The beautiful, mysterious science of how you hear | Jim Hudspeth

106,566 views ・ 2020-04-15

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Transcriber: Joseph Geni Reviewer: Camille MartΓ­nez
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Can you hear me OK?
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Audience: Yes.
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Jim Hudspeth: OK. Well, if you can, it's really amazing,
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because my voice is changing the air pressure where you sit
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by just a few billionths of the atmospheric level,
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yet we take it for granted
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that your ears can capture that infinitesimal signal
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and use it to signal to the brain the full range of auditory experiences:
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the human voice, music, the natural world.
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How does your ear do that?
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And the answer to that is:
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through the cells that are the real hero of this presentation --
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the ear's sensory receptors,
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which are called "hair cells."
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Now, these hair cells are unfortunately named,
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because they have nothing at all to do with the kind of hair
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of which I have less and less.
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These cells were originally named that by early microscopists,
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who noticed that emanating from one end of the cell
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was a little cluster of bristles.
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With modern electron microscopy, we can see much better
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the nature of the special feature that gives the hair cell its name.
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That's the hair bundle.
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It's this cluster of 20 to several hundred fine cylindrical rods
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that stand upright at the top end of the cell.
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And this apparatus is what is responsible for your hearing me right this instant.
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Now, I must say that I am somewhat in love with these cells.
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I've spent 45 years in their company --
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(Laughter)
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and part of the reason is that they're really beautiful.
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There's an aesthetic component to it.
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Here, for example, are the cells
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with which an ordinary chicken conducts its hearing.
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These are the cells that a bat uses for its sonar.
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We use these large hair cells from a frog for many of our experiments.
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Hair cells are found all the way down to the most primitive of fishes,
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and those of reptiles often have this really beautiful,
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almost crystalline, order.
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But above and beyond its beauty,
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the hair bundle is an antenna.
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It's a machine for converting sound vibrations into electrical responses
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that the brain can then interpret.
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At the top of each hair bundle, as you can see in this image,
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there's a fine filament connecting each of the little hairs,
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the stereocilia.
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It's here marked with a little red triangle.
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And this filament has at its base a couple of ion channels,
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which are proteins that span the membrane.
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And here's how it works.
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This rat trap represents an ion channel.
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It has a pore that passes potassium ions and calcium ions.
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It has a little molecular gate that can be open, or it can be closed.
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And its status is set by this elastic band which represents that protein filament.
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Now, imagine that this arm represents one stereocilium
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and this arm represents the adjacent, shorter one
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with the elastic band between them.
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When sound energy impinges upon the hair bundle,
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it pushes it in the direction towards its taller edge.
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The sliding of the stereocilia puts tension in the link
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until the channels open and ions rush into the cell.
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When the hair bundle is pushed in the opposite direction,
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the channels close.
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And, most importantly,
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a back-and-forth motion of the hair bundle,
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as ensues during the application of acoustic waves,
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alternately opens and closes the channel,
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and each opening admits millions and millions of ions into the cell.
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Those ions constitute an electrical current
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that excites the cell.
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The excitation is passed to a nerve fiber,
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and then propagates into the brain.
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Notice that the intensity of the sound
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is represented by the magnitude of this response.
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A louder sound pushes the hair bundle farther,
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opens the channel longer,
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lets more ions in
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and gives rise to a bigger response.
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Now, this mode of operation has the advantage of great speed.
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Some of our senses, such as vision,
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use chemical reactions that take time.
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And as a consequence of that,
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if I show you a series of pictures at intervals of 20 or 30 per second,
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you get the sense of a continuous image.
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Because it doesn't use reactions,
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the hair cell is fully 1,000 times faster than our other senses.
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We can hear sounds at frequencies as great as 20,000 cycles per second,
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and some animals have ever faster ears.
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The ears of bats and whales, for example, can respond to their sonar pulses
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at 150,000 cycles a second.
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But this speed doesn't entirely explain why the ear performs so well.
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And it turns out that our hearing benefits from an amplifier,
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something called the "active process."
