1
00:00:00,741 --> 00:00:02,383
Sleep.

2
00:00:02,383 --> 00:00:05,204
It's something we spend about
a third of our lives doing,

3
00:00:05,204 --> 00:00:08,525
but do any of us really understand what it's all about?

4
00:00:08,525 --> 00:00:10,740
Two thousand years ago, Galen,

5
00:00:10,740 --> 00:00:12,880
one of the most prominent medical researchers

6
00:00:12,880 --> 00:00:13,939
of the ancient world,

7
00:00:13,939 --> 00:00:16,258
proposed that while we're awake,

8
00:00:16,258 --> 00:00:19,620
our brain's motive force, its juice,

9
00:00:19,620 --> 00:00:22,190
would flow out to all the other parts of the body,

10
00:00:22,190 --> 00:00:26,204
animating them but leaving the brain all dried up,

11
00:00:26,204 --> 00:00:27,820
and he thought that when we sleep,

12
00:00:27,820 --> 00:00:30,358
all this moisture that filled the rest of the body

13
00:00:30,358 --> 00:00:32,102
would come rushing back,

14
00:00:32,102 --> 00:00:33,913
rehydrating the brain

15
00:00:33,913 --> 00:00:36,459
and refreshing the mind.

16
00:00:36,459 --> 00:00:38,880
Now, that sounds completely ridiculous to us now,

17
00:00:38,880 --> 00:00:40,921
but Galen was simply trying to explain

18
00:00:40,921 --> 00:00:42,528
something about sleep

19
00:00:42,528 --> 00:00:45,185
that we all deal with every day.

20
00:00:45,185 --> 00:00:47,109
See, we all know based on our own experience

21
00:00:47,109 --> 00:00:49,821
that when you sleep, it clears your mind,

22
00:00:49,821 --> 00:00:51,283
and when you don't sleep,

23
00:00:51,283 --> 00:00:54,210
it leaves your mind murky.

24
00:00:54,210 --> 00:00:56,722
But while we know a great deal more about sleep now

25
00:00:56,722 --> 00:00:58,526
than when Galen was around,

26
00:00:58,526 --> 00:01:01,406
we still haven't understood why it is that sleep,

27
00:01:01,406 --> 00:01:04,035
of all of our activities, has this incredible

28
00:01:04,035 --> 00:01:06,754
restorative function for the mind.

29
00:01:06,754 --> 00:01:08,254
So today I want to tell you about

30
00:01:08,254 --> 00:01:09,610
some recent research

31
00:01:09,610 --> 00:01:12,368
that may shed new light on this question.

32
00:01:12,368 --> 00:01:15,573
We've found that sleep may actually be

33
00:01:15,573 --> 00:01:17,946
a kind of elegant design solution

34
00:01:17,946 --> 00:01:20,523
to some of the brain's most basic needs,

35
00:01:20,523 --> 00:01:22,469
a unique way that the brain

36
00:01:22,469 --> 00:01:25,292
meets the high demands and the narrow margins

37
00:01:25,292 --> 00:01:30,291
that set it apart from all the other organs of the body.

38
00:01:30,291 --> 00:01:33,346
So almost all the biology that we observe

39
00:01:33,346 --> 00:01:35,800
can be thought of as a series of problems

40
00:01:35,800 --> 00:01:37,841
and their corresponding solutions,

41
00:01:37,841 --> 00:01:41,321
and the first problem that every organ must solve

42
00:01:41,321 --> 00:01:43,819
is a continuous supply of nutrients to fuel

43
00:01:43,819 --> 00:01:45,560
all those cells of the body.

44
00:01:45,560 --> 00:01:48,138
In the brain, that is especially critical;

45
00:01:48,138 --> 00:01:50,355
its intense electrical activity uses up

46
00:01:50,355 --> 00:01:53,213
a quarter of the body's entire energy supply,

47
00:01:53,213 --> 00:01:54,843
even though the brain accounts

48
00:01:54,843 --> 00:01:58,180
for only about two percent of the body's mass.

