Who killed Beethoven? Hepatitis B, says forensic DNA analysis

The hunt to identify details of the maestro’s death finally ends as ancestral DNA forensics enter the equation.

July 25, 2023 05:04 pm | Updated 05:07 pm IST

Researchers used ancestry DNA databases to identify what caused Ludwig von Beethoven’s death almost two centuries ago.

Researchers used ancestry DNA databases to identify what caused Ludwig von Beethoven’s death almost two centuries ago. | Photo Credit: The Hindu

Ludwig von Beethoven was born in 1770 in Bonn, Germany. His approach to music composition changed the way people appreciated music – from just a pastime pleasurable hearing to a transformational powerhouse intervention. Beethoven died in 1827 and decades prior to his death, he suffered multiple illnesses, so it was difficult to connect symptoms and signs of grave illness which remained a mystery even after his demise. Beethoven knew he was unwell and was dying. His hearing was progressively declining. He had multiple gastrointestinal issues from bloating to diarrhoea which haunted him since he was 20 years of age. He asked his favourite physician, Johann Adam Schmidt that upon his death, he describe his illness and make his diagnosis public. Unfortunately, tragedy struck and Dr. Johann died early. Beethoven outlived him by 18 years and his request was denied. 

Thus started one of the greatest medical investigations that featured some of the most intensive clinical and basic science research to find the maestro’s actual cause of death. And the answers came 200 years later. 

After his death, Beethoven’s associates found multiple stacks of letters that the music maestro had written to his brothers, which described his illness, the painful ordeal and about him contemplating suicide to get out of the hell cycle. The collection of letters came to be known as the Heiligenstadt Testament of 1802. Around the time of his death, his admirers snipped numerous locks of his hair and kept them as personal collections. The eight locks were named thus: Müller, Bermann, Halm-Thayer, Moscheles, Stumpff, Cramolini-Brown, Hiller, and Kessler Lock Collections.

The quest to find the cause of Beethoven’s death relied heavily on bibliographic sources, including Beethoven’s letters, conversation books and diaries, and the accounts of his contemporaries, including doctor’s notes, autopsy reports, and descriptions of bone material after exhumations in 1863 (for moving to a new sarcophagus) and 1888 (for moving to a new cemetery). Additionally, analyses of tissue sources claimed to originate from the music composer have been performed, including toxicological analyses of hairs from private collections of unknown authenticity and palaeopathological examinations of skull fragments.

In 2007, a group of researchers led by Christian Reiter of the Medical University of Vienna claimed that the cause of Beethoven’s death was lead poisoning. They claimed that his doctor had probably killed him because he had repeatedly used lead-based salts to clean wounds and during drug administrations which eventually poisoned him, resulting in his death. This conclusion was made after chemical analysis of one of the collected hair locks was analysed exhaustively. The lead poisoning theory of Beethoven’s death stuck with the medical and music community for decades. 

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Beethoven suffered from three major issues – progressive hearing loss, recurrent abdominal pain and diarrhoea and two attacks of jaundice, the last one towards the end of 1826, culminating in his death. He had fluid in his abdomen that had to be removed using a large bore needle. The composer received abdominal punctures four times on his deathbed, draining up to 14 litres of fluid from his abdominal cavity each time – a procedure known as large-volume paracentesis of ascites. The lead poisoning theory was unable to substantiate all of the disease-related challenges Beethoven faced, especially the autopsy finding of chronic liver damage or cirrhosis. 

The truth remained buried until now in 2023 when the indomitable Tristan Begg, from the Department of Archaeology, University of Cambridge, used modern DNA extraction techniques along with a masterful method called genome-wide association studies using ancestry DNA databases on the seemingly worthless item recovered from Beethoven centuries ago – all eight locks of his hair found by private collectors.

Genetic data are used to estimate the geographic origins of a person’s recent ancestors in genetic ancestry testing. It entails comparing the frequencies of a large number of DNA variants measured in an individual to the frequencies of these variants in reference populations collected from around the world – a large database created as a result of various companies performing direct-to-consumer DNA analysis on personally and voluntarily submitted samples. The geographic region with the highest frequency of an individual variant is thought to be the most likely location of an ancestor who passed the variant on to the person being tested. Traditional ancestry analysis includes testing for the mitochondrial DNA (transmitted only by females and reflecting the origin of one maternal ancestor) and the Y chromosomal DNA (transmitted only from father to son and reflecting the origin of one paternal ancestor).

In Beethoven’s case, the DNA sequencing on four and an additional one of the eight locks was found to come from from the same individual, a male of European heritage – meaning, the others were not authentic. And surprisingly, the three locks with less authenticity came from three other unrelated individuals. Interestingly, analysis of one of those hair samples – the so-called Hiller Lock – showed high levels of lead and that it came from a woman likely of North African, Middle Eastern, or Jewish ancestry, which was the reason for wrong diagnosis of lead poisoning in the first place by the previous group of researchers.

So, what did Beethoven die of? He had died of liver disease. His autopsy showed cirrhosis. But what was killing his liver? The brilliant genome analysis found two genes that are now notoriously known to cause liver cirrhosis – the PNPLA-3 gene and HFE-gene mutation both of which are associated with chronic liver damage. 

But they did not act alone. There had to be a driving factor which caused the chronic damage. And the researchers found it. One of humankind’s most ancient friend, but also its greatest foe – alcohol. From interviews and documented conversations with friends and contemporaries, it was evident that the maestro consumed a significant amount of alcohol, which, along with genetic mutations resulted in cirrhosis and his death. But Tristan Begg and his colleagues were not ready for what was coming next. Along with the genetic mutation and the alcohol was another tiny but devastatingly ancient pathogen which they found in his hair strand on DNA analysis. And they knew that this little monster drove Beethoven to his death with everything else in the back seat — the Hepatitis B virus.

And two centuries after his death, and medical science’s fascination with research and diagnosis, and with our curiosity with Beethoven that led us to probe every corner of his life – his letters, his writings, his medical records, and now his very DNA — the cause of the brilliant musician’s death was finally unravelled - cirrhosis brought on by alcohol and a multiple-gene-related inherited liver risk driven to failure by the presence of Hepatitis B virus infection. This is why medical science exists. And as our scientific tools become sharper, we look forward to unravelling the mysteries of human health (and death) to prevent and defeat suffering.

But did I tell you the biggest scandal of all in this hardcore analysis project which flabbergasted even the researchers? Ancestral DNA analysis revealed that the Y-chromosome that Beethoven inherited was not of Aert van Beethoven – his presumed biological father, but another man, strongly suggestive of an extramarital paternity event, which mind-numbingly means that “Beethoven may not have been a Beethoven.”

(The author is senior consultant in hepatology & physician-scientist, The Liver Institute, Rajagiri Hospital, Kochi, Kerala (abbyphilips@theliverinst.in). He is on Twitter as @theliverdr)

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