1
00:00:26,820 --> 00:00:29,840
It's a part of Texas that was still
majority Hispanic.

2
00:00:32,119 --> 00:00:35,920
Football reigned, you know, everybody,
Friday nights, that's what it was all

3
00:00:35,920 --> 00:00:36,920
about.

4
00:00:37,540 --> 00:00:42,220
And it was an oil boom town, too,
although there was a lot of agriculture

5
00:00:42,220 --> 00:00:43,220
as well.

6
00:00:48,880 --> 00:00:53,280
My mother's family's been there since
probably the 1840s, I think.

7
00:00:55,530 --> 00:00:59,390
My dad was a doctor who, you know, took
care of people in the neighborhood, did

8
00:00:59,390 --> 00:01:00,390
house calls.

9
00:01:01,930 --> 00:01:05,630
My father moved to Dallas in the 30s
sometime. I don't remember exactly when,

10
00:01:05,690 --> 00:01:11,610
but I was born in 1948, and we lived, I
think, here, actually, because there was

11
00:01:11,610 --> 00:01:17,050
a washing machine out in the yard, and I
got my arm caught in the ringer one

12
00:01:17,050 --> 00:01:22,250
time. It pulled me up and, you know, got
stuck, and I was hanging, you know, by

13
00:01:22,250 --> 00:01:24,350
my arm, and some people, neighbors came
out.

14
00:01:29,550 --> 00:01:31,490
I have two brothers, Murphy and Mike.

15
00:01:36,370 --> 00:01:37,710
My mother,

16
00:01:39,150 --> 00:01:40,550
she was a housewife.

17
00:01:42,370 --> 00:01:46,450
She was a good influence on us. Just
kind of give us a little discipline.

18
00:01:46,530 --> 00:01:50,490
We'd get to wash the dishes on Sunday
and things like that.

19
00:01:51,150 --> 00:01:53,790
Of course, that may have been a little
bit before Jim's time.

20
00:01:54,050 --> 00:01:55,330
I think he got out of that.

21
00:01:59,470 --> 00:02:03,690
I didn't really know what was going on
in those days. Nobody talked about it.

22
00:02:04,330 --> 00:02:11,070
I knew she was sick, and she had these
burns on her throat, and,

23
00:02:11,270 --> 00:02:13,970
you know, she was in bed a lot.

24
00:02:19,190 --> 00:02:23,810
I remember one day I had some good
friends, had a kid my age, and his

25
00:02:23,810 --> 00:02:25,770
mother was going to take us to the
swimming pool.

26
00:02:26,130 --> 00:02:28,350
I'm just about to get in the car, and
somebody came running out.

27
00:02:28,680 --> 00:02:31,980
I said, hey, you've got to come back.
You can't go.

28
00:02:33,340 --> 00:02:35,440
So I went in, and she was dying.

29
00:02:38,200 --> 00:02:41,680
So she died that morning.

30
00:02:42,360 --> 00:02:46,180
And I found out later, I really didn't
know what it was, but I found out later

31
00:02:46,180 --> 00:02:47,180
that it was lymphoma.

32
00:02:47,340 --> 00:02:52,460
She had been getting radiation therapy,
hence the burns on her neck.

33
00:02:57,450 --> 00:03:00,770
I sat on the bed with her and held her
hand while she died.

34
00:03:04,550 --> 00:03:08,490
There was a big hole, a lot of
loneliness.

35
00:03:12,710 --> 00:03:15,430
I was 11 years old when my mom died.

36
00:03:18,390 --> 00:03:22,930
My father was just heartbroken. He
seemed to lose interest in things.

37
00:03:23,050 --> 00:03:24,810
Anyway, he was gone a lot.

38
00:03:27,020 --> 00:03:30,180
I ended up living with sort of a foster
home.

39
00:03:30,480 --> 00:03:34,440
I mean, not in the sense that I was
given away or everything, but a

40
00:03:34,440 --> 00:03:38,700
counselor from high school teamed me up
with a family who had a boy about my

41
00:03:38,700 --> 00:03:39,700
age.

42
00:03:39,840 --> 00:03:43,120
So that's when my dad was away. I stayed
with them all the time.

43
00:03:48,680 --> 00:03:51,660
I liked to wander around in the woods. I
lived right at the edge of town and used

44
00:03:51,660 --> 00:03:53,100
to wander in the woods by my home.

45
00:03:53,380 --> 00:03:56,400
I just felt it was comforting to have a
harmonica and just...

46
00:03:56,680 --> 00:04:00,620
to the wagon on

47
00:04:00,620 --> 00:04:22,460
behalf

48
00:04:22,460 --> 00:04:24,760
of the nobel assembly at carolinska
institute

49
00:04:25,470 --> 00:04:28,290
I wish to convey to you our warmest
congratulations.

50
00:04:29,190 --> 00:04:34,310
May I now ask you to step forward to
receive the Nobel Prize from the hands

51
00:04:34,310 --> 00:04:35,710
of His Majesty the King.

52
00:05:04,180 --> 00:05:05,680
Innovation is extremely difficult.

53
00:05:07,240 --> 00:05:08,620
We were all very skeptical.

54
00:05:09,620 --> 00:05:12,700
Many people said, Jim Allison, you're
wasting your time.

55
00:05:15,380 --> 00:05:19,080
I knew that this is a way to cure
cancer. I knew that that was a way. And

56
00:05:19,080 --> 00:05:21,780
I'll be damned if I'm going to let that
just lay around.

57
00:05:49,450 --> 00:05:53,830
I guess my dad encouraged me to mess
around my Gilbert chemistry set in the

58
00:05:53,830 --> 00:05:58,250
garage, you know, and dissect frogs and
horned toads and things.

59
00:06:00,610 --> 00:06:04,530
He told me about the bombs he used to
make, so he would construct these little

60
00:06:04,530 --> 00:06:09,790
bombs out in the woods, and he said, in
this very Jim way, when you talk with

61
00:06:09,790 --> 00:06:13,750
scientists later in life, you realize a
lot of us were bomb makers in the

62
00:06:13,750 --> 00:06:14,750
beginning.

63
00:06:18,920 --> 00:06:22,480
When I started learning about what
science really was and how to do it, you

64
00:06:22,480 --> 00:06:25,880
know, I started doing more intelligent
things than making bombs.

65
00:06:29,660 --> 00:06:36,020
One of my teachers who taught advanced
mathematics, physics, chemistry, I

66
00:06:36,020 --> 00:06:38,040
thought he was one of the greatest
teachers I ever had.

67
00:06:38,300 --> 00:06:42,800
But I tried to have a few conversations
with him about evolution, selection of

68
00:06:42,800 --> 00:06:43,840
the fittest, Darwin.

69
00:06:44,580 --> 00:06:46,440
And he just said, no, you know.

70
00:06:47,620 --> 00:06:51,840
It's not real. I did not allow. We will
not teach that here. We will not discuss

71
00:06:51,840 --> 00:06:52,840
it.

72
00:06:53,420 --> 00:06:57,600
I refused to take the course because I
knew that there was no biology in it.

73
00:06:57,660 --> 00:07:01,800
The syllabus, there was no biology in
it. So it was a pretty ugly time. And it

74
00:07:01,800 --> 00:07:05,360
was basically me versus him.

75
00:07:07,340 --> 00:07:12,000
I was still taking advanced physics from
him while I was having this fight with

76
00:07:12,000 --> 00:07:14,340
the school because he was the head of
the science program. He was the one that

77
00:07:14,340 --> 00:07:16,200
made sure that evolution wasn't taught.

78
00:07:17,100 --> 00:07:18,820
He really did start taking it out on me.

79
00:07:20,840 --> 00:07:24,640
Back in those days, you know, you could
use boards to paddle students, so I

80
00:07:24,640 --> 00:07:29,080
seemed to be getting in trouble all the
time and getting a couple of licks just

81
00:07:29,080 --> 00:07:30,340
for walking by, you know.

82
00:07:36,120 --> 00:07:37,900
I just thought I was a troublemaker.

83
00:07:38,340 --> 00:07:40,880
I wasn't. I was just trying to do what
was right.

84
00:07:42,140 --> 00:07:43,500
That's the way it is, you know.

85
00:07:44,080 --> 00:07:45,160
If you, uh...

86
00:07:46,120 --> 00:07:48,920
don't agree with something, you need to
stand your ground.

87
00:07:50,460 --> 00:07:52,480
And if it hurts, it hurts, you know.

88
00:07:53,100 --> 00:07:54,520
That's the way it is, you know.

89
00:07:58,240 --> 00:08:01,120
When he was little, we said he was
hard-headed.

90
00:08:02,440 --> 00:08:07,200
We never did call Jim this to his face,
but, you know, this guy, we called him

91
00:08:07,200 --> 00:08:11,660
Diamond Head because his head was the
hardest substance known to man.

