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(lively piano music)

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- [Voiceover] Our hands, our eyes, our face,

Official YIFY movies site: YTS.MX

our whole body is a swarm of billions of cells.

At the heart of each of them nestles the DNA

we received from our parents and pass on to our children.

- What exactly is transmitted from one generation

to the next, from one cell to the next?

We know that DNA is transmitted, but not only DNA.

- [Voiceover] Identical twins have the same DNA,

the same genome, yet they're physically different.

How is this possible?

- And then we view the genome as a book

then it can be read in many different ways.

- [Voiceover] Scientists have long thought that DNA alone

ruled our biological destiny.

Today, they're discovering another world.

- We've become more and more aware that DNA

doesn't explain everything

and more and more capable of integrating

the ideas about the impact of the environment.

- [Voiceover] All over the world,

Biologists are exploring this new mystery.

- My work consists in looking at the heart of cells

of new knowledge and going where no one has been before.

- [Voiceover] A scientific adventure where the researchers

are gradually discovering what influences our DNA

throughout our lives, our identity,

and perhaps our heredity.

(lively piano music)

(bright music)

In the natural world,

one insect has always fascinated, the bee.

Its destiny never ceases to amaze and puzzle

the specialists.

They are gradually elucidating

the mysteries of its development.

(calm music)

There are hundreds of species of bees in existence

including this one, the domestic bee,

which lives in a highly organized society.

- I'm standing in front of a colony of bees.

A colony of bees means a large number of workers,

maybe 20, 30, or 40,000.

And there's just one queen, the mother of all those bees.

You can see the queen here.

She has a dot of red paint on the thorax

put there by the bee keeper to help him find her.

Although she's quite clearly different

from the other bees around her,

she doesn't have the same shape, she's longer.

You can also see that her thorax is slightly larger.

The queen's distinctive feature is fertility.

She's the only one able to mate,

so her job is to lay eggs.

(calm music)

- [Voiceover] A queen is therefore very different

from the other workers in her colony,

and yet in the very first days of their lives,

the queen's larvae and the worker's larvae are identical.

How is it that occasionally

one of them steps from the ranks?

(calm music)

It wasn't until the 1950s that this mysterious process

was understood.

- What makes one larva a queen rather than a worker

is largely explained by what it eats.

A larva eats royal jelly for three days

and then if it is destined to become a worker,

its food will be changed and the royal jelly

will progressively be mixed with larval mush

that contains honey and pollen.

The queen larva, however, will continue to eat

royal jelly for the rest of its time as a larva.

(buzzing)

- [Voiceover] Thus, a simple change in diet

can cause profound differences between

two living beings that were so similar

when they started out their lives.

But how can you explain that an external element can have

such an impact on their growth?

Isn't that supposed to be governed by their DNA?

To understand this process,

you have to go back to the origins

or one of biology's most fascinating

scientific adventures, the sequencing of the human genome.

(calm music)

We have long sought to understand the laws of heredity

and the way character is transmitted

from one generation to another.

In the mid-20th century,

we discovered that DNA was the medium of heredity.

In humans, at the heart of a cell,

the nucleus, are 23 pairs of chromosomes.

Each chromosome is made up of two strands of DNA.

Composed of four bases represented by the letters

A, T, G, C, the DNA of a human being

contains three billion letters

which assemble themselves into phrases to form genes.

The genes are used to make the proteins

which make up the building block of living organisms.

In the early 2000s, the sequencing of the human genome

with straws of detailed map of over 25,000

genes was completed.

It was a significant scientific breakthrough

and hopes were high.

(questing music)

- Today, we celebrate the revelation

of the first draft of the human book of life.

- [Voiceover] Scientific journals published the genome map

with pride of place of being given to the almighty gene.

Genome sequencing raised the wildest expectations.

Genes for obesity and schizophrenia will be discovered.

Cancer will be eradicated.

The promises of science seemed endless.

- We are probably, as scientists, a little bit to blame

that we told everybody how important DNA was.

- We said we have deciphered the human genome.

Decipher means taking an encrypted message

and making it intelligible.

But we read the genome and understood nothing.

