[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.76,0:00:04.94,Default,,0000,0000,0000,,I want to talk to you\Nabout the future of medicine,
Dialogue: 0,0:00:04.96,0:00:09.06,Default,,0000,0000,0000,,but before I do that, I want to talk\Na little bit about the past.
Dialogue: 0,0:00:09.08,0:00:12.70,Default,,0000,0000,0000,,Now, throughout much\Nof the recent history of medicine,
Dialogue: 0,0:00:12.72,0:00:16.54,Default,,0000,0000,0000,,we've thought about illness and treatment
Dialogue: 0,0:00:16.56,0:00:19.94,Default,,0000,0000,0000,,in terms of a profoundly simple model.
Dialogue: 0,0:00:19.96,0:00:22.66,Default,,0000,0000,0000,,In fact, the model is so simple
Dialogue: 0,0:00:22.68,0:00:25.74,Default,,0000,0000,0000,,that you could summarize it in six words:
Dialogue: 0,0:00:25.76,0:00:29.84,Default,,0000,0000,0000,,have disease, take pill, kill something.
Dialogue: 0,0:00:31.08,0:00:35.82,Default,,0000,0000,0000,,Now, the reason\Nfor the dominance of this model
Dialogue: 0,0:00:35.84,0:00:38.46,Default,,0000,0000,0000,,is of course the antibiotic revolution.
Dialogue: 0,0:00:38.48,0:00:41.66,Default,,0000,0000,0000,,Many of you might not know this,\Nbut we happen to be celebrating
Dialogue: 0,0:00:41.68,0:00:45.74,Default,,0000,0000,0000,,the hundredth year of the introduction\Nof antibiotics into the United States,
Dialogue: 0,0:00:45.76,0:00:47.38,Default,,0000,0000,0000,,but what you do know
Dialogue: 0,0:00:47.40,0:00:51.64,Default,,0000,0000,0000,,is that that introduction\Nwas nothing short of transformative.
Dialogue: 0,0:00:52.88,0:00:56.74,Default,,0000,0000,0000,,Here you had a chemical,\Neither from the natural world
Dialogue: 0,0:00:56.76,0:00:59.50,Default,,0000,0000,0000,,or artificially synthesized\Nin the laboratory,
Dialogue: 0,0:00:59.52,0:01:02.78,Default,,0000,0000,0000,,and it would course through your body,
Dialogue: 0,0:01:02.80,0:01:05.58,Default,,0000,0000,0000,,it would find its target,
Dialogue: 0,0:01:05.60,0:01:07.26,Default,,0000,0000,0000,,lock into its target --
Dialogue: 0,0:01:07.28,0:01:09.50,Default,,0000,0000,0000,,a microbe or some part of a microbe --
Dialogue: 0,0:01:09.52,0:01:12.96,Default,,0000,0000,0000,,and then turn off a lock and a key
Dialogue: 0,0:01:13.96,0:01:17.50,Default,,0000,0000,0000,,with exquisite deftness,\Nexquisite specificity,
Dialogue: 0,0:01:17.52,0:01:21.82,Default,,0000,0000,0000,,and you would end up taking\Na previously fatal, lethal disease,
Dialogue: 0,0:01:21.84,0:01:24.98,Default,,0000,0000,0000,,a pneumonia, syphilis, tuberculosis,
Dialogue: 0,0:01:25.00,0:01:29.04,Default,,0000,0000,0000,,and transforming that\Ninto a curable, or treatable illness.
Dialogue: 0,0:01:30.08,0:01:31.56,Default,,0000,0000,0000,,You have a pneumonia,
Dialogue: 0,0:01:32.48,0:01:33.86,Default,,0000,0000,0000,,you take penicillin,
Dialogue: 0,0:01:33.88,0:01:35.42,Default,,0000,0000,0000,,you kill the microbe,
Dialogue: 0,0:01:35.44,0:01:37.58,Default,,0000,0000,0000,,and you cure the disease.
Dialogue: 0,0:01:37.60,0:01:40.54,Default,,0000,0000,0000,,So seductive was this idea,
Dialogue: 0,0:01:40.56,0:01:44.74,Default,,0000,0000,0000,,so potent the metaphor of lock and key
Dialogue: 0,0:01:44.76,0:01:46.30,Default,,0000,0000,0000,,and killing something,
Dialogue: 0,0:01:46.32,0:01:48.34,Default,,0000,0000,0000,,that it really swept through biology.
Dialogue: 0,0:01:48.36,0:01:50.48,Default,,0000,0000,0000,,It was a transformation like no other,
Dialogue: 0,0:01:52.16,0:01:55.34,Default,,0000,0000,0000,,and we've really spent the last 100 years
Dialogue: 0,0:01:55.36,0:01:58.82,Default,,0000,0000,0000,,trying to replicate that model\Nover and over again
Dialogue: 0,0:01:58.84,0:02:00.08,Default,,0000,0000,0000,,in noninfectious diseases,
Dialogue: 0,0:02:00.10,0:02:04.22,Default,,0000,0000,0000,,in chronic diseases like diabetes\Nand hypertension and heart disease.
Dialogue: 0,0:02:05.12,0:02:08.76,Default,,0000,0000,0000,,And it's worked,\Nbut it's only worked partly.
Dialogue: 0,0:02:09.12,0:02:10.78,Default,,0000,0000,0000,,Let me show you.
Dialogue: 0,0:02:10.80,0:02:13.70,Default,,0000,0000,0000,,You know, if you take the entire universe
Dialogue: 0,0:02:13.72,0:02:17.22,Default,,0000,0000,0000,,of all chemical reactions\Nin the human body,
Dialogue: 0,0:02:17.24,0:02:20.54,Default,,0000,0000,0000,,every chemical reaction\Nthat your body is capable of,
Dialogue: 0,0:02:20.56,0:02:23.58,Default,,0000,0000,0000,,most people think that that number\Nis on the order of a million.
