If Beethoven, who died in the early 1800s, had gone deaf today, his experience would have been very different.
That is thanks to the cochlear implant. Developed in the 1960s, it is the first ever bionic device created to restore a sensory organ and has now been fitted in over a million people.
Although not perfect, almost every recipient will eventually understand speech, even in modest background noise.
Yet, beside incremental improvements to the implant's algorithms and coding systems over 40 years of operation, the underlying technology has largely remained unchanged, even though the number of research publications on the topic have tripled per decade in the last 30 years.
This could soon change. New research is seeking to combine gene therapy with improvements in the mechanical engineering of the cochlear implant to improve hearing outcomes for patients.
This endeavour is ever more important, given it's expected that one in every 10 people will have disabling hearing loss by 2050, and because researchers are starting to find evidence of a link between dementia and this sensory loss.
The cochlea is a small, hollow, snail-shaped structure in the inner ear that connects to the auditory nerve. Three-and-a-half-thousand acoustic hair cells in the inner and outer cochlea convert vibration of sound into an electrical signal into the brain.
These cells are like 'keys on a piano' and range from low to high frequency, explains Dr Robert Gay, director of pharmaceutical approaches at Cochlear, a Sydney-based manufacturer of the device.
For many people with profound hearing loss, these hair cells are damaged, lost or mutated, but a residual population may still exist that can be stimulated.
The Cochlear Implant, which is surgically implanted into the cochlea, contains 22 very small electrodes – bionic replacements for the defunct hair cells – at the end of a very thin tip that is around 400 micrometres wide.
The external device acts like a hearing aid, taking in sound and speech, where a processor converts the sound waves into a digital code that is then sent to the transmitter coil and transmitted across the skin into the electrodes. The electrodes stimulate the auditory nerve, which then transmits the sound to the brain.
"The plasticity of the brain embraces the signals from the artificial 'piano keys' and learns to interpret them as if they were coming from the ones a person was born with," explains Gay.
Though undoubtedly a medical marvel, the sound output from the cochlear implant is far from pitch perfect. People who previously had natural hearing say sound is robotic or electronic, making music enjoyment difficult, and its software stack cannot very well process for tonal languages, such as Cantonese or Thai. For a small number of eligible people, it doesn't work at all.
The scope for addressing these limitations through mechanical engineering is now limited, according to experts, which is why researchers have turned to pharmaceutical and biological interventions.
One such study is a first-in-human clinical trial, conducted by four Australian universities, to use gene augmentation therapy to improve hearing outcomes in cochlear implant patients.
The trial, involving 15 implant recipients, hopes to address the 'neural gap' challenge of cochlear implants that affects hearing dynamics and pitch perception. This is, put simply, the gap between the electrode array and the wasted-away auditory neurons. The gap makes the selective recruitment of discrete subpopulations of neurons normally associated with particular sound frequencies (tonotopy) challenging.
The Cochlear Implant Neurotrophin Gene Therapy (CINGT) clinical trial hopes to bridge the gap by delivering small DNA molecules (neurotrophic factors BDNF and NT3) that have previously been shown in animal studies to stimulate rapid directed regrowth of neurons towards the implant electrode array.
It's hoped the treatment can bring the nerve fibres closer to the cochlear implant electrodes for much more local recruitment of the neurites. This could more authentically recreate the tonotopic map [the spatial separation of frequencies within the inner ear] to improve pitch perception.
"This could be improved even further in 'next-generation' cochlear implants where closer nerve proximity would make increased electrode density beneficial," explains Professor Gary Housley, who holds the chair of physiology at the University of New South Wales and is leading the trial.
Notably, delivery of the DNA into the targeted area of the ear is done by a patented method, called bionic array electric gene electrotransfer (BaDGE), developed at UNSW. The cochlear array has been reengineered to put a superfine lumen through the centre from which DNA can be pumped.
The process is a technological breakthrough and nullifies the need to use a technique called electrotransfer, which requires high currents that can damage tissue, says Housley.
"We adapted the electrode array to create an electric lens, an asymmetrical compression of the electric field, which is very efficient at making DNA stick to cells without damaging tissue. The DNA solution is inert except within the focus on the electric field."
Housley and his team are confident they have proved the process doesn't cause harm to patients or make hearing outcomes worse, but they need to complete data analysis to determine whether better hearing outcomes have been achieved. The full study results are expected later this year.
"We know we have successfully reengineered the cochlear implant array to establish a new, super-efficient gene delivery technology," he says, "In the future, if we can repair the ear with therapeutics, the array in the cochlear implant may become a delivery instrument, with patients requiring it only temporarily – but that's looking decades into the future."
Cochlear is also running a clinical trial that seeks to protect auditory neurons from trauma – such as when an implant is inserted – with a cochlear implant that releases an anti-inflammatory drug therapy directly to the cochlea that could be neuro-protective and potentially improve hearing outcomes.
Image credit: Science Photo Library
Another team of researchers at the University Medical Centre Göttingen in Germany are hoping to start clinical trials in 2027 to prove the efficacy of a cochlear implant they have developed that uses optogenetic gene therapy and an optical stimulator instead of conventional electrode arrays.