The actual deciphering is what we do afterwards

what we've not finished doing

and it'll take some time.

- [Voiceover] The scientists know they're only

at the start of the adventure.

They have in their hands a text

that is difficult to interpret.

- DNA is not the only critical thing.

We cannot explain everything just by looking

at DNA sequence.

We need it to know what the sequence is,

but biological complexity and biological systems

are not just about DNA.

They're about the way DNA is used,

the way DNA is read, the way DNA is transmitted.

- [Voiceover] A few months after the announcement

of the sequencing of the human genome,

the review Science for the first time

devoted an entire issue to epigenetics,

a new scientific field that explores what influences

the expression of DNA

for there are too many questions unanswered.

- People were searching for something else

that might explain the beauty,

the complexity of who we are.

- [Voiceover] In Australia, researchers are striving

to understand the fate of bees.

Their genome has just been entirely sequenced.

And there's a big surprise.

There is no genetic difference between the larvae

of a worker bee and a larvae of a queen.

They share the same DNA.

So if the difference between larvae is not genetic,

perhaps it's epigenetic.

Might this famous royal jelly be able to influence

bee larvae genes to the point where it can turn them

into a queen?

The process begins at a larval stage.

After three days, worker larva and queen larva

are no longer fed in the same way.

It's a change that profoundly alters their development.

- Here, we see that they metamorphosed

at different rates.

The queens grow faster than the workers.

After around two weeks here,

a queen is ready to emerge,

whereas a worker will take three weeks.

- [Voiceover] So it is the feed, the royal jelly,

which makes the difference.

But how does it act on the the larva genes?

- In chemical terms what happens is an epigenetic mechanism.

The methylation of the DNA which triggers

these various growth programs.

- [Voiceover] Bee DNA contains around 10,000 genes.

As with all living organisms, some genes are active

or expressed as they say, others are inactive.

The expression of genes can be inactivated

by what is called the methylation of the DNA.

It's a simple chemical mark that attaches itself to the gene

and in a way enables it to be turned off

like a switch.

- If there's a lot of DNA methylation during early growth

then you'll get workers, whereas if the DNA methylation

is turned off then you get queens.

In the same way that food activates

a certain epigenetic program that enables

either queens or workers to be created,

here we're injecting molecules into these eggs

to stop DNA methylation.

And so, all these eggs will grow into queens.

- [Voiceover] Thus is the amazing recipe for making queens

revealed to us.

There is no queen DNA nor worker DNA,

just chemical modifications around their genes

which play a key role in their growth.

This applies to bees,

does it also apply to other species, other queens?

Jonathan Weitzman has his own ideas on the matter.

- Another example from nature,

I'm British, to the left is our queen,

queen by birth, so we can say she's a genetic queen.

To the right are the bees who have just one queen

but she's not born to be queen.

In time, one of the bees becomes a queen

because she eats royal jelly.

So you can see in England, there are two ways

of becoming a queen, either genetically on the left

or by interaction with your environment,

you can, in a few rare cases, become a queen.

(laughter)

- [Voiceover] What are we made of?

Who are we?

Whether it's a matter of scientists or cells,

DNA doesn't explain all the diversity of life.

Cells from our liver, our eye, or our hand

all have the same genome.

And yet they're almost as varied as the researchers.

So how do you explain such diversity?

(applauding)

This question fascinates Jonathan Weitzman.

He explores the issue of identity starting with that

of ourselves.

- In our body we have hundreds of different cell types,

cells that behave differently to have different

characteristics, and they transmit those different

characteristics to their daughter cells.

The hepatocytes in the liver, the neurons in the brain,

the lymphocytes in the blood,

the keratinocytes in the skin,

all these cells are behaved differently.

They use the genome differently.

And yet they all come from the same original cell,

the fertilized egg.

How did the first cell give all these diversity

of cellular states with the same genome?

- [Voiceover] It is a question that Scottish biologist,

Conrade Waddington, began to answer in the 1940s.

He was the first to coin the term epigenetic.

Fascinated by the growth of organisms,

Waddington wondered how an embryo became a bean

made up of many varied cells that all sprang

from a single cell.