Dialogue: 0,0:02:23.60,0:02:24.90,Default,,0000,0000,0000,,Let's call it a million.
Dialogue: 0,0:02:24.92,0:02:26.62,Default,,0000,0000,0000,,And now you ask the question,
Dialogue: 0,0:02:26.64,0:02:29.30,Default,,0000,0000,0000,,what number or fraction of reactions
Dialogue: 0,0:02:29.32,0:02:31.14,Default,,0000,0000,0000,,can actually be targeted
Dialogue: 0,0:02:31.16,0:02:35.98,Default,,0000,0000,0000,,by the entire pharmacopoeia,\Nall of medicinal chemistry?
Dialogue: 0,0:02:36.00,0:02:38.04,Default,,0000,0000,0000,,That number is 250.
Dialogue: 0,0:02:39.68,0:02:42.22,Default,,0000,0000,0000,,The rest is chemical darkness.
Dialogue: 0,0:02:42.24,0:02:48.42,Default,,0000,0000,0000,,In other words, 0.025 percent\Nof all chemical reactions in your body
Dialogue: 0,0:02:48.44,0:02:52.56,Default,,0000,0000,0000,,are actually targetable\Nby this lock and key mechanism.
Dialogue: 0,0:02:53.68,0:02:56.74,Default,,0000,0000,0000,,You know, if you think\Nabout human physiology
Dialogue: 0,0:02:56.76,0:03:00.22,Default,,0000,0000,0000,,as a vast global telephone network
Dialogue: 0,0:03:00.24,0:03:04.12,Default,,0000,0000,0000,,with interacting nodes\Nand interacting pieces,
Dialogue: 0,0:03:04.60,0:03:07.78,Default,,0000,0000,0000,,then all of our medicinal chemistry
Dialogue: 0,0:03:07.80,0:03:10.06,Default,,0000,0000,0000,,is operating on one tiny corner
Dialogue: 0,0:03:10.08,0:03:12.78,Default,,0000,0000,0000,,at the edge, the outer edge,\Nof that network.
Dialogue: 0,0:03:12.80,0:03:16.62,Default,,0000,0000,0000,,It's like all of our\Npharmaceutical chemistry
Dialogue: 0,0:03:16.64,0:03:20.42,Default,,0000,0000,0000,,is a pole operator in Wichita, Kansas
Dialogue: 0,0:03:20.44,0:03:23.40,Default,,0000,0000,0000,,who is tinkering with about\N10 or 15 telephone lines.
Dialogue: 0,0:03:24.88,0:03:27.04,Default,,0000,0000,0000,,So what do we do about this idea?
Dialogue: 0,0:03:28.16,0:03:30.52,Default,,0000,0000,0000,,What if we reorganized this approach?
Dialogue: 0,0:03:32.08,0:03:35.46,Default,,0000,0000,0000,,In fact, it turns out\Nthat the natural world
Dialogue: 0,0:03:35.48,0:03:40.54,Default,,0000,0000,0000,,gives us a sense of how one\Nmight think about illness
Dialogue: 0,0:03:40.56,0:03:42.22,Default,,0000,0000,0000,,in a radically different way,
Dialogue: 0,0:03:42.24,0:03:45.96,Default,,0000,0000,0000,,rather than disease, medicine, target.
Dialogue: 0,0:03:47.08,0:03:50.46,Default,,0000,0000,0000,,In fact, the natural world\Nis organized hierarchically upwards,
Dialogue: 0,0:03:50.48,0:03:52.34,Default,,0000,0000,0000,,not downwards, but upwards,
Dialogue: 0,0:03:52.36,0:03:58.60,Default,,0000,0000,0000,,and we begin with a self-regulating,\Nsemi-autonomous unit called a cell.
Dialogue: 0,0:03:59.64,0:04:02.86,Default,,0000,0000,0000,,These self-regulating,\Nsemi-autonomous units
Dialogue: 0,0:04:02.88,0:04:07.70,Default,,0000,0000,0000,,give rise to self-regulating,\Nsemi-autonomous units called organs,
Dialogue: 0,0:04:07.72,0:04:10.72,Default,,0000,0000,0000,,and these organs coalesce\Nto form things called humans,
Dialogue: 0,0:04:11.92,0:04:15.82,Default,,0000,0000,0000,,and these organisms\Nultimately live in environments,
Dialogue: 0,0:04:15.84,0:04:19.44,Default,,0000,0000,0000,,which are partly self-regulating\Nand partly semi-autonomous.
Dialogue: 0,0:04:20.92,0:04:23.74,Default,,0000,0000,0000,,What's nice about this scheme,\Nthis hierarchical scheme
Dialogue: 0,0:04:23.76,0:04:26.46,Default,,0000,0000,0000,,building upwards rather than downwards
Dialogue: 0,0:04:26.48,0:04:29.86,Default,,0000,0000,0000,,is that it allows us\Nto think about illness as well
Dialogue: 0,0:04:29.88,0:04:31.21,Default,,0000,0000,0000,,in a somewhat different way.
Dialogue: 0,0:04:32.40,0:04:34.52,Default,,0000,0000,0000,,Take a disease like cancer.
Dialogue: 0,0:04:36.12,0:04:37.42,Default,,0000,0000,0000,,Since the 1950s,
Dialogue: 0,0:04:37.44,0:04:42.97,Default,,0000,0000,0000,,we've tried rather desperately to apply\Nthis lock and key model to cancer.
Dialogue: 0,0:04:42.99,0:04:45.88,Default,,0000,0000,0000,,We've tried to kill cells
Dialogue: 0,0:04:45.90,0:04:50.25,Default,,0000,0000,0000,,using a variety of chemotherapies \Nor targeted therapies,
Dialogue: 0,0:04:50.28,0:04:52.70,Default,,0000,0000,0000,,and as most of us know, that's worked.
