Hair samples provide insight into Beethoven’s genetic make-up

Hair samples provide insight into Beethoven’s genetic make-up

This lock of Ludwig van Beethoven’s hair provided DNA samples of the composer. © Ira F. Brilliant Center for Beethoven Studies/ San Jose State University

Ludwig van Beethoven is one of the most famous German composers of the classical era, and because of his increasing hearing loss he is also considered a deeply tragic figure. In order to find out more about Beethoven's illnesses and the cause of his death, scientists have now genetically examined eight hair samples that were thought to be the composer's locks of hair. Five of these locks turned out to be authentic and could therefore be used for DNA analyses. These reveal that Beethoven had no clearly verifiable genetic cause for the hearing loss, but a high risk of liver cirrhosis. In combination with a relatively high alcohol consumption and a hepatitis infection, this could have caused the composer's death.

Ludwig van Beethoven was born in Bonn in 1770 and attracted attention early on for his musical talent. A steep career as a pianist and composer followed. However, around 1799 Beethoven developed a progressive hearing loss characterized by gradual hearing loss, tinnitus and finally deafness. She forced the composer to give up his musical career at around the age of 40 and concentrate only on composing, which was also made difficult by his deafness. But the hearing loss was not the only ailment that plagued Beethoven: Even during his years in Bonn, the composer suffered from "miserable" gastrointestinal complaints with diarrhea and painful colic, which continued and worsened in Vienna. From the summer of 1821 onwards, he suffered from liver problems: the composer suffered from jaundice several times and probably developed cirrhosis of the liver. She is also believed to be the most likely cause of his death at the age of just 56.

Ludwig van Beethoven
Portrait of Ludwig van Beethoven made around 1820. © Beethoven House Bonn

Five of the eight locks of hair are authentic

Since then, physicians and historians have tried again and again to find out what illnesses were behind Beethoven's serious illnesses. The composer also hoped for clarification: in 1802 he asked his brothers in a letter to have his illness examined by his doctor after his death and to publish the result. But despite the evaluation of numerous historical documents, an autopsy report and even two exhumations in 1863 and 1888, there were no clear diagnoses - neither for the hearing loss and digestive problems nor for the cause of death. In order to create more clarity, an international research team led by first author Tristan Begg from the University of Cambridge has now genetically examined eight locks of hair that are said to have come from Ludwig van Beethoven and are kept in public and private collections.

The DNA analyzes revealed that five of the eight locks of hair came from the same individual - a man of European descent and genetic similarities to people in North Rhine-Westphalia - the composer's region of birth. The DNA of the hair samples also showed a degradation typical of a 19th-century origin. The team takes this as proof that these five locks of hair are actually Ludwig van Beethoven's hair. One of the other three locks of hair that the 15-year-old musician Ferdinand Hiller is said to have cut off the composer's head shortly after his death turned out to be a woman's hair. "Now that we know that the 'Hiller lock' came from a woman and not Beethoven, none of the previous analyzes based solely on this hair sample apply to Beethoven," says Begg. This invalidates the thesis based on analyzes of this hair, according to which Beethoven is said to have suffered from lead poisoning: Since the hair did not come from him, the diagnosis is also incorrect.

clues to the cause of death

The analyzes of the five authentic hair samples provided valuable information on the composer's cause of death. "We cannot say with certainty what Beethoven died of, but at least we can now prove the existence of a significant hereditary risk for liver cirrhosis," says co-author Johannes Krause from the Max Planck Institute for Evolutionary Anthropology in Leipzig. In Beethoven's genome, the team found, among other things, two copies of a gene variant that is considered to be one of the strongest risk genes for liver cirrhosis. There was also evidence of an infection with the hepatitis B virus, which must have taken place in the months before the composer's first jaundice. "In view of the known medical history, it is very likely that a combination of genetic predisposition, hepatitis B infection and alcohol consumption led to Beethoven's death," says Begg. Because historical records suggest that Beethoven regularly drank enough alcohol to damage his liver. "If Beethoven's alcohol consumption was high enough for a sufficiently long period of time, interaction with his genetic risk factors provides a possible explanation for his liver cirrhosis," says Begg.

However, the research team could not identify any clear genetic causes for Beethoven's deafness or his gastrointestinal problems. No genes for hereditary or genetically determined hearing loss could be found in his genome. "Although no clear genetic cause for Beethoven's hearing loss could be identified, one cannot be completely ruled out," emphasizes co-author Axel Schmidt from the University Hospital Bonn. “The reference data needed to interpret individual genomes is constantly improving. It is therefore possible that Beethoven's genome will provide clues to the origin of his hearing loss in the future." The DNA analyzes also show that Beethoven's stubborn gastrointestinal complaints could not be due to gluten or lactose intolerance, and there are also no genetic signs of irritable bowel syndrome.

A family secret

On the other hand, the genetic analyzes revealed something surprising in another respect. To find out more about Beethoven's lineage, the researchers compared his genome with that of three descendants of his nephew Karl, as well as with five male relatives from the Beethoven line living in Belgium. According to historical documents, the ancestors of Ludwig von Beethoven's father came from Belgium. Both he and today's Belgian descendants of this line go back to Aert von Beethoven, who lived in the 16th century. Because the name, like the Y chromosome, is passed down the paternal line, the scientists expected a match between the Y chromosomal genome in Beethoven and his current namesakes. But that was not the case: the genomes of the five Belgian relatives showed the expected similarities, but none of their Y chromosomes matched Ludwig van Beethoven's. "By combining DNA data and archival documents, we were able to identify a discrepancy between Ludwig van Beethoven's legal and biological genealogy," explains co-author Maarten Larmuseau of the Catholic University of Leuven.

The scientists conclude that there must have been at least one fling in Ludwig van Beethoven's paternal lineage - possibly a "cuckoo child" fathered by a father other than the husband. However, when this extramarital procreation occurred cannot be determined more precisely on the basis of the genetic data available to date. However, the researchers locate her somewhere in the direct paternal line between the fathering of Hendrik van Beethoven in Kampenhout, Belgium, around 1572 and the fathering of Ludwig van Beethoven in Bonn in 1770 - seven generations later. In fact, a Beethoven biographer had previously expressed doubts that Beethoven's grandfather Ludwig van Beethoven was really the father of Beethoven's father Johann van Beethoven because there was no corresponding baptismal entry. However, there is no clear historical evidence for this hypothesis.

"By making Beethoven's genome available to the public, and perhaps in the future adding more authentic hair samples to the original chronological order, we hope to one day be able to answer the remaining questions about Beethoven's diseases and genealogy," says Begg.

Source: Tristan Begg (University of Cambridge) et al., Current Biology, doi: 10.1016/j.cub.2023.02.041

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