Translator: Rhonda Jacobs Reviewer: Leonardo Silva
Good morning, Vienna.
Okay, many cultures use the expression 'night and day'
to describe opposites that are somehow surprising:
Twins that behave completely differently despite that they look the same;
someone who's drastically changed their behaviour,
perhaps going from drinking way too much to nothing at all.
'It's like night and day'.
Of course when we say this, it's actually a metaphor
that refers to the stunning transformation
that the Earth goes through every day as it rotates on its axis,
alternately sampling warmer light environments
and darker cold ones.
It's like night and day, there's nothing as different from night than day.
And we pass between these two states every single day without exception.
Evolution is all about developing adaptations to special environments
through genetic change.
And so it stands to reason evolution has given us a mechanism
to deal with this special environment, a mechanism embedded in our genes,
and a mechanism that actually samples and tastes the environment
that's alternating with high predictability.
And that mechanism is the biological clock,
or the circadian clock.
So what is the circadian clock and what does it do for us?
One of the most impressive examples that I know about
are experiments that take people like you or me
and put them into a time-free environment.
A subject goes into a specially designed apartment,
usually just a single room,
that has no access to information from the outside world.
So there's no clock on the wall, there's no window
and there's no noise from outside activities.
In this situation, a subject lives not with a precise 24-hour rhythm,
they don't maintain that,
but they go to a circa-24-hour rhythm in sleep-wake behaviour, for instance.
They basically sleep and wake with the same interval every day,
but it's a little bit less than 24 hours or a little bit more than 24 hours,
so it's a persistent oscillation in our behaviour
in the absense of daily time cues.
And this is called the circadian rhythm.
With the word 'circadian' coming from the Latin
for 'about a day'.
So -
so I think about how this works,
that you have no information from outside and you still can do this quite reliably
in constant conditions.
This is what we mean by an internal clock, a biological clock or a circadian clock.
So it's an alarm clock that's built into our heads
that's telling us when to wake up.
And then I have to say that I've been studying the circadian clock
for over 20 years now,
and I still am incredibly impressed and amazed,
and it's still almost unbelievable to me
that we, who are so complex and strong-willed in our behaviours,
show this persistent, self-sustained circadian rhythm
in sleeping and waking, for instance, and in many other things also.
But I've seen so many examples of this 24-hour timing mechanism
in bacteria and fungi and plants and humans and other animals
that there's no question in my mind that it's a fundamental part of biology.
So as you probably know,
experiments that put humans or any other living organism
into a time-free environment like I just described
are actually highly artificial,
and they actually never really happen in real life.
And you also probably know that your sleep-wake cycle
is actually, on average, exactly 24 hours.
This process of adjustment of this circa-24-hour rhythm
to exactly 24 hours is called circadian entrainment,
and for our sleep-wake behaviour
it's mediated by specialised cells in our retina that sense light.
The biological clock, however,
is built of many more cells than just a few cells in the eye or the brain.
Basically, all of our cells are oscillating.
What do these cellular oscillations look like?
Well, we can measure oscillations in RNA levels, for instance.
The genes express your RNA levels in individual cells,
and you see here a tracing of cells
that are carrying on for five or six or seven days
in constant conditions.
So about ten percent of the genes in any given cell
are expressed with a circadian rhythm.
Of these, some of the proteins will also be rhythmic,
and metabolism will become rhythmic also.
And so you get a network of oscillations in each cell
that eventually come together
so that you get higher functions that are also rhythmic.
Now, these cellular oscillations are generally not entrained by light;
light entrainness is unique to cells emanating from the eye, in the eye,
or connected to the eye, those cells.
These peripheral cells, in general,
will entrain to cycles in our body temperature,
so our temperature is one to two degrees higher at the end of the afternoon
than it is at the end of the night.
So now you should start to get a picture of the circadian clock
in a human, for instance.
It's all kinds of oscillating cells -
really, literally, all kinds of cells that are oscillating.
They're responding to various time cues:
light, temperature,
also nutritional status and hormone levels, for instance,
and then they come together to regulate many, many processes.
