[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.65,0:00:04.94,Default,,0000,0000,0000,,I want to talk to you\Nabout the future of medicine,
Dialogue: 0,0:00:04.94,0:00:09.08,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: 0,0:00:12.70,0:00:15.86,Default,,0000,0000,0000,,we've thought about illness and treatment
Dialogue: 0,0:00:15.86,0:00:19.97,Default,,0000,0000,0000,,in terms of a profoundly simple model.
Dialogue: 0,0:00:19.97,0:00:22.68,Default,,0000,0000,0000,,In fact, the model is so simple
Dialogue: 0,0:00:22.68,0:00:25.66,Default,,0000,0000,0000,,that you could summarize it in six words:
Dialogue: 0,0:00:25.66,0:00:31.04,Default,,0000,0000,0000,,have disease, take pill, kill something.
Dialogue: 0,0:00:31.04,0:00:35.34,Default,,0000,0000,0000,,Now, the reason for\Nthe dominance of this model
Dialogue: 0,0:00:35.34,0:00:38.47,Default,,0000,0000,0000,,is of course the antibiotic revolution.
Dialogue: 0,0:00:38.47,0:00:41.68,Default,,0000,0000,0000,,Many of you might not know this,\Nbut we happen to be celebrating
Dialogue: 0,0:00:41.68,0:00:45.51,Default,,0000,0000,0000,,the hundredth year of the introduction\Nof antibiotics into the United States,
Dialogue: 0,0:00:45.51,0:00:47.23,Default,,0000,0000,0000,,but what you do know
Dialogue: 0,0:00:47.23,0:00:52.31,Default,,0000,0000,0000,,is that that introduction\Nwas nothing short of transformative.
Dialogue: 0,0:00:52.31,0:00:56.75,Default,,0000,0000,0000,,Here you had a chemical,\Neither from the natural world
Dialogue: 0,0:00:56.75,0:00:59.51,Default,,0000,0000,0000,,or artificially synthesized\Nin the laboratory,
Dialogue: 0,0:00:59.51,0:01:02.81,Default,,0000,0000,0000,,and it would course through your body,
Dialogue: 0,0:01:02.81,0:01:05.59,Default,,0000,0000,0000,,it would find its target,
Dialogue: 0,0:01:05.59,0:01:07.40,Default,,0000,0000,0000,,lock into its target --
Dialogue: 0,0:01:07.40,0:01:09.52,Default,,0000,0000,0000,,a microbe or some part of a microbe --
Dialogue: 0,0:01:09.52,0:01:12.46,Default,,0000,0000,0000,,and then turn off a lock and a key
Dialogue: 0,0:01:12.46,0:01:17.53,Default,,0000,0000,0000,,with exquisite deftness,\Nexquisite specificity,
Dialogue: 0,0:01:17.53,0:01:21.82,Default,,0000,0000,0000,,and you would end up taking\Na previously fatal, lethal disease,
Dialogue: 0,0:01:21.82,0:01:24.49,Default,,0000,0000,0000,,a pneumonia, syphilis, tuberculosis,
Dialogue: 0,0:01:24.49,0:01:30.18,Default,,0000,0000,0000,,and transforming that into a curable,\Nor treatable illness.
Dialogue: 0,0:01:30.18,0:01:32.80,Default,,0000,0000,0000,,You have a pneumonia,\Nyou take penicillin,
Dialogue: 0,0:01:32.80,0:01:35.43,Default,,0000,0000,0000,,you kill the microbe,
Dialogue: 0,0:01:35.43,0:01:37.58,Default,,0000,0000,0000,,and you cure the disease.
Dialogue: 0,0:01:37.58,0:01:40.72,Default,,0000,0000,0000,,So seductive was this idea,
Dialogue: 0,0:01:40.72,0:01:44.53,Default,,0000,0000,0000,,so potent the metaphor of lock and key
Dialogue: 0,0:01:44.53,0:01:46.32,Default,,0000,0000,0000,,and killing something,
Dialogue: 0,0:01:46.32,0:01:48.92,Default,,0000,0000,0000,,that it really swept through biology.
Dialogue: 0,0:01:48.92,0:01:51.89,Default,,0000,0000,0000,,It was a transformation like no other,
Dialogue: 0,0:01:51.89,0:01:55.44,Default,,0000,0000,0000,,and we've really spent the last 100 years
Dialogue: 0,0:01:55.44,0:01:58.60,Default,,0000,0000,0000,,trying to replicate that model\Nover and over again
Dialogue: 0,0:01:58.60,0:02:00.76,Default,,0000,0000,0000,,in noninfectious diseases,
Dialogue: 0,0:02:00.76,0:02:05.15,Default,,0000,0000,0000,,in chronic diseases like diabetes\Nand hypertension and heart disease.
Dialogue: 0,0:02:05.15,0:02:09.26,Default,,0000,0000,0000,,And it's worked,\Nbut it's only worked partly.
Dialogue: 0,0:02:09.26,0:02:11.09,Default,,0000,0000,0000,,Let me show you.
Dialogue: 0,0:02:11.09,0:02:13.71,Default,,0000,0000,0000,,You know, if you take the entire universe
Dialogue: 0,0:02:13.71,0:02:17.24,Default,,0000,0000,0000,,of all chemical reactions\Nin the human body,
Dialogue: 0,0:02:17.24,0:02:20.89,Default,,0000,0000,0000,,every chemical reaction\Nthat your body is capable of,
Dialogue: 0,0:02:20.89,0:02:23.18,Default,,0000,0000,0000,,most people think that that number\Nis on the order of a million.
Dialogue: 0,0:02:23.18,0:02:24.94,Default,,0000,0000,0000,,Let's call it a million.