92
00:08:24,650 --> 00:08:27,610
Jim graduates from high school at age
16.

93
00:08:31,710 --> 00:08:36,929
He goes to the University of Texas in
Austin, determined to become a

94
00:08:36,929 --> 00:08:37,929
biologist.

95
00:08:44,870 --> 00:08:46,810
There was this knock on the door.

96
00:08:47,290 --> 00:08:52,910
The door opens, and this scrawny kid
pokes his head in and says, You got a

97
00:08:52,910 --> 00:08:53,910
job?

98
00:08:55,910 --> 00:08:59,570
I said, there's one job left, but you
may not like it.

99
00:09:00,170 --> 00:09:01,310
It's just a dishwasher.

100
00:09:02,510 --> 00:09:03,870
And he said, I'll take it.

101
00:09:06,250 --> 00:09:11,670
We would take a piece of cheesecloth and
put a little bit of acetone on it and

102
00:09:11,670 --> 00:09:14,650
rub off the number of each test tube.

103
00:09:15,410 --> 00:09:17,690
And literally there were thousands of
them.

104
00:09:18,970 --> 00:09:22,330
And so he got the idea, well, maybe I
could take those.

105
00:09:22,860 --> 00:09:27,220
test tubes and spray them with a solid
stream of acetone.

106
00:09:28,140 --> 00:09:35,060
This was back in the 60s. And just about
everybody smoked then, including in the

107
00:09:35,060 --> 00:09:40,800
lab. Jim sprayed his test tubes with
acetone and then sat back to have a

108
00:09:40,800 --> 00:09:42,660
cigarette. And boom!

109
00:09:44,460 --> 00:09:50,220
And we all run in from the lab, and
here's Jim with a blackened face.

110
00:09:50,460 --> 00:09:52,540
His eyebrows were all singed.

111
00:09:53,520 --> 00:09:59,320
I was about to fire him, but in the
short time he'd been there, Jim had just

112
00:09:59,320 --> 00:10:04,160
got along and knew all the graduate
students and the others, and they

113
00:10:04,160 --> 00:10:08,660
besieged me on his behalf. Look, can you
find something else for Jim to do?

114
00:10:08,880 --> 00:10:11,700
He's quite a character. Let's keep him
around.

115
00:10:29,370 --> 00:10:36,110
In the summer of 1966, he came for a
fraternity party that I went to with

116
00:10:36,110 --> 00:10:37,110
someone else.

117
00:10:40,730 --> 00:10:46,390
He was the most amazing thing I'd ever
seen in my life.

118
00:10:48,470 --> 00:10:51,150
I never dated anyone else in college.

119
00:10:51,430 --> 00:10:53,150
We were together from then on.

120
00:10:56,330 --> 00:10:59,950
It was a really kind of magical time to
be in college.

121
00:11:00,770 --> 00:11:03,390
It was so much fun, so much going on.

122
00:11:07,070 --> 00:11:11,750
We were lucky enough to be in college in
Austin just as everything was beginning

123
00:11:11,750 --> 00:11:12,750
to happen there.

124
00:11:13,410 --> 00:11:16,250
That really made it when Willie Nelson
moved there.

125
00:11:18,290 --> 00:11:23,170
I think the first time I saw him live
was playing on a flatbed truck at a Ford

126
00:11:23,170 --> 00:11:25,170
dealership of South Lamar in Austin.

127
00:11:40,460 --> 00:11:43,900
But everyone was also real serious about
their studies.

128
00:11:45,260 --> 00:11:47,760
Jim was passionate about science.

129
00:11:50,300 --> 00:11:54,220
When I was at the University of Texas,
the number one thing I learned in the

130
00:11:54,220 --> 00:11:56,660
lab was just how important it is just to
persevere.

131
00:12:00,220 --> 00:12:03,420
Not be so disappointed. You give up.
Just keep working.

132
00:12:09,930 --> 00:12:14,350
We could never go anywhere without going
by the lab, checking on this or that,

133
00:12:14,470 --> 00:12:15,630
experimenting process.

134
00:12:18,250 --> 00:12:22,810
T-cells were discovered when I was in
college, and I took an undergraduate

135
00:12:22,810 --> 00:12:29,530
class, and my professor Bill Mandy
taught one lecture about T-cells because

136
00:12:29,530 --> 00:12:31,690
almost nothing was known about them.

137
00:12:34,170 --> 00:12:37,230
The human immune system circulates in
our blood.

138
00:12:37,760 --> 00:12:39,340
and protects us from disease.

139
00:12:41,680 --> 00:12:45,980
We now know that at the center of the
immune system is the T-cell.

140
00:12:47,660 --> 00:12:50,240
T-cells are a type of white blood cell.

141
00:12:50,480 --> 00:12:54,160
And these are the cells that actually
respond against viral infections,

142
00:12:54,480 --> 00:12:57,960
bacterial infections, and they start the
fight to keep you healthy.

143
00:13:02,260 --> 00:13:07,200
These cells that go all over your body
and manage to protect you and not kill

144
00:13:07,200 --> 00:13:08,129
you.

145
00:13:08,130 --> 00:13:11,290
And still, to me, just wondrous.

146
00:13:16,150 --> 00:13:19,610
I wanted to try to do something,
something that Barry Kiddo always

147
00:13:19,610 --> 00:13:23,290
taught, was, you know, you should try to
do things.

148
00:13:23,550 --> 00:13:26,510
If you're going to do this stuff, you
ought to at least do things that help

149
00:13:26,510 --> 00:13:27,510
people.

150
00:13:29,750 --> 00:13:31,430
My mother had three brothers.

151
00:13:33,050 --> 00:13:34,590
One died from melanoma.

152
00:13:36,520 --> 00:13:42,220
In those days, melanoma was a death
sentence, so he didn't even get therapy.

153
00:13:42,400 --> 00:13:46,260
When he was diagnosed, he just said,
that's it. You know, had a really good

154
00:13:46,260 --> 00:13:47,820
time for the months that he had.

155
00:13:48,520 --> 00:13:53,700
The other brother was a former rancher
who could roll a bullderm cigarette with

156
00:13:53,700 --> 00:13:57,200
one hand while he was on a horse, you
know, but he paid for that. He had lung

157
00:13:57,200 --> 00:14:01,500
cancer and died from that. I saw him in
an oxygen tent when he got to the point

158
00:14:01,500 --> 00:14:06,150
that his, you know, his emphysema or
whatever was so bad, he needed... helped

159
00:14:06,150 --> 00:14:09,470
to breathe those made kind of an
impression

160
00:14:09,470 --> 00:14:19,910
my

161
00:14:19,910 --> 00:14:25,090
own lab was not involved with cancer
when jim came to work with this

162
00:14:25,090 --> 00:14:31,650
but he had had a tremendously difficult
relationship with cancer

163
00:14:35,180 --> 00:14:39,900
So my graduate school, he convinced me
that perhaps we could look at something

164
00:14:39,900 --> 00:14:41,120
in the cancer field.

165
00:14:43,200 --> 00:14:47,860
There was an enzyme called asparaginase
that when injected into kids with

166
00:14:47,860 --> 00:14:50,620
leukemia could induce remissions.

167
00:14:51,380 --> 00:14:55,180
I first thought they were cured, but it
turned out they weren't. I mean, they

168
00:14:55,180 --> 00:14:56,900
were for a time, but then they always
came back.

169
00:15:00,170 --> 00:15:04,930
My thesis project was to find other
asparaginases from other bacteria that

170
00:15:04,930 --> 00:15:07,690
would be so different that they could be
used in succession.

171
00:15:08,770 --> 00:15:15,630
We pulled water out of the local stream
and surveyed that for asparaginase

172
00:15:15,630 --> 00:15:16,630
activity.

173
00:15:17,510 --> 00:15:19,170
Jim purified that.

174
00:15:21,350 --> 00:15:24,210
And in mice, that worked very well
indeed.

175
00:15:28,170 --> 00:15:33,350
Jim's work on asparaginease convinces
him the immune system plays an important

176
00:15:33,350 --> 00:15:35,230
role in responding to cancer.

177
00:16:00,810 --> 00:16:02,430
I was a bigger kid growing up.

178
00:16:03,050 --> 00:16:06,330
I really ate way too much sugar. I know
that now.

179
00:16:07,650 --> 00:16:09,150
I played a lot of sports.

180
00:16:10,150 --> 00:16:11,290
Basketball was my thing.

181
00:16:12,010 --> 00:16:15,510
I played my first year of high school
and then injured my knee pretty darn

182
00:16:15,510 --> 00:16:16,510
bad.

