Why Didn't Tuberculosis Wipe Out Humanity in the Paleolithic Era?

Why Didn't Tuberculosis Wipe Out Humanity in the Paleolithic Era?
CDC via AP
Why Didn't Tuberculosis Wipe Out Humanity in the Paleolithic Era?
CDC via AP
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Tuberculosis may be the greatest plague of humankind. Bacterial and brutally infectious, it attacks the lungs, causing a painful, hacking cough. It also sends the body's metabolism into overdrive, resulting in rapid weight loss, drenching sweats, and utter exhaustion.

Tuberculosis is responsible for as many as one billion deaths in the last 200 years alone, but its murderous history extends back even further, to as long as 75,000 years ago. It was at this time, when, as scientists from the Swiss Tropical and Public Health Institute previously argued in 2018, that Mycobacterium tuberculosis first emerged and found a home in humans.

In a recent issue of the journal Scientific Reports, Spanish researchers Pere-Joan Cardona, Martí Català and Clara Prats asked, and attempted to answer, a different, more blunt question: How did a devastating disease like tuberculosis not eradicate humankind altogether?

They examined a time about 40,000 to 50,000 years ago, when the human population, existing almost entirely in Africa, may have numbered in just the tens of thousands.

"Organized into small tribes of around 50 individuals, these humans were nomadic hunter gatherers, had a good health status thanks to a lifestyle based on a varied diet, low work intensity and moderate exercise. This resulted in a life expectancy of around 33 years," the authors described.

A tuberculosis infection could easily upend this picturesque Paleolithic existence. Cardona and his colleagues suggest that early strains of tuberculosis began as latent infections which generally remained dormant and only occasionally killed the weak, old, and young. By 48,000 years ago, however, modern lineages emerged that were far more deadly, yet still could persist in a latent stage. (About a quarter of all humans are currently infected with latent tuberculosis.) The researchers created a disease transmission model based on known facts about modern tuberculosis and estimated population dynamics of ancient human hunter-gatherers which showed that tuberculosis could quickly kill off an entire nomadic tribe and spread to others.

Towards the end of the Paleolithic (50,000 to 10,000 years ago), humans started to cluster into larger settlements, and they almost certainly brought tuberculosis with them. In this situation, the disease could have brought humanity to the brink of extinction, the researchers say.

Thankfully, it didn't. To overcome tuberculosis, humans would have needed to undergo a massive population increase, multiplying by twenty times in just a hundred years, the researchers estimated. Females also likely developed some form of resistance to the bacterium which greatly contributed to humanity's survival.

"The explanation for this resistance could lie in the enhanced level of regulatory T cells (Tregs) generated by oestrogens," Cardona and his colleagues wrote. "As demonstrated in a non-human primate experimental model, latently infected animals with increased levels of Tregs exhibit less progress to active tuberculosis."

Over tens of thousands of years, humans have co-evolved with Mycobacterium tuberculosis. It has shaped us, and we have shaped it. Vaccination and improved sanitation have rendered the disease rare in the developed world, but it still remains the deadliest infectious disease of humans in the world, killing 1.5 million people in 2018 alone.

Source: Cardona, P., Català, M. & Prats, C. "Origin of tuberculosis in the Paleolithic predicts unprecedented population growth and female resistance." Sci Rep 10, 42 (2020) doi:10.1038/s41598-019-56769-1

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