Dialogue: 0,0:02:24.94,0:02:26.80,Default,,0000,0000,0000,,And now you ask the question,
Dialogue: 0,0:02:26.80,0:02:29.40,Default,,0000,0000,0000,,what number or fraction of reactions
Dialogue: 0,0:02:29.40,0:02:31.14,Default,,0000,0000,0000,,can actually be targeted
Dialogue: 0,0:02:31.14,0:02:35.66,Default,,0000,0000,0000,,by the entire pharmacopia,\Nall of medicinal chemistry?
Dialogue: 0,0:02:35.66,0:02:39.22,Default,,0000,0000,0000,,That number is 250.
Dialogue: 0,0:02:39.22,0:02:42.33,Default,,0000,0000,0000,,The rest is chemical darkness.
Dialogue: 0,0:02:42.33,0:02:48.51,Default,,0000,0000,0000,,In other words, 0.025 percent\Nof all chemical reactions in your body
Dialogue: 0,0:02:48.51,0:02:53.83,Default,,0000,0000,0000,,are actually targetable\Nby this lock and key mechanism.
Dialogue: 0,0:02:53.83,0:02:57.29,Default,,0000,0000,0000,,You know, if you think about\Nhuman physiology
Dialogue: 0,0:02:57.29,0:03:01.49,Default,,0000,0000,0000,,as a vast global telephone network
Dialogue: 0,0:03:01.49,0:03:04.74,Default,,0000,0000,0000,,with interacting nodes\Nand interacting pieces,
Dialogue: 0,0:03:04.74,0:03:07.76,Default,,0000,0000,0000,,then all of our medicinal chemistry
Dialogue: 0,0:03:07.76,0:03:10.22,Default,,0000,0000,0000,,is all operating on one tiny corner
Dialogue: 0,0:03:10.22,0:03:12.89,Default,,0000,0000,0000,,at the edge, the outer edge,\Nof that network.
Dialogue: 0,0:03:12.89,0:03:16.65,Default,,0000,0000,0000,,It's like all of our\Npharmaceutical chemistry
Dialogue: 0,0:03:16.65,0:03:20.44,Default,,0000,0000,0000,,is a pole operator in Wichita, Kansas
Dialogue: 0,0:03:20.44,0:03:24.36,Default,,0000,0000,0000,,who is tinkering with\Nabout 10 or 15 telephone lines.
Dialogue: 0,0:03:24.36,0:03:28.24,Default,,0000,0000,0000,,So what do about this idea?
Dialogue: 0,0:03:28.24,0:03:31.14,Default,,0000,0000,0000,,What if we reorganized this approach?
Dialogue: 0,0:03:31.14,0:03:36.16,Default,,0000,0000,0000,,In fact, it turns out\Nthat the natural world
Dialogue: 0,0:03:36.16,0:03:40.57,Default,,0000,0000,0000,,gives us a sense of how one\Nmight think about illness
Dialogue: 0,0:03:40.57,0:03:42.56,Default,,0000,0000,0000,,in a radically different way,
Dialogue: 0,0:03:42.56,0:03:47.23,Default,,0000,0000,0000,,rather than disease, medicine, target.
Dialogue: 0,0:03:47.23,0:03:51.25,Default,,0000,0000,0000,,In fact, the natural world\Nis organized hierarchically upwards,
Dialogue: 0,0:03:51.25,0:03:53.13,Default,,0000,0000,0000,,not downwards, but upwards,
Dialogue: 0,0:03:53.13,0:03:59.68,Default,,0000,0000,0000,,and we begin with a self-regulating,\Nsemi-autonomous unit called a cell.
Dialogue: 0,0:03:59.68,0:04:02.83,Default,,0000,0000,0000,,These self-regulating,\Nsemi-autonomous units
Dialogue: 0,0:04:02.83,0:04:08.17,Default,,0000,0000,0000,,give rise to self-regulating,\Nsemi-autonomous units called organs,
Dialogue: 0,0:04:08.17,0:04:12.03,Default,,0000,0000,0000,,and these organs coalesce\Nto form things called humans,
Dialogue: 0,0:04:12.03,0:04:16.21,Default,,0000,0000,0000,,and these organisms ultimately live\Nin environments,
Dialogue: 0,0:04:16.21,0:04:21.04,Default,,0000,0000,0000,,which are partly self-regulating\Nand partly semi-autonomous.
Dialogue: 0,0:04:21.04,0:04:23.77,Default,,0000,0000,0000,,What's nice about this scheme,\Nthis hierarchical scheme
Dialogue: 0,0:04:23.77,0:04:26.37,Default,,0000,0000,0000,,building upwards rather than downwards
Dialogue: 0,0:04:26.37,0:04:29.90,Default,,0000,0000,0000,,is that it allows us to think\Nabout illness as well
Dialogue: 0,0:04:29.90,0:04:32.38,Default,,0000,0000,0000,,in a somewhat different way.
Dialogue: 0,0:04:32.38,0:04:35.66,Default,,0000,0000,0000,,Take a disease like cancer.
Dialogue: 0,0:04:35.66,0:04:40.29,Default,,0000,0000,0000,,Since the 1950s, we've tried\Nrather desperately to apply
Dialogue: 0,0:04:40.29,0:04:42.96,Default,,0000,0000,0000,,this lock and key model to cancer.
Dialogue: 0,0:04:42.96,0:04:50.44,Default,,0000,0000,0000,,We've tried to kill cells using a variety\Nof chemotherapies or targeted therapies,
Dialogue: 0,0:04:50.44,0:04:52.74,Default,,0000,0000,0000,,and as most of us know, that's worked.
