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Portrait of Beethoven by Scott Gentling
Scott Gentling (1942-2011).Beethoven.[undated].Graphite on paper.Amon Carter Museum of American Art, Fort Worth, Texas.2018.70, CC BY-SA 4.0, via Wikimedia Commons

Beethoven, one of the great musical geniuses of the 19th century, was deaf when he wrote some of his best known works. He had progressive hearing loss starting in his 20’s and was functionally deaf during his late period when he wrote his most expressive and innovative sonatas, string quartets, and the Ninth Symphony (Ode to Joy). Beethoven also suffered from gastrointestinal symptoms most of his adult life and died of liver failure. In 1802, he requested that his medical conditions be disclosed to the public after his death in a letter to his brothers known as the Heiligenstadt Testament.

Historians and musicologists have speculated if he had a heritable disorder or infectious disease that contributed to his hearing loss and death. Alcoholism was suspected as a factor in his liver disease. There was a family history of alcohol dependence and some of his associates claimed he drank heavily, though others said he did not drink more than was typical at that time.

Recent advances in ancient DNA methods presented an opportunity to learn more about Beethoven’s medical conditions. A team of 32 international researchers used eight surviving locks of Beethoven’s hair for their analysis. Several locks were taken by friends when Beethoven died in 1827 and others were given to friends and associates while he was alive.  Over the years they were sold and passed down to others and the provenance of some were questionable. The locks were analyzed in this new study to determine their authenticity, using a novel geo-genetic triangulation technique. Additionally, the researchers “analyzed Beethoven’s genome for genetic causes of and risk for somatic disorders in addition to metagenomic screening for evidence of infections, followed by targeted DNA capture.” (Begg, et al, 2023)

Five of the locks were determined to originate from a single individual or monozygotic twins and had damage patterns that authenticated them for early 19th century origin. A non-matching lock called the Hiller lock was used in previous genetic and forensic testing featured in the book and movie, Beethoven’s Hair. It was found to be from a woman, invalidating results indicating lead poisoning as a contributor to Beethoven’s hearing loss and other maladies.

Analysis on the Y chromosome revealed a surprise finding. Five living men from the Beethoven patrilineage had a common ancestor in Aert van Beethoven (1535-1609). But their Y chromosomes did not match with any of the five authenticated Beethoven hair samples. The researchers conclude that there was at least one extra pair paternity event in Beethoven’s ancestry. Further analysis of descendants of Beethoven’s brother Karl leaves open the possibility that the two may have been half brothers.

Beethoven’s GI symptoms were consistent with Crohn’s disease or ulcerative colitis. His hearing loss could have been associated. Other possible related causes for the hearing loss were otosclerosis, sarcoidosis or systemic lupus erythematosus. A genome wide association study eliminated most of these as possibilities, except for lupus where there was some elevated polygenic risk. 

Celiac disease and lactose intolerance were both eliminated as possible causes of his gastrointestinal symptoms through testing for associated alleles. He actually had some elevated genetic protections against irritable bowel syndrome, making it also unlikely. 

They analyzed 55 genes where variants could cause monogenic post-lingual hearing loss and 209 related to pre-lingual hearing loss. There were no positive findings.

In summary, we could not reliably evaluate most hypothesized multifactorial causes of Beethoven’s hearing loss, nor did we identify a monogenic origin.”

(Begg, et al, 2023)

Beethoven’s polygenic risk for liver cirrhosis was found to be elevated in his PNPLA3 gene and his HFE gene. This combined with heavy drinking could have caused his liver failure. Additionally, hepatitis B DNA was found in the Stumpff Lock hair which was the best preserved sample. Researchers could not tell how long he’d had the hepatitis B infection. The positive lock was taken at his death and represented the final months of his life. Tristan Begg, the lead author of the study, wrote more about the possible role of hepatitis B in Beethoven’s liver failure on William Meredith’s blog. Meredith is a Beethoven scholar who participated in the genome study.

Though not addressed directly in the paper, the study brings to an end the theory that Beethoven was black. Noting the similarities in their appearance, the bi-racial composer Samuel Coleridge-Taylor was the first to raise the possibility. Many contemporaries of Beethoven described him as dark, brown or ruddy in complexion and noted his broad, rounded nose which can be seen in his life mask taken in 1812. The idea has persisted since Coleridge-Taylor introduced it, and was repeated by Malcolm X and a 1969 Rolling Stones article titled “Beethoven was black and proud!” More recently it was the subject of scholarly articles and even a Twitter meme. This genomic analysis confirms that Beethoven’s ancestry was greater than 99% European, with the strongest autosomal match with present day North Rhine-Westphalia in Germany.

Although there was no definitive finding on Beethoven’s hearing loss, there was plenty to advance the existing knowledge base and establish leads for future research. The study demonstrates how much can be learned from a few strands of centuries old hair through new genetic analysis tools.

References

Begg TJA, Schmidt A, Kocher A, et al. Genomic analyses of hair from Ludwig van Beethoven. Curr Biol. 2023 Apr 24;33(8):1431-1447.e22. doi: 10.1016/j.cub.2023.02.041. Epub 2023 Mar 22. PMID: 36958333.