So cognitive performance changes over the course of the day.
The perception of pain peaks in the evening.
Physical performance like grip strength peaks mid-afternoon,
and components of our blood
like the metabolic state of cells or hormone levels
is also circulating with predictable rhythms over the course of the day.
Andre Gide wrote a wonderfully perceptive sentence:
'... if I were not there to make them acquainted,
my morning's self would not know my evening's.'
This is really perfect - we are different people, night and day.
So, what does this mean for us in everyday life?
The circadian clock regulates the timing of our behaviour.
It determines our chronotype.
Chronotype is measured by asking people when they sleep
on a free day with no obligations.
And like many behaviours, it shows a distribution.
You get a few people who are sleeping very early in the day;
you get most people who are sleeping at similar times to each other;
and then you get some people who are sleeping quite late.
(Laughter)
And yes, you can see that teenagers and young adults
are disproportionately represented in this late population.
They sleep much later than young children and older adults.
That makes me think back to actually what Gide wrote
about being different people morning and evening
and I think that this explains a lot of the conflict
between parents and teenagers -
that basically, the timing of their behaviours is totally misaligned,
that's all it is.
(Laughter)
Okay, so ...
So I told you about age and how that regulates chronotype,
and so think about this also, that as you go through life, then,
you naturally pass through a series of chronotypes
going from early to late and then early again, okay?
So what else regulates chronotype, or the timing of our behaviour?
One of the answers is genes.
And the most compelling - not the most compelling, excuse me -
the first data that informed us about the genes
that are involved in regulating the circadian clock
came from fruit flies,
and we now have a lot of genes that regulate the circadian clock
in isolated human cells.
Interestingly, when we look at humans themselves,
it's much more difficult to figure out
which genes are involved in regulating chronotype.
The most compelling examples come from large family pedigrees
where an extreme chronotype is inherited as a dominant trait.
However, the DNA sequences responsible for those traits
are actually not found in the general population,
so my conclusion from these observations
is that the genes that are involved in regulating chronotype
are actually many,
with each having individual small effects in the general population at least,
and therefore very hard to track by standard genetics methods.
Another way that the chronotype is regulated is with light.
So I mentioned that the clock is designed to actually sample the environment,
so perhaps it's not surprising that it actually checks in
and uses some of the information from the environment.
So, how do we know that this is so?
If you live in a higher light environment compared to a lower light environment -
so someone who gets outside compared to someone who's inside all the time -
you'll generally have an earlier chronotype vs. a later one, respectively.
If you live in the eastern part of a time zone like in Vienna
compared to the western part of the time zone,
you'll have an earlier vs. a later chronotype,
and of course this is because we express chronotype as local time,
whereas your clock is reading sun time.
There's some evidence that we entrain differently
in the summer - that's earlier in the summer -
than in the winter, where we entrain later.
It might also help you to think about jet lag
to understand intuitively how light feeds into the clock.
So with jet lag you've flown across time zones,
and it takes a really surprisingly long time
to readjust to the new time, and you feel really bad in the process
as your clock is running ahead or lagging behind
of the new sun time.
Eventually you find a relatively stable phase of circadian entrainment
that's consistent for your chronotype in your new environment.
You feel better; you can sleep again; and you get your energy back.
So, what are the implications about all of this for you
in your everyday life?
First of all, I think it's pretty clear
that you will have a fundamentally different circadian clock,
and therefore chronotype, from your neighbours.
So you have different genes, you have a different age,
and you have a different life history.
I want to do a little experiment here.
I want to let you understand that
by actually comparing yourself to others,
which is actually a really good way to make people understand this quickly,
so I'm going to ask you to raise your hand and tell us, and report to us,
when you prefer to go to sleep on a free day with no social obligations.
Okay?
So who goes to bed before midnight?
Okay, look around and see how many hands are up.
How about midnight to 1:00?
1:00 to 2:00?
2:00 to 3:00?
(Laughter)
And after 3:00?
There should be some people here after 3:00.
