(mysterious music)
("5th Symphony" by Beethoven)
Destiny is beyond our control,
our fate already set, perhaps from the onset of disease
or being born with a special ability.
(balls thwacking loudly)
You may think our lives are determined
by the genes we're born with,
but that is not the case.
(elegant music with vocalizations)
According to the latest scientific findings,
there's a remarkable system within our genes.
There's the hope that you can change fate.
And that system is DNA switches.
Within our DNA is an element that acts like a switch,
changing our lives dramatically,
depending on whether it's set to on or off.
This is the field of epigenetics.
(sobbing)
For example, let's take disease.
We all have genes that can prevent them.
One of the triggers for cancer and diabetes
is when certain switches are turned off.
But if you flip it back on.
So I have great news for you in terms of your CAT scan.
So it has not grown at all, which is excellent news.
We now know there are switches
for all kinds of genes,
like those for obesity, memory, or musical ability.
All these genes may be controllable.
Studies are even exploring whether DNA in sperm
could be passed on to children in a healthier state
by treating the future father-to-be.
Try to identify how we can
positively influence our next generation.
I believe that epigenetic signals
can indeed change the destiny.
These DNA switches exist
in the bodies of all of us.
Join us on a journey into this extraordinary world.
So what are these DNA switches
that can change our destinies?
Cutting edge research is taking place
at this laboratory in Spain.
This is Professor Manel Esteller
from Bellvitge Biomedical Research Institute.
What we are doing here is extracting
the genetic material, the DNA.
Floating right there are fragments of DNA.
(intriguing music)
Using futuristic technology, scientists have shed new light
on the workings of this mysterious microscopic world.
So all, each point, it's a small sequence of DNA.
These dots, in green and red,
show the state of DNA switches being scanned.
Green means the switch is turned on, red is off.
We now have the technology to study in a very fast manner,
in a few days, something that took us before years to do.
Now in five days, you can obtain this complete epigenome,
the complete circuit of switch-on
and switch-offs in our genome.
This is what we call epigenetics.
Epi means beyond, beyond genetics.
Let's learn more
about how this mechanism works.
(mysterious music)
Our bodies are made up of roughly 40 trillion cells,
with DNA contained in every single one.
(ticking)
Its structure is distinctive
with its unmistakable double helix.
98% of our genome used to be called junk DNA,
until we realized its significance.
The remaining 2% form our genes, the blueprints for life.
Genes contain instruction manuals
on how to make parts of our body,
such as the heart, stomach, and gut.
But that's not all.
There are genes that increase our stamina,
that enhance musical ability,
there are even genes that prevent diseases
like cancer and diabetes,
information packets that could save our life.
And there's a system that fundamentally alters
how our genes work, the DNA switches.
For example, they can enhance creativity.
(violins play slowly) There you go.
In fact, we all have this gene.
All right, your first driving, are you ready?
Put it on your first string.
But crucially, Good.
what decides our fate
is whether it's on or off.
At least one switch like this exists for every gene,
and it's believed that there are over 20,000 of them.
Scientists now believe that the keys to our composition,
health, and abilities, are held by DNA switches.
So how do these switches manipulate our destinies?
(electronic warbling)
We're about to reveal their secrets.
(intense music) (footsteps falling loudly)
Scientists studying twins have helped us understand
this fascinating new field.
This is Doctor Nancy Segal
at the California State University, who is a twin herself.
You can see that when they take off their shirts,
the hair on the chest is in exactly
the same lines and swirls,
they hold the can with the pinky finger underneath,
and you can see the same bald heads,
and mustaches, and glasses.
Doctor Segal was particularly interested
in identical twins and has studied over 1000 pairs so far.
Well identical twins are this great mystery
because they're so much alike,
and yet a particular pair who matches on so many things
can differ in one very profound way,
and diseases seems to be one of them.
So this is Erica and this is Monica.
Erica's always had like this little bit of roundness
in her face and I have the Hoffman long chin.
But not then, it's mostly, I would,
I think it came from our eyes, Monica and Erica
are identical twins. Look a little different.
Very 'cause I have my dad's.
(gentle music)
Since they came from the same fertilized egg,
they share the exact same DNA.
In case something happens,
in case we fight. But four years ago,
their lives changed dramatically.
Monica was diagnosed with breast cancer.
She was treated with chemotherapy,
but last year the cancer returned.
On the other hand, Erica is a picture of health,
with no signs of illness at all.
Of course I cried, the shock.
It was more not knowing yet, 'cause they tell you
oh you have breast cancer, it's this, it's that,
it's stage, blah, blah, blah, blah,
and it just like was a lot.
