Mina Bissell: Experiments that point to a new understanding of cancer

103,231 views ・ 2012-07-16

TED


Please double-click on the English subtitles below to play the video.

00:00
Translator: Morton Bast Reviewer: Thu-Huong Ha
0
0
7000
00:15
Now, I don't usually like cartoons,
1
15692
2722
00:18
I don't think many of them are funny,
2
18414
2510
00:20
I find them weird. But I love this cartoon from the New Yorker.
3
20924
5223
00:26
(Text: Never, ever think outside the box.) (Laughter)
4
26147
2612
00:28
So, the guy is telling the cat,
5
28759
2469
00:31
don't you dare think outside the box.
6
31228
5371
00:36
Well, I'm afraid I used to be the cat.
7
36599
3307
00:39
I always wanted to be outside the box.
8
39906
3058
00:42
And it's partly because I came to this field
9
42964
3482
00:46
from a different background, chemist and a bacterial geneticist.
10
46446
5213
00:51
So, what people were saying to me
11
51659
2602
00:54
about the cause of cancer, sources of cancer,
12
54261
3191
00:57
or, for that matter, why you are who you are,
13
57452
3081
01:00
didn't make sense.
14
60533
1874
01:02
So, let me quickly try and tell you why I thought that
15
62407
3047
01:05
and how I went about it.
16
65454
2601
01:08
So, to begin with, however,
17
68055
2432
01:10
I have to give you a very, very quick lesson
18
70487
4426
01:14
in developmental biology,
19
74913
1767
01:16
with apologies to those of you who know some biology.
20
76680
4062
01:20
So, when your mom and dad met,
21
80742
3014
01:23
there is a fertilized egg,
22
83756
2674
01:26
that round thing with that little blip.
23
86430
2121
01:28
It grows and then it grows,
24
88551
3055
01:31
and then it makes this handsome man.
25
91606
4153
01:35
(Applause)
26
95759
1415
01:37
So, this guy, with all the cells in his body,
27
97174
5658
01:42
all have the same genetic information.
28
102832
4212
01:47
So how did his nose become his nose, his elbow his elbow,
29
107044
4375
01:51
and why doesn't he get up one morning
30
111419
2176
01:53
and have his nose turn into his foot?
31
113595
2560
01:56
It could. It has the genetic information.
32
116155
3240
01:59
You all remember, dolly,
33
119395
1208
02:00
it came from a single mammary cell.
34
120603
2681
02:03
So, why doesn't it do it?
35
123284
1934
02:05
So, have a guess of how many cells he has in his body.
36
125218
5503
02:10
Somewhere between 10 trillion to 70 trillion cells in his body.
37
130721
7402
02:18
Trillion!
38
138123
1640
02:19
Now, how did these cells, all with the same genetic material,
39
139763
4638
02:24
make all those tissues?
40
144401
2208
02:26
And so, the question I raised before
41
146609
3144
02:29
becomes even more interesting if you thought about
42
149753
3614
02:33
the enormity of this in every one of your bodies.
43
153367
4586
02:37
Now, the dominant cancer theory would say
44
157953
3000
02:40
that there is a single oncogene
45
160953
2312
02:43
in a single cancer cell, and it would make you
46
163265
3704
02:46
a cancer victim.
47
166969
2649
02:49
Well, this did not make sense to me.
48
169618
3666
02:53
Do you even know how a trillion looks?
49
173284
3182
02:56
Now, let's look at it.
50
176466
1719
02:58
There it comes, these zeroes after zeroes after zeroes.
51
178185
5041
03:03
Now, if .0001 of these cells got mutated,
52
183226
6818
03:10
and .00001 got cancer, you will be a lump of cancer.
53
190044
5257
03:15
You will have cancer all over you. And you're not.
54
195301
2296
03:17
Why not?
55
197597
2309
03:19
So, I decided over the years,
56
199906
3722
03:23
because of a series of experiments
57
203628
1928
03:25
that this is because of context and architecture.
