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As printed in Hearing Health, volume 19:1, Spring 2003


Compiled by Karyn Butts, Managing Editor

In hearing research, there is an impressive and dynamic chain of
action that stretches over 2,500 years, from Pythagoras' assertion
that sound is a vibration in the air to present-day studies of our
most complex biological systems. The resulting ac***ulation of
knowledge has revolutionized our understanding of the ear and our
ability to treat hearing loss and other ear disorders.

Many of the most profound and relevant of these breakthroughs occurred
during the last five decades in the areas of anatomy and physiology,
cochlear and neural function and genetics. Drawing from these new
insights, doctors proceeded to develop surgical techniques that can
overcome most forms of conductive hearing loss, engineers to create
increasingly sophisticated hearing technology and scientists to
identify genes responsible for deafness.

The momentum continues as the scientific community and its supporters
rally around the hope of finding ways to reverse sensorineural hearing
loss, treat genetic causes and discover the very sites and specifics
of the auditory role of the brain. The possibilities are breathtaking
but the gains of the past leave us poised for the revolutionary
discoveries of tomorrow. Following is a look at where hearing science
has been and is now plus a glimpse at where it may lead.

The 1950s: Money, temporal bone pathology and the transistor
In the early 1950s, Colette Ramsey Baker lost her hearing due to
otosclerosis, the buildup of bone in the middle ear. At the time,
doctors knew little about this condition and hearing in general, a
frustrating fact that inspired her to establish the Deafness Research
Foundation (DRF), one of the first organizations to provide financial
resources dedicated to unraveling the mysteries of hearing loss.

The earliest funding from DRF, combined with support from other
emerging revenue sources, enabled scientists to focus their
investigations on the temporal bone, the temple region of the skull
that houses a major portion of the human auditory system. Their
findings had far-reaching implications, giving rise to treatment
methods still in use today.

Among the greatest contributors to the understanding of temporal bone
pathology was Harold Schuknecht, M.D. His microscopic study of
temporal bones, acquired posthumously from individuals with
well-do***ented auditory disorders, revealed mysterious causes of
presbycusis (age-related hearing loss), temporal bone infections and
otosclerosis.

Surgical procedures to treat these conditions were developed and
refined as a direct result of the work of Schuknecht and his
contemporaries. Foremost is the stapedectomy, the replacement of a
middle ear bone (the stapes) when it is immobilized by otosclerosis
and no longer vibrates in response to sound waves. While we take this
surgery for granted today, this was an incredible breakthrough for
people who otherwise faced living with permanent conductive hearing
loss.

In 1960, several clinics, research institutions, individual doctors
and funding organizations, DRF among them, collaborated to create the
National Temporal Bone Banks Program to encourage temporal bone
donations and conserve existing collections of temporal specimens. The
development of a national registry increased researchers' access to
more samples for their studies.

Meanwhile, hearing-impaired consumers were among the initial
beneficiaries of the electronic revolution. In fact, hearing
instruments – not radios – were the first commercial products to
utilize the transistor after its invention in 1947. These new
semiconductor hearing aids were more powerful and smaller than their
predecessors. Further progress brought behind-the-ear models to the
marketplace by the mid-1960s.

Ever since, one device improvement after another significantly
increases the capabilities of hearing aids to help consumers manage
their hearing loss. Among the advances: miniaturized components,
changes in battery size and power, improved circuitry, custom
programming for individual needs, digital signaling and
multidirectional microphones. There seems no end to innovative hearing
technology.

The 1960s and 1970s: A Nobel laureate, cochlear function and newborn
hearing screening
The chain of action in hearing research next propelled the field from
intense study of the physical aspects of the auditory system and the
ear to inquiries into the function of the cochlea. In 1961, the Nobel
Institute honored Georg von Békésy, Ph.D., with the prize in Medicine
and Physiology for his 1928 discovery of the mechanics of the standing
waves in the cochlea. Central to his pioneering work was the
development of nondestructive techniques for cochlear dissection and
the creation of a mechanical model of the inner ear. Together they led
to his most important revelations: how sound travels within the inner
ear and how specific discrete areas of the cochlea are stimulated,
important for tuning and pitch perception.

Von Békésy's seminal accomplishments eventually led to further
discoveries about cochlear function. In 1978, David Kemp, Ph.D., found
that in the process of receiving sound, our ears also emit sounds.
Called otoacoustic emissions (OAEs), they can be detected with a
sensitive microphone placed in the ear c**** of a hearing person.
Kemp's startling discovery of these automatic physiological responses
led to the development of equipment that can objectively test hearing,
even in newborns, because absence of OAEs usually indicates hearing
loss.

