CIENCIA (Secretos de Nuestra Herencia)
La humanidad está en los albores de una nueva disciplina: la epigenética. La investigación en esta área sugiere que la dieta, los contaminantes, el estrés y una serie de otros factores ambientales pueden alterar la expresión génica. Estas marcas "epigenéticas", que explican en particular por qué los gemelos son a veces tan diferentes, o por qué una abeja se convierte en reina en lugar de trabajadora, son transmisibles a los niños, incluso a los nietos. Contrariamente a lo que la genética ha estado sugiriendo durante años, nada parece definitivo. Estamos ante una nueva revolución en el campo de la biología.
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TVTranscript
00:00The hands, the eyes, the face, our body is a swarm of billions of cells that treasure
00:12the DNA that our parents have passed on to us and that our children inherit.
00:18What exactly is transmitted from one generation to another, from one cell to another?
00:23We know that DNA is transmitted, but it is not the only thing.
00:30Monozygotic twins or identical twins have the same genome.
00:34So, why are they not always the same?
00:39The genome is like a book that can be read in very different ways.
00:44For a long time, scientists have believed that DNA controlled our biological destiny.
00:52But things are not that simple.
00:56The advancement of technology and its new tools allow us to affirm that, in the study
01:01of DNA, we must consider the impact of the environment.
01:07Biologists from all over the world are investigating this new mystery.
01:11Exploration is to search in all cells, to know new knowledge and to go where people
01:16have not been before.
01:18It is a scientific adventure that will allow us to discover the hidden factors that alter
01:22our DNA, our identity and perhaps our genetic heritage.
01:37The human being has always been fascinated by the laborious bee.
01:44Its nature never ceases to raise questions to scientists who, little by little, are unraveling
01:49the mysteries of its development.
01:56There are thousands of species.
01:59Perhaps the best known is the domestic bee or the honeybee.
02:05A colony like the one I have in front of me is made up of a large number of workers
02:10that can range between 20,000, 30,000 and even 40,000 and a single queen bee that is
02:17the mother of all the others.
02:20The queen of this colony is easily distinguishable because they have placed a red dot on her back
02:25to always know where she is.
02:28Her body is different from that of her daughters.
02:30Its silhouette is longer and has a slightly wider thorax.
02:36The queen is the only fertile bee, the only one that can mate and her mission in life
02:41is to lay eggs.
02:55The queen is very different from the workers that pollinate around her.
02:59However, in its earliest stage, all the larvae are identical.
03:03What is the mechanism that turns one of them into a queen?
03:16The mystery was not unraveled until the middle of the 20th century.
03:26The process that makes a larva become a queen instead of a worker is based on the
03:31food that it receives.
03:34Larvae eat royal jelly for three days.
03:37Then, if they are destined to become workers, their diet varies.
03:42Royal jelly is mixed with larval papilla, made up of pollen and honey.
03:48Instead, the future queen will continue to be fed royal jelly during the rest of her
03:53larval stage.
03:57What shows that a simple nutritional change can make a significant difference between
04:02two similar beings during the first days of their life.
04:07But how is it possible that an external element can have such an impact on their development?
04:13Isn't that supposed to be controlled by DNA?
04:19To understand this process, it is necessary to go back to the origins of one of the most
04:24fascinating aspects of biology.
04:27The sequencing of the human genome.
04:34Scientists spent a long time trying to understand the way in which the characters of one generation
04:40to another are transmitted.
04:41And finally, in 1952, the exclusive role of DNA was completely ratified.
04:51The nucleus of each human cell contains 23 pairs of chromosomes.
04:57Each chromosome is made up of two chains of DNA.
05:04It has four nitrogenous bases, represented by the letters A, T, G and C.
05:10The DNA of a human being has 3 billion letters that are assembled to form the genes, which
05:16in turn synthesize the proteins, the basic parts of living beings.
05:22The sequencing of the human genome, which exposes the detailed map of our 25,000 genes, ended
05:28in the year 2000, which opened the door to immense possibilities.
05:40This is today's headline.
05:42Today, we feel happy to unveil the first draft of the great book of human life.
05:57Scientific journals published the map of the all-powerful genome.
06:01Its almost complete sequencing aroused the most incredible hopes, such as the discovery
06:06of the genes of obesity and schizophrenia and the eradication of cancer.
