Scientists for the first time sequenced the genome of Beethoven and found out what he was sick with

(ORDO NEWS) — The DNA of one of the world’s most famous composers, Ludwig van Beethoven, who died in the first half of the 19th century, has been deciphered from strands of his hair preserved by friends, admirers and collectors.

A team of archaeologists and geneticists from the Max Planck Institute for the History of Humanity, the University of Tübingen and the University Hospital Bonn (Germany), as well as the University of Cambridge (UK) and the Catholic University of Leuven (Belgium) sequenced for the first time about two-thirds of the genome of the German composer, the last representative of the “Viennese classical schools” of Ludwig van Beethoven and found out what diseases he had a genetic predisposition to.

In 1802, the 32-year-old Beethoven wrote a letter to his brothers (Heiligenstadt Testament), in which he complained of deafness, which made him “live like an exile” and think about death.

Despite this, the composer continued to work and create for another 25 years – only “virtue and art” kept him from committing suicide.

The letter was kept in a secret compartment in the musician’s desk and was found on March 27, 1827, the day after Beethoven’s death.

As it turned out, the doctor Johann Adam Schmidt was entrusted with making public information about progressive hearing loss (so that “the world could reconcile with me after death”) and studying the disease.

In addition to bilateral, non-congenital, progressive and predominantly sensorineural hearing loss, the pianist suffered from gastrointestinal problems, colic, diarrhea, and liver disease, including bouts of jaundice.

An autopsy revealed that he had cirrhosis of the liver, pancreatitis, and an enlarged spleen.

Researchers could not agree on what exactly killed the composer at the age of 56 and whether his liver disease was the result of alcoholism. Some contemporaries insisted that Beethoven drank in moderation.

But one close friend claimed that around 1825-1826 the musician drank at least a liter of wine at dinner every day.

“Beethoven outlived Dr. Schmidt by 18 years, but medical biographers have since really tried to determine the most likely causes of Beethoven’s various health complaints.

The research was based mainly on documentary sources, including Beethoven’s letters, diaries, as well as stories of contemporaries, doctors’ notes, autopsy reports and descriptions of bone material after exhumations in 1863 and 1888.

We decided to analyze the composer’s genome in order to find out the possible genetic and infectious causes of his illnesses.

We limited the study to three groups of somatic diseases that dominate the medical biographical literature,” the authors of the new work explained.

The object of study were eight strands of hair attributed to Ludwig van Beethoven. They were kept in public and private collections and are estimated to date between November 1821 and March 1827.

As the analysis showed, five strands belonged either to one person or to monozygotic twins who lived at the beginning of the 19th century.

“Given the history of the origin of the samples, we considered the obtained genetic data to be strong evidence of the identity of these five strands of hair and proceeded from the working hypothesis that they are genuine.

We determined that the sample called “Stumpf Lok” was better preserved than the others, and sequenced the genome (with an average of 24-fold coverage of each site),” the scientists said.

Further, the authors of the study found out that the person who owned the strand of hair was German. His ancestors were more than 99% European, mostly natives of modern North Rhine-Westphalia in Germany.

To further confirm the authenticity of the samples, the scientists compared the Y chromosome from Beethoven’s genome with Y chromosomes sequenced from five living males belonging to the great pianist’s family.

The results turned out to be “almost identical”: the descendants are only distantly related genealogically, but have matching Y-chromosome haplogroups (this is consistent with the version of their origin from a common paternal ancestor from the 16th century).

According to the scientists, the genome data is a new and unbiased primary source that should improve our understanding of Beethoven’s health problems.

However, the approach had limitations: firstly, such chromosomal rearrangements as deletions and duplications associated with many cases of hearing loss were not taken into account in the analysis due to lack of data.

Secondly, despite all the advances in medicine, the genetic causes of many diseases are not yet fully understood, especially when it comes to conditions caused by the interaction of many hereditary and environmental factors.

“Because of these limitations, we have not identified a molecular genetic cause for Beethoven’s hearing loss. Important differential diagnoses such as otosclerosis could not be assessed due to lack of reference data.

To substantiate the previously put forward hypothesis of plumbism as a causative or contributing factor in Beethoven’s hearing loss, it is necessary to wait for analyzes of samples authenticated using genetic testing, ”added the authors of the article.

They also failed to obtain a molecular genetic explanation for Beethoven’s gastrointestinal problems.

However, some diagnoses have become less likely: for example, celiac disease (a congenital disease associated with protein intolerance to certain cereals) and lactose intolerance, according to the researchers, can be excluded from the list and no longer considered.

The most important findings concern liver disease. The increased polygenic risk index for cirrhosis suggests that Beethoven inherited a significant genetic predisposition to this chronic disease.

According to the results of the analysis, it is difficult to assume that the composer suffered from clinically significant hemochromatosis – a violation of iron metabolism with its accumulation in tissues and organs.

But scientists didn’t completely rule out the possibility that liver health was affected by iron overload , which is characterized by excessive drinking of alcohol (especially wine), due to mutations in the HFE gene.

“If Beethoven regularly drank enough alcohol, the combined risk associated with a genetic predisposition could provide a plausible explanation for his liver disease.

In addition, we found out that the composer had viral hepatitis B (HBV, an infectious disease that causes serious liver damage. For at least the months preceding death, ”the researchers said.

Again, it is not yet possible to determine the nature and period of occurrence of this infection. But all together – genetic predisposition, viral hepatitis B and alcohol consumption – probably explains the severe liver disease that resulted in Beethoven’s death.

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