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Ukazujem Revíziu 8 vytvorenú 10/27/2017 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
    great-grandkids.

  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 these graveyards may hold the
  21. proof to their radical ideas.

  22. Here we have multiple generation in
    the same graveyard.
  23. This group of people could really
    contribute to a sea of change in the
  24. way we think about inheritance.

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

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

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

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

  35. Marcus Pembrey is one of a select brand of
    scientists, a brand who are daring to
  36. challenge an orthodoxy. They believe the
    lives of our parents, grandparents, and
  37. even our great grandparents can directly
    effect our well-being, despite never
  38. experiencing these things ourselves.
  39. To many of people, these ideas are
    regarded as scientific heresy.

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

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

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

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

  67. Named after Harry Angelman, the
    pediatrician who first described Angelman

  68. Syndrome, he described them as "happy
    puppet children" because it described some
  69. of their apparent features. They have a
    jerky movement when they are walking.
  70. These children have no speech, they are
    severely incapacitated in terms of learning,
  71. but are uncharacteristically happy,
    they're smiling all of the time.

  72. The condition was caused by a genetic
    fault, a key sequence of DNA was missing,
  73. deleted from chromosome 15.

  74. Then we came across a paradox; at the same
    the same change, the same deletion,
  75. had been clearly associated with a quite
    different syndrome, much milder in terms
  76. of intellectual impairment, the
    Prader-Willi Syndrome.

  77. These children are characterized by being
    very floppy at birth, but once they
  78. started eating properly they then had
    an insatiable appetite and would get
  79. very, VERY large.

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

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

  85. It appeared to Pembrey as if the simple
    view of inheritance was beginning to
  86. unravel. But his doubts were contrary to
    the tide of optimism sweeping the scientific
  87. community.
  88. In the early 1990's, the biggest project
    ever undertaken in human biology was
  89. captivating the world.

  90. The human genome project will be seen as
    the outstanding achievement in the history
  91. of Mankind.

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



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

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


  100. We were thinking of genes in a very
    mechanical way; we were thinking of them
  101. just in terms of the sequence of the letters.
    We were working out what all the letters
  102. were in the book.

  103. Scientists estimated that the human genome,
    the book of life,
  104. would contain around 100,000 genes.

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

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

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

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

  115. 30,000 genes didn't appear to be enough
    to explain human complexity, there had
  116. to be something they missed.
  117. The first hints of what was missing lay in
    the curious curious paradox of the
  118. Prader-Willi and Angelman Syndromes.
    Two quite different diseases caused by
  119. exactly the same genetic fault. When
    Pembrey looked at the inheritance
  120. patterns for the conditions, he noticed
    something even stranger...

  121. What really mattered was the origin of
    the chromosome 15 that had the deletion.
  122. If the deletion was one the chromosome 15
    that the child inherited from the father,
  123. then you had Prader-Willi Syndrome. If the
    deletion was inherited from the mother,
  124. then you the Angelman Syndrome.

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

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

  129. 15 know where it came from? There must
    have been a tag or imprint impressed on
  130. that chromosome during egg or sperm
    formation in the previous generation to
  131. say "hi, I came from mother," or "I came
    from father" and we are functioning
  132. differently. And that is the key, although
    the DNA sequences the same, the
  133. different sets of genes were being silenced
    depending on if they came from the
  134. mother or the father.

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

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

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

  144. And you can think of it like a lightswitch...
  145. Turn on the gene, the light is on, the gene is
    active, it makes the cell do a certain thing.
  146. Or, the light switch is off and everything
    is dark, it is off. The switches remain turned
  147. on or off and that gives the cells their
    identity.

  148. The activity of genes was being controlled
    by a switch, the attachment of a simple
  149. chemical that dictated whether a gene was
    switched on, or off.

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

  151. Epigenetics...act...upon the...genes.

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

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

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

  161. So clearly we have additional levels of
    complexity that we now need to
  162. understand that are well beyond the DNA.
    The next huge challenge for modern biology
  163. is to now decipher the epigenetic code, to
    understand all the combinations of switches
  164. that exist.

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

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

  173. Doctors recommended IVF treatment.
  174. In the UK alone, around 8,000 babies are
    conceived every year using assisted
  175. reproduction techniques like IVF. After
    the third attempt, Stephanie became
  176. pregnant with Kiren.

