16th-Century Child Mummy Had Oldest Known Case of Hepatitis B

Long thought to suffer from smallpox, the genome of the 500-year-old mummy shows signs of HPB

Hep B
The mummified remains of a small child that bears evidence of an ancient Hepatitis B infection. Gino Fornaciari, University of Pisa

Some 500 years ago, a two year old died, and its remains were laid in a crypt of the Basilica of Saint Domenico Maggiore in Naples, Italy. There it lay for hundreds of years, the body slowly mummifying in the dry conditions of the basilica.

In the 1980s, researchers examined the remains, diagnosing the child with the earliest known case of small pox. But a new genomic test tells a different story. As Nicholas St. Fleur at The New York Times reports, the child may actually have oldest known case of hepatitis B.

As Ed Cara at Gizmodo reports, when the child mummy was autopsied in the 1980s, researchers noted a rash across the child's body that was consistent with small pox. Electron microscope scans also seemed to show the oval-shaped Variola virus indicative of the disease.

But in 2016, researchers examining another case of ancient small pox, found in a sixteenth-century Lithuanian mummy, decided to reexamine the Maggiore mummy with the hopes of studying how the disease evolved over time, St. Fleur reports. They sequenced the mummy's DNA and examined it, but found no trace of the smallpox virus. Instead, they discovered a fragment of hepatitis.

Further study of the mummy helped researchers realize that the rash or dots on the child’s face could have been caused by Gianotti-Crosti syndrome, one of the potential symptoms of hepatitis B (HBV). They published their work last week in the journal PLOS Pathogens.

According to the Centers for Disease control, some 350 million people currently live with the virus. Up to one-third of humans will be infected during their lifetime, according to the press release. The virus infects the liver and is spread by contact with blood and bodily fluids of infected people. Long term infections, known as chronic HBV, can cause lasting liver damage. But there is still much to learn about the history of this disease and the new study is uncovering clues to its complex past.

In the five centuries since the HBV infected the child in Naples, the virus had barely evolved, according to a press release. The find is surprising since most viruses evolve quickly, sometimes even in mere days. This could be a sign of contamination, St. Fleur reports. But a year and a half of validation work suggests that the virus is indeed as old as the rest of the mummy DNA and is unlikely a relic of contamination. 

The researchers also analyzed the HBV virus using other ancient strains of the disease, discovering that indeed it does evolve incredibly slowly, barely changing in 500 years. Hendrik Poinar, an evolutionary geneticist with the McMaster Ancient DNA Centre and co-author of the study tells St. Fleur it is still possible the virus is contamination, but he says the odds are it's not. “I’m 80-20 at this point, or maybe 90-10, that it’s not contamination,” he says.

The fact that Hep B hasn’t evolved makes sense, study co-author Edward Holmes tells Rachel Becker at The Verge. “HBV is a very unusual virus,” he says, pointing out that its DNA is short and rigid, and that mutations often just disable the virus. “On the one hand this makes the virus very small and efficient but on the other it means that very few mutations actually work.”

So why is it important to figure out the history of diseases like smallpox and hepatitis? “The more we understand about the behavior of past pandemics and outbreaks, the greater our understanding of how modern pathogens might work and spread, and this information will ultimately help in their control,” Poinar says in the press release.

As anyone suffering from this winter’s influenza (which is part of a major global flu outbreak this year) may bemoan, medical science doesn’t have a firm grasp on how viruses evolve and which ones will infect humans. The consequences can be dire. One hundred years ago, in 1918, up to 100 million people died in the worst flu outbreak in human history. While living conditions and healthcare have gotten much better since then, humanity is still vulnerable to fast-moving, virulent pathogens.

Yet studies like this latest work will help in the battle, teasing through the history—and eventually helping to anticipate the future—of such viruses. As Lizzie Wade at Smithsonian Magazine reported in March last year, the Lithuanian mummy—another child who died of smallpox—suggests that smallpox is relatively new. Researchers had long believed even Egyptian mummies suffered from smallpox, but "molecular clock” studies suggest the disease didn't arise till the sixteenth or seventeenth century. Earlier cases may have been the result of a different scourge.

Only with better understanding of these diseases will we be able to protect ourselves from future outbreaks.

Editor's Note 1/9/2018: This article was corrected to note that winter influenza cases (not cases of stomach flu) are part of this year's global flu problems.

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