06:11The promises of science seemed to have no end.
06:17It is very likely that scientists are largely to blame for so much talk about the importance
06:23of DNA.
06:24They proclaimed that we had decrypted the human genome.
06:28Deciphering is taking a encrypted message and making its reading intelligible.
06:32But reading the translation does not imply understanding its meaning.
06:36It was then that we started decoding, which will still take us some time.
06:46Scientists know that this adventure has just begun and that the text they have in their
06:52hands is very difficult to interpret.
06:56We cannot answer all the questions by looking only at the DNA sequence.
07:03We need to know the whole genome.
07:06Our biological complexity does not respond only to the characteristics of the DNA.
07:10It also depends on how it is used, read and transmitted.
07:17A few months after the sequencing of the human genome, Science magazine first dedicated
07:23an entire issue to epigenetics, the study of the factors that interact with the genes
07:28and its possible hereditary transmission.
07:33The unanswered questions began to accumulate.
07:43Scientists were looking for new elements to explain the beauty and complexity of the
07:48human being.
07:49In Australia, a research laboratory is trying to better understand the laborious bee, sequencing
08:00all its genome.
08:03The results show that there is no genetic difference between the larvae of the queen
08:08and the workers.
08:10They all share the same DNA.
08:23If the difference is not genetic, it may be epigenetic.
08:28Everything seems to ratify that the royal jalea is capable of creating an interaction
08:32with the initial genes of the larva and convert these into genes of the queen.
08:39The process begins during the larval state.
08:42After three days, the future queen receives an exclusive feeding.
08:46A change that will profoundly modify its development.
08:51After the metamorphosis, the nymphs progress at a different pace.
08:56The development of the queens is much faster than that of the workers.
09:01A queen will be ready to emerge in just two weeks, but the workers will need
09:06one more week.
09:10So it is the royal jalea that makes the difference.
09:13But how does it work on the genes of the larva?
09:21The methylation of DNA, an epigenetic mechanism, is what triggers these different
09:26development programs.
09:30The DNA of the bee contains about 10,000 genes.
09:33And as in all living organisms, some of its genes are expressed in scientific language,
09:39while others remain inactive.
09:43The expression of the genes can be silenced by the methylation of the DNA, a kind of
09:49chemical mark that is added to a gene and allows to turn it off, as if it were a switch.
09:54If the methylation of the DNA is intense in the initial stages, we will have worker bees.
10:03But if we suppress the methylation, we will have queens.
10:07In the same way that feeding activates an epigenetic program that determines the creation
10:12of workers or queens, we inject into these eggs some molecules that interrupt the methylation
10:18of the DNA, which will allow them all to become queens.
10:26The system used to create a queen is surprising and shows that certain chemical modifications
10:32in identical genes can play a crucial role in the development of a living being.
10:38The unique case of bees could be reproduced in other species?
10:43Jonathan Weitzman has his own opinion on this.
10:48I will give you an example.
10:50I am British and this is my queen.
10:53She was born a queen, so we could say that she is a genetic queen.
10:58On the right you can see the queen of bees, but the queen was not in her genes.
11:03Over time, a larva becomes a queen because it is fed with royal jelly.
11:09As you can see, in England there are two ways to become a queen.
11:13You can be the genetic queen, and in some cases, not very often, you can become a queen
11:19by interacting with the real environment.
11:25What are we made of? Who are we?
11:28Whether it is scientists or cells, DNA does not explain our immense diversity.
11:34The cells of the liver, the eye or the hand have the same genome.
11:40However, they are almost as different as scientists.
11:43How is it possible to be so complex?
11:48Jonathan Weitzman is passionate about this topic.
11:51He keeps asking questions about the behavior of our cells.
11:57In our body there are hundreds of types of cells
12:00with very different behaviors and characteristics
12:03that will transmit to the next generation of cells.
12:07The cells of the liver, the neurons, the lymphocytes in the blood, the skin cells,
12:13all of them behave differently and use the genome in a very different way.
12:19And yet, they all come from the same original source, the fertilized egg.
12:25And I wonder, how can this original cell give rise to such a diversity of cellular states
12:31starting from the same genome?