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The active process enhances our hearing
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and makes possible all the remarkable features that I've already mentioned.
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Let me tell you how it works.
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First of all, the active process amplifies sound,
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so you can hear, at threshold, sounds that move the hair bundle
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by a distance of only about three-tenths of a nanometer.
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That's the diameter of one water molecule.
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It's really astonishing.
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The system can also operate
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over an enormously wide dynamic range.
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Why do we need this amplification?
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The amplification, in ancient times, was useful
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because it was valuable for us to hear the tiger before the tiger could hear us.
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And these days, it's essential as a distant early warning system.
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It's valuable to be able to hear fire alarms
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or contemporary dangerous such as speeding fire engines or police cars or the like.
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When the amplification fails, our hearing's sensitivity plummets,
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and an individual may then need an electronic hearing aid
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to supplant the damaged biological one.
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This active process also enhances our frequency selectivity.
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Even an untrained individual can distinguish two tones
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that differ by only two-tenths of a percent,
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which is one-thirtieth of the difference between two piano notes,
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and a trained musician can do even better.
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This fine discrimination is useful
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in our ability to distinguish different voices
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and to understand the nuances of speech.
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And, again, if the active process deteriorates,
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it becomes harder to carry out verbal communication.
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Finally, the active process is valuable in setting the very broad range
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of sound intensities that our ears can tolerate,
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from the very faintest sound that you can hear, such as a dropped pen,
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to the loudest sound that you can stand --
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say, a jackhammer or a jet plane.
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The amplitude of sounds spans a range of one millionfold,
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which is more than is encompassed by any other sense
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or by any man-made device of which I'm aware.
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And again, if this system deteriorates,
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an affected individual may have a hard time
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hearing the very faintest sounds
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or tolerating the very loudest ones.
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Now, to understand how the hair cell does its thing,
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one has to situate it within its environment within the ear.
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We learn in school that the organ of hearing
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is the coiled, snail-shaped cochlea.
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It's an organ about the size of a chickpea.
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It's embedded in the bone on either side of the skull.
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We also learn that an optical prism
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can separate white light into its constituent frequencies,
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which we see as distinct colors.
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In an analogous way,
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the cochlea acts as sort of an acoustic prism
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that splits apart complex sounds into their component frequencies.
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So when a piano is sounded,
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different notes blend together into a chord.
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The cochlea undoes that process.
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It separates them and represents each at a different position.
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In this picture, you can see where three notes --
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middle C and the two extreme notes on a piano --
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are represented in the cochlea.
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The lowest frequencies go all the way up to the top of the cochlea.
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The highest frequencies, down to 20,000 Hz,
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go all the way to the bottom of the cochlea,
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and every other frequency is represented somewhere in between.
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And, as this diagram shows,
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successive musical tones are represented a few tens of hair cells apart
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along the cochlear surface.
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Now, this separation of frequencies
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is really key in our ability to identify different sounds,
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because very musical instrument,
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every voice,
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emits a distinct constellation of tones.
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The cochlea separates those frequencies,
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and the 16,000 hair cells then report to the brain
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how much of each frequency is present.
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The brain can then compare all the nerve signals
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and decide what particular tone is being heard.
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But this doesn't explain everything that I want to explain.
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Where's the magic?
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I told you already about the great things that the hair cell can do.
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How does it carry out the active process
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and do all the remarkable features that I mentioned at the outset?
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The answer is instability.
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We used to think that the hair bundle was a passive object,
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it just sat there, except when it was stimulated.
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But in fact, it's an active machine.
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It's constantly using internal energy to do mechanical work
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and enhance our hearing.
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So even at rest, in the absence of any input,
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an active hair bundle is constantly trembling.
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It's constantly twitching back and forth.
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But when even a weak sound is applied to it,
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it latches on to that sound and begins to move very neatly
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in a one-to-one way with it,
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and by so doing, it amplifies the signal about a thousand times.
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This same instability also enhances our frequency selectivity,
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for a given hair cell tends to oscillate best
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at the frequency at which it normally trembles
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when it's not being stimulated.
