You Can Hear, Thanks to the Darwin Fish

By Tara Guastella

Photo by lapradei/Flickr

I never thought that fish would be an evolutionary ancestor to humans. Monkeys and chimpanzees, yes—but fish?

It turns out that a certain fish, known as Polypterus and related species, have tiny holes in the top of their head called spiracles. A team of researchers in California recently showed how a small valve opens a bony lid over these spiracles that allows air to be sucked in and pumped out when the fish surface.

Strangely enough those same holes allowing the fish to breathe have modified themselves over time to become Eustachian tubes. Enabling us to hear, these tubes are small passageways on either side of the head that connect the upper part of the throat to the middle ear. They supply fresh air, drain fluid, and keep air pressure between the nose and the ear at a steady level.

Hearing in early amphibians developed from the spiracles adapting to become the tympanic membrane (also known as the eardrum), a thin cone-shaped membrane that separates the external ear from the middle ear. The tympanic membrane is similar to skin and transmits sound to the brain through the stapes, the tiniest bone in the body.

Interestingly, the stapes evolved from a long bone, known as the hyomandibular bone, that braced the lower jaws of sharks and other early jawed fish. This bone eventually shrank in size to form the stapes.

The other two inner ear bones alongside the stapes—the malleus and the incus—also formed from bones that braced the articulation of the upper and lower jaws. These bones decreased in size and became restricted to the inner ear. So, these three little bones that enable us to hear derived from the larger jaw bones of ancient fish.

If not for the evolutionary experiments of these prehistoric fish breathing air through the top of their heads, humans may never have evolved a keen sense of hearing.

Now that you know how our hearing evolved, learn more about how hearing works and how the human ear processes sound. Watch our captioned How Hearing Works video.

How Can a Chicken Cure Hearing Loss & Tinnitus? Find out in our new PSA!

By Tara Guastella

I’m so excited to share that we have recently launched a new Public Service Announcement (PSA): Chirp the News! The PSA introduces HHF’s new mascot, a baby chicken.

Why a baby chicken?

The key to restoring hearing in humans is to regenerate cells deep within the inner ear. In fact, most types of hearing loss in humans results from damage to these cells, called hair cells. While humans cannot regenerate hair cells in the inner ear after they are damaged, chickens can. In fact, most animals other than mammals can regenerate these delicate cells, restoring their hearing spontaneously after damage.

This knowledge is the basis for our Hearing Restoration Project (HRP). The HRP is a consortium of over a dozen top scientists from across the world working collaboratively to take what we know happens in chickens and translate that to people. Our HRP scientists estimate clinical trials testing a genuine, biologic cure for hearing loss can occur within the next decade. Since over 90 percent of tinnitus cases occur with an underlying hearing loss, a cure for hearing loss is also likely the key to a cure for tinnitus.

Most scientific research is conducted in isolation: one researcher or one lab trying to solve a major health issue. Our unique HRP consortium model is breaking the mold by encouraging our scientists to work as a team sharing data, tools, resources, and ideas. By working collaboratively, the timeline to a cure is expedited: five times as fast with the power of collaboration.

We won’t be able to get to a cure for hearing loss and tinnitus without your help—please donate today and be a part of the cure.

Innovative Science Meets Innovative Technology

By Yishane Lee

This month our own Tara Guastella was interviewed for a piece on the blog for Exponent Partners. Exponent Partners is HHF’s technology partner who implemented our new online grants management system called Foundation Connect in mid- to late 2012. Foundation Connect has greatly increased HHF’s efficiency, transparency, and accountability, allowing us to match our innovative hearing research with innovative grants management.

In the interview, Tara speaks about HHF’s mission and research efforts, highlighting why hearing research affects everyone and how the new system has benefitted HHF:

HHF’s mission is to prevent and cure hearing loss and tinnitus through groundbreaking research. Our HRP researchers are specifically studying regrowth of the tiny sensory cells inside everyone’s ears, called hair cells, which allow us to hear. Every time we damage them with exposure to loud noise, or the cells are otherwise destroyed—such as by certain drugs or simply aging—we are at risk for hearing loss.