I was mad and everyone says all, you know,
think about God, and I'm like really,
you wanna put God in the situation, I still don't.
(sobbing)
They have exactly the same DNA,
so why did only one get cancer?
According to an analysis of 16,000 sets of twins,
it's believed that the chances of both twins getting cancer
through inherited genes is only around 8%.
So even in twins with matching DNA,
it's rare for both to suffer from the same affliction.
What's in the remaining 92% that causes us to get cancer?
Until recently, we thought it was connected
to the environment we grew up in, or our lifestyles.
But now research is telling us that these DNA switches
may be playing a big role.
How do we look in?
The new finding comes
from Professor Stephen Baylin,
a global authority on cancer research
at Johns Hopkins University.
Off, on, and that's how we look
at genes in the laboratory.
So this is a code.
Professor Baylin took an interest
in several genes that suppress cancer.
Take breast cancer as an example.
It develops in the mammary gland that produces milk.
(electronic warbling)
These are the first pictures from inside the mammary gland,
captured by an electron microscope.
The spheres you can see inside are the source of breastmilk.
The milk is actually produced by these cells
surrounding the mammary gland.
And to ensure that there's an adequate supply,
cells in the mammary gland have to keep multiplying.
(whooshing and gurgling)
But when they grow beyond control,
it can end up as breast cancer.
It's times like these where genes
that can suppress cancer become indispensable.
They have the power to stop cells
from dividing out of control.
While Professor Baylin was studying his group
of 215 cancer patients, he realized that all of them
had the gene that suppresses cancer.
So why were their cells still multiplying?
He checked to see if a phenomenon
called DNA methylation had occurred,
which would mean that the switches were turned off.
And astonishingly, he discovered that in over 60%
of these cancer patients DNA methylation had taken place.
That is the switch for the gene
that suppresses cancer was turned off.
And we really are beginning to understand
that when that cancer turns that switch off on the gene,
that has very poor prognosis
that that creates for the patient
in making that cancer start.
So why were the switches turned off?
And how do these master controllers determine our fate?
Why is one twin sick and the other healthy?
We're inside a cell.
The intricate bundles you see are clusters of DNA.
Let's get a better look.
The gene that suppresses cancer is highlighted in white.
And when this DNA switch is in the on position,
a set of instruction contained inside
is scanned by a reader.
(clicking)
(dinging)
And molecules that suppress cancer are produced.
This stops the cells from multiplying uncontrollably,
and curbs the growth of cancer.
This is when the DNA switch is on and in a healthy state.
However, what happens when the DNA switch is turned off?
(slow tempo music) (gurgling)
This doesn't look good.
The important gene that suppresses cancer,
rope-like here in pink, is completely crumpled up.
In that state, it's not possible to make molecules
that curb cancer or even read the information it contains.
What could be happening here?
Let's go back and see what happens
before the gene gets scrunched up.
(whooshing)
Look, orange molecules are drifting all around this area.
They are responsible for distorting the DNA.
They are called DNA methyl transferase.
And what do they do?
You can see them attaching tiny grain-like substances
to the gene, just 10 millionths of a millimeter in size.
They act like magnets.
Take a look, those tiny grains
are pulling molecules toward them.
Then other sections start attaching themselves,
and ultimately the gene that suppresses cancer in pink
ends up collapsing onto itself.
When the DNA switch is set to on,
the DNA is unfolded, the molecules
that prevent the growth of cancer can be produced.
But when the switch it set to off,
it's not possible to read the instructions,
so these healing molecules cannot be made.
In cancer patients, this switch is thought to be turned off,
perhaps due to an increase of DNA methyl transferase.
It's possible that these switches can be turned off or on
in all 20,000 genes in our bodies.
There are ones that can only change before birth,
and others that can change easily
after we're born. (speaking in foreign language)
Some switches are better for us if they are turned off.
The position of these DNA buttons can determine
our body type, our artistic or physical capabilities,
or our susceptibility to disease.
It's staggering to think that such things
are taking place in our bodies.
(electronic warbling)
But could we influence the DNA switches?
(dramatic music)
It's thought that our lifestyles, like diet and exercise,
can greatly affect them.
Take for example what we eat.
(speaking in foreign language)
At the University of Navarra,
some interesting studies are taking place.
(conversation in foreign language)
(sizzling)
By asking the participants to consume a Mediterranean diet,
rich in olive oil and nuts,
they're examining how food might affect outcomes.
Bon appetit. (glasses clink)
DNA was collected from blood samples
taken from the participants.
By checking whether DNA methylation had taken place or not,
the state of thousands of switches was analyzed.
The researchers discovered that switches that are linked
to preventing metabolic syndrome,
like obesity and high blood pressure,
had changed in the participants.