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So, this apparatus not only gives us our remarkably acute hearing,
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but also gives us the very sharp tuning.
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I want to offer you a short demonstration
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of something related to this.
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I'll ask the people who are running the sound system
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to turn up its sensitivity at one specific frequency.
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So just as a hair cell is tuned to one frequency,
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the amplifier will now enhance a particular frequency in my voice.
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Notice how specific tones emerge more clearly from the background.
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This is exactly what hair cells do.
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Each hair cell amplifies and reports one specific frequency
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and ignores all the others.
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And the whole set of hair cells, as a group, can then report to the brain
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exactly what frequencies are present in a given sound,
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and the brain can determine what melody is being heard
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or what speech is being intended.
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Now, an amplifier such as the public address system
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can also cause problems.
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If the amplification is turned up too far,
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it goes unstable and begins to howl
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or emit sounds.
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And one wonders why the active process doesn't do the same thing.
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Why don't our ears beam out sounds?
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And the answer is that they do.
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In a suitably quiet environment, 70 percent of normal people
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will have one or more sounds coming out of their ears.
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(Laughter)
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I'll give you an example of this.
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You will hear two emissions at high frequencies
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coming from a normal human ear.
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You may also be able to discern background noise,
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like the microphone's hiss,
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the gurgling of a stomach, the heartbeat, the rustling of clothes.
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(Hums, microphone hiss, dampened taps, clothes rustling)
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This is typical.
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Most ears emit just a handful of tones,
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but some can emit as many as 30.
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Every ear is unique, so my right ear is different from my left,
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my ear is different from your ear,
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but unless an ear is damaged,
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it continues to emit the same spectrum of frequencies
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over a period of years or even decades.
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So what's going on?
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It turns out that the ear can control its own sensitivity,
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its own amplification.
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So if you're in a very loud environment, like a sporting event
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or a musical concert,
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you don't need any amplification,
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and the system is turned down all the way.
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If you are in a room like this auditorium,
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you might have a little bit of amplification,
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but of course the public address system does most of the work for you.
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And finally, if you go into a really quiet room
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where you can hear a pin drop,
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the system is turned up almost all the way.
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But if you go into an ultraquiet room such as a sound chamber,
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the system turns itself up to 11,
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it goes unstable
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and it begins to emit sound.
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And these emissions constitute a really strong demonstration
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of just how active the hair cell can be.
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So in the last minute, I want to turn to another question that might come up,
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which is: Where do we go from here?
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And I would say that there are three issues
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that I would really like to address in the future.
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The first is: What is the molecular motor
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that's responsible for the hair cell's amplification?
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Somehow, nature has stumbled across a system
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that can oscillate or amplify at 20,000 cycles per second,
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or even more.
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That's much faster than any other biological oscillation,
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and we would like to understand where it comes from.
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The second issue is how the hair cell's amplification is adjusted
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to deal with the acoustic circumstances.
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Who turns the knob to increase or decrease the amplification
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in a quiet or in a loud environment?
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And the third issue is one that concerns all of us,
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which is what we can do about the deterioration of our hearing.
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Thirty million Americans,
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and more than 400 million people worldwide,
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have significant problems on a daily basis
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with understanding speech in a noisy environment
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or over the telephone.
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Many have even worse deficits.
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Moreover, these deficits tend to get worse with time,
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because when human hair cells die,
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they're not replaced by cell division.
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But we know that nonmammalian animals can replace their cells,
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and those creatures' cells are dying and being replaced throughout life,
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so the animals maintain normal hearing.
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Here's an example from a little zebra fish.
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The cell at the top will undergo a division
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to produce two new hair cells.
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They dance for a little bit,
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and then settle down and go to work.
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So we believe that if we can decode the molecular signals that are used
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by these other animals to regenerate their hair cells,
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we'll be able to do the same thing for humans.
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And our group and many other groups are now engaged in research
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trying to resurrect these amazing hair cells.
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Thank you for your attention.
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(Applause)
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