0:00:00.873,0:00:02.295 Take a moment 0:00:02.319,0:00:03.835 and think about a virus. 0:00:04.913,0:00:06.706 What comes to your mind? 0:00:06.730,0:00:07.983 An illness? 0:00:08.007,0:00:09.333 A fear? 0:00:09.357,0:00:11.363 Probably something really unpleasant. 0:00:11.387,0:00:13.934 And yet, viruses are not all the same. 0:00:13.958,0:00:17.489 It's true, some of them cause[br]devastating disease. 0:00:17.513,0:00:21.600 But others can do the exact opposite --[br]they can cure disease. 0:00:21.624,0:00:23.656 These viruses are called "phages." 0:00:24.125,0:00:27.434 Now, the first time I heard[br]about phages was back in 2013. 0:00:27.458,0:00:29.609 My father-in-law, who's a surgeon, 0:00:29.633,0:00:32.053 was telling me about a woman[br]he was treating. 0:00:32.077,0:00:35.196 The woman had a knee injury,[br]required multiple surgeries, 0:00:35.220,0:00:36.673 and over the course of these, 0:00:36.697,0:00:39.569 developed a chronic[br]bacterial infection in her leg. 0:00:39.593,0:00:40.853 Unfortunately for her, 0:00:40.877,0:00:43.910 the bacteria causing the infection[br]also did not respond 0:00:43.934,0:00:46.401 to any antibiotic that was available. 0:00:46.807,0:00:50.196 So at this point, typically, the only[br]option left is to amputate the leg 0:00:50.220,0:00:52.632 to stop the infection[br]from spreading further. 0:00:53.268,0:00:56.799 Now, my father-in-law was desperate[br]for a different kind of solution, 0:00:56.823,0:01:01.325 and he applied for an experimental,[br]last-resort treatment using phages. 0:01:01.727,0:01:03.593 And guess what? It worked. 0:01:03.617,0:01:07.783 Within three weeks of applying the phages,[br]the chronic infection had healed up, 0:01:07.807,0:01:10.474 where before, no antibiotic was working. 0:01:10.998,0:01:14.913 I was fascinated by this weird conception: 0:01:15.522,0:01:17.743 viruses curing an infection. 0:01:18.617,0:01:22.093 To this day, I am fascinated[br]by the medical potential of phages. 0:01:22.117,0:01:25.785 And I actually quit my job last year[br]to build a company in this space. 0:01:26.760,0:01:28.160 Now, what is a phage? 0:01:29.465,0:01:33.171 The image that you see here was taken[br]by an electron microscope. 0:01:33.195,0:01:36.929 And that means what we see on the screen[br]is in reality extremely tiny. 0:01:37.250,0:01:41.017 The grainy thing in the middle[br]with the head, the long body 0:01:41.041,0:01:42.490 and a number of feet -- 0:01:42.514,0:01:45.204 this is the image of a prototypical phage. 0:01:45.228,0:01:46.450 It's kind of cute. 0:01:46.474,0:01:48.029 (Laughter) 0:01:48.958,0:01:50.958 Now, take a look at your hand. 0:01:51.829,0:01:56.075 In our team, we've estimated[br]that you have more than 10 billion phages 0:01:56.099,0:01:57.566 on each of your hands. 0:01:57.940,0:01:59.678 What are they doing there? 0:01:59.702,0:02:00.950 (Laughter) 0:02:00.974,0:02:03.768 Well, viruses are good at infecting cells. 0:02:03.792,0:02:06.006 And phages are great[br]at infecting bacteria. 0:02:06.030,0:02:08.458 And your hand, just like[br]so much of our body, 0:02:08.482,0:02:10.918 is a hotbed of bacterial activity, 0:02:10.942,0:02:14.180 making it an ideal[br]hunting ground for phages. 0:02:14.204,0:02:17.053 Because after all, phages hunt bacteria. 0:02:17.910,0:02:21.486 It's also important to know that phages[br]are extremely selective hunters. 0:02:22.014,0:02:25.947 Typically, a phage will only infect[br]a single bacterial species. 0:02:26.648,0:02:29.640 So in this rendering here,[br]the phage that you see 0:02:29.664,0:02:32.830 hunts for a bacterium[br]called Staphylococcus aureus, 0:02:32.854,0:02:36.109 which is known as MRSA[br]in its drug-resistant form. 0:02:36.133,0:02:38.266 It causes skin or wound infections. 0:02:39.069,0:02:41.828 The way the phage hunts is with its feet. 0:02:42.364,0:02:44.862 The feet are actually extremely[br]sensitive receptors, 0:02:44.886,0:02:47.761 on the lookout for the right surface[br]on a bacterial cell. 0:02:48.158,0:02:49.410 Once it finds it, 0:02:49.434,0:02:52.363 the phage will latch on[br]to the bacterial cell wall 0:02:52.387,0:02:53.987 and then inject its DNA. 0:02:54.371,0:02:56.037 DNA sits in the head of the phage 0:02:56.061,0:02:58.850 and travels into the bacteria[br]through the long body. 0:02:59.307,0:03:01.998 At this point, the phage[br]reprograms the bacteria 0:03:02.022,0:03:04.395 into producing lots of new phages. 