English titulky

← vimeo.com/.../238478130

Získať kód na vloženie
1 Language

Ukazujem Revíziu 3 vytvorenú 10/20/2017 od DLC.

  1. Nesynchronizované
  2. Nesynchronizované

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

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

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

    The science of inheritance is being turned
    on its head.
  17. Nesynchronizované
    We're changing the view of what
    inheritance is.
  18. Nesynchronizované
  19. Nesynchronizované

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

    Here we have multiple generation in
    the same grave.
  26. Nesynchronizované
    This group of people could really
    contribute to a sea of change in the
  27. Nesynchronizované
    way we think about inheritance.
  28. Nesynchronizované

    They have come to this churchyard to
    find grandmothers and granddaughters,
  29. Nesynchronizované
    grandfathers and grandsons. Connecting
    people who lived almost a hundred years
  30. Nesynchronizované
    apart, in entirely new ways. Uncovering
    links that confound scientific thinking.
  31. Nesynchronizované

    Up until now, inheritance was just, just,
    the genes, the DNA sequence. I suspect
  32. Nesynchronizované
    that we're going to be able to demonstrate
    that the inheritance is more than that.
  33. Nesynchronizované
    This is a grandson as it were in our
    study...
  34. Nesynchronizované

    It is the culmination of more than
    twenty years of work, and for the
  35. Nesynchronizované
    first time Pembrey is confronting the
    magnitude of their discovery.
  36. Nesynchronizované

    It has really come alive for me, coming
    here, more than I had expected it to.
  37. Nesynchronizované
    I'm really quite sort of emotional about
    it. Wonderful!
  38. Nesynchronizované
  39. Nesynchronizované

    Marcus Pembrey is one of a select brand of
    scientists, a brand that is willing to
  40. Nesynchronizované
    challenge an orthodoxy. They believe the
    lives of our parents, grandparents, and
  41. Nesynchronizované
    even our great grandparents can directly
    effect our well-being, despite never
  42. Nesynchronizované
    experiencing these things ourselves.
  43. Nesynchronizované
    To many of people, these ideas are
    regarded as scientific heresy.
  44. Nesynchronizované

    You cannot predict where these important
    will be, the only thing that you can do is
  45. Nesynchronizované
    follow your instinct.
  46. Nesynchronizované

    Conventional biology has always believed
    that our genetic inheritance is set in
  47. Nesynchronizované
    stone at the moment of our conception. At
    that instant, we receive a set of
  48. Nesynchronizované
    chromosomes from both our mother and our
    father.
  49. Nesynchronizované
    Within these chromosomes are the genes,
    strips of coded DNA, the basic unit of
    inheritance.
  50. Nesynchronizované
    After conception, it was presumed assumed that our
    genes were locked away inside every cell
  51. Nesynchronizované
    of the body, protected untouched from the
    way you live.
  52. Nesynchronizované
    So what you do in your life may effect you,
    but your genes remain untainted, unchanged
  53. Nesynchronizované
    for future generations.
  54. Nesynchronizované
    In classic genetics, your parents and
    grandparents simply pass on their genes,
  55. Nesynchronizované
    the experiences they accumulated in a
    lifetime are never inherited, lost forever
  56. Nesynchronizované
    as the genes pass untouched generation
    after generation.
  57. Nesynchronizované
    The biology of inheritance was a reassuringly
    pure process, or so it seemed.
  58. Nesynchronizované
  59. Nesynchronizované
    In the early '80's, Marcus Pembrey headed
    the clinical genetic department at
  60. Nesynchronizované
    Great Ormond Street Hospital for Children.
  61. Nesynchronizované
    He was frequently treating families with
    unusual genetic conditions.
  62. Nesynchronizované

    We were constantly coming across families
    which didn't fit the rules, that didn't fit
  63. Nesynchronizované
    any of the patterns that genetics were
    supposed to fit, so you think of
  64. Nesynchronizované
    chromosome abnormalities and, uh, you
    check the chromosomes and they are normal.
  65. Nesynchronizované
    So you then to start imagining as it were,
    you know, what might be underlying this
  66. Nesynchronizované
    and you are really driven to try and work
    it out because the families really needed
  67. Nesynchronizované
    some help.
  68. Nesynchronizované

