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Scientists sequence Beethoven's genome for clues into his painful past

Scientists have sequenced the genome of Ludwig van Beethoven from two-century-old locks of hair, and found clues about the ailments that plagued him in life.



So there's this letter that Beethoven, the great classical composer, wrote to his brothers when he was in his early 30s. He rails against his deafness and asks that his various health problems be described after his death. Well, a new study does just that. Science reporter Ari Daniel has more.

ARI DANIEL, BYLINE: When he was a kid, Tristan Begg listened to all kinds of music.

TRISTAN BEGG: AC/DC, Led Zeppelin, Mozart, ragtime blues.

DANIEL: But then came Christmas 2007, when Begg was 17. One of his presents was a record player, and when he dropped the needle on this - Beethoven's "Moonlight Sonata" - his world would never be the same.

BEGG: It was the first dun, dun-dun (ph).


BEGG: I had to catch myself to stop myself from crying. That sparked this obsession, both with the music and with the man.

DANIEL: That obsession inspired Begg to later pursue a master's project in Germany, one involving a hunt for evidence that Beethoven's afflictions had a genetic basis; the first being his hearing loss, the second a set of debilitating gastrointestinal issues.

BEGG: These were attacks of often, he describes, violent diarrhea.

DANIEL: And finally, there was Beethoven's liver disease, involving jaundice and bean-sized nodules in his liver.

BEGG: That seems to have been the primary cause of his death.

DANIEL: Begg first had to get his hands on Beethoven's DNA, which he managed to do - ancient DNA from locks of hair likely from the 1800s and supposedly originating from the great composer's head.

BEGG: Your genome starts out in these enormous stretches of DNA. The average fragment length we were getting from these hairs was about 15 nucleotides long.

DANIEL: Which is super short. Begg had to sequence Beethoven's entire genome from those fragments.

BEGG: So you have to use some of the most advanced ancient DNA techniques in the world.

DANIEL: But the results were depressing.

BEGG: Those three locks of hair came from three different people. I thought the project had failed.

DANIEL: Begg moved on to the University of Cambridge to do a Ph.D. in biological anthropology on a different topic altogether. But then a few new locks of hair surfaced, all originating from the same person, who almost certainly was Ludwig van Beethoven.

BEGG: Suddenly, the project had a pulse again.

DANIEL: Begg focused on sequencing the best-preserved sample, which he then surveyed for evidence of disease. First, there was his deafness, which, alas, didn't turn up anything conclusive. Then there were the GI troubles.

BEGG: We did find that he was modestly protected against irritable bowel syndrome.

DANIEL: And that he was likely not lactose or gluten intolerant, so nothing definitive there either. But then, Begg looked into possible causes of liver disease. One gene in particular leapt out.

BEGG: It would have roughly tripled his risk for developing the full spectrum of liver disease.

DANIEL: The gene's not too concerning on its own, but...

BEGG: It does become a problem if you're drinking substantial quantities of alcohol.

DANIEL: Which Beethoven probably did. Plus, Begg found other DNA in his hair shafts from hepatitis B virus.

BEGG: This is globally one of the major causes of cirrhosis and liver cancer.

DANIEL: And all three factors - the gene, the drinking and the hepatitis B - they would have all interacted.

BEGG: It really comes as no surprise he died of cirrhosis at the age of 56.

DANIEL: Begg and his colleagues published their findings in the journal Current Biology. George Church, a molecular technologist at the Harvard Medical School who wasn't involved in the project, says it's solid research. He just wished the DNA had yielded more answers.

GEORGE CHURCH: Yeah, I think the disappointing thing was the lack of explanation for hearing loss. It's not the fault of the authors. It's the fault of the specimens.

DANIEL: For some, this study helps bring the composer to life. Toronto-based concert pianist Luke Welch says it lays bare that the man's physical struggle was real, something he feels when playing Beethoven's music.

LUKE WELCH: The demand he puts on the performer are really extreme. You really have to fight through certain passages to make it as cohesive as he wants.

DANIEL: And is there beauty in the struggle?

WELCH: The beauty is the struggle.

DANIEL: As for Tristan Begg, he says now that his genetic opus has published, it'll be Beethoven's "Third Symphony", "The Eroica", that he'll listen to first.

BEGG: Your feelings are in the best hands.

DANIEL: And I wonder whether Beethoven might have thought that his locks of hair, his DNA, have been in some pretty good hands too.

For NPR News, I'm Ari Daniel.

(SOUNDBITE OF LUDWIG VAN BEETHOVEN'S "SYMPHONY NO. 3") Transcript provided by NPR, Copyright NPR.