- Conrad Waddington drew a picture of a landscape,

of a mountain, and at the top of a mountain

he placed a cell or a bead,

and the idea was that at the top of the mountain,

the cell could become many different things

depending on which path down the mountain it took.

So at the top of the mountain

is like the multipotent stem cell

that can become any different type of cell.

And as the cell moves down the mountain,

it becomes more and more committed

to a particular path depending on

which valley it goes in to.

And that will determine its fate.

(calm music)

- [Voiceover] Liver cells, heart cells,

skin cells, brain cells,

the fate and the identity of our cells are not only

etched in our DNA,

other mechanisms come into play,

so that cells differentiate and more especially

that they keep the memory of their identity.

- We all know that we began as an egg.

From that point, each being develops

with this epigenetic function

that enables genetic data to be read.

There's something a bit magic and all that.

It's wonderful to think that we're trying to understand

how it works, how I or how this plant are made

from this genetic data which has been changing

for two billion years.

And then these epigenetics can read the system

and make the plant or the human being that I'm looking at.

- The genome were not changed during the

differentiation process,

what will change is the way that genome is used.

And that's epigenetic mechanisms that will control that,

that will determine which parts of the genome are used

and which parts of the genome are not used.

- [Voiceover] The way our cells are expressed

is therefore critical to our growth

and that of our cells.

- There had been many ways to think about epigenetics.

One metaphor that that does work well is music.

So, music is written with lines and dots

and yet the lines and dots are critical

to playing the music.

(calm piano music)

But every time those lines and dots are played

by a musician or by an orchestra,

they will sound different.

(lively piano music)

So the music written down could be like the DNA

and the expression of that requires a musician

and an interpretation.

- [Voiceover] The same genetic partition can have

several interpretations.

Who better to understand this than twins?

Born from the same egg, identical twins

share the same DNA.

Are there differences of interpretation in their genome?

- I love garlic.

- I hate garlic.

- He runs much faster than I do.

- He needs to practice more than I do.

- My French isn't bad.

- I don't speak French.

(comical music)

- [Voiceover] Jonathan Weitzman and his twin, Mathew,

are both researchers.

They share the same DNA And the same questions

about identity.

- Yeah, maybe we're both interested in genetics

because we've always been interested in

what's transmitted, what makes us who we are.

- We're a combination of our genome,

our epigenome, our experiences.

That's what makes me who I am today.

But those experiences and the changes

in our epigenome will tell me who I am tomorrow.

(comical music)

- The genome is relatively static.

The epigenome is in comparison relatively dynamic.

Identity, who we are, is something that changes

all the time throughout life.

And so, the epigenome must in some way

carry memories of that past and probably contribute

to defining who we are.

So the longer we live, the more our epigenomes will diverge.

And there are studies that have shown

or begun to show that this is the case.

(calm music)

- [Voiceover] So our genes are being influenced

throughout our lives.

Our experiences have an impact on our expression.

How is this expressed in two people with the same DNA

like identical twins?

That's what Manel Esteller set out to find

here in Barcelona.

(foreign language)

- Studies on twins show that the DNA conditions what we are

and the disease we develop,

but it's not a closed book.

These studies are essential in demonstrating

that there is a certain genetic determinism,

but not 100%.

- [Voiceover] Studies on identical twins is a way

to better asses the influence of epigenetics

on the development of individuals.

But do they also play a role

in the appearance of illnesses?

- Studies on identical twins are also important

in the field of cancer research.

With sisters who have inherited the genetic mutation

that gives them a higher risk, let's say 80%, 90%

of contracting breast cancer.

It can happen that one of the sisters

develops cancer at 60 and the other never or at 90.

How is this possible that the DNA is the same?

Well, it's because there are epigenetic differences.

- [Voiceover] So there are epigenetic differences

between twins, differences which are sometimes

the sign of anomalies and could be used as flags

in checking for he appearance of illnesses like cancer.

(calm music)

By exploring these new territories,

teams like that of Edith Heard at the Institut Curie

bring renewed hope to this field.

- We know that cancer is a genetic disease.

