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Chopin’s Heart in the Genomic Era

この文章は既に日本語で公開しているが、英語版も作っていたので載せることにする。

 

I wrote this piece in 2,008 without uploading it till last year. Its Japanese version was uploaded in November, 2,015. At that time, the situation surrounding this kind of research has changed dramatically. The major reason for this change is a technological innovation and its spreading in the field of genome research. This changed my mind and I decided to upload the piece with some additional description. Below is the English version of the Japanese original.

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A short article entitled “Chopin’s Heart” was in Science magazine.

Frédéric Chopin died in France in 1849 at the age of 39 of what his death certificate recorded as "tuberculosis of the lungs and larynx." After his death, friends had the composer's heart removed, submerged in a jar of cognac, and placed in a Warsaw church in his native Poland in accordance with his wishes.

Now Polish scientists want to reopen the jar to see whether Chopin actually died of cystic fibrosis. Michal Witt of Warsaw's International Institute of Molecular and Cell Biology has argued that Chopin had childhood symptoms matching a mild form of the genetic illness, including respiratory infections, weakness, and delayed puberty. As an adult, Chopin was slight of stature, had a hard time climbing stairs, and occasionally had to be carried offstage after concerts. "If it turned out that Chopin had cystic fibrosis, this would be very special news for all those affected with CF," Witt says.

Witt hopes to persuade Polish authorities to open the niche where Chopin's heart is stored by 2010, the 200th anniversary of his birth. "It's a good moment to check, and once we have it in our hands it's a small matter to do a CT [computed tomography] scan and DNA test," says Tadeusz Dobosz, a geneticist at Wrocaw Medical University. Poland's Culture Ministry is considering the request.

-Science, 321, 181, 2008.

 

To me this article was a small excitement. Research on cause of death of historical persons is recognized as a distinct field of science. I refer the cause on the death of Amadeus Mozart (1756-1791).

Mozart became a member of the Freemasons bya solitisation of Joseph Haydn. The study described that Mozart was murdered with arsenic by the society because he revealed some secrets of Freemasons to the public in his opera “The Magic Flute”. Like the case of Mozart, a majority of these studies was carried out assuming relationships between the person and others from letters and references and diagnosing disease from symptoms, usually subtle ones, appearing on his or her portraits. These data, of course, are based on assumptions. Because Mozart died in poverty and his body was buried in a public cemetery of Vienna together with common people, his body was unidentifiable. However, if there are tissues preserved and available for molecular analyses, they would provide materials that can be utilized for testing genetic diseases. It is theoretically possible to diagnose a genetic disease by sequencing DNA isolated from any organ or tissue.

As for the Chopin case, the first question is the preservation condition of his heart. Commercial cognac contains 40% ethanol. The condition of 40% alcohol at room temperature for more than 150 years is not an excellent preservation condition of an organ for any pathological examinations. Although it is postulated that the temperature in the church of Warsaw, where the jar of Chopin’s heart has been installed, might be cool enough for proper preservation, still it would be far from an optimal condition. Cognac immediately after aging in a barrel has 70% alcohol before shipping to the market. If the doctor, a friend of Chopin, used this undiluted cognac, the condition would be better.

Cystic fibrosis (CF) is an autosomal recessive disease causing progressive disability and often early death. Difficulty in breathing is the most serious symptom and results from frequent lung infections that are treated in these days with, though not cured by, antibiotics and other medications. As Chopin had a respiratory symptom, he was diagnosed for tuberculosis (TB). But of course, there was no knowledge on the definite etiology of TB in that era. CFTR, the responsible gene for CF, locates on the short arm of chromosome 7 and encodes CFTR protein consisting with 1,480 amino-acid residues. Interestingly, a single mutation causing the deletion of phenylalanine 508 (DF508) is found in more than 90% of patients all over the world. If Chopin suffered from CF and his germline mutation is DF508, the Polish pathologists will be able to identify its homozygous mutation in the DNA extracted from a piece of the tissue of his “fixed” heart and diagnose Chopin as CF. However, the Polish researchers are assuming that Chopin’s CF might be a mild form. If this is the case, the DF508 mutation which usually results in typical symptoms of CF would be unlikely. In addition to DF508, there are more than 1,400 recorded mutations responsible for CF, making it possible for researchers to conduct much more extensive mutation analyses throughout the whole CF gene to definitely diagnose Chopin as CF. This will take time, labor, and a sufficient amount of DNA from a substantial volume of the tissue, which is most precious.

Frederic Chopin (1810-1849) was born in Poland. Polish people are proud of Chopin. However, many French people think Chopin as French. This situation is similar to the case of Marie Curie, who was also born in Poland and lived in Paris and became famous there for her outstanding scientific discoveries. But, Chopin’s father was French. This makes French people feel familiar with Chopin. There is a petite hotel named "Hotel Chopi" at Passage Jouffroy close to the Opera in the center of Paris. When Chopin arrived in Paris at the age of 21, he settled down near Passage Jouffroy. But, unfortunately the building has not been preserved properly. After that, Chopin never went back to his home land and only his heart returned after his death. Chopin had as few as 30 recitals in his whole life. It is said that this is because of his identity as a piano composer but not a pianist. But, this might be due to his health problem.

 

In June 2008, a spokeswoman for the Culture Ministry of Poland announced that ministry officials decided that “this was neither the time to give approval, nor was it justified by the potential knowledge to be gained.” Chopin’s heart will continue to sleep for a while or forever.

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Additional descrition, 11/14/2015

Technologies of the next-generation DNA sequencing have changed many fields of biomedical science. This is successfully acomplished by combining the novel technology of direct DNA sequencing and high-throughput DNA analyeses on a big computer. By these technologies, we can obtain the whole genome sequence of a person from a small amount of genomic DNA, that is 100-200 ng. This amount of DNA can be recovered from 100,000 cells, which equivaletes 100 µg cells. We just take a tiny piece of the Chopin’s heart and extract DNA as a usual method. Nowadays, even from Neanderthals scienctist can take DNA for its sequencing. From Chopin’s heart, there shouldn’t be a problem!

Now, the technical problems would be gone. Then, how do people think about the ethical side?

 

(Pamela O'Brien helped me in English writing.)