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← A new superweapon in the fight against cancer

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Showing Revision 11 created 04/13/2016 by Brian Greene.

  1. Cancer affects all of us --
  2. especially the ones that come
    back over and over again,
  3. the highly invasive
    and drug-resistant ones,
  4. the ones that defy medical treatment,
  5. even when we throw our best drugs at them.
  6. Engineering at the molecular level,
  7. working at the smallest of scales,
  8. can provide exciting new ways
  9. to fight the most aggressive
    forms of cancer.
  10. Cancer is a very clever disease.

  11. There are some forms of cancer,
  12. which, fortunately, we've learned
    how to address relatively well
  13. with known and established
    drugs and surgery.
  14. But there are some forms of cancer
  15. that don't respond to these approaches,
  16. and the tumor survives or comes back,
  17. even after an onslaught of drugs.
  18. We can think of these
    very aggressive forms of cancer

  19. as kind of supervillains in a comic book.
  20. They're clever, they're adaptable,
  21. and they're very good at staying alive.
  22. And, like most supervillains these days,
  23. their superpowers come
    from a genetic mutation.
  24. The genes that are modified
    inside these tumor cells
  25. can enable and encode for new
    and unimagined modes of survival,
  26. allowing the cancer cell to live through
  27. even our best chemotherapy treatments.
  28. One example is a trick
    in which a gene allows a cell,

  29. even as the drug approaches the cell,
  30. to push the drug out,
  31. before the drug can have any effect.
  32. Imagine -- the cell effectively
    spits out the drug.
  33. This is just one example
    of the many genetic tricks
  34. in the bag of our supervillain, cancer.
  35. All due to mutant genes.
  36. So, we have a supervillain
    with incredible superpowers.

  37. And we need a new and powerful
    mode of attack.
  38. Actually, we can turn off a gene.
  39. The key is a set of molecules
    known as siRNA.
  40. siRNA are short sequences of genetic code
  41. that guide a cell to block a certain gene.
  42. Each siRNA molecule
    can turn off a specific gene
  43. inside the cell.
  44. For many years since its discovery,
  45. scientists have been very excited
  46. about how we can apply
    these gene blockers in medicine.
  47. But, there is a problem.

  48. siRNA works well inside the cell.
  49. But if it gets exposed to the enzymes
  50. that reside in our bloodstream
    or our tissues,
  51. it degrades within seconds.
  52. It has to be packaged, protected
    through its journey through the body
  53. on its way to the final target
    inside the cancer cell.
  54. So, here's our strategy.

  55. First, we'll dose the cancer cell
    with siRNA, the gene blocker,
  56. and silence those survival genes,
  57. and then we'll whop it with a chemo drug.
  58. But how do we carry that out?
  59. Using molecular engineering,
  60. we can actually design a superweapon
  61. that can travel through the bloodstream.
  62. It has to be tiny enough
    to get through the bloodstream,
  63. it's got to be small enough
    to penetrate the tumor tissue,
  64. and it's got to be tiny enough
    to be taken up inside the cancer cell.
  65. To do this job well,
  66. it has to be about one one-hundredth
    the size of a human hair.
  67. Let's take a closer look
    at how we can build this nanoparticle.

  68. First, let's start
    with the nanoparticle core.
  69. It's a tiny capsule that contains
    the chemotherapy drug.
  70. This is the poison that will
    actually end the tumor cell's life.
  71. Around this core, we'll wrap a very thin,
  72. nanometers-thin blanket of siRNA.
  73. This is our gene blocker.
  74. Because siRNA is strongly
    negatively charged,
  75. we can protect it
  76. with a nice, protective layer
    of positively charged polymer.
  77. The two oppositely charged
    molecules stick together
  78. through charge attraction,
  79. and that provides us
    with a protective layer
  80. that prevents the siRNA
    from degrading in the bloodstream.
  81. We're almost done.
  82. (Laughter)

  83. But there is one more big obstacle
    we have to think about.

  84. In fact, it may be the biggest
    obstacle of all.
  85. How do we deploy this superweapon?
  86. I mean, every good weapon
    needs to be targeted,
  87. we have to target this superweapon
    to the supervillain cells
  88. that reside in the tumor.
  89. But our bodies have a natural
    immune-defense system:

  90. cells that reside in the bloodstream
  91. and pick out things that don't belong,
  92. so that it can destroy or eliminate them.
  93. And guess what? Our nanoparticle
    is considered a foreign object.
  94. We have to sneak our nanoparticle
    past the tumor defense system.
  95. We have to get it past this mechanism
    of getting rid of the foreign object
  96. by disguising it.
  97. So we add one more
    negatively charged layer