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

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

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

  189. When Kiren was born it was clear he did
    have Beckwith-Wiedemann syndrome.

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

  192. Kiren also had surgery to reduce the size
    of his tongue and every few months he has
  193. scans to check for tumors.

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

  199. After we had seen how relatively easy it
    was to change the switches in mouse embryos,
  200. we thought perhaps it could be the same in
    human embryos.
  201. We saw in IVF you have the embryo for a
    brief period of time in a culture dish, and so we
  202. were asking the question whether as with
    the mouse embryo, just the mere fact of
  203. having human embryos in a culture dish or
    having been manipulated could alter their
  204. epigenetic switches.

  205. Wulf knew that Beckwith-Wiedemann syndrome
    was caused by a faulty switch.

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

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

  209. What we found was an increased occurrence
    of this epigenetic syndrome in the IVF
  210. population.

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

  214. And we did feel frustrated that Kiren had
    Beckwith-Wiedemann syndrome because we
  215. had IVF, but at that time it seemed like the
    right decision to make.

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

  219. Wulf had shown that simple changes in the
    environment could switch a gene on or off,
  220. but there was more...
  221. Everyone thought that any altered switches
    could not be inherited. He took some mice
  222. with altered gene switches and bred them.

  223. Our expectation was that as the altered
    genome was passed to the children that
  224. any epigenetic changes would be wiped
    clean.

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

  228. The epigenetic switch thrown in one
    generation, was clearly also present in
  229. the second generation.

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

  234. This meant the genes were not locked away,
    a simple environmental event could effect
  235. way genes worked, and that could be inherited.
    It was if a memory of an event could be
  236. passed down through generations. It was
    something many scientists regarded as
  237. impossible. If this effect could be observed
    in humans, the implication would be profound.
  238. It would mean that what we experience could
    effect not just us, but our children
  239. and our grandchildren.
  240. While these observations were emerging
    from laboratories, Pembrey was still
  241. working at Great Ormond Street. He began
    to wonder why these links between
  242. generations would exist.

  243. Now my reputation was a made as a clinical
    geneticist, so I was much freer to speculate
  244. outside my main career. I also like to stir
    things up a bit, and it amuses me to
  245. speculate because I have nothing to lose,
    and if I'm right, well then that's very
  246. amusing (laughs).

  247. He speculated why genes would
    carry a memory from one generation
  248. to a next. What evolutionary purpose
    could it serve?

  249. Maybe imprinting was used as a
    means of some trans-generational adaptation.

  250. He thought it could be used by a mother to
    send messages to her baby in the next
  251. generation.

  252. Something that always troubled me since I
    was a medical student was what stops the
  253. baby's head jamming up in the birth canal?
    The baby of course was grown in one
  254. generation, but the mother's pelvis was
    grown in the previous generation.
  255. But what if the mother was starving as she
    was growing, so she had a small pelvis?
  256. Maybe her her eggs had captured that
    information and were instructing the growth
  257. genes of the future babies to not work so
    much and the baby to not grow too much, so
  258. as not to jam up the birth canal, so there
    was some coordination between the growth
  259. of two generations. That struck me as
    highly reasonable.

  260. He published his ideas in a largely obscure
    journal and forgot about it. After all,
  261. there was no evidence for any of this, it
    was pure speculation.
  262. Then four years later, Marcus received as
    email from a doctor in Sweden.

  263. It really came as a bolt out of the blue,
    I just got an email in May 2000 saying my
  264. paper was the only thing he could find in
    the literature that in any way sort of
  265. tied-in with his basic observations.

  266. The email was sent by Olov Bygren. He was
    studying the population records of an
  267. obscure town in Sweden, Överkalix. What
    made these records unique were their
  268. detail; they recorded births and deaths
    over hundreds of years. But they also
  269. provided accurate details of the harvests.
    More significantly, Överkalix position on
  270. the Arctic Circle meant that it was
    particularly vulnerable to famine.

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

  274. Bygren appeared to be seeing links between
    generations that confounded his expectations.

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

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

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

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

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

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

  291. She was convinced that the stress in the
    children was caused by the continual
  292. retelling of the stories by their parents.

  293. Our studies had really convinced me that
    it were the later experiences of the child
  294. as the child was growing up, bombarded by
    years and years of symptoms from the parents
  295. that accounted for the effect that we
    observed.