49
00:01:58,180 --> 00:01:59,792
So the circulatory system

50
00:01:59,792 --> 00:02:02,223
solves the nutrient delivery problem

51
00:02:02,223 --> 00:02:04,763
by sending blood vessels to supply nutrients

52
00:02:04,763 --> 00:02:08,106
and oxygen to every corner of our body.

53
00:02:08,106 --> 00:02:11,120
You can actually see it in this video here.

54
00:02:11,120 --> 00:02:12,702
Here, we're imaging blood vessels

55
00:02:12,702 --> 00:02:15,597
in the brain of a living mouse.

56
00:02:15,597 --> 00:02:18,117
The blood vessels form a complex network

57
00:02:18,117 --> 00:02:20,465
that fills the entire brain volume.

58
00:02:20,465 --> 00:02:22,266
They start at the surface of the brain,

59
00:02:22,266 --> 00:02:25,147
and then they dive down into the tissue itself,

60
00:02:25,147 --> 00:02:27,508
and as they spread out, they supply nutrients

61
00:02:27,508 --> 00:02:33,273
and oxygen to each and every cell in the brain.

62
00:02:33,276 --> 00:02:36,246
Now, just as every cell requires

63
00:02:36,246 --> 00:02:38,137
nutrients to fuel it,

64
00:02:38,137 --> 00:02:41,277
every cell also produces waste as a byproduct,

65
00:02:41,277 --> 00:02:42,823
and the clearance of that waste

66
00:02:42,823 --> 00:02:45,090
is the second basic problem

67
00:02:45,090 --> 00:02:47,882
that each organ has to solve.

68
00:02:47,882 --> 00:02:50,465
This diagram shows the body's lymphatic system,

69
00:02:50,465 --> 00:02:52,895
which has evolved to meet this need.

70
00:02:52,895 --> 00:02:55,707
It's a second parallel network of vessels

71
00:02:55,707 --> 00:02:57,721
that extends throughout the body.

72
00:02:57,721 --> 00:02:59,678
It takes up proteins and other waste

73
00:02:59,678 --> 00:03:01,602
from the spaces between the cells,

74
00:03:01,602 --> 00:03:04,414
it collects them, and then dumps them into the blood

75
00:03:04,414 --> 00:03:06,675
so they can be disposed of.

76
00:03:06,675 --> 00:03:08,464
But if you look really closely at this diagram,

77
00:03:08,464 --> 00:03:09,858
you'll see something

78
00:03:09,858 --> 00:03:12,186
that doesn't make a lot of sense.

79
00:03:12,186 --> 00:03:14,943
So if we were to zoom into this guy's head,

80
00:03:14,943 --> 00:03:17,136
one of the things that you would see there

81
00:03:17,136 --> 00:03:21,298
is that there are no lymphatic vessels in the brain.

82
00:03:21,298 --> 00:03:24,392
But that doesn't make a lot of sense, does it?

83
00:03:24,392 --> 00:03:27,597
I mean, the brain is this intensely active organ

84
00:03:27,597 --> 00:03:30,162
that produces a correspondingly
large amount of waste

85
00:03:30,162 --> 00:03:32,739
that must be efficiently cleared.

86
00:03:32,739 --> 00:03:35,701
And yet, it lacks lymphatic vessels, which means that

87
00:03:35,701 --> 00:03:37,497
the approach that the rest of the body takes

88
00:03:37,497 --> 00:03:39,482
to clearing away its waste

89
00:03:39,482 --> 00:03:42,491
won't work in the brain.

90
00:03:42,491 --> 00:03:44,539
So how, then, does the brain solve

91
00:03:44,539 --> 00:03:46,293
its waste clearance problem?