We know that changes at the DNA sequence level

are important in the cancer process.

However, we're starting to realize more and more

that it's also an epigenetic disease,

that there are changes in gene expression

that don't necessarily involve a change

in DNA sequence that are actually implicated

in the progression of tumors.

- [Voiceover] Edith Heard's team has just broken new ground

in understanding these mechanisms.

The researchers focused particularly on a fascinating

chromosome in female mammals, the X chromosome.

In human beings and in most mammals,

the sex is determined by the X and Y chromosomes.

Females inherit two X's and males, one X and one Y.

But with 100 genes on the Y against 1,300 on the X,

there's a clear imbalance.

To restore the balance, one of the two X chromosomes

is inactivated in females right at the start

of their embryonic development.

In fact, it's an epigenic mechanism which contributes

to silencing one of the X chromosomes

and above all of maintaining that silence

throughout a female's life.

- X inactivation is essential.

If one of the two X chromosomes is not shut down

during development of the female,

the embryo dies very early on.

This illustrates how important it is

to get gene dosage right.

If you have an excess of expression of genes

from the X chromosome, that leads to lethality.

(lively piano music)

- [Voiceover] Feline or human being,

this process is in fact inevitable in most female mammals.

To Edith Heard, this vital phenomenon

provides a lot information on how normal

and cancerous cells function.

Throughout our existence,

our cells are renewed by division.

And with each division, epigenetic mechanisms

keep the memory of the X inactivation.

But what happens when the cell losses that memory?

That's what researcher Ronan Chaligne is trying to find out.

In their normal state, in the nucleus of these cells,

the inactive X is very inhibited as in this diagram.

But in the breast cancer, its aspect changes.

- In tumor cells, we've discovered in recent years

that the inactive X was still present

but there was a change in its silent state.

This inactive X has a formal relaxed, less dense structure.

We've noticed that in cancer cells where the

epigenetic mechanisms are disturbed and deregulated,

there's a reactivation of certain inactive X genes

which are normally suppressed.

- [Voiceover] But the fact that some genes are reactivated

favors the growth of tumors.

This research opens new avenues of action against cancer.

- Epigenetic changes also provide hope in cancer

because epigenetic changes can be reversed.

Unlike DNA sequence mutations that can't really be reversed

in any easy way, this contrast with an epigenetic change

which can indeed be reprogrammed or reversed

with certain molecules.

So currently, there's great hope that

some types of cancer could actually be treated

by drugs that target the epigenetic machinery.

- [Voiceover] Molecules which target these processes,

epi-drugs, are currently undergoing trials.

But researchers have discovered that medication

marketed several years ago

unwittingly affect epigenetic mechanisms.

- In fact, one drug that has been used for many,

many decades turns out to be an epi-drug.

Decitabine, as its called, is used to treat

myelodysplastic syndrome which is actually

a blood disorder that leads eventually to leukemia.

And so it was discovered many, many years ago

as a successful treatment in slowing down

the progression of this disease.

So this is an example of an epi-drug that is used

in the clinic that is successful.

What's important to know though

is we don't actually understand the targets

of these epi-drugs.

We know that some of them can work in the clinic

but the challenge now is to understand how they do it.

(lively piano music)

- [Voiceover] Epi-drugs present a promising lead

in the fight against cancer.

The role of epigenetics in the development

of individuals and of certain diseases

is gradually becoming clearer.

But in the same way that genes are passed

from one generation to another,

could these mechanisms that influence

the gene expression also be transmissible?

- At what type of information is transmitted

to the next generation is still a very open question.

We know that characteristics have been transmitted

but I look like my father and my mother.

My son and my daughter look like me.

So, where does this come from?

We focus a lot on the DNA

mainly because we could.

It's easy to measure.

It's easy to find the sequence.

Now, we're interested more and more

in what's transmitted with the DNA

or around the DNA or above the DNA.

(calm music)

- [Voiceover] How can we get a better insight

into this transmission?

Currently the best clues are supplied by plants.

Geneticist Vincent Colot has carried out research

on a little plant from the same family as mustard,

a plant called Arabidopsis or mouse-ear cress.

