In 1802, a despairing Beethoven wrote a letter asking that after his death, doctors describe his illness to the world so people would understand what he had endured. In 2023, scientists sequenced his genome from five locks of his hair and answered him — 196 years late, and not with the answers anyone expected

In October 1802, in a small village outside Vienna called Heiligenstadt, Ludwig van Beethoven sat down to write a letter to his brothers.

He was 31 years old. He had been progressively losing his hearing for six years and understood, by that autumn, that his deafness would not reverse. In the letter, he described a specific kind of loneliness — how he had begun avoiding people because he could not bear the humiliation of appearing to ignore them when he simply could not hear what they said. He wrote that only his sense of duty to the music he had not yet composed had kept him from ending his life.

Toward the end of the letter, he addressed a specific request to his brothers. When he was dead, he wrote, they should ask his physician — a man named Dr. Johann Adam Schmidt — to describe his illness in detail, and to make that description public.

“So that so far as possible at least the world may become reconciled with me after my death,” he wrote.

He then folded the letter, hid it in his writing desk, and did not tell anyone it existed for the next twenty-five years.

The letter that was never delivered

Beethoven outlived Dr. Schmidt by 18 years.

Schmidt died in 1809. Beethoven kept composing — through the deafness, through worsening gastrointestinal problems, through recurring episodes of jaundice, through a specific set of health complaints that would follow him for the rest of his life. He also kept the Heiligenstadt letter in a hidden compartment of his writing desk, unopened and unread by anyone else.

He died in Vienna in March 1827, aged 56. The morning after his death, two of his associates going through his belongings discovered the compartment. Inside were several documents. One of them was the letter he had written 25 years earlier in Heiligenstadt.

The document was published shortly afterwards. The specific request contained within it — that his physician describe his illness and make the description public — could not be fulfilled. Schmidt had been dead for 18 years. Beethoven’s own autopsy, conducted the day after his death, provided some observations but no definitive diagnosis. The specific medical question the composer had wanted answered would remain, in the standard biographical view, open.

For 196 years, various doctors and biographers proposed theories. Otosclerosis. Paget’s disease. Syphilis. Lead poisoning. Autoimmune conditions. Each was consistent with some subset of the documented symptoms and inconsistent with others. None commanded consensus.

Then, in 2023, a team of scientists took an approach nobody in 1802 could have imagined.

Five locks of hair

The sequencing of Beethoven’s genome, published in the journal Current Biology in March 2023, drew on a specific quirk of nineteenth-century culture: the habit of preserving locks of famous people’s hair.

Beethoven’s hair had been widely collected in the years around his death and passed down through private collections and museum holdings. A team led by Tristan Begg at the University of Cambridge, working with Johannes Krause at the Max Planck Institute for Evolutionary Anthropology in Leipzig, gathered eight locks that were claimed to be Beethoven’s from institutions and private owners in Europe and the United States.

Five of the eight, when compared genetically, turned out to have come from the same European male. The other three were from other people entirely — earlier DNA analyses of Beethoven had, unknowingly, sometimes been working with someone else’s hair.

The five authentic locks were the material the team needed. Using techniques developed in the previous decade for extracting DNA from ancient human remains, and adapting them for the specific challenges of historical hair samples, the team sequenced Beethoven’s genome to 24-fold coverage from the best-preserved lock — a specimen called the Stumpff Lock, which had been kept in a private collection with unusually good documentation.

The genome that emerged was almost complete. It was the first genome of any historical figure sequenced from hair to this level of resolution, and it made possible a genuinely direct test of the biographical questions Beethoven himself had raised.

What the DNA answered

The findings, when they came, were partially satisfying and partially strange.

The team found that Beethoven had a strong genetic predisposition to liver disease. Multiple risk variants across genes involved in fat metabolism, alcohol processing, and hepatic inflammation appeared in his genome. This was consistent with the two documented episodes of jaundice in his last seven years and with the general assumption — held by biographers for two centuries — that liver failure had contributed to his death. The genetic evidence made the assumption specific and testable.

More strikingly, hair samples from the final months of Beethoven’s life contained DNA fragments from hepatitis B virus. This was direct molecular evidence that Beethoven had been infected with a virus known to cause liver damage, at some point in the year or so before his death. Combined with his genetic predisposition and his well-documented alcohol consumption, the specific cause of his fatal illness came into a clearer view than ever before. Beethoven had almost certainly died of liver failure caused by the combined action of three factors: heritable susceptibility, chronic alcohol use, and viral hepatitis.

The team also found something Beethoven had not asked about. His Y-chromosome — the paternal-line genetic marker — did not match the Y-chromosomes of his known modern paternal-line relatives, several of whom had contributed DNA samples for comparison. This meant that at some point in Beethoven’s paternal ancestry, there had been an extramarital event that had introduced a different Y-chromosome into what was assumed to be a continuous family line. The composer, or one of his male ancestors within a few generations, had a biological father different from his official one.

What the DNA could not answer

The specific question Beethoven had actually wanted answered — the cause of his deafness — remained open.

The team looked. They found no genetic explanation. The specific variants known to cause otosclerosis, the leading historical hypothesis, were not present in his genome. Nor were the variants for Paget’s disease of the bone, another suspect. Nor for the various forms of hereditary sensorineural hearing loss the team examined. The chronic gastrointestinal issues that had plagued Beethoven for decades were similarly unresolved. The DNA offered no smoking gun for the specific medical experiences that had defined his life.

The lead author, Tristan Begg, was careful in the accompanying Cambridge announcement to note that this did not mean no genetic cause existed. Several possible explanations for the deafness could not be reliably evaluated with the specific data the team had. The genome was informative about many things and silent about others.

What it produced, in the end, was a specific and imperfect answer to a request Beethoven had made 196 years earlier. He had wanted the world to understand what he had endured. The world now knows he had a predisposition to liver disease, that he was infected with hepatitis B in his final months, and that somewhere in his paternal ancestry there was a name that was not on the family tree.

It does not know why he could not hear. That specific silence, which he had spent the second half of his life composing through, has not yet been broken.