It's clear that the consumption of olive oil
and the consumption of nuts induced
a specific epigenetic changes
that can explain some of the healthy benefit.
Therefore an epigenetic regulation of inflammatory processes
is important to understand the disease,
but also in some cases to manage, either by the diet
or with other therapeutic procedures to treat this disease.
Meanwhile in a laboratory in Sweden,
researchers are looking to see
if the triggers can be flipped with exercise.
Participants in this study have been asked
to do endurance exercises, together with light resistance,
four times a week.
Three months later,
the results showed changes in DNA switches
related to muscle structure,
and revealed that those involved
in the prevention of disease,
like diabetes and cardiovascular disease, were also altered.
With exercise, you change, you revert that
in a more healthy direction becomes gene expression.
And there are clear signs and I'm quite convinced
that epigenetics do play a role
in that adaptational process.
We can all appreciate how a good diet
and regular exercise is beneficial,
but it's remarkable that they can even affect our DNA.
(intriguing music)
Although details of this mechanism aren't yet clear,
it's currently thought that lifestyle can affect the amount
of DNA methyl transferase produced.
(electronic warbling)
The very latest studies are using drugs
as another way to affect DNA switches.
The doctor in charge of this clinical trial
is Professor Stephen Baylin, the researcher who discovered
how DNA switches can affect cancer.
He's developed a drug that acts directly on DNA.
It's being tested on lung cancer patients
who did not respond to conventional treatments.
We will take this drug, add it to cancer cells,
and that will help turn back on genes
that are abnormally silenced in the cancer cell.
The drug's impact is extraordinary.
Once inside the body, the drug targets the gene
that produces molecules which suppress cancer.
If the drug is absorbed by the gene,
even when DNA methyl transferase is present,
its affects are dampened down.
This is how DNA could maintain its normal appearance,
rather than being curled up into bundles.
(electronic warbling)
The gene can be scanned
to make the all-important cancer suppressing molecules.
Let's go back and see how well this drug has done.
(people speaking over each other)
The results of the trials are being reported
back to the patients.
These are your lungs.
So I have great news for you in terms of your CAT scan.
So it has not grown at all, which is excellent news.
And it means that the treatment that we're doing right now
is helping prevent your cancer from growing.
45 patients with late-stage lung cancer
took part in his clinical trials.
Encouraging results were seen in about 1/3,
and one even became tumor free after treatment.
So this man probably would have been expected
to only live a few months.
The arrow here points to the cancer,
it's this big white blob.
Now we start the therapy, two months later,
this is six months later, and this is eight months later.
And almost everything is gone,
and he went to see his football games
and he did things that he wanted to do.
This is the hope.
(chiming)
So could it be possible to manipulate
our many different DNA switches to improve our abilities,
such as memory, endurance, musical abilities,
and change our fate?
(peaceful music)
In the last decade, a vast amount of research
has been published on the switches,
and studies are exploring ways to alter our genetic destiny.
For example, we're looking into improving memory by running.
When you exercise, levels of DNA methyl transferase decrease
so strands of DNA become untangled,
and the switch for developing neurons in the brain
flips to the on position.
That's why exercise can improve memory.
In order to improve musical ability,
it's essential to listen to lots of music.
(applauding)
When you listen to music,
DNA switches that produce neurotransmitters
involved in hearing become switched on.
This is thought to increase your ability
to differentiate musical tones.
You may have been born with a special talent,
but this alone does not explain the origin of your gift.
(slow violin music)
There is now more emphasis on the crucial role
of these DNA switches, which can be changed
through our own efforts and surroundings.
Ambitious studies are now taking place around the world,
with hopes of reducing aging in skin,
preventing diabetes, or increasing our lifespan.
(waves crashing) (kids cheering)
You may be capable of changing your fate
by manipulating DNA switches.
But there's even more to this fascinating story.
In fact, not only can you choose to change your own fate,
it may be possible to influence your child's,
or even your grandchild's destiny.
(fast tempo music)
Cutting edge research in this field is taking place
at the University of Copenhagen in Denmark.
(fast whirring)
Research has shown that exercise
can change the DNA switches in a father's sperm.
An hour of endurance training, five times a week,
for six weeks can do the trick.
It's not just a question
of being able to produce healthy sperm,
the idea is to treat their metabolic syndrome
through weight loss before conceiving a child.
(electronic warbling)
By ensuring their DNA switch is on healthy,
they're hoping that this will be inherited by their baby.
I wanted to be a father myself at some point.
I will definitely take it into consideration.
However, (alarm buzzing)
such ideas would have been thought unthinkable
in science until now.
