1 00:00:00,760 --> 00:00:04,936 I want to talk to you about the future of medicine. 2 00:00:04,960 --> 00:00:09,056 But before I do that, I want to talk a little bit about the past. 3 00:00:09,080 --> 00:00:12,696 Now, throughout much of the recent history of medicine, 4 00:00:12,720 --> 00:00:16,536 we've thought about illness and treatment 5 00:00:16,560 --> 00:00:19,936 in terms of a profoundly simple model. 6 00:00:19,960 --> 00:00:22,656 In fact, the model is so simple 7 00:00:22,680 --> 00:00:25,736 that you could summarize it in six words: 8 00:00:25,760 --> 00:00:29,840 have disease, take pill, kill something. 9 00:00:31,080 --> 00:00:35,816 Now, the reason for the dominance of this model 10 00:00:35,840 --> 00:00:38,456 is of course the antibiotic revolution. 11 00:00:38,480 --> 00:00:41,656 Many of you might not know this, but we happen to be celebrating 12 00:00:41,680 --> 00:00:45,736 the hundredth year of the introduction of antibiotics into the United States. 13 00:00:45,760 --> 00:00:47,376 But what you do know 14 00:00:47,400 --> 00:00:51,640 is that that introduction was nothing short of transformative. 15 00:00:52,880 --> 00:00:56,736 Here you had a chemical, either from the natural world 16 00:00:56,760 --> 00:00:59,496 or artificially synthesized in the laboratory, 17 00:00:59,520 --> 00:01:02,776 and it would course through your body, 18 00:01:02,800 --> 00:01:05,576 it would find its target, 19 00:01:05,600 --> 00:01:07,256 lock into its target -- 20 00:01:07,280 --> 00:01:09,496 a microbe or some part of a microbe -- 21 00:01:09,520 --> 00:01:12,960 and then turn off a lock and a key 22 00:01:13,960 --> 00:01:17,496 with exquisite deftness, exquisite specificity. 23 00:01:17,520 --> 00:01:21,816 And you would end up taking a previously fatal, lethal disease -- 24 00:01:21,840 --> 00:01:24,976 a pneumonia, syphilis, tuberculosis -- 25 00:01:25,000 --> 00:01:29,040 and transforming that into a curable, or treatable illness. 26 00:01:30,080 --> 00:01:31,560 You have a pneumonia, 27 00:01:32,480 --> 00:01:33,856 you take penicillin, 28 00:01:33,880 --> 00:01:35,416 you kill the microbe 29 00:01:35,440 --> 00:01:37,576 and you cure the disease. 30 00:01:37,600 --> 00:01:40,536 So seductive was this idea, 31 00:01:40,560 --> 00:01:44,736 so potent the metaphor of lock and key 32 00:01:44,760 --> 00:01:46,296 and killing something, 33 00:01:46,320 --> 00:01:48,336 that it really swept through biology. 34 00:01:48,360 --> 00:01:50,480 It was a transformation like no other. 35 00:01:52,160 --> 00:01:55,336 And we've really spent the last 100 years 36 00:01:55,360 --> 00:01:58,816 trying to replicate that model over and over again 37 00:01:58,840 --> 00:02:00,079 in noninfectious diseases, 38 00:02:00,103 --> 00:02:04,223 in chronic diseases like diabetes and hypertension and heart disease. 39 00:02:05,120 --> 00:02:08,759 And it's worked, but it's only worked partly. 40 00:02:09,120 --> 00:02:10,776 Let me show you. 41 00:02:10,800 --> 00:02:13,696 You know, if you take the entire universe 42 00:02:13,720 --> 00:02:17,216 of all chemical reactions in the human body, 43 00:02:17,240 --> 00:02:20,536 every chemical reaction that your body is capable of, 44 00:02:20,560 --> 00:02:23,576 most people think that that number is on the order of a million. 45 00:02:23,600 --> 00:02:24,896 Let's call it a million. 46 00:02:24,920 --> 00:02:26,616 And now you ask the question, 47 00:02:26,640 --> 00:02:29,296 what number or fraction of reactions 48 00:02:29,320 --> 00:02:31,136 can actually be targeted 49 00:02:31,160 --> 00:02:35,976 by the entire pharmacopoeia, all of medicinal chemistry? 50 00:02:36,000 --> 00:02:38,040 That number is 250. 51 00:02:39,680 --> 00:02:42,216 The rest is chemical darkness. 