183
00:16:17,230 --> 00:16:21,090
Kind of lucky that I did because I
couldn't play basketball anymore, but I

184
00:16:21,090 --> 00:16:28,010
joined the marching band where I ended
up meeting my soon

185
00:16:28,010 --> 00:16:29,010
-to-be husband.

186
00:16:31,920 --> 00:16:34,020
I was finishing up my graduate year.

187
00:16:36,940 --> 00:16:40,840
I had what, you know, feels like
bronchitis. You were coughing, breathing

188
00:16:40,840 --> 00:16:41,960
was a little bit of an issue.

189
00:16:47,540 --> 00:16:50,060
Progressively over the next couple of
months, I didn't get better.

190
00:16:51,020 --> 00:16:54,660
I was walking up a hill one day and I
could not take a deep breath.

191
00:16:57,119 --> 00:17:00,980
My mother worked for a primary care
doctor, and she's like, oh, sweetie,

192
00:17:01,080 --> 00:17:04,220
when you get home, come on, see him, and
we'll get this sorted out.

193
00:17:05,819 --> 00:17:09,700
Little did I know that just a few weeks
before that, I was going to develop a

194
00:17:09,700 --> 00:17:14,560
mass growing out of my chest, and I
thought it was breast cancer because of

195
00:17:14,560 --> 00:17:15,560
where it's located.

196
00:17:16,480 --> 00:17:23,260
So going to see her doctor, they noticed
the tumor, and they did a biopsy, and my

197
00:17:23,260 --> 00:17:24,260
world changed.

198
00:17:49,480 --> 00:17:53,680
I went to Scripps because I wanted to
learn about the immune system. I wanted

199
00:17:53,680 --> 00:17:55,580
to ask questions about how the immune
system worked.

200
00:18:01,040 --> 00:18:05,720
Strangely enough, there was a group of
expatriate Texans there.

201
00:18:06,360 --> 00:18:10,680
And we would all go to a little bar
called a Stingery.

202
00:18:13,720 --> 00:18:17,240
And there was a band there that he would
sometimes play harmonica with.

203
00:18:22,190 --> 00:18:26,650
Columbia Records was having their annual
convention in San Diego, and Willie

204
00:18:26,650 --> 00:18:29,690
Nelson's record, The Red-Headed
Stranger, had just gone platinum, so

205
00:18:29,690 --> 00:18:31,710
they decided to have a big party for
him.

206
00:18:32,010 --> 00:18:35,430
The guy that was in the sheriff's
department, he was a real devotee of our

207
00:18:35,430 --> 00:18:39,090
band, came and told me about this, you
know, and said, we're doing security for

208
00:18:39,090 --> 00:18:43,590
it. He let me go in, you know, let me
through security to go to this private

209
00:18:43,590 --> 00:18:44,590
party.

210
00:18:45,330 --> 00:18:46,510
Willie Nelson came over.

211
00:18:46,860 --> 00:18:49,900
And he said, well, you know someplace we
could go picking tomorrow night? Because

212
00:18:49,900 --> 00:18:52,080
I got tomorrow night off, and I'd sure
like to play some music.

213
00:18:53,360 --> 00:18:56,060
So I said, well, it's talent night at
the Stingery.

214
00:18:59,060 --> 00:19:02,380
So we loaded up in our little VW camper.

215
00:19:04,400 --> 00:19:07,980
We walked in, and people just fell on
the floor.

216
00:19:09,560 --> 00:19:12,020
Willie basically asked, you guys mad if
I played?

217
00:19:13,830 --> 00:19:16,330
He and his drummer and his bass player
started playing.

218
00:19:18,470 --> 00:19:20,870
They played for three hours at least.

219
00:19:26,450 --> 00:19:30,590
And, you know, it was a little dive bar,
and there was about eight people at this

220
00:19:30,590 --> 00:19:31,590
place, you know.

221
00:19:32,730 --> 00:19:37,750
There was one payphone on the wall, and
so those eight or so went up, called

222
00:19:37,750 --> 00:19:42,070
people, and pretty soon the place filled
up, and people called other people, and

223
00:19:42,070 --> 00:19:43,430
it was full, and the people were...

224
00:19:43,680 --> 00:19:44,680
out on the street.

225
00:19:45,460 --> 00:19:48,700
It was amazing. I didn't have to buy a
beer at that place for about two years

226
00:19:48,700 --> 00:19:49,700
after that.

227
00:19:57,700 --> 00:20:02,180
An old college roommate of mine, he
heard that MD Anderson was opening a new

228
00:20:02,180 --> 00:20:03,360
laboratory near Austin.

229
00:20:04,480 --> 00:20:07,040
To tell you the truth, the main reason I
went there is because I thought I would

230
00:20:07,040 --> 00:20:08,040
have freedom.

231
00:20:10,530 --> 00:20:13,470
The first time I connected with Jim was
I think in about 1980.

232
00:20:13,790 --> 00:20:15,470
I was a postdoc in New Mexico.

233
00:20:16,310 --> 00:20:19,050
I went to MD Anderson, and they asked me
to give a seminar.

234
00:20:19,290 --> 00:20:23,490
And they said, well, you're being
live-streamed to Smithville, Texas.

235
00:20:24,190 --> 00:20:29,950
And so I gave my seminar, and they said,
do we have any questions from

236
00:20:29,950 --> 00:20:33,190
Smithville? And I'm thinking, where in
the hell is Smithville?

237
00:20:34,010 --> 00:20:35,010
And then...

238
00:20:35,200 --> 00:20:39,520
This voice comes over with this, you
know, nice Texas accent and asked me

239
00:20:39,520 --> 00:20:40,920
this incredible question.

240
00:20:41,140 --> 00:20:45,200
With a given molecule on a pathway, for
example, the MAP kinase pathway,

241
00:20:45,300 --> 00:20:49,480
which... He got right to the heart of,
you know, the hardest question he could

242
00:20:49,480 --> 00:20:51,320
ask about the science I was doing at the
time.

243
00:20:52,640 --> 00:20:56,600
I consider Jim my brother,
scientifically as well as personally.

244
00:20:57,240 --> 00:21:00,680
I would consider him my best friend for
the last 30-odd years.

245
00:21:06,730 --> 00:21:10,570
I really wanted to understand the immune
system and things, so I really wanted to

246
00:21:10,570 --> 00:21:14,790
know how T-cells worked. And at the
time, all we really knew was that T

247
00:21:14,790 --> 00:21:18,310
-cells went around the body and took
care of stuff that didn't hurt you.

248
00:21:20,290 --> 00:21:24,950
Scientists know that T-cells distinguish
between healthy cells and threatening

249
00:21:24,950 --> 00:21:29,550
ones by using a molecule on their
surface called the T-cell receptor.

250
00:21:31,550 --> 00:21:33,710
But they don't know how the receptor
works.

251
00:21:36,970 --> 00:21:41,190
We didn't know how those white blood
cells, these T cells, would actually

252
00:21:41,190 --> 00:21:44,870
recognize the virus as being different
and needing to be eliminated.

253
00:21:45,230 --> 00:21:50,950
And that was the holy grail in the late
70s and early 80s. All the top labs in

254
00:21:50,950 --> 00:21:52,690
immunology, that was the quest.

255
00:21:55,050 --> 00:21:58,630
I read the literature and there was a
lot of stuff that was contradictory, a

256
00:21:58,630 --> 00:22:00,270
lot of stuff that seemed like fantasy.

257
00:22:00,590 --> 00:22:04,670
I could not possibly imagine how some of
the mechanisms that were proposed

258
00:22:04,670 --> 00:22:11,660
actually... I said, well, either I'm a
total moron and can't follow this

259
00:22:11,660 --> 00:22:16,640
complicated stuff, or people are just,
you know, it's all nonsense.

260
00:22:17,100 --> 00:22:21,140
So finally I said, forget it. I'm not
going to pay any attention to the

261
00:22:21,140 --> 00:22:22,140
literature.

262
00:22:22,400 --> 00:22:25,740
Part of Jim's success is the fact that
he's an iconoclast.

263
00:22:26,040 --> 00:22:27,400
You know, he doesn't care.

264
00:22:28,030 --> 00:22:30,250
He doesn't care that he's not following
convention.

265
00:22:30,550 --> 00:22:33,450
He's following his own thoughts, his own
motivations.

266
00:22:33,750 --> 00:22:40,210
He's willing to do it in the face of his
colleagues not necessarily believing

267
00:22:40,210 --> 00:22:41,210
him.

268
00:22:47,470 --> 00:22:52,090
I got a notice that Irv Weissman from
Stanford, who is a very noted

269
00:22:52,090 --> 00:22:54,590
immunologist, was giving a lecture.

270
00:22:55,130 --> 00:22:58,810
So I drove three hours from Smithville
into Houston.

271
00:23:01,490 --> 00:23:04,810
I was driving back, replaying his talk
in my head.

