can you hear me okay
okay well if you can it's it's really
amazing because my voice is changing the
air pressure where you sit by just a few
billions of the atmospheric level yet we
take it for granted that your ears can
capture that infinite decimal signal and
use it to signal to the brain the full
range of auditory experiences the human
voice music the natural world how does
he do that and the answer to that is
through the cells that are the real hero
of this presentation the ears sensory
receptors which are called hair cells
now these hair cells are unfortunately
named because they have nothing at all
to do with the kind of hair of which I
have less and less these cells were
originally named that by early
microscopists who noticed that emanating
from one end of the cell was a little
cluster of bristles with modern electron
microscopy we can see much better the
nature of the special feature that gives
the hair cell its name that's the hair
bundle it's this cluster of twenty to
several hundred fine cylindrical rods
that stand upright at the top end of the
cell and this apparatus is what is
responsible for you're hearing me right
this instant
now I must say that I'm somewhat in love
with you cells
I've spent 45 years in their company
and part of the reason is they're really
beautiful there's an aesthetic component
to it here for example are the cells
with which an ordinary chicken conducts
its hearing these are the cells of a bat
uses for its sonar we use these large
hair cells from a frog for many of our
experiments hair cells are found all the
way down to the most primitive of fishes
and those of reptiles often have this
really beautiful almost crystalline
order but above and beyond its beauty
the hair bundle is an antenna
it's a machine for converting sound
vibration
into electrical responses that the brain
can then interpret at the top of each
hair bundle as you can see in this image
there's a fine filament connecting each
of the little hairs the stereocilia it's
here marked with a little red triangle
and this filament has at its base a
couple of ion channels which are
proteins that span the membrane and
here's how it works
this Rattrap represents an ion channel
it has a pore that passes potassium ions
and calcium ions it has a little
molecular gate that can be open or it
can be closed and its status is set by
this elastic band which represents that
protein filament now imagine that this
arm represents one stereo cilium and
this arm represents the adjacent shorter
one with the elastic band between when
sound energy impaired impinges upon the
hair bundle it pushes it in the
direction towards his taller edge the
sliding of a stereocilia puts tension in
the link until the channels open and
ions rush into the cell when the hair
bundles pushed in the opposite direction
the channels close and most importantly
a back-and-forth motion of the hair
bundle as ensues during the application
of acoustic waves Oh alternately opens
and closes the channel and each opening
admits millions and millions of ions
into the cell those ions constitute an
electrical current that excites the cell
the excitation is passed to a nerve
fiber and then propagates into the brain
notice that the intensity of the sound
is represented by the magnitude of this
response a louder sound pushes their
bundle farther opens the channel longer
lets more ions in and give rise to a
bigger response now this mode of
operation has the advantage of great
speed some of our senses such as vision
use chemical reactions that take time
and as a consequence of that if I show
you a series of pictures at intervals of
twenty or thirty per second you get the
sense of a continuous image because it
doesn't use reactions the hair cell is
fully a thousand times
then I read their sentences we can hear
sound at frequencies as great as 20,000
cycles per second and some animals have
even faster ears the ears of bats and
whales for example can respond to their
sonar pulses at a hundred and fifty
thousand cycles a second but this speed
doesn't entirely explain while the ear
performs so well and it turns out that
our hearing benefits from an amplifier
something called the active process the
active process enhances our hearing and
makes possible all the remarkable
features that have already mentioned let
me tell you how it works first of all
the active process amplifies sound so
you can hear at threshold sounds is that
move the hair bundle by a distance of
only about 3/10 of a nanometer that
that's the diameter of one water
molecule it's really astonishing the the
system can also operate over an enormous
ly wide dynamic range why do we need
this amplification the amplification in
ancient times was useful because it was
valuable for us to hear the tiger before
the tiger could hear us and these days
it's essential as a distant early
warning system it's valuable to be able
to hear fire alarms or contemporary
dangers such as speeding fire engines or
police cars of the like when the
amplification fails they are hearings
sensitivity plummets and an if
individual may then need an electronic
hearing aid to supplant the damage
biological one this active process also
enhances our frequency selectivity
even an untrained individual can
distinguish two tones that differ by
only two-tenths of a percent which is
one thirtieth of the difference between
two piano notes at a trained musician
can do even better this fine
discrimination is useful in our ability
to distinguish different voices and
understand the nuances of speech and
again if the active process deteriorates
it becomes harder to care
verbal communication and finally the
active process is valuable in setting
the very broad range of sound
intensities that our ears can tolerate
from the very faintest sound that you
can hear such as a drop to pin to the
loudest sound that you can stand say a
jackhammer or a jet plane the amplitude
of sounds spans an app of 1 million fold
which is more than is encompassed by any
other sense or by any man-made device of
which I'm aware and again if the system
deteriorates an affected individual may
have a hard time hearing the very faint
of sounds or tolerating the very loudest
ones now to understand how the hair cell
does its thing one has to situate it
within its environment within the ear we
learn in school that the organ of
hearing is the coiled snail shaped
cochlea it's an organ about the size of
a chickpea it's embedded in the bone on
either side of the skull we also learn
that an optical prism can separate white
light into its constituent frequencies
