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Ukazujem Revíziu 7 vytvorenú 10/25/2017 od DLC.

  1. We are on the brink of uncovering
    a hidden world, a world that
  2. connects past and future generations
    in ways we never imagined possible.
  3. What this means is that an environmental
    exposure that your grandmother had
  4. could cause a disease in you, even though
    have never been exposed to the toxin,
  5. and you are going to pass it on to your

  6. These extraordinary discoveries have the
    to effect every aspect of our lives.
  7. It's not just the genes, but also the
    environment of the early life
  8. of your ancestors. It's not so much
    you are what you eat, but you are what
  9. your mother ate, and maybe you are what
    your grandmother ate. And if you take our
  10. data, maybe you are what your grandmother
    or grandfather had.

  11. It will change the way we think about our
    relationship with every generation.
  12. Makes me feel closer to my children;
    what I experienced in terms of environment
  13. will have some type of legacy in my
    children and grandchildren.

  14. The science of inheritance is being turned
    on its head.
  15. We're changing the view of what
    inheritance is.

  16. This small Swedish town may hold
    the evidence to launch a medical
  17. revolution. Överkalix lies huddled on the
    edge of the Arctic Circle
  18. Inaccessible and remote, it was cutoff
    from the rest of the world for most of
  19. its history. Marcus Pembrey has traveled
    here to meet his colleague, Olov Bygren.
  20. They believe that the stories lying
    buried in this graveyard may hold the
  21. proof to their radical ideas.

  22. Here we have multiple generation in
    the same grave.
  23. This group of people could really
    contribute to a sea of change in the
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    way we think about inheritance.
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    They have come to this churchyard to
    find grandmothers and granddaughters,
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    grandfathers and grandsons. Connecting
    people who lived almost a hundred years
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    apart, in entirely new ways. Uncovering
    links that confound scientific thinking.
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    Up until now, inheritance was just, just,
    the genes, the DNA sequence. I suspect
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    that we're going to be able to demonstrate
    that the inheritance is more than that.
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    This is a grandson as it were in our
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    It is the culmination of more than
    twenty years of work, and for the
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    first time Pembrey is confronting the
    magnitude of their discovery.
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    It has really come alive for me, coming
    here, more than I had expected it to.
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    I'm really quite sort of emotional about
    it. Wonderful!
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    Marcus Pembrey is one of a select brand of
    scientists, a brand that is willing to
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    challenge an orthodoxy. They believe the
    lives of our parents, grandparents, and
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    even our great grandparents can directly
    effect our well-being, despite never
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    experiencing these things ourselves.
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    To many of people, these ideas are
    regarded as scientific heresy.
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    You cannot predict where these important
    will be, the only thing that you can do is
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    follow your instinct.
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    Conventional biology has always believed
    that our genetic inheritance is set in
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    stone at the moment of our conception. At
    that instant, we receive a set of
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    chromosomes from both our mother and our
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    Within these chromosomes are the genes,
    strips of coded DNA, the basic unit of
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    After conception, it was presumed assumed that our
    genes were locked away inside every cell
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    of the body, protected untouched from the
    way you live.
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    So what you do in your life may effect you,
    but your genes remain untainted, unchanged
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    for future generations.
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    In classic genetics, your parents and
    grandparents simply pass on their genes,
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    the experiences they accumulated in a
    lifetime are never inherited, lost forever
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    as the genes pass untouched generation
    after generation.
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    The biology of inheritance was a reassuringly
    pure process, or so it seemed.
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    In the early '80's, Marcus Pembrey headed
    the clinical genetic department at
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    Great Ormond Street Hospital for Children.
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    He was frequently treating families with
    unusual genetic conditions.
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    We were constantly coming across families
    which didn't fit the rules, that didn't fit
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    any of the patterns that genetics were
    supposed to fit, so you think of
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    chromosome abnormalities and, uh, you
    check the chromosomes and they are normal.
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    So you then to start imagining as it were,
    you know, what might be underlying this
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    and you are really driven to try and work
    it out because the families really needed
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    some help.
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    The more families he saw, the more the
    rules of inheritance appeared to break
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    Diseases and conditions that simply didn't
    fit with the textbook conventions.
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    One condition in particular caught his eye,
    Angelman Syndrome.
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    Named after Harry Angelman, the
    pediatrician who first described Angelman

