Beethoven’s genome reveals his chronic illnesses and fatal liver disease

Perhaps as an apology to posterity, in case any note was out of place in his scores, in 1802, Ludwig Van Beethoven would have asked his brothers to make his deafness problem known in depth. They were to convey to the doctor, JA Schmidt, the musician’s request to describe his progressive hearing loss so that, “as far as possible, at least the world will be reconciled to me after my death”.

Now, more than two siglos later, a team of researchers has partially fulfilled his desire, explaining his illnesses in an article that today is published in the journal Current Biology, thanks to the DNA that was extracted and reconstructed from mechones that had been preserved from your hair.

various pathologies

scientists from Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany) sought to unravel the pathologies suffered by the great composer born in Cologne (Germany) in 1770 and died in Vienna (Austria) in 1827, to contextualize his best-known disease, deafness.

Only a genetic test would let you know if some of your health problems could be linked to your hearing loss.

In fact, his hearing loss and other illnesses kept him away from the stage for over ten years, until the premiere of the Ninth Symphony in 1824, when he heard nothing more. About that gala, it is said that while the audience applauded enthusiastically, Beethoven had to be told to go up on stage to receive the ovation, as he had not realized that the room was celebrating his music and kept gesticulating with his back. .

Hence the value of a genetic analysis that would allow us to know with certainty whether some of his health problems, in addition to the well-known digestive and inflammatory conditions, could be linked to deafness, something that has often been speculated about.

“Our main objective was to shed light on Beethoven’s health problems, including progressive hearing loss, which began in his late 20s and 20s and led to functional deafness in 1818,” reported Johannes Krause. , lead author of the recent study, in his presentation. .

We could not find a definitive cause for Beethoven’s deafness or gastrointestinal problems.

Johannes Krause, lead author of the study

“We couldn’t find a definitive cause for Beethoven’s deafness or gastrointestinal problems,” Krause said. However, the German researcher noted that they found “a number of significant genetic risk factors for liver disease.”

Furthermore, they found “evidence of a hepatitis B virus infection, which likely occurred in the months preceding the composer’s final illness” and which may “have contributed to his death”.

Scientists intuit that Beethoven’s genetic predisposition and his widely accepted consumption of alcohol constitute “plausible explanations” for the severe liver disease that ended his days.

His genetic predisposition and alcohol consumption constitute “plausible explanations” for the severe liver disease that ended his life.

johannes krause

Consulted by SINC, Markus Nöthen, another of the researchers, in this case, from Bonn University Hospitalresponds: “Based on historical reports of disease symptoms and post-mortem examination, it is generally accepted that the cause of death was liver failure.”

Nöthen notes that the aim of the study was “to clarify whether, in addition to alcohol use, a genetic predisposition and an infection contributed to liver disease or cirrhosis” and that they found “strong evidence for both.”

Surprise in the father’s line of succession

DNA analysis often produces surprising data. This case was no exception, as the study opened another door of exploration, such as the affiliation of the musician’s ancestors.

The fact is that the team discovered that “Beethoven’s Y chromosome does not match that of any of the five current relatives who have the same surname and share, according to genealogical records, a common ancestor with Beethoven’s paternal line.”

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This points to an “extramarital event” in the line of kinship on Ludwig van Beethoven’s father’s side and, more precisely, in one of the seven generations from 1572 to 1770.

The team found that “Beethoven’s Y chromosome does not match that of any of the five current relatives who have the same last name and share a common ancestor.”

Asked how they were able to determine at which point in the evolutionary branch the aforementioned ‘extramarital slip’ occurred, Toomas Kivisild, from the Catholic University of Leuven (Belgium), explains: “The five living Belgian Van Beethoven, whose Y chromosome we have studied share an ancestor common patrilineal relationship with Ludwig van Beethoven in Aert Van Beethoven, who lived in Kampenhout, present-day Belgium, in the late 16th century. accuracy of genealogy and assume that Aert van Beethoven carried the same Y-chromosome lineage as these living descendants.”

Kivisild continues: “According to the genealogical record, Ludwig van Beethoven is descended from Aert Van Beethoven’s eldest son, Hendrik, born in 1572. Since there is a mismatch between the reconstructed sequence of Aert Van Beethoven and Ludwig van Beethoven, we can conclude that paternity outside the couple occurred in one of the seven generations that separate the births of Hendrik Van Beethoven and Ludwig van Beethoven. In the absence of further evidence, we cannot specify when this event occurred.”

authenticated samples

The idea for the paper came from Tristan Begg, now at the University of Cambridge in the UK, and study co-author William Meredith nearly a decade ago. According to the journal’s introductory note, they were prompted by Beethoven’s request for post-mortem studies to describe his illness and make it public.

In the research now reported, the team – which also includes Toomas Kivisild – relied on recent improvements in ancient DNA analysis. These upgrades make it possible to sequence the entire genome from small amounts of historical hair.

First, several locks of hair attributed to Beethoven were analyzed, confirming that only five were from the same European man. They deemed these five samples to be “almost certainly authentic” and used them to sequence Beethoven’s DNA with 24-fold genomic coverage.

It was based on the estimates of medical biographers, who had already suggested that Beethoven suffered from many hereditary diseases. But the researchers in this study could not find an explanation for his hearing disorder or his gastrointestinal problems in his genome. They confirmed instead that the composer was genetically predisposed to liver disease.

It is known that the DNA extracted from Beethoven’s hair is genetically more similar to that of the inhabitants of present-day North Rhine-Westphalia

However, they ruled out lead poisoning which had been speculated in some previous analyses, based on material that did not belong to Beethoven but to a woman. Hence the recommendation to always use authenticated samples.

Finally, DNA extracted from Beethoven’s hair is known to be genetically more similar to that of inhabitants of present-day North Rhine-Westphalia, consistent with Beethoven’s known German ancestry, Begg claims. Future work on Beethoven’s samples collected over time may shed light on when he was infected with hepatitis B.

Meanwhile, further studies of his close relatives may help to clarify his biological relationship to contemporary descendants of the Beethoven family.

Reference:

J. Krause et al. “Genomic analysis of Ludwig van Beethoven’s hair”. current biology (2023)

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