Tobias Moser, professor of auditory neuroscience at the Institute for Auditory Neuroscience and InnerEarLab at the university, who is heading the multi-million-euro research project, believes it could be the 'game-changing' moment the cochlear implant has been missing all these years.
The technology aims to address the poor quality of sound encoding of the implant by using light, instead of electrical current, to focus and stimulate the auditory neurons more efficiently. Currently, the large lateral spread of electrical current from each electrode means too many auditory neurons are stimulated at the same time, which is why a user might find it hard to converse in a busy, noisy environment.
The research, which started in 2007, is based on an optogenetics method that emerged around the millennium and has been shown to work in rodents. It was discovered that a genetic trigger – in this case f-Chrimson, which is delivered to the neurons via a harmless viral vector containing the DNA information – can make auditory neurons light-sensitive. This creates a light-activated ion channel that allows ions to cross the membrane and charge the auditory neuron, firing an action potential that travels to the brain and is identified as sound.
According to the researchers,the technique could allow future cochlear implants to transfer sound stimuli via up to 30 independent stimulation channels, using microscale light sources such as laser-coupled waveguides in the cochlear implant. This could provide significant improvement in pitch discrimination and volume, potentially much closer to those of a normal hearing person, they say.
The new cochlear implant would use hermetically sealed laser diode arrays to emit light, which is then focused onto polymer waveguides, like optical fibres, replacing the electrical input. Initial investigations suggest the device could be mass-manufactured and worn for up to 20 years.
"The idea of using optical stimulation to overcome the bottleneck of poor spectral selectivity could be transforming. People could have much more information available to their brains," says Moser. "The cochlear implant is nothing other than a brain link and we're essentially working on making this interface more powerful."
To achieve clinical trials by 2027, the team need to develop the chip that drives the laser diodes and secure venture capital funding, among other things. Other challenges include addressing safety concerns, and some evidence of auditory neuro losses over time.
Others are also looking at developing light-based cochlear implants, including researchers at The University of Melbourne.
Gene therapy treatments for cochlear implant users are 5-20 years away, depending on who is being asked. But, besides developing the technology, another barrier to adoption could be the price: a gene-therapy treatment currently available to restore genetic-related sight loss costs a considerable $800,000.
Nevertheless, Cochlear's Gay believes "niche areas" of hearing loss can be cured with gene therapy. In 30 years' time, he expects the cochlear device could have advanced to the point it will be concealed within a patient's skull, it will contain more than 22 electrodes, and possibly be delivering drugs and reporting back on infections.
Raymond L Goldsworthy, an associate professor of research otolaryngology at Keck School of Medicine of University of Southern California and a cochlear implant recipient of 30 years, is equally optimistic.
"In 20-30 years', time I think hearing loss could be restored close to normal," he says. "I used to think it was the cochlear implant versus neuro regeneration, but both are making great progress and it'll probably be a hybrid approach, with the implant still used but neural regeneration bridging the gap."
The ear: An unexpected innovation space
Beyond gene therapy, restoring hearing and amplifying sound is emerging as an exciting innovation space, thought to be driven by the growing population of older people, with a range of novel technologies under development.
Raymond L Goldsworthy, and colleagues, at the Bionic Ear Lab at the University of Southern California, have developed sound-
processing algorithms that could be used with smart glasses to enhance hearing for both cochlear implant and hearing aid users.
"Microphones embedded on the legs of eyeglasses and connected to a hearing device could help someone better pick up the acoustic environment to create more or less super hearing – they could hear out into the world, not unlike a spider does, which uses its web in a hearing sort of way," Goldsworthy explains.
Conversely, people with normal hearing could use it to control, and protect, the output volume in their ears, such as at a concert, notes Goldsworthy. He is waiting for Google and Facebook to make the architecture available to develop the idea further.
Listen2Future, a multi-million-euro EU and industry-funded three-year research project that started this year, hopes to make hearing aids from piezoelectric MEMS microphone technology. The project will consider how to develop materials, manufacturing processes and software for the scandium-based technology which could provide dramatic improvements.
"This technology can bring cheaper, smaller, more robust, less power-hungry hearing aids that can help deliver over-the-counter devices," says project lead Dr Andreja Rojko, from Infineon Technologies Austria.
Dr Nick Gompertz, a former NHS doctor, worked with researchers at the University of Bath to develop the Earswitch – an earphone device equipped with a camera and sensors that can monitor the voluntary movement of the tensor tympani, a strap-like muscle in the middle ear that dampens the sound produced by chewing.
People with brainstem stroke or certain neurological conditions such as ALS or MND may retain the ability to control this muscle, so could use the device to operate a special keyboard, much like Stephen Hawking did with a twitch of his cheek.
After receiving a £1.5m grant from the National Institute for Health and Care Research, Earswitch plans to have a Class One medical device available by mid-2024. The company is also seeking grant funding to progress EarControl, an eye and gaze-tracking device associated with the ear.
"Many things can be achieved with a simple switch; we're providing an interface, similar to a mouse, that other people can do exciting stuff with, such as developing complex controls," says Gompertz.