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    Syndrome, he described them as "happy
    puppet children" because it described some
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    of their apparent features. They have a
    jerky movement when they are walking.
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    These children have no speech, they are
    severely incapacitated in terms of learning,
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    but are uncharacteristically happy,
    they're smiling all of the time.
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    The condition was caused by a genetic
    fault, a key sequence of DNA was missing,
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    deleted from chromosome 15.
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    Then we came across a paradox; at the same
    the same change, the same deletion,
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    was clearly associated with a quite
    different syndrome, much milder in terms
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    of impairment, the Prader-Willi Syndrome.
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    These children are characterized by being
    very floppy at birth, but once they
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    started eating properly they then had
    an insatiable appetite and would get
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    very, VERY large.
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    What Pembrey saw simply made no sense.
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    Here were two completely different
    diseases, Angelman Syndrome and
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    Prader-Willi Syndrome being caused by
    exactly the same genetic fault.
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    So here we were in a bizarre situation
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    How could anyone propose that the same
    deletion cause a different syndrome?
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    It appeared to Pembrey as if the simple
    view of inheritance was beginning to
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    unravel. But his doubts were contrary to
    the tide of optimism sweeping the scientific
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    In the early 1990's, the biggest project
    ever undertaken in human biology was
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    captivating the world.
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    The human genome project will be seen as
    the outstanding achievement in the history
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    of Mankind.
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    The human genome project was to be the
    pinnacle of work on understanding human
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    genes and genetics. It seemed as if the
    secrets of life were at our fingertips.
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    The human genome is like a bible where
    everything was written down. The hope,
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    the expectation, was once we had that book
    in front of us, and all the letters we could
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    just read down the pages, then we would
    understand how the body was put together.
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    It would offer a complete understanding of
    human biology at a molecular level.
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    The hope was that once the code was written
    down, scientists could find the genetic cause
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    and cure for every disease.
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    We were thinking of genes in a very
    mechanical way; we were thinking of them
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    just in terms of the sequence of the letters.
    We were working out what all the letters
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    were in the book.
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    Scientists estimated that the human genome,
    the book of life,
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    would contain around 100,000 genes.
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    And then when they started sequencing they
    realized there may be fewer than 100,000
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    genes, then it popped down to 60,000, then
    it popped down to 50,000... It slowly went
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    down to a much smaller number. In fact,
    we found that the human genome is
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    probably not as complex and doesn't have
    as many genes as plants do.
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    So that then made us really question, well,
    "if the genome has less genes in this
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    species than in this species, and we're more
    complex, potentially, what is going on here?"
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    Now scientists estimate there are probably
    less than 30,000 genes.
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    We believed, I believed naively, that we would
    be able to find the genetic components of

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    common diseases. That's proven to be very
    difficult, as the idea of one gene, one
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    disease does not explain it all.
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    30,000 genes didn't appear to be enough
    to explain human complexity, there had
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    to be something they missed.
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    The first hints of what was missing lay in
    the curious curious paradox of the
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    Prader-Willi and Angelman Syndromes.
    Two quite different diseases caused by
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    exactly the same genetic fault. When
    Pembrey looked at the inheritance
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    patterns for the conditions, he noticed
    something even stranger...
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    What really mattered was the origin of
    the chromosome 15 that had the deletion.
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    If the deletion was one the chromosome 15
    that the child inherited from the father,
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    then you had Prader-Willi Syndrome. If the
    deletion was inherited from the mother,
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    then you the Angelman Syndrome.
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    It was a complete surprise that the same
    missing strip of DNA could cause one
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    disease when it came from the mother, and
    a completely different disease when it
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    came from the father. It's as if the genes knew
    where they came from.
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    You're got a developing fetus manifesting
    this condition, how does the chromosome