Dialogue: 0,0:04:52.72,0:04:54.58,Default,,0000,0000,0000,,It's worked for diseases like leukemia.
Dialogue: 0,0:04:54.60,0:04:56.98,Default,,0000,0000,0000,,It's worked for some forms\Nof breast cancer,
Dialogue: 0,0:04:57.00,0:05:00.74,Default,,0000,0000,0000,,but eventually you run\Nto the ceiling of that approach,
Dialogue: 0,0:05:00.76,0:05:03.26,Default,,0000,0000,0000,,and it's only in the last 10 years or so
Dialogue: 0,0:05:03.28,0:05:06.42,Default,,0000,0000,0000,,that we've begun to think\Nabout using the immune system,
Dialogue: 0,0:05:06.44,0:05:09.54,Default,,0000,0000,0000,,remembering that in fact the cancer cell\Ndoesn't grow in a vacuum.
Dialogue: 0,0:05:09.56,0:05:11.62,Default,,0000,0000,0000,,It actually grows in a human organism,
Dialogue: 0,0:05:11.64,0:05:13.94,Default,,0000,0000,0000,,and could you use the organismal capacity,
Dialogue: 0,0:05:13.96,0:05:17.10,Default,,0000,0000,0000,,the fact that human beings\Nhave an immune system, to attack cancer?
Dialogue: 0,0:05:17.13,0:05:21.33,Default,,0000,0000,0000,,In fact, it's led to the some of the most\Nspectacular new medicines in cancer.
Dialogue: 0,0:05:22.48,0:05:25.81,Default,,0000,0000,0000,,And finally, I mean, there's the level\Nof the environment, isn't there?
Dialogue: 0,0:05:26.16,0:05:29.14,Default,,0000,0000,0000,,You know, we don't think of cancer\Nas altering the environment.
Dialogue: 0,0:05:29.16,0:05:34.06,Default,,0000,0000,0000,,But let me give you an example\Nof a profoundly carcinogenic environment.
Dialogue: 0,0:05:34.08,0:05:35.28,Default,,0000,0000,0000,,It's called a prison.
Dialogue: 0,0:05:36.16,0:05:41.30,Default,,0000,0000,0000,,You take loneliness, you take depression,\Nyou take confinement,
Dialogue: 0,0:05:41.32,0:05:42.52,Default,,0000,0000,0000,,and you add to that,
Dialogue: 0,0:05:43.40,0:05:45.96,Default,,0000,0000,0000,,rolled up in a little\Nwhite sheet of paper,
Dialogue: 0,0:05:47.00,0:05:50.78,Default,,0000,0000,0000,,one of the most potent neurostimulants\Nthat we know, called nicotine,
Dialogue: 0,0:05:50.80,0:05:55.74,Default,,0000,0000,0000,,and you add to that one of the most potent\Naddictive substances that you know,
Dialogue: 0,0:05:55.76,0:05:56.98,Default,,0000,0000,0000,,and you have
Dialogue: 0,0:05:57.00,0:05:58.52,Default,,0000,0000,0000,,a pro-carcinogenic environment.
Dialogue: 0,0:05:59.52,0:06:01.98,Default,,0000,0000,0000,,But you can have anti-carcinogenic\Nenvironments too.
Dialogue: 0,0:06:02.00,0:06:04.70,Default,,0000,0000,0000,,There are attempts to create milieus,
Dialogue: 0,0:06:04.72,0:06:07.48,Default,,0000,0000,0000,,change the hormonal milieu\Nfor breast cancer, for instance.
Dialogue: 0,0:06:08.44,0:06:11.86,Default,,0000,0000,0000,,We're trying to change the metabolic\Nmilieu for other forms of cancer.
Dialogue: 0,0:06:11.88,0:06:14.30,Default,,0000,0000,0000,,Or take another disease, like depression.
Dialogue: 0,0:06:14.32,0:06:16.98,Default,,0000,0000,0000,,Again, working upwards,
Dialogue: 0,0:06:17.00,0:06:21.02,Default,,0000,0000,0000,,since the 1960s and 1970s,\Nwe've tried, again, desperately
Dialogue: 0,0:06:21.04,0:06:25.22,Default,,0000,0000,0000,,to turn off molecules\Nthat operate between nerve cells --
Dialogue: 0,0:06:25.24,0:06:27.42,Default,,0000,0000,0000,,serotonin, dopamine --
Dialogue: 0,0:06:27.44,0:06:29.26,Default,,0000,0000,0000,,and tried to cure depression that way,
Dialogue: 0,0:06:29.28,0:06:31.72,Default,,0000,0000,0000,,and that's worked,\Nbut then that reached the limit.
Dialogue: 0,0:06:33.00,0:06:35.62,Default,,0000,0000,0000,,And we now know that what you\Nreally probably need to do
Dialogue: 0,0:06:35.64,0:06:38.62,Default,,0000,0000,0000,,is to change the physiology\Nof the organ, the brain,
Dialogue: 0,0:06:38.64,0:06:40.78,Default,,0000,0000,0000,,rewire it, remodel it,
Dialogue: 0,0:06:40.80,0:06:43.38,Default,,0000,0000,0000,,and that, of course,\Nwe know study upon study has shown
Dialogue: 0,0:06:43.40,0:06:45.12,Default,,0000,0000,0000,,that talk therapy does exactly that,
Dialogue: 0,0:06:45.14,0:06:47.40,Default,,0000,0000,0000,,and study upon study\Nhas shown that talk therapy
Dialogue: 0,0:06:47.42,0:06:50.54,Default,,0000,0000,0000,,combined with medicines, pills,
Dialogue: 0,0:06:50.56,0:06:52.99,Default,,0000,0000,0000,,really is much more effective\Nthan either one alone.
