.2023.102348. 

  4. Oona Y-C. Lee, Houdini H.T. Wu, Gurdyal S. Besra, David E. Minnikin, Heidi Y. Jaeger, Frank Maixner, Albert Zink, Mihály Gasparik, Ildikó Pap, Zsolt Bereczki, György Pálf. (2023) Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary, Tuberculosis, Volume 143, Supplement, 102420, ISSN 1472-9792, https://doi.org/10.1016/j.tube.2023.102420. 

  5. Sakamoto, K. (2012). The pathology of Mycobacterium tuberculosis infection. Veterinary pathology, 49(3), 423-439.

  6. World Health Organization. (2020). Global tuberculosis report 2020: executive summary.

This post is not a substitute for professional advice. If you believe that you may be experiencing a medical emergency, please contact your primary care physician, or go to the nearest Emergency Room. Results from ongoing research are constantly evolving. This post contains information that was last updated in May 2026.


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