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    15 know where it came from? There must
    have been a tag or imprint impressed on
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    that chromosome during egg or sperm
    formation in the previous generation to
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    say "hi, I came from mother," or "I came
    from father" and we are functioning
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    differently. And that is the key, although
    the DNA sequences the same, the
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    different sets of genes were being silenced
    depending on if they came from the
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    mother or the father.
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    It showed there was clearly more to
    inheritance than simply the coded DNA.
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    We then realized we were dealing with
    what is now known as genomic imprinting.
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    What genomic imprinting means, is in a
    nutshell, genes have a memory of where
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    they came from.
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    Something other than just the DNA was
    capable of moving between generations.
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    It was a tantalizing glimpse into this
    unknown and unexpected world. A
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    hidden layer acting on, and able to
    directly control how our genes function.
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    It meant that inheritance was not simply about
    which genes you inherited, but whether
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    those genes were silenced, switched on
    or off.
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    And you can think of it like a lightswitch...
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    Dawn the gene, the light is on, the gene is
    active, it makes the cell do a certain thing.
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    Or, the light switch is off and everything
    is dark, it is off. The gene remains turned
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    on or off and that gives the cells their
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    The activity of genes was being controlled
    by a switch, the attachment of a certain
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    chemical that dictated whether a gene was
    switched on, or off.
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    Whether those genes are turned on or off
    is called epigenetics.
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    Epigenetics...act...upon the...genes.
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    Not only is the sequence important of the
    DNA, which we've studied for a long time,
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    the past few decades, but we now understand
    that in addition to that there is this underlying
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    epigenetic phenomena that allows the genes
    to get turned on or off.
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    Epigenetics could explain how a human could
    be created with less than 30,000 genes, and
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    why the genome project didn't provide all
    of the answers.
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    Now if we actually put epigenetics on top
    of it, where it makes it much more
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    complicated if genes get activated to a
    certain level and so forth, then you
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    have a complexity that can start explain biology
    much more effectively than the simple
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    sequence of the DNA.
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    So clearly we have additional levels of
    complexity that we now need to
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    understand that are well beyond the DNA.
    The next huge challenge for modern biology
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    is to now decipher the epigenetic code, to
    understand all the combinations of switches
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    that exist.
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    An accurate chemical map of the human
    genome tells us surprisingly little about
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    how it actually works. Transcribing the
    code of the genes, the genome project,
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    is not an end, but simply a beginning.
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    If inheritance was not just about DNA,
    if these gene switches were so important,
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    just what could turn them on, or off?
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    Stepahnie and Amon Mullins have two
    children, Kiren and Charlotte.
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    When you are trying to conceive and you
    see all of your friends around you getting
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    pregnant, having children, as each month
    goes on you become more and more desperate.
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    Doctors recommended IVF treatment.
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    In the UK alone, around 8,000 babies are
    conceived every year using assisted
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    reproduction techniques like IVF. After
    the third attempt, Stephanie became
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    pregnant with Kiren.
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    At the time, they didn't really highlight
    any risk to us, and then we went for a
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    routine scan, and I did feel that the scan
    was taking an awful long time.
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    Basically what they found was something
    called an exomphalos on Kiren's abdomen
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    which basically means that part of the
    bowel is still on the outside of the
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    Doctors suspected that Kiren might be
    suffering from Beckwith Wiedemann
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    syndrome, a rare condition where babies
    are born very large, have oversized
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    tongues, and high risk of developing
    childhood cancers.
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    They couldn't say for 100% that the baby
    did have Beckwith Wiedemann syndrome,
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    but it was showing signs, they could see
    his tongue protruding on the scan and
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    they said he had very big thighs... But
    until Kiren was born, we didn't know how
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    severely effected he would be.
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    When Kiren was born it was clear he did
    have Beckwith Wiedemann syndrome.
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    Within a few hours of the birth, Kiren had
    to have surgery to put the bowel that was
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    basically on the outside of the abdomen
    put back inside and repaired.
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    Kiren also had surgery to reduce the size
    of his tongue and every few months he has
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    scans to check for tumors.
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    Cases of Beckwith Wiedemann syndrome caught
    the attention of Wulf Reich.
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    Wulf Reich worked in developmental genetics.
    He was fascinated by this emerging epigenetic
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    ghost world. He wanted to know what could
    throw the switches on or off.
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    To his surprise, he found by simply placing
    a mouse embryo in a petri dish could cause
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    genes to switch on or off.
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    After we had seen how relatively easy it
    was to change the switches in mouse embryos,
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    we thought perhaps it could be the same in
    human embryos.
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    We though in IVF you have the embryo for a
    brief period of time in a culture dish, and so we
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    were asking the question whether as with
    the mouse embryo, just the mere fact of
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    having human embryos in a culture dish or
    having been manipulated could alter their
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    genetic switches.
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    Wulf knew that Beckwith Wiedemann syndrome
    was caused by a faulty switch.
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    So what we were looking at was a group of
    babies, children, that had the
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    Beckwith Wiedemann syndrome. What proportion
    of those had been conceived with IVF?
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    Could IVF be switching genes on or off?
    Could IVF itself causethe syndrome?
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    What we found was an increased occurrence
    of this epigenetic syndrome in the IVF
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    Although the disease is extremely rare,
    the chance seemed to increase 3-4 times
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    with IVF. It seemed the simple act of
    removing the embryo from its natural
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    environment could trigger the disease.
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    And we did feel frustrate that Kiren had
    Beckwith Wiedemann syndrome because we
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    had IVF, but at that time it seemed like the
    right decision to make.
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    And I think we should look again at the IVF
    procedures, the conditions that are being
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    used, and carry out better and more precise
    experiments to see how we can avoid
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    throwing these epigenetic switches.
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    Wulf had shown that simple changes in the
    environment could switch a gene on or off,
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    but there was more...
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    Everyone thought that any altered switches
    could not be inherited. He took some mice
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    with altered gene switches and bred them.
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    Our expectation was that as the altered
    genome was passed to the children that
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    any epigenetic changes would be wiped
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    When he looked at the gene profile of the
    offspring, he was amazed.
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    You have these dots you are looking at,
    and each dot tells you that a gene was on.
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    And all of a sudden someone said "wow,
    look at that!"
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    The epigenetic switch thrown in one
    generation, was clearly also present in
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    the second generation.
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    Nobody had seen this kind of thing before,
    and everyone looking at this gel was saying
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    "no, that can't be right. This must be the
    wrong gel." You know, how you get excited
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    about it and then you thing this is wrong,
    you're not on the right track. And we were
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    very excited, as excited as scientists
    ever get.
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    This meant the genes were not locked away,
    a simple environmental event could effect
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    way genes worked, and that could be inherited.
    It was if a memory of an event could be
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    passed down through generations. It was
    something many scientists regarded as
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    impossible. If this effect could be observed
    in humans, the implication would be profound.
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    It would mean that what we experience could
    effect not just us, but our children
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    and our grandchildren.
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    While these observations were emerging
    from laboratories, Pembrey was still
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    working at Great Ormond Street. He began
    to wonder why these links between
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    generations would exist.
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    Now my reputation was a made as a clinical
    geneticist, so I was much freer to speculate
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    outside my main career. I also like to stir
    things up a bit, and it amuses me to
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    speculate because I have nothing to lose,
    and if I'm right, well then that's very
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    amusing (laughs).
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    He speculated why genes would
    carry a memory from one generation
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    to a next. What evolutionary purpose
    could it serve?
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    Maybe imprinting was used as a
    means of some trans-generational adaptation.
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    He thought it could be used by a mother to
    send messages to her baby in the next
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    Something that always troubled me since I
    was a medical student was what stops the
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    baby's head jamming up in the birth canal?
    The baby of course was grown in one
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    generation, but the mother's pelvis was
    grown in the previous generation.
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    But what if the mother was starving as she
    was growing, so she had a small pelvis?
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    Maybe her her eggs had captured that
    information and were instructing the growth
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    genes of the future babies to not work so
    much and the baby to not grow too much, so
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    as not to jam up the birth canal, so there
    was some coordination between the growth
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    of two generations. That struck me as
    highly reasonable.
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    He published his ideas in a largely obscure
    journal and forgot about it. After all,
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    there was no evidence for any of this, it
    was pure speculation.
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    Then four years later, Marcus received as
    email from a doctor in Sweden.
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    It really came as a bolt out of the blue,
    I just got an email in May 2000 saying my
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    paper was the only thing he could find in
    the literature that in any way sort of
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    tied-in with his basic observation.
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    The email was sent by Olov Bygren. He was
    studying the population records of an
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    obscure town in Sweden, Överkalix. What
    made these records unique were their
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    detail; they recorded births and deaths
    over hundreds of years. But they also
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    provided accurate details of the harvests.
    More significantly, Överkalix position on
  280. Nesynchronizované
    the Arctic Circle meant that it was
    particularly vulnerable to famine.
  281. Nesynchronizované
  282. Nesynchronizované