(calm music)

- Arabidopsis is a plant which is of great interest

to geneticists because it is very prolific.

It has a very short development time,

in other words, it can go from seed to seed

in less than two months and the cherry on a cake,

we know it has a very compact genome.

- [Voiceover] Can Arabidopsis pass on to subsequent

generations visible changes such as longer or shorter roots

or early or later flowering without this

being written in the DNA?

To find out, researchers induced epigenetic modifications

in an Arabidopsis plant.

They then crossed this plant with a wild plant.

And after successive crossbreeding,

they obtained a family of plants over several generations.

The first major discovery, these epigenetic modifications

are transmitted and remained stable

through at least 16 generations.

The second observation, these modifications

are associated with visible changes such us root length

or the flowering period.

So, for the first time,

scientists are able to show evidence

that characteristics can be transmitted over a large

number of generations without any change

in the DNA sequencing.

- What we also found was that this epigenetic variation

passed on through the generations

has a lower stability than that of the states

of DNA sequencing.

The sequence of the DNA is 80 GC written in a particular way

and transmitted with extreme fidelity

unlike the epigenetic state which evidently appeared

to be less stable.

In other words, this transmission we're measuring

will last for certain number of generations,

tens or even hundreds of generations,

but certainly not millions of generations.

(calm music)

- [Voiceover] Thanks to this experiment,

scientists have evidence of the transmission

of epigenetic marks which modify certain aspects

of the plant.

In this case, the modifications have been induced

in a first generation of plants in the laboratory.

But what happens in nature?

Can these changes be induced by the environment

in case of drought, for example?

- We're facing an unknown, the part environment plays

over the way genes function.

But how far does that environment dictate

heritable changes over generations?

That's an open question.

Does environment play a part?

- [Voiceover] To answer this question,

Vincent Colot and his researchers at INRA have launched

a new experiment.

They have installed hundreds of genetically identical plants

on the conveyor belts of this system

that's unique in the world, the Phenoscope.

(jazzy music)

The mechanical rotation system exposes the Arabidopsis

plants to the same light and enables only the watering

to be varied to measure its impact.

- The question we're trying to answer now is

what are the conditions that lead to the appearance

of epigenetic variations.

Is the environment itself capable of inducing

this type of change?

And if so, are the changes we observe as stable as those

we've managed to establish experimentally in the laboratory

over how many generations and with what range?

That's more or less the range of questions

we can tackle, thanks to this totally unique

experimental system, the Phenoscope.

(calm music)

- [Voiceover] The result of this research

are eagerly awaited.

They will enable us to see whether environmental factors

such as drought can influence the plant genome

over several generations.

What do we know of other species?

What can we say about the impact of environment

on our own genome?

- It's an ongoing search and debate

to understand exactly what is transmitted

to the next generation, how much other information

is transmitted.

Do we transmit information about the environment

in which we live?

Some people think it may be quite subtle, fine tuning.

Some people think that it may have a very big impact.

(calm music)

- [Voiceover] Thousands of kilometers away

in the American Northwest, a researcher is convinced

that environment plays a major role

in our organism and that it leaves lasting traces

transmissible via epigenetic mechanisms.

A specialist in reproductive biology,

Michael Skinner, came to epigenetics rather by accident.

An error manipulation enabled him to study the effects

of pesticides on several generations of rats.

- Most scientific observations are not

necessarily plant and so this is what you would call

a serendipitous observation.

So we were studying the effects of this fungicide

on the gestating female

and we wanted to see what would happen

if a fetus was exposed to its health

when it was born and grew up to become an adult.

- [Voiceover] The American researchers' study

focuses on the effects of pesticides.

They were looking to gauge their impact

on the fertility of male rats.

They had therefore injected pesticide into pregnant females.

When the babies were born, there were no anomalies.

But as adults, the male sperm count

signaled a drop in fertility.

These males reproduced for the first time.

Their offspring in turn presented defective sperm.

The crossbreeding continued through to their

great-grandchildren.

Then came a surprise.

The same anomalies were observed in the male descendants

though there was no more direct exposure to pesticides

neither via injection nor via the maternal uterus.