92
00:03:46,293 --> 00:03:49,982
Well, that seemingly mundane question

93
00:03:49,982 --> 00:03:53,390
is where our group first jumped into this story,

94
00:03:53,390 --> 00:03:55,411
and what we found

95
00:03:55,411 --> 00:03:57,746
as we dove down into the brain,

96
00:03:57,746 --> 00:04:00,637
down among the neurons and the blood vessels,

97
00:04:00,637 --> 00:04:02,820
was that the brain's solution

98
00:04:02,820 --> 00:04:05,383
to the problem of waste clearance,

99
00:04:05,383 --> 00:04:07,200
it was really unexpected.

100
00:04:07,200 --> 00:04:10,050
It was ingenious,

101
00:04:10,050 --> 00:04:13,168
but it was also beautiful.

102
00:04:13,168 --> 00:04:14,835
Let me tell you about what we found.

103
00:04:14,835 --> 00:04:17,389
So the brain has this large pool

104
00:04:17,389 --> 00:04:20,850
of clean, clear fluid called cerebrospinal fluid.

105
00:04:20,850 --> 00:04:22,169
We call it the CSF.

106
00:04:22,169 --> 00:04:26,149
The CSF fills the space that surrounds the brain,

107
00:04:26,149 --> 00:04:27,672
and wastes from inside the brain

108
00:04:27,672 --> 00:04:29,894
make their way out to the CSF,

109
00:04:29,894 --> 00:04:33,157
which gets dumped, along with 
the waste, into the blood.

110
00:04:33,157 --> 00:04:34,277
So in that way, it sounds a lot like

111
00:04:34,277 --> 00:04:36,869
the lymphatic system, doesn't it?

112
00:04:36,869 --> 00:04:39,625
But what's interesting is that the fluid and the waste

113
00:04:39,625 --> 00:04:41,357
from inside the brain,

114
00:04:41,357 --> 00:04:43,764
they don't just percolate their way randomly

115
00:04:43,764 --> 00:04:46,138
out to these pools of CSF.

116
00:04:46,138 --> 00:04:49,861
Instead, there is a specialized network of plumbing

117
00:04:49,861 --> 00:04:53,753
that organizes and facilitates this process.

118
00:04:53,753 --> 00:04:55,902
You can see that in these videos.

119
00:04:55,902 --> 00:04:58,940
Here, we're again imaging into the brain

120
00:04:58,940 --> 00:05:00,424
of living mice.

121
00:05:00,424 --> 00:05:02,347
The frame on your left shows

122
00:05:02,347 --> 00:05:04,406
what's happening at the brain's surface,

123
00:05:04,406 --> 00:05:05,970
and the frame on your right shows

124
00:05:05,970 --> 00:05:07,916
what's happening down below the surface of the brain

125
00:05:07,916 --> 00:05:09,639
within the tissue itself.

126
00:05:09,639 --> 00:05:11,898
We've labeled the blood vessels in red,

127
00:05:11,898 --> 00:05:13,922
and the CSF that's surrounding the brain

128
00:05:13,922 --> 00:05:15,745
will be in green.

129
00:05:15,745 --> 00:05:17,545
Now, what was surprising to us

130
00:05:17,545 --> 00:05:20,796
was that the fluid on the outside of the brain,

131
00:05:20,796 --> 00:05:23,608
it didn't stay on the outside.

132
00:05:23,608 --> 00:05:27,011
Instead, the CSF was pumped back into

133
00:05:27,011 --> 00:05:28,884
and through the brain

134
00:05:28,884 --> 00:05:31,916
along the outsides of the blood vessels,

135
00:05:31,916 --> 00:05:34,300
and as it flushed down into the brain

136
00:05:34,300 --> 00:05:36,100
along the outsides of these vessels,

137
00:05:36,100 --> 00:05:38,912
it was actually helping to clear away,

138
00:05:38,912 --> 00:05:41,353
to clean the waste from the spaces

139
00:05:41,353 --> 00:05:44,199
between the brain's cells.