    In the 19th Century, this was a very
    isolated area, they could not have any
  283. Nesynchronizované
    from the outside as it was so poor they
    had a hard time when there was a famine,
  284. Nesynchronizované
    and they really had a good time when the
    harvests were good.
  285. Nesynchronizované

    Bygren began seeing links between
    generations that confounded his expectations.
  286. Nesynchronizované

    I sent Marcus Pembrey an email saying we
    had some data that could interest him.
  287. Nesynchronizované

    I was extremely excited to get this
    completely out of the blue, and for the
  288. Nesynchronizované
    first time it seemed there was some data
    that we could really begin to explore, so
  289. Nesynchronizované
    that was the beginning of our collaboration.
  290. Nesynchronizované

    Överkalix offered Pembrey a unique
    opportunity, to see if the events that
  291. Nesynchronizované
    happened in one generation could effect
    another, decades later.
  292. Nesynchronizované
  293. Nesynchronizované
    While Pembrey and Bygren sifted through
    their Överkalix data, someone else had
  294. Nesynchronizované
    stumbled on another group that caught
    them by surprise.
  295. Nesynchronizované
    Rachel Yehuda is a psychologist. She's
    interested on how people respond to stress.
  296. Nesynchronizované

    Trans-generational effects were not on my
    radar at all, until we opened up a clinic
  297. Nesynchronizované
    for the treatment of Holocaust survivors.
  298. Nesynchronizované

    While treating the Holocaust survivors for
    stress, she was surprised that many of the
  299. Nesynchronizované
    children of the survivors were they
    themselves suffering stress effects.
  300. Nesynchronizované

    About five children of Holocaust survivors
    were calling us for every Holocaust
  301. Nesynchronizované
    survivor. What these children said was that
    they were casualties of the Holocaust, too,
  302. Nesynchronizované
    that they had been effected by the
    Holocaust indirectly.
  303. Nesynchronizované

