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← How a long-forgotten virus could help us solve the antibiotics crisis

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Showing Revision 7 created 11/16/2018 by Oliver Friedman.

  1. Take a moment
  2. and think about a virus.
  3. What comes to your mind?
  4. An illness?
  5. A fear?
  6. Probably something really unpleasant.
  7. And yet, viruses are not all the same.
  8. It's true, some of them cause
    devastating disease.
  9. But others can do the exact opposite --
    they can cure disease.
  10. These viruses are called "phages."
  11. Now, the first time I heard
    about phages was back in 2013.

  12. My father-in-law, who's a surgeon,
  13. was telling me about a woman
    he was treating.
  14. The woman had a knee injury,
    required multiple surgeries,
  15. and over the course of these,
  16. developed a chronic
    bacterial infection in her leg.
  17. Unfortunately for her,
  18. the bacteria causing the infection
    also did not respond
  19. to any antibiotic that was available.
  20. So at this point, typically, the only
    option left is to amputate the leg
  21. to stop the infection
    from spreading further.
  22. Now, my father-in-law was desperate
    for a different kind of solution,
  23. and he applied for an experimental,
    last-resort treatment using phages.
  24. And guess what? It worked.
  25. Within three weeks of applying the phages,
    the chronic infection had healed up,
  26. where before, no antibiotic was working.
  27. I was fascinated by this weird conception:
  28. viruses curing an infection.
  29. To this day, I am fascinated
    by the medical potential of phages.
  30. And I actually quit my job last year
    to build a company in this space.
  31. Now, what is a phage?

  32. The image that you see here was taken
    by an electron microscope.
  33. And that means what we see on the screen
    is in reality extremely tiny.
  34. The grainy thing in the middle
    with the head, the long body
  35. and a number of feet --
  36. this is the image of a prototypical phage.
  37. It's kind of cute.
  38. (Laughter)

  39. Now, take a look at your hand.

  40. In our team, we've estimated
    that you have more than 10 billion phages
  41. on each of your hands.
  42. What are they doing there?
  43. (Laughter)

  44. Well, viruses are good at infecting cells.

  45. And phages are great
    at infecting bacteria.
  46. And your hand, just like
    so much of our body,
  47. is a hotbed of bacterial activity,
  48. making it an ideal
    hunting ground for phages.
  49. Because after all, phages hunt bacteria.
  50. It's also important to know that phages
    are extremely selective hunters.
  51. Typically, a phage will only infect
    a single bacterial species.
  52. So in this rendering here,
    the phage that you see
  53. hunts for a bacterium
    called Staphylococcus aureus,
  54. which is known as MRSA
    in its drug-resistant form.
  55. It causes skin or wound infections.
  56. The way the phage hunts is with its feet.

  57. The feet are actually extremely
    sensitive receptors,
  58. on the lookout for the right surface
    on a bacterial cell.
  59. Once it finds it,
  60. the phage will latch on
    to the bacterial cell wall
  61. and then inject its DNA.
  62. DNA sits in the head of the phage
  63. and travels into the bacteria
    through the long body.
  64. At this point, the phage
    reprograms the bacteria
  65. into producing lots of new phages.
  66. The bacteria, in effect,
    becomes a phage factory.
  67. Once around 50-100 phages have accumulated
    within the bacteria cell,
  68. the phages are then able
    to release a protein
  69. that disrupts the bacteria cell wall.
  70. As the bacteria bursts,
    the phages move out
  71. and go on the hunt again
    for a new bacteria to infect.
  72. Now, I'm sorry, this probably
    sounded like a scary virus again.

  73. But it's exactly this ability of phages --
  74. to multiply within the bacteria
    and then kill them --
  75. that make them so interesting
    from a medical point of view.
  76. The other part that I find
    extremely interesting
  77. is the scale at which this is going on.
  78. Now, just five years ago,
    I really had no clue about phages.
  79. And yet, today I would tell you
    they are part of a natural principle.
  80. Phages and bacteria go back
    to the earliest days of evolution.
  81. They have always existed in tandem,
    keeping each other in check.
  82. So this is really the story of yin
    and yang, of the hunter and the prey,
  83. at a microscopic level.
  84. Some scientists have even estimated
  85. that phages are the most
    abundant organism on our planet.
  86. So even before we continue
    talking about their medical potential,
  87. I think everybody should know
    about phages and their role on earth:
  88. they hunt, infect and kill bacteria.
  89. Now, how come we have something
    that works so well in nature,

  90. every day, everywhere around us,
  91. and yet, in most parts of the world,
  92. we do not have a single drug on the market
  93. that uses this principle
    to combat bacterial infections?
  94. The simple answer is: no one
    has developed this kind of a drug yet,
  95. at least not one that conforms
    to the Western regulatory standards
  96. that set the norm
    for so much of the world.
  97. To understand why,
    we need to move back in time.
  98. This is a picture of Félix d'Herelle.

  99. He is one of the two scientists
    credited with discovering phages.
  100. Except, when he discovered them
    back in 1917, he had no clue
  101. what he had discovered.
  102. He was interested in a disease
    called bacillary dysentery,
  103. which is a bacterial infection
    that causes severe diarrhea,
  104. and back then, was actually
    killing a lot of people,
  105. because after all, no cure for bacterial
    infections had been invented.
  106. He was looking at samples from patients
    who had survived this illness.
  107. And he found that something
    weird was going on.
  108. Something in the sample
    was killing the bacteria
  109. that were supposed to cause the disease.
  110. To find out what was going on,
    he did an ingenious experiment.