  296. However, in Edinburgh, Johnathan Seckl
    was interested in stress exposure in
  297. pregnant women and wondered if stress
    effects could be transmitted to their
  298. children. He started some experiments with
    pregnant rats to see if exposing them to
  299. stress hormones had any effect on their
    offspring.

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

  302. To see if this was infecting the genes
    themselves, he decided to breed them and
  303. see if the stress effects could be found in
    generations never exposed to the stress
  304. hormone.

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

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

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

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

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

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

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

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

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

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

  342. It appeared that epigenetics might be
    responsible, that an event had altered
  343. the stress response in the children.

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

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

  348. Now, here is the bit where we have to
    speculate,
  349. the animal work would suggest that this
    might then persist into the next generation.

  350. If they find the same stress effects in
    the children's children of 9/11, then it
  351. it will be clear that a genetic memory of
    a stressful event can travel through the
  352. generations.

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

  355. the work of Yehuda and Seckl offers
    tantalizing evidence of solid proof of
  356. inherited epigenetic effects in humans.
  357. But they need data that extend beyond
    just one generation.
  358. The only way forward was to look back to
    the past. In Sweden, Pembrey and Bygren
  359. had data that provided the chance to study
    the effects of famine through many
  360. generations.
  361. Olov Bygren was looking to see if poor
    nutrition had an effect on health, when
  362. he stumbled on something curious.

  363. It appeared that a famine could effect
    people almost a hundred years later,
  364. even if they never suffered a famine
    themselves. He wanted to know how
  365. this might be possible, so he asked
    Marcus Pembrey.

  366. Olov first reported that the food supply
    of the ancestors was effecting the
  367. longevity, or mortality rate, of the
    grandchildren. So I was very excited, I
  368. responded immediately.

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

  371. Specifically, I wanted to know the results
    of the diabetes, because this is one I
  372. thought might involve the imprinting.

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

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

  380. It looked as if there were clear links
    through the generations, between
  381. grandparents and grandchildren.
    They found that the life expectancy of
  382. grandchildren was being directly effected
    by the diet of the grandparent. It
  383. appeared that Overkilex held the key to
    the first evidence of epigenetic
  384. inheritance in humans.

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

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

  391. We wanted to tease out when you could
    trigger in the ancestor a
  392. trans-generational response.

  393. So he and Bygren went back to the data
    and looked again. The more they looked,
  394. the more patters started to appear.

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

  400. They discovered that when a famine was
    able to trigger and effect was different
  401. for the grandmother than the grandfather.
    The grandmother appeared susceptible while
  402. she herself was still in the womb, while
    the grandfather was effected just before
  403. puberty.

  404. And the timing of the sensitive period was
    telling us it was tied in with the
  405. formation of the eggs and the sperm.

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

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

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

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

  421. The diagram showed a significant
    link between generations, between the diet
  422. in one and the life expectancy in another.

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

  425. It's up there with, I'm sort of a
    fair-weather supporter of Liverpool,
  426. it's up there with Liverpool winning the
    champion's league.

  427. You can only have it once in your lifetime.

  428. This is going to become a famous diagram,
    I am convinced by that, I get so excited
  429. every time I see it, it's just so amazing.
  430. Just every time I look at it...
    I find it really exciting, it's fantastic.

  431. Pembrey and Bygren had the first conclusive
    proof of an environmental effect being
  432. inherited in humans.
  433. The impact of a famine being captured by
    the genes, in the eggs and sperm, and the
  434. memory of this event was being carried
    forward to effect the grandchildren
  435. generations later.

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

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

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

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

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

  455. His discoveries were a revelation.

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

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

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

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

  473. These results are provocative. Some find
    them a little difficult to accept. But its
  474. quite clear now that a number of
    laboratories are finding the similar
  475. findings in the very systems in the very
    systems they are interested in. So the
  476. phenomena are there.

  477. Epigenetics has the capacity, the
    ability, to reach into every aspect of our
  478. lives, and links our past, present and
    future in previously unimagined ways.

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

  481. It could explain a lot of diseases, very
    common diseases, such as Alzheimer's
  482. disease of the brain, diabetes, which are
    very difficult to explain currently
  483. genetically. Maybe a lot of these very
    common diseases are actually caused by
  484. epigenetics, which is...

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

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