52 00:02:42,240 --> 00:02:48,416 In other words, 0.025 percent of all chemical reactions in your body 53 00:02:48,440 --> 00:02:52,560 are actually targetable by this lock and key mechanism. 54 00:02:53,680 --> 00:02:56,736 You know, if you think about human physiology 55 00:02:56,760 --> 00:03:00,216 as a vast global telephone network 56 00:03:00,240 --> 00:03:04,120 with interacting nodes and interacting pieces, 57 00:03:04,600 --> 00:03:07,776 then all of our medicinal chemistry 58 00:03:07,800 --> 00:03:10,056 is operating on one tiny corner 59 00:03:10,080 --> 00:03:12,776 at the edge, the outer edge, of that network. 60 00:03:12,800 --> 00:03:16,616 It's like all of our pharmaceutical chemistry 61 00:03:16,640 --> 00:03:20,416 is a pole operator in Wichita, Kansas 62 00:03:20,440 --> 00:03:23,400 who is tinkering with about 10 or 15 telephone lines. 63 00:03:24,880 --> 00:03:27,040 So what do we do about this idea? 64 00:03:28,160 --> 00:03:30,520 What if we reorganized this approach? 65 00:03:32,080 --> 00:03:35,456 In fact, it turns out that the natural world 66 00:03:35,480 --> 00:03:40,536 gives us a sense of how one might think about illness 67 00:03:40,560 --> 00:03:42,216 in a radically different way, 68 00:03:42,240 --> 00:03:45,960 rather than disease, medicine, target. 69 00:03:47,080 --> 00:03:50,456 In fact, the natural world is organized hierarchically upwards, 70 00:03:50,480 --> 00:03:52,336 not downwards, but upwards, 71 00:03:52,360 --> 00:03:58,600 and we begin with a self-regulating, semi-autonomous unit called a cell. 72 00:03:59,640 --> 00:04:02,856 These self-regulating, semi-autonomous units 73 00:04:02,880 --> 00:04:07,696 give rise to self-regulating, semi-autonomous units called organs, 74 00:04:07,720 --> 00:04:10,720 and these organs coalesce to form things called humans, 75 00:04:11,920 --> 00:04:15,816 and these organisms ultimately live in environments, 76 00:04:15,840 --> 00:04:19,440 which are partly self-regulating and partly semi-autonomous. 77 00:04:20,920 --> 00:04:23,736 What's nice about this scheme, this hierarchical scheme 78 00:04:23,760 --> 00:04:26,456 building upwards rather than downwards, 79 00:04:26,480 --> 00:04:29,856 is that it allows us to think about illness as well 80 00:04:29,880 --> 00:04:31,214 in a somewhat different way. 81 00:04:32,400 --> 00:04:34,520 Take a disease like cancer. 82 00:04:36,120 --> 00:04:37,416 Since the 1950s, 83 00:04:37,440 --> 00:04:42,967 we've tried rather desperately to apply this lock and key model to cancer. 84 00:04:42,991 --> 00:04:45,880 We've tried to kill cells 85 00:04:45,905 --> 00:04:50,252 using a variety of chemotherapies or targeted therapies, 86 00:04:50,276 --> 00:04:52,696 and as most of us know, that's worked. 87 00:04:52,720 --> 00:04:54,578 It's worked for diseases like leukemia. 88 00:04:54,602 --> 00:04:56,976 It's worked for some forms of breast cancer, 89 00:04:57,000 --> 00:05:00,736 but eventually you run to the ceiling of that approach. 90 00:05:00,760 --> 00:05:03,256 And it's only in the last 10 years or so 91 00:05:03,280 --> 00:05:06,416 that we've begun to think about using the immune system, 92 00:05:06,440 --> 00:05:09,536 remembering that in fact the cancer cell doesn't grow in a vacuum. 93 00:05:09,560 --> 00:05:11,616 It actually grows in a human organism. 94 00:05:11,640 --> 00:05:13,936 And could you use the organismal capacity, 95 00:05:13,960 --> 00:05:17,103 the fact that human beings have an immune system, to attack cancer? 96 00:05:17,127 --> 00:05:21,327 In fact, it's led to the some of the most spectacular new medicines in cancer. 97 00:05:22,480 --> 00:05:25,814 And finally there's the level of the environment, isn't there? 98 00:05:26,160 --> 00:05:29,136 You know, we don't think of cancer as altering the environment. 