    She was convinced that the stress in the
    children was caused by the continual
  304. Nesynchronizované
    retelling of the stories by their parents.
  305. Nesynchronizované

    Our studies had really convinced me that
    it were the later experiences of the child
  306. Nesynchronizované
    as the child was growing up, bombarded by
    years and years of symptoms from the parents
  307. Nesynchronizované
    that accounted for the effect that we
  308. Nesynchronizované

    However, in Edinburgh, Johnathan Seckl
    was interested in stress exposure in
  309. Nesynchronizované
    pregnant women and wondered if stress
    effects could be transmitted to their
  310. Nesynchronizované
    children. He started some experiments with
    pregnant rats to see if exposing them to
  311. Nesynchronizované
    stress hormones had any effect on their
  312. Nesynchronizované

    And we found for the rest of their lifespan,
    those animals themselves had altered
  313. Nesynchronizované
    stress responses and showed behavior that
    looked like anxiety.
  314. Nesynchronizované

    To see if this was infecting the genes
    themselves, he decided to breed them and
  315. Nesynchronizované
    see if the stress effects could be found in
    generations never exposed to the stress
  316. Nesynchronizované
  317. Nesynchronizované

    And their daughters and sons also go the
    propensity for abnormal stress responses.
  318. Nesynchronizované

    For Seckl, the only explanation was that
    a stressful even was throwing the switch
  319. Nesynchronizované
    on a gene, that was then being inherited.
  320. Nesynchronizované
  321. Nesynchronizované
    His work might have stopped there, until
    world events took a hand. When on 9/11 the
  322. Nesynchronizované
    planes crashed and the towers came down,
    Yehuda and Seckl were critically aware of
  323. Nesynchronizované
    the potential of the impact to be far
    reaching, even effecting generations yet
  324. Nesynchronizované
    to be born. Aelsa Gillium was working in
    a building next to the towers.
  325. Nesynchronizované

    As I left my building coming out through
    the doors, there was a lot of ash floating
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    through the air, and some office papers.
    I knew if I looked up, I may see somehting
  327. Nesynchronizované
    I didn't want to see. Just the thought that
    people had died close to me, I broke down.
  328. Nesynchronizované
    I got very upset. I wanted to get out of
    the environment. Being pregnant, I did not
  329. Nesynchronizované
    want to open myself up to more emotional
    uncertainty and emotional distress.
  330. Nesynchronizované

    After the events of 9/11 unfolded, Yehuda
    and Seckl teamed up to study women, like
  331. Nesynchronizované
    Aelsa, who were pregnant at the time.
  332. Nesynchronizované

    There were a lot of different opportunities
    to study what the effects of 9/11 would be
  333. Nesynchronizované
    on the children who might be born to
    parents who developed post-traumatic
  334. Nesynchronizované
    stress disorder in response to 9/11, and
    particularly those who had been exposed
  335. Nesynchronizované
    in utero.
  336. Nesynchronizované

    When exposed to a stressful event, a
    person produces cortisol, a hormone that
  337. Nesynchronizované
    helps regulate the body's response to that
    stress. If cortisol levels are too low, a
  338. Nesynchronizované
    person finds coping with stress very
    difficult and are prone to PTSD,
  339. Nesynchronizované
    Post-Traumatic Stress Disorder. But could
    this effect be transmitted to their offspring?
  340. Nesynchronizované

    They found nearly 200 women, of whom, a
    number had actually been in the twin towers.
  341. Nesynchronizované
    About half of them developed PTSD. We then
    looked at those women and found they had
  342. Nesynchronizované
    abnormal cortisol in their saliva. The most
    striking result was so did their babies. The
  343. Nesynchronizované
    argument in the Holocaust survivors had
    been their children show abnormal stress
  344. Nesynchronizované
    hormones because they themselves had
    been stressed by listening to this tale
  345. Nesynchronizované
    recounted by their parents of their awful
    exposures during the 1940's. That could
  346. Nesynchronizované
    not be the case with the 9/11 survivors,
    these babies were one year old.
  347. Nesynchronizované

    Not only did infants have lower cortisol
    levels, but they were different depending
  348. Nesynchronizované
    on how pregnant the mother was on 9/11.
  349. Nesynchronizované

    The main effect was only seen with mothers
    with PTSD who were pregnant in the last
  350. Nesynchronizované
    third of pregnancy. Mothers with equal
    levels of PTSD who were in the first and
  351. Nesynchronizované
    second third of pregnancy at 9/11, there
    was very little effect on the babies cortisol.
  352. Nesynchronizované