Dialogue: 0,0:04:52.74,0:04:54.32,Default,,0000,0000,0000,,It's worked for diseases like leukemia.
Dialogue: 0,0:04:54.32,0:04:56.89,Default,,0000,0000,0000,,It's worked for some forms\Nof breast cancer,
Dialogue: 0,0:04:56.89,0:05:00.75,Default,,0000,0000,0000,,but eventually you run\Nto the ceiling of that approach,
Dialogue: 0,0:05:00.75,0:05:03.46,Default,,0000,0000,0000,,and it's only in the last 10 years or so
Dialogue: 0,0:05:03.46,0:05:06.44,Default,,0000,0000,0000,,that we've begun to think\Nabout using the immune system,
Dialogue: 0,0:05:06.44,0:05:09.14,Default,,0000,0000,0000,,remembering that in fact the cancer cell\Ndoesn't grow in a vacuum.
Dialogue: 0,0:05:09.14,0:05:11.74,Default,,0000,0000,0000,,It actually grows in a human organism,
Dialogue: 0,0:05:11.74,0:05:14.09,Default,,0000,0000,0000,,and could you use the organismal capacity,
Dialogue: 0,0:05:14.09,0:05:17.16,Default,,0000,0000,0000,,the fact that human beings\Nhave an immune system, to attack cancer?
Dialogue: 0,0:05:17.16,0:05:22.03,Default,,0000,0000,0000,,In fact, it's led to the some of the most\Nspectacular new medicines in cancer.
Dialogue: 0,0:05:22.03,0:05:24.65,Default,,0000,0000,0000,,And finally, I mean, there's the level\Nof the environment, isn't there.
Dialogue: 0,0:05:24.65,0:05:29.08,Default,,0000,0000,0000,,You know, we don't think of cancer\Nas altering the environment.
Dialogue: 0,0:05:29.08,0:05:34.10,Default,,0000,0000,0000,,Let me give you an example\Nof a profoundly carcinogenic environment.
Dialogue: 0,0:05:34.10,0:05:36.21,Default,,0000,0000,0000,,It's called a prison.
Dialogue: 0,0:05:36.21,0:05:41.55,Default,,0000,0000,0000,,You take loneliness, you take depression,\Nyou take confinement,
Dialogue: 0,0:05:41.55,0:05:43.40,Default,,0000,0000,0000,,and you add to that,
Dialogue: 0,0:05:43.40,0:05:47.11,Default,,0000,0000,0000,,rolled up in a little white\Nsheet of paper,
Dialogue: 0,0:05:47.11,0:05:50.22,Default,,0000,0000,0000,,one of the most potent neurostimulants\Nthat we know, called nicotine,
Dialogue: 0,0:05:50.22,0:05:55.91,Default,,0000,0000,0000,,and you add to that one of the most potent\Naddictive substances that you know,
Dialogue: 0,0:05:55.91,0:05:59.98,Default,,0000,0000,0000,,and you have a pro-carcinogenic\Nenvironment.
Dialogue: 0,0:05:59.98,0:06:02.09,Default,,0000,0000,0000,,But you can have anti-carcinogenic\Nenvironments too.
Dialogue: 0,0:06:02.09,0:06:05.57,Default,,0000,0000,0000,,There are attempts to create milieus,
Dialogue: 0,0:06:05.57,0:06:08.45,Default,,0000,0000,0000,,change the hormonal milieu\Nfor breast cancer, for instance.
Dialogue: 0,0:06:08.45,0:06:11.89,Default,,0000,0000,0000,,We're trying to change the metabolic\Nmilieu for other forms of cancer.
Dialogue: 0,0:06:11.89,0:06:14.40,Default,,0000,0000,0000,,Or take another disease, like depression.
Dialogue: 0,0:06:14.40,0:06:16.100,Default,,0000,0000,0000,,Again, working others,
Dialogue: 0,0:06:16.100,0:06:20.76,Default,,0000,0000,0000,,since the 1960s and 1970s,\Nwe've tried, again, desperately
Dialogue: 0,0:06:20.76,0:06:25.19,Default,,0000,0000,0000,,to turn off molecules that operate\Nbetween nerve cells --
Dialogue: 0,0:06:25.19,0:06:27.72,Default,,0000,0000,0000,,serotonin, dopamine --
Dialogue: 0,0:06:27.72,0:06:30.37,Default,,0000,0000,0000,,and tried to cure depression that way,\Nand that's worked,
Dialogue: 0,0:06:30.37,0:06:33.11,Default,,0000,0000,0000,,but then that reached the limit.
Dialogue: 0,0:06:33.11,0:06:35.48,Default,,0000,0000,0000,,And we now know that what you\Nreally probably need to do
Dialogue: 0,0:06:35.48,0:06:38.43,Default,,0000,0000,0000,,is to change the physiology\Nof the organ, the brain,
Dialogue: 0,0:06:38.43,0:06:40.89,Default,,0000,0000,0000,,rewire it, remodel it,
Dialogue: 0,0:06:40.89,0:06:43.51,Default,,0000,0000,0000,,and that of course, we know\Nstudy upon study has shown
Dialogue: 0,0:06:43.51,0:06:45.48,Default,,0000,0000,0000,,that talk therapy does exactly that,
Dialogue: 0,0:06:45.48,0:06:48.03,Default,,0000,0000,0000,,and study upon study has shown\Nthat talk therapy combined
Dialogue: 0,0:06:48.03,0:06:50.56,Default,,0000,0000,0000,,with medicines, pills,
Dialogue: 0,0:06:50.56,0:06:53.100,Default,,0000,0000,0000,,really is much more effective\Nthan either one alone.
