Beethoven's hair gene sequencing research is out! Revealing the real cause of death

In March 2023, the journal Contemporary Biology, a subsidiary of the authoritative journal Cell, published an interesting research result, which not only determined the cause of death of composer Beethoven more than 200 years ago, but also uncovered the "family scandal" of the great artist. What was the opportunity that made the "mystery of Beethoven's death" public? What methods did scientists use to uncover this two-century-long secret?

The answer is simply a few locks of Beethoven's own hair.

Beethoven's die-hard fan, Tristan Berg, a PhD in anthropology at the University of Cambridge, has been studying Beethoven's health for many years, trying to figure out his well-known progressive hearing loss. But after sequencing the genome of Beethoven's hair, he made more noteworthy discoveries.

Research shows that a gene called PNPLA3 was found in the DNA extracted from Beethoven's hair, and people who carry this gene fragment are three times more likely to suffer from liver disease than normal people. Not only that, if you carry this gene and have a habit of drinking a lot, the probability of liver disease will soar. Combined with historical descriptions, Beethoven was indeed a person who loved alcohol, which can be proved by his correspondence with friends.

In addition, Dr. Berg also found the DNA of hepatitis B virus in Beethoven's hair shaft (the part of the hair that is exposed), indicating that Beethoven was very likely infected with hepatitis B, which is also one of the main causes of cirrhosis and even liver cancer.

Combining the above studies, we can conclude that: first, he was born with a liver disease-susceptible gene; second, his lifestyle, his habit of alcoholism; and third, his health, he had hepatitis B. In Dr. Berg's words, it was not surprising that Beethoven died of liver cirrhosis at the age of 56.

In addition to discovering the cause of Beethoven's death from liver disease, the genome sequencing also revealed a "family scandal." When researchers compared Beethoven's Y chromosome with the genes of five living descendants of Beethoven's family, they found that there was no match. There was a big difference between the two, which means that at some time between 1572 and 1770, Beethoven's paternal ancestor branch had an "extra paternal" event. That is to say, among Beethoven's female ancestors, there must have been at least one who had an affair and gave birth, leaving the genes of other people in the Beethoven family bloodline.

Through the discussion of Beethoven’s “serious gossip,” scientists not only determined his background and circumstances, but also demonstrated to the public more possibilities of genome sequencing.

The human genome contains a vast amount of information. When doing DNA identification, technicians will not check all of this information, but will focus on finding key markers that can represent individual differences. For example, SNP (single nucleotide polymorphism) refers to the difference in a single base pair. In some cases, these differences will also change the amino acids corresponding to the gene encoding, resulting in differences in single amino acids in the protein, namely SAP (single amino acid polymorphism). In short, if the protein components in the sample can be analyzed and the amino acid differences are found, then it will have the potential to become an individual "specific tag" just like the nucleotide differences.

Whether at a crime scene or at archaeological sites, hair is one of the most common biological samples. This is because the keratin and keratin-associated proteins that make up the hair skeleton are very stable and can persist for many years. Researchers have found through a series of comparative studies that the SAP information found in hair can well predict the SNP information present in the genome, with an accuracy rate of up to 98%. This responds to the public's doubts about whether it is possible to conduct genetic analysis on ancient people through hair.

The fact that the whole genome can be sequenced using only hair is indeed a delightful discovery in the scientific community, but ethically, it makes people panic. Can the privacy and security of human genes be guaranteed? How can the problem of genetic discrimination be solved? Is there a risk of genetic information being abused? These are all major events that will inevitably happen when humans enter the genetic age.

These are not only discussions on the moral and social risks of genetic technology, but also debates on the value and existence of future human beings. The state has continuously issued relevant laws and regulations, such as the Genetic Privacy Law, the Genetic Information Non-Discrimination Law, and the Genetic Information Transfer Law, etc. As every individual in society, we must also pay more attention to genetic privacy and protect our own legitimate rights and interests and even personal safety.

This article is a work supported by Science Popularization China Starry Sky Project

Author: Tiangeng

Reviewer: Tao Ning (Associate Researcher, Institute of Biophysics, Chinese Academy of Sciences)

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.