Clark P. ‘Beethoven was black’: why the radical idea still has power today. The Guardian. 7 Sep 2020. https://www.theguardian.com/music/2020/sep/07/beethoven-was-black-why-the-radical-idea-still-has-power-today

Cells in brain organoids made from human stem cells can mature to resemble those of a postnatal brain. S. Pasca - Pasca Laboratory/Stanford University.

In a recent article in the American Journal of Bioethics, Henry T. Greely explores the ethical implications of improved human brain models used in research.  Mr. Greely identifies challenges with using human and animal subjects for brain research, and explores the ethics of improved simulacrum of living brains created and used in research: 

The dilemma? When we avoid unethical research by making living models of human brains, we may make our models so good that they themselves deserve some of the kinds of ethical and legal respect that have hindered brain research in human beings. If it looks like a human brain and acts like a human brain, at what point do we have to treat it like a human brain—or a human being?

Mr Greely identifies four types of human brain surrogates: genetically edited non-human animals, human/non-human brain chimeras, human neural organoids, and living ex vivo brain tissues.  For each surrogate type, Mr. Greely describes the science behind the surrogates and current directions of the research.  Mr. Greely also discusses potential problems with each of these surrogates including welfare of the surrogates, consent and welfare of the “human parts” of the surrogates, possible non-research implications of the research, possible non-research uses of the surrogates, humanization of non-humans,  and the rights of the surrogates. 

Drawing on references from both science and science fiction to illustrate both technologies and applications, the article is a fascinating read!

If you're interested in reading more about genetics, check out GW's Genetics Journal Club led by Dr. Chuck Macri.

Greely HT. Human Brain Surrogates Research: The Onrushing Ethical Dilemma. Am J Bioeth. 2021 Jan;21(1):34-45. doi: 10.1080/15265161.2020.1845853. PMID: 33373556.

Stop/Unethical - Think/Grey - Go/EthicalA scientist wrongfully imprisoned?  Or, a scientist who ignored ethical principles and scientific standards?

Dr. He Jiankui earned a PhD from Rice University in 2010, did postdoctoral work at Stanford University, and returned to China in 2012 to work in the Southern University of Science and Technology.  In 2018, Dr. Jiankui confirmed reports that he had edited the genomes of embryos using CRISPR, transferred them to women's uteruses, and that a set of twin girls had been born.  Subsequently, Dr. Jiankui was placed on unpaid leave and eventually dismissed from Southern University of Science and Technology.  In late 2019, Dr. Jiankui was sentenced to three years in prison and fined about $430,000 U.S. dollars for having "forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos into two women."

So what happened?  Did Dr. Jiankui go too far, too fast?  Or, did China stifle a cutting edge researcher?  Read these articles to understand the science, ethics, and researchers involved in this story:

For more discussion, check out additional articles in Dr. Chuck Macri’s Genetics Journal Club

20170808-clinical-genomicsAre you interested in how genomics can be used in clinical care?  A recent review in The Lancet discusses future directions for clinical application and discusses how specific technologies can be applied including: family health history, clinically important genomic variation, SNP array genotyping, and genome sequencing.  The article also discusses clinically relevant issues such as the disclosure of information to patients, the process of sharing genomic test results with patients, and patient-oriented resources and genomic medicine studies.

For more discussion, check out additional articles in Dr. Chuck Macri's Genetics Journal Club  as well as additional full-text articles is available in Himmelfarb Library's full-text collection:

To get background information on genomics, consult a title from Himmelfarb's book collection which includes:

  • Pyeritz, R., Korf, B., & Grody, W. (2019). Emery and Rimoin’s principles and practice of medical genetics and genomics. Foundations (Seventh edition.). London, U.K: Academic Press is an imprint of Elsevier.
  • Moody, S. (2015). Principles of developmental genetics (2nd edition.). London: Elsevier Academic Press.  Himmelfarb Stacks: QH453.P756 2015

    • Congratulations to Sally Moody, PhD, chair of the Department of Anatomy & Cell Biology at #GWSMHS, whose book Principles of Developmental Genetics, 2nd Ed., was selected for Doody Enterprises, Inc. Core Titles in the Health Sciences.   The list of the most distinguished titles is used by librarians worldwide to develop and update their collections with the titles deemed most essential in over 120 specialties across clinical medicine, nursing, allied health, and basic sciences.

 

Image citation: Del Aguila, E. (No date). Image of young child with double helix [Online image].  Retrieve from https://www.nih.gov/news-events/news-releases/nih-accelerates-use-genomics-clinical-care on September 3, 2019.

genetherapyWhat's the state of the art for gene therapy?  It can be challenging to remain abreast of this fast-moving field but a recent review article in the New England Journal of Medicine can help update your knowledge.  In Gene Therapy, Dr. Katherine High and Dr. Maria Roncarolo describe the basic principles of in vivo and ex vivo gene therapy as well as specific therapies in use and in development.  The article also includes an interactive infographic to support learning and teaching as well as an interview with Dr. High.

