Six of the Most Ancient Diseases in the World

The onset of the COVID-19 pandemic in late 2019 was devastating—but it also marked an unprecedented moment when an entirely new disease emerged. While this was a recent phenomenon, many other diseases have been lurking for centuries, long before their identification and the discovery of treatments. Here are six diseases that must have left ancient healers puzzled—and continue to challenge us today.

Cancer // At Least 1.7 Million Years Old

While the true origins of cancer may remain unclear, recent studies suggest it is one of the oldest known diseases to humanity.

In 2016, a study published in the South African Journal of Science revealed the world’s oldest known human malignant tumor, found on a 1.7-million-year-old toe bone from a hominin discovered in South Africa’s Swartkrans Cave. Advanced 3-D imaging revealed the tumor to be osteosarcoma, a type of cancer that affects bone-forming cells. Another study from the same research team identified the earliest known benign tumor in a hominin: an osteoid osteoma found on the vertebrae of a 1.98-million-year-old Australopithecus sediba at the Malapa fossil site in South Africa.

In a more recent discovery, a 2250-year-old Egyptian mummy named M1 was diagnosed with prostate cancer through a CT scan. The scan revealed lesions in the spine and pelvis, indicating the cancer had spread to the bones. Fortunately, today there are numerous treatment options available for prostate cancer at different stages.

Tuberculosis // At Least 70,000 Years Old

Tuberculosis, primarily a lung infection, is one of the deadliest diseases known to humanity. It spreads through microscopic droplets in the air when an infected person speaks, sneezes, or exhales, and may be the deadliest bacterium in human history.

Its origins are ancient. Paleomicrobiologists—scientists who examine microbes in prehistoric tissues—suggest that TB was present in Paleolithic humans in Africa around 70,000 years ago. As humans migrated globally, the disease followed. During the 17th and 18th centuries, it was referred to by various names, including consumption, white plague, or phthisis (pronounced 'THI-suhss').

By the time the bacterium responsible for TB, Mycobacterium tuberculosis, was identified by German physician Robert Koch in 1882, it was killing one in every seven people in the U.S. and Europe.

Early symptoms of TB infection include coughing, fever, and fatigue. The disease often advances into a latent stage, where no symptoms are shown, before becoming active when the immune system can no longer contain the spread of the bacterium. In the active phase, the infected person may cough up blood, feel constantly tired, and lose their appetite. Active infections are treated with antibiotics, and latent TB can be managed before severe symptoms arise.

Though treatable, tuberculosis still claimed 1.3 million lives in 2022 and is now the world’s second-deadliest infectious disease, following COVID-19. It has also earned a Guinness World Record as the oldest contagious disease. Quite an achievement, wouldn't you say?

Dental Caries // At Least 15,000 Years Old

Dental caries, also known as tooth decay, is the most prevalent disease in the United States—and humans have been enduring it for millennia.

It was once believed that Paleolithic hunter-gatherers avoided dental issues due to their low-carb diets, with dental caries emerging only when people transitioned to farming grains and other starchy foods. These foods break down into sugars in the mouth, and bacteria like Streptococcus mutans metabolize the sugars into acids that decay teeth.

A 2014 study from the Natural History Museum in London revealed a surprising discovery at the site of a hunter-gatherer society in Morocco that lived as long as 15,000 years ago. Skeletal remains from the site displayed severe tooth decay—so extensive that many individuals would have had to chew food on the roots of their teeth. The likely culprits were the acorns and pine nuts they consumed regularly, which were rich in fermented carbohydrates. Lead author Louise Humphrey shared with NPR that the prevalence of ancient dental caries was closely linked to the availability of foraged foods.

Tooth decay can lead to cavities, pain, and even tooth loss, but it is preventable with proper oral hygiene and dental care. Unfortunately for this group, the first primitive toothbrush, the 'chew stick,' didn’t come into use for cleaning teeth until around 3000 BCE.