0:03:04.419,0:03:07.351 The bacteria, in effect,[br]becomes a phage factory. 0:03:07.704,0:03:11.664 Once around 50-100 phages have accumulated[br]within the bacteria cell, 0:03:11.688,0:03:14.077 the phages are then able[br]to release a protein 0:03:14.101,0:03:16.177 that disrupts the bacteria cell wall. 0:03:16.514,0:03:19.680 As the bacteria bursts,[br]the phages move out 0:03:19.704,0:03:22.459 and go on the hunt again[br]for a new bacteria to infect. 0:03:23.371,0:03:26.466 Now, I'm sorry, this probably[br]sounded like a scary virus again. 0:03:27.220,0:03:29.863 But it's exactly this ability of phages -- 0:03:29.887,0:03:32.578 to multiply within the bacteria[br]and then kill them -- 0:03:32.602,0:03:35.739 that make them so interesting[br]from a medical point of view. 0:03:35.763,0:03:38.040 The other part that I find[br]extremely interesting 0:03:38.064,0:03:40.318 is the scale at which this is going on. 0:03:40.342,0:03:43.826 Now, just five years ago,[br]I really had no clue about phages. 0:03:43.850,0:03:47.314 And yet, today I would tell you[br]they are part of a natural principle. 0:03:47.694,0:03:51.702 Phages and bacteria go back[br]to the earliest days of evolution. 0:03:51.726,0:03:55.227 They have always existed in tandem,[br]keeping each other in check. 0:03:55.765,0:03:59.637 So this is really the story of yin[br]and yang, of the hunter and the prey, 0:03:59.661,0:04:01.245 at a microscopic level. 0:04:02.005,0:04:04.236 Some scientists have even estimated 0:04:04.260,0:04:07.990 that phages are the most[br]abundant organism on our planet. 0:04:08.863,0:04:11.934 So even before we continue[br]talking about their medical potential, 0:04:11.958,0:04:15.122 I think everybody should know[br]about phages and their role on earth: 0:04:15.146,0:04:17.546 they hunt, infect and kill bacteria. 0:04:18.550,0:04:21.511 Now, how come we have something[br]that works so well in nature, 0:04:21.535,0:04:23.926 every day, everywhere around us, 0:04:23.950,0:04:25.704 and yet, in most parts of the world, 0:04:25.728,0:04:27.744 we do not have a single drug on the market 0:04:27.768,0:04:30.776 that uses this principle[br]to combat bacterial infections? 0:04:31.458,0:04:35.276 The simple answer is: no one[br]has developed this kind of a drug yet, 0:04:35.300,0:04:38.459 at least not one that conforms[br]to the Western regulatory standards 0:04:38.483,0:04:40.684 that set the norm[br]for so much of the world. 0:04:41.251,0:04:44.089 To understand why,[br]we need to move back in time. 0:04:45.298,0:04:47.496 This is a picture of FĂ©lix d'Herelle. 0:04:47.520,0:04:50.966 He is one of the two scientists[br]credited with discovering phages. 0:04:50.990,0:04:54.746 Except, when he discovered them[br]back in 1917, he had no clue 0:04:54.770,0:04:56.243 what he had discovered. 0:04:56.720,0:05:00.008 He was interested in a disease[br]called bacillary dysentery, 0:05:00.032,0:05:02.905 which is a bacterial infection[br]that causes severe diarrhea, 0:05:02.929,0:05:05.373 and back then, was actually[br]killing a lot of people, 0:05:05.397,0:05:09.141 because after all, no cure for bacterial[br]infections had been invented. 0:05:09.165,0:05:13.075 He was looking at samples from patients[br]who had survived this illness. 0:05:13.099,0:05:15.332 And he found that something[br]weird was going on. 0:05:15.356,0:05:17.712 Something in the sample[br]was killing the bacteria 0:05:17.736,0:05:19.926 that were supposed to cause the disease. 0:05:19.950,0:05:22.990 To find out what was going on,[br]he did an ingenious experiment. 0:05:23.395,0:05:25.515 He took the sample, filtered it 0:05:25.539,0:05:28.794 until he was sure that only something[br]very small could have remained, 0:05:28.818,0:05:33.063 and then took a tiny drop and added it[br]to freshly cultivated bacteria. 0:05:33.087,0:05:35.263 And he observed[br]that within a number of hours, 0:05:35.287,0:05:37.252 the bacteria had been killed. 