Dialogue: 0,0:06:53.84,0:06:57.42,Default,,0000,0000,0000,,Can we imagine a more immersive\Nenvironment that will change depression?
Dialogue: 0,0:06:57.44,0:07:01.50,Default,,0000,0000,0000,,Can you lock out the signals\Nthat elicit depression?
Dialogue: 0,0:07:01.52,0:07:07.00,Default,,0000,0000,0000,,Again, moving upwards along this\Nhierarchical chain of organization.
Dialogue: 0,0:07:07.76,0:07:10.46,Default,,0000,0000,0000,,What's really at stake perhaps here
Dialogue: 0,0:07:10.48,0:07:13.74,Default,,0000,0000,0000,,is not the medicine itself but a metaphor.
Dialogue: 0,0:07:13.76,0:07:15.82,Default,,0000,0000,0000,,Rather than killing something,
Dialogue: 0,0:07:15.84,0:07:19.54,Default,,0000,0000,0000,,in the case of the great\Nchronic degenerative diseases --
Dialogue: 0,0:07:19.56,0:07:23.06,Default,,0000,0000,0000,,kidney failure, diabetes,\Nhypertension, osteoarthritis --
Dialogue: 0,0:07:23.08,0:07:26.65,Default,,0000,0000,0000,,maybe what we really need to do is change\Nthe metaphor to growing something.
Dialogue: 0,0:07:26.68,0:07:28.62,Default,,0000,0000,0000,,And that's the key, perhaps,
Dialogue: 0,0:07:28.64,0:07:31.14,Default,,0000,0000,0000,,to reframing our thinking about medicine.
Dialogue: 0,0:07:31.16,0:07:34.62,Default,,0000,0000,0000,,Now, this idea of changing,
Dialogue: 0,0:07:34.64,0:07:36.98,Default,,0000,0000,0000,,of creating a perceptual\Nshift, as it were,
Dialogue: 0,0:07:37.00,0:07:40.30,Default,,0000,0000,0000,,came home to me to roost in a very\Npersonal matter about 10 years ago.
Dialogue: 0,0:07:40.32,0:07:43.10,Default,,0000,0000,0000,,About 10 years ago --\NI've been a runner most of my life --
Dialogue: 0,0:07:43.12,0:07:45.10,Default,,0000,0000,0000,,I went for a run, a Saturday morning run,
Dialogue: 0,0:07:45.12,0:07:47.78,Default,,0000,0000,0000,,I came back and woke up\Nand I basically couldn't move.
Dialogue: 0,0:07:47.80,0:07:49.82,Default,,0000,0000,0000,,My right knee was swollen up,
Dialogue: 0,0:07:49.84,0:07:53.36,Default,,0000,0000,0000,,and you could hear that ominous crunch\Nof bone against bone.
Dialogue: 0,0:07:54.24,0:07:59.14,Default,,0000,0000,0000,,And one of the perks of being a physician\Nis that you get to order your own MRIs.
Dialogue: 0,0:07:59.16,0:08:03.14,Default,,0000,0000,0000,,And I had an MRI the next week,\Nand it looked like that.
Dialogue: 0,0:08:03.16,0:08:07.46,Default,,0000,0000,0000,,Essentially, the meniscus of cartilage\Nthat is between bone
Dialogue: 0,0:08:07.48,0:08:10.90,Default,,0000,0000,0000,,had been completely torn\Nand the bone itself had been shattered.
Dialogue: 0,0:08:10.92,0:08:13.38,Default,,0000,0000,0000,,Now, if you're looking at me\Nand feeling sorry,
Dialogue: 0,0:08:13.40,0:08:15.22,Default,,0000,0000,0000,,let me tell you a few facts.
Dialogue: 0,0:08:15.24,0:08:19.42,Default,,0000,0000,0000,,If I was to take an MRI\Nof every person in this audience,
Dialogue: 0,0:08:19.44,0:08:21.50,Default,,0000,0000,0000,,60 percent of you would show signs
Dialogue: 0,0:08:21.52,0:08:24.30,Default,,0000,0000,0000,,of bone degeneration\Nand cartilage degeneration like this.
Dialogue: 0,0:08:24.32,0:08:28.10,Default,,0000,0000,0000,,85 percent of all women by the age of 70
Dialogue: 0,0:08:28.12,0:08:31.38,Default,,0000,0000,0000,,would show moderate to severe\Ncartilage degeneration.
Dialogue: 0,0:08:31.40,0:08:33.70,Default,,0000,0000,0000,,50 to 60 percent\Nof the men in this audience
Dialogue: 0,0:08:33.72,0:08:35.06,Default,,0000,0000,0000,,would also have such signs.
Dialogue: 0,0:08:35.08,0:08:36.86,Default,,0000,0000,0000,,So this is a very common disease.
Dialogue: 0,0:08:36.88,0:08:38.98,Default,,0000,0000,0000,,Well, the second perk of being a physician
Dialogue: 0,0:08:39.00,0:08:42.14,Default,,0000,0000,0000,,is that you can get\Nto experiment on your own ailments.
Dialogue: 0,0:08:42.16,0:08:44.38,Default,,0000,0000,0000,,So about 10 years ago we began,
Dialogue: 0,0:08:44.40,0:08:46.82,Default,,0000,0000,0000,,we brought this process\Ninto the laboratory,
Dialogue: 0,0:08:46.84,0:08:48.86,Default,,0000,0000,0000,,and we began to do simple experiments,
Dialogue: 0,0:08:48.88,0:08:51.34,Default,,0000,0000,0000,,mechanically trying\Nto fix this degeneration.