272
00:23:06,070 --> 00:23:09,630
I remember it just sort of clicked. I
said, I know how to find the T-cell

273
00:23:09,630 --> 00:23:10,630
receptor.

274
00:23:17,150 --> 00:23:19,270
Race scientists are creative people.

275
00:23:19,790 --> 00:23:23,050
They're not just focused on their
detailed work.

276
00:23:23,330 --> 00:23:25,030
They're thinking beyond.

277
00:23:25,410 --> 00:23:29,170
There's a creativity to this work, and
frankly, if not for the creative

278
00:23:29,170 --> 00:23:31,670
scientists, we would make little
progress.

279
00:23:32,530 --> 00:23:38,930
I saw miles and miles of Texas All the
stars

280
00:23:38,930 --> 00:23:45,470
up in the sky I saw miles and miles of

281
00:23:45,470 --> 00:23:46,470
Texas

282
00:23:46,990 --> 00:23:51,430
drove back that night just rolling in my
head and everything and you know the

283
00:23:51,430 --> 00:23:55,570
next few days just lying down the path i
find the t-cell receptor

284
00:23:55,570 --> 00:24:02,150
over the next few months

285
00:24:02,150 --> 00:24:07,470
jim uses the latest genetic engineering
techniques to test his hypothesis

286
00:24:09,900 --> 00:24:13,200
Work hard all day, get an incubation
period or something, go to the beer

287
00:24:13,200 --> 00:24:16,680
hall, knock down some beers, go back and
finish the experiment.

288
00:24:17,600 --> 00:24:21,420
Go to sleep, get up, start it all over
again.

289
00:24:23,600 --> 00:24:26,160
I think the guy is just incredibly
passionate.

290
00:24:26,939 --> 00:24:31,000
So he'll spend a night going out to a
honky tonk and he'll be out all night

291
00:24:31,000 --> 00:24:32,480
and he'll drink and he'll have a great
time.

292
00:24:32,840 --> 00:24:37,140
And then there's that same energy that
would put him in the lab at Smithville.

293
00:24:37,260 --> 00:24:41,920
They're doing a 36 hour experiment and
he's staying up for that. And he's just

294
00:24:41,920 --> 00:24:45,840
as driven and turned on by that whole
experience of being in the lab.

295
00:24:55,020 --> 00:24:57,360
We went to a conference in California.

296
00:24:59,100 --> 00:25:03,120
This is where you present your data.
You're not well-known enough to be

297
00:25:03,120 --> 00:25:06,840
invited to get up on the podium and give
a talk at that point. You're relegated

298
00:25:06,840 --> 00:25:08,580
to putting your work on a poster board.

299
00:25:08,940 --> 00:25:12,840
So Jim had a poster there, and I
remember walking over to look at his

300
00:25:12,840 --> 00:25:17,540
poster, and we'd just kind of met
recently then, and he pointed to this

301
00:25:17,540 --> 00:25:20,660
spot on the poster and says, that's the
T-cell receptor.

302
00:25:21,640 --> 00:25:22,820
And he was right.

303
00:25:32,750 --> 00:25:37,190
His contributions to our understanding
of the T-cell receptor, the molecule

304
00:25:37,190 --> 00:25:42,350
most centrally identified as the thing
that recognizes the target and allows

305
00:25:42,350 --> 00:25:43,490
for it to be eliminated.

306
00:25:44,350 --> 00:25:45,350
Extremely important.

307
00:25:49,070 --> 00:25:53,710
He was the first one to actually purify
the molecule by which T-cells recognize

308
00:25:53,710 --> 00:25:54,870
everything.

309
00:25:56,090 --> 00:25:58,650
This is how T-cells recognize infectious
disease.

310
00:25:59,850 --> 00:26:03,610
This is how T-cells are recognizing
things they shouldn't recognize when you

311
00:26:03,610 --> 00:26:04,610
get autoimmune diseases.

312
00:26:05,190 --> 00:26:06,970
So this was a seminal discovery.

313
00:26:10,430 --> 00:26:16,470
Jim was invited to major immunology
conferences, and it was recognized that

314
00:26:16,470 --> 00:26:18,130
this constituted a real breakthrough.

315
00:26:47,370 --> 00:26:51,750
When they came back and said, Sharon,
you have melanoma, I was completely

316
00:26:51,750 --> 00:26:52,750
shaken.

317
00:26:53,450 --> 00:26:54,450
Unbelievable.

318
00:26:56,170 --> 00:26:57,830
I couldn't believe that that was my
life.

319
00:26:58,450 --> 00:26:59,530
I thought I was going to die.

320
00:27:06,250 --> 00:27:07,209
Good job.

321
00:27:07,210 --> 00:27:12,330
The doctor canceled all his patients and
shut his office door and got on the

322
00:27:12,330 --> 00:27:16,470
phone and said, I have a 22-year-old
patient here who needs to see you now.

323
00:27:17,550 --> 00:27:21,250
And he was on the phone all day, but I
had an appointment with Sloan by the end

324
00:27:21,250 --> 00:27:22,250
of it.

325
00:27:23,830 --> 00:27:26,570
So then I saw Dr. Walchuk just a couple
days later.

326
00:27:28,110 --> 00:27:31,870
Sharon Belbin, when I first met her, was
23 years old.

327
00:27:32,650 --> 00:27:38,990
She was seen by an oncologist near her
home in the New Jersey Shore, who called

328
00:27:38,990 --> 00:27:42,930
me and said, you need to see this young
woman. So I see her, and it's a room

329
00:27:42,930 --> 00:27:46,290
full of very sad.

330
00:27:46,810 --> 00:27:52,650
you know, family members trying to get
their head around this seemingly

331
00:27:52,650 --> 00:27:53,710
unbelievable situation.

332
00:27:56,210 --> 00:27:59,510
We started her on chemotherapy very
quickly thereafter.

333
00:28:01,110 --> 00:28:06,330
So I had chemotherapy Monday, Tuesday,
Wednesday, and got married that

334
00:28:06,330 --> 00:28:07,330
Saturday.

335
00:28:08,370 --> 00:28:12,210
We decided to go through the wedding
because it's for better or worse.

336
00:28:13,020 --> 00:28:16,180
I mean, we were joking around a couple
days before and we were just like, okay,

337
00:28:16,260 --> 00:28:18,940
well, we are going to get the worst over
with right in the beginning and then the

338
00:28:18,940 --> 00:28:20,000
rest of life will be great.

339
00:28:21,120 --> 00:28:25,560
And Rob is really probably a saint and
don't tell him I said that.

340
00:28:29,580 --> 00:28:35,020
Who can look at somebody and say, here's
a terminal diagnosis and I'm going to

341
00:28:35,020 --> 00:28:36,020
marry you anyway?

342
00:28:46,280 --> 00:28:52,240
In 1981, there was a bill that was
introduced by a very conservative state

343
00:28:52,240 --> 00:28:56,800
senator from East Texas saying that
creationism needed to be taught in

344
00:28:56,800 --> 00:28:57,800
schools.

345
00:28:59,180 --> 00:29:04,760
One of his teachers from Alice had
actually been elected as the state

346
00:29:04,760 --> 00:29:07,740
representative from Alice, not the...

347
00:29:08,030 --> 00:29:09,250
the science teacher, of course.

348
00:29:09,530 --> 00:29:13,790
And she called him up and said, someone
has introduced a bill to outlaw the

349
00:29:13,790 --> 00:29:18,250
teaching of evolution in the public
schools, and we've got a hearing coming

350
00:29:18,250 --> 00:29:20,030
up, and we need someone to come and
talk.

351
00:29:20,370 --> 00:29:24,890
She said, he's going to have 300 people
here supporting the bill, deposing

352
00:29:24,890 --> 00:29:28,070
evolution, and so if we don't have
somebody here speaking to the other

353
00:29:28,070 --> 00:29:33,030
side, it's likely to pass a committee
out to the House floor, and God knows

354
00:29:33,030 --> 00:29:34,030
what's going to happen.

355
00:29:39,690 --> 00:29:43,170
I tried to find other people who would
do it. I only found one other scientist

356
00:29:43,170 --> 00:29:44,510
that was willing to do that.

357
00:29:45,170 --> 00:29:49,070
I'm here tonight speaking before this
committee because I feel that in this

358
00:29:49,070 --> 00:29:53,830
highly technological age, an education
in science is essential if members of

359
00:29:53,830 --> 00:29:57,610
our society are to be able to understand
and deal with complex and diverse

360
00:29:57,610 --> 00:29:58,890
problems facing them.

361
00:29:59,650 --> 00:30:02,050
Science is something that you can use.

362
00:30:02,690 --> 00:30:06,290
It's not just a couch for the past. It
does that. It also allows you to...