12:33The Scottish biologist Conrad Waddington,
12:36the first to use the term epigenetic,
12:39began to answer this question in the 1940s.
12:44Waddington kept asking himself how a embryo could become
12:48a being composed of varied and numerous cells
12:51from a single cell.
12:54Conrad Waddington drew a landscape with a mountain,
12:58and at the top he placed several cells
13:01represented by balls of the same color
13:04that, as they descended through their irregular slopes,
13:08could become different cells depending on the path they took.
13:14So, at the top, when they start to slide from the summit,
13:17their course is uncertain.
13:19At that moment, they can become different cells,
13:22and as the cell moves down that path,
13:25it becomes more and more narrow,
13:28depending on which valley it goes into,
13:31and that position will be shaped.
13:39Cells of the liver, of the heart, of the skin, of the brain,
13:44the destiny and the identity of our cells
13:47is not only engraved in the DNA.
13:50Other mechanisms work so that the cells
13:53differentiate and store the memory of their identity.
13:58We are all aware that the origin was an egg,
14:02and from there, each living being was perfecting
14:05an epigenetic mechanism to read genetic information.
14:09There is something magical about all this.
14:12I find it wonderful to think that we are beginning
14:15to understand how it works,
14:19that we are understanding how a small plant
14:22can be created from genetic information
14:25that has been modified for 2 billion years,
14:29and that we are learning to read the coding system
14:32that has made that plant, or the human being that I have in front of me.
14:37The genome does not change during cell differentiation,
14:40what changes is the way to use it,
14:43and it is the epigenetic mechanisms that determine
14:46which part is used and which part is not.
14:52The way our genes are expressed
14:55is decisive for the development of our cells.
14:59There are many ways to explain what epigenetics consists of.
15:03The metaphor that works best is music.
15:06Musical scores have lines and characters
15:09that set the guidelines for playing the music.
15:16But every time those signs are interpreted
15:19by different artists, they sound different.
15:26In this metaphor, the score is the DNA.
15:29But for the melody to sound,
15:32we need musicians,
15:35and for the melody to sound,
15:38we need musicians,
15:41and for the melody to sound,
15:44we need musicians and an interpretation.
16:03The same genetic score
16:06can be interpreted in different ways.
16:10Monophygotic twins are the perfect example.
16:14They come from the same ovum and share the same DNA.
16:19But their genome seems to have been interpreted by different musicians.
16:24I love garlic.
16:25I hate it.
16:26He runs much faster than me.
16:28He needs training.
16:30My French is not bad.
16:32I don't even speak it.
16:37Jonathan Weitzman and his twin brother, Matthew,
16:40are researchers.
16:42They share the same DNA
16:44and the same concerns about identity.
16:47Maybe we're interested in genetics
16:49because we've always been fascinated
16:51by hereditary transmission,
16:53what makes us who we are.
16:55We're a combination of our genome,
16:57of our epigenome,
16:59and of our experiences.
17:01That's what makes me who I am today.
17:03But those new experiences
17:05and the changes in my epigenome
17:07will make me who I am tomorrow.
17:12The genome is relatively static.
17:14The epigenome, in comparison,
17:16is relatively dynamic.
17:18Identity, who we are,
17:20changes over time in our life.
17:22And so the epigenome,
17:24in a certain way,
17:26acts as the carrier
17:28of the memory of our past
17:30and contributes to define
17:32what we are at every moment.
17:34So the longer we live,
17:36the more our epigenomes diverge.
17:38And there was something
17:41that was identified
17:43by recent investigations.
17:51Throughout life,
17:53genes interact with many factors.
17:55Our experiences
17:57condition their expression.
17:59But how does that influence
18:01two monocygotic twins
18:03that share the same DNA?
18:05This is what researcher
18:07Manel Esteller is trying to find out
18:09Manel Esteller
18:11How are you?
18:13Fine. Hello.
18:15Berta?
18:17Yes. Grisela.
18:19Welcome.
18:21As you know, we are studying epigenetics.
18:23Alterations or changes
18:25that you can have
18:27in your genetic material
18:29despite being twins.
18:31They are normal changes.
18:33There is nothing to worry about.
18:35I can explain some differences
18:37You are now more equal
18:39or more different than 10 years ago.
18:41Do you differ little
18:43or are you still very close?