  98. around this nanoparticle,
  99. which serves two purposes.
  100. First, this outer layer is one
    of the naturally charged,
  101. highly hydrated polysaccharides
    that resides in our body.
  102. It creates a cloud of water molecules
    around the nanoparticle
  103. that gives us an invisibility
    cloaking effect.
  104. This invisibility cloak allows
    the nanoparticle
  105. to travel through the bloodstream
  106. long and far enough to reach the tumor,
  107. without getting eliminated by the body.
  108. Second, this layer contains molecules

  109. which bind specifically to our tumor cell.
  110. Once bound, the cancer cell
    takes up the nanoparticle,
  111. and now we have our nanoparticle
    inside the cancer cell
  112. and ready to deploy.
  113. Alright! I feel the same way. Let's go!

  114. (Applause)

  115. The siRNA is deployed first.

  116. It acts for hours,
  117. giving enough time to silence
    and block those survival genes.
  118. We have now disabled
    those genetic superpowers.
  119. What remains is a cancer cell
    with no special defenses.
  120. Then, the chemotherapy drug
    comes out of the core
  121. and destroys the tumor cell
    cleanly and efficiently.
  122. With sufficient gene blockers,
  123. we can address many
    different kinds of mutations,
  124. allowing the chance to sweep out tumors,
  125. without leaving behind any bad guys.
  126. So, how does our strategy work?

  127. We've tested these nanostructure
    particles in animals
  128. using a highly aggressive form
    of triple-negative breast cancer.
  129. This triple-negative breast cancer
    exhibits the gene
  130. that spits out cancer drug
    as soon as it is delivered.
  131. Usually, doxorubicin -- let's call
    it "dox" -- is the cancer drug

  132. that is the first line of treatment
    for breast cancer.
  133. So, we first treated our animals
    with a dox core, dox only.
  134. The tumor slowed their rate of growth,
  135. but they still grew rapidly,
  136. doubling in size
    over a period of two weeks.
  137. Then, we tried
    our combination superweapon.

  138. A nanolayer particle with siRNA
    against the chemo pump,
  139. plus, we have the dox in the core.
  140. And look -- we found that not only
    did the tumors stop growing,
  141. they actually decreased in size
  142. and were eliminated in some cases.
  143. The tumors were actually regressing.
  144. (Applause)

  145. What's great about this approach
    is that it can be personalized.

  146. We can add many different layers of siRNA
  147. to address different mutations
    and tumor defense mechanisms.
  148. And we can put different drugs
    into the nanoparticle core.
  149. As doctors learn how to test patients
  150. and understand certain
    tumor genetic types,
  151. they can help us determine which patients
    can benefit from this strategy
  152. and which gene blockers we can use.
  153. Ovarian cancer strikes
    a special chord with me.

  154. It is a very aggressive cancer,
  155. in part because it's discovered
    at very late stages,
  156. when it's highly advanced
  157. and there are a number
    of genetic mutations.
  158. After the first round of chemotherapy,
  159. this cancer comes back
    for 75 percent of patients.
  160. And it usually comes back
    in a drug-resistant form.
  161. High-grade ovarian cancer
  162. is one of the biggest
    supervillains out there.
  163. And we're now directing our superweapon
  164. toward its defeat.
  165. As a researcher,

  166. I usually don't get to work with patients.
  167. But I recently met a mother
  168. who is an ovarian cancer survivor,
    Mimi, and her daughter, Paige.
  169. I was deeply inspired
    by the optimism and strength
  170. that both mother and daughter displayed
  171. and by their story of courage and support.
  172. At this event, we spoke
    about the different technologies
  173. directed at cancer.
  174. And Mimi was in tears
  175. as she explained how learning
    about these efforts
  176. gives her hope for future generations,
  177. including her own daughter.
  178. This really touched me.
  179. It's not just about building
    really elegant science.
  180. It's about changing people's lives.
  181. It's about understanding
    the power of engineering
  182. on the scale of molecules.
  183. I know that as students like Paige
    move forward in their careers,

  184. they'll open new possibilities
  185. in addressing some of the big
    health problems in the world --
  186. including ovarian cancer, neurological
    disorders, infectious disease --
  187. just as chemical engineering has
    found a way to open doors for me,
  188. and has provided a way of engineering
  189. on the tiniest scale,
    that of molecules,
  190. to heal on the human scale.
  191. Thank you.

  192. (Applause)