99 00:05:29,160 --> 00:05:34,056 But let me give you an example of a profoundly carcinogenic environment. 100 00:05:34,080 --> 00:05:35,280 It's called a prison. 101 00:05:36,160 --> 00:05:41,296 You take loneliness, you take depression, you take confinement, 102 00:05:41,320 --> 00:05:42,520 and you add to that, 103 00:05:43,400 --> 00:05:45,960 rolled up in a little white sheet of paper, 104 00:05:47,000 --> 00:05:50,776 one of the most potent neurostimulants that we know, called nicotine, 105 00:05:50,800 --> 00:05:55,736 and you add to that one of the most potent addictive substances that you know, 106 00:05:55,760 --> 00:05:58,556 and you have a pro-carcinogenic environment. 107 00:05:59,520 --> 00:06:01,976 But you can have anti-carcinogenic environments too. 108 00:06:02,000 --> 00:06:04,696 There are attempts to create milieus, 109 00:06:04,720 --> 00:06:07,482 change the hormonal milieu for breast cancer, for instance. 110 00:06:08,440 --> 00:06:11,856 We're trying to change the metabolic milieu for other forms of cancer. 111 00:06:11,880 --> 00:06:14,296 Or take another disease, like depression. 112 00:06:14,320 --> 00:06:16,976 Again, working upwards, 113 00:06:17,000 --> 00:06:21,016 since the 1960s and 1970s, we've tried, again, desperately 114 00:06:21,040 --> 00:06:25,216 to turn off molecules that operate between nerve cells -- 115 00:06:25,240 --> 00:06:27,416 serotonin, dopamine -- 116 00:06:27,440 --> 00:06:29,256 and tried to cure depression that way, 117 00:06:29,280 --> 00:06:31,720 and that's worked, but then that reached the limit. 118 00:06:33,000 --> 00:06:35,620 And we now know that what you really probably need to do 119 00:06:35,644 --> 00:06:38,616 is to change the physiology of the organ, the brain, 120 00:06:38,640 --> 00:06:40,776 rewire it, remodel it, 121 00:06:40,800 --> 00:06:43,376 and that, of course, we know study upon study has shown 122 00:06:43,400 --> 00:06:45,115 that talk therapy does exactly that, 123 00:06:45,139 --> 00:06:47,395 and study upon study has shown that talk therapy 124 00:06:47,419 --> 00:06:50,536 combined with medicines, pills, 125 00:06:50,560 --> 00:06:52,989 really is much more effective than either one alone. 126 00:06:53,840 --> 00:06:57,416 Can we imagine a more immersive environment that will change depression? 127 00:06:57,440 --> 00:07:01,496 Can you lock out the signals that elicit depression? 128 00:07:01,520 --> 00:07:07,000 Again, moving upwards along this hierarchical chain of organization. 129 00:07:07,760 --> 00:07:10,456 What's really at stake perhaps here 130 00:07:10,480 --> 00:07:13,736 is not the medicine itself but a metaphor. 131 00:07:13,760 --> 00:07:15,816 Rather than killing something, 132 00:07:15,840 --> 00:07:19,536 in the case of the great chronic degenerative diseases -- 133 00:07:19,560 --> 00:07:23,056 kidney failure, diabetes, hypertension, osteoarthritis -- 134 00:07:23,080 --> 00:07:26,652 maybe what we really need to do is change the metaphor to growing something. 135 00:07:26,676 --> 00:07:28,616 And that's the key, perhaps, 136 00:07:28,640 --> 00:07:31,136 to reframing our thinking about medicine. 137 00:07:31,160 --> 00:07:34,616 Now, this idea of changing, 138 00:07:34,640 --> 00:07:36,976 of creating a perceptual shift, as it were, 139 00:07:37,000 --> 00:07:40,296 came home to me to roost in a very personal manner about 10 years ago. 140 00:07:40,320 --> 00:07:43,096 About 10 years ago -- I've been a runner most of my life -- 141 00:07:43,120 --> 00:07:45,096 I went for a run, a Saturday morning run, 142 00:07:45,120 --> 00:07:47,776 I came back and woke up and I basically couldn't move. 143 00:07:47,800 --> 00:07:49,816 My right knee was swollen up, 144 00:07:49,840 --> 00:07:53,360 and you could hear that ominous crunch of bone against bone. 145 00:07:54,240 --> 00:07:59,136 And one of the perks of being a physician is that you get to order your own MRIs. 146 00:07:59,160 --> 00:08:03,136 And I had an MRI the next week, and it looked like that. 147 00:08:03,160 --> 00:08:07,456 Essentially, the meniscus of cartilage that is between bone 148 00:08:07,480 --> 00:08:10,896 had been completely torn and the bone itself had been shattered. 