    The more families he saw, the more the
    rules of inheritance appeared to break
  69. Nesynchronizované
    down.
  70. Nesynchronizované
    Diseases and conditions that simply didn't
    fit with the textbook conventions.
  71. Nesynchronizované
    One condition in particular caught his eye,
    Angelman Syndrome.
  72. Nesynchronizované

    Named after Harry Angelman, the
    pediatrician who first described Angelman

  73. Nesynchronizované
    Syndrome, he described them as "happy
    puppet children" because it described some
  74. Nesynchronizované
    of their apparent features. They have a
    jerky movement when they are walking.
  75. Nesynchronizované
    These children have no speech, they are
    severely incapacitated in terms of learning,
  76. Nesynchronizované
    but are uncharacteristically happy,
    they're smiling all of the time.
  77. Nesynchronizované
  78. Nesynchronizované

    The condition was caused by a genetic
    fault, a key sequence of DNA was missing,
  79. Nesynchronizované
    deleted from chromosome 15.
  80. Nesynchronizované

    Then we came across a paradox; at the same
    the same change, the same deletion,
  81. Nesynchronizované
    was clearly associated with a quite
    different syndrome, much milder in terms
  82. Nesynchronizované
    of impairment, the Prader-Willi Syndrome.
  83. Nesynchronizované

  84. Nesynchronizované
    These children are characterized by being
    very floppy at birth, but once they
  85. Nesynchronizované
    started eating properly they then had
    an insatiable appetite and would get
  86. Nesynchronizované
    very, VERY large.
  87. Nesynchronizované

    What Pembrey saw simply made no sense.
  88. Nesynchronizované
    Here were two completely different
    diseases, Angelman Syndrome and
  89. Nesynchronizované
    Prader-Willi Syndrome being caused by
    exactly the same genetic fault.
  90. Nesynchronizované

    So here we were in a bizarre situation
    really.
  91. Nesynchronizované
    How could anyone propose that the same
    deletion cause a different syndrome?
  92. Nesynchronizované

    It appeared to Pembrey as if the simple
    view of inheritance was beginning to
  93. Nesynchronizované
    unravel. But his doubts were contrary to
    the tide of optimism sweeping the scientific
  94. Nesynchronizované
    community.
  95. Nesynchronizované
    In the early 1990's, the biggest project
    ever undertaken in human biology was
  96. Nesynchronizované
    captivating the world.
  97. Nesynchronizované

    The human genome project will be seen as
    the outstanding achievement in the history
  98. Nesynchronizované
    of Mankind.
  99. Nesynchronizované

    The human genome project was to be the
    pinnacle of work on understanding human
  100. Nesynchronizované
    genes and genetics. It seemed as if the
    secrets of life were at our fingertips.
  101. Nesynchronizované


  102. Nesynchronizované

    The human genome is like a bible where
    everything was written down. The hope,
  103. Nesynchronizované
    the expectation, was once we had that book
    in front of us, and all the letters we could
  104. Nesynchronizované
    just read down the pages, then we would
    understand how the body was put together.
  105. Nesynchronizované

    It would offer a complete understanding of
    human biology at a molecular level.
  106. Nesynchronizované
    The hope was that once the code was written
    down, scientists could find the genetic cause
  107. Nesynchronizované
    and cure for every disease.
  108. Nesynchronizované

  109. Nesynchronizované

    We were thinking of genes in a very
    mechanical way; we were thinking of them
  110. Nesynchronizované
    just in terms of the sequence of the letters.
    We were working out what all the letters
  111. Nesynchronizované
    were in the book.
  112. Nesynchronizované

    Scientists estimated that the human genome,
    the book of life,
  113. Nesynchronizované
    would contain around 100,000 genes.
  114. Nesynchronizované