140
00:05:44,199 --> 00:05:46,111
If you think about it,

141
00:05:46,111 --> 00:05:49,588
using the outsides of these blood vessels like this

142
00:05:49,588 --> 00:05:52,107
is a really clever design solution,

143
00:05:52,107 --> 00:05:54,829
because the brain is enclosed

144
00:05:54,829 --> 00:05:56,652
in a rigid skull

145
00:05:56,652 --> 00:05:58,755
and it's packed full of cells,

146
00:05:58,755 --> 00:06:01,500
so there is no extra space inside it

147
00:06:01,500 --> 00:06:05,100
for a whole second set of vessels
like the lymphatic system.

148
00:06:05,100 --> 00:06:06,359
Yet the blood vessels,

149
00:06:06,359 --> 00:06:08,317
they extend from the surface of the brain

150
00:06:08,317 --> 00:06:10,926
down to reach every single cell in the brain,

151
00:06:10,926 --> 00:06:12,164
which means that fluid

152
00:06:12,164 --> 00:06:15,460
that's traveling along the outsides of these vessels

153
00:06:15,460 --> 00:06:19,260
can gain easy access to the entire brain's volume,

154
00:06:19,260 --> 00:06:21,444
so it's actually this really clever way

155
00:06:21,444 --> 00:06:25,209
to repurpose one set of vessels, the blood vessels,

156
00:06:25,209 --> 00:06:27,998
to take over and replace the function

157
00:06:27,998 --> 00:06:31,181
of a second set of vessels, the lymphatic vessels,

158
00:06:31,181 --> 00:06:33,592
to make it so you don't need them.

159
00:06:33,592 --> 00:06:35,909
And what's amazing is that no other organ

160
00:06:35,909 --> 00:06:37,550
takes quite this approach

161
00:06:37,550 --> 00:06:40,610
to clearing away the waste from between its cells.

162
00:06:40,610 --> 00:06:46,430
This is a solution that is entirely unique to the brain.

163
00:06:46,430 --> 00:06:48,698
But our most surprising finding

164
00:06:48,698 --> 00:06:50,801
was that all of this,

165
00:06:50,801 --> 00:06:53,151
everything I just told you about,

166
00:06:53,151 --> 00:06:56,469
with all this fluid rushing through the brain,

167
00:06:56,469 --> 00:07:00,653
it's only happening in the sleeping brain.

168
00:07:00,653 --> 00:07:02,103
Here, the video on the left

169
00:07:02,103 --> 00:07:04,364
shows how much of the CSF is moving

170
00:07:04,364 --> 00:07:07,970
through the brain of a living mouse while it's awake.

171
00:07:07,970 --> 00:07:09,843
It's almost nothing.

172
00:07:09,843 --> 00:07:11,418
Yet in the same animal,

173
00:07:11,418 --> 00:07:14,623
if we wait just a little while until it's gone to sleep,

174
00:07:14,623 --> 00:07:17,380
what we see is that the CSF

175
00:07:17,380 --> 00:07:19,798
is rushing through the brain,

176
00:07:19,798 --> 00:07:21,958
and we discovered that at the same time

177
00:07:21,958 --> 00:07:24,570
when the brain goes to sleep,

178
00:07:24,570 --> 00:07:27,233
the brain cells themselves seem to shrink,

179
00:07:27,233 --> 00:07:29,270
opening up spaces in between them,

180
00:07:29,270 --> 00:07:31,407
allowing fluid to rush through

181
00:07:31,407 --> 00:07:34,140
and allowing waste to be cleared out.

182
00:07:34,140 --> 00:07:36,654
So it seems that Galen may actually have been

183
00:07:36,654 --> 00:07:38,910
sort of on the right track when he wrote about

184
00:07:38,910 --> 00:07:41,610
fluid rushing through the brain

185
00:07:41,610 --> 00:07:43,252
when sleep came on.