149 00:08:10,920 --> 00:08:13,376 Now, if you're looking at me and feeling sorry, 150 00:08:13,400 --> 00:08:15,216 let me tell you a few facts. 151 00:08:15,240 --> 00:08:19,416 If I was to take an MRI of every person in this audience, 152 00:08:19,440 --> 00:08:21,496 60 percent of you would show signs 153 00:08:21,520 --> 00:08:24,296 of bone degeneration and cartilage degeneration like this. 154 00:08:24,320 --> 00:08:28,096 85 percent of all women by the age of 70 155 00:08:28,120 --> 00:08:31,376 would show moderate to severe cartilage degeneration. 156 00:08:31,400 --> 00:08:33,696 50 to 60 percent of the men in this audience 157 00:08:33,720 --> 00:08:35,056 would also have such signs. 158 00:08:35,080 --> 00:08:36,856 So this is a very common disease. 159 00:08:36,880 --> 00:08:38,976 Well, the second perk of being a physician 160 00:08:39,000 --> 00:08:42,135 is that you can get to experiment on your own ailments. 161 00:08:42,159 --> 00:08:44,376 So about 10 years ago we began, 162 00:08:44,400 --> 00:08:46,816 we brought this process into the laboratory, 163 00:08:46,840 --> 00:08:48,856 and we began to do simple experiments, 164 00:08:48,880 --> 00:08:51,336 mechanically trying to fix this degeneration. 165 00:08:51,360 --> 00:08:56,176 We tried to inject chemicals into the knee spaces of animals 166 00:08:56,200 --> 00:08:58,856 to try to reverse cartilage degeneration, 167 00:08:58,880 --> 00:09:03,416 and to put a short summary on a very long and painful process, 168 00:09:03,440 --> 00:09:05,216 essentially it came to naught. 169 00:09:05,240 --> 00:09:06,440 Nothing happened. 170 00:09:06,880 --> 00:09:11,656 And then about seven years ago, we had a research student from Australia. 171 00:09:11,680 --> 00:09:13,205 The nice thing about Australians 172 00:09:13,205 --> 00:09:16,521 is that they're habitually used to looking at the world upside down. 173 00:09:16,546 --> 00:09:17,703 (Laughter) 174 00:09:17,727 --> 00:09:21,816 And so Dan suggested to me, "You know, maybe it isn't a mechanical problem. 175 00:09:21,840 --> 00:09:25,840 Maybe it isn't a chemical problem. Maybe it's a stem cell problem." 176 00:09:27,760 --> 00:09:29,656 In other words, he had two hypotheses. 177 00:09:29,680 --> 00:09:33,496 Number one, there is such a thing as a skeletal stem cell -- 178 00:09:33,520 --> 00:09:37,040 a skeletal stem cell that builds up the entire vertebrate skeleton, 179 00:09:37,064 --> 00:09:39,596 bone, cartilage and the fibrous elements of skeleton, 180 00:09:39,620 --> 00:09:41,485 just like there's a stem cell in blood, 181 00:09:41,510 --> 00:09:43,945 just like there's a stem cell in the nervous system. 182 00:09:43,969 --> 00:09:47,529 And two, that maybe that, the degeneration or dysfunction of this stem cell 183 00:09:47,554 --> 00:09:51,056 is what's causing osteochondral arthritis, a very common ailment. 184 00:09:51,080 --> 00:09:54,296 So really the question was, were we looking for a pill 185 00:09:54,320 --> 00:09:56,936 when we should have really been looking for a cell. 186 00:09:56,960 --> 00:09:59,816 So we switched our models, 187 00:09:59,840 --> 00:10:02,960 and now we began to look for skeletal stem cells. 188 00:10:03,560 --> 00:10:06,056 And to cut again a long story short, 189 00:10:06,080 --> 00:10:09,000 about five years ago, we found these cells. 