Knowing within days of birth if a child can hear allows parents,
educators and healthcare professionals to make sure that a child
starts life with the necessary tools and services for language
acquisition. This is a monumental improvement over previous decades
when a child's hearing loss was left undetected for the critical early
developmental years.

The 1980s and 1990s: Hair cells, cochlear implants and federal funding
Scientists soon turned their attention to discovering the source of
the recently identified OAE phenomenon. A singular breakthrough came
in 1985 when William Brownell, Ph.D., noticed that the hair cells that
line the outer areas of the cochlea change shape in response to sound
or electrical stimulation. Beyond providing a plausible explanation of
OAEs, thought to result from this motion, his work provided the first
indication that the ear is not a passive organ but that healthy outer
hair cells actively amplify sound. Many other teams of researchers
have gone on to identify other properties and functions of hair cells
but Brownell's discovery represented a paradigm shift in our
understanding and study of the ear and hearing.

Growing knowledge of the cochlea and how it transmits sound to the
brain boosted efforts in the technological arena. William House, M.D.,
and other leading researchers, alongside teams of engineers, surgeons,
audiologists and speech-therapists, continued work begun in the 1950s
on a fascinating biomedical device: the cochlear implant (CI).

The CI is a tiny surgically implanted device that bypasses damaged
areas of the cochlea and creates electrical impulses the brain
interprets as sound. Its amazing capabilities became apparent through
clinical trials that began in 1973 and led to approval for use in
adults in the 1980s. As of 2002, the U.S. Food and Drug Administration
estimates that 59,000 people throughout the world have CIs, concrete
evidence of the effect of this "medical miracle" for people who are
deaf or have severe-to-profound hearing loss.

The success of implant technology aside, much is still unknown about
the cochlea. Researchers are involved in ongoing investigations on how
hair cell damage occurs and how it can be prevented. It was always
assumed that hair cells and nerve cells were produced only during
embryonic development. That meant that our hair cells must survive
without replenishment for an entire lifetime.

Then in a burst of discovery in the mid-1980s, three separate groups
of scientists, led respectively by Jeffrey Corwin, Ph.D., Douglas
Cotanche, Ph.D., and Edwin Rubel, Ph.D., found that certain sharks and
birds grow new hair cells after severe damage from exposure to noise
or ototoxic drugs. This major revelation ignited the field's
collective curiosity.

A surge of studies began in an attempt to identify what factors
control or stimulate hair cell regeneration and whether they are
present in mammals. Some teams even began considering how to develop
specialized cells that could be implanted into a damaged cochlea and
influenced to become new hair cells.

The eventual goal? That hair cell regeneration research will open a
door to mitigating and possibly repairing hair cell loss, creating a
biological cochlear replacement.

Yet another kind of revolutionary shift occurred in 1988 when Congress
established the National Institute on Deafness and Other Communication
Disorders (NIDCD) within the National Institutes of Health (NIH) and
appropriated billions of dollars to fund research on hearing loss and
human communication. The authorization of this new federal entity
represented a commitment to progress in hearing research and increased
the pool of available resources to the field.

The 21st Century: Genetics and the brain
Still dynamic and seemingly irrepressible, the chain of action that
started with early anatomical and physiological studies of the ear has
reached a point where scientists are better equipped than ever before
to look at the human body's most complex systems: the genome and the
brain.

Research into the genetic causes of hearing loss has been underway for
many years. Experts believe, however, that recent efforts to sequence
the human genome and define all the genes and ultimately proteins,
that control our whole body will rapidly accelerate progress and lead
to exciting breakthroughs.

For a few decades, investigators have known about several genetic
mutations responsible for certain types of syndromic deafness, a
condition where deafness is not the only symptom (e.g., Waardenburg
syndrome or Usher syndrome). When a mutation exists, a person's hair
cells do not function properly, causing hearing loss.

1997 marked the first time researchers identified a mutation
underlying sensorineural deafness unaccompanied by other symptoms. The
gene, connexin 26, is named after the proteins associated with it that
play an important role in activating hair cells. Identifying connexin
26 is a big first step toward developing any kind of therapy or drug
that could overcome mutations and consequent deafness.