Explore additional genetics articles by searching Himmelfarb Library‘s PubMed which provides direct links to articles in our online collections or Health Information @ Himmelfarb to locate e-books, print books, and other materials with information on genetics.

To learn more about these issues and other genetics topics, participate in the SMHS’s online Genetics Journal Club.  

genomicspubsq

Next-generation genomic data will affect prenatal testing decisions and the quality of information communicated to patients. Existing and emerging reproductive technologies shape societal attitudes and norms about reproductive decision-making, reproductive autonomy, disability, and diversity. Reproductive decision-making and autonomy
are also hindered by existing health disparities, particularly when they limit access to reliable genetic and genomic testing services, resources for counseling, and sufficient medical follow-up care. Finally, epigenetic changes play a role in reproductive health disparities. This seminar will explore ways to engage the public in discussions that can
lead to policy and research initiatives to address these challenges.

When: April 8, 2019 5 – 7 p.m.
Where: Ross Hall 117
Registration:  
The event is free and open to the public. Registration is required by April 5: https://tinyurl.com/univsem2

Presenters

  • Barbara Harrison, MS, CGC, Assistant Professor, Department of Pediatrics, Division of Medical Genetics, Howard University
  • Mark W. Leach, JD, MA, Attorney, Bioethics Specialist for the National Center for Prenatal and Postnatal Resources at University of Kentucky
  • Charles J. Macri, MD, FACOG, FACMGG, Division Director of Maternal Fetal Medicine; Director of the Wilson Genetics Center; The George Washington University School of Medicine and Health Sciences
  • Sonia M. Suter, JD, MS, John R. and Inge P. Stafford Research Professor of Law, GW Law School

 

Respondent

Shawneequa Callier, JD, MA
Associate Professor, Director, Doctoral Research, Translational Health Sciences, PhD program, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences

14766388005_021e288b59_oThe Genetics Journal Club for this month features the article Molecular Support for Heterogonesis Resulting in Sesquizygotic Twinning that was recently published in the New England Journal of Medicine.  The article describes boy-girl twins whose maternal DNA was identical, and who share paternal DNA as with genetic siblings.  The authors propose that sesquizygosis is a newly identified and rare third type of twinning along with monozygotic (identical) and dizygotic (fraternal) twins .   The article describes the authors' research to identify other pairs of sesquizygotic twins, a case report regarding this set of twins who are now four years old, and theories regarding how sesquizygosis occurs.

Explore additional genetics articles by searching Himmelfarb Library's PubMed which provides direct links to articles in our online collections.

 

Image citation: Anonymous (1922).  Single ovum twins [online image] from Plass, E.D. (1922). Obstetrics for nurses.  New York: Appleton and Company.

lawpolprecmed
How do law, policy, precision medicine and health equity relate to one another?  A free webcast conference on November 29 will explore these issues; participants may also register for free in-person attendance.
Law, Genomic Medicine & Health Equity: How Can Law Support Genomics and Precision Medicine to Advance the Health of Underserved Populations? will explore how to ensure that the promise of precision medicine is fulfilled across all populations and that it doesn't recreate or exacerbate health disparities.  This conference will feature speakers including clinicians, scientists and activists to explore the intersection of law, policy, genomics, and health disparities.
To learn more about genetics topics, participate in the GW SMHS’s online Genetics Journal Club.

8249906174_145e319ebd_oNew research published in JAMA Internal Medicine looks at the inverse relationship between coffee drinking and mortality. In this population-based study, researchers used baseline demographic data to estimate hazard ratios for coffee intake and mortality, and also looked at the potential effect of specific genes which are known to modify caffeine metabolism.

In Association of Coffee Drinking With Mortality by Genetic Variation in Caffeine Metabolism: Findings From the UK Biobank, Lotfield, Cornelis, and Caporaso seek to answer the question:

"Moderate coffee consumption has been inversely associated with mortality; however, does heavy intake, particularly among those with common genetic polymorphisms that impair caffeine metabolism, increase risk of mortality?"

To understand their research and find an interesting example of population-based genetic research, read the full article - and and enjoy your favorite caffeine beverage guilt-free while you read!

To learn more about these issues and other genetics topics, participate in the SMHS’s online Genetics Journal Club.

 

Image citation: Foong, C. (2012).  coffee [Online image].  Available at https://www.flickr.com/photos/cherylfoong/8249906174

PPSAn article recently published in the New England Journal of Medicine explores the inherent tension between public health and precision medicine as public health has worked to improve the health of populations and precision medicine seeks to improve the health of individuals via their unique genome.    In “Precision” Public Health — Between Novelty and Hype, Merlin Chowkwanyun, Ronald Bayer, and Sandro Galea explore what precision medicine might mean for public health and ask:

  • What does a shift toward precision medicine mean for public health?

  • Will precision public health provide an opportunity reenvision and empower public health or is it an abandonment of public health’s core aim of enhancing health at a population level?

  • How will public health integrate individual genome specific data and interventions with its broader mission?


To learn more about these issues and other genetics topics, participate in the SMHS’s online Genetics Journal Club.