Moreover, with each generation,

epigenetic modifications were discovered

and correlated with sperm anomalies.

- 90% of the males had this reproductive abnormality

that was carried for four generations.

And so, that showed us that we had

a phenomena that was not following classic genetics,

it was definitely different.

And so we follow that up to show

that there was this epigenetic

transgenerational inheritance.

- [Voiceover] Have these results been confirmed?

Not really.

But no one has reproduced a study in the same conditions.

Michael Skinner claims to have shown that pesticides

can cause non-genetic anomalies

that are transmissible in rodents.

Some decry the work as too partial

with hasty conclusions that undermine

the concepts of heredity and trigger debate.

- You're not doing something controversial,

you're not doing something really important.

You know, the subtle of changes are not important,

it's a matter of you're not gonna make

the big steps in science.

So if all of the scientists started thinking that way,

then there would be challenges

to all of our dogmas much, much more rigorously

than there is today.

But instead, we have this tendency to accept the dogma

and work within it without challenging it.

So that's not the best way science

should be done in my mind.

- [Voiceover] Here and there,

experiments similar to that of Micheal Skinner

were conducted.

Here in Zurich, Isabelle Mansuy's team

was also seeking proof that epigenetic heritage

was linked to the environment.

But this time the subject was stress.

Is it biologicaly transmissible?

- We use the mouse as an animal model

to test the theory that exposure to traumatic stress

during childhood can alter

the epigenetic mechanisms permanently

and modify adult behavior.

- [Voiceover] To create trauma in suckling mice,

the young were separated from their mothers

unexpectedly and repeatedly.

- What we were able to show is that

exposure to periods of chronic stress

altered the mouse's behavior.

And also in parallel altered a certain number

of epigenetic mechanisms in the brain and in offspring

and that these epigenetic modifications

were passed through the generations.

- [Voiceover] The baby mice that grew up in this conditions

were depressed as adults.

They evaluated danger less well and took more risks,

disorders that they pass on to their descendants

as far as their great grandchildren.

- An important lesson we can draw from these results

is that not everything resides in the genes.

But the environmental factors to which we are exposed

in particular trauma during childhood are very important

and can determine our behavior in our life

across several generations.

What excites me about the field of epigenetics

is the consequences,

the applications for human beings,

especially in psychiatry

because there are many psychiatric illnesses

like depressions, schizophrenia,

personality disorders that aren't known.

We don't know the causes, we don't know the mechanisms

and we think that our research into epigenetics

could lead to a better understanding of these diseases.

- [Voiceover] It is much too early to say

whether we can pass on stress as the mouse could.

According to the work of Isabelle Mansuy

and Michael Skinner, genomes are like sponges,

absorbing the slightest effects of the environment.

(lively piano music)

Effects that leave traces that are passed on

for several generations.

(dramatic piano music)

These conclusion are the subject of debate

within the scientific community.

- In fact, if you think about it,

if we were that susceptible to environmentally induced

epigenetic changes, we'd be a mess.

All cell types will change identity, probably tumors,

and actually we'll probably not even be here.

We wouldn't be alive.

- [Voiceover] How far are we affected by our environment?

And what do we pass on to our children?

In reality, the influence of epigenetics

comes up against limits that have just been discovered.

In sperm and ova, then at the moment of fertilization,

a large portion of the epigenetic marks are erased

enabling a kind of reboot for the new generation.

But this spring cleaning is incomplete,

some marks remain in place.

Which ones and why?

That's the mystery that Wolf Reik and his team

are working to solve in Cambridge.

- On aspect of the transgenerational epigenetics

is probably incomplete erasure.

We would like to understand what's going on.

A choice between what's erased and what is not erased,

and also if that choice could be changed.

So for example, if the environmental conditions

are different, if the food supply is different,

if the nutrition is different,

is there a mechanism by which it could switch

this choice between erasing information

and giving it to future generations.

It is a very, very exciting question.

- [Voiceover] This selecting erasing

can be seen under the microscope.

These are very early embryo cells.

The nuclei are blue

with practically no epigenetic marks.