And that's because sperm goes on to become a fertilized egg
and changes into many different types of cells.
(dramatic music)
We used to think that once the sperm was ready
to fertilize the egg,
its DNA switches would go through a factory reset.
So even if you became overweight through overeating,
or you put on muscle through lifting weights,
or had become smarter through study,
the status of the parent's DNA switches were thought
to be limited to just their lifetime,
and could not be passed on to their children.
But Professor Barres's study challenges this idea.
Here in this slide.
His research suggests that exercising regularly
may be beneficial for future generations,
on a genetic level.
I think it was received with a surprise because it was,
the field is quite new,
and the dogma of a fixed genetic transmission
as the only mean to transfer information
is still very present.
(slow piano music)
Professor Barres's research was inspired
by an earlier study on the population
of a remote area in northern Sweden.
Above the Arctic Circle, is the remote village of Overkalix.
(ominous music)
Residents of Overkalix are often diagnosed
with cardiovascular disease and diabetes at an early age.
Both are linked to problems in metabolism.
Soren Karlsson, who was born in this village,
suffered a heart attack but managed to make a good recovery.
(speaking in foreign language)
Why were so many people struck by disease
at an early age in this village?
Researchers honed in on a potential cause,
epigenetics, the DNA switches
that have now caught the attention of scientists worldwide.
Professor Lars Olov Bygren meticulously analyzed records
of birth, death, and crop harvests
to uncover genetic histories spanning generations.
Bygren discovered that when men here
ate well years before puberty,
their grandchildren had higher risk
of dying from cardiovascular disease.
It was very bounty food in the environment.
And we found in the paternal line,
a response over three generations,
that was quite interesting.
What did this mean exactly?
One generation Professor Barres's research
tries to explain the mechanics
of such trans-generational effects.
In Overkalix, since the villagers grandfathers
had eaten so well,
their DNA switch may have temporarily switched over
to a state that can increase the risk
of diabetes and cardiovascular disease,
and this may have been carried through their sperm
with lasting effects on their children and grandchildren.
Professor Barres's research suggests that these changes
in the DNA may cross over generations
and cause metabolic problems
in their children and grandchildren.
Experiments in mice have shown
similar trans-generational effects.
(slow tempo music) (squeak)
When mice were given a high calorie diet,
their body fat ratio increased by 20% and they became obese.
Their offspring were fed a low calorie diet,
but even then their body fat ratio rocketed up
as high as 70%.
And in the following generation,
their body fat ratio was still 20% higher than normal.
In other words, if the grandparent's generation
was eating a calorie-laden diet,
even if their child or grandchild ate normally,
they were predisposed to obesity.
Professor Barres then looked for further evidence
to back up his theories, this time in people.
So this is our lab, this is where we do our experiments.
Our research is to study. To test his theory,
Professor Barres compared the sperm
from 10 obese men and 13 lean men.
[Professor Barres] Interested in studying sperm cells.
Using the latest technology,
he analyzed the state of the DNA switches in their sperm.
(mystical music)
This is a high resolution image of the sperm.
(electronic warbling)
If you take a look at the cross section
of the head of the sperm cell,
packed tightly in here is DNA.
So what's happening in its switches?
The results showed that the sperm of obese men
had certain switches that weren't reset.
They were set differently from the lean men,
and remarkably these switches were involved
in appetite control and metabolism.
This opens up the intriguing possibility
of a parent passing on their lifestyle traits
to the next generation,
a phenomenon scientists have long refuted,
since the theory of inheritance of acquired characteristics
was introduced in the 19th century by Jean-Baptiste Lamarck.
It is a shocking and very intriguing observation
that's been put forward,
or referred as Lamarckian theory of evolution,
where an acquired trait could be passed on
from one generation to the next.
Professor Barres took his research further
to see the impact of exercise on sperm.
He found that obese men who lose weight
may be able to flip their sperm's coating for the better.
This opens up the possibility
of reversing the downward spiral of passing on
metabolic syndrome to children or grandchildren.
I think it's a positive thing
that you can actually change your children
and also affect their health in a positive way.
I would believe that if environmental factors
such as diet and exercise,
can change the epigenetic content of our gamete,
it's likely to affect our children health later,
or predispose to some disease.
Try to identify how we can positively influence
our next generation in order to favor this.
Your body not only holds the keys to your fate,
but the power to control the destinies
of children yet unborn.
It's astonishing to think
that even DNA switches can be passed down.
It's a theory that's still being debated among scientists,
but if found to be true,
this stunning discovery will re-write biology textbooks.
But we should ask, why is it even necessary
to pass on these switches in the first place.
It might help to think like this.
