In 1802, under a June Sun, a 31-year-old Beethoven paced through the countryside around Vienna. Rays of sunshine pierced through the trees, the hard soil crunched beneath his feet and birds conducted their own orchestra. But Beethoven didn’t marvel at these details; he was preoccupied by thoughts of suicide. Some years earlier, he had started to lose his hearing, and although it wasn’t yet severe, he was still struggling immensely with his condition. Living with hearing loss made his life a “wretched existence” that drove him into despair, he wrote. He still persevered with his work, and went on to create timeless music. But he found little joy in the process.
I observed a similar struggle at first hand, as my twin brother Islam, when we were 18 years old, started to lose his hearing. I noticed changes in his personality, too. He was always the outgoing troublemaker, but became quiet and withdrawn. Because hearing loss isn’t visible, I didn’t know what he was going through, which also made it difficult for me to be there for him.
Today, 466 million people worldwide have disabling hearing loss, and over 900 million are expected to have it by 2050, according to the World Health Organization. Its impact is often underestimated compared with other disabilities, but people with hearing loss constantly experience communication difficulties in their everyday lives. They often mishear speech and find it very difficult to follow conversations. These miscommunications can lead to individuals feeling isolated as they struggle to take part in social interactions, ultimately leading them to withdraw from society. As Helen Keller once wrote: “Blindness cuts us off from things, but deafness cuts us off from people.”
To this day, there is still no cure for sensorineural hearing loss (the most common type, and the one Beethoven had). We have advanced technological devices that amplify sound, such as hearing aids and cochlear implants, but these still don’t restore hearing. In my and my brother’s lifetimes, I’d like to see research make that possible.
Sensorineural hearing loss occurs as a result of damage to the inner ear organ, called the cochlea, which has intricate sound-sensing hair cells that are responsible for hearing. In humans and other mammals, any damage to hair cells is irreversible. Other animals, such as birds, fish, amphibians and reptiles, can spontaneously regenerate their cochlear hair cells, meaning that any hearing loss they develop is only temporary.
Scientists have been studying the regeneration process of hair cells in non-mammals, and have identified various genes and proteins that have central roles. These can be targeted to stimulate support cells in the cochlea to in turn create more hair cells and replace those that died.
Some of these cell therapies have been successful in restoring the hearing of mice and guinea pigs: a breakthrough! These advances have led to the development of more therapies, and one such therapy is now being tested for the first time in humans. The REGAIN clinical trial (REgeneration of inner ear hair cells with GAmma-secretase INhibitors), an international collaboration led by researchers at University College London, is testing a molecule called γ-secretase inhibitor that could potentially restore hearing by encouraging supporting cells to transform into new hair cells themselves.
If it works, such a scientific advance could transform hearing health care as we know it. My own research investigates the impact hearing loss has on people’s mental well-being. Many people share Beethoven’s despair when they realize that their hearing can’t be restored. Hope is an essential element for good mental health.
Other members of the deaf community see themselves as a cultural minority, rather than as a disabled group to be ‘cured’. My and other scientists’ research aims to help those who feel disadvantaged by deafness and want to be able to hear.
Islam and I come from interracial parents, so we look very different. I have white, freckled skin, and his is olive (he gets perfect suntans, and I turn into a tomato). I have blue eyes, and his are hazelnut. I have normal hearing, whilst he has severe hearing loss. He and I have shared the many chapters of our lives, and when things became difficult as his hearing declined, what helped us cope was being able to make sense of it all together. Communication, self-expression, hearing and being heard (even through sign language) are basic human needs. I hope that when I voice support to my brother in the future, that he’ll be able to hear it, receive it and not feel alone.
When Beethoven lost his hearing, he secluded himself from society — but one thing that gave him strength was the hope that his hearing could be regained one day. But each medical remedy he attempted failed. In 1802, he wrote: “But, think that for six years now I have been hopelessly afflicted, made worse by senseless physicians, from year to year deceived with hopes of improvement, finally compelled to face the prospect of a lasting malady (whose cure will take years or perhaps be impossible).”
Beethoven’s dream of regaining his hearing did not come true for him, but through the scientific advance of regeneration of hair cells, it could become a reality 217 years after his June walk. On his deathbed, it is said that Beethoven’s last words were “I shall hear in heaven!” Luckily for us, those facing hearing difficulties could soon be able to hear on Earth.
Nature 575, 53-54 (2019)