186
00:07:43,252 --> 00:07:46,705
Our own research, now it's 2,000 years later,

187
00:07:46,705 --> 00:07:48,775
suggests that what's happening is that

188
00:07:48,775 --> 00:07:50,834
when the brain is awake

189
00:07:50,834 --> 00:07:52,948
and is at its most busy,

190
00:07:52,948 --> 00:07:55,310
it puts off clearing away the waste

191
00:07:55,310 --> 00:07:58,381
from the spaces between its cells until later,

192
00:07:58,381 --> 00:08:00,240
and then, when it goes to sleep

193
00:08:00,240 --> 00:08:02,588
and doesn't have to be as busy,

194
00:08:02,588 --> 00:08:05,165
it shifts into a kind of cleaning mode

195
00:08:05,165 --> 00:08:06,852
to clear away the waste

196
00:08:06,852 --> 00:08:08,360
from the spaces between its cells,

197
00:08:08,360 --> 00:08:10,777
the waste that's accumulated throughout the day.

198
00:08:10,777 --> 00:08:13,185
So it's actually a little bit like how you or I,

199
00:08:13,185 --> 00:08:16,267
we put off our household chores during the work week

200
00:08:16,267 --> 00:08:17,729
when we don't have time to get to it,

201
00:08:17,729 --> 00:08:20,990
and then we play catch up on all
the cleaning that we have to do

202
00:08:20,990 --> 00:08:23,748
when the weekend rolls around.

203
00:08:23,748 --> 00:08:27,020
Now, I've just talked a lot about waste clearance,

204
00:08:27,020 --> 00:08:28,472
but I haven't been very specific

205
00:08:28,472 --> 00:08:29,866
about the kinds of waste

206
00:08:29,866 --> 00:08:32,161
that the brain needs to be clearing

207
00:08:32,161 --> 00:08:34,704
during sleep in order to stay healthy.

208
00:08:34,704 --> 00:08:36,301
The waste product that these recent studies

209
00:08:36,301 --> 00:08:38,719
focused most on is amyloid-beta,

210
00:08:38,719 --> 00:08:41,914
which is a protein that's made
in the brain all the time.

211
00:08:41,914 --> 00:08:43,772
My brain's making amyloid-beta right now,

212
00:08:43,772 --> 00:08:45,930
and so is yours.

213
00:08:45,930 --> 00:08:47,932
But in patients with Alzheimer's disease,

214
00:08:47,932 --> 00:08:50,531
amyloid-beta builds up and aggregates

215
00:08:50,531 --> 00:08:52,544
in the spaces between the brain's cells,

216
00:08:52,544 --> 00:08:55,970
instead of being cleared away 
like it's supposed to be,

217
00:08:55,970 --> 00:08:57,980
and it's this buildup of amyloid-beta

218
00:08:57,980 --> 00:09:00,193
that's thought to be one of the key steps

219
00:09:00,193 --> 00:09:02,814
in the development of that terrible disease.

220
00:09:02,814 --> 00:09:05,908
So we measured how fast amyloid-beta is cleared

221
00:09:05,908 --> 00:09:07,640
from the brain when it's awake

222
00:09:07,640 --> 00:09:09,418
versus when it's asleep,

223
00:09:09,418 --> 00:09:11,296
and we found that indeed,

224
00:09:11,296 --> 00:09:13,186
the clearance of amyloid-beta

225
00:09:13,186 --> 00:09:17,705
is much more rapid from the sleeping brain.

226
00:09:17,705 --> 00:09:19,384
So if sleep, then,

227
00:09:19,384 --> 00:09:21,342
is part of the brain's solution

228
00:09:21,342 --> 00:09:23,352
to the problem of waste clearance,

229
00:09:23,352 --> 00:09:25,728
then this may dramatically change how we think

230
00:09:25,728 --> 00:09:27,963
about the relationship between sleep,

231
00:09:27,963 --> 00:09:31,319
amyloid-beta, and Alzheimer's disease.

