What Do the Lunatic Fringe, a Cheap Date, Groucho Marx, and the Sonic Hedgehog Have in Common?

By Yishane Lee

At a presentation Hearing Restoration Project scientist Neil Segil, Ph.D., made to a small audience at the HHF offices earlier this year, I was surprised (and delighted) to learn that a gene had the name of Lunatic Fringe—which is not to be confused with the Manic Fringe or the Radical Fringe. Dr. Segil mentioned the gene because it can affect the Notch signaling pathway, a form of cell communication that creates mosaic patterns of different cell types, like the kind we see in the inner ear for hearing. I wondered, how did the gene get this name?

The privilege for people who discover things is that they get to name it—be it a star, mountain, or gene. And the scientists who worked on genetically mapping the fruit fly, which has been studied for over a century, have a sense of humor.

Besides the fringe genes, there are these fruit fly genes that have been found or created: the Tinman refers to a gene that makes it hard to develop a heart; the Groucho Marx refers to a gene that produces excess facial bristles; the Cheap Date gene means the fruit fly is extra-sensitive to alcohol; the Ken and Barbie fruit fly lacks genitalia; and fruit flies with the I’m Not Dead Yet (INDY) gene live longer than usual. (See a list of funny fruit fly gene names.)

The problem, though, is that we discover we actually share quite a lot of ancestry—and therefore, genes—with the fruit fly, including those that cause hereditary diseases, telling a patient that he has a genetic condition related to a mutation in the Lunatic Fringe gene is not going to, well, fly. (Two faulty copies of the Lunatic Fringe gene, which encodes the development of the limbs and other parts of the body, leads to spinal defect known as spondylocostal dysostosis.)

So while these catchy names and the conditions they refer to are easy to remember, a few years ago the Human Genome Organization (HUGO) gene naming committee was petitioned to change them. And, faster than you can say Sonic Hedgehog (another gene name that was changed), the Lunatic Fringe—at least officially—became the LNFG.

Read more about genes related to hearing loss, including the HRP’s use of next-generation DNA sequencing.

Tell us what your favorite gene name is here in the comments!

Ears: The New Fingerprints?

By Tara Guastella

All ears are the same, right? Wrong.

Ears are actually unique to each and every person, so much so that they are comparable in uniqueness to the fingerprint. Research has even suggested that ears may be a more effective identification tool than a fingerprint through the use of a new “image ray transform” technology. This technology shines beams of light on the tubular features of the outer ear, creating an image from the way light reflects off the ear’s curves.

What makes the ear so unique? One’s ears are fully formed at birth and age gracefully over time, making them an ideal body part to confirm identity. Fingerprints can change due to the development of calluses from repeated labor which can make them less reliable.

In almost every crime scene TV drama, you’re likely to see characters dusting for fingerprints. When we will see them dusting for earprints? Well, I guess it’s a lot less likely that your average criminal is pressing an ear against an object while committing a crime. Yet in 1998, the first murder conviction on the basis of ear identification occurred in England. The convicted suspect pressed his ear up against a newly washed window in the house (where the murder took place) to listen for movement.

Airports also regularly use biometric facial recognition programs in their security programs. The addition of earprints to this type of security could also prove a valuable way to identify travelers as well as any potential threats.

Earprints come with limitations when it comes to identification, however. Ears can be altered in shape through plastic surgery or from an accident. Wearing earrings or eyeglasses or having hair pushed behind the ear can also alter the shape of an earprint.

While an earprint will likely will not substitute the fingerprint in terms of identification capability, it could be a valuable addition for solving mysteries, saving lives, and likely many other uses.

Do Chickens Hold the Key to a Cure for Hearing Loss?

Chickens have the amazing ability to restore their own hearing, and this trait is inspiring a nonprofit organization in their search for a cure for hearing loss in humans.

The Hearing Health Foundation’s “Chirp the News” video features the group’s new mascot: a baby chick. Locked within the ears of this chick is the potential to restore hearing and cure tinnitus, or ringing in the ears. According to the National Institute on Deafness and Other Communication Disorders, about 36 million adults in the U.S. have some form of hearing loss, and 25 million are affected by tinnitus.

“As someone who lives with hearing loss every day, I am personally thrilled with the prospects for a cure,” said Shari Eberts, chairman of the Hearing Health Foundation’s Board of Directors, in an email to Healthline. “Life with hearing loss can be frustrating. Sometimes you miss the joke when everyone else is laughing, and sometimes you miss important information because you don't hear it. Supportive family and friends can make living with hearing loss easier, but a genuine cure would be life changing.” 

The Chicken’s Magic Ears

The secret to the chicken’s auditory magic is that supporting cells in its inner ear can replace hair cells that have been damaged by loud noises or other causes.

And chickens aren’t the only animals that can restore their own damaged hearing. All vertebrates other than mammals can do the same. And preliminary research has shown that mice can regain some of their hearing using supporting cells that turn into hair cells—in the lab, at least. 

Researchers supported by the Hearing Health Foundation hope to find a way to coax the supporting cells in the inner ears of people to transform into functional hair cells. Their goal is to have a cure within a decade.

The 10-Year Road to a Cure

For people with hearing loss, waiting a decade for a cure can seem like a lifetime. But in the world of research, this is a very short time to travel from initial scientific discoveries all the way to successful clinical trials in humans.

To speed the research along, the Hearing Health Foundation is supporting a collaboration known as the Hearing Restoration Project (HRP) that involves researchers from more than ten institutions, including Harvard Medical School.

To find a successful cure for hearing loss, researchers have plenty o work ahead of them—including identifying how supporting cells in the chicken's ear turn into hair cells, as well as finding potential compounds or drugs that can make this happen in people.

Eberts is optimistic that the project will hit its mark, and so is Ed Rubel, a professor of hearing science at the University of Washington and a member of the project team.

“With sufficient funding,” he says, “the consortium can discover effective pathways and hopefully some lead compounds to promote hair cell regeneration in the mammalian inner ear in the 10-year time frame.”

Many Eggs in Many Baskets

In his lab at the University of Washington, Rubel is working on one piece of the puzzle that may one day lead to hair cell regeneration in people. 

“The project on my own has to do with developing a new mouse model to test the pathways and, eventually, the drugs that come out of the HRP,” he said.

The mice developed in his laboratory will be shared among members of the consortium, so they can avoid having to develop their own mice. This kind of sharing is an important aspect of the collaboration, something that Eberts expects will save time and money.

For Rubel, working with the HRP has other benefits.

“The wonderful thing about the consortium,” he says, “is that it includes only people who really want to play in that kind of sandbox—that want to share information, share early-stage information, share the other things that they’re doing in their laboratories, and work together.”

As a person with hearing loss, Eberts supports the push to highlight the project's potential.

“Even though we are in the early stages of the research, we think it is very important that the public learn about our efforts,” she said. “We want them to know that there is hope for a cure and that there are researchers who consider curing hearing loss and tinnitus to be their life’s most important work.”

This article was repurposed with permission from Healthline.

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.