0:05:37.276,0:05:41.053 He then repeated this,[br]again filtering, taking a tiny drop, 0:05:41.077,0:05:43.651 adding it to the next batch[br]of fresh bacteria. 0:05:43.675,0:05:46.182 He did this in sequence 50 times, 0:05:46.206,0:05:48.071 always observing the same effect. 0:05:48.095,0:05:50.817 And at this point,[br]he made two conclusions. 0:05:50.841,0:05:54.278 First of all, the obvious one:[br]yes, something was killing the bacteria, 0:05:54.302,0:05:55.798 and it was in that liquid. 0:05:55.822,0:05:58.607 The other one: it had to be[br]biologic in nature, 0:05:58.631,0:06:02.306 because a tiny drop was sufficient[br]to have a huge impact. 0:06:02.853,0:06:06.077 He called the agent he had found[br]an "invisible microbe" 0:06:06.101,0:06:07.906 and gave it the name "bacteriophage," 0:06:07.930,0:06:10.363 which, literally translated,[br]means "bacteria eater." 0:06:10.800,0:06:13.792 And by the way, this is one[br]of the most fundamental discoveries 0:06:13.816,0:06:15.125 of modern microbiology. 0:06:15.149,0:06:19.363 So many modern techniques go back[br]to our understanding of how phages work -- 0:06:19.387,0:06:21.681 in genomic editing,[br]but also in other fields. 0:06:21.705,0:06:24.664 And just today, the Nobel Prize[br]in chemistry was announced 0:06:24.688,0:06:28.569 for two scientists who work with phages[br]and develop drugs based on that. 0:06:29.631,0:06:31.758 Now, back in the 1920s and 1930s, 0:06:31.782,0:06:34.695 people also immediately saw[br]the medical potential of phages. 0:06:34.719,0:06:36.378 After all, albeit invisible, 0:06:36.402,0:06:38.925 you had something[br]that reliably was killing bacteria. 0:06:39.489,0:06:42.950 Companies that still exist today,[br]such as Abbott, Squibb or Lilly, 0:06:42.974,0:06:44.574 sold phage preparations. 0:06:45.204,0:06:48.260 But the reality is, if you're starting[br]with an invisible microbe, 0:06:48.284,0:06:50.691 it's very difficult to get[br]to a reliable drug. 0:06:51.117,0:06:53.109 Just imagine going to the FDA today 0:06:53.133,0:06:55.439 and telling them all about[br]that invisible virus 0:06:55.463,0:06:57.056 you want to give to patients. 0:06:57.752,0:07:00.672 So when chemical antibiotics[br]emerged in the 1940s, 0:07:00.696,0:07:02.787 they completely changed the game. 0:07:02.811,0:07:04.819 And this guy played a major role. 0:07:04.843,0:07:06.137 This is Alexander Fleming. 0:07:06.161,0:07:07.970 He won the Nobel Prize in medicine 0:07:07.994,0:07:10.129 for his work contributing[br]to the development 0:07:10.153,0:07:12.120 of the first antibiotic, penicillin. 0:07:12.871,0:07:16.998 And antibiotics really work[br]very differently than phages. 0:07:17.022,0:07:19.799 For the most part, they inhibit[br]the growth of the bacteria, 0:07:19.823,0:07:22.895 and they don't care so much[br]which kind of bacteria are present. 0:07:23.196,0:07:25.126 The ones that we call broad-spectrum 0:07:25.150,0:07:28.742 will even work against[br]a whole bunch of bacteria out there. 0:07:28.766,0:07:31.260 Compare that to phages,[br]which work extremely narrowly 0:07:31.284,0:07:32.727 against one bacterial species, 0:07:32.751,0:07:34.806 and you can see the obvious advantage. 0:07:35.575,0:07:38.426 Now, back then, this must have felt[br]like a dream come true. 0:07:38.450,0:07:41.649 You had a patient[br]with a suspected bacterial infection, 0:07:41.673,0:07:43.268 you gave him the antibiotic, 0:07:43.292,0:07:46.451 and without really needing to know[br]anything else about the bacteria 0:07:46.475,0:07:47.649 causing the disease, 0:07:47.673,0:07:49.188 many of the patients recovered. 0:07:49.212,0:07:51.569 And so as we developed[br]more and more antibiotics, 0:07:51.593,0:07:55.278 they, rightly so, became the first-line[br]therapy for bacterial infections. 0:07:55.831,0:08:00.069 And by the way, they have contributed[br]tremendously to our life expectancy. 0:08:00.093,0:08:02.799 We are only able to do[br]complex medical interventions 0:08:02.823,0:08:04.466 and medical surgeries today 0:08:04.490,0:08:05.863 because we have antibiotics, 0:08:05.887,0:08:08.393 and we don't risk the patient[br]dying the very next day 0:08:08.417,0:08:12.264 from the bacterial infection that he might[br]contract during the operation. 