232
00:09:31,319 --> 00:09:33,277
A series of recent clinical studies

233
00:09:33,277 --> 00:09:35,110
suggest that among patients

234
00:09:35,110 --> 00:09:38,204
who haven't yet developed Alzheimer's disease,

235
00:09:38,204 --> 00:09:41,270
worsening sleep quality and sleep duration

236
00:09:41,270 --> 00:09:43,288
are associated with a greater amount

237
00:09:43,288 --> 00:09:46,100
of amyloid-beta building up in the brain,

238
00:09:46,100 --> 00:09:47,967
and while it's important to point out

239
00:09:47,967 --> 00:09:49,677
that these studies don't prove

240
00:09:49,677 --> 00:09:51,866
that lack of sleep or poor sleep

241
00:09:51,866 --> 00:09:54,273
cause Alzheimer's disease,

242
00:09:54,273 --> 00:09:56,883
they do suggest that the failure of the brain

243
00:09:56,883 --> 00:09:58,795
to keep its house clean

244
00:09:58,795 --> 00:10:01,551
by clearing away waste like amyloid-beta

245
00:10:01,551 --> 00:10:03,453
may contribute to the development

246
00:10:03,453 --> 00:10:07,070
of conditions like Alzheimer's.

247
00:10:07,070 --> 00:10:08,975
So what this new research tells us, then,

248
00:10:08,975 --> 00:10:11,302
is that the one thing that all of you

249
00:10:11,302 --> 00:10:12,710
already knew about sleep,

250
00:10:12,710 --> 00:10:15,363
that even Galen understood about sleep,

251
00:10:15,363 --> 00:10:18,434
that it refreshes and clears the mind,

252
00:10:18,434 --> 00:10:19,975
may actually be a big part

253
00:10:19,975 --> 00:10:22,292
of what sleep is all about.

254
00:10:22,292 --> 00:10:23,810
See, you and I, we go to sleep

255
00:10:23,810 --> 00:10:25,543
every single night,

256
00:10:25,543 --> 00:10:28,546
but our brains, they never rest.

257
00:10:28,546 --> 00:10:30,380
While our body is still

258
00:10:30,380 --> 00:10:33,451
and our mind is off walking in dreams somewhere,

259
00:10:33,451 --> 00:10:35,127
the elegant machinery of the brain

260
00:10:35,127 --> 00:10:37,107
is quietly hard at work

261
00:10:37,107 --> 00:10:39,300
cleaning and maintaining

262
00:10:39,300 --> 00:10:42,135
this unimaginably complex machine.

263
00:10:42,135 --> 00:10:43,176
Like our housework,

264
00:10:43,176 --> 00:10:45,925
it's a dirty and a thankless job,

265
00:10:45,925 --> 00:10:48,180
but it's also important.

266
00:10:48,180 --> 00:10:50,583
In your house, if you stop cleaning your kitchen

267
00:10:50,583 --> 00:10:52,491
for a month,

268
00:10:52,491 --> 00:10:54,930
your home will become completely unlivable

269
00:10:54,930 --> 00:10:56,537
very quickly.

270
00:10:56,537 --> 00:10:58,625
But in the brain, the consequences

271
00:10:58,625 --> 00:11:01,556
of falling behind may be much greater

272
00:11:01,556 --> 00:11:04,284
than the embarrassment of dirty countertops,

273
00:11:04,284 --> 00:11:06,848
because when it comes to cleaning the brain,

274
00:11:06,848 --> 00:11:09,224
it is the very health and function

275
00:11:09,224 --> 00:11:12,169
of the mind and the body that's at stake,

276
00:11:12,169 --> 00:11:14,410
which is why understanding these

277
00:11:14,410 --> 00:11:18,682
very basic housekeeping functions of the brain today

278
00:11:18,682 --> 00:11:21,675
may be critical for preventing and treating

279
00:11:21,675 --> 00:11:24,703
diseases of the mind tomorrow.

280
00:11:24,703 --> 00:11:26,751
Thank you.

281
00:11:26,751 --> 00:11:28,518
(Applause)