    And then when they started sequencing they
    realized there may be fewer than 100,000
  115. Nesynchronizované
    genes, then it popped down to 60,000, then
    it popped down to 50,000... It slowly went
  116. Nesynchronizované
    down to a much smaller number. In fact,
    we found that the human genome is
  117. Nesynchronizované
    probably not as complex and doesn't have
    as many genes as plants do.
  118. Nesynchronizované
    So that then made us really question, well,
    "if the genome has less genes in this
  119. Nesynchronizované
    species than in this species, and we're more
    complex, potentially, what is going on here?"
  120. Nesynchronizované

    Now scientists estimate there are probably
    less than 30,000 genes.
  121. Nesynchronizované

    We believed, I believed naively, that we would
    be able to find the genetic components of

  122. Nesynchronizované
    common diseases. That's proven to be very
    difficult, as the idea of one gene, one
  123. Nesynchronizované
    disease does not explain it all.
  124. Nesynchronizované

    30,000 genes didn't appear to be enough
    to explain human complexity, there had
  125. Nesynchronizované
    to be something they missed.
  126. Nesynchronizované
    The first hints of what was missing lay in
    the curious curious paradox of the
  127. Nesynchronizované
    Prader-Willi and Angelman Syndromes.
    Two quite different diseases caused by
  128. Nesynchronizované
    exactly the same genetic fault. When
    Pembrey looked at the inheritance
  129. Nesynchronizované
    patterns for the conditions, he noticed
    something even stranger...
  130. Nesynchronizované

    What really mattered was the origin of
    the chromosome 15 that had the deletion.
  131. Nesynchronizované
    If the deletion was one the chromosome 15
    that the child inherited from the father,
  132. Nesynchronizované
    then you had Prader-Willi Syndrome. If the
    deletion was inherited from the mother,
  133. Nesynchronizované
    then you the Angelman Syndrome.
  134. Nesynchronizované

    It was a complete surprise that the same
    missing strip of DNA could cause one
  135. Nesynchronizované
    disease when it came from the mother, and
    a completely different disease when it
  136. Nesynchronizované
    came from the father. It's as if the genes knew
    where they came from.
  137. Nesynchronizované

    You're got a developing fetus manifesting
    this condition, how does the chromosome

  138. Nesynchronizované
    15 know where it came from? There must
    have been a tag or imprint impressed on
  139. Nesynchronizované
    that chromosome during egg or sperm
    formation in the previous generation to
  140. Nesynchronizované
    say "hi, I came from mother," or "I came
    from father" and we are functioning
  141. Nesynchronizované
    differently. And that is the key, although
    the DNA sequences the same, the
  142. Nesynchronizované
    different sets of genes were being silenced
    depending on if they came from the
  143. Nesynchronizované
    mother or the father.
  144. Nesynchronizované

    It showed there was clearly more to
    inheritance than simply the coded DNA.
  145. Nesynchronizované

    We then realized we were dealing with
    what is now known as genomic imprinting.
  146. Nesynchronizované
    What genomic imprinting means, is in a
    nutshell, genes have a memory of where
  147. Nesynchronizované
    they came from.
  148. Nesynchronizované

    Something other than just the DNA was
    capable of moving between generations.
  149. Nesynchronizované
    It was a tantalizing glimpse into this
    unknown and unexpected world. A
  150. Nesynchronizované
    hidden layer acting on, and able to
    directly control how our genes function.
  151. Nesynchronizované
    It meant that inheritance was not simply about
    which genes you inherited, but whether
  152. Nesynchronizované
    those genes were silenced, switched on
    or off.
  153. Nesynchronizované

    And you can think of it like a lightswitch...
  154. Nesynchronizované
    Dawn the gene, the light is on, the gene is
    active, it makes the cell do a certain thing.
  155. Nesynchronizované
    Or, the light switch is off and everything
    is dark, it is off. The gene remains turned
  156. Nesynchronizované
    on or off and that gives the cells their
    identity.
  157. Nesynchronizované

    The activity of genes was being controlled
    by a switch, the attachment of a certain
  158. Nesynchronizované
    chemical that dictated whether a gene was
    switched on, or off.
  159. Nesynchronizované

    Whether those genes are turned on or off
    is called epigenetics.
  160. Nesynchronizované

