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← Hacking bacteria to fight cancer - Tal Danino

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Showing Revision 2 created 01/06/2020 by lauren mcalpine .

  1. In 1884, a patient’s luck seemed
    to go from bad to worse.
  2. This patient had a rapidly growing
    cancer in his neck,
  3. and then came down with an unrelated
    bacterial skin infection.
  4. But soon, something unexpected happened:
  5. as he recovered from the infection,
    the cancer also began to recede.
  6. When a physician named William Coley
    tracked the patient down 7 years later,
  7. no visible signs of the cancer remained.
  8. Coley believed something remarkable
    was happening:
  9. that the bacterial infection
    had stimulated the patient’s immune system
  10. to fight off the cancer.
  11. Coley’s fortunate discovery
    led him to pioneer

  12. the intentional injection of bacteria
    to successfully treat cancer.
  13. Over a century later, synthetic biologists
    have found an even better way
  14. to use these once unlikely allies—
  15. by programming them to safely
    deliver drugs directly to tumors.
  16. Cancer occurs when normal functions
    of cells are altered,

  17. causing them to rapidly multiply
    and form growths called tumors.
  18. Treatments like radiation, chemotherapy,
    and immunotherapy
  19. attempt to kill malignant cells,
    but can affect the entire body
  20. and disrupt healthy tissues
    in the process.
  21. However, some bacteria like E. coli

  22. have the unique advantage of being able
    to selectively grow inside tumors.
  23. In fact, the core of a tumor forms
    an ideal environment
  24. where they can safely multiply,
    hidden from immune cells.
  25. Instead of causing infection,
  26. bacteria can be reprogrammed
    to carry cancer-fighting drugs,
  27. acting as Trojan Horses
    that target the tumor from within.
  28. This idea of programming bacteria
    to sense and respond in novel ways
  29. is a major focus of a field called
    Synthetic Biology.
  30. But how can bacteria be programmed?

  31. The key lies in manipulating their DNA.
  32. By inserting particular genetic sequences
    into bacteria,
  33. they can be instructed
    to synthesize different molecules,
  34. including those
    that disrupt cancer growth.
  35. They can also be made
    to behave in very specific ways
  36. with the help of biological circuits.
  37. These program different behaviors
    depending on the presence, absence,
  38. or combination of certain factors.
  39. For example, tumors have low oxygen
    and pH levels
  40. and over-produce specific molecules.
  41. Synthetic biologists can program bacteria
    to sense those conditions,
  42. and by doing so, respond to tumors
    while avoiding healthy tissue.
  43. One type of biological circuit,

  44. known as a synchronized lysis circuit,
    or SLC,
  45. allows bacteria
    to not only deliver medicine,
  46. but to do so on a set schedule.
  47. First, to avoid harming healthy tissue,
  48. production of anti-cancer drugs
    begins as bacteria grow,
  49. which only happens
    within the tumor itself.
  50. Next, after they’ve produced the drugs,
  51. a kill-switch causes
    the bacteria to burst
  52. when they reach a critical population
    threshold.
  53. This both releases the medicine
    and decreases the bacteria’s population.
  54. However, a certain percentage
    of the bacteria remain alive
  55. to replenish the colony.
  56. Eventually their numbers grow large enough
    to trigger the kill switch again,
  57. and the cycle continues.
  58. This circuit can be fine-tuned
    to deliver drugs
  59. on whatever periodic schedule
    is best to fight the cancer.
  60. This approach has proven promising
    in scientific trials using mice.

  61. Not only were scientists able
    to successfully eliminate lymphoma tumors
  62. injected with bacteria,
  63. but the injection also stimulated
    the immune system,
  64. priming immune cells
    to identify and attack untreated lymphomas
  65. elsewhere in the mouse.
  66. Unlike many other therapies,

  67. bacteria don’t target a specific type
    of cancer,
  68. but rather the general characteristics
    shared by all solid tumors.
  69. Nor are programmable bacteria
    limited to simply fighting cancer.
  70. Instead, they can serve
    as sophisticated sensors
  71. that monitor sites of future disease.
  72. Safe probiotic bacteria could perhaps
    lie dormant within our guts,
  73. where they’d detect, prevent,
    and treat disorders
  74. before they have the chance
    to cause symptoms.
  75. Advances in technology
    have created excitement around a future

  76. of personalized medicine
    driven by mechanical nanobots.
  77. But thanks to billions of years
    of evolution
  78. we may already have a starting point
  79. in the unexpectedly biological
    form of bacteria.
  80. Add synthetic biology to the mix,
  81. and who knows what might soon be possible.