Normally, in humans, these cells do not grow back. However, researchers funded by HHF have found promising leads in the hair cells of chickens, which naturally regrow. The research suggests that regeneration of these cells could be induced in mammals. This would combat one of the most widespread forms of acquired hearing loss. It is estimated that 10 percent of Americans between the ages of 20 and 69 may have suffered hearing loss from noise exposure.

This type of loss is also highly associated with tinnitus, or ringing in the ears, found in 90 percent of tinnitus cases. Researchers are hopeful that once hearing is restored, tinnitus will similarly be alleviated. This would bring great benefit to the nearly 50 million Americans who experience hearing loss or tinnitus, including one in five teens and 60 percent of recently returning veterans.

HHF funds not only this research toward a cure but also many other hearing topic areas, including auditory processing disorders, genetic hearing loss, and the vestibular (balance) system, to name a few.

“Fifty years ago, restoring hearing to a person with hearing loss seemed like a dream,” Guastella said. “Since then, HHF has contributed to many of today’s current treatment options such as cochlear implants, new therapies for ear infections, and therapy for otosclerosis [an abnormal bone growth in the ear].”

Guastella noted, “When we first launched the HRP, one of our goals was to make the application and review process as easy and efficient as we could. We wanted our consortium scientists to dedicate as much time as possible to advancing the research in their labs rather than spending time applying for grants.”

The system has increased the capacity of the foundation. “We were able to process double the amount of letters of inquiry the year after we implemented the solution. We can quickly respond to inquiries about our past grantees as well,” Guastella said. “And everything is more user-friendly.” Now HHF’s internal grants administration matches the cutting-edge research they support.

Read the rest of the Exponent Partners blog post here.

What Do a Leather Pouch and a Fruit Fly Have in Common?

By Yishane Lee

What is the utricle? Merriam-Webster defines it as “a small anatomical pouch; the part of the membranous labyrinth of the inner ear into which the semicircular canals open.” But to you and me, it may help provide the solution to hair cell regeneration in the inner ear.

Like the cochlea, the utricle is located in the inner ear and it contains hair cells that are used to detect gravity (versus the sound waves that the cochlear hair cells detect). In a major step forward, Hearing Restoration Project scientist Dr. Jennifer Stone and her colleagues at the University of Washington pioneered the technique of isolating the utricle from the adult mouse and growing it in a dish in the lab.

Why is this important? It is providing for the first time the ability to directly access and experimentally manipulate hair cells and support cells in a lab setting. In other words, we can grow and do experiments on the utricle (a word derived from the Latin for leather bag). The cochlea has proven to be too delicate to isolate and grow in a dish.

As Dr. Andy Groves, Baylor College of Medicine, and an HRP colleague writes in the Winter 2014 issue of Hearing Health:

“Dr. Stone’s lab found that within a few days after hair cells are killed in the utricle, the surrounding supporting cells take the very first genetic steps to activate the program to make hair cells—but then they stop before the hair cells actually form. It is as though the supporting cells have received a signal to regenerate new hair cells, but they cannot ‘seal the deal’ and complete the regeneration program. This situation is very different from the cochlea, where absolutely no hair cell regeneration steps occur in adults.”

Drs. Grove and Stone, along with Dr. Neil Segil of the University of Southern California, are working together to figure out why regeneration takes the first steps and then stops. One area they are focusing on is the Notch signaling pathway, an evolutionarily determined method of cell communication. Notch signaling, among other things, determines the mosaic patterns of various cell types, including the mosaic that organizes the inner ear’s hair cells and supporting cells. The dysfunction of Notch signaling (a name that comes from a notch found in the wings of a fruit fly) has been linked to various cancers and diseases, and as a result it has become a focus of drug intervention.

Read about all of our HRP projects here, and stay tuned for more HRP updates throughout the year.