Dialogue: 0,0:08:51.36,0:08:56.18,Default,,0000,0000,0000,,We tried to inject chemicals\Ninto the knee spaces of animals
Dialogue: 0,0:08:56.20,0:08:58.86,Default,,0000,0000,0000,,to try to reverse cartilage degeneration,
Dialogue: 0,0:08:58.88,0:09:03.42,Default,,0000,0000,0000,,and to put a short summary\Non a very long and painful process,
Dialogue: 0,0:09:03.44,0:09:05.22,Default,,0000,0000,0000,,essentially it came to naught.
Dialogue: 0,0:09:05.24,0:09:06.44,Default,,0000,0000,0000,,Nothing happened.
Dialogue: 0,0:09:06.88,0:09:11.66,Default,,0000,0000,0000,,And then about seven years ago,\Nwe had a research student from Australia.
Dialogue: 0,0:09:11.68,0:09:14.68,Default,,0000,0000,0000,,The nice thing about Australians\Nis that they're habitually used
Dialogue: 0,0:09:14.70,0:09:16.52,Default,,0000,0000,0000,,to looking at the world upside down --
Dialogue: 0,0:09:16.55,0:09:17.70,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:09:17.73,0:09:21.82,Default,,0000,0000,0000,,And so Dan suggested to me, "You know,\Nmaybe it isn't a mechanical problem.
Dialogue: 0,0:09:21.84,0:09:25.84,Default,,0000,0000,0000,,Maybe it isn't a chemical problem.\NMaybe it's a stem cell problem."
Dialogue: 0,0:09:27.76,0:09:29.66,Default,,0000,0000,0000,,In other words, he had two hypotheses.
Dialogue: 0,0:09:29.68,0:09:33.50,Default,,0000,0000,0000,,Number one, there is such a thing\Nas a skeletal stem cell.
Dialogue: 0,0:09:33.52,0:09:37.04,Default,,0000,0000,0000,,A skeletal stem cell that builds up\Nthe entire vertebrate skeleton:
Dialogue: 0,0:09:37.06,0:09:39.60,Default,,0000,0000,0000,,bone, cartilage, and the fibrous\Nelements of skeleton,
Dialogue: 0,0:09:39.62,0:09:41.48,Default,,0000,0000,0000,,just like there's a stem cell in blood,
Dialogue: 0,0:09:41.51,0:09:43.94,Default,,0000,0000,0000,,just like there's a stem cell\Nin the nervous system,
Dialogue: 0,0:09:43.97,0:09:47.53,Default,,0000,0000,0000,,and two, that maybe that, the degeneration\Nor dysfunction of this stem cell
Dialogue: 0,0:09:47.55,0:09:51.06,Default,,0000,0000,0000,,is what's causing osteochondral arthritis,\Na very common ailment.
Dialogue: 0,0:09:51.08,0:09:54.30,Default,,0000,0000,0000,,So really the question was,\Nwere we looking for a pill
Dialogue: 0,0:09:54.32,0:09:56.94,Default,,0000,0000,0000,,when we should have really\Nbeen looking for a cell.
Dialogue: 0,0:09:56.96,0:09:59.82,Default,,0000,0000,0000,,So we switched our models,
Dialogue: 0,0:09:59.84,0:10:02.96,Default,,0000,0000,0000,,and now we began\Nto look for skeletal stem cells,
Dialogue: 0,0:10:03.56,0:10:06.06,Default,,0000,0000,0000,,and to cut again a long story short,
Dialogue: 0,0:10:06.08,0:10:09.00,Default,,0000,0000,0000,,about five years ago,\Nwe found these cells.
Dialogue: 0,0:10:09.80,0:10:12.30,Default,,0000,0000,0000,,They live inside the skeleton.
Dialogue: 0,0:10:12.32,0:10:15.22,Default,,0000,0000,0000,,Here's a schematic and then\Na real photograph of one of them.
Dialogue: 0,0:10:15.24,0:10:17.18,Default,,0000,0000,0000,,The white stuff is bone,
Dialogue: 0,0:10:17.20,0:10:20.22,Default,,0000,0000,0000,,and these red columns that you see\Nand the yellow cells
Dialogue: 0,0:10:20.24,0:10:23.50,Default,,0000,0000,0000,,are cells that have arisen\Nfrom one single skeleton stem cell,
Dialogue: 0,0:10:23.52,0:10:26.82,Default,,0000,0000,0000,,columns of cartilage, columns of bone\Ncoming out a single cell.
Dialogue: 0,0:10:26.84,0:10:30.14,Default,,0000,0000,0000,,These cells are fascinating.\NThey have four properties.
Dialogue: 0,0:10:30.16,0:10:33.94,Default,,0000,0000,0000,,Number one is that they live\Nwhere they're expected to live.
Dialogue: 0,0:10:33.96,0:10:36.34,Default,,0000,0000,0000,,They live just underneath\Nthe surface of the bone,
Dialogue: 0,0:10:36.36,0:10:37.90,Default,,0000,0000,0000,,underneath cartilage.
Dialogue: 0,0:10:37.92,0:10:40.54,Default,,0000,0000,0000,,You know, in biology,\Nit's location, location, location.
Dialogue: 0,0:10:40.56,0:10:44.82,Default,,0000,0000,0000,,And they move into the appropriate areas\Nand form bone and cartilage.
Dialogue: 0,0:10:44.84,0:10:46.10,Default,,0000,0000,0000,,That's one.
Dialogue: 0,0:10:46.12,0:10:47.66,Default,,0000,0000,0000,,Here's an interesting property.
Dialogue: 0,0:10:47.68,0:10:50.34,Default,,0000,0000,0000,,You can take them out\Nof the vertebrate skeleton,
Dialogue: 0,0:10:50.36,0:10:52.94,Default,,0000,0000,0000,,you can culture them\Nin petri dishes in the laboratory,
Dialogue: 0,0:10:52.96,0:10:54.94,Default,,0000,0000,0000,,and they are dying to form cartilage.