    Epigenetics...act...upon the...genes.
  161. Nesynchronizované

    Not only is the sequence important of the
    DNA, which we've studied for a long time,
  162. Nesynchronizované
    the past few decades, but we now understand
    that in addition to that there is this underlying
  163. Nesynchronizované
    epigenetic phenomena that allows the genes
    to get turned on or off.
  164. Nesynchronizované

    Epigenetics could explain how a human could
    be created with less than 30,000 genes, and
  165. Nesynchronizované
    why the genome project didn't provide all
    of the answers.
  166. Nesynchronizované

    Now if we actually put epigenetics on top
    of it, where it makes it much more
  167. Nesynchronizované
    complicated if genes get activated to a
    certain level and so forth, then you
  168. Nesynchronizované
    have a complexity that can start explain biology
    much more effectively than the simple
  169. Nesynchronizované
    sequence of the DNA.
  170. Nesynchronizované

    So clearly we have additional levels of
    complexity that we now need to
  171. Nesynchronizované
    understand that are well beyond the DNA.
    The next huge challenge for modern biology
  172. Nesynchronizované
    is to now decipher the epigenetic code, to
    understand all the combinations of switches
  173. Nesynchronizované
    that exist.
  174. Nesynchronizované

    An accurate chemical map of the human
    genome tells us surprisingly little about
  175. Nesynchronizované
    how it actually works. Transcribing the
    code of the genes, the genome project,
  176. Nesynchronizované
    is not an end, but simply a beginning.
  177. Nesynchronizované
  178. Nesynchronizované
    If inheritance was not just about DNA,
    if these gene switches were so important,
  179. Nesynchronizované
    just what could turn them on, or off?
  180. Nesynchronizované
    Stepahnie and Amon Mullins have two
    children, Kiren and Charlotte.
  181. Nesynchronizované

    When you are trying to conceive and you
    see all of your friends around you getting
  182. Nesynchronizované
    pregnant, having children, as each month
    goes on you become more and more desperate.
  183. Nesynchronizované

    Doctors recommended IVF treatment.
  184. Nesynchronizované
    In the UK alone, around 8,000 babies are
    conceived every year using assisted
  185. Nesynchronizované
    reproduction techniques like IVF. After
    the third attempt, Stephanie became
  186. Nesynchronizované
    pregnant with Kiren.
  187. Nesynchronizované

    At the time, they didn't really highlight
    any risk to us, and then we went for a
  188. Nesynchronizované
    routine scan, and I did feel that the scan
    was taking an awful long time.
  189. Nesynchronizované
    Basically what they found was something
    called an exomphalos on Kiren's abdomen
  190. Nesynchronizované
    which basically means that part of the
    bowel is still on the outside of the
  191. Nesynchronizované
    abdomen.
  192. Nesynchronizované

    Doctors suspected that Kiren might be
    suffering from Beckwith Wiedemann
  193. Nesynchronizované
    syndrome, a rare condition where babies
    are born very large, have oversized
  194. Nesynchronizované
    tongues, and high risk of developing
    childhood cancers.
  195. Nesynchronizované

    They couldn't say for 100% that the baby
    did have Beckwith Wiedemann syndrome,
  196. Nesynchronizované
    but it was showing signs, they could see
    his tongue protruding on the scan and
  197. Nesynchronizované
    they said he had very big thighs... But
    until Kiren was born, we didn't know how
  198. Nesynchronizované
    severely effected he would be.
  199. Nesynchronizované

    When Kiren was born it was clear he did
    have Beckwith Wiedemann syndrome.
  200. Nesynchronizované

    Within a few hours of the birth, Kiren had
    to have surgery to put the bowel that was
  201. Nesynchronizované
    basically on the outside of the abdomen
    put back inside and repaired.
  202. Nesynchronizované

    Kiren also had surgery to reduce the size
    of his tongue and every few months he has
  203. Nesynchronizované
    scans to check for tumors.
  204. Nesynchronizované
  205. Nesynchronizované