363
00:30:06,480 --> 00:30:10,320
understand what's going to happen in the
future to situations that you've never

364
00:30:10,320 --> 00:30:13,000
seen before, that have never arisen.
That's what science is.

365
00:30:13,720 --> 00:30:17,760
That is the chief problem with
creationism, purporting to be a science.

366
00:30:17,960 --> 00:30:22,040
It cannot be used to construct
explanations of newly observed fact. It

367
00:30:22,040 --> 00:30:26,120
does not give us any help whatsoever in
understanding how bacteria acquire

368
00:30:26,120 --> 00:30:30,240
resistance, how tumor cells arise, or
how they are eliminated by the immune

369
00:30:30,240 --> 00:30:34,440
system. He talks about using the immune
system to cure cancer.

370
00:30:34,880 --> 00:30:36,380
at that point, even in 1981.

371
00:30:37,160 --> 00:30:42,440
I said, I challenge this man to use his
creation science, such as it is, to

372
00:30:42,440 --> 00:30:45,740
understand how a tumor escapes the
immune system.

373
00:30:53,420 --> 00:30:55,900
It's hilarious, the limits of their
arguments.

374
00:30:56,480 --> 00:31:01,300
Probably the best one was, if you put a
Ford in a field, it rusts. It don't turn

375
00:31:01,300 --> 00:31:02,300
into no Cadillac.

376
00:31:02,800 --> 00:31:05,460
You know, I said, oh, yeah, okay, I got
it.

377
00:31:06,140 --> 00:31:08,080
Obviously, I can't be anything like
evolution.

378
00:31:43,880 --> 00:31:47,240
Pretty soon after that, he got an offer
from the University of California at

379
00:31:47,240 --> 00:31:48,880
Berkeley to go out there.

380
00:31:49,120 --> 00:31:52,840
After the T-cell receptor, I was offered
a full professorship at Berkeley.

381
00:31:53,340 --> 00:31:57,720
And I was really happy out at
Smithville, living in Austin, working in

382
00:31:57,720 --> 00:32:01,940
Smithville, just doing science. It was
as clean as it could get. I was doing

383
00:32:01,940 --> 00:32:04,560
exactly what I wanted to. I didn't have
to answer to anybody.

384
00:32:04,900 --> 00:32:06,840
I didn't have to do any administration
or anything.

385
00:32:07,360 --> 00:32:10,880
So the idea of going into some big-time
place and having to...

386
00:32:11,560 --> 00:32:12,980
You know, compete was a little scary.

387
00:32:15,960 --> 00:32:18,940
An old friend of mine called me up and
said, what are you doing?

388
00:32:19,640 --> 00:32:22,120
And I told him that I'm comfortable
here. I'm happy here.

389
00:32:22,960 --> 00:32:26,100
He says, yeah, in 20 years you're going
to be sitting there with your feet up on

390
00:32:26,100 --> 00:32:28,140
the porch saying I could have been a
contender.

391
00:32:29,720 --> 00:32:33,220
I kind of went, yeah, I understand what
you mean.

392
00:32:57,710 --> 00:33:02,770
When I decide who to hire in my lab, I
always am looking for one thing, really,

393
00:33:02,870 --> 00:33:03,870
and that's curiosity.

394
00:33:06,190 --> 00:33:08,110
Berkeley drew me in in a lot of
different ways.

395
00:33:08,430 --> 00:33:11,430
It's filled with very smart people, but
very freaky people, and they all sort of

396
00:33:11,430 --> 00:33:14,750
intermingle, and you don't ever know
what's a crazy idea and what's a great

397
00:33:14,750 --> 00:33:15,750
idea.

398
00:33:16,850 --> 00:33:19,410
Even at Berkeley, Jim was a standout.

399
00:33:19,870 --> 00:33:21,110
He didn't look like the other people.

400
00:33:21,760 --> 00:33:25,080
Berkeley has its own conservative
liberal side of it, which is that, you

401
00:33:25,080 --> 00:33:29,180
know, you can be liberal up to a point,
but Texas is actually too far. You know,

402
00:33:29,200 --> 00:33:32,600
it's like you're carrying a gun and I
don't know, all kinds of things that

403
00:33:32,600 --> 00:33:33,339
could be bad.

404
00:33:33,340 --> 00:33:37,260
And so Jim was like just over that line
and represented just the, you know,

405
00:33:37,260 --> 00:33:38,820
additional frontier even of Berkeley.

406
00:33:40,040 --> 00:33:42,780
But also immunology was not considered a
science.

407
00:33:44,180 --> 00:33:47,340
The classic people said, oh, immunology,
that's sort of a pseudo-discipline.

408
00:33:47,340 --> 00:33:48,420
That's really like almost like...

409
00:33:48,860 --> 00:33:52,200
giving holistic medicine or something,
right? It's like, what is that? You

410
00:33:52,200 --> 00:33:53,200
don't even know what that is.

411
00:33:54,600 --> 00:33:57,420
So Jim's lab has a feel of being like a
pirate ship.

412
00:33:59,540 --> 00:34:03,800
There are personalities doing their own
crazy stuff, and yet there is a, you

413
00:34:03,800 --> 00:34:06,800
know, dedication to the purpose of
driving the boat forward.

414
00:34:11,719 --> 00:34:12,960
I was working a lot.

415
00:34:13,440 --> 00:34:16,880
Not as hard as the people in the lab, of
course. I mean, they were working all

416
00:34:16,880 --> 00:34:17,880
the time.

417
00:34:19,400 --> 00:34:21,300
But we also all partied together.

418
00:34:22,340 --> 00:34:25,600
You know, I just had some incredible
parties.

419
00:34:33,179 --> 00:34:38,480
There is the rigid thought process that
is like connect the dots A to B to C to,

420
00:34:38,500 --> 00:34:40,880
you know, like that. And that you do
during the daytime.

421
00:34:42,940 --> 00:34:46,860
But I think there's a whole element of
the idea of unwinding and not letting

422
00:34:46,860 --> 00:34:47,860
the mind go linear.

423
00:34:48,170 --> 00:34:53,870
and just saying, what if nothing we
thought was right?

424
00:34:59,090 --> 00:35:04,010
Jim's work on the T-cell receptor has
sparked a race to discover more secrets

425
00:35:04,010 --> 00:35:05,010
of the T-cell.

426
00:35:06,290 --> 00:35:11,430
Soon a French scientist finds a new
protein on the surface of T-cells called

427
00:35:11,430 --> 00:35:12,810
CTLA-4.

428
00:35:14,700 --> 00:35:19,600
Most researchers assume that it
activates the immune system like the T

429
00:35:19,600 --> 00:35:20,600
-cell receptor.

430
00:35:22,320 --> 00:35:24,780
But Jim doesn't assume anything.

431
00:35:26,780 --> 00:35:33,780
The only right way to do science is not
to do experiments to give you an answer

432
00:35:33,780 --> 00:35:35,920
that's consistent with what you think
you ought to get.

433
00:35:36,640 --> 00:35:41,940
But do the killer experiment that can
only be right if you're right.

434
00:35:44,730 --> 00:35:48,070
Jim started looking at the data on
CTLA-4 critically.

435
00:35:48,650 --> 00:35:53,050
And he and Max Crumble, his graduate
student, started saying, well, let's see

436
00:35:53,050 --> 00:35:57,230
what the real data is. If we do
experiments, is that true or not?

437
00:35:57,470 --> 00:36:00,030
So we just had this stupid question,
like, what does it do?

438
00:36:00,630 --> 00:36:02,210
And it wasn't, like, just cure cancer.

439
00:36:02,510 --> 00:36:03,570
It's like, what does that do?

440
00:36:04,330 --> 00:36:05,530
Are you shooting, Jim?

441
00:36:05,910 --> 00:36:08,490
Yes. Well, it's Christmas. It's 1991.

442
00:36:10,030 --> 00:36:12,150
And we're loving up the pinata here.

443
00:36:21,540 --> 00:36:28,400
To study CTLA-4 in a mouse, Cromwell
must build a mouse antibody, a

444
00:36:28,400 --> 00:36:32,580
Y-shaped protein that will trigger a
reaction from CTLA-4.

445
00:36:45,960 --> 00:36:46,960
Okay, let's go.

446
00:36:53,480 --> 00:36:57,420
What made that whole three-year stretch
for me very difficult was that I didn't

447
00:36:57,420 --> 00:36:58,680
get any progress scientifically.

448
00:37:01,260 --> 00:37:03,720
Robert's first, fourth birthday. Robert,
look over here.

449
00:37:05,600 --> 00:37:07,040
Are you Batman?

450
00:37:07,320 --> 00:37:10,220
And this is really common. For three
years, nada.

451
00:37:12,340 --> 00:37:13,820
You know, like, everything I did...