Dialogue: 0,0:10:54.96,0:10:57.68,Default,,0000,0000,0000,,Remember how we couldn't\Nform cartilage for love or money?
Dialogue: 0,0:10:57.71,0:10:59.62,Default,,0000,0000,0000,,These cells are dying to form cartilage.
Dialogue: 0,0:10:59.65,0:11:02.66,Default,,0000,0000,0000,,They form their own furls\Nof cartilage around themselves.
Dialogue: 0,0:11:02.68,0:11:04.30,Default,,0000,0000,0000,,They're also, number three,
Dialogue: 0,0:11:04.32,0:11:08.50,Default,,0000,0000,0000,,the most efficient repairers\Nof fractures that we've ever encountered.
Dialogue: 0,0:11:08.52,0:11:11.82,Default,,0000,0000,0000,,This is a little bone,\Na mouse bone that we fractured
Dialogue: 0,0:11:11.84,0:11:13.38,Default,,0000,0000,0000,,and then let it heal by itself.
Dialogue: 0,0:11:13.40,0:11:16.42,Default,,0000,0000,0000,,These stem cells have come in\Nand repaired, in yellow, the bone,
Dialogue: 0,0:11:16.44,0:11:19.06,Default,,0000,0000,0000,,in white, the cartilage,\Nalmost completely.
Dialogue: 0,0:11:19.08,0:11:22.62,Default,,0000,0000,0000,,So much so that if you label them\Nwith a fluorescent dye
Dialogue: 0,0:11:22.64,0:11:26.38,Default,,0000,0000,0000,,you can see them like some kind\Nof peculiar cellular glue
Dialogue: 0,0:11:26.40,0:11:28.26,Default,,0000,0000,0000,,coming into the area of a fracture,
Dialogue: 0,0:11:28.28,0:11:31.26,Default,,0000,0000,0000,,fixing it locally,\Nand then stopping their work.
Dialogue: 0,0:11:31.28,0:11:33.62,Default,,0000,0000,0000,,Now, the fourth one is the most ominous,
Dialogue: 0,0:11:33.64,0:11:37.78,Default,,0000,0000,0000,,and that is that their numbers\Ndecline precipitously,
Dialogue: 0,0:11:37.80,0:11:42.50,Default,,0000,0000,0000,,precipitously, tenfold,\Nfiftyfold, as you age.
Dialogue: 0,0:11:42.52,0:11:44.10,Default,,0000,0000,0000,,And so what had happened, really,
Dialogue: 0,0:11:44.12,0:11:46.98,Default,,0000,0000,0000,,is that we found ourselves\Nin a perceptual shift.
Dialogue: 0,0:11:47.00,0:11:49.74,Default,,0000,0000,0000,,We had gone hunting for pills
Dialogue: 0,0:11:49.76,0:11:52.26,Default,,0000,0000,0000,,but we ended up finding theories,
Dialogue: 0,0:11:52.28,0:11:53.50,Default,,0000,0000,0000,,and in some ways,
Dialogue: 0,0:11:53.52,0:11:56.14,Default,,0000,0000,0000,,we had hooked ourselves\Nback onto this idea:
Dialogue: 0,0:11:56.16,0:11:59.06,Default,,0000,0000,0000,,cells, organisms, environments,
Dialogue: 0,0:11:59.08,0:12:01.66,Default,,0000,0000,0000,,because we were now thinking\Nabout bone stem cells,
Dialogue: 0,0:12:01.68,0:12:05.12,Default,,0000,0000,0000,,we were thinking about arthritis\Nin terms of a cellular disease.
Dialogue: 0,0:12:05.84,0:12:08.13,Default,,0000,0000,0000,,And then the next question was,\Nare there organs?
Dialogue: 0,0:12:08.15,0:12:10.39,Default,,0000,0000,0000,,Can you build this\Nas an organ outside the body?
Dialogue: 0,0:12:10.41,0:12:14.26,Default,,0000,0000,0000,,Can you implant cartilage\Ninto areas of trauma?
Dialogue: 0,0:12:14.28,0:12:16.26,Default,,0000,0000,0000,,And perhaps most interestingly,
Dialogue: 0,0:12:16.28,0:12:18.66,Default,,0000,0000,0000,,can you ascend right up\Nand create environments?
Dialogue: 0,0:12:18.68,0:12:21.74,Default,,0000,0000,0000,,You know, we know\Nthat exercise remodels bone,
Dialogue: 0,0:12:21.76,0:12:24.18,Default,,0000,0000,0000,,but come on, none of us\Nis going to exercise.
Dialogue: 0,0:12:24.20,0:12:29.38,Default,,0000,0000,0000,,So could you imagine ways of passively\Nloading and unloading bone
Dialogue: 0,0:12:29.40,0:12:34.22,Default,,0000,0000,0000,,so that you can recreate\Nor regenerate degenerating cartilage?
Dialogue: 0,0:12:34.24,0:12:36.62,Default,,0000,0000,0000,,And perhaps more interesting,\Nand more importantly,
Dialogue: 0,0:12:36.64,0:12:40.10,Default,,0000,0000,0000,,the question is, can you apply this model\Nmore globally outside medicine?
Dialogue: 0,0:12:40.12,0:12:44.18,Default,,0000,0000,0000,,What's at stake, as I said before,\Nis not killing something,
Dialogue: 0,0:12:44.20,0:12:45.64,Default,,0000,0000,0000,,but growing something.
Dialogue: 0,0:12:46.28,0:12:51.10,Default,,0000,0000,0000,,And it raises a series of, I think,\Nsome of the most interesting questions
Dialogue: 0,0:12:51.12,0:12:53.64,Default,,0000,0000,0000,,about how we think\Nabout medicine in the future.
