• Fri. Dec 1st, 2023
Who killed Beethoven?  Hepatitis B, says forensic DNA analysis

Ludwig von Beethoven was born in 1770 in Bonn, Germany. His approach to music composition has changed the way people appreciate music – from a mere pastime of pleasurable listening to a transformative powerhouse interaction. Beethoven died in 1827, decades before his death, and he had multiple illnesses, so it was difficult to connect the signs and symptoms of a serious illness that remained a mystery even after his death. Beethoven knew he was not well and dying. His hearing gradually declined. He has had multiple digestive problems since the age of 20, ranging from diarrhea to diarrhea. He asked his favorite physician, Johann Adam Schmidt, to describe his illness and make his diagnosis public after his death. Unfortunately, tragedy struck and Dr. Johann died early. Beethoven outlived him by 18 years, and his request was rejected.

Thus began one of the greatest medical investigations involving the most intensive clinical and basic science research to discover the maestro’s true cause of death. After 200 years, the answers came.

After his death, Beethoven’s associates discovered multiple letters written by the musician to his brothers, in which he reflected on his illness, painful trials, and thoughts of suicide to escape the hellish cycle. The collection of letters became known as the Heiligenstadt Act of 1802. At the time of his death, his admirers plucked several locks of his hair and kept them as personal collections. The eight locks are named: Müller, Berman, Hamm-Thyer, Moscheles, Stumpf, Cramolini-Brown, Hiller, and Kessler Lock Collections.

The search for Beethoven’s cause of death relies on bibliographical sources, including Beethoven’s letters, conversation books, and diaries, doctor’s notes, autopsy reports, and accounts of his contemporaries. In addition, analyzes of tissue sources claimed to originate from the composer have been conducted, including toxicological analyzes of hairs from private collections of unknown authenticity and paleopathological examinations of skull fragments.

In 2007, a group of researchers led by Christian Reiter of the Medical University of Vienna claimed lead poisoning was the cause of Beethoven’s death. They claimed that his doctor may have killed him because he repeatedly used lead-based salts to clean his wounds, eventually poisoning him to death. This conclusion came after a thorough analysis of the chemical analysis of one of the hair locks collected. The lead poisoning theory of Beethoven’s death held sway in the medical and musical community for decades.

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Three major problems afflicted Beethoven – progressive hearing loss, recurrent abdominal pain, diarrhea, and two bouts of jaundice, the last of which, in late 1826, resulted in his death. There was fluid in the abdomen that had to be removed with a large needle. The composer received four abdominal punctures on his deathbed, each time draining 14 liters of fluid from the abdominal cavity – a procedure called large-volume paracentesis of ascites. The lead poisoning hypothesis could not prove all of the challenges associated with illness that Beethoven faced, particularly the postmortem finding of chronic liver failure or cirrhosis.

In 2023 the truth was buried until the indomitable Tristan Begg from the Department of Archeology at Cambridge University. Modern DNA extraction techniques were used along with the masterful method of genome-wide association studies. Using genealogical DNA databases on the seemingly worthless species recovered from Beethoven centuries ago – and eight locks of his hair found by private collectors.

Genetic ancestry testing uses genetic data to estimate the geographic origin of a person’s most recent ancestors. This means comparing the frequencies of a large number of DNA variants measured in an individual with the frequencies of these variants from reference populations around the world—a large database created as a result of direct-to-consumer DNA analysis performed by various companies on individually 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 transmitted the variant to the person being tested. Traditional ancestry analysis involves testing for mitochondrial DNA (transmitted only from females and reflecting a maternal ancestor’s origin) and Y chromosomal DNA (passed only from father to son and reflecting a paternal ancestor’s origin).

In Beethoven’s case, DNA sequencing of four and an additional eight loci found that they came from the same individual, a man of European heritage — meaning the others are inauthentic. Surprisingly, the three less authentic locks came from three other unrelated individuals. Interestingly, analysis of one of those hair samples — called Hiller’s locks — showed high levels of lead, and it came from women of North African, Middle Eastern, or Jewish descent, which is why previous researchers misdiagnosed lead poisoning in the first place.

So, what did Beethoven die of? He died of liver disease. His autopsy revealed cirrhosis. But what is killing his liver? A brilliant genome analysis identified two genes known to cause liver cirrhosis – the PNPLA-3 gene and the HFE-gene mutation, both of which are associated with chronic liver damage.

But they did not act alone. There must be a driving factor that causes chronic damage. Researchers found that. Mankind’s oldest friend, but also its greatest enemy – alcohol. From interviews and documented conversations with friends and contemporaries, it was clear that the maestro consumed a significant amount of alcohol, which, along with genetic changes, resulted in cirrhosis and death. But Tristan Begg and his colleagues were not ready to come next. Along with the genetic mutation and alcohol was another small but devastating ancient pathogen found in his hair during DNA analysis. They knew that the hepatitis B virus – this little monster – took a backseat to Beethoven’s death.

Two centuries after his death, medical science’s fascination with research and diagnosis, and our curiosity about Beethoven, have led us to investigate every corner of his life—his letters, his writings, his medical records, and now his DNA. Virus infection. This is why medicine exists. As our scientific tools become sharper, we hope to unravel the mysteries of human health (and death) in order to prevent and defeat suffering.

But did I tell you the biggest scam in this hardcore analysis project that shocked even the researchers? Ancestral DNA analysis revealed that the Y-chromosome Beethoven inherited did not belong to his presumed biological father, Ert van Beethoven, but to another man, strongly suggesting an extramarital paternity event.

(The author is Senior Consultant and Physician-Scientist in Hepatology, The Liver Institute, Rajagiri Hospital, Kochi, Kerala (abbyphilips@theliverinst.in). He is on Twitter as @theliverdr)

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