452
00:37:14,190 --> 00:37:15,490
really didn't amount to anything.

453
00:37:19,990 --> 00:37:25,550
Running laboratories, it's not easy to
have people do the experiments you want

454
00:37:25,550 --> 00:37:26,550
them to do.

455
00:37:27,370 --> 00:37:32,550
I regret at times not being able to
motivate people to do the kinds of

456
00:37:32,550 --> 00:37:34,930
experiments that I was sure needed to be
done.

457
00:37:35,510 --> 00:37:37,630
But Jim has that ability to do that.

458
00:37:38,000 --> 00:37:42,300
So because of that, people in this lab
have done things that were crazy at some

459
00:37:42,300 --> 00:37:46,100
times, but he also was able to get
people to do the things that he was

460
00:37:46,100 --> 00:37:47,100
really passionate about.

461
00:37:53,820 --> 00:37:58,680
While Max struggles to make his
antibody, another lab beats him to it.

462
00:38:00,320 --> 00:38:05,560
Peter Linsley, a scientist working with
the drug company Bristol-Myers Squibb,

463
00:38:05,790 --> 00:38:10,410
publishes results saying that CTLA-4 is
an activating receptor.

464
00:38:11,130 --> 00:38:15,530
When it's engaged, it revs up the immune
response against targets.

465
00:38:17,110 --> 00:38:19,890
Then these papers came out and said it's
a positive regulator.

466
00:38:20,790 --> 00:38:25,030
So, you know, that attitude was, well,
we've been scooped, you know, it's done.

467
00:38:25,250 --> 00:38:29,930
Except I said, I don't think so. There's
something about, you know, I saw some

468
00:38:29,930 --> 00:38:34,390
holes in that paper, and so we're going
to test this fucker to see if it's...

469
00:38:34,620 --> 00:38:35,620
really right.

470
00:38:40,320 --> 00:38:45,780
You have this picture of Einstein
sitting at the whiteboard, hair frayed,

471
00:38:45,880 --> 00:38:48,340
you know, writing equations that no one
can see.

472
00:38:50,460 --> 00:38:55,180
Really what he's doing is saying there's
a fundamental question, an assumption

473
00:38:55,180 --> 00:39:00,560
people have made that doesn't make sense
if you look at this in a clear-eyed way.

474
00:39:00,760 --> 00:39:03,920
What if I step back here and just
observe?

475
00:39:04,549 --> 00:39:08,850
and say, these pieces of information
need to be put together in a different

476
00:39:08,850 --> 00:39:15,010
way. I think that is what pioneers do,
and weirdly, it's childlike.

477
00:39:21,950 --> 00:39:25,170
This is a hard thing. It took me a while
to be able to say this to people, but I

478
00:39:25,170 --> 00:39:28,890
think there was a formative moment when
I was in Jim's office, and I actually

479
00:39:28,890 --> 00:39:29,890
started to cry.

480
00:39:29,950 --> 00:39:32,790
Because I'd been working on something
for so long, and he told me something

481
00:39:32,790 --> 00:39:34,090
again, a mistake that I'd made.

482
00:39:34,730 --> 00:39:36,350
And, you know, I just started to cry.

483
00:39:36,870 --> 00:39:40,250
And then I got over that. I mean, there
was a period of that that you just have

484
00:39:40,250 --> 00:39:42,750
to get through and just say, okay, go
back at it.

485
00:39:45,530 --> 00:39:50,930
Crummel finally makes his CTLA-4
antibody and launches Jim's experiments.

486
00:39:52,150 --> 00:39:57,770
He quickly demonstrates that Linsley's
idea of how CTLA-4 works is wrong.

487
00:39:59,150 --> 00:40:04,430
The experiment proves that engaging
CTLA-4 doesn't activate the immune

488
00:40:04,430 --> 00:40:06,930
response. It stops it.

489
00:40:12,470 --> 00:40:18,610
Jim and Max Crummel, as well as Jeff
Bluestone and his grad students, turned

490
00:40:18,610 --> 00:40:22,990
the thing completely around and said,
nope, all these prior papers saying that

491
00:40:22,990 --> 00:40:27,910
CTLA-4 is another gas pedal, that's not
correct. It's actually a brake.

492
00:40:29,450 --> 00:40:34,550
Like Jim, I was able to figure out
CTLA-4, and I was shocked.

493
00:40:35,370 --> 00:40:37,810
CTLA-4 was the wackiest thing in the
world, right?

494
00:40:38,250 --> 00:40:41,750
Nobody believed that you would actually
have a whole system in place to shut

495
00:40:41,750 --> 00:40:45,130
down the most important thing going on
in your body, which is an immune

496
00:40:45,130 --> 00:40:48,510
response, and you're going to shut this
thing down and make sure it doesn't

497
00:40:48,510 --> 00:40:53,670
work? The body does not want an
overexuberant immune system, because if

498
00:40:53,670 --> 00:40:56,950
we did have one, we would all be
suffering from autoimmune disease.

499
00:40:59,370 --> 00:41:04,570
Autoimmune diseases, like multiple
sclerosis, are caused when the immune

500
00:41:04,570 --> 00:41:06,370
system attacks healthy cells.

501
00:41:07,750 --> 00:41:12,010
Jim's discovery prompts many
immunologists to think about curing

502
00:41:12,010 --> 00:41:13,010
these diseases.

503
00:41:13,830 --> 00:41:19,410
They will engage CTLA-4 and stop T cells
from going on the attack.

504
00:41:21,870 --> 00:41:24,310
Jim heads in a different direction.

505
00:41:26,700 --> 00:41:30,920
There's this big part of the immune
system that is built on stopping itself.

506
00:41:31,780 --> 00:41:34,200
Now what the heck does that have to do
with cancer?

507
00:41:43,900 --> 00:41:47,640
Cancers, we know they have mutations. We
know they're different from normal. They

508
00:41:47,640 --> 00:41:50,960
should be visible to the immune system.
And for a long time we struggled.

509
00:41:51,960 --> 00:41:54,900
Why can't the immune system see cancer?
It can see flu.

510
00:41:56,460 --> 00:42:00,520
GEM theorizes that tumors have evolved
to trick the immune system.

511
00:42:00,960 --> 00:42:05,040
They engage CTLA-4, turning on the
T-cell's break.

512
00:42:06,420 --> 00:42:09,440
This stops T-cells from attacking the
tumors.

513
00:42:10,440 --> 00:42:16,520
If you were a cancer, it would certainly
be advantageous if you contacted that

514
00:42:16,520 --> 00:42:19,580
receptor and turned off all those
T-cells that might otherwise come to

515
00:42:19,580 --> 00:42:21,180
kill you. This would make sense.

516
00:42:22,240 --> 00:42:24,680
At the time, it was a crazy idea. Nobody
thought.

517
00:42:25,050 --> 00:42:26,750
Tumors were trying to turn off the
immune system.

518
00:42:27,410 --> 00:42:29,610
But he said, well, what if I block this?

519
00:42:29,830 --> 00:42:33,310
Why don't we see what that does to
certain cancers?

520
00:42:34,310 --> 00:42:39,490
Jim hypothesizes that if he inserts an
antibody to block the connection between

521
00:42:39,490 --> 00:42:45,490
the tumor and CTLA-4, the T cell will be
free to attack the tumor.

522
00:42:54,279 --> 00:42:55,840
Jim had all these tumors in the freezer.

523
00:42:58,240 --> 00:43:01,540
So I was making antibodies as fast as I
could, and a guy named Dana Leach came.

524
00:43:01,700 --> 00:43:03,540
He was a postdoc in the lab, new
postdoc.

525
00:43:03,820 --> 00:43:06,840
And Jim gave him the tumor models, and,
you know, I gave him the antibody.

526
00:43:09,060 --> 00:43:12,880
The student who was doing the experiment
had put the tumors in the mice and gone

527
00:43:12,880 --> 00:43:14,160
away for the holidays.

528
00:43:15,440 --> 00:43:18,300
And so it was actually left to Jim to
check on these mice. And, you know,

529
00:43:18,340 --> 00:43:21,800
shortly before Christmas, I think, he
saw the tumors are growing.

530
00:43:22,160 --> 00:43:23,360
Maybe nothing's going on.

531
00:43:24,520 --> 00:43:28,040
Kind of sad about that. It's not a happy
thing to see, but, you know, that's what

532
00:43:28,040 --> 00:43:29,040
the data was.

533
00:43:32,520 --> 00:43:35,740
We had Thanksgiving and Christmas
together for probably, you know, almost

534
00:43:35,740 --> 00:43:36,740
20 years.

535
00:43:37,380 --> 00:43:38,720
I remember that Christmas.

536
00:43:38,920 --> 00:43:42,800
He was mumbling about, you know, the
student taking off and going on holiday.

