Beethoven's genome sheds light on health and history

In 1802, Ludwig van Beethoven asked his doctor to describe his illness and to make this record public; the composer’s health and cause of death have been debated ever since. Over 200 years later, an international team of scientists set out to fulfil the great man’s request, using whole-genome sequencing and five locks of hair.

The research team was led by the University of Cambridge, the Ira F. Brilliant Center for Beethoven Studies and American Beethoven Society, KU Leuven, FamilyTreeDNA, the University Hospital Bonn and the University of Bonn, the Beethoven-Haus Bonn and the Max Planck Institute for Evolutionary Anthropology. Their results, which were published in the journal Current Biology, uncover important information about Beethoven’s health and pose new questions about his ancestry and cause of death.

Authenticating Beethoven’s hair

The team conducted authentication tests on eight hair samples acquired from public and private collections in the UK, continental Europe and the US. In doing so, the researchers discovered that at least two of the locks did not originate from Beethoven, including a famous lock once believed to have been cut from the recently deceased composer’s head by 15-year-old musician Ferdinand Hiller but which in actual fact was female in origin. Previous analyses of the ‘Hiller lock’ supported the suggestion that Beethoven had lead poisoning — a possible factor in his health complaints, including his hearing loss — so analyses based solely on this lock are now considered inaccurate.

The five samples identified as being authentic belong respectively to the Ira F. Brilliant Center for Beethoven Studies in California; to a private collector, American Beethoven Society member Kevin Brown; and to the Beethoven-Haus Bonn. The DNA from these five locks of hair — all dating from the last seven years of Beethoven’s life — was found to originate from a single individual matching the composer’s documented ancestry.

Beethoven’s whole genome was sequenced from one of Brown’s samples, the ‘Stumpff lock’, which emerged as the best-preserved sample. The team found the strongest connection between the DNA extracted from the Stumpff lock and people living in present-day North Rhine-Westphalia, consistent with Beethoven’s German ancestry.

The Stumpff lock in a laboratory at the Max Planck Institute for the Science of Human History, Germany. Image credit: Anthi Tiliakou.

Clues to Beethoven’s health

Beethoven famously suffered from progressive hearing loss, beginning in his mid- to late-20s and eventually leading to him being functionally deaf by 1818. He also suffered from gastrointestinal problems and had at least two attacks of jaundice, a symptom of liver disease. Cirrhosis (scarring of the liver) has long been viewed as the most likely cause of his death at the age of 56 in 1827.

“We did discover a number of significant genetic risk factors for liver disease,” said Johannes Krause, from the Max Planck Institute. “We also found evidence of an infection with hepatitis B virus in at latest the months before the composer’s final illness. Those likely contributed to his death.”

“We can surmise from Beethoven’s ‘conversation books’, which he used during the last decade of his life, that his alcohol consumption was very regular, although it is difficult to estimate the volumes being consumed,” added lead author Tristan Begg, currently based at the University of Cambridge, who co-conceived the idea for the study almost a decade ago.

“While most of his contemporaries claim his consumption was moderate by early 19th century Viennese standards, there is not complete agreement among these sources, and this still likely amounted to quantities of alcohol known today to be harmful to the liver. If his alcohol consumption was sufficiently heavy over a long enough period of time, the interaction with his genetic risk factors presents one possible explanation for his cirrhosis.”

The research team thus suggests that Beethoven’s hepatitis B infection might have driven his severe liver disease, exacerbated by his alcohol intake and genetic risk. However, they caution that the nature and timing of this infection — which would have influenced its relationship with Beethoven’s liver disease — could not be determined, and that the true extent of his alcohol consumption remains unknown.

‘Beethoven on his deathbed’, 29/3/1827, lithograph by Josef Danhauser after his own drawing. Image credit: Beethoven-Haus Bonn.

Beethoven’s hearing loss has been linked to several potential causes, among them diseases with various degrees of genetic contributions, but investigation of the hair samples did not reveal a simple genetic origin. Dr Axel Schmidt, from the Institute of Human Genetics at the University Hospital of Bonn, said, “Although a clear genetic underpinning for Beethoven’s hearing loss could not be identified, the scientists caution that such a scenario cannot be strictly ruled out. Reference data, which are mandatory to interpret individual genomes, are steadily improving. It is therefore possible that Beethoven’s genome will reveal hints for the cause of his hearing loss in the future.”

It proved impossible to find a genetic explanation for Beethoven’s gastrointestinal complaints, though the researchers argue that coeliac disease and lactose intolerance are highly unlikely based on the genomic data. Beethoven was also found to have a certain degree of genetic protection against risk of irritable bowel syndrome (IBS), rendering this a less likely explanation.

“We cannot say definitely what killed Beethoven, but we can now at least confirm the presence of significant heritable risk, and an infection with hepatitis B virus,” Krause said. “We can also eliminate several other less plausible genetic causes.”

“Taken in view of the known medical history, it is highly likely that it was some combination of these three factors, including his alcohol consumption, acting in concert, but future research will have to clarify the extent to which each factor was involved,” Begg added.

A family mystery

In one final surprise, the team analysed the genetics of five modern-day relatives of Beethoven in Belgium carrying his last name and sharing a common ancestor with his paternal line, according to genealogical records — and found that these relatives did not match the Y chromosome found in the hair samples. The team concluded that this was likely to be the result of at least one “extra-pair paternity event” — a child resulting from an extramarital relationship — in Beethoven’s direct paternal line.

The study suggests that this event occurred in the direct paternal line between the conception of Hendrik van Beethoven in Belgium in 1572, and the conception of Ludwig van Beethoven in Germany in 1770. Although doubt had earlier been raised concerning the paternity of Beethoven’s father owing to the absence of a baptismal record, the researchers could not determine the generation during which this event took place. It is hoped that more studies of the composer’s close relatives might help to clarify his biological relationship to modern descendants of the Beethoven family.

“We hope that by making Beethoven’s genome publicly available for researchers, and perhaps adding further authenticated locks to the initial chronological series, remaining questions about his health and genealogy can someday be answered,” Begg concluded.

Top image caption: Portrait of Beethoven by Joseph Karl Stieler, 1820. Image credit: Beethoven-Haus Bonn.