Even though such interventions are far down the road, patients
presently benefit from improved genetic counseling based on emerging
knowledge of connexin 26 and other mutations. It is important to keep
in mind, however, that there are numerous other genes that also
control the development of the inner ear. Indeed, we can now estimate
that over 100 genes are related to deafness and hearing loss and to
date, more than 30 of these have been identified.

Clearly, there is a lot of work to be done in this area. The future of
genetic research holds promises we cannot yet imagine and, at the same
time, raises sensitive questions about the ethics of potential
therapies that could allow us to genetically change a fetus so that it
would not have hearing loss.

Another complex area in hearing science, one that also could yield
future treatment options, is exploring the workings of the brain's
auditory cortex and the role of the central nervous system in our
hearing or inability to hear. To be sure, while the ear detects
sounds, it is the brain that "hears" through electrochemical energy
passed from the cochlea through the brainstem and into the auditory
cortex where perception takes place.

A major breakthrough in studying the brain came in the late 1980s and
early 1990s when two types of functional brain imaging were developed.
In contrast to the familiar MRI and CT scans that provide a static
anatomic view of the brain's physical appearance, functional imaging
allows us to assess processes of the brain as it works.

Positron emission tomography (PET) scans utilize a radioactive tracer
in the bloodstream and special equipment to track the location and
rate of blood flow in the brain during different types of stimulation.
In 1998, Alan Lockwood, M.D., used this technique to identify specific
sites in the brain that may be associated with tinnitus.

His study involved patients able to control their tinnitus by
clenching their jaw. Using PET scans, the research team monitored the
subject's blood flow while they tightened and relaxed their jaws.
Lockwood's results tracked the possible origin of tinnitus to sites in
the temporal lobe opposite of the affected ear and also showed that
the hippocampus, the part of the brain responsible for emotions, was
activated in tinnitus patients but not in control subjects. This may
indicate a possible source of the negative psychological symptoms many
tinnitus patients describe.

On the heels of PET scans, Segeii Ogawa, Ph.D., of Bell Laboratories
developed functional magnetic resonance imaging (fMRI) revolutionizing
the way we study the brain. Functional MRI also tracks blood flow but
does so without injecting a patient with a radioactive tracer. Unlike
PET scanning, a person can undergo repeated fMRIs without apparent
risk. This is important to investigators who often rely upon
replication for accurate results.

Multidisciplinary teams currently use both PET and fMRI scans to study
a wide range of hearing-related issues including language acquisition,
tinnitus, central auditory processing disorder and presbycusis. We
have more clues than ever as to the differences between learning a
visual language like American Sign Language and a spoken language, how
the age-related changes in the auditory cortex make make speech
comprehension more difficult and what causes central auditory
processing disorder.

Though we have only scratched the surface of comprehending the ways
the brain processes and interprets sound and language, the future may
provide breakthroughs in identifying and manipulating chemicals in the
brain to treat conditions like tinnitus and presbycusis at the source.

Our tour through the past fifty years of research reveals several
conclusions. First, each of the discoveries touched upon here are
distinct links in an intricate chain of action that continues to
propel science toward even more refined knowledge.

Next, none of these discoveries were achieved in isolation. Pioneers
credited along the way relied on collegial collaboration and financial
support that enabled them to carry out their investigations.

Finally, this era of rapid progress made reminds us of the importance
of hearing. We study this sense because it is a major part of how we
communicate and interact with the world around us.

It is no exaggeration to say that the future of hearing research is
limitless. Dedicated scientists, engineers and clinicians will
continue to pursue every piece of the puzzle. Their curiosity and
imagination can be thwarted only by lack of support.

It is our national responsibility to ensure that momentum continues
and that findings in the laboratories and in clinical trials translate
into real-life applications. This is essential for an improved quality
of life for not only the millions of Americans who have hearing loss
and their significant others but also for people worldwide and future
generations. Scientific research is key to achieving the dream of a
lifetime of healthy hearing for all.

Contributors to this piece include: George Gates, M.D., Mychelle
Balthazard, M.P.H., Douglas Cotanche, Ph.D., and Elizabeth Keithley,
Ph.D.

tailspin

Thank you for sharing this fascinating article.

I have been told to start thinking real hard about a cochlear implant. I
keep holding on to the hope that some how, some way there will be a means to
reverse my hearing loss. Realistically, I doubt that it will happen in my
lifetime.

Nixon promised to cure cancer back in the 70's. We are closer but we have a
long, long way to go yet. I fear this may be the case with curing or
reversing hearing loss. I hope I am wrong.

Good luck to all of us.