58
205556
4880
03:30
And let me quickly tell you
59
210436
2177
03:32
some crucial experiment that was able to actually show this.
60
212613
3927
03:36
To begin with, I came to work with this virus
61
216540
3911
03:40
that causes that ugly tumor in the chicken.
62
220451
3393
03:43
Rous discovered this in 1911.
63
223844
3360
03:47
It was the first cancer virus discovered,
64
227204
3565
03:50
and when I call it "oncogene," meaning "cancer gene."
65
230769
4891
03:55
So, he made a filtrate, he took this filter
66
235660
2912
03:58
which was the liquid after he passed the tumor through a filter,
67
238572
4256
04:02
and he injected it to another chicken, and he got another tumor.
68
242828
4001
04:06
So, scientists were very excited,
69
246829
2711
04:09
and they said, a single oncogene can do it.
70
249540
2168
04:11
All you need is a single oncogene.
71
251708
2296
04:14
So, they put the cells in cultures, chicken cells,
72
254004
2895
04:16
dumped the virus on it,
73
256899
2035
04:18
and it would pile up,
74
258934
1449
04:20
and they would say, this is malignant and this is normal.
75
260383
3021
04:23
And again this didn't make sense to me.
76
263404
2018
04:25
So for various reasons, we took this oncogene,
77
265422
3286
04:28
attached it to a blue marker,
78
268708
2312
04:31
and we injected it into the embryos.
79
271020
3008
04:34
Now look at that. There is that beautiful feather in the embryo.
80
274028
4193
04:38
Every one of those blue cells are a cancer gene
81
278221
4279
04:42
inside a cancer cell, and they're part of the feather.
82
282500
4416
04:46
So, when we dissociated the feather and put it in a dish,
83
286916
4600
04:51
we got a mass of blue cells.
84
291516
2712
04:54
So, in the chicken you get a tumor,
85
294228
1466
04:55
in the embryo you don't,
86
295694
1704
04:57
you dissociate, you put it in a dish, you get another tumor.
87
297398
3992
05:01
What does that mean?
88
301390
1223
05:02
That means that microenvironment
89
302613
2984
05:05
and the context which surrounds those cells
90
305597
4009
05:09
actually are telling the cancer gene and the cancer cell what to do.
91
309606
6927
05:16
Now, let's take a normal example.
92
316533
3312
05:19
The normal example, let's take the human mammary gland.
93
319845
3185
05:23
I work on breast cancer.
94
323030
1480
05:24
So, here is a lovely human breast.
95
324510
3007
05:27
And many of you know how it looks,
96
327517
1948
05:29
except that inside that breast, there are all these
97
329465
2853
05:32
pretty, developing, tree-like structures.
98
332318
3377
05:35
So, we decided that what we like to do
99
335695
2898
05:38
is take just a bit of that mammary gland,
100
338593
2960
05:41
which is called an "acinus,"
101
341553
2032
05:43
where there are all these little things inside the breast
102
343585
3641
05:47
where the milk goes, and the end of the nipple
103
347226
3543
05:50
comes through that little tube when the baby sucks.
104
350769
3544
05:54
And we said, wonderful! Look at this pretty structure.
105
354313
3407
05:57
We want to make this a structure, and ask the question,
106
357720
3769
06:01
how do the cells do that?
107
361489
1704
06:03
So, we took the red cells --
108
363193
1792
06:04
you see the red cells are surrounded by blue,
109
364985
3248
06:08
other cells that squeeze them, and behind it
110
368233
3329
06:11
is material that people thought was mainly inert,
111
371562
3718
06:15
and it was just having a structure to keep the shape,
112
375280
3597
06:18
and so we first photographed it
113
378877
2928
06:21
with the electron microscope years and years ago,
114
381805
2768
06:24
and you see this cell is actually quite pretty.
