x Abu Dhabi, UAEFriday 21 July 2017

Scientist wants to find cause of Beethoven's death through genomics

A scientist explains how genomics could provide answers to questions about the life and death of the great composer, writes Alice Haine

The German biologist and pianist Nikolaus Rajewsky played compositions by Beethoven during a recent lecture in Abu Dhabi. Silvia Razgova / The National
The German biologist and pianist Nikolaus Rajewsky played compositions by Beethoven during a recent lecture in Abu Dhabi. Silvia Razgova / The National

When German composer and pianist Ludwig van Beethoven died in 1827 at the age of 56, he was profoundly deaf, having started to lose his hearing 30 years before.

But it wasn't only deafness that had made his later years hard to bear. He also complained of crippling stomach pain and bleeding from his ears and nose.

Since then, doctors and historians have debated the reasons for his illness with different schools of thought settling on lead poisoning, syphilis and murine typhus - a from of typhus transmitted by fleas on rats.

With no conclusive answer, it seems the mystery will stay buried forever. Or will it?

After all, imagine what we could learn about this great composer if we used today's technology to sequence his genome.

This was a question posed by the German scientist, Nikolaus Rajewsky, at a public lecture organised by NYU Abu Dhabi Institute.

Rajewsky, a professor of biology at New York University and the scientific coordinator at the Berlin Institute for Medical Systems Biology, spent two hours examining Beethoven's health, music and ancestry through the lens of modern genomics, interspersing his intellectual musings with his own performances of Beethoven's compositions.

"Beethoven's diseases were a transforming event," says Rajewsky. "He lost his hearing, and for a musician that's a tragic thing, particularly as he was making his living working as a pianist. He could not work as a performing artist anymore, so he contemplated suicide, but then decided to focus on his composition, which he felt he could do without his hearing. It was a very brave decision."

What Rajewsky finds interesting was a letter written by Beethoven that some consider almost like a will, making it clear he wanted his health problems understood after his death.

For this reason, Rajewsky, internationally acclaimed for his pioneering research into the processes of gene regulation, has taken his knowledge of modern genomics and applied it to Beethoven.

While Rajewsky is quick to point out that he cannot offer any groundbreaking insights, he feels it is an interesting topic that can be explored further, particularly at a time when so much is being invested in the field of genomics.

For many scientists today, personalised medicine - all made possible by the sequencing of the human genome 10 years ago - will be the future of medicine, with doctors prescribing treatments to patients that work specifically for their genetic make up.

While to ascertain the cause of Beethoven's diseases would be impossible right now, it is possible to sequence his genome.

"This is not just a complete intellectual exercise - it's something that could become reality," says the 44-year-old scientist.

"It means we could read his entire hereditary information and find out where his ancestors came from. You could also look for relatives and explore his family tree to a very interesting degree."

This would be made possible by two factors. The first is that actual locks of the composer's hair are stored at a Beethoven research centre in California.

When he died, many of his followers cut locks from his hair as souvenirs, meaning he was almost bald by the time he was buried.

Some of these locks reportedly made their way from Europe to the US during the Second World War and they have since been authenticated by matching them up with a fragment of Beethoven's skull - believed to have been taken when his body was exhumed in 1863 for medical tests.

The second factor making tracing his ancestry possible is that such a service already exists. For US$200 (Dh734), anyone can send a swab of DNA to initiatives such as The Genographic Project orchestrated by National Geographic. The project looks at the sequence within an individual's genome and then maps this to the geographic location so they are able to compute which populations around the world are mixed in someone's DNA.

Such information provides great insights into a person's ancestry, so imagine what you could discover about Beethoven.

But what could it tell us about his health?

While Rajewsky is adamant that the mystery of Beethoven's illness and subsequent death could not yet be solved, he does say sequencing the genome could identify risk factors for him.

"We could find out whether he had a rare genetic disease, but I think that's a remote possibility," he adds.

"What is clear is that with regards to his artistry, there is currently nothing that you can learn from his DNA.

"A simple example of this is that Beethoven had absolute pitch [the ability to identify or re-create a note without the benefit of an external reference]. This is a genetic trait as there is not a single case of a person being trained to acquire this.

"People have tried to map the locations in the genome which are responsible for this and it turns out it is a complex trait - there are many locations in the genome that are linked to this ability. So it would be close to impossible to deduce whether Beethoven had absolute pitch or not, though we know he did so it's something of a positive control.

"However, the technology to sequence the genome has been available just 10 years so we have just started to explore this; 100 years from now we will be much better at reading more from DNA.

"Sequencing Beethoven's DNA is certainly more interesting than looking at a lock of his hair in the museum. And I think this is something Beethoven would have liked."

Why Rajewsky, a man hailed for his great scientific achievements, chose to focus his lecture on Beethoven is curious.

He says he only became interested in the tragic composer in recent years, but it is clear he has a deep admiration for him.

"His music has been transforming in my life and he was one of the most original artists ever. If you look at his music, you will not find a single bar repeated and I think it will be modern for a very long time.

"He was also a very touching human being, full of emotions and life, a sincere man and incredibly inventive with a fascinating personality."

Later, as Rajewsky rehearses his performance of Beethoven's music, he appears lost in another world.

He started playing the piano at the age of six and though his education led him to study maths and physics at the University of Cologne, he couldn't quite turn his back on music, so he also completed a course in piano.

This created a dilemma in his mid-20s when he had to decide between a career in music or science.

"It was a gradual process but I think life as a performing artist is not so easy unless you are a superstar. All you need to do is break your finger and it's all over. As a scientist there is more freedom to go in different directions."

Since then he has made significant scientific discoveries, though he plays down his achievements.

"I'm just a curious person having fun working with other interested scientists and human beings."

But he says following his kind of science means giving up many things in life.

"It's not a nine to five job. There are many things I find interesting that I didn't pursue. I would like to go more to theatres, opera, poetry readings or dancing but I cannot. Berlin is full of culture and I can only enjoy a tiny fraction of that."

However, he still plays the piano, usually in the early morning "because I am fresh and nobody disturbs me".

With this in mind I ask why he chose Beethoven's Sonata 30, op 109, written in a period when he was going deaf and part of the Diabelli Variations - the last major piano piece Beethoven wrote - to play during his lecture.

"The Diabelli Variations are rarely played and I did not want something that is played all the time; I wanted to play something from the period of his life when it was really moulded by his disease," Rajewsky explains.

"When you become deaf it's not only a problem for making music but also as a composer you're not participating in other peoples lives anymore. You can't go to a concert because there's not much to hear so you can only look at written scores by other people. It's a general focusing on yourself that's happened.

"I wouldn't say it changed his music, but it was an important component in his development."

So what did Rajewsky conclude from his investigations into Beethoven?

"I don't have any grand conclusions to offer. I think it's clear that genomics is very powerful and has just started on the road in transforming things, and I think it's clear that for Beethoven's artistic abilities, you cannot reduce a human to its DNA - that's another lesson here."

 

Alice Haine is a senior features writer for The National.