Dialogue: 0,0:06:53.100,0:06:57.46,Default,,0000,0000,0000,,Can we imagine a more immersive\Nenvironment that will change depression?
Dialogue: 0,0:06:57.46,0:07:01.68,Default,,0000,0000,0000,,Can you lock out the signals\Nthat elicit depression?
Dialogue: 0,0:07:01.68,0:07:07.88,Default,,0000,0000,0000,,Again, moving upwards along this\Nhierarchical chain of organization.
Dialogue: 0,0:07:07.88,0:07:10.46,Default,,0000,0000,0000,,What's really at stake perhaps here
Dialogue: 0,0:07:10.46,0:07:12.32,Default,,0000,0000,0000,,is not the medicine itself but a metaphor.
Dialogue: 0,0:07:12.32,0:07:15.96,Default,,0000,0000,0000,,Rather than killing something,
Dialogue: 0,0:07:15.96,0:07:19.68,Default,,0000,0000,0000,,in the case of the great\Nchronic degenerative diseases --
Dialogue: 0,0:07:19.68,0:07:23.30,Default,,0000,0000,0000,,kidney failure, diabetes,\Nhypertension, osteoarthritis --
Dialogue: 0,0:07:23.30,0:07:26.64,Default,,0000,0000,0000,,maybe what we really need to do is change\Nthe metaphor to growing something.
Dialogue: 0,0:07:26.64,0:07:28.57,Default,,0000,0000,0000,,And that's the key, perhaps,
Dialogue: 0,0:07:28.57,0:07:31.22,Default,,0000,0000,0000,,to reframing our thinking about medicine.
Dialogue: 0,0:07:31.22,0:07:34.54,Default,,0000,0000,0000,,Now, this idea of changing,
Dialogue: 0,0:07:34.54,0:07:36.84,Default,,0000,0000,0000,,of creating a perceptual shift,\Nas it were,
Dialogue: 0,0:07:36.84,0:07:40.20,Default,,0000,0000,0000,,came home to me to roost in a very,\Nvery personal matter about 10 years ago.
Dialogue: 0,0:07:40.20,0:07:42.73,Default,,0000,0000,0000,,About 10 years ago --\NI've been a runner most of my life --
Dialogue: 0,0:07:42.73,0:07:44.82,Default,,0000,0000,0000,,I went for a run, a Saturday morning run,
Dialogue: 0,0:07:44.82,0:07:47.82,Default,,0000,0000,0000,,I came back and woke up\Nand I basically couldn't move.
Dialogue: 0,0:07:47.82,0:07:50.00,Default,,0000,0000,0000,,My right knee was swollen up,
Dialogue: 0,0:07:50.00,0:07:53.39,Default,,0000,0000,0000,,and you could hear that ominous crunch\Nof bone against bone.
Dialogue: 0,0:07:53.39,0:07:59.17,Default,,0000,0000,0000,,And one of the perks of being a physician\Nis that you get to order your own MRIs.
Dialogue: 0,0:07:59.17,0:08:03.17,Default,,0000,0000,0000,,And I had an MRI the next week,\Nand it looked like that.
Dialogue: 0,0:08:03.17,0:08:07.46,Default,,0000,0000,0000,,Essentially, the meniscus of cartilage\Nthat is between bone
Dialogue: 0,0:08:07.46,0:08:10.99,Default,,0000,0000,0000,,had been completely torn\Nand the bone itself had been shattered.
Dialogue: 0,0:08:10.99,0:08:13.41,Default,,0000,0000,0000,,Now, if you're looking at me\Nand feeling sorry,
Dialogue: 0,0:08:13.41,0:08:15.24,Default,,0000,0000,0000,,let me tell you a few facts.
Dialogue: 0,0:08:15.24,0:08:19.35,Default,,0000,0000,0000,,If I was to take an MRI\Nof every person in this audience,
Dialogue: 0,0:08:19.35,0:08:21.54,Default,,0000,0000,0000,,60 percent of you would show signs
Dialogue: 0,0:08:21.54,0:08:24.32,Default,,0000,0000,0000,,of bone degeneration\Nand cartilage degeneration like this;
Dialogue: 0,0:08:24.32,0:08:28.13,Default,,0000,0000,0000,,85 percent of all women by the age of 70
Dialogue: 0,0:08:28.13,0:08:31.38,Default,,0000,0000,0000,,would show moderate to severe\Ncartilage degeneration;
Dialogue: 0,0:08:31.38,0:08:34.96,Default,,0000,0000,0000,,50 to 60 percent of the men in\Nthis audience would also have such signs.
Dialogue: 0,0:08:34.96,0:08:37.26,Default,,0000,0000,0000,,So this is a very common disease.
Dialogue: 0,0:08:37.26,0:08:39.37,Default,,0000,0000,0000,,Well, the second perk of being a physician
Dialogue: 0,0:08:39.37,0:08:42.25,Default,,0000,0000,0000,,is that you can get to experiment\Non your own ailments.
Dialogue: 0,0:08:42.25,0:08:45.52,Default,,0000,0000,0000,,So about 10 years ago we began,
Dialogue: 0,0:08:45.52,0:08:47.40,Default,,0000,0000,0000,,we brought this process\Ninto the laboratory,
Dialogue: 0,0:08:47.40,0:08:49.03,Default,,0000,0000,0000,,and we began to do simple experiments,
Dialogue: 0,0:08:49.03,0:08:53.28,Default,,0000,0000,0000,,mechanically trying\Nto fix this degeneration.