Royal Arch Masons Renew Investment in HHF and CAPD Research

By Tara Guastella

I am thrilled to report that for the third year HHF has received a generous gift of $100,000 from the Royal Arch Masons in support of of our 2013 Emerging Researchers studying central auditory processing disorder (CAPD).

CAPD is an umbrella term for a variety of disorders that affect the way the brain processes auditory information. The outer, middle, and inner ear of individuals who have CAPD are usually normal in structure and function (peripheral hearing). But they aren’t able to fully process the information they hear, which leads to difficulties in recognizing and interpreting sounds, especially those that compose speech. It is thought that these difficulties arise from a dysfunction in the central nervous system—the brain.

Individuals who have CAPD have difficulty concentrating when in an environment that is not perfectly quiet or has some "controlled" noise in the background. Understanding a verbal message will also be a problem when trying to listen to a speaker if someone else is talking or if ambient noise is present in the background.

People with CAPD often have to work harder than others just trying to receive auditory information in a meaningful way. It is a very frustrating situation for individuals when they can hear "perfectly" but cannot process auditory speech information in a meaningful way.

One of our Royal Arch Masons–funded researchers, Ross Maddox, Ph.D., is beginning a line of research investigating the specific behavioral effects of audio-visual binding and its processing in the brain. Behavioral tests with brain imaging will be used to investigate the importance of combining information across the visual and auditory senses, and establish relationships in brain activity and behavior, an effort that could inspire new audio-logical therapies.

For over 30 years, the Royal Arch Masons have supported CAPD research efforts, making it a priority to increase funds to this much needed area of research. We are honored that the Royal Arch Masons have chosen HHF as a recipient of this support, and we are inspired by the progress of our Royal Arch Masons–funded Emerging Researchers.

We are incredibly grateful for the continued support of the Royal Arch Masons and thank them for their annual contribution.

3 Days, 14 Scientists, 1 Goal

By Tara Guastella

From November 10 to 12, the annual meeting of the Hearing Restoration Project consortium took place in Seattle to discuss progress of their research toward a cure for hearing loss and tinnitus.  

The weekend started with a team-building outing at two of Seattle's iconic attractions: Chihuly Glass Museum and the Space Needle. The group first admired a colorful array of beautiful glass sculptures at the museum, followed by a marvelous 360-degree view of Seattle. The group then enjoyed a relaxed dinner together before the real work of the meeting was to commence.

Early Monday morning, each group of researchers began presenting their progress on the five funded HRP projects. Each of the groups presented their initial findings on the genomics of mouse, chicken, and zebrafish studies. This work helps us learn how these animals are capable of inner ear hair cell regeneration in order to identify ways to translate this to humans. Each member of the consortium contributed to the discussion on how we can compare this cross-species data, something that would not be possible without the collaborative design of the HRP.

The progress of the work on each project led to a discussion of how to update the HRP’s Strategic Research Plan to reflect what we have learned through the first year and a half of funding these HRP projects. Check back on our website for the updated plan, to be published online soon, as well as in a future issue of Hearing Health magazine.

See more meeting photos in our Facebook album.

A Tiny Frog That Hears Without an Eardrum

By Yishane Lee

An intriguing discovery in one of the world’s smallest frogs points to the power of hearing through bone conduction.

Gardiner’s Seychelles frogs, named for islands off the coast of East Africa where they are found, evolved without a middle ear or an eardrum, both of which transmit sound waves to our inner ear. Scientists had always assumed that the tiny vertebrates (which measure just 11 millimeters) could not hear at all. But the frogs croak, and animals usually create sound only in response to hearing sound.

So they must be hearing—but how?

French researchers recently discovered the answer. In an article published in the Proceedings of the National Academy of Sciences in September, they say that the frogs hear with their mouths.

The scientists first used recordings of frog sounds to verify that the frog could hear. It did: Male frogs hopped closer to the sound and croaked in response only to calls from their own species.