18:45Physically, I think
18:47we are differentiating a little.
18:49The features are changing.
18:51Yes.
18:53Monocygotic twins
18:55can also be different
18:57if you look at the fingerprints.
18:59Do you see them different?
19:01This is a purely epigenetic change
19:03without any genetic alteration
19:06They are very similar
19:08but they can be distinguished.
19:10There are certain differences.
19:12This is the appearance
19:14at birth.
19:16I was born with this stain
19:18and she did not.
19:20What is this change due to?
19:22We do not know.
19:24It could be that there was
19:26a small genetic mutation
19:28or it could be an epigenetic change
19:30associated with it.
19:32We will not know until we look at it in detail.
19:34You are genetically identical
19:36but epigenetically you are diverging.
19:38You are diverging
19:40because lifestyles are different.
19:42You can see it physically
19:44and also in the growth
19:46that you will have
19:48and also in the diseases.
19:50This will change
19:52and it will be very important
19:54for these two individuals
19:56who are not photocopies.
19:58The conclusions derived
20:00from the study of twins
20:02and diseases
20:04but it is not a closed book.
20:06These studies were key
20:08to demonstrate
20:10that there is genetic determinism
20:12but not 100%.
20:14Studies with identical twins
20:16allow us to evaluate
20:18the influence of epigenetics
20:20on development.
20:22But does it also intervene
20:24in the appearance of diseases?
20:27The study of monocytotic twins
20:29is also important in cancer
20:31because we sometimes have
20:33the question of people
20:35who have a dominant mutation
20:37that considers a risk
20:39of 80-90% of breast cancer
20:41and one of the sisters
20:43has breast cancer at 60
20:45and the other does not
20:47or has it at 90.
20:49How is it possible
20:51if her DNA is the same?
20:53Because there are epigenetic differences
20:55between identical twins
20:57that could reveal anomalies
20:59and even serve as markers
21:01to control the appearance
21:03of diseases as serious
21:05as cancer.
21:17The research team
21:19led by Edith Heard
21:21of the Coogee Institute
21:23has brought new hopes
21:25in this field.
21:27We already knew
21:29that cancer is a genetic disease
21:31and that some changes
21:33in the DNA play
21:35a relevant role
21:37in its appearance.
21:39But our research shows
21:41that it is also
21:43an epigenetic disease
21:45and reaffirms our conviction
21:47that changes in the expression
21:49of genes,
21:52as well as in the expression
21:54of genes,
21:56can be caused
21:58by a mutation
22:00in the DNA.
22:02This is the case
22:04of the X chromosome.
22:06The X chromosome
22:08represents
22:10a mutation
22:12in the DNA
22:14of the X chromosome
22:16and the X chromosome
22:18of the Y chromosome
22:20The females have
22:22two X chromosomes
22:24and the males one X
22:26and another Y.
22:28The Y only has 100 genes
22:30compared to the 1,300
22:32that the X treasures.
22:34So, to balance the balance,
22:36one of the female chromosomes
22:38is inactivated at the beginning
22:40of embryonic development.
22:42An epigenetic mechanism
22:44known as genetic dose compensation
22:46that helps keep one of the X chromosomes
22:48inactivated throughout the life
22:50of the female.
22:52The inactivation
22:54of the X chromosome
22:56is essential.
22:58If one of them
23:00is not inactivated
23:02during the development
23:04of the female,
23:06the embryo will die immediately.
23:08The genetic balance
23:10is essential.
23:12An excess of expression
23:14of the X chromosome genes
23:17including felines
23:19and human beings
23:21is essential.
23:27This vital phenomenon
23:29provides a lot of information
23:31about the functioning
23:33of healthy cells
23:35and cancerous cells.
23:37As a general rule,
23:39our cells double
23:41their DNA
23:43and are divided into two equal cells
23:45The X chromosome
23:47is inactivated
23:49during the development
23:51of the female.
23:53But what happens
23:55when a cell
23:57loses this memory?
23:59Researcher Ronan Salignet
24:01is an expert
24:03in this field.
24:05In normal state,
24:07the inactive X chromosome
24:09occupies a small part
24:11of the cell nucleus.
24:14In tumor cells
24:16there is a change
24:18in the silent state
24:20of the inactive X chromosome.
