Beethoven's death: Whole-genome sequencing from hair reveals Hepatitis B

More than 200 years ago, Ludwig van Beethoven asked for postmortem examinations to diagnose his fatal illness and make it known to the world. Now, a team of researchers has partially fulfilled that request by analyzing DNA they lifted and pieced together from locks of his hair, according to a new study published in Current Biology on March 22.

Not only do the findings finally reveal evidence of a life-threatening liver infection, but they also point to an 'extramarital' event on Beethoven's father's side and call to question a widely-held belief that he died from lead poisoning. 

How did Beethoven die?

In the new study, the team made use of recent advancements in ancient DNA analysis, which allowed for whole-genome sequencing from small amounts of historical hair.

"We were unable to find a definitive cause for Beethoven's deafness or gastrointestinal problems," Krause says. "However, we did discover a number of significant genetic risk factors for liver disease," said Johannes Krause from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, in a press release. 

"We also found evidence of infection with hepatitis B virus in, at the latest, the months before the composer's final illness. Those likely contributed to his death," he disclosed. 

The Stumpff Lock in a laboratory at the Max Planck Institute for the Science of Human History, Germany.

Anthi Tiliakou 

The researchers point out that prior studies that suggested Beethoven had lead poisoning were based on a sample that wasn't even Beethoven's. Instead, it was from a female. They argue that future investigations looking for lead, opiates, and mercury must be based on reliable samples.

Also, Krause's team found that none of the five modern relatives with the same last name as Beethoven, who have a common ancestor with his paternal line (based on genealogical records), share the same Y chromosome.

This discovery suggests an extramarital 'event' on Beethoven's father's side somewhere along the generations, according to Tristan Begg, currently a professor at the University of Cambridge, U.K.

In line with Beethoven's known German origin, the study also showed that the DNA retrieved from his hair is genetically most comparable to those living in modern-day North Rhine-Westphalia.

"Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven's severe liver disease, which culminated in his death," stated the team. 

They conclude that further research on Beethoven's samples, which were gathered over time, may help to determine when he contracted hepatitis B. Besides that, new research on his near relatives could also shed light on his biological connection to modern Beethoven descendants.

Study abstract

Ludwig van Beethoven (1770–1827) remains among the most influential and popular classical music composers. Health problems significantly impacted his career as a composer and pianist, including progressive hearing loss, recurring gastrointestinal complaints, and liver disease. In 1802, Beethoven requested that following his death, his disease be described and made public. Medical biographers have since proposed numerous hypotheses, including many substantially heritable conditions. Here we attempt a genomic analysis of Beethoven in order to elucidate potential underlying genetic and infectious causes of his illnesses. We incorporated improvements in ancient DNA methods into existing protocols for ancient hair samples, enabling the sequencing of high-coverage genomes from small quantities of historical hair. We analyzed eight independently sourced locks of hair attributed to Beethoven, five of which originated from a single European male. We deemed these matching samples to be almost certainly authentic and sequenced Beethoven’s genome to 24-fold genomic coverage. Although we could not identify a genetic explanation for Beethoven’s hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease. Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven’s severe liver disease, which culminated in his death. Unexpectedly, an analysis of Y chromosomes sequenced from five living members of the Van Beet-hoven patrilineage revealed the occurrence of an extra-pair paternity event in Ludwig van Beethoven’s patrilineal ancestry.

 22.03.2023

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