which we see as distinct colors in an
analogous way the cochlea acts as sort
of an acoustic prism that splits apart
complex sounds into their component
frequencies so when a piano was sounded
different notes blend together into a
chord the cochlea undoes that process it
separates them and represents each at a
different position in this picture you
can see were three notes middle C and
the two extreme notes on a piano or
represented in the cochlear the lowest
frequencies go all the way up to the top
of the cochlear the highest frequencies
down to 20,000 Hertz go all the way to
the bottom of the cochlear and every
other frequency is represented somewhere
in between and as this diagram shows
successive musical tones are represented
a few tens of hair cells apart along the
cochlear surface now the separation of
frequencies is really key and our
ability to identify different sounds
because every musical instrument every
voice emits a distinct constellation of
tones
the cochlea separates those frequencies
and the 16-thousand hair cells didn't
report to the brain how much of each
frequency is present the brain can then
compare all the nerve signals and decide
what particular tone is being heard but
this doesn't explain everything that I
want to explain where's the magic I told
you already about the great things that
the hair cell can do how does it carry
out the active process and do all the
remarkable features that I mentioned at
the outset the answer is instability we
used to think that the hair bundle was a
passive object it just sat there except
when it was stimulated but in fact it's
an active machine it's constantly using
internal energy to do mechanical work
and enhance our hair so even at rest in
the absence of any input an active hair
bundle is constantly trembling it's
constantly twitching back and forth but
when even a weak sound is applied to it
it latches on to that sound it begins to
move very neatly in a one-to-one way
with it and by so doing it it amplifies
the signal about a thousand times
this same instability also enhances our
frequency selectivity for a given hair
cell tends to oscillate best at the
frequency at which it normally trembles
when it's not being stimulated so this
apparatus not only it gives us our
remarkably acute hearing but also gives
us the very sharp tuning I want to offer
you a short demonstration of something
related to this I'll ask the people who
are running the sound system to turn up
its sensitivity at one specific
frequency so just as a hair cell is
tuned to one frequency the amplifier
will now enhance a particular frequency
in my voice
notice how specific tones emerge more
clearly from the background this is
exactly what hair cells do each hair
cell amplifies and reports one specific
frequency and ignores all the other and
the whole set of hair cells as a group
can then report to the
brain exactly what frequencies are
present in a given sound and the brain
can determine what melody is being heard
or what speech is being attended now an
amplifier such as the public address
system can also cause problems if the
amplification is turned up too far it
goes unstable and begins to howl or emit
sounds and one wonders why the active
process doesn't do the same thing why
don't I ears beam out sounds and the
answer is that they do in a suitably
quiet environment seventy percent of
normal people will have one or more
sounds coming out of their ears I'll
give you an example of this this you
will hear two emissions at high
frequencies coming from a normal human
ear you may also be able to discern
background noise like the microphones
hiss the gurgling of a stomach the
heartbeat the rustling of clothes
this is typical most ears emit just a
handful of tones but some can emit as
many as 30 every year is unique so my
right ear is different from my left my
ear is different from your ear
but unless any air is damaged it
continues to admit the same spectrum of
frequencies over a period of years or
even decades so what's going on it turns
out that the ear can control its own
sensitivity its own amplification so if
you're in a very loud environment like a
sporting event or a musical concert you
don't need any amplification and the
system is turned down all the way if you
are in a room like this auditorium you
might have a little bit of amplification
but of course the public address system
does most of the work for you and
finally if you go into a really quiet
room where you can hear a pin drop the
system has turned up almost all the way
but if you go into an ultra quiet room
such as a sound chamber the system turns
itself up to 11 it goes unstable and it
begins to emit sound and these emissions
constitute a really strong demonstration
of just how active the hair cell can be
so in the last minute I want to turn to
another question that might come up
which is where do we go from here and I
would say if there are three issues that
I would really like to address in the
future the first is what is the
molecular motor that's responsible for
the hair cells amplification somehow
nature is stumble across a system that
can oscillate or amplify at 20,000
cycles per second or even more that's
much faster than any other biological
oscillation and we would like to
understand where it comes from the
second issue is how the hair cells
amplification is adjusted to deal with
the acoustic circumstances who turns the
knob to increase or decrease the
amplification in a quiet or an allowed
environment and the third issue is one
that concerns all of us which is what we
can do about the deterioration of our
hearing thirty million Americans and
more than 400 million people worldwide
have significant problem
on a daily basis with understanding
speech in a noisy environment or over
the telephone many have even worse
deficits moreover these deficits tend to
get worse with time
because when human hair cells die
they're not replaced by cell division
but we know that non-mammalian animals
can replace their cells in those
creatures cells are dying and being
replaced throughout life so the animals
maintain normal here here's an example
from a little zebrafish the cell at the
top will undergo a division to produce
two new hair cells they dance for a
little bit and then settle down and go
to work so we believe that if we can
decode the molecular signals that are
used by these other animals to
regenerate their hair cells we'll be
able to do the same thing for humans in
our group and many other groups are now
engaged in research trying to resurrect
these amazing hair cells thank you for
your attention
[Applause]