Malaria // At Least 5500 Years Old

During World War II, U.S. soldiers in the Philippines and New Guinea were severely impacted by malaria, and many Americans still associate the disease with the war. Public health initiatives and other factors led to the elimination of malaria in the U.S. by 1951.

But malaria's history stretches back much further. A 2024 study published in the journal Nature examined genetic material from ancient human remains found in 16 countries, revealing traces of malaria in specimens over 5500 years old. The researchers believe the disease may be even older.

Malaria is caused by a blood parasite from the genus Plasmodium, which is transmitted by the female Anopheles mosquito. Humans become infected with malaria if bitten by an infected mosquito. The initial symptoms include fever, chills, and weakness, but if untreated, malaria can lead to organ failure and death. It is a major cause of illness in sub-Saharan Africa, where Anopheles mosquitoes bite humans 98 percent of the time and spread infections widely. The majority of the victims are children under 5 years old. The World Health Organization (WHO) reported 249 million malaria cases and 608,000 deaths globally in 2022.

Malaria can be diagnosed and treated in various ways depending on the patient's condition and the type of symptoms. In 2021, the World Health Organization (WHO) approved the first malaria vaccine.

Lyme Disease // At Least 5300 Years Old

Lyme disease was first recognized in 1975, but its origins can be traced back much further—to the Copper Age, approximately 5300 years ago.

The bacterium responsible for Lyme disease, Borrelia burgdorferi, was identified through mitochondrial DNA analysis in the bones of Ötzi the Iceman, the oldest known European mummy. Ötzi, who was found in the Ötztal Alps in 1991, died around 3300 BCE from an arrow wound in his left shoulder. The injury likely led to his death due to blood loss, exposure, and shock, as detailed in a 2013 paper in Inflammopharmacology. While we can't say for sure whether Ötzi suffered from Lyme disease, it likely did not contribute to his death.

Lyme disease was not officially recognized until 5275 years later, in 1975, when a group of children in Lyme, Connecticut, developed symptoms resembling rheumatoid arthritis. As more people in nearby areas experienced the same symptoms, scientists pinpointed Borrelia burgdorferi, a bacterium transmitted by deer ticks, as the cause in 1981.

Why did Lyme disease appear so suddenly? A 1994 study suggests that reforestation in the Northeast U.S. beginning in the 1920s provided new habitats for deer. The subsequent creation of suburban areas with meadow patches and wooded spaces, perfect for both deer and humans, led to more encounters with deer ticks carrying the bacteria.

Common signs of Lyme disease include fever, chills, muscle aches, and fatigue, which can progress to symptoms resembling arthritis, heart palpitations, and a red skin rash in the shape of a target. If diagnosed early, Lyme disease can be treated effectively with antibiotics.

Leishmaniasis is a disease with a long history, dating back at least 4000 years.

This insect-borne illness is caused by parasites in the genus Leishmania, which inhabit female sandflies of the Phlebotomus genus. Humans are infected through the bites of these sandflies, and Leishmaniasis is most commonly found in tropical and subtropical regions worldwide.

According to the World Health Organization (WHO), up to 1 million cases of Leishmaniasis are reported annually, with the majority being cutaneous Leishmaniasis that leads to skin sores. The rarer forms of the disease—visceral and mucocutaneous Leishmaniasis—are more serious. Only a small proportion of those infected will develop symptoms, and treatments vary based on the parasite species and other factors.

In a 2006 study published in Emerging Infectious Diseases, researchers analyzed tissues from 42 ancient Egyptian and Nubian mummies, dating back to the Middle Kingdom (2050–1650 BCE). They discovered mitochondrial DNA from Leishmania in four of these mummies, confirming that Leishmaniasis has been around for at least 4000 years. Egyptian medical texts from 1500 BCE even mention a skin condition resembling Leishmaniasis, known as the 'Nile pimple.' The pathogens in the Leishmania group likely emerged even earlier, possibly during the Mesozoic Era (252 to 66 million years ago).