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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 accumulation 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-documented 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 canal
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 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. cientific 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.
Related article:
The Scientific
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