The lives of many amazingly creative people were tragically cut short by the disease: Johannes Vermeer, Wolfgang Amadeus Mozart, Jane Austen, Franz Schubert, and Emily Brontë are some famous examples. Ludwig van Beethoven’s was not so short: he was 56 when he died in 1827. However, it was short enough to make us wonder what else he could have accomplished if he had been in better health.
For much of his adult life, Beethoven was frequently plagued by pain and ill-health, not to mention hearing loss. The German composer thought anxiously about these afflictions, especially his deafness, and hoped that one day they would be understood and the explanation made public.
Sometimes he got desperate and thought about suicide; sometimes she stopped composing.
Entire books have been written on Beethoven’s health, based on records from the time. However, my colleagues and I approach the issue from a different perspective. We wonder what clues Beethoven’s genome, that is, his DNA, could provide.
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And we’ve found some answers and some surprises, as we explain in new research published in Current Biology.
Where does the DNA come from?
Extracting and analyzing DNA from the remains of a dead person (or other animal) is challenging, much more so than from living tissue. However, enormous technical advances have transformed the field of ancient DNA studies.
Generally, the best sources of DNA from human remains are the teeth and petrosal bone of the skull, but we did not have any of Beethoven’s bones or teeth.
What was there was hair. In Beethoven’s time, it was common to collect locks from famous people or loved ones. Dozens of locks attributed to Beethoven are kept in public and private collections.
However, unrooted hair is a less manageable source of DNA. This DNA usually exists in short and sometimes degraded sequences. They must be meticulously reconstructed with specialized computer programs to obtain the most complete genomic sequence possible.
How do we know that the samples are by Beethoven?
Our project used samples of eight locks of hair attributed to Beethoven and obtained from independent sources. Of these, five contained DNA from the same male person, with a degree of deterioration commensurate with their origin in the early 19th century.
In collaboration with the ancestry company FamilyTreeDNA, we have traced this person’s ancestry back to Central and Western Europe. We’re sure it’s Beethoven, as two of the locks exist alongside records of unbroken provenance dating back to the 1820s.
Three other remains, genetically identical to the other two, also had good provenance records (though not completely unbroken).
The combination of excellently documented provenances with a perfect genetic match between five independently sourced samples made it very difficult to doubt that these hair samples came from Beethoven.
Three strands of hair remained. Two of them were clearly genetically different from the other five: one is female. We do not know how they came to be attributed to Beethoven.
Ira F. Brilliant Center for Beethoven Studies, San Jose State University / William Meredith, Author provided
One of the misattributions is significant in itself, because it was the basis for earlier research concluding that Beethoven had suffered from lead poisoning. Our results show that this conclusion is no longer valid.
The eighth strand contained too little DNA to be declared authentic or not.
What we learned about Beethoven’s health
We didn’t expect to find a genetic basis for Beethoven’s best-known health problem, his deafness, and we did. Beethoven suffered from adult-onset hearing loss, which can only rarely be attributed to primarily genetic causes.
However, for many years he suffered from other health problems, especially gastrointestinal (pain and diarrhoea) and liver.
Working with the medical genetics team at the University of Bonn, we did not discover that Beethoven was especially genetically susceptible to any particular gastrointestinal condition, such as inflammatory bowel disease, irritable bowel syndrome, celiac disease, or lactose intolerance ( as some have hypothesized). Our main findings related to liver diseases.
We already knew from documentation that Beethoven suffered from bouts of jaundice. Research has now shown that he had two copies of a particular variant of the PNPLA3 gene, which is linked to cirrhosis of the liver. He also had single copies of two variants of a gene that causes hemochromatosis, a disease that damages the liver.
Surprisingly, the tests also revealed that Beethoven was infected with the hepatitis B virus in the last months of his life (and perhaps earlier). Hepatitis B infection may have been common in Europe at the time, but details about it are scant.
In addition, alcohol consumption may have increased the risk of Beethoven’s liver disease. There has been controversy over the extent and nature of his drinking, which is referenced—but not quantified—in surviving records.
We carefully reviewed the records and concluded that Beethoven’s alcohol consumption was probably not exceptional for the time and place, but still could have reached levels now considered harmful.
Beethoven family revelations
One more surprise awaited us. As part of our work, we try to relate Beethoven’s genome to those of living members of the Beethoven lineage. To do this we focus on the Y chromosome, which is only inherited in the male line (following a pattern similar to that of surnames in most European traditions).
Five men with the last name Beethoven provided their DNA samples. They were not closely related to each other and lived in present-day Belgium, from which the surname comes. They all shared essentially the same Y chromosome, which could be attributed to descent from a common male ancestor: Aert van Beethoven (1535-1609).
The surprise was that Ludwig van Beethoven’s locks had a different Y chromosome. After considering other explanations, we deduced that at some point in the seven generations between Aert and Ludwig, someone’s father for social and legal purposes was not his biological father.
But we couldn’t figure out, based on the available evidence, which generation it might have been.
And now that?
We will make the genome we have sequenced available to the public, as there may be more to discover from further analyses.
Beyond Beethoven, our project is an example of the vast possibilities that open up in the field of DNA analysis. It shows that significant results can be obtained even from DNA sources as unpromising as historical locks of hair.
To date, population genetics has rarely taken its analyzes down to the level of a single individual. This is difficult, but we show that it is not impossible.
Who could be next? Maybe another person who has a specific question to answer, or even someone who wanted to answer that question.