    It suggested to us that it couldn't just
    be about genetics, but there was something
  353. Nesynchronizované
    that was being transmitted in the late
    of pregnancy where the mother's symptoms
  354. Nesynchronizované
    were having some effect on the development
    on the offspring's cortisol system.
  355. Nesynchronizované

    It appeared that epigenetics might be
    responsible, that an event had altered
  356. Nesynchronizované
    the stress response in the children.
  357. Nesynchronizované

    What these findings did was suggest to us
    we needed to be looking where we hadn't
  358. Nesynchronizované
    even considered looking before.
  359. Nesynchronizované

    To know for certain this was an epigenetic
    effect, they'll need to be sure their
  360. Nesynchronizované
    observations were't simply due to high
    levels of stress hormones in the womb.
  361. Nesynchronizované

    Now, here is the bit where we have to
  362. Nesynchronizované
    the animal work would suggest that this
    might then persist into the next generation.
  363. Nesynchronizované

    If they find the same stress effects in
    the children's children of 9/11, then it
  364. Nesynchronizované
    it will be clear that a genetic memory of
    a stressful event can travel through the
  365. Nesynchronizované
  366. Nesynchronizované

    That's the key thing next to find out; the
    9/11 population will be very, very
  367. Nesynchronizované
    important for us to be able to follow what
    is a single, discreet event.
  368. Nesynchronizované

    the work of Yehuda and Seckl offers
    tantalizing evidence of solid proof of
  369. Nesynchronizované
    inherited epigenetic effects in humans.
  370. Nesynchronizované
    But they need data that extend beyond
    just one generation.
  371. Nesynchronizované
    The only way forward was to look back to
    the past. In Sweden, Pembrey and Bygren
  372. Nesynchronizované
    had data that provided the chance to study
    the effects of famine through many
  373. Nesynchronizované
  374. Nesynchronizované
  375. Nesynchronizované
    Olov Bygren was looking to see if poor
    nutrition had an effect on health, when
  376. Nesynchronizované
    he stumbled on something curious.
  377. Nesynchronizované

  378. Nesynchronizované
    It appeared that a famine could effect
    people almost a hundred years later,
  379. Nesynchronizované
    even if they never suffered a famine
    themselves. He wanted to know how
  380. Nesynchronizované
    this might be possible, so he asked
    Michael Pembrey.
  381. Nesynchronizované

    First he reported that the food supply
    of the ancestors was effecting the
  382. Nesynchronizované
    mortality rate, or longevity, of the
    grandchildren. So I was very excited, I
  383. Nesynchronizované
    responded immediately.
  384. Nesynchronizované

    Pembrey had a hunch that the incidence of
    one disease, diabetes, might be an
  385. Nesynchronizované
    indicator that epigenetics was involved.
  386. Nesynchronizované

    Specifically, I wanted to know the results
    of the diabetes, because this is one I
  387. Nesynchronizované
    thought might involve the imprinting.
  388. Nesynchronizované

    So Olov trolled the records for any deaths
    due to diabetes, and then looked back
  389. Nesynchronizované
    to see if there was anything unusual about
    the diet of their grandparents.
  390. Nesynchronizované

    A few months later, he emailed me back to
    say indeed they had shown a strong
  391. Nesynchronizované
    association between the food supply of the
    father's father and the chance of diabetes
  392. Nesynchronizované
    being shown on the death certificate of
    the grandchild. So of course, I was really
  393. Nesynchronizované
    rather excited by that because it really
    did look as though there was some
  394. Nesynchronizované
    trans-generational effect going on there.
  395. Nesynchronizované

    It looked as if there were clear links
    through the generations, between
  396. Nesynchronizované
    grandparents and grandchildren.
    They found that the life expectancy of
  397. Nesynchronizované
    grandchildren was being directly effected
    by the diet of the grandparent. It
  398. Nesynchronizované
    appeared that Overkilex held the key to
    the first evidence of epigenetic
  399. Nesynchronizované
    inheritance in humans.
  400. Nesynchronizované

    It really did look as if there was some
    new mechanism transmitting environmental
  401. Nesynchronizované
    exposure information from one generation
    to the next.
  402. Nesynchronizované

    Because these ideas were so heretical,
    Pembrey knew the results could be
  403. Nesynchronizované
    dismissed as nothing more than a curiosity.
  404. Nesynchronizované
    They needed to get an understanding of
    how this was happening, how could the
  405. Nesynchronizované
    grandparent capture the information that
    effecting the grandchildren?
  406. Nesynchronizované

    We wanted to tease out when you could
    trigger in the ancestor a
  407. Nesynchronizované
    trans-generational response.
  408. Nesynchronizované

    So he and Bygren went back to the data
    and looked again. The more they looked,
  409. Nesynchronizované
    the more patters started to appear.
  410. Nesynchronizované