Our ancestors lived in an unpredictable world,
where food could suddenly become scarce.
It was beneficial to eat whenever food was available.
These switches may have been a way
of providing clues to their future offspring
about the nutritional environment when they are born.
There have even been studies which demonstrate
how the experience of fear can be passed down.
(squeaking) (whooshing)
In this study, mice were given something to sniff,
and right after were given a bit of a fright.
This was repeated a few times.
As they sensed danger, their DNA switch relating
to that specific sense of smell was altered.
(electronic warbling)
So whenever they got a sniff of that same smell,
they became afraid and the altered switch
was inherited by future generations.
(chanting) (clapping)
Passing on information about dangers promotes survival.
Perhaps our ancestors used these DNA switches
to pass on messages to us, even before we invented words.
(gurgling)
The world of DNA switches is unbelievably complex.
(buzzing)
But why is such a system in place in our bodies?
The latest studies are shedding light on its real purpose.
March 1, 2016, (inspiring music)
a spacecraft with precious cargo, the first of its kind,
makes its way back to Earth
from the International Space Station.
(dull roar)
The Soyuz spacecraft was descending
under parachute in the overcast sky.
Emerging from the spaceship is Scott Kelly,
who spent almost a year inside the ISS.
Scott Kelly, Scott Kelly back on Mother Earth
after 340 days in space, Dan.
The special cargo he brought back
are blood samples, (mystical music)
collected in space during his year-long stay.
What we're interested in are his DNA switches.
Scott Kelly is an identical twin,
and his brother is also an astronaut.
Scott's blood was analyzed to see how his switches
had altered before and after his trip to space.
This was compared to his brother's Earth-bound DNA.
The studies that I found most interesting
was the DNA part of it, because NASA had never done
any research in the areas of DNA.
They could compare me and my brother Mark,
and they found some interesting stuff.
The scientist responsible
for this detailed analysis was Doctor Christopher Mason.
And then plot them here, so here's the genes
on this section, different genes as we examine them,
and you can see it's like the big changes.
And so what's extraordinary is we saw thousands of genes
that changed their expression,
and also were really epigenetically disrupted
as soon as you got up into space.
Amazingly, during Scott Kelly's 340 days in space,
over 9000 of his DNA switches were altered.
It was an extraordinary revelation.
Because of the high levels of radiation in space,
DNA gets damaged easily,
increasing the risk of getting cancer.
In order to mitigate this, the switch to repair
any DNA damage gets switched on.
Also, in the zero-gravity environment of space,
our bones progressively get weaker.
To try to prevent this, the switch to increase molecules
to build bone switches itself on.
For us on Earth, those two switches would never flip.
That'd be great if our bodies are even smarter
than I thought and are turning these genes on and off
to compensate or to acclimate to this new environment.
What's interesting is we see the body
has never evolved in space, so suddenly it's confused.
It's trying to take all the lessons from millions of years
of evolution and apply it to space.
And epigenetics is the fastest way
to adapt to the new environment and change your genes.
(bird calling)
Our bodies seem to harbor infinite potential,
even being able to adapt
in an unfamiliar territory like space.
(New Age music)
Our ancestors faced so many challenges,
such as extreme changes in temperature and starvation,
due to rapid changes in their environment.
(musical chanting)
DNA switches may have boosted their chance of survival,
allowing them to quickly
and flexibly overcome environmental challenges
during the course of just one lifetime.
And so humanity prospered.
(whooshing)
(gurgling)
We can think of it like this.
DNA does set us on our path,
but we have the power to help it
guide us toward a better future.
Genes are part of our destiny.
This is like playing poker.
You receive these cards, and you have good cards,
but with good cards, if you are a bad player,
you will lose the game, and vice versa.
Switches really, they push you to be one way or the other.
I think fate you can change,
'cause we all control our own destiny, our future.
We make our own path.
Unfortunately when you get cancer,
it's a timeline in your life that you can't change.
But I do think afterwards you can pick your own journey.
You can figure out how, where you wanna go in life.
Our genome, the enigma within us.
Research is shedding light on how our fates can be changed.
(children babbling)
Doctors in Japan took on a new challenge last year.
There are about 7000 children in Japan
suffering from childhood cancers.
It's now understood that in most of these children,
their DNA switches that suppress cancer had been turned off.
In a clinical trial lasting three years,
they're hoping to develop a new treatment by testing a drug
to flip that switch back on.
(speaking in foreign language)
(triumphant music with vocalizations)
Sheltered within our bodies,
genes are the blueprints for life.
As genes are passed down from parent to child,
and then onto the next child,
this precise yet flexible system
holds the key to humanity's future.