Dialogue: 0,0:08:53.28,0:08:56.41,Default,,0000,0000,0000,,We tried to inject chemicals\Ninto the knee spaces of animals
Dialogue: 0,0:08:56.41,0:08:59.04,Default,,0000,0000,0000,,to try to reverse cartilage degeneration,
Dialogue: 0,0:08:59.04,0:09:03.24,Default,,0000,0000,0000,,and to put a short summary\Non a very long and painful process,
Dialogue: 0,0:09:03.24,0:09:05.40,Default,,0000,0000,0000,,essentially it came to naught.
Dialogue: 0,0:09:05.40,0:09:07.05,Default,,0000,0000,0000,,Nothing happened.
Dialogue: 0,0:09:07.05,0:09:11.88,Default,,0000,0000,0000,,And then about seven years ago,\Nwe had a research student from Australia.
Dialogue: 0,0:09:11.88,0:09:14.41,Default,,0000,0000,0000,,Now, the nice thing about Australians\Nis that they're habitually used
Dialogue: 0,0:09:14.41,0:09:17.66,Default,,0000,0000,0000,,to looking at the world upside down,\Nand so -- (Laughter) --
Dialogue: 0,0:09:17.66,0:09:21.84,Default,,0000,0000,0000,,Dan suggested to me, "You know,\Nmaybe it isn't a mechanical problem.
Dialogue: 0,0:09:21.84,0:09:27.89,Default,,0000,0000,0000,,Maybe it isn't a chemical problem.\NMaybe it's a stem cell problem."
Dialogue: 0,0:09:27.89,0:09:30.05,Default,,0000,0000,0000,,In other words, he had two hypotheses.
Dialogue: 0,0:09:30.05,0:09:33.60,Default,,0000,0000,0000,,Number one, there is such a thing\Nas a skeletal stem cell
Dialogue: 0,0:09:33.60,0:09:37.71,Default,,0000,0000,0000,,that builds up the entire\Nvertebrate skeleton:
Dialogue: 0,0:09:37.71,0:09:39.89,Default,,0000,0000,0000,,bone, cartilage,\Nand the fibrous elements of skeleton,
Dialogue: 0,0:09:39.89,0:09:41.43,Default,,0000,0000,0000,,just like there's a stem cell in blood,
Dialogue: 0,0:09:41.43,0:09:43.28,Default,,0000,0000,0000,,just like there's a stem cell\Nin the nervous system,
Dialogue: 0,0:09:43.28,0:09:47.16,Default,,0000,0000,0000,,and two, that maybe that, the degeneration\Nor dysfunction of this stem cell
Dialogue: 0,0:09:47.16,0:09:50.36,Default,,0000,0000,0000,,that is causing osteochondral arthritis,\Na very common ailment.
Dialogue: 0,0:09:50.36,0:09:54.31,Default,,0000,0000,0000,,So really the question was,\Nwere we looking for a pill
Dialogue: 0,0:09:54.31,0:09:56.75,Default,,0000,0000,0000,,when we should have really\Nbeen looking for a cell.
Dialogue: 0,0:09:56.75,0:09:59.88,Default,,0000,0000,0000,,So we switched our models,
Dialogue: 0,0:09:59.88,0:10:03.67,Default,,0000,0000,0000,,and now we began to look\Nfor skeletal stem cells,
Dialogue: 0,0:10:03.67,0:10:06.22,Default,,0000,0000,0000,,and to cut again a long story short,
Dialogue: 0,0:10:06.22,0:10:10.26,Default,,0000,0000,0000,,about five years ago,\Nwe found these cells.
Dialogue: 0,0:10:10.26,0:10:12.32,Default,,0000,0000,0000,,They live inside the skeleton.
Dialogue: 0,0:10:12.32,0:10:15.34,Default,,0000,0000,0000,,Here's a schematic and then\Na real photograph of one of them.
Dialogue: 0,0:10:15.34,0:10:17.27,Default,,0000,0000,0000,,The white stuff is bone,
Dialogue: 0,0:10:17.27,0:10:19.57,Default,,0000,0000,0000,,and these red columns that you see\Nand the yellow cells
Dialogue: 0,0:10:19.57,0:10:23.74,Default,,0000,0000,0000,,are cells that have arisen\Nfrom one single skeleton stem cell,
Dialogue: 0,0:10:23.74,0:10:26.93,Default,,0000,0000,0000,,columns of cartilage, columns of bone\Ncoming out a single cell.
Dialogue: 0,0:10:26.93,0:10:29.85,Default,,0000,0000,0000,,These cells are fascinating.\NThey have four properties.
Dialogue: 0,0:10:29.85,0:10:32.82,Default,,0000,0000,0000,,Number one is that they live\Nwhere they're expected to live.
Dialogue: 0,0:10:32.82,0:10:36.19,Default,,0000,0000,0000,,They live just underneath\Nthe surface of the bone,
Dialogue: 0,0:10:36.19,0:10:38.16,Default,,0000,0000,0000,,underneath cartilage.
Dialogue: 0,0:10:38.16,0:10:40.46,Default,,0000,0000,0000,,You know, in biology,\Nit's location, location, location,
Dialogue: 0,0:10:40.46,0:10:43.69,Default,,0000,0000,0000,,and they move into the appropriate areas\Nand form bone and cartilage. That's one.
Dialogue: 0,0:10:43.69,0:10:46.94,Default,,0000,0000,0000,,Here's an interesting property.
Dialogue: 0,0:10:46.94,0:10:50.17,Default,,0000,0000,0000,,You can take them out\Nof the vertebrate skeleton,
Dialogue: 0,0:10:50.17,0:10:52.98,Default,,0000,0000,0000,,you can culture them\Nin petri dishes in the laboratory,
Dialogue: 0,0:10:52.98,0:10:55.14,Default,,0000,0000,0000,,and they are dying to form cartilage.