190 00:10:09,800 --> 00:10:12,296 They live inside the skeleton. 191 00:10:12,320 --> 00:10:15,216 Here's a schematic and then a real photograph of one of them. 192 00:10:15,240 --> 00:10:17,176 The white stuff is bone, 193 00:10:17,200 --> 00:10:20,216 and these red columns that you see and the yellow cells 194 00:10:20,240 --> 00:10:23,496 are cells that have arisen from one single skeletal stem cell -- 195 00:10:23,520 --> 00:10:26,816 columns of cartilage, columns of bone coming out of a single cell. 196 00:10:26,840 --> 00:10:30,136 These cells are fascinating. They have four properties. 197 00:10:30,160 --> 00:10:33,936 Number one is that they live where they're expected to live. 198 00:10:33,960 --> 00:10:36,336 They live just underneath the surface of the bone, 199 00:10:36,360 --> 00:10:37,896 underneath cartilage. 200 00:10:37,920 --> 00:10:40,540 You know, in biology, it's location, location, location. 201 00:10:40,564 --> 00:10:44,816 And they move into the appropriate areas and form bone and cartilage. 202 00:10:44,840 --> 00:10:46,096 That's one. 203 00:10:46,120 --> 00:10:47,656 Here's an interesting property. 204 00:10:47,680 --> 00:10:50,336 You can take them out of the vertebrate skeleton, 205 00:10:50,360 --> 00:10:52,936 you can culture them in petri dishes in the laboratory, 206 00:10:52,960 --> 00:10:54,936 and they are dying to form cartilage. 207 00:10:54,960 --> 00:10:57,682 Remember how we couldn't form cartilage for love or money? 208 00:10:57,706 --> 00:10:59,625 These cells are dying to form cartilage. 209 00:10:59,650 --> 00:11:02,655 They form their own furls of cartilage around themselves. 210 00:11:02,680 --> 00:11:04,296 They're also, number three, 211 00:11:04,320 --> 00:11:08,496 the most efficient repairers of fractures that we've ever encountered. 212 00:11:08,520 --> 00:11:11,816 This is a little bone, a mouse bone that we fractured 213 00:11:11,840 --> 00:11:13,376 and then let it heal by itself. 214 00:11:13,400 --> 00:11:16,416 These stem cells have come in and repaired, in yellow, the bone, 215 00:11:16,440 --> 00:11:19,056 in white, the cartilage, almost completely. 216 00:11:19,080 --> 00:11:22,616 So much so that if you label them with a fluorescent dye 217 00:11:22,640 --> 00:11:26,376 you can see them like some kind of peculiar cellular glue 218 00:11:26,400 --> 00:11:28,256 coming into the area of a fracture, 219 00:11:28,280 --> 00:11:31,256 fixing it locally and then stopping their work. 220 00:11:31,280 --> 00:11:33,616 Now, the fourth one is the most ominous, 221 00:11:33,640 --> 00:11:37,776 and that is that their numbers decline precipitously, 222 00:11:37,800 --> 00:11:42,496 precipitously, tenfold, fiftyfold, as you age. 223 00:11:42,520 --> 00:11:44,096 And so what had happened, really, 224 00:11:44,120 --> 00:11:46,976 is that we found ourselves in a perceptual shift. 225 00:11:47,000 --> 00:11:49,736 We had gone hunting for pills 226 00:11:49,760 --> 00:11:52,256 but we ended up finding theories. 227 00:11:52,280 --> 00:11:53,496 And in some ways 228 00:11:53,520 --> 00:11:56,136 we had hooked ourselves back onto this idea: 229 00:11:56,160 --> 00:11:59,056 cells, organisms, environments, 230 00:11:59,080 --> 00:12:01,656 because we were now thinking about bone stem cells, 231 00:12:01,680 --> 00:12:05,120 we were thinking about arthritis in terms of a cellular disease. 232 00:12:05,840 --> 00:12:08,126 And then the next question was, are there organs? 233 00:12:08,150 --> 00:12:10,389 Can you build this as an organ outside the body? 234 00:12:10,413 --> 00:12:14,256 Can you implant cartilage into areas of trauma? 235 00:12:14,280 --> 00:12:16,256 And perhaps most interestingly, 236 00:12:16,280 --> 00:12:18,656 can you ascend right up and create environments? 