24:22It has a more relaxed
24:24and much denser structure.
24:26In cancerous cells
24:28with altered epigenetic mechanisms,
24:30in the inactive X chromosome
24:32the reactivation
24:34of some genes
24:36that are normally off occurs.
24:38It seems to be shown
24:40that the reactivation
24:42is a discovery
24:44that opens new paths
24:46in the scientific crusade
24:48against cancer.
24:50Epigenetics is a branch
24:52of very promising biology
24:54in the fight against cancer
24:56because epigenetic modifications
24:58are reversible.
25:00Correcting a genetic mutation
25:02is very complicated.
25:04But epigenetic alterations
25:06can be reprogrammed
25:08with certain molecules.
25:10There is great hope
25:12that some cancers
25:14can be treated with drugs
25:16designed to influence
25:18the epigenetic machinery.
25:20Some epigenetic drugs
25:22are already in the test phase.
25:24But researchers have discovered
25:26that certain drugs
25:28that have been in the market for years
25:30already act on the epigenetic mechanisms.
25:36A drug used for decades
25:39has turned out to be an epigenetic drug.
25:41We are talking about decitabine,
25:43indicated in the treatment
25:45of myelodysplastic syndrome,
25:47a blood disease
25:49that can lead to leukemia.
25:51Years ago, it was found
25:53that this drug slowed
25:55the progression of the disease.
25:57It is an example of an epigenetic drug
25:59successfully used.
26:01However, it is important to emphasize
26:03that we have not yet fully understood
26:05the epigenetic mechanism
26:07of these drugs.
26:09We know that some have shown
26:11their effectiveness.
26:13The challenge now is to understand
26:15how they act.
26:17Epigenetic drugs are opening
26:19new paths in the fight
26:21against cancer.
26:23The influence of epigenetics
26:25on the development of the body
26:27and in some diseases
26:29is increasingly palpable.
26:33But if genes are transmitted
26:35from one generation to another,
26:37could not the mechanisms
26:39that alter the expression
26:41of these genes also be transmitted?
26:57The type of information
26:59transmitted to the next generation
27:01remains an open issue.
27:04We know that genes
27:06transmit physical features.
27:08I look like my father and my mother
27:10and my son and my daughter
27:12look like me.
27:14But what else do we inherit?
27:16We have researched DNA a lot.
27:18Mainly because with today's technology
27:20it is quite easy to examine
27:22a DNA sequence.
27:24So now what interests us most
27:26is to know what is transmitted
27:28along with that DNA,
27:30what travels with it.
27:34Understanding the elements
27:36of this transmission
27:38is a difficult task
27:40in which plants can help us.
27:44Geneticist Van San Colo
27:46carries out his research
27:48in a species of the same family
27:50as the mustard plant,
27:52the Thaliana arabidopsis.
28:00Arabidopsis is a very interesting plant
28:02for a geneticist
28:04because it is very prolific
28:06and because it has a very short
28:08development time.
28:10Its life cycle in the laboratory
28:12can be completed in two months
28:14and also has a very compact genome.
28:18Can Arabidopsis transmit
28:20visible changes
28:22to its offspring,
28:24such as roots of different lengths
28:26or a more or less early flowering
28:28without altering its DNA?
28:30To find out
28:32the researchers made
28:34epigenetic modifications
28:36in a plant of this species.
28:40Then they made a cross
28:42with a wild specimen
28:44and after a series of successive crosses
28:46they examined the following generations
28:48carefully.
28:53The analysis showed
28:55that the epigenetic modifications
28:57were transmitted
29:00to at least 16 generations.
29:06These modifications were associated
29:08with visible changes
29:10such as the length of the roots
29:12or the flowering period.
29:14For the first time,
29:16some scientists had proof
29:18that some characteristics
29:20can be transmitted
29:22to a large number of generations
29:24without altering the DNA sequence.
29:26We have found
29:28that the epigenetic variations
29:30transmitted through generations
29:32have less stability
29:34than the changes transmitted
29:36by the DNA sequences.
29:38These very long phrases
29:40composed by the letters A, P, C and D
29:42are transmitted with extreme fidelity.
29:46But we have proven
29:48that the epigenetic states
29:50are much less stable.
29:52Its transmission will last
29:55tens or even hundreds
29:57but not millions of generations.