And purple are the few marks retained

that were transmitted by the parents.

But take a look a few days later,

the cells, now more developed

at a more advanced embryonic stage,

are already harboring a constellation

of new epigenetic marks linked to their growth.

- Probably for the last 10 years or so,

we have been very actively studying this erasure process

because it really fascinated us.

I think there are many unexplored areas,

it's probably true

that the epigenome

is influenced by nutrition, by the food that we have,

where we grow up, and environment and things like that,

and also potentially, what happened to our parents,

in terms of the environment, the food and things like that.

- [Voiceover] A few phases from Wolf Reik's laboratory,

still in Cambridge, a team of researchers

wanted to clarify another issue.

Is food capable of marking our DNA?

And if so, do we pass this on to our descendants?

Anne Ferguson-Smith is examining the impact

of food deprivation on a pregnant mouse

on her young and on subsequent generations.

- When a mother is caloricly restricted during pregnancy,

she's gonna have quite profound effects on her offspring.

And this particular mouse model

is a 50% caloric restriction.

That's a very severe undernourishment.

And the mice are born small, the babies are very small

and they go on in adulthood to get fat

and diabetic.

They don't metabolize glucose properly or insulin properly

and they have, disease is very similar

to what we see in our population today

with this increase incidence of adiposity,

obesity, and diabetes.

In this model, if you continue to undernourish

the embryo after birth, the symptoms don't arise

and actually the animals are very healthy.

- [Voiceover] It's as if the baby mice exposed

to food deprivation in the womb

were programmed to adapt to this shortage.

And when they grow up in an environment

where food is abundant,

they are no longer well adapted

and develop diabetes and obesity.

The next generation, the grandchildren,

show the same symptoms.

How many generations can be affected by these illnesses?

The research on mice is continuing.

But how can we find out whether food is capable

of having such an influence in humans?

- So obviously, one can't do experiments

on human populations like this.

But we do know that in history

there are situations where there have been similar

environmental compromises to pregnant women.

In particular, the Dutch Hunger Winter

of the Second World War.

- [Voiceover] During the winter of 1944,

part of the Netherlands suffered greatly from famine.

In order to punish them for their support of the allies,

the Nazi occupants blocked all food deliveries.

The survivors and the descendants

are of particular interest to researchers in epigenetics.

- So these are very moving pictures

and in fact, here, there are pregnant women

and you can really see the challenges

that they must be facing

in this time of deprivation.

The children of these pregnant women

have been analyzed and had been shown

to have increased incidence of adult-onset diseases

such as diabetes, obesity,

neurological disorders

such as anxiety and depression and schizophrenia.

And also an increase incidence of cardio-vascular disease.

But what has been discovered is that

the offspring of the sons of these women

are heavier as adults.

So this does tells us that the environment

is having some kind of effect

over at least a couple of generations.

(calm music)

- [Voiceover] Research devoted to the impact

of the environment on the genome has only just begun

and there are number of mysteries to be cleared up.

- So genetics is wonderful.

It's the most important mechanism for transmitting

healthy and unhealthy outcomes

from one generation to the other.

But what is emerging now is that

there's something else on top of the genetics

that can have an impact on health and well-being

from one generation to the next.

And to me it's an extremely exciting prospect,

trying to understand what that mechanism

might be, that non-genetic mechanism

for conferring this intergenerational effect.

- What excites me about epigenetics is that,

it gives us lots of waste to express a static genome

and it gives us a way to look at the traces

of environmental impacts and the traces of our own

personal histories on the way genomes behave.

And I think what I like particularly

is that it's reversible.

It's sort of of optimistic

that nothing is set in stone.

- Effectively, this widens the field of genetics.

We're not dealing with something

that is passed on unchangingly.

But there's a wealth of possibilities

between an almost evanescent transmission

to something that is virtually engraved in marble.

And epigenetics occupies a large part

of what isn't written in stone.

- [Voiceover] Epigenetics is now in full swing.

Research is growing all the time.

But it will take a few more years

and a good many studies

to fully grasp the subtleties of life's lush musical score.

(lively piano music)