115
384573
3056
06:27
It has a bottom, it has a top,
116
387629
2463
06:30
it is secreting gobs and gobs of milk,
117
390092
2681
06:32
because it just came from an early pregnant mouse.
118
392773
3192
06:35
You take these cells, you put them in a dish,
119
395965
2327
06:38
and within three days, they look like that.
120
398292
3345
06:41
They completely forget.
121
401637
3160
06:44
So you take them out, you put them in a dish,
122
404797
2800
06:47
they don't make milk. They completely forget.
123
407597
2663
06:50
For example, here is a lovely yellow droplet of milk
124
410260
4899
06:55
on the left, there is nothing on the right.
125
415159
2255
06:57
Look at the nuclei. The nuclei in the cell on the left
126
417414
3729
07:01
is in the animal, the one on the right is in a dish.
127
421143
3496
07:04
They are completely different from each other.
128
424639
2736
07:07
So, what does this tell you?
129
427375
2025
07:09
This tells you that here also, context overrides.
130
429400
4967
07:14
In different contexts, cells do different things.
131
434367
3385
07:17
But how does context signal?
132
437752
2745
07:20
So, Einstein said that
133
440497
2542
07:23
"For an idea that does not first seem insane, there is no hope."
134
443039
6653
07:29
So, you can imagine the amount of skepticism
135
449692
5960
07:35
I received -- couldn't get money,
136
455652
2401
07:38
couldn't do a whole lot of other things,
137
458053
1943
07:39
but I'm so glad it all worked out.
138
459996
1729
07:41
So, we made a section of the mammary gland of the mouse,
139
461725
3815
07:45
and all those lovely acini are there,
140
465540
3183
07:48
every one of those with the red around them are an acinus,
141
468723
4211
07:52
and we said okay, we are going to try and make this,
142
472934
3694
07:56
and I said, maybe that red stuff
143
476628
3232
07:59
around the acinus that people think there's just a structural scaffold,
144
479860
5125
08:04
maybe it has information,
145
484985
1940
08:06
maybe it tells the cells what to do, maybe it tells the nucleus what to do.
146
486925
4566
08:11
So I said, extracellular matrix, which is this stuff
147
491491
4283
08:15
called ECM, signals and actually tells the cells what to do.
148
495774
4391
08:20
So, we decided to make things that would look like that.
149
500165
3767
08:23
We found some gooey material
150
503932
2880
08:26
that had the right extracellular matrix in it,
151
506812
2875
08:29
we put the cells in it, and lo and behold,
152
509687
2539
08:32
in about four days, they got reorganized
153
512226
2821
08:35
and on the right, is what we can make in culture.
154
515047
3408
08:38
On the left is what's inside the animal, we call it in vivo,
155
518455
4496
08:42
and the one in culture was full of milk,
156
522951
2584
08:45
the lovely red there is full of milk.
157
525535
2800
08:48
So, we Got Milk, for the American audience.
158
528335
3416
08:51
All right. And here is this beautiful human cell,
159
531751
5344
08:57
and you can imagine that here also, context goes.
160
537095
4946
09:02
So, what do we do now?
161
542041
2716
09:04
I made a radical hypothesis.
162
544757
2224
09:06
I said, if it's true that architecture is dominant,
163
546981
6663
09:13
architecture restored to a cancer cell
164
553644
4486
09:18
should make the cancer cell think it's normal.
165
558130
2989
09:21
Could this be done?
166
561119
1484
09:22
So, we tried it.
167
562603
2528
09:25
In order to do that, however,
168
565131
2038
09:27
we needed to have a method of distinguishing normal from malignant,
169
567169
4885
09:32
and on the left is the single normal cell,
170
572054
3997
09:36
human breast, put in three-dimensional gooey gel
171
576051
3963
09:40
that has extracellular matrix, it makes all these beautiful structures.
172
580014
3864
09:43
On the right, you see it looks very ugly,
173
583878
2888
09:46
the cells continue to grow,
174
586766
1648
09:48
the normal ones stop.