Then, they used X-rays to examine the frog’s anatomy. The theory that the frogs were using their lungs to capture sound vibrations was discounted when it was discovered that their lungs are too small to catch the right wavelength. (Other frogs and many fish do use their lungs to hear.) So they focused attention on the frog’s head.

After creating 3-D simulations of sound entering a frog’s skull, the researchers found that the frog’s oral cavity resonates at nearly the same frequency as its call. The frog, they found, has unusually thin layers of tissue between the mouth and inner ear meaning that, in essence, the frog’s mouth amplifies sound waves.

“Our models show how bone conduction enhanced by the resonating role of the mouth allows these seemingly deaf frogs to communicate effectively without a middle ear,” the authors wrote. “The presence of a middle ear is not a necessary condition for terrestrial hearing, despite being the most versatile solution for life on land.”

Since the Seychelles islands, located in the western Indian Ocean, are relatively isolated, hearing through the mouth may be an ancient way that animals heard, before the middle ear and eardrum evolved, they added.

Read the abstract here.

All Hail Supporting Cells

By Yishane Lee

We have the ability to hear, thanks to the sensitive hair cells located in our ears. They are called hair cells because of their hair-like shape, long and thin (resembling the hairs on your head yet having nothing to do with them). When these hair cells die or are damaged, it is permanent. And so is the resulting loss of hearing. Unlike in other species—such as birds, fish, and amphibians—in mammals including humans, once these cells die, they don’t grow back or repair themselves, which makes it even more critical to keep them alive.

Supporting cells, as their name suggests, support hair cells both structurally and nutritionally. But a new study of supporting cells in the inner ears of mice reveals yet another role—one that is hugely important for researchers working to restore hearing in mammals.

Writing in July in an online edition of the Journal of Clinical Investigation, scientists at the National Institute on Deafness and Other Communication Disorders (NIDCD), found that supporting cells can actually actively help repair damaged sensory hair cells.

Supporting cells and a chemical they produce called heat shock protein 70 (HSP70) appear to play a critical role in protecting damaged hair cells from death in the ears of mice. Senior study author Lisa Cunningham, Ph.D., said, “Our study indicates that when the inner ear is under stress, the cell that responds by generating protective proteins is not a hair cell, but a supporting cell.” Cunningham and her team are collaborating with a clinical team at the NIDCD to design a clinical trial. It will look at ways to induce the production of HSP70 in the inner ear.

Further, our Hearing Restoration Project consortium members Albert Edge, Ph.D. of Harvard Medical School, Stefan Heller, Ph.D. of Stanford University, and Elizabeth Oesterle, Ph.D. of University of Washington are trying to figure out what happens to supporting cells after hair cells die or are damaged. Their project, “Supporting Cell Fate Mapping,” has so far found that some promising news regarding supporting cells and their function. In “Making a Map,” an article in the Fall issue of Hearing Health, Dr. Oesterle writes:

“After some severe insults (damage), the nonsensory supporting cells in the [auditory] epithelium [the organ of Corti] can retain some normal cellular identity for long periods of time. This is encouraging because in non-mammals it is the supporting cells that give rise to new replacement hair cells after hair cells are lost. After various severe insults, our data suggest that the supporting cells die and neighboring cells—cells that are normally abutting the sensory epithelium—move in.”

Both recent research results show that while we still have more to learn about the roles of supporting cells, their support they provide may be crucial to the search for a cure for hearing loss and tinnitus.

Congratulations to Our Former Emerging Researchers

By Tara Guastella

The primary goal of our Emerging Research Grant (ERG) program is to prepare scientists new to hearing and balance research to earn funding through the National Institutes of Health (NIH). It is with that in mind that we are thrilled to congratulate the latest crop of ERG alumni who have received NIH support.

For the past 55 years, we have proudly provided thousands of hearing researchers with the seed funding to make it possible to compete successfully for NIH awards and further their research careers. With the tightening funding climate in Washington, it is truly a remarkable achievement to obtain these awards.