0:08:12.288,0:08:16.178 So we started to forget about phages,[br]especially in Western medicine. 0:08:16.638,0:08:20.372 And to a certain extent, even when[br]I was growing up, the notion was: 0:08:20.396,0:08:24.228 we have solved bacterial infections;[br]we have antibiotics. 0:08:25.185,0:08:27.908 Of course, today,[br]we know that this is wrong. 0:08:28.553,0:08:30.950 Today, most of you[br]will have heard about superbugs. 0:08:30.974,0:08:33.111 Those are bacteria[br]that have become resistant 0:08:33.135,0:08:37.649 to many, if not all, of the antibiotics[br]that we have developed 0:08:37.673,0:08:39.273 to treat this infection. 0:08:39.760,0:08:41.094 How did we get here? 0:08:41.118,0:08:44.092 Well, we weren't as smart[br]as we thought we were. 0:08:44.578,0:08:47.521 As we started using[br]antibiotics everywhere -- 0:08:47.545,0:08:50.934 in hospitals, to treat and prevent;[br]at home, for simple colds; 0:08:50.958,0:08:53.220 on farms, to keep animals healthy -- 0:08:53.244,0:08:54.644 the bacteria evolved. 0:08:55.509,0:08:59.358 In the onslaught of antibiotics[br]that were all around them, 0:08:59.382,0:09:02.401 those bacteria survived[br]that were best able to adapt. 0:09:03.017,0:09:05.867 Today, we call these[br]"multidrug-resistant bacteria." 0:09:06.283,0:09:08.418 And let me put a scary number out there. 0:09:08.442,0:09:10.895 In a recent study commissioned[br]by the UK government, 0:09:10.919,0:09:13.315 it was estimated that by 2050, 0:09:13.339,0:09:17.457 ten million people could die every year[br]from multidrug-resistant infections. 0:09:17.871,0:09:21.014 Compare that to eight million deaths[br]from cancer per year today, 0:09:21.038,0:09:23.192 and you can see[br]that this is a scary number. 0:09:23.792,0:09:26.587 But the good news is,[br]phages have stuck around. 0:09:27.014,0:09:30.220 And let me tell you, they are not[br]impressed by multidrug resistance. 0:09:30.244,0:09:31.395 (Laughter) 0:09:31.419,0:09:37.172 They are just as happily killing[br]and hunting bacteria all around us. 0:09:38.028,0:09:41.329 And they've also stayed selective,[br]which today is really a good thing. 0:09:41.353,0:09:44.837 Today, we are able to reliably identify[br]a bacterial pathogen 0:09:44.861,0:09:47.355 that's causing an infection[br]in many settings. 0:09:47.379,0:09:50.477 And their selectivity will help us[br]avoid some of the side effects 0:09:50.501,0:09:54.045 that are commonly associated[br]with broad-spectrum antibiotics. 0:09:54.609,0:09:58.442 But maybe the best news of all is:[br]they are no longer an invisible microbe. 0:09:58.466,0:09:59.791 We can look at them. 0:09:59.815,0:10:01.260 And we did so together before. 0:10:01.284,0:10:03.132 We can sequence their DNA. 0:10:03.156,0:10:04.752 We understand how they replicate. 0:10:04.776,0:10:06.664 And we understand the limitations. 0:10:06.688,0:10:08.055 We are in a great place 0:10:08.079,0:10:12.093 to now develop strong and reliable[br]phage-based pharmaceuticals. 0:10:12.117,0:10:14.299 And that's what's happening[br]around the globe. 0:10:14.323,0:10:17.078 More than 10 biotech companies,[br]including our own company, 0:10:17.102,0:10:20.687 are developing human-phage applications[br]to treat bacterial infections. 0:10:20.711,0:10:24.918 A number of clinical trials[br]are getting underway in Europe and the US. 0:10:25.751,0:10:28.061 So I'm convinced[br]that we're standing on the verge 0:10:28.085,0:10:30.045 of a renaissance of phage therapy. 0:10:30.069,0:10:34.297 And to me, the correct way to depict[br]the phage is something like this. 0:10:34.855,0:10:37.347 (Laughter) 0:10:37.371,0:10:40.847 To me, phages are the superheroes[br]that we have been waiting for 0:10:40.871,0:10:43.960 in our fight against[br]multidrug-resistant infections. 0:10:44.617,0:10:47.125 So the next time you think about a virus, 0:10:47.149,0:10:48.749 keep this image in mind. 0:10:49.236,0:10:52.220 After all, a phage might[br]one day save your life. 0:10:52.810,0:10:54.000 Thank you. 0:10:54.024,0:10:59.992 (Applause)