Dialogue: 0,0:12:55.04,0:12:57.92,Default,,0000,0000,0000,,Could your medicine\Nbe a cell and not a pill?
Dialogue: 0,0:12:58.84,0:13:01.22,Default,,0000,0000,0000,,How would we grow these cells?
Dialogue: 0,0:13:01.24,0:13:04.26,Default,,0000,0000,0000,,What we would we do to stop\Nthe malignant growth of these cells?
Dialogue: 0,0:13:04.28,0:13:08.18,Default,,0000,0000,0000,,We heard about the problems\Nof unleashing growth.
Dialogue: 0,0:13:08.20,0:13:10.98,Default,,0000,0000,0000,,Could we implant\Nsuicide genes into these cells
Dialogue: 0,0:13:11.00,0:13:12.44,Default,,0000,0000,0000,,to stop them from growing?
Dialogue: 0,0:13:13.04,0:13:16.98,Default,,0000,0000,0000,,Could your medicine be an organ\Nthat's created outside the body
Dialogue: 0,0:13:17.00,0:13:18.94,Default,,0000,0000,0000,,and then implanted into the body?
Dialogue: 0,0:13:18.96,0:13:21.70,Default,,0000,0000,0000,,Could that stop some of the degeneration?
Dialogue: 0,0:13:21.72,0:13:23.62,Default,,0000,0000,0000,,What if the organ needed to have memory?
Dialogue: 0,0:13:23.65,0:13:28.42,Default,,0000,0000,0000,,In cases of diseases of the nervous system\Nsome of those organs had memory.
Dialogue: 0,0:13:28.44,0:13:30.90,Default,,0000,0000,0000,,How could we implant\Nthose memories back in?
Dialogue: 0,0:13:30.92,0:13:32.74,Default,,0000,0000,0000,,Could we store these organs?
Dialogue: 0,0:13:32.76,0:13:35.90,Default,,0000,0000,0000,,Could each organ have to be developed\Nfor an individual human being
Dialogue: 0,0:13:35.93,0:13:37.13,Default,,0000,0000,0000,,and put back?
Dialogue: 0,0:13:38.52,0:13:41.14,Default,,0000,0000,0000,,And perhaps most puzzlingly,
Dialogue: 0,0:13:41.16,0:13:42.97,Default,,0000,0000,0000,,could your medicine be an environment?
Dialogue: 0,0:13:44.16,0:13:45.82,Default,,0000,0000,0000,,Could you patent an environment?
Dialogue: 0,0:13:45.84,0:13:49.30,Default,,0000,0000,0000,,You know, in every culture,
Dialogue: 0,0:13:49.32,0:13:52.26,Default,,0000,0000,0000,,shamans have been using\Nenvironments as medicines.
Dialogue: 0,0:13:52.28,0:13:54.60,Default,,0000,0000,0000,,Could we imagine that for our future?
Dialogue: 0,0:13:56.08,0:13:59.46,Default,,0000,0000,0000,,I've talked a lot about models.\NI began this talk with models.
Dialogue: 0,0:13:59.48,0:14:02.18,Default,,0000,0000,0000,,So let me end with some thoughts\Nabout model building.
Dialogue: 0,0:14:02.20,0:14:04.30,Default,,0000,0000,0000,,That's what we do as scientists.
Dialogue: 0,0:14:04.32,0:14:07.62,Default,,0000,0000,0000,,You know, when an architect\Nbuilds a model,
Dialogue: 0,0:14:07.64,0:14:10.94,Default,,0000,0000,0000,,he or she is trying to show you\Na world in miniature.
Dialogue: 0,0:14:10.96,0:14:13.86,Default,,0000,0000,0000,,But when a scientist is building a model,
Dialogue: 0,0:14:13.88,0:14:16.40,Default,,0000,0000,0000,,he or she is trying to show you\Nthe world in metaphor.
Dialogue: 0,0:14:17.60,0:14:21.46,Default,,0000,0000,0000,,He or she is trying to create\Na new way of seeing.
Dialogue: 0,0:14:21.48,0:14:25.60,Default,,0000,0000,0000,,The former is a scale shift.\NThe latter is a perceptual shift.
Dialogue: 0,0:14:26.92,0:14:31.86,Default,,0000,0000,0000,,Now, antibiotics created\Nsuch a perceptual shift
Dialogue: 0,0:14:31.88,0:14:35.70,Default,,0000,0000,0000,,in our way of thinking about medicine\Nthat it really colored, distorted,
Dialogue: 0,0:14:35.72,0:14:39.64,Default,,0000,0000,0000,,very successfully, the way we've thought\Nabout medicine for the last hundred years.
Dialogue: 0,0:14:40.40,0:14:44.82,Default,,0000,0000,0000,,But we need new models\Nto think about medicine in the future.
Dialogue: 0,0:14:44.84,0:14:46.32,Default,,0000,0000,0000,,That's what's at stake.
Dialogue: 0,0:14:47.48,0:14:50.82,Default,,0000,0000,0000,,You know, there's\Na popular trope out there
Dialogue: 0,0:14:50.84,0:14:54.82,Default,,0000,0000,0000,,that the reason we haven't had\Nthe transformative impact
Dialogue: 0,0:14:54.84,0:14:56.82,Default,,0000,0000,0000,,on the treatment of illness
Dialogue: 0,0:14:56.84,0:14:59.70,Default,,0000,0000,0000,,is because we don't have\Npowerful enough drugs,
Dialogue: 0,0:14:59.72,0:15:01.08,Default,,0000,0000,0000,,and that's partly true,
Dialogue: 0,0:15:02.12,0:15:03.62,Default,,0000,0000,0000,,but perhaps the real reason is
Dialogue: 0,0:15:03.64,0:15:06.84,Default,,0000,0000,0000,,that we don't have powerful enough\Nways of thinking about medicines.