So you've just reconstructed the chronotype distribution
right here in this room.
So now you see how it works.
I recently came across a dramatic story concerning chronotype.
This is a picture of the famous castle Neuschwanstein.
It was built by Ludwig II,
who became the king of Bavaria in 1864 at the age of 18.
Twenty-two years later he was forcibly removed from the throne
when he was pronounced insane
by a board of psychiatrists who had never examined him.
Ludwig may have had some troubles in the mental health department -
I think no one can know for sure; it's history.
What we do know
is that despite some considerable popularity with his subjects,
the government was deeply disturbed
that through his palaces and castles that he was building,
he was pushing the state to the brink of bankruptcy.
They wanted him out.
When I read a bit more about the daily life of Ludwig,
I became suspicious of the diagnosis of mental illness.
Certainly, he wasn't coping very well in general,
and he practised some eccentric behaviours,
but the most specific description concerned the timing of his behaviour.
He ordered breakfast at 6:00 in the evening,
lunch at midnight,
and dinner in the early morning
before retiring to bed to sleep through the day.
Very rarely one finds a reversed chronotype like Ludwig had.
He seems indeed to have been most relaxed at Schloss Linderhof here,
where he famously was riding around
in his sleigh through the night around the grounds.
In contrast,
his official duties would have taken place during the daylight hours,
which was unfortunately during his night time.
Think about how you would feel if you had to negotiate anything
in the middle of your night.
Ludwig found himself negotiating the independence of Bavaria
in the middle of his night, and he lost it.
This misstep essentially created the German Empire.
(Laughter)
I find myself wondering if the chronotype of Ludwig II
changed the history of the world.
(Laughter)
That's of course impossible to say,
but extreme examples like this are very useful for making a point,
and the point here is that like other living creatures,
we have our own individual circadian clock
that in combination with our age and our light exposure
will make us a certain chronotype.
Our clock directs the timing of our behaviour.
Our chronotype is so strong
that it sometimes isolates us like it did Ludwig II.
It does this in small ways.
When we want to be with someone who has a different chronotype,
maybe we feel like doing something that they don't feel like doing.
Our chronotype is so strong
that sometimes we have to modify it with an alarm clock,
otherwise we might get in trouble with work or school.
Both of these scenarios are suboptimal.
One of them results in social relationships that suffer,
and the other results in sleep deprivation
as a result of the clash of the biological and the social clock;
this is a condition we call social jet lag.
And sleep deprivation is known to lead to a variety of problems
ranging from poor performance to illness.
Is there anything, then, that you can do to fine-tune your chronotype
so that you can have more harmonious time with family and friends,
and you can lose less sleep to your work?
Can you unshackle yourself from your clock?
The answer is: almost certainly.
If you think back to what I said regulates chronotype -
that would be genes, light and age -
two of those things you can't change overnight.
But light is something that we can work with.
It's easy to find, it's cheap and it's not unpleasant.
So the only problem is that we don't have very good prescriptions
for how light will interact with your specific chronotype,
because remember, you have a unique collection of clock genes
that we don't really understand yet,
so we don't know how they would react to light.
There is a general rule that most people, however,
if they increase the light they get in the morning
and decrease the light they get in the evening,
for instance, from computers and televisions,
that they will tend to move earlier in their chronotype
and therefore have to use their alarm clock less.
Okay?
Okay, 80 percent of you out there are alarm clock users.
This should remind you every single day that you have a circadian clock.
Your clock is showing itself in your individual cells;
it's showing itself in your family and in your community.
Despite the alarm clock, which I hope you'll use now much less,
the circadian clock is a wonderful addition to our poor existence.
It gives us more versions of ourselves.
We are, after all, different people morning and evening.
Get to know you.
And since I'm a scientist, I have to acknowledge my dear colleagues,
because no scientist stands up here alone without a huge team behind them.
Maria and David who are here today,
Till Roenneberg who's rewritten the book on human behaviour,
and many chronobiologists,
and please do discover your chronotype at this web address: [www.euclock.org]
Thank you very much.
(Applause)