Dialogue: 0,0:10:55.14,0:10:57.27,Default,,0000,0000,0000,,Remember how we couldn't\Nform cartilage for love or money?
Dialogue: 0,0:10:57.27,0:10:59.41,Default,,0000,0000,0000,,These cells are dying to form cartilage.
Dialogue: 0,0:10:59.41,0:11:02.73,Default,,0000,0000,0000,,They form their own furls\Nof cartilage around themselves.
Dialogue: 0,0:11:02.73,0:11:04.52,Default,,0000,0000,0000,,They're also, number three,\Nthe most efficient repairers
Dialogue: 0,0:11:04.52,0:11:09.02,Default,,0000,0000,0000,,of fractures that we've ever encountered.
Dialogue: 0,0:11:09.02,0:11:11.28,Default,,0000,0000,0000,,This is a little bone, a mouse bone\Nthat we fractured
Dialogue: 0,0:11:11.28,0:11:13.16,Default,,0000,0000,0000,,and then let it heal by itself.
Dialogue: 0,0:11:13.16,0:11:16.22,Default,,0000,0000,0000,,These stem cells have come in\Nand repaired, in yellow, the bone,
Dialogue: 0,0:11:16.22,0:11:19.07,Default,,0000,0000,0000,,in white, the cartilage,\Nalmost completely,
Dialogue: 0,0:11:19.07,0:11:21.72,Default,,0000,0000,0000,,so much so that if you label them\Nwith a fluorescent dye
Dialogue: 0,0:11:21.72,0:11:26.48,Default,,0000,0000,0000,,you can see them like some kind of\Npeculiar cellular glue
Dialogue: 0,0:11:26.48,0:11:28.41,Default,,0000,0000,0000,,coming into the area of a fracture,\Nfixing it locally,
Dialogue: 0,0:11:28.41,0:11:31.38,Default,,0000,0000,0000,,and then stopping their work.
Dialogue: 0,0:11:31.38,0:11:34.06,Default,,0000,0000,0000,,Now, the fourth one is the most ominous,
Dialogue: 0,0:11:34.06,0:11:37.87,Default,,0000,0000,0000,,and that is that their numbers\Ndecline precipitously,
Dialogue: 0,0:11:37.87,0:11:42.54,Default,,0000,0000,0000,,precipitously, tenfold,\Nfiftyfold, as you age.
Dialogue: 0,0:11:42.54,0:11:45.58,Default,,0000,0000,0000,,And so what had happened, really,\Nis that we found ourselves
Dialogue: 0,0:11:45.58,0:11:47.23,Default,,0000,0000,0000,,in perceptual shift.
Dialogue: 0,0:11:47.23,0:11:49.97,Default,,0000,0000,0000,,We had gone hunting for pills
Dialogue: 0,0:11:49.97,0:11:52.29,Default,,0000,0000,0000,,but we ended up finding theories,
Dialogue: 0,0:11:52.29,0:11:56.14,Default,,0000,0000,0000,,and in some ways, we had hooked ourselves\Nback onto this idea:
Dialogue: 0,0:11:56.14,0:11:58.91,Default,,0000,0000,0000,,cells, organisms, environments,
Dialogue: 0,0:11:58.91,0:12:02.11,Default,,0000,0000,0000,,because we were now thinking\Nabout bone stem cells,
Dialogue: 0,0:12:02.11,0:12:05.85,Default,,0000,0000,0000,,we were thinking about arthritis\Nin terms of a cellular disease.
Dialogue: 0,0:12:05.85,0:12:08.02,Default,,0000,0000,0000,,And then the next question was,\Nare there organs?
Dialogue: 0,0:12:08.02,0:12:10.41,Default,,0000,0000,0000,,Can you build this as an organ\Noutside the body?
Dialogue: 0,0:12:10.41,0:12:13.87,Default,,0000,0000,0000,,Can you implant cartilage\Ninto areas of trauma?
Dialogue: 0,0:12:13.87,0:12:16.27,Default,,0000,0000,0000,,And perhaps most interestingly,
Dialogue: 0,0:12:16.27,0:12:18.70,Default,,0000,0000,0000,,can you ascend right up\Nand create environments?
Dialogue: 0,0:12:18.70,0:12:21.82,Default,,0000,0000,0000,,You know, we know\Nthat exercise remodels bone,
Dialogue: 0,0:12:21.82,0:12:24.19,Default,,0000,0000,0000,,but come on, none of us\Nis going to exercise.
Dialogue: 0,0:12:24.19,0:12:29.41,Default,,0000,0000,0000,,So could you imagine ways of passively\Nloading and unloading bone
Dialogue: 0,0:12:29.41,0:12:34.36,Default,,0000,0000,0000,,so that you can recreate\Nor regenerate degenerating catilage?
Dialogue: 0,0:12:34.36,0:12:37.56,Default,,0000,0000,0000,,And perhaps more interesting,\Nand more importantly,
Dialogue: 0,0:12:37.56,0:12:39.82,Default,,0000,0000,0000,,the question is, can you apply this model\Nmore globally outside medicine?
Dialogue: 0,0:12:39.82,0:12:44.18,Default,,0000,0000,0000,,What's at stake, as I said before,\Nis not killing something,
Dialogue: 0,0:12:44.18,0:12:46.32,Default,,0000,0000,0000,,but growing something.
Dialogue: 0,0:12:46.32,0:12:50.17,Default,,0000,0000,0000,,And it raises a series of, I think,\Nsome of the most interesting questions
Dialogue: 0,0:12:50.17,0:12:54.49,Default,,0000,0000,0000,,about how we think\Nabout medicine in the future.
