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  • Genomic Analysis of Ludwig van Beethoven Reveals Details About His Past

    German composer and pianist Ludwig van Beethoven remains one of the world’s most revered musicians. He is well known for his famous pieces such as Moonlight Sonata, Ode to Joy, Für Elise, and the Fifth and Ninth Symphonies. During Beethoven’s life, he suffered many health issues including progressive hearing loss, liver disease, and chronic gastrointestinal problems, although these issues didn’t prevent him from continuing his work.

    In a letter discovered shortly after his death, Beethoven requested that after he passed, he wanted his favorite physician, Dr. Johann Adam Schmidt, to describe his “malady” to the world. Beethoven ended up outliving Dr. Schmidt by 18 years, and over two centuries after his death in 1827, a team of researchers are working to fulfill his request and determine the exact cause of his condition.

    “Our primary goal was to shed light on Beethoven’s health problems, which famously include progressive hearing loss, beginning in his mid-to late-20s and eventually leading to him being functionally deaf by 1818,” said the leading author of the study, Johannes Krause from the Max Planck Institute for Evolutionary Anthropology.

    “We were unable to find a definitive cause for Beethoven’s deafness or gastrointestinal problems,” Krause added. “However, we did discover a number of significant genetic risk factors for liver disease. We also found evidence of an infection with hepatitis B virus in the [final] months before the composer’s final illness. Those likely contributed to his death.”

    Due to improved methods for studying ancient DNA, the research team was able to gather this information after extracting DNA from locks of Beethoven’s hair. Five of the eight locks examined were confirmed to be from the same European male, and these were used to sequence his genome to 24-fold genomic coverage. The resulting data was used to perform ancestry analyses to examine Beethoven’s genealogy, in addition to extensive analysis for identifying genetic causes of and risk for somatic disease. Furthermore, the team used metagenomic screening to find evidence of infections, along with targeted DNA capture.

    During the investigation of Beethoven’s genealogy, the team noted that his Y chromosome didn’t match the five modern-day relatives that share a common ancestor with his paternal line based on genealogical records. “This finding suggests an extrapair paternity event in his paternal line between the conception of Hendrik van Beethoven in Kampenhout, Belgium in c.1572 and the conception of Ludwig van Beethoven seven generations later in 1770, in Bonn, Germany,” said first author Tristan Begg from the University of Cambridge, U.K.

    Beethoven’s health conditions were originally studied by medical biographers that speculated them to be heritable. Conversely, the genomic analysis suggested that his hearing problems and gastrointestinal issues were not related to anything genetic. The results did show that Beethoven was genetically predisposed to liver disease and further investigation of the isolated DNA showed evidence of a hepatitis B infection. The researchers believe that the infection, along with his genetic predisposition and alcohol consumption, were plausible explanations for his severe liver disease.

    In addition, a previous analysis proposed Beethoven had suffered from lead poising. It was discovered that the sample used for that analysis was from a female and future studies will need to authenticate the DNA before performing this type of testing.

    After a thorough analysis of Beethoven’s DNA, it was determined that genetically he would be most similar to people living in modern-day North Rhine-Westphalia, consistent with his known German ancestry. Future studies on Beethoven will include analysis of additional locks of his hair to find informative biomarkers, the beginning of his hepatitis infection, and any additional contributors to disease. Lastly, further investigations into living and deceased relatives may explain his connection with modern decedents.

    Read the original study published in Current Biology.

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