30:08This experiment has shown
30:10that it is possible
30:12to transmit certain epigenetic marks
30:14that modify some aspects of the plant.
30:17In this case,
30:19the modifications were induced
30:21in the laboratory in a controlled way.
30:23But what happens in nature?
30:29Could some changes
30:31be induced by the environment?
30:33For example, by a drought?
30:36It is a great mystery.
30:38The environment influences
30:40the functioning of genes
30:42but we still do not know
30:44how far hereditary changes
30:46that affect several generations
30:48can dictate.
30:50Does the environment play a role?
30:53To try to find the answer
30:55to this question,
30:57Van Sankolo and his team
30:59have installed hundreds of plants
31:01genetically identical
31:03in the mechanical bands
31:05of a unique device in the world,
31:07the X-ray.
31:16Thanks to this mechanical rotation system,
31:18all plants receive the same light,
31:20which allows them
31:22to measure the impact
31:24of the different irrigation intensities.
31:30These are the questions
31:32that concern us.
31:34What are the conditions
31:36that cause the appearance
31:38of epigenetic variations?
31:40Is the environment capable
31:42of inducing this type of change?
31:44And if so,
31:46will the changes we observe
31:48be as stable as those
31:51of the previous generation?
31:53And until when?
31:55These are the unknowns
31:57that we try to clear
31:59thanks to this unique system
32:01called the X-ray.
32:09The results of this research
32:11will allow us to elucidate
32:13whether some environmental factors
32:15such as drought
32:17can influence the plant genome
32:19and how the environment
32:21affects the rest of the species.
32:23What do we know
32:25about its impact
32:27on our own genome?
32:29There are many open investigations
32:31to try to know
32:33exactly what type of information
32:35is inherited
32:37in addition to the genetics.
32:39Does the environment
32:41in which we live
32:43affect the data
32:45we transmit?
32:47Some researchers think
32:49that its influence is very subtle,
32:51but others are convinced
32:53that its impact is considerable.
33:12In the American Northwest,
33:14a researcher is convinced
33:17that the environment
33:19plays a crucial role
33:21in the functioning
33:23of our body
33:25and that it leaves
33:27lasting and transmissible
33:29traces through
33:31epigenetic mechanisms.
33:33This specialist in biology
33:35of reproduction
33:37came to epigenetics
33:39almost by accident.
33:41A manipulation error
33:43allowed him to study
33:45what is known
33:47as serendipity,
33:49an unexpected discovery,
33:51a kind of stroke of luck.
33:53We wanted to study
33:55the effects of a fungicide
33:57on gestating rats,
33:59evaluate the way
34:01it affected the fetuses
34:03exposed
34:05and analyze
34:07the consequences
34:09that the offspring
34:11would have
34:13on the male rats.
34:15A small dose
34:17of these substances
34:19was inoculated
34:21in females in gestation.
34:23The offspring looked normal,
34:25but when they reached adulthood,
34:27the males presented
34:29anomalies in the sperm
34:31that caused a decrease
34:33in fertility.
34:35In the next generation,
34:37in the grandchildren
34:39of the inoculated females,
34:42and then
34:44the surprise jumped.
34:46The youngest males presented
34:48the same anomalies
34:50without having been exposed
34:52to pesticides,
34:54neither by injection
34:56nor in the uterus.
34:58In addition,
35:00in each generation
35:02epigenetic modifications
35:04related to sperm anomalies
35:06were discovered.
35:0890% of the males
35:10in this generation
35:12did not follow
35:14the canons of classic genetics,
35:16so we continue to investigate
35:18to show that the epigenetic factors
35:20can be transmitted
35:22for several generations.
35:24No laboratory has carried out
35:26a similar study
35:28or obtained the same results.
35:34But Skinner assures
35:36that pesticides can create
35:38non-genetic and yet
35:40transmissible diseases.
35:44For some,
35:46it is a very limited work
35:48with hasty conclusions
35:50that only incite controversy.
35:52If what you do
35:54does not arouse controversy,
35:56it is not important.
35:58With subtle changes
36:00that do not alter the accepted concepts,
36:02you will never make a great progress
36:04in the field of science.
36:07If all scientists
36:09worked with an open mind,
36:11as I try to do,
36:13many dogmas would be questioned
36:15considered immovable.