Dialogue: 0,0:12:54.49,0:12:58.90,Default,,0000,0000,0000,,Could your medicine be a cell\Nand not a pill?
Dialogue: 0,0:12:58.90,0:13:01.22,Default,,0000,0000,0000,,How would we grow these cells?
Dialogue: 0,0:13:01.22,0:13:04.27,Default,,0000,0000,0000,,What we would we do to stop\Nthe malignant growth of these cells?
Dialogue: 0,0:13:04.27,0:13:07.91,Default,,0000,0000,0000,,We heard about the problems\Nof unleashing growth.
Dialogue: 0,0:13:07.91,0:13:11.09,Default,,0000,0000,0000,,Would we have to implant\Nsuicide genes into these cells
Dialogue: 0,0:13:11.09,0:13:13.20,Default,,0000,0000,0000,,to stop them from growing?
Dialogue: 0,0:13:13.20,0:13:16.06,Default,,0000,0000,0000,,Could your medicine be an organ\Nthat's created outside the body
Dialogue: 0,0:13:16.06,0:13:18.94,Default,,0000,0000,0000,,and then implanted into the body?
Dialogue: 0,0:13:18.94,0:13:21.70,Default,,0000,0000,0000,,Could that stop some of the degeneration?
Dialogue: 0,0:13:21.70,0:13:23.63,Default,,0000,0000,0000,,What if the organ needed to have memory?
Dialogue: 0,0:13:23.63,0:13:28.43,Default,,0000,0000,0000,,In cases of diseases of the nervous system\Nsome of those organs had memory.
Dialogue: 0,0:13:28.43,0:13:30.91,Default,,0000,0000,0000,,How could we implant\Nthose memories back in?
Dialogue: 0,0:13:30.91,0:13:32.84,Default,,0000,0000,0000,,Could we store these organs?
Dialogue: 0,0:13:32.84,0:13:35.72,Default,,0000,0000,0000,,Could each organ have to be developed\Nfor an individual human being
Dialogue: 0,0:13:35.72,0:13:38.55,Default,,0000,0000,0000,,and put back?
Dialogue: 0,0:13:38.55,0:13:41.18,Default,,0000,0000,0000,,And perhaps most puzzlingly,
Dialogue: 0,0:13:41.18,0:13:44.17,Default,,0000,0000,0000,,could your medicine be an environment?
Dialogue: 0,0:13:44.17,0:13:46.10,Default,,0000,0000,0000,,Could you patent an environment?
Dialogue: 0,0:13:46.10,0:13:52.32,Default,,0000,0000,0000,,In every culture, shamans have been\Nusing environments as medicines.
Dialogue: 0,0:13:52.32,0:13:55.46,Default,,0000,0000,0000,,Could we imagine that for our future?
Dialogue: 0,0:13:55.46,0:13:59.60,Default,,0000,0000,0000,,I've talked a lot about models.\NI began this talk with models.
Dialogue: 0,0:13:59.60,0:14:02.32,Default,,0000,0000,0000,,So let me end with some thoughts\Nabout model building.
Dialogue: 0,0:14:02.32,0:14:04.32,Default,,0000,0000,0000,,That's what we do as scientists.
Dialogue: 0,0:14:04.32,0:14:07.66,Default,,0000,0000,0000,,You know, when an architect\Nbuilds a model,
Dialogue: 0,0:14:07.66,0:14:10.86,Default,,0000,0000,0000,,he or she is trying to show you\Na world in miniature.
Dialogue: 0,0:14:10.86,0:14:13.88,Default,,0000,0000,0000,,But when a scientist is building a model,
Dialogue: 0,0:14:13.88,0:14:16.81,Default,,0000,0000,0000,,he or she is trying to show you\Nthe world in metaphor.
Dialogue: 0,0:14:16.81,0:14:21.64,Default,,0000,0000,0000,,He or she is trying to create\Na new way of seeing.
Dialogue: 0,0:14:21.64,0:14:26.98,Default,,0000,0000,0000,,The former is a scale shift.\NThe latter is a perceptual shift.
Dialogue: 0,0:14:26.98,0:14:31.44,Default,,0000,0000,0000,,Now, antibiotics created\Nsuch a perceptual shift
Dialogue: 0,0:14:31.44,0:14:35.73,Default,,0000,0000,0000,,in our way of thinking about medicine\Nthat it really colored, distorted,
Dialogue: 0,0:14:35.73,0:14:40.21,Default,,0000,0000,0000,,very successfully, the way we've thought\Nabout medicine for the last hundred years.
Dialogue: 0,0:14:40.21,0:14:44.83,Default,,0000,0000,0000,,But we need new models\Nto think about medicine in the future.
Dialogue: 0,0:14:44.83,0:14:46.69,Default,,0000,0000,0000,,That's what's at stake.
Dialogue: 0,0:14:46.69,0:14:50.64,Default,,0000,0000,0000,,You know, there's\Na popular trope out there
Dialogue: 0,0:14:50.64,0:14:54.89,Default,,0000,0000,0000,,that the reason we haven't had\Nthe transformative impact
Dialogue: 0,0:14:54.89,0:14:56.86,Default,,0000,0000,0000,,on the treatment of illness
Dialogue: 0,0:14:56.86,0:14:59.74,Default,,0000,0000,0000,,is because we don't have\Npowerful enough drugs,
Dialogue: 0,0:14:59.74,0:15:01.50,Default,,0000,0000,0000,,and that's partly true,
Dialogue: 0,0:15:01.50,0:15:05.37,Default,,0000,0000,0000,,but perhaps the real reason is\Nthat we don't have powerful enough
Dialogue: 0,0:15:05.37,0:15:08.44,Default,,0000,0000,0000,,ways of thinking about medicines.