    We were able to look at the food supply
    every year in the grandfather and the
  411. Nesynchronizované
    grandmother, from the moment they were
    conceived, right through until the age of
  412. Nesynchronizované
    20. We found that there are only certain
    periods in the ancestor's development when
  413. Nesynchronizované
    they can trigger this trans-generational
    response. They're what I might call
  414. Nesynchronizované
    "sensitive periods of development."
  415. Nesynchronizované

    They discovered that when a famine was
    able to trigger and effect was different
  416. Nesynchronizované
    for the grandmother than the grandfather.
    The grandmother appeared susceptible while
  417. Nesynchronizované
    she herself was still in the womb, while
    the grandfather was effected just before
  418. Nesynchronizované
  419. Nesynchronizované

    And the timing of the sensitive period was
    telling us it was tied in with the
  420. Nesynchronizované
    formation of the eggs and the sperm.
  421. Nesynchronizované

    This was critical, because now they knew
    how it was happening. Environmental
  422. Nesynchronizované
    information was being imprinted on the
    eggs and sperm at the time of their
  423. Nesynchronizované
    formation. At last, a clear picture of an
    inherited environmental effect was beginning
  424. Nesynchronizované
    to emerge. All they needed to do now was
    compile their findings. Bygren drew up a
  425. Nesynchronizované
    rough diagram and sent it to Pembrey.
  426. Nesynchronizované

    Hand drawn, this is what Olov sent me.
    You know, he was too excited to wait for
  427. Nesynchronizované
    the thing to be drawn out properly. He sent
    me the data, and in fact I was recovering
  428. Nesynchronizované
    from having something done to my heart.
    So, he sent it saying "I hope this helps
  429. Nesynchronizované
    you get better quickly." Because it was so
  430. Nesynchronizované

    When Pembrey plotted out the diagram, he
    was immediately struck by its significance.
  431. Nesynchronizované

    Once I had plotted out the full extent of
    those results, it was so beautiful, and
  432. Nesynchronizované
    such a clear pattern that I knew then,
    quite definitely we're dealing with a
  433. Nesynchronizované
    trans-generational response. It was so
    coherent, and that's important in science
  434. Nesynchronizované
    that the effect was coherent in some way,
    that it was tying in to when eggs and sperm
  435. Nesynchronizované
    were being formed.
  436. Nesynchronizované

    The diagram showed a significant
    link between generations, between the diet
  437. Nesynchronizované
    in one and the life expectancy in another.
  438. Nesynchronizované

    When you think that you have found
    something important, in the understanding
  439. Nesynchronizované
    of disease itself, you can imagine that
    this is something really special.
  440. Nesynchronizované

    It's up there with, I'm sort of a
    fair-weather supporter of Liverpool,
  441. Nesynchronizované
    it's up there with Liverpool winning the
    championship big.
  442. Nesynchronizované

    You can only have it once in your lifetime.
  443. Nesynchronizované

    This is going to become a famous diagram,
    I am convinced by that, I get so excited
  444. Nesynchronizované
    every time I see it, it's just so amazing.
  445. Nesynchronizované

    I find it really exciting, it's fantastic.
  446. Nesynchronizované

    Pembrey and Bygren had the first conclusive
    proof of an environmental effect being
  447. Nesynchronizované
    inherited in humans.
  448. Nesynchronizované
  449. Nesynchronizované
    The impact of a famine being captured by
    the genes, in the eggs and sperm, and the
  450. Nesynchronizované
    memory of this event was being carried
    forward to effect the grandchildren
  451. Nesynchronizované
    generations later.
  452. Nesynchronizované

    We are changing the view of what
    inheritance is. You can't, in life, in
  453. Nesynchronizované
    ordinary development and living, separate
    out the gene from the environmental effect
  454. Nesynchronizované
    they're so intertwined.
  455. Nesynchronizované

    Pembrey and Bygren's work showed clearly
    what our grandparents ate could effect our
  456. Nesynchronizované
    health. Increasingly, it appeared as if all
    sorts of environmental events were
  457. Nesynchronizované
    capable of effecting the genes. And in
    Washington State, Mike Skinner stumbled on
  458. Nesynchronizované
    some results with profound implications.
    He triggered an effect with commonly used
  459. Nesynchronizované
    pesticides and fungicides. He exposed a
    pregnant rat with high doses of these
  460. Nesynchronizované
    pesticides and then looked for effects in
    her offspring.
  461. Nesynchronizované

    And so I treated the animal, the pregnant
    mother, with these compound, and then we
  462. Nesynchronizované
    started seeing, between six months to a
    year, a whole host of other diseases we
  463. Nesynchronizované
    didn't expect. And this ranged between
    tumors, such as breast and skin tumors,
  464. Nesynchronizované
    uh, prostate disease, uh, kidney disease,
    and immune dysfunction.
  465. Nesynchronizované