36:17But the usual tendency
36:19is to accept the dogmas
36:21and work with them
36:23without daring to change them.
36:25For me that is not
36:27the best way to do science.
36:29Michael Skinner's concern
36:31is shared today
36:33by many laboratories.
36:35We have used mice
36:37to test the hypothesis
36:39that exposure to an episode
36:41of traumatic stress
36:43during childhood
36:45can permanently alter
36:47epigenetic mechanisms
36:49and modify behavior
36:51during adulthood.
37:05The offspring are separated
37:07from the mother suddenly
37:09and on repeated occasions.
37:17We have found that exposure
37:19to periods of chronic stress
37:21alters the behavior of the mouse
37:23and modifies a certain
37:25number of epigenetic mechanisms
37:27in the brain.
37:29And what is most important,
37:31these alterations are transmitted
37:34to the second generation
37:36and also to the third.
37:38Adults who suffered
37:40these episodes of stress
37:42during childhood
37:44are depressive,
37:46evaluate the danger worse
37:48and take more risks.
37:50Their mental disorder
37:52will be transmitted
37:54to their children
37:56and even to their grandchildren.
37:58What this experiment shows
38:00is that not everything
38:02but the mental disorders
38:04and childhood traumas
38:06are very important factors
38:08that can determine
38:10our behavior
38:12during several generations.
38:18The most exciting thing
38:20about epigenetics
38:22are the benefits
38:24that its knowledge
38:26can report to the human being.
38:28There are many psychiatric diseases
38:30whose causes are not known
38:34and deepening
38:36the epigenetic mechanisms
38:38could allow us
38:40to better understand
38:42these diseases.
38:44It is still too early
38:46to say that the epigenetics
38:48of men and mice
38:50is comparable.
38:53But the work
38:55of Mansu
38:57and Skinner
38:59seems to suggest
39:01that the genome
39:03would be almost defenseless
39:05against the attacks
39:07of its environment
39:09and that it would leave
39:11transmissible marks
39:13for several generations.
39:17Conclusions
39:19that cause controversy
39:21in the scientific community.
39:23If we were so sensitive
39:25to the epigenetic changes
39:27induced by the environment,
39:29it would be a real mess.
39:31The cells would change identity,
39:33we would have a lot of tumors,
39:35we would not even be alive.
39:37To what extent
39:39are we permeable
39:41to the environment?
39:43And what do we transmit
39:45to our children?
39:47The influence
39:49of epigenetics
39:51collides
39:53with limits
39:55that have just been discovered.
39:57After fertilization,
39:59the epigenetics
40:01of mice
40:03and chickens
40:06are erased
40:08by the epigenetic marks
40:10provided by the sexual cells
40:12, allowing
40:14a kind of
40:16new generation.
40:22However,
40:24cleaning is not total.
40:26Some marks remain.
40:28But which and why?
40:30Wolf Reich and his team
40:32work in Cambridge
40:34to solve this mystery.
40:38It is very likely
40:40that epigenetic transmission
40:42between generations
40:44is related to the fact
40:46that the erasure of the marks
40:48is never complete.
40:50We would like to understand
40:52what is the mechanism
40:54that decides which part
40:56of the information is erased
40:58and which part is not.
41:00We would also like to find out
41:02if there is a resource
41:04that we can activate
41:06that allows us
41:08to choose between erasing
41:10the information
41:12or transmitting it
41:14to future generations.
41:16It is a very exciting question.
41:18Selective erasure
41:20is very well appreciated
41:22when observing groups
41:24of very early embryonic cells
41:26in the microscope .
41:28The nuclei, in blue,
41:31the few marks transmitted
41:33by the parents
41:35that have not been erased
41:37appear in violet color.
41:39But a few days later,
41:41the embryonic cells,
41:43already in a more advanced state,
41:45contain a constellation
41:47of new epigenetic marks
41:49linked to their development.
41:51We have been studying thoroughly
41:53the erasure process for 10 years
41:55and I find it more and more fascinating.
41:57There are still many questions
41:59to be answered.