Dialogue: 0,0:15:08.44,0:15:11.20,Default,,0000,0000,0000,,It's certainly true that
Dialogue: 0,0:15:11.20,0:15:14.80,Default,,0000,0000,0000,,it would be lovely to have new medicines,
Dialogue: 0,0:15:14.80,0:15:19.47,Default,,0000,0000,0000,,but perhaps what's really at stake\Nare three more intangible ends:
Dialogue: 0,0:15:19.47,0:15:23.51,Default,,0000,0000,0000,,mechanisms, models, metaphors.
Dialogue: 0,0:15:23.51,0:15:25.43,Default,,0000,0000,0000,,Thank you.
Dialogue: 0,0:15:25.43,0:15:31.52,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:15:33.70,0:15:36.95,Default,,0000,0000,0000,,Chris Anderson: I really\Nlike this metaphor.
Dialogue: 0,0:15:36.95,0:15:40.71,Default,,0000,0000,0000,,How does it link in?\NThere's a lot of talk
Dialogue: 0,0:15:40.71,0:15:43.92,Default,,0000,0000,0000,,in technologyland about\Nthe personalization of medicine,
Dialogue: 0,0:15:43.92,0:15:45.71,Default,,0000,0000,0000,,that we have all this data\Nand that medical treatments of the future
Dialogue: 0,0:15:45.71,0:15:51.89,Default,,0000,0000,0000,,will be for you specifically,\Nyour genome, your current context.
Dialogue: 0,0:15:51.89,0:15:55.67,Default,,0000,0000,0000,,Does that apply to this model\Nyou've got here?
Dialogue: 0,0:15:55.67,0:15:57.35,Default,,0000,0000,0000,,Siddhartha Mukherjee: It's\Na very interesting question.
Dialogue: 0,0:15:57.35,0:16:00.09,Default,,0000,0000,0000,,You know, we've thought\Nabout personalization of medicine
Dialogue: 0,0:16:00.09,0:16:02.39,Default,,0000,0000,0000,,very much in terms of genomics.
Dialogue: 0,0:16:02.39,0:16:05.17,Default,,0000,0000,0000,,That's because the gene\Nis such a dominant metaphor,
Dialogue: 0,0:16:05.17,0:16:08.19,Default,,0000,0000,0000,,again, to use that same word,\Nin medicine today,
Dialogue: 0,0:16:08.19,0:16:11.63,Default,,0000,0000,0000,,that we think the genome will drive\Nthe personalization of medicine.
Dialogue: 0,0:16:11.63,0:16:15.11,Default,,0000,0000,0000,,But of course the genome\Nis just the bottom
Dialogue: 0,0:16:15.11,0:16:17.64,Default,,0000,0000,0000,,of a long chain of being, as it were.
Dialogue: 0,0:16:17.64,0:16:22.50,Default,,0000,0000,0000,,That chain of being, really the first\Norganized unit of that, is the cell.
Dialogue: 0,0:16:22.50,0:16:25.44,Default,,0000,0000,0000,,So, if we are really going to deliver\Nin medicine in this way,
Dialogue: 0,0:16:25.44,0:16:28.35,Default,,0000,0000,0000,,we have to think of personalizing\Ncellular therapies,
Dialogue: 0,0:16:28.35,0:16:31.48,Default,,0000,0000,0000,,and then personalizing\Norgan or organismal therapies,
Dialogue: 0,0:16:31.48,0:16:35.34,Default,,0000,0000,0000,,and ultimately personalizing\Nemersion therapies for the environment.
Dialogue: 0,0:16:35.34,0:16:37.80,Default,,0000,0000,0000,,So I think at every stage, you know,
Dialogue: 0,0:16:37.80,0:16:40.70,Default,,0000,0000,0000,,there's that metaphor,\Nthere's turtles all the way.
Dialogue: 0,0:16:40.70,0:16:43.11,Default,,0000,0000,0000,,Well, in this, there's\Npersonalization all the way.
Dialogue: 0,0:16:43.11,0:16:46.20,Default,,0000,0000,0000,,CA: So when you say\Nmedicine could be a cell
Dialogue: 0,0:16:46.20,0:16:48.22,Default,,0000,0000,0000,,and not a pill,
Dialogue: 0,0:16:48.22,0:16:49.85,Default,,0000,0000,0000,,I mean, you're talking about\Npotentially your own cells.
Dialogue: 0,0:16:49.85,0:16:52.70,Default,,0000,0000,0000,,SM: Absolutely.\NCA: So converted to stem cells,
Dialogue: 0,0:16:52.70,0:16:57.30,Default,,0000,0000,0000,,perhaps tested against all kinds\Nof drugs or something, and prepared.
Dialogue: 0,0:16:57.30,0:16:59.90,Default,,0000,0000,0000,,SM: And there's no perhaps.\NThis is what we're doing.
Dialogue: 0,0:16:59.90,0:17:03.62,Default,,0000,0000,0000,,This is what's happening, and in fact,\Nwe're slowly moving,
Dialogue: 0,0:17:03.62,0:17:07.42,Default,,0000,0000,0000,,not away from genomics,\Nbut incorporating genomics
Dialogue: 0,0:17:07.42,0:17:11.56,Default,,0000,0000,0000,,into what we call multi-order,\Nsemi-autonomous, self-regulating systems,
Dialogue: 0,0:17:11.56,0:17:14.83,Default,,0000,0000,0000,,like cells, like organs,\Nlike environments.
Dialogue: 0,0:17:14.83,0:17:18.19,Default,,0000,0000,0000,,CA: Thank you so much.\NSM: Thank you.