537
00:43:44,440 --> 00:43:48,020
I had family visiting and everything,
and so I did something that was

538
00:43:48,020 --> 00:43:51,460
unforgivable, really. If he had done it,
I would have fired him, probably.

539
00:43:52,030 --> 00:43:55,670
I skipped a couple of readings for the
Christmas holidays.

540
00:43:58,530 --> 00:44:02,050
A few days later, though, Jim
remembered, oh, yeah, I'm supposed to be

541
00:44:02,050 --> 00:44:05,290
checking on this guy's mice because he's
still off celebrating Christmas with his

542
00:44:05,290 --> 00:44:09,710
family, and came back to find that, you
know, in the mice that had received the

543
00:44:09,710 --> 00:44:10,870
antibody, the tumors were gone.

544
00:44:16,490 --> 00:44:19,270
Which was one of these, you know, truly
one of these aha moments when I went,

545
00:44:19,330 --> 00:44:22,050
oh, Jesus, you know, this is something
big.

546
00:44:22,550 --> 00:44:26,050
Because I've been doing tumor immunology
enough by then to know this experiment

547
00:44:26,050 --> 00:44:30,090
was so cool. You didn't need a
statistician. They were all alive or all

548
00:44:30,090 --> 00:44:31,470
dead, you know.

549
00:44:32,930 --> 00:44:34,370
These tumors have disappeared.

550
00:44:34,830 --> 00:44:35,930
I mean, this is impossible.

551
00:44:36,310 --> 00:44:38,150
This is not possible.

552
00:44:39,040 --> 00:44:42,940
That's how mind-boggling you have to
think of this as, because the human

553
00:44:42,940 --> 00:44:47,600
body, with 480 million years of
evolution behind it, can't get rid of

554
00:44:47,600 --> 00:44:48,600
this stuff.

555
00:44:48,660 --> 00:44:50,300
And now the tumors have disappeared.

556
00:44:52,260 --> 00:44:57,780
From then on, for the next decade,
essentially he had one goal, to get that

557
00:44:57,780 --> 00:44:59,580
made into a drug for cancer patients.

558
00:45:11,470 --> 00:45:14,970
It didn't come out of cancer, but once
it was there, it was there.

559
00:45:15,910 --> 00:45:18,870
And I'd be damned if I'm going to let
that just lay around.

560
00:45:19,970 --> 00:45:22,730
This is a way to cure cancer. I knew
that that was a way.

561
00:45:45,710 --> 00:45:51,330
In my teen years and in my college days,
I was the dork, the one that studied

562
00:45:51,330 --> 00:45:55,090
really hard, got good grades, because I
was the first in my family to go to

563
00:45:55,090 --> 00:45:58,870
college. I had a lot to live up to with
that, so I had to make sure that while

564
00:45:58,870 --> 00:46:02,770
friends were out partying, their grades
were Cs, I needed to get As, and I knew

565
00:46:02,770 --> 00:46:08,250
it. Knowing what I know now of what life
had in store for me, maybe I would have

566
00:46:08,250 --> 00:46:09,250
had a little bit more fun.

567
00:46:09,430 --> 00:46:10,650
I probably would have.

568
00:46:22,860 --> 00:46:27,900
We started her on chemotherapy, and that
chemotherapy really didn't work for her.

569
00:46:27,980 --> 00:46:29,540
So we tried another kind of
chemotherapy.

570
00:46:31,760 --> 00:46:36,020
I know that chemotherapy is supposed to
kill cancer. It can give you back your

571
00:46:36,020 --> 00:46:37,020
life.

572
00:46:37,220 --> 00:46:39,920
Chemotherapy made me feel like I had
cancer.

573
00:46:40,400 --> 00:46:42,440
I felt like death warmed over.

574
00:46:43,240 --> 00:46:46,500
I got severe peripheral neuropathy from
the chemotherapy.

575
00:46:47,240 --> 00:46:49,160
That's numbness and tingling in your
hands and feet.

576
00:46:49,400 --> 00:46:52,020
It wasn't just hands and feet, though.
It went up my leg.

577
00:46:52,380 --> 00:46:53,740
And I couldn't hold a pencil to write.

578
00:46:54,860 --> 00:46:56,580
Your skin peels off.

579
00:46:56,820 --> 00:46:57,779
All of it.

580
00:46:57,780 --> 00:46:58,780
Peels off.

581
00:46:59,380 --> 00:47:02,040
So it looks like you have a massive
sunburn everywhere.

582
00:47:02,360 --> 00:47:03,580
I was itchy everywhere.

583
00:47:04,820 --> 00:47:07,200
It was like an itch that you could never
stop.

584
00:47:09,440 --> 00:47:11,620
And that chemotherapy didn't work for
her.

585
00:47:11,820 --> 00:47:14,240
And then I sent her to get high-dose
interleukin-2.

586
00:47:15,440 --> 00:47:17,700
My chest started to fill up with fluid.

587
00:47:19,000 --> 00:47:21,840
I remember sitting across just like this
from my...

588
00:47:22,110 --> 00:47:27,270
Mom, in the family room of her house,
and I would have to go, Mom, what are we

589
00:47:27,270 --> 00:47:28,270
going to do?

590
00:47:28,730 --> 00:47:29,830
That was my breathing.

591
00:47:30,590 --> 00:47:32,610
And the high-dose interleukin-2 didn't
work.

592
00:47:33,170 --> 00:47:37,270
At the same time, though, I had an MRI
done, which I had not had done

593
00:47:37,270 --> 00:47:39,790
previously, and they found a brain
tumor.

594
00:47:40,250 --> 00:47:42,910
So she needed radiation to her brain.

595
00:47:46,830 --> 00:47:50,610
You know when you break your neck and
that thing sits on your shoulders and

596
00:47:50,610 --> 00:47:52,110
they screw it into your head?

597
00:47:52,850 --> 00:47:57,950
That's what they put on you when you
have to be bolted to a table when they

598
00:47:57,950 --> 00:47:58,950
give you brain radiation.

599
00:47:59,710 --> 00:48:04,410
So I had somebody come at me with a
drill and screw things into my head

600
00:48:04,410 --> 00:48:05,850
while fully awake and conscious.

601
00:48:06,130 --> 00:48:09,870
The life expectancy of someone with
metastatic melanoma at the time was

602
00:48:09,870 --> 00:48:13,410
about seven months. So we are way into
that at this point.

603
00:48:22,760 --> 00:48:24,640
We published the paper in 1996.

604
00:48:27,440 --> 00:48:28,740
Everybody kind of went, wow.

605
00:48:29,760 --> 00:48:32,600
And that was kind of it.

606
00:48:41,340 --> 00:48:47,300
We were all very skeptical of the
science of cancer immunology. I wasn't

607
00:48:47,300 --> 00:48:48,300
sure.

608
00:48:48,330 --> 00:48:53,150
that what he had done successfully in a
mouse, in a very controlled setting,

609
00:48:53,370 --> 00:48:57,850
would ultimately translate to a method
that would work in a human being.

610
00:48:58,230 --> 00:49:01,750
You're going to be hearing a good deal
more about something called interferon

611
00:49:01,750 --> 00:49:02,750
these days.

612
00:49:02,810 --> 00:49:07,990
Skepticism about an immunotherapy drug
for cancer stems from the 1980s.

613
00:49:08,050 --> 00:49:11,630
Researchers are now calling a new cancer
treatment the most promising in 30

614
00:49:11,630 --> 00:49:16,450
years. When attempts at using the immune
system to fight cancer offer an enormous

615
00:49:16,450 --> 00:49:17,450
promise.

616
00:49:18,190 --> 00:49:22,210
called interleukin-2. And then,
devastating disappointment.

617
00:49:22,530 --> 00:49:25,090
Because fewer patients than expected
seemed to benefit.

618
00:49:25,310 --> 00:49:29,890
For years, there were clinical trials,
and none of these worked. We started to

619
00:49:29,890 --> 00:49:33,970
see some bad side effects. And I can
tell you, these were not happy meetings

620
00:49:33,970 --> 00:49:34,968
to attend.

621
00:49:34,970 --> 00:49:39,750
They all started with, we did this
experiment in animals in our lab, and it

622
00:49:39,750 --> 00:49:43,310
looked great, and then we did a clinical
trial, and nobody got better.

623
00:49:45,200 --> 00:49:49,380
Years of that had led to a view that
immunotherapy would just never work.

624
00:49:52,820 --> 00:49:59,600
20 or 30 years ago, cancer was not a
very big thing for drug companies.

625
00:49:59,980 --> 00:50:02,260
The drugs didn't work that well.

626
00:50:02,480 --> 00:50:04,540
The patients didn't live that long.

627
00:50:05,020 --> 00:50:10,400
The much more lucrative drugs were for
heart disease or diabetes.