    He bread these rats to see if the effects
    persisted into subsequent generations.
  466. Nesynchronizované

    And the next step was for us to go to the
    next generation, and then the third
  467. Nesynchronizované
    generation out, and the same disease state
    occurs. So after we did several repeats
  468. Nesynchronizované
    and got the third generation showing it,
    and then a fourth generation, we stepped
  469. Nesynchronizované
    back and realized the phenomena was real.
    We started seeing this major diseases
  470. Nesynchronizované
    occur in approximately 85% of all the
    the animals of every single generation.
  471. Nesynchronizované

    His discoveries were a revelation.
  472. Nesynchronizované

    We knew that if and individual was exposed
    to an environmental toxin, they can get a
  473. Nesynchronizované
    disease state potentially. The new
    phenomena is the environmental toxin no
  474. Nesynchronizované
    longer effects just the individual exposed,
    but two or three generations down the line.
  475. Nesynchronizované
    I knew that epigenetics existed, I knew it
    was a controlling factor for DNA activity,
  476. Nesynchronizované
    whether genes are silenced or not, but to
    say that epigenetics would have a major
  477. Nesynchronizované
    role in disease development, I had no
    concept for that. The fact that genetics
  478. Nesynchronizované
    could have such a huge impact, and could
    explain a whole host of things we couldn't
  479. Nesynchronizované
    explain before took a while to actually sink in.
  480. Nesynchronizované

    The exposure of a single animal to a toxin
    was causing a whole range of diseases in
  481. Nesynchronizované
    almost every individual of following
    generations. And because epigenetics
  482. Nesynchronizované
    effects have been observed in humans, this
    may have implications for us, too.
  483. Nesynchronizované

    What this means then is what your
    grandmother was exposed to when
  484. Nesynchronizované
    she was pregnant could cause a disease
    in you, even though you had no exposure,
  485. Nesynchronizované
    and you are going to pass it on to your
    great grandchildren.
  486. Nesynchronizované
  487. Nesynchronizované

    The work of these scientists is at last
    throwing a spotlight onto the mysterious
  488. Nesynchronizované
    hidden world of epigenetics. They appear
    to show the lives of our ancestors have a
  489. Nesynchronizované
    capacity to effect us directly.
  490. Nesynchronizované

    These results are provocative. Some find
    them a little difficult to accept. But its
  491. Nesynchronizované
    quite clear now that a number of
    laboratories are finding the similar
  492. Nesynchronizované
    findings in the very systems in the very
    systems they are interested in. So the
  493. Nesynchronizované
    phenomena are there.
  494. Nesynchronizované

    Epigenetics have the capacity have the
    ability to reach into every aspect of our
  495. Nesynchronizované
    lives, and links our past, present and
    future in previously unimagined ways.
  496. Nesynchronizované

    I think this will be the next revolution
    in molecular biology. This could really
  497. Nesynchronizované
    be a paradigm shift we did not expect,
    it could explain a lot of things.
  498. Nesynchronizované

    It could explain a lot of diseases, very
    common diseases, such as Alzheimer's
  499. Nesynchronizované
    disease of the brain, diabetes, which are
    very difficult to explain currently
  500. Nesynchronizované
    genetically. Maybe a lot of these very
    common diseases are actually caused by
  501. Nesynchronizované
    epigenetics, which is...
  502. Nesynchronizované

    We are just at the beginning, there is
    much that is unknown. But what is clear,
  503. Nesynchronizované
    is that it will change the way we think
    about ourselves, forever.
  504. Nesynchronizované

    I thought of nothing else really for the
    last five years. It is said the first time
  505. Nesynchronizované
    one had a photograph of the Earth, you
    know, this sort of delicate thing soaring
  506. Nesynchronizované
    through, sailing through the universe you
    know, it had a huge effect on this sort of
  507. Nesynchronizované
    "save the planet" type feeling, you know.
    I'm sure that's part of why the future
  508. Nesynchronizované
    generation think in a planetary kind of
    way, because they've actually seen that
  509. Nesynchronizované
    picture... And this might be the same, it
    may get to a point that they realize that
  510. Nesynchronizované
    um, you live your life as a sort of, I
    don't know, a sort of guardian of your
  511. Nesynchronizované
    genome. Sort of mean you gotta be careful
    of it, because it's not just you, you
  512. Nesynchronizované
    can't be selfish, because you can't say
    "I'll smoke" or whatever it is, because
  513. Nesynchronizované
    you're prepared to die early. You also are
    looking after it for your children and
  514. Nesynchronizované
  515. Nesynchronizované