[Rhonda]: But specifically with regards to the, the master clock, light is what regulates
this master.
[Satchin]: Yeah.
[Rhonda]: It's what sets it.
[Satchin]: Yeah.
[Rhonda]: So can you...and this was some of your early findings.
[Satchin]: Yeah.
[Rhonda]: Can you talk a little bit about that?
[Satchin]: So for a long time people knew that light resets our clock, and in fact,
in nature, with change of season, the sunrise and the sunset time do change, and we have
to adapt to that sunrise and sunset time, otherwise animals cannot go to sleep and wake
up at the right time.
So what is interesting was for a very long time, people couldn't figure out what, where
is the light receptor that resets the clock, because there are many blind people out there
who cannot see anything but they can reset their clock.
So if they go from east coast to west coast, they fly, then they also have typical jet
lag and after three to four days they get used to the new time zone.
And similarly, there are laboratory animals that are blind, they can't see a thing, but
if you change their light-dark cycle, then they readjust in six to seven days.
They actually readjust the same way as mice with normal vision.
So this was kind of an unanswered question in vision science for 75 years.
What is this extra light receptor in the eye?
And we knew that it was in the eye because many people who go to war and lose both of
their eyes because of gunshot wounds, and people who have cancer or a tumor growth in
both eyes and the eyes are removed, they can't reset their clocks.
So they, kind of run free.
They kind of free run, because our clock is not exactly 24 hours.
And our clock is very close to 24 hours, 24 hours, 15 minutes, 24 and a half hours, something
like that.
So, if we cannot entrain our clock to light-dark cycle, then every day we'll be working off
15 minutes or 30 minutes late.
And then after 10 to 15 days, we'll be completely out of sync with the society.
And that's what happens with this [inaudible 00:10:57].
If you combine these two observations, people without their eyes cannot reset their clock
and blind people can still reset their clock, then that essentially tells us that there
must some special light receptor.
So almost 16 years ago, three different groups figured out that there is a new light-sensing
molecule that must be present in some of the remaining cells of the retina in blind people,
and our group was one among them who discovered this new light receptor called melanopsin.
It's actually from frog melanosomes.
So this is a clear example of how basic science actually leads to understanding human health.
So if you put a frog under light, then the frog's skin will change its color.
And because frog skin has a light sensor that detects light, and then puts kind of a natural
sunscreen.
[Rhonda]: Like melanin making…
[Satchin]: Yeah, and so it spreads melanosomes.
So melanin pigments are spread.
And interestingly, the same protein that spreads melanosomes in frog skin is also present in
human retina and mouse retina, and only in 1000 to…sorry, 2000 to 5000 cells.
And these are special light-sensitive ganglion cells, we call them, and these cells sense
light in the blue spectrum and send that information straight to this suprachiasmatic nucleus or
the master clock.
And that's how every day, in the morning, with the first sight of light, these melanopsin
cells sense light and then tell the SCN that this is morning and this is time to sync up.
So that's what it is called.
[Rhonda]: Okay.
So that first bright light exposure...
[Satchin]: Yeah.
[Rhonda]: ...sets the clock and tells your body, you know, "Okay, this is the start."
So then you start to change gene expression, things are going on in the brain, you're more
mentally aware of things that happen.
All these little changes happen throughout the day that are on this rhythm.
[Satchin]: Yeah.
[Rhonda]: What happens, then, if you, let's say, you don't have...let's say you live in
a very dark apartment or, you know, a dark apartment in the winter in Sweden or somewhere,
you know, where it's, like, dark, you know, so you don't get that bright light exposure.
How does that affect...
[Satchin]: Yeah.
[Rhonda]: ...someone's circadian clock?
[Satchin]: So you kind of use this interesting term, bright light.
And actually, that's very important for melanopsin because we know we have rhodopsin that's extremely
sensitive to light and that helps us to see the star and enjoy the moonlight, but that's
very low amount of light.
And actually, a clock is not sensitive to that amount of light.
Just imagine, if our clock was sensitive to dim light, then we'd be completely what because
even in nature, the lightning or starlight or moonlight that we can see can reset our
clock.
So, one interesting thing with melanopsin, it's very less sensitive to light.
It's a very lousy photoreceptor.
So that means you need a lot of light.
For example, you may need almost 1000 lux of light to fully activate melanopsin.
And then another interesting part of melanopsin is it integrates light over time.
So that means it actually remembers how much light exposure you previously had.
So for example, if I switch on a flash, then for 100 milliseconds you see a thing and then
after the flash is gone, your visual system restart, you don't see that thing.
But melanopsin stays active for several seconds after lights are off.
So that characteristic helps you to count how many minutes you had exposure to light.
So in that way, not only you need bright light, you also need several minutes of bright light
before it's fully active and can do all of its function, particularly to reset the clock
or to do few other functions, and I'll get to that.
So, when we discovered melanopsin, we thought that these cells connect only to the master
clock, but what we're learning more and more is it has multiple different functions.
It also connects to part of the brain that suppresses or that regulates sleep, so that
means many of us know that it's very hard to sleep in a lighted room and that's because
of melanopsin because it senses light, and in diurnal organisms like us, it does know
there is light, so you're not sleepy, so you stay awake.
It also indirectly connects to part of the brain that produces melatonin, and melatonin
is the sleep hormone.
So, when we have lot of light and also for a very long period of time, then it shuts
down melatonin.
It helps us stay awake.
But during daytime, in the morning when we wake up, we need that big jolt of light for
melanopsin to really activate and suppress the melatonin, make us more alert and reset
the clock, and turn on hundreds of genes in the SCN and start secretion of many neuropeptides
and all that stuff.
So that's why it's becoming…we are learning a lot about what quality of light and how
much of light do we need in the first half of the day to keep us awake, and how little
light or what kind of light we need in the evening or second half of the day so that
we can go to bed well.
So in dim environment, it becomes...means, many people know that dim light or cloudy
days make us depressed, but now we have a molecular biology explanation why is that.
At the same time, it also tells us maybe if we have blue-shifted light during the first
half of the day that may help us to stay awake, to stay alert, and also to reduce depression.
But in the evening, we actually should stay away from that light.
So it's a very interesting thing about our environment because so far everything in our
environment, whether it's carbon monoxide, carbon dioxide, oxygen, temperature, everything
can be set at a set point throughout 24 hours.
And this is interesting stuff about light.
We need more of that in the first half of the day, and as little as possible in the
last half of the day or in the evening.
So it's a very interesting area.
[Rhonda]: And modern day society is also not very conducive to that, those needs because
we have artificial light, we have televisions, we have computer screens, we have iPhones
and Android phones, and you know, so everything's emitting this bright light or blue light...
[Satchin]: Yeah.
[Rhonda]:... which is what's activating the melanopsin recep-...
[Satchin]: Yeah.
[Rhonda]: ...or melanopsin and inhibiting melatonin production.