ベートーベンの死因は肝硬変？ 毛髪でゲノム解析

【ワシントンＤ．ＣＡＦＰ＝時事】ドイツなどの国際研究チームは２２日、作曲家ベートーベン（１７７０～１８２７年）の髪の毛からＤＮＡを抽出し、ゲノム（全遺伝情報）を解読したと発表した。飲酒など複合要因に伴う肝硬変が、５６歳での死につながったと推定されるという。（写真はゲノム解読に使われたベートーベンの髪の毛。米サンノゼ州立大学ベートーベン研究センター提供。）
　学術誌カレント・バイオロジーに同日掲載された論文の共著者で、独ボン大学病院人類遺伝学研究所のマルクス・ノーテン氏によると、肝臓病リスクを高める遺伝子変異やＢ型肝炎ウイルスに感染した痕跡が見つかった。
　ベートーベンが悩まされていたとされる進行性難聴や胃腸障害、肝疾患について遺伝的要因の可能性を探った結果、「遺伝的な体質と慢性的な飲酒、Ｂ型肝炎感染などの相互作用で引き起こされたと考えられる」という。
　独マックス・プランク進化人類学研究所のヨハネス・クラウゼ氏は、１９世紀初頭にはＢ型肝炎は「かなり一般的だった」可能性が高いとし、ベートーベンも「少なくとも亡くなる前の最後の数か月間はＢ型肝炎ウイルスに感染していた」との見解を示した。
　ただし今回の研究では、最終的に完全に聞こえなくなった進行性難聴の遺伝的原因を特定することはできなかった。
　■家族の秘密
　国際研究チームはさらに遺伝子データと古文書を照合し、ベートーベンの法律上の家系と生物学的な系統に矛盾があることも突き止めた。
　エストニアのタルトゥ大学ゲノム研究所のトーマス・キビシルド氏は、ベートーベン誕生までの７世代の間に父方の直系で婚外子が存在した痕跡が確認されたと述べた。
　論文の主著者で英ケンブリッジ大学博士課程に在籍するトリスタン・ベッグ氏は、婚外子であることは「おそらく秘密とされる性質」の出来事で、記録に残っていなくても不思議ではないと説明。場合によってはベートーベン自身が婚外子だった可能性もあり得ると述べた。【翻訳編集ＡＦＰＢＢＮｅｗｓ】
〔ＡＦＰ＝時事〕（2023/03/23-17:07）

Ludwig van Beethoven died in Vienna nearly 200 years ago after a lifetime of composing some of the most influential works in classical music.
Ever since, biographers have sought to explain the causes of the German composer's death at the age of 56, his progressive hearing loss and his struggles with chronic illness.
An international team of researchers who sequenced Beethoven's genome using authenticated locks of his hair may now have some answers.
Liver failure, or cirrhosis, was the likely cause of Beethoven's death brought about by a number of factors, including his alcohol consumption, they said.
We looked at possible genetic causes of his three main symptom complexes -- the progressive hearing loss, the gastrointestinal symptoms and the liver disease ultimately leading to his death due to liver failure, said Markus Nothen of the Institute of Human Genetics at the University Hospital of Bonn, one of the co-authors.
Beethoven, Nothen said, had a strong genetic disposition to liver disease and sequences of the hepatitis B virus were detected in his hair.
We believe the disease arose from an interplay of genetic disposition, well documented chronic alcohol consumption and hepatitis B infection, Nothen said.
- No explanation for deafness -
Johannes Krause of the Max Planck Institute for Evolutionary Anthropology said hepatitis B was probably quite common at that time in the early 19th century.
At least in the last few months before his death he was infected with hepatitis B virus, Krause said.
The authors of the study, published in the Cell Press journal Current Biology on Wednesday, were unable to determine any genetic causes for the progressive hearing loss that eventually left Beethoven completely deaf by 1818.
The researchers analyzed eight locks of hair said to be from Beethoven and determined that five of them were almost certainly authentic, said Tristan Begg, a PhD student at the University of Cambridge and the lead author of the study.
Because we reconstructed the genome from ultra-short DNA fragments, we only confidently mapped about two-thirds of it, he said.
One of the most-famous strands of hair, known as the Hiller Lock, which has been the subject of previous research and found to contain high levels of lead, was revealed not to be from Beethoven at all but from a woman.
- Family secret -
Beethoven, who was born in Bonn in 1770 and died in 1827, battled gastrointestinal problems at various times of his life as well as jaundice.
There were periods of acute illness where he was unable to work, for example, his month-long period of acute illness in the spring of 1825, Begg said.
The researchers, by studying Beethoven's DNA data and archival documents, also uncovered a discrepancy in his legal and biological genealogy.
They found an extra-pair paternity event -- a child resulting from an extramarital relationship -- in Beethoven's direct paternal line, said Toomas Kivisild of the Institute of Genomics at the University of Tartu.
Kivisild said it occurred some time within seven generations that separate a common ancestor, Aert van Beethoven, at the end of the 16th century and Beethoven's birth in 1770.
Begg said it was no surprise it was not recorded.
You wouldn't necessarily expect an extra-pair paternity event to be documented, he said, it being probably clandestine in nature.
You cannot rule out that Beethoven himself may have been illegitimate, Begg said.
I'm not advocating that, he stressed. I'm simply saying that's a possibility and you have to consider it.
Beethoven had asked in an 1802 letter to his brothers that his health problems, particularly his hearing loss, be described after his death.
He had the wish to be studied post-mortem, Krause said.
And it is kind of, basically, his wish that we are fulfilling to some degree with this project.