  111. He took the sample, filtered it
  112. until he was sure that only something
    very small could have remained,
  113. and then took a tiny drop and added it
    to freshly cultivated bacteria.
  114. And he observed
    that within a number of hours,
  115. the bacteria had been killed.
  116. He then repeated this,
    again filtering, taking a tiny drop,
  117. adding it to the next batch
    of fresh bacteria.
  118. He did this in sequence 50 times,
  119. always observing the same effect.
  120. And at this point,
    he made two conclusions.
  121. First of all, the obvious one:
    yes, something was killing the bacteria,
  122. and it was in that liquid.
  123. The other one: it had to be
    biologic in nature,
  124. because a tiny drop was sufficient
    to have a huge impact.
  125. He called the agent he had found
    an "invisible microbe"
  126. and gave it the name "bacteriophage,"
  127. which, literally translated,
    means "bacteria eater."
  128. And by the way, this is one
    of the most fundamental discoveries
  129. of modern microbiology.
  130. So many modern techniques go back
    to our understanding of how phages work --
  131. in genomic editing,
    but also in other fields.
  132. And just today, the Nobel Prize
    in chemistry was announced
  133. for two scientists who work with phages
    and develop drugs based on that.
  134. Now, back in the 1920s and 1930s,

  135. people also immediately saw
    the medical potential of phages.
  136. After all, albeit invisible,
  137. you had something
    that reliably was killing bacteria.
  138. Companies that still exist today,
    such as Abbott, Squibb or Lilly,
  139. sold phage preparations.
  140. But the reality is, if you're starting
    with an invisible microbe,
  141. it's very difficult to get
    to a reliable drug.
  142. Just imagine going to the FDA today
  143. and telling them all about
    that invisible virus
  144. you want to give to patients.
  145. So when chemical antibiotics
    emerged in the 1940s,
  146. they completely changed the game.
  147. And this guy played a major role.
  148. This is Alexander Fleming.

  149. He won the Nobel Prize in medicine
  150. for his work contributing
    to the development
  151. of the first antibiotic, penicillin.
  152. And antibiotics really work
    very differently than phages.
  153. For the most part, they inhibit
    the growth of the bacteria,
  154. and they don't care so much
    which kind of bacteria are present.
  155. The ones that we call broad-spectrum
  156. will even work against
    a whole bunch of bacteria out there.
  157. Compare that to phages,
    which work extremely narrowly
  158. against one bacterial species,
  159. and you can see the obvious advantage.
  160. Now, back then, this must have felt
    like a dream come true.

  161. You had a patient
    with a suspected bacterial infection,
  162. you gave him the antibiotic,
  163. and without really needing to know
    anything else about the bacteria
  164. causing the disease,
  165. many of the patients recovered.
  166. And so as we developed
    more and more antibiotics,
  167. they, rightly so, became the first-line
    therapy for bacterial infections.
  168. And by the way, they have contributed
    tremendously to our life expectancy.
  169. We are only able to do
    complex medical interventions
  170. and medical surgeries today
  171. because we have antibiotics,
  172. and we don't risk the patient
    dying the very next day
  173. from the bacterial infection that he might
    contract during the operation.
  174. So we started to forget about phages,
    especially in Western medicine.

  175. And to a certain extent, even when
    I was growing up, the notion was:
  176. we have solved bacterial infections;
    we have antibiotics.
  177. Of course, today,
    we know that this is wrong.
  178. Today, most of you
    will have heard about superbugs.
  179. Those are bacteria
    that have become resistant
  180. to many, if not all, of the antibiotics
    that we have developed
  181. to treat this infection.
  182. How did we get here?

  183. Well, we weren't as smart
    as we thought we were.
  184. As we started using
    antibiotics everywhere --
  185. in hospitals, to treat and prevent;
    at home, for simple colds;
  186. on farms, to keep animals healthy --
  187. the bacteria evolved.
  188. In the onslaught of antibiotics
    that were all around them,
  189. those bacteria survived
    that were best able to adapt.
  190. Today, we call these
    "multidrug-resistant bacteria."
  191. And let me put a scary number out there.
  192. In a recent study commissioned
    by the UK government,
  193. it was estimated that by 2050,
  194. ten million people could die every year
    from multidrug-resistant infections.
  195. Compare that to eight million deaths
    from cancer per year today,
  196. and you can see
    that this is a scary number.
  197. But the good news is,
    phages have stuck around.

  198. And let me tell you, they are not
    impressed by multidrug resistance.
  199. (Laughter)

  200. They are just as happily killing
    and hunting bacteria all around us.

  201. And they've also stayed selective,
    which today is really a good thing.
  202. Today, we are able to reliably identify
    a bacterial pathogen
  203. that's causing an infection
    in many settings.
  204. And their selectivity will help us
    avoid some of the side effects
  205. that are commonly associated
    with broad-spectrum antibiotics.
  206. But maybe the best news of all is:
    they are no longer an invisible microbe.
  207. We can look at them.
  208. And we did so together before.
  209. We can sequence their DNA.
  210. We understand how they replicate.
  211. And we understand the limitations.
  212. We are in a great place
  213. to now develop strong and reliable
    phage-based pharmaceuticals.
  214. And that's what's happening
    around the globe.

  215. More than 10 biotech companies,
    including our own company,
  216. are developing human-phage applications
    to treat bacterial infections.
  217. A number of clinical trials
    are getting underway in Europe and the US.
  218. So I'm convinced
    that we're standing on the verge
  219. of a renaissance of phage therapy.
  220. And to me, the correct way to depict
    the phage is something like this.
  221. (Laughter)

  222. To me, phages are the superheroes
    that we have been waiting for

  223. in our fight against
    multidrug-resistant infections.
  224. So the next time you think about a virus,

  225. keep this image in mind.
  226. After all, a phage might
    one day save your life.
  227. Thank you.

  228. (Applause)