Scientists say they have sequenced the genome of composer Ludwig van Beethoven.
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INA FASSBENDER/AFP via Getty Images
Scientists say they have sequenced the genome of composer Ludwig van Beethoven.
INA FASSBENDER/AFP via Getty Images
Ludwig van Beethoven lived a miserable life. His suffering was so great that in 1802 – in his late thirties – the classical composer and pianist wrote a letter to his brothers describing how his illnesses had caused how his life deteriorated and isolated him from society.
In this message, called Will HeiligenstadtBeethoven asked to make public the physical ailments that plagued him throughout his life after his death.
“As soon as I die, if Dr. Schmid is still alive, ask him to describe my illness on my behalf and attach this document to my medical history so that as little as possible the world can be reconciled to me after my death,” he wrote in his native German.
Beethoven is considered one of the greatest composers in the Western tradition.
The Henry Guttmann Collection / Getty Images
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The Henry Guttmann Collection / Getty Images
Beethoven is considered one of the greatest composers in the Western tradition.
The Henry Guttmann Collection / Getty Images
Now, scientists have done something better: They have sequenced Beethoven’s genome. The findings, published in the journal Current biologygives clues about the health challenges that shaped him as a musician.
Beethoven famously suffered from progressive hearing loss, which made social interactions a source of growing anxiety, and he ended his career as a performing musician in his mid-40s. . He also struggled with chronic gastrointestinal problems and liver disease, which only added to his misery.
Despite these difficulties, Beethoven is still considered one of the greatest composers of Western music.
His work has attracted countless listeners, including Tristan bega doctoral student in biological anthropology at the University of Cambridge, and one of the researchers involved in the gene sequencing project.
As a child, Begg listened to all kinds of music.
“ACDC, Led Zeppelin, Mozart, Prokofiev,” he recalls. “Old Ragtime Blues Favorite – Blind Blake, Mississippi John Hurt.”
But then Christmas Day 2007 came, when Begg was 17 years old. One of his holiday gifts was a phonograph. He put a needle in Beethoven Moonlight Editionand his world will never be the same.
“It really hit me. It was the first ‘dun dun dun’,” says Begg, referring to the tune that emerges subtly but powerfully after half a minute. “I heard that… I had to calm myself, stop myself from crying. That caused this obsession, both with the music and with the man.”
Tristan Begg plays piano at Jane Austen’s house in 2014.
James Begg
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James Begg
Tristan Begg plays piano at Jane Austen’s house in 2014.
James Begg
That obsession prompted Begg a few years later to pursue a Master’s project in Germany. It involves finding evidence that Beethoven’s afflictions may have a genetic background. The first is his hearing loss.
The second is his set of debilitating GI problems. These are frequent attacks of “severe diarrhea,” says Begg. “They can last for days. They are also accompanied by intestinal pain.”
And finally, it was Beethoven’s liver disease – complete with jaundice, bleeding in the esophagus and pea-sized nodules in the liver identified at autopsy. “It was this liver disease that “appeared to be the main cause of his death,” Begg said.
To find out if any of these health problems have a genetic cause, Begg first had to get his hands on Beethoven’s DNA. He guesses he’ll find it in curls that likely date back to the 1800s and are believed to have originated in the great composer’s head.
But extracting genetic information from ancient DNA related to these rare strands is an enormous challenge.
“Your genome starts from these huge chunks of DNA,” says Begg, billions of nucleotides long. But “the average length of the DNA fragment that we obtained from these hairs is about 15 nucleotides long” – super short pieces.
Thus, the DNA sequencing task that Begg faced was like rebuilding a huge multi-volume encyclopedia from several hundred thousand sentence fragments.
“So you have to use some of the most advanced ancient DNA techniques in the world,” says Begg.
But when he used those techniques, he discovered – to great dismay – that the three curls came from three different people. (One was indeed authentic but Begg didn’t know it at the time.)