42:01For example,
42:03we consider it very likely
42:05that food affects the epigenome
42:07and that it is affected
42:09by what we eat,
42:11by the situation
42:13and climate of the place
42:15where we grew up
42:17and by the environment
42:19in which we are immersed
42:21and also by the penalties
42:23that our parents had to face
42:25and by the composition
42:28of the food.
42:30A team of researchers
42:32tries to clarify
42:34if food is able
42:36to mark the DNA
42:38and if the affected DNA
42:40can be transmitted
42:42to the next generations.
42:54Anne Ferguson Smith
42:56What is the impact
42:58of food deprivation
43:00on pregnant mice,
43:02on their young
43:04and on their copious offspring?
43:06The malnutrition of the mother
43:08during pregnancy
43:10has important effects
43:12on the young.
43:14Pregnant females
43:16of our experiment
43:18receive half
43:20of the usual caloric dose,
43:22a fairly severe nutritional cut.
43:24They become fat
43:26and diabetic.
43:28They do not normally assimilate
43:30glucose or insulin,
43:32which causes them to suffer
43:34diseases very similar
43:36to those that the human being
43:38suffers in today's society.
43:40Their fat content increases
43:42and obesity and diabetes
43:44make their appearance.
43:46However, if after birth
43:48we continue to feed
43:50these little mice,
43:53the mice exposed
43:55to food deprivation
43:57in the mother's womb
43:59seem to adapt
44:01to the caloric shortage.
44:03And so,
44:05when they grow up
44:07in an environment
44:09where food is abundant,
44:11they are easy prey
44:13for diabetes and obesity.
44:15The grandchildren of the mothers
44:17who started the experiment
44:19have the same symptoms.
44:21How many generations
44:23could be affected
44:25by these diseases?
44:27Research with mice continues.
44:33But,
44:35in our case,
44:37will feeding influence
44:39in the same way?
44:41We cannot carry out
44:43this type of experiment with humans,
44:45but throughout history
44:47there have been times
44:49when pregnant women
44:51have had to face similar
44:53situations and penalties
44:55as happened during the Dutch famine
44:57of World War II.
44:59During the winter
45:01of 1944-1945,
45:03the Nazis blocked
45:05the supply of food
45:07to the population of the Netherlands
45:09as punishment for their support
45:11to the Allies.
45:13An atrocious episode
45:15that has provided valuable data
45:18These moving images
45:20show the hard tests
45:22that pregnant women
45:24had to live
45:26during that period of deprivation.
45:28The health of their children
45:30has been the subject
45:32of a thorough study.
45:34And the results show
45:36that they are more likely
45:38to suffer diseases
45:40such as diabetes and obesity,
45:42to suffer neurological disorders
45:44such as depression and schizophrenia
45:46The follow-up of the grandchildren
45:48has shown that they,
45:50in adulthood,
45:52also suffer an obesity
45:54higher than average,
45:56which shows that the conditions
45:58of the environment
46:00affect at least two generations.
46:02Research on the impact
46:04of the environment
46:06on the genome
46:08has only just begun.
46:10There are still many mysteries
46:12to be solved.
46:14It is the most important
46:16and powerful transmission mechanism,
46:18which allows to transfer
46:20the characteristics of an individual
46:22to its descendants.
46:24But today we know that there is something else,
46:26something that has a great impact
46:28on health and well-being
46:30and that can be inherited
46:32by the next generation.
46:34I am passionate about trying to understand
46:36how these non-genetic mechanisms work,
46:38whose effects can be prolonged
46:40for several generations.
46:44What fascinates me most
46:46about epigenetics is that
46:48it provides many nuances
46:50to interpret a genome
46:52that we considered static.
46:54It allows us to examine
46:56the marks left by the environment,
46:58those marks chiseled
47:00in the course of each personal history
47:02in the behavior of the genome.
47:04And what I like most
47:06is that its effects are reversible.
47:08It is comforting to think
47:10that there is nothing immovable.
47:13It is a science
47:15that expands the field of genetics.
47:17Not everything is transmitted
47:19in an immutable way.
47:21In the information that is inherited,
47:23there are many transitory data
47:25that accompany those recorded in stone.
47:27Well, epigenetics occupies
47:29a large part of that
47:31that is not recorded in marble.
47:33Research on epigenetics
47:35is in full swing.
47:39But it will take many more years
47:41to interpret all the tones
47:43of such a prolific score.