It is with great pleasure that we share:

2012 Emerging Researcher, Wei Min Chen, Ph.D., University of Virginia, received two awards from National Human Genome Research Institute (NHGRI) for work in complex genetics research identifying genetic predictors of certain diseases.

2012 Emerging Researcher, Sung Ho Huh, Ph.D., Washington University, received a National Institute on Deafness and Communication Disorders (NIDCD) award studying cellular and molecular functions of cochlear development.

2012 & 2013 Emerging Researcher, Israt Jahan, M.B.B.S, Ph.D., University of Iowa, received a NIDCD award for her work in hair cell regeneration.

2011 & 2013 Emerging Researcher, Carolyn Ojano-Dirain, Ph.D., University of Florida, received a NIDCD award for her work in aminoglycoside-induced ototoxicity.

2012 & 2013 Emerging Researcher, Lina Reiss, Ph.D., Orgeon Health & Science University, received a NIDCD award for her work in binaural hearing loss and hearing devices.

Isabelle Roux, Ph.D.

2012 Emerging Researcher, Isabelle Roux, Ph.D., Johns Hopkins University, received a NIDCD award for her research in hair cells and their interaction with nerve fibers that provide feedback from the brain to the ear.

2012 Emerging Researcher, Rebecca Seal, Ph.D., University of Pittsburgh, received two National Institute of Neurological Disorders and Stroke (NINDS) awards for work studying the central nervous system.

2009 Emerging Researcher, Ruili Xie, Ph.D., University of North Carolina, Chapel Hill, received an award from the NIDCD for research on age-related hearing loss and noise-induced hearing loss.

We congratulate these researchers for their extraordinary research efforts and look forward to learning of their progress into the future.

The Case for Genetic Testing

By Yishane Lee

Genetic causes account for roughly half of hearing loss cases in infants, according to the Centers for Disease Control and Prevention. Many cases of progressive hearing loss that occur after infancy and childhood also have a genetic component.

At least 1,000 mutations in 64 genes linked to hearing loss have been identified. Thanks to rapid advances in genetic sequencing, identifying virtually all the genetic causes of hearing loss may occur within the decade, according to a recent report in the journal Genetic Testing and Molecular Biomarkers.

Researchers are using “targeted resequencing” to locate gene mutations in certain regions in the human genome that are linked to diseases much more quickly than sequencing the entire genome. In our Fall 2013 issue of Hearing Health magazine, Xue Zhong Liu, M.D., Ph.D., reviews the advances in sequencing technology and how this will affect the future treatment of hearing loss.

Because genetics can play such a significant role in hearing loss, genetic testing can answer questions you have about the cause of your or a loved one’s hearing loss. If the testing uncovers a mutation, it can help explain the hearing loss, its severity or progression, and whether other symptoms may become apparent. For instance, a person with Usher syndrome has not only hearing loss but also eventual blindness. You can proactively take steps to manage treatment and outcome. Knowing the genetic cause of a hearing loss can also help you predict whether the condition will be passed along to your children, or whether the children of other family members may have the condition. 

Last summer, Hearing Health magazine presented an overview of genetic causes of hearing loss, including Connexin 26 disorder. This is the most common cause of congenital hearing loss not related to a syndrome (with other symptoms, such as a thyroid problem). Mutations in the GJB2 gene affect development of the cochlea in the inner ear. Everyone carries two copies of the GJB2 gene (which encodes the protein connexin 26), and the mutations are usually recessive. So, two parents with one mutation each can have normal hearing. But if their child gets two faulty copies of the gene, the child will have a hearing loss. In fact, the majority of children born with hearing loss have normal hearing parents.

There are limits to genetic testing, however. For one thing not all the genes are known—yet. Also, a positive result for a mutation does not necessarily mean a person will get the condition associated with the mutation. And a negative result doesn’t mean you won’t get the particular condition, too—it may be that a different mutation in the same gene wasn’t detected, or there could be another mutation in a different gene that may cause the condition.

We have compiled a list of several dozen genetic testing centers nationwide that have specialized testing for hearing loss. Find a testing center near you.