175
588414
1576
09:49
And you see here in higher magnification
176
589990
2832
09:52
the normal acinus and the ugly tumor.
177
592822
4352
09:57
So we said, what is on the surface of these ugly tumors?
178
597174
4224
10:01
Could we calm them down --
179
601398
2168
10:03
they were signaling like crazy and they have pathways all messed up --
180
603566
4920
10:08
and make them to the level of the normal?
181
608486
3064
10:11
Well, it was wonderful. Boggles my mind.
182
611550
4720
10:16
This is what we got.
183
616270
2161
10:18
We can revert the malignant phenotype.
184
618431
3679
10:22
(Applause)
185
622110
2568
10:24
And in order to show you that the malignant phenotype
186
624678
3112
10:27
I didn't just choose one,
187
627790
1718
10:29
here are little movies, sort of fuzzy,
188
629508
2770
10:32
but you see that on the left are the malignant cells,
189
632278
3656
10:35
all of them are malignant,
190
635934
1344
10:37
we add one single inhibitor in the beginning,
191
637278
4800
10:42
and look what happens, they all look like that.
192
642078
3457
10:45
We inject them into the mouse, the ones on the right,
193
645535
3447
10:48
and none of them would make tumors.
194
648982
2240
10:51
We inject the other ones in the mouse, 100 percent tumors.
195
651222
3536
10:54
So, it's a new way of thinking about cancer,
196
654758
2672
10:57
it's a hopeful way of thinking about cancer.
197
657430
2400
10:59
We should be able to be dealing with these things at this level,
198
659830
3976
11:03
and these conclusions say that growth and malignant behavior
199
663806
5912
11:09
is regulated at the level of tissue organization
200
669718
3872
11:13
and that the tissue organization is dependent
201
673590
3992
11:17
on the extracellular matrix and the microenvironment.
202
677582
3696
11:21
All right, thus form and function interact dynamically and reciprocally.
203
681278
7631
11:28
And here is another five seconds of repose,
204
688909
4120
11:33
is my mantra. Form and function.
205
693029
4422
11:37
And of course, we now ask, where do we go now?
206
697451
3646
11:41
We'd like to take this kind of thinking into the clinic.
207
701097
2995
11:44
But before we do that, I'd like you to think
208
704092
3924
11:48
that at any given time when you're sitting there,
209
708016
3588
11:51
in your 70 trillion cells,
210
711604
3013
11:54
the extracellular matrix signaling to your nucleus,
211
714617
3473
11:58
the nucleus is signaling to your extracellular matrix
212
718090
3078
12:01
and this is how your balance is kept and restored.
213
721168
5994
12:07
We have made a lot of discoveries,
214
727162
2215
12:09
we have shown that extracellular matrix talks to chromatin.
215
729377
3088
12:12
We have shown that there's little pieces of DNA
216
732465
3447
12:15
on the specific genes of the mammary gland
217
735912
3823
12:19
that actually respond to extracellular matrix.
218
739735
2864
12:22
It has taken many years, but it has been very rewarding.
219
742599
3697
12:26
And before I get to the next slide, I have to tell you
220
746296
4391
12:30
that there are so many additional discoveries to be made.
221
750687
5112
12:35
There is so much mystery we don't know.
222
755799
2528
12:38
And I always say to the students and post-docs I lecture to,
223
758327
4361
12:42
don't be arrogant, because arrogance kills curiosity.
224
762688
5663
12:48
Curiosity and passion.
225
768351
2192
12:50
You need to always think, what else needs to be discovered?
226
770543
3897
12:54
And maybe my discovery needs to be added to
227
774440
2975
12:57
or maybe it needs to be changed.
228
777415
1792
12:59
So, we have now made an amazing discovery,
229
779207
3504
13:02
a post-doc in the lab who is a physicist asked me,
230
782711
3104
13:05
what do the cells do when you put them in?
