March 28, 2023
Credit: Susanna Sabin
My NY Times feed directed me to a report published last Wednesday in the journal Current Biology on an analysis of locks of hair from Ludwig van Beethoven. When Beethoven died (March 27, 1827) at the age of 56 it was his wish that his ailments be studied and shared so “as far as possible at least the world will be reconciled to me after my death.” Beethoven had chronic health issues, including progressive hearing loss that began in his mid- to late-20s and left him functionally deaf by his mid-40s, recurring gastrointestinal complaints, and severe liver disease. Beethoven wrote a letter to his brothers in 1802, the Heiligenstadt Testament, asking that his doctor, Johann Adam Schmidt, be allowed to determine and share the nature of his “illness” once Beethoven died. Beethoven outlived the doctor by 18 years and the testament was discovered in a hidden compartment in his writing desk after he died. Hair samples helped scientists discover insights about family history, chronic health problems, and what may have contributed to his death. The wish has been partially honored by the sequencing of his genome.
When I looked online, I found whole genome sequencing (WGS) is the process of determining the entirety, or near entirety, of the DNA sequence of an organism’s genome. This entails sequencing an organism’s chromosomal DNA as well as DNA contained in the mitochondria. Genome sequencing has largely been used as a research tool but was introduced to clinics in 2014. Personalized medicine in the future may use this data as an important tool to guide possible treatments and may lay the foundation for predicting disease susceptibility and drug response. WGS is different than DNA profiling, which only determines the likelihood that genetic material came from a specific individual or group, and does not contain information on genetic relationships, origin, or whether the person is susceptible to specific diseases. Research on Beethoven’s hair samples used WGS.
There have been questions concerning what ailed Beethoven in life and cause d his death. During the last seven years Beethoven experienced at least two attacks of jaundice from the liver disease that led to a general belief that he died from cirrhosis. Medical biographers have combed Beethoven’s letters and diaries, his autopsy, notes from his physicians, and even notes taken by examiners when his body was twice exhumed (1863 and 1888), with hopes of piecing together his complicated medical history. This new research took the study further by using eight samples of hair cut from his head in the seven years prior to his death. While a definitive cause was not determined, there were several significant genetic risk factors for liver disease along with evidence of a hepatitis B infection in the last months before his final illness. Letters written by Beethoven, and those of his friends, show that he regularly consumed alcohol, and at least a liter of wine with lunch each day. Alcohol combined with genetic risk factors for liver disease and his hepatitis B infection might have created the perfect storm for his failing health. The report ended with the disclaimer that additional research is needed.
THOUGHTS: When genetic profile for Beethoven was determined the researchers compared it with the DNA of his living relatives in Belgium but did not find a complete match. Some relatives shared a paternal ancestor in the late 1500’s and early 1600’s, but there was no Y-chromosome match. This suggests an extramarital affair on Beethoven’s father’s side that resulted in a child sometime between the 1572 conception of Hendrik van Beethoven and the conception of Ludwig van Beethoven in 1770. It is doubtful this is the finding Beethoven wanted to share with the world. While inquiring minds may want to know, the findings are rarely what we expect. Act for all. Change is coming and it starts with you.