Dialogue: 0,0:15:08.56,0:15:10.98,Default,,0000,0000,0000,,It's certainly true that
Dialogue: 0,0:15:11.00,0:15:14.78,Default,,0000,0000,0000,,it would be lovely to have new medicines,
Dialogue: 0,0:15:14.80,0:15:19.46,Default,,0000,0000,0000,,but perhaps what's really at stake\Nare three more intangible ends:
Dialogue: 0,0:15:19.48,0:15:23.30,Default,,0000,0000,0000,,mechanisms, models, metaphors.
Dialogue: 0,0:15:23.32,0:15:24.66,Default,,0000,0000,0000,,Thank you.
Dialogue: 0,0:15:24.68,0:15:31.52,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:15:33.60,0:15:37.02,Default,,0000,0000,0000,,Chris Anderson:\NI really like this metaphor.
Dialogue: 0,0:15:37.04,0:15:38.58,Default,,0000,0000,0000,,How does it link in?
Dialogue: 0,0:15:38.60,0:15:41.74,Default,,0000,0000,0000,,There's a lot of talk in technologyland
Dialogue: 0,0:15:41.76,0:15:43.90,Default,,0000,0000,0000,,about the personalization of medicine,
Dialogue: 0,0:15:43.92,0:15:47.34,Default,,0000,0000,0000,,that we have all this data\Nand that medical treatments of the future
Dialogue: 0,0:15:47.36,0:15:51.86,Default,,0000,0000,0000,,will be for you specifically,\Nyour genome, your current context.
Dialogue: 0,0:15:51.88,0:15:55.82,Default,,0000,0000,0000,,Does that apply to this model\Nyou've got here?
Dialogue: 0,0:15:55.84,0:15:58.46,Default,,0000,0000,0000,,Siddhartha Mukherjee:\NIt's a very interesting question.
Dialogue: 0,0:15:58.48,0:16:00.70,Default,,0000,0000,0000,,We've thought about\Npersonalization of medicine
Dialogue: 0,0:16:00.72,0:16:02.26,Default,,0000,0000,0000,,very much in terms of genomics.
Dialogue: 0,0:16:02.28,0:16:04.86,Default,,0000,0000,0000,,That's because the gene\Nis such a dominant metaphor,
Dialogue: 0,0:16:04.88,0:16:07.86,Default,,0000,0000,0000,,again, to use that same word,\Nin medicine today,
Dialogue: 0,0:16:07.88,0:16:11.62,Default,,0000,0000,0000,,that we think the genome will drive\Nthe personalization of medicine.
Dialogue: 0,0:16:11.64,0:16:14.74,Default,,0000,0000,0000,,But of course the genome\Nis just the bottom
Dialogue: 0,0:16:14.76,0:16:18.58,Default,,0000,0000,0000,,of a long chain of being, as it were.
Dialogue: 0,0:16:18.60,0:16:22.42,Default,,0000,0000,0000,,That chain of being, really the first\Norganized unit of that, is the cell.
Dialogue: 0,0:16:22.44,0:16:25.42,Default,,0000,0000,0000,,So, if we are really going to deliver\Nin medicine in this way,
Dialogue: 0,0:16:25.44,0:16:28.26,Default,,0000,0000,0000,,we have to think of personalizing\Ncellular therapies,
Dialogue: 0,0:16:28.28,0:16:31.46,Default,,0000,0000,0000,,and then personalizing\Norgan or organismal therapies,
Dialogue: 0,0:16:31.48,0:16:35.30,Default,,0000,0000,0000,,and ultimately personalizing\Nimmersion therapies for the environment.
Dialogue: 0,0:16:35.32,0:16:38.42,Default,,0000,0000,0000,,So I think at every stage, you know --
Dialogue: 0,0:16:38.44,0:16:40.86,Default,,0000,0000,0000,,There's that metaphor,\Nthere's turtles all the way.
Dialogue: 0,0:16:40.88,0:16:43.26,Default,,0000,0000,0000,,Well, in this, there's\Npersonalization all the way.
Dialogue: 0,0:16:43.28,0:16:46.18,Default,,0000,0000,0000,,CA: So when you say\Nmedicine could be a cell
Dialogue: 0,0:16:46.20,0:16:48.02,Default,,0000,0000,0000,,and not a pill,
Dialogue: 0,0:16:48.04,0:16:50.30,Default,,0000,0000,0000,,you're talking about\Npotentially your own cells.
Dialogue: 0,0:16:50.32,0:16:52.70,Default,,0000,0000,0000,,SM: Absolutely.\NCA: So converted to stem cells,
Dialogue: 0,0:16:52.72,0:16:57.26,Default,,0000,0000,0000,,perhaps tested against all kinds\Nof drugs or something, and prepared.
Dialogue: 0,0:16:57.28,0:16:59.82,Default,,0000,0000,0000,,SM: And there's no perhaps.\NThis is what we're doing.
Dialogue: 0,0:16:59.84,0:17:03.58,Default,,0000,0000,0000,,This is what's happening,\Nand in fact, we're slowly moving,
Dialogue: 0,0:17:03.60,0:17:07.42,Default,,0000,0000,0000,,not away from genomics,\Nbut incorporating genomics
Dialogue: 0,0:17:07.44,0:17:12.18,Default,,0000,0000,0000,,into what we call multi-order,\Nsemi-autonomous, self-regulating systems,
Dialogue: 0,0:17:12.20,0:17:14.82,Default,,0000,0000,0000,,like cells, like organs,\Nlike environments.
Dialogue: 0,0:17:14.84,0:17:18.20,Default,,0000,0000,0000,,CA: Thank you so much. SM: Thank you.