237 00:12:18,680 --> 00:12:21,736 You know, we know that exercise remodels bone, 238 00:12:21,760 --> 00:12:24,176 but come on, none of us is going to exercise. 239 00:12:24,200 --> 00:12:29,376 So could you imagine ways of passively loading and unloading bone 240 00:12:29,400 --> 00:12:34,216 so that you can recreate or regenerate degenerating cartilage? 241 00:12:34,240 --> 00:12:36,621 And perhaps more interesting, and more importantly, 242 00:12:36,645 --> 00:12:40,096 the question is, can you apply this model more globally outside medicine? 243 00:12:40,120 --> 00:12:44,176 What's at stake, as I said before, is not killing something, 244 00:12:44,200 --> 00:12:45,640 but growing something. 245 00:12:46,280 --> 00:12:51,096 And it raises a series of, I think, some of the most interesting questions 246 00:12:51,120 --> 00:12:53,640 about how we think about medicine in the future. 247 00:12:55,040 --> 00:12:57,920 Could your medicine be a cell and not a pill? 248 00:12:58,840 --> 00:13:01,216 How would we grow these cells? 249 00:13:01,240 --> 00:13:04,256 What we would we do to stop the malignant growth of these cells? 250 00:13:04,280 --> 00:13:08,176 We heard about the problems of unleashing growth. 251 00:13:08,200 --> 00:13:10,976 Could we implant suicide genes into these cells 252 00:13:11,000 --> 00:13:12,440 to stop them from growing? 253 00:13:13,040 --> 00:13:16,976 Could your medicine be an organ that's created outside the body 254 00:13:17,000 --> 00:13:18,936 and then implanted into the body? 255 00:13:18,960 --> 00:13:21,696 Could that stop some of the degeneration? 256 00:13:21,720 --> 00:13:23,625 What if the organ needed to have memory? 257 00:13:23,649 --> 00:13:28,416 In cases of diseases of the nervous system some of those organs had memory. 258 00:13:28,440 --> 00:13:30,896 How could we implant those memories back in? 259 00:13:30,920 --> 00:13:32,736 Could we store these organs? 260 00:13:32,760 --> 00:13:35,903 Would each organ have to be developed for an individual human being 261 00:13:35,927 --> 00:13:37,127 and put back? 262 00:13:38,520 --> 00:13:41,136 And perhaps most puzzlingly, 263 00:13:41,160 --> 00:13:42,970 could your medicine be an environment? 264 00:13:44,160 --> 00:13:45,816 Could you patent an environment? 265 00:13:45,840 --> 00:13:49,296 You know, in every culture, 266 00:13:49,320 --> 00:13:52,256 shamans have been using environments as medicines. 267 00:13:52,280 --> 00:13:54,600 Could we imagine that for our future? 268 00:13:56,080 --> 00:13:59,456 I've talked a lot about models. I began this talk with models. 269 00:13:59,480 --> 00:14:02,176 So let me end with some thoughts about model building. 270 00:14:02,200 --> 00:14:04,296 That's what we do as scientists. 271 00:14:04,320 --> 00:14:07,616 You know, when an architect builds a model, 272 00:14:07,640 --> 00:14:10,936 he or she is trying to show you a world in miniature. 273 00:14:10,960 --> 00:14:13,856 But when a scientist is building a model, 274 00:14:13,880 --> 00:14:16,404 he or she is trying to show you the world in metaphor. 275 00:14:17,600 --> 00:14:21,456 He or she is trying to create a new way of seeing. 276 00:14:21,480 --> 00:14:25,600 The former is a scale shift. The latter is a perceptual shift. 277 00:14:26,920 --> 00:14:31,856 Now, antibiotics created such a perceptual shift 278 00:14:31,880 --> 00:14:35,696 in our way of thinking about medicine that it really colored, distorted, 279 00:14:35,720 --> 00:14:39,640 very successfully, the way we've thought about medicine for the last hundred years. 280 00:14:40,400 --> 00:14:44,816 But we need new models to think about medicine in the future. 281 00:14:44,840 --> 00:14:46,320 That's what's at stake. 