    Cases of Beckwith Wiedemann syndrome caught
    the attention of Wulf Reich.
  206. Nesynchronizované
    Wulf Reich worked in developmental genetics.
    He was fascinated by this emerging epigenetic
  207. Nesynchronizované
    ghost world. He wanted to know what could
    throw the switches on or off.
  208. Nesynchronizované
    To his surprise, he found by simply placing
    a mouse embryo in a petri dish could cause
  209. Nesynchronizované
    genes to switch on or off.
  210. Nesynchronizované

    After we had seen how relatively easy it
    was to change the switches in mouse embryos,
  211. Nesynchronizované
    we thought perhaps it could be the same in
    human embryos.
  212. Nesynchronizované
    We though in IVF you have the embryo for a
    brief period of time in a culture dish, and so we
  213. Nesynchronizované
    were asking the question whether as with
    the mouse embryo, just the mere fact of
  214. Nesynchronizované
    having human embryos in a culture dish or
    having been manipulated could alter their
  215. Nesynchronizované
    genetic switches.
  216. Nesynchronizované

    Wulf knew that Beckwith Wiedemann syndrome
    was caused by a faulty switch.
  217. Nesynchronizované

    So what we were looking at was a group of
    babies, children, that had the
  218. Nesynchronizované
    Beckwith Wiedemann syndrome. What proportion
    of those had been conceived with IVF?
  219. Nesynchronizované

    Could IVF be switching genes on or off?
    Could IVF itself causethe syndrome?
  220. Nesynchronizované

    What we found was an increased occurrence
    of this epigenetic syndrome in the IVF
  221. Nesynchronizované
    population.
  222. Nesynchronizované

    Although the disease is extremely rare,
    the chance seemed to increase 3-4 times
  223. Nesynchronizované
    with IVF. It seemed the simple act of
    removing the embryo from its natural
  224. Nesynchronizované
    environment could trigger the disease.
  225. Nesynchronizované

    And we did feel frustrate that Kiren had
    Beckwith Wiedemann syndrome because we
  226. Nesynchronizované
    had IVF, but at that time it seemed like the
    right decision to make.
  227. Nesynchronizované

    And I think we should look again at the IVF
    procedures, the conditions that are being
  228. Nesynchronizované
    used, and carry out better and more precise
    experiments to see how we can avoid
  229. Nesynchronizované
    throwing these epigenetic switches.
  230. Nesynchronizované

    Wulf had shown that simple changes in the
    environment could switch a gene on or off,
  231. Nesynchronizované
    but there was more...
  232. Nesynchronizované
  233. Nesynchronizované
    Everyone thought that any altered switches
    could not be inherited. He took some mice
  234. Nesynchronizované
    with altered gene switches and bred them.
  235. Nesynchronizované

    Our expectation was that as the altered
    genome was passed to the children that
  236. Nesynchronizované
    any epigenetic changes would be wiped
    clean.
  237. Nesynchronizované

    When he looked at the gene profile of the
    offspring, he was amazed.
  238. Nesynchronizované
    every
    You have these dots you are looking at,
    and each dot tells you that a gene was on.
  239. Nesynchronizované
    And all of a sudden someone said "wow,
    look at that!"
  240. Nesynchronizované

    The epigenetic switch thrown in one
    generation, was clearly also present in
  241. Nesynchronizované
    the second generation.
  242. Nesynchronizované

    Nobody had seen this kind of thing before,
    and everyone looking at this gel was saying
  243. Nesynchronizované
    "no, that can't be right. This must be the
    wrong gel." You know, how you get excited
  244. Nesynchronizované
    about it and then you thing this is wrong,
    you're not on the right track. And we were
  245. Nesynchronizované
    very excited, as excited as scientists
    ever get.
  246. Nesynchronizované

    This meant the genes were not locked away,
    a simple environmental event could effect
  247. Nesynchronizované
    way genes worked, and that could be inherited.
    It was if a memory of an event could be
  248. Nesynchronizované
    passed down through generations. It was
    something many scientists regarded as
  249. Nesynchronizované
    impossible. If this effect could be observed
    in humans, the implication would be profound.
  250. Nesynchronizované
    It would mean that what we experience could
    effect not just us, but our children and
  251. Nesynchronizované
    grandchildren.
  252. Nesynchronizované
    24:35