“Bored is the word,” he says of the realization. “I think the project failed at the time.”
Begg went on to pursue a doctorate in an entirely different subject. But then one of the study’s sponsors, a member of the American Beethoven Association, get a few new curls. When examined, they all descended from the same person and that individual was almost certainly Ludwig van Beethoven.
“Suddenly,” said Begg, “the project has a pulse again.”
The sequencing work can now begin in earnest. He focused on the best preserved samples to look for evidence of genetic disease.
First, there is the matter of his deafness, which, alas, is inconclusive. That may be because we don’t fully know the link between risk and heredity of otosclerosis, a condition often characterized by abnormal bone growth in the middle ear and the leading explanation. leading cause of Beethoven’s hearing loss.
Second, there are GI issues. “We found that he was modestly protected from irritable bowel syndrome,” says Begg. Also, Beethoven is most likely lactose or gluten intolerant. So there’s nothing definitive there.
The real problem came when Begg looked at the possible causes of Beethoven’s liver disease. A special gene, called PNPLA3, jump out. “It would have almost tripled his risk of developing the full spectrum of liver disease,” says Begg.
On its own, genes aren’t too worrisome. But “it becomes a problem if you drink large amounts of alcohol.” And that is something that Beethoven may have done by many accounts.
In addition, Begg found other DNA in Beethoven’s hair — from the hepatitis B virus. “It’s one of the major causes of cirrhosis and liver cancer globally,” says Begg.
Tristan Begg pulls hairs from a strand of hair in the lab at the Max Planck Institute for the Science of Human History in Germany as part of Beethoven’s genome sequencing effort.
Anthi Tiliakou
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Anthi Tiliakou
Tristan Begg pulls hairs from a strand of hair in the lab at the Max Planck Institute for the Science of Human History in Germany as part of Beethoven’s genome sequencing effort.
Anthi Tiliakou
And all three factors – genes, alcohol consumption and hepatitis B – will all interact. “Which way you cut it,” he said, “it’s really no surprise that he died of cirrhosis, ultimately, at the age of 56.”
Church of George, a molecular technologist at Harvard Medical School who was not involved in the study, said it was a solid study. He just wishes DNA had yielded more answers.
“I think what is disappointing is the lack of explanation for hearing loss,” says Church. “It’s not the fault of the authors. It’s the fault of the specimens.”
Perhaps in the future, technology will be improved to better understand the origins of Beethoven’s deafness.
“There are so many things you can do tomorrow that you didn’t do yesterday,” Church said.
An unexpected discovery. When Begg compared Beethoven’s Y chromosome with five living members of the van Beethoven family today, “they were very different,” he said. That means that sometime between 1572 and 1770, a “paternity event” occurred in the Beethoven family line. In other words, Church said, “some premarital or extramarital sex” resulted in an individual having another father in Beethoven’s recent ancestry.
For some, this study helps bring the composer to life. Luke Welcha concert pianist in Toronto, says it’s clear that “a man’s physical struggles are real”, which he feels when playing Beethoven’s music, especially his late symphonies and piano sonatas.
These sonatas, Welch said, “are a big difference from his earlier piano sonatas, and you can tell he’s completely in a different mind from anything that’s ever been done before.” his contemporaries composed.”
Welch explains: “The demands he puts on the performers are really harsh. “To the listener, it sounds very natural. But to the performer, you really have to struggle through certain passages to make it as coherent and cohesive as he wants it to be.”
In other words, he summed it up, “Beauty To be struggle.”
As for Begg – who has spent many years studying Beethoven’s DNA – he says that now that his genetic work has been published, Beethoven’s Eroica (third symphony) he will hear first.
“It took a while to appreciate it, but it’s an incredible piece of music,” he said. “He never wastes a note. He doesn’t waste your time. Your feelings are in the best hands.”
Perhaps Beethoven would feel the same way – that his locks and DNA were also in the hands of good people.