282 00:14:47,480 --> 00:14:50,816 You know, there's a popular trope out there 283 00:14:50,840 --> 00:14:54,816 that the reason we haven't had the transformative impact 284 00:14:54,840 --> 00:14:56,816 on the treatment of illness 285 00:14:56,840 --> 00:14:59,696 is because we don't have powerful-enough drugs, 286 00:14:59,720 --> 00:15:01,080 and that's partly true. 287 00:15:02,120 --> 00:15:03,616 But perhaps the real reason is 288 00:15:03,640 --> 00:15:06,840 that we don't have powerful-enough ways of thinking about medicines. 289 00:15:08,560 --> 00:15:10,976 It's certainly true that 290 00:15:11,000 --> 00:15:14,776 it would be lovely to have new medicines. 291 00:15:14,800 --> 00:15:19,456 But perhaps what's really at stake are three more intangible M's: 292 00:15:19,480 --> 00:15:23,296 mechanisms, models, metaphors. 293 00:15:23,320 --> 00:15:24,656 Thank you. 294 00:15:24,680 --> 00:15:31,520 (Applause) 295 00:15:33,600 --> 00:15:37,016 Chris Anderson: I really like this metaphor. 296 00:15:37,040 --> 00:15:38,576 How does it link in? 297 00:15:38,600 --> 00:15:41,736 There's a lot of talk in technologyland 298 00:15:41,760 --> 00:15:43,896 about the personalization of medicine, 299 00:15:43,920 --> 00:15:47,336 that we have all this data and that medical treatments of the future 300 00:15:47,360 --> 00:15:51,856 will be for you specifically, your genome, your current context. 301 00:15:51,880 --> 00:15:55,816 Does that apply to this model you've got here? 302 00:15:55,840 --> 00:15:58,456 Siddhartha Mukherjee: It's a very interesting question. 303 00:15:58,480 --> 00:16:00,696 We've thought about personalization of medicine 304 00:16:00,720 --> 00:16:02,256 very much in terms of genomics. 305 00:16:02,280 --> 00:16:04,856 That's because the gene is such a dominant metaphor, 306 00:16:04,880 --> 00:16:07,856 again, to use that same word, in medicine today, 307 00:16:07,880 --> 00:16:11,616 that we think the genome will drive the personalization of medicine. 308 00:16:11,640 --> 00:16:14,736 But of course the genome is just the bottom 309 00:16:14,760 --> 00:16:18,576 of a long chain of being, as it were. 310 00:16:18,600 --> 00:16:22,416 That chain of being, really the first organized unit of that, is the cell. 311 00:16:22,440 --> 00:16:25,416 So, if we are really going to deliver in medicine in this way, 312 00:16:25,440 --> 00:16:28,256 we have to think of personalizing cellular therapies, 313 00:16:28,280 --> 00:16:31,456 and then personalizing organ or organismal therapies, 314 00:16:31,480 --> 00:16:35,296 and ultimately personalizing immersion therapies for the environment. 315 00:16:35,320 --> 00:16:38,416 So I think at every stage, you know -- 316 00:16:38,440 --> 00:16:40,856 there's that metaphor, there's turtles all the way. 317 00:16:40,880 --> 00:16:43,261 Well, in this, there's personalization all the way. 318 00:16:43,285 --> 00:16:46,176 CA: So when you say medicine could be a cell 319 00:16:46,200 --> 00:16:48,016 and not a pill, 320 00:16:48,040 --> 00:16:50,296 you're talking about potentially your own cells. 321 00:16:50,320 --> 00:16:52,696 SM: Absolutely. CA: So converted to stem cells, 322 00:16:52,720 --> 00:16:57,256 perhaps tested against all kinds of drugs or something, and prepared. 323 00:16:57,280 --> 00:16:59,816 SM: And there's no perhaps. This is what we're doing. 324 00:16:59,840 --> 00:17:03,576 This is what's happening, and in fact, we're slowly moving, 325 00:17:03,600 --> 00:17:07,415 not away from genomics, but incorporating genomics 326 00:17:07,440 --> 00:17:12,175 into what we call multi-order, semi-autonomous, self-regulating systems, 327 00:17:12,200 --> 00:17:14,816 like cells, like organs, like environments. 328 00:17:14,829 --> 00:17:16,207 CA: Thank you so much. 329 00:17:16,227 --> 00:17:17,517 SM: Pleasure. Thanks.