231
785815
2177
13:07
What do they do in the beginning when they do?
232
787992
3294
13:11
I said, I don't know, we couldn't look at them.
233
791286
1481
13:12
We didn't have high images in the old days.
234
792767
2593
13:15
So she, being an imager and a physicist,
235
795360
2695
13:18
did this incredible thing.
236
798055
1744
13:19
This is a single human breast cell in three dimensions.
237
799799
4376
13:24
Look at it. It's constantly doing this.
238
804175
2528
13:26
Has a coherent movement.
239
806703
2096
13:28
You put the cancer cells there, and they do go all over,
240
808799
4334
13:33
they do this. They don't do this.
241
813133
1904
13:35
And when we revert the cancer cell, it again does this.
242
815037
4008
13:39
Absolutely boggles my mind.
243
819045
2184
13:41
So the cell acts like an embryo. What an exciting thing.
244
821229
5344
13:46
So I'd like to finish with a poem.
245
826573
2856
13:49
Well I used to love English literature,
246
829429
3064
13:52
and I debated in college, which one should I do?
247
832493
2607
13:55
And unfortunately or fortunately, chemistry won.
248
835100
4612
13:59
But here is a poem from Yeats. I'll just read you the last two lines.
249
839712
5724
14:05
It's called "Among the School Children."
250
845436
2659
14:08
"O body swayed to music / O brightening glance /
251
848095
4521
14:12
How [can we know] the dancer from the dance?"
252
852616
3150
14:15
And here is Merce Cunningham,
253
855766
1911
14:17
I was fortunate to dance with him when I was younger,
254
857677
2984
14:20
and here he is a dancer,
255
860661
2193
14:22
and while he is dancing, he is both the dancer and the dance.
256
862854
3304
14:26
The minute he stops, we have neither.
257
866158
3701
14:29
So it's like form and function.
258
869859
3474
14:33
Now, I'd like to show you a current picture of my group.
259
873333
5779
14:39
I have been fortunate to have had these magnificant
260
879112
3528
14:42
students and post-docs who have taught me so much,
261
882640
3224
14:45
and I have had many of these groups come and go.
262
885864
3263
14:49
They are the future and I try to make them not be afraid
263
889127
4577
14:53
of being the cat and being told,
264
893704
3703
14:57
don't think outside the box.
265
897407
1593
14:59
And I'd like to leave you with this thought.
266
899000
2495
15:01
On the left is water coming through the shore,
267
901495
4745
15:06
taken from a NASA satellite.
268
906240
1895
15:08
On the right, there is a coral.
269
908135
3049
15:11
Now if you take the mammary gland and spread it
270
911184
4002
15:15
and take the fat away, on a dish it looks like that.
271
915186
3445
15:18
Do they look the same? Do they have the same patterns?
272
918631
3352
15:21
Why is it that nature keeps doing that over and over again?
273
921983
3952
15:25
And I'd like to submit to you
274
925935
2360
15:28
that we have sequenced the human genome,
275
928295
2177
15:30
we know everything about the sequence of the gene,
276
930472
2880
15:33
the language of the gene, the alphabet of the gene,
277
933352
2431
15:35
But we know nothing, but nothing,
278
935783
3239
15:39
about the language and alphabet of form.
279
939022
4663
15:43
So, it's a wonderful new horizon,
280
943685
3044
15:46
it's a wonderful thing to discover for the young
281
946729
3750
15:50
and the passionate old, and that's me.
282
950479
2480
15:52
So go to it!
283
952959
2048
15:55
(Applause)
284
955007
11500
About this website

This site will introduce you to YouTube videos that are useful for learning English. You will see English lessons taught by top-notch teachers from around the world. Double-click on the English subtitles displayed on each video page to play the video from there. The subtitles scroll in sync with the video playback. If you have any comments or requests, please contact us using this contact form.

https://forms.gle/WvT1wiN1qDtmnspy7