628
00:50:11,770 --> 00:50:16,690
chronic diseases that people would take
drugs for for the rest of their lives.

629
00:50:19,570 --> 00:50:24,430
Jim first goes to BMS who had held the
patents and Peter Lindsley worked for

630
00:50:24,430 --> 00:50:25,430
them at the time.

631
00:50:27,310 --> 00:50:31,890
The guys at BMS had told him, we like
CTLA-4 but we think it has other

632
00:50:31,890 --> 00:50:32,890
applications.

633
00:50:33,670 --> 00:50:37,210
But in fact they weren't doing anything
clinically with it at all.

634
00:50:38,640 --> 00:50:41,380
I was very disappointed in the initial
response, but it got more and more

635
00:50:41,380 --> 00:50:42,380
frustrating with time.

636
00:50:43,100 --> 00:50:46,300
It was just no, place after place after
place.

637
00:50:47,860 --> 00:50:52,340
The scientists would get happy, you
know, and excited, and attorneys would

638
00:50:52,340 --> 00:50:57,020
say, no, no, no, no, no, you can't do
this because Bristol-Myers Squibb

639
00:50:57,020 --> 00:50:59,060
already has filed for a patent on their
antibody.

640
00:50:59,720 --> 00:51:02,360
And I said, have you read their patent?
Their patent is backwards.

641
00:51:03,920 --> 00:51:06,900
But still, you know, the company would
say, well, BMS has got more lawyers

642
00:51:06,900 --> 00:51:07,900
than...

643
00:51:08,339 --> 00:51:12,600
We'd had a big company and so too bad

644
00:51:12,600 --> 00:51:19,560
So there were all kinds of things that
like stood in the way of this

645
00:51:19,560 --> 00:51:23,060
happening and I would say You know his
experiment in this was to just keep

646
00:51:23,060 --> 00:51:26,220
fighting to say there's something here.
There's something here something here

647
00:51:26,220 --> 00:51:32,980
And that's where I really give him
credit It's like a bloodhound on the

648
00:51:32,980 --> 00:51:37,420
scent. He's not going to get taken off
the scent until he's found the fox.

649
00:51:42,480 --> 00:51:49,160
I would always

650
00:51:49,160 --> 00:51:54,120
plan vacations places where he could not
get a phone call and he could not be

651
00:51:54,120 --> 00:51:55,400
connected to the internet.

652
00:51:56,600 --> 00:51:59,560
Dad is doing a great job of shopping.

653
00:52:01,110 --> 00:52:02,890
Robert, go over there and stand by dad.

654
00:52:03,310 --> 00:52:04,310
Okay.

655
00:52:11,370 --> 00:52:18,030
It was about two years that nobody would
listen, and

656
00:52:18,030 --> 00:52:20,210
so it was getting depressing.

657
00:52:28,270 --> 00:52:30,710
My brother Mike had metastatic prostate
cancer.

658
00:52:31,350 --> 00:52:34,690
He presented with a lot of joint pain,
which is how they found him.

659
00:52:37,630 --> 00:52:42,930
We often had Thanksgiving with Mike for
many years in Berkeley. He'd come out,

660
00:52:42,970 --> 00:52:44,590
and so I got to know him quite well.

661
00:52:45,850 --> 00:52:51,050
Mike got diagnosed in his 50s with
metastatic prostate cancer to the bone.

662
00:52:51,390 --> 00:52:55,350
That's how he was first diagnosed, and
that pretty much is a death sentence.

663
00:52:55,820 --> 00:52:59,780
And that also, during this time, while
Jim was trying to march forward this new

664
00:52:59,780 --> 00:53:04,840
therapy, he really wanted to be able to
give this to his brother. I need to get

665
00:53:04,840 --> 00:53:06,580
it into people. I need to get it into
patients.

666
00:53:11,740 --> 00:53:17,120
Jim turns his search towards smaller and
smaller biotech companies, looking for

667
00:53:17,120 --> 00:53:19,740
anyone willing to take a gamble on his
idea.

668
00:53:23,760 --> 00:53:28,600
In Boulder, Colorado, he finds Alan
Korman, who is creating drugs for

669
00:53:28,600 --> 00:53:29,600
autoimmune disease.

670
00:53:30,920 --> 00:53:33,280
My interest was in immunology.

671
00:53:33,500 --> 00:53:38,040
I didn't really know much about cancer
biology or cancer therapy.

672
00:53:41,320 --> 00:53:47,800
I think it was useful not to be biased
by the current thinking of how to go

673
00:53:47,800 --> 00:53:48,800
after cancer.

674
00:53:50,060 --> 00:53:55,340
The concept of jumping into a problem
and being the naive one is really

675
00:53:55,340 --> 00:53:59,100
useful. The people that have been in
that field very long can do the exact

676
00:53:59,100 --> 00:54:01,480
same thing. I think you get tunnel
vision.

677
00:54:03,280 --> 00:54:08,540
Corman's job will be to take the CTLA-4
antibody that Jim and Max developed for

678
00:54:08,540 --> 00:54:12,780
mice and make it into a drug that can
work safely in humans.

679
00:54:13,540 --> 00:54:16,320
The drug will be called ipilimumab.

680
00:54:17,770 --> 00:54:22,930
I ended up collaborating with someone
that I knew from graduate school, a guy

681
00:54:22,930 --> 00:54:24,050
named Nils Lomberg.

682
00:54:25,690 --> 00:54:31,710
Nils Lomberg works for Metarex, a small
biotech company based in San Francisco.

683
00:54:33,630 --> 00:54:35,490
I got a call from Alan.

684
00:54:36,010 --> 00:54:40,350
We started talking about the idea of
ipilimumia. Ipilimumia hadn't been

685
00:54:40,350 --> 00:54:45,330
created yet, and I convinced him to let
me in on this. I was fascinated.

686
00:54:46,810 --> 00:54:51,950
Jim and Alan Corman and Nils Lahnberg
all get together at the bar in the

687
00:54:51,950 --> 00:54:55,330
basement of the Hotel Boulderado, right
in downtown Boulder.

688
00:54:58,370 --> 00:55:01,570
Jim's primary concern was that we move
quickly.

689
00:55:01,810 --> 00:55:05,510
I think he was very skeptical of the
whole biotech pharmaceutical industry.

690
00:55:05,630 --> 00:55:06,870
He didn't think we had the urgency.

691
00:55:09,570 --> 00:55:13,950
I ended up sitting up with him most of
the night with a bottle of whiskey.

692
00:55:15,160 --> 00:55:18,320
Out of that conversation, we had a
handshake agreement.

693
00:55:20,380 --> 00:55:25,140
And with that handshake, we started work
back in California, back in the lab.

694
00:55:28,560 --> 00:55:32,020
466 days later, we had ipilimumab in a
patient.

695
00:55:33,220 --> 00:55:35,120
And I think that's a world's record.

696
00:55:47,720 --> 00:55:53,800
Phase one tests a relatively small
number of people, generally, for safety.

697
00:55:54,480 --> 00:55:57,600
Sometimes they get a little hint of
whether the drug's working, but

698
00:55:57,600 --> 00:56:02,920
generally it's just to make sure that
the drug is not going to harm somebody.

699
00:56:03,540 --> 00:56:10,200
We picked a dose that was, you know, a
coin toss that was based,

700
00:56:10,360 --> 00:56:13,760
you know, somewhat loosely on what we
had done in the mouse.

701
00:56:14,560 --> 00:56:18,900
But clearly, you know, we didn't know
enough about how to figure out its

702
00:56:18,900 --> 00:56:19,900
potency.

703
00:56:21,520 --> 00:56:26,220
When we were developing the phase one
clinical trials, there were many stops

704
00:56:26,220 --> 00:56:27,098
and starts.

705
00:56:27,100 --> 00:56:30,700
There were many times when it was
wondered whether or not the clinical

706
00:56:30,700 --> 00:56:31,820
trial could even start.

707
00:56:32,280 --> 00:56:35,660
Which tumor type should we do it in?
Should it be all comers? Should we focus

708
00:56:35,660 --> 00:56:36,680
on melanoma patients?

709
00:56:37,060 --> 00:56:40,640
How many patients should we enroll in
the phase one clinical trial? How much

710
00:56:40,640 --> 00:56:42,760
of a budget did we have to enroll these
patients?

711
00:56:43,280 --> 00:56:46,900
What was the starting dose of the drug
that we were going to give? Were we

712
00:56:46,900 --> 00:56:49,800
taking the starting dose just based on
mouse data? Which, by the way, is what

713
00:56:49,800 --> 00:56:50,800
we did.

714
00:57:00,490 --> 00:57:05,430
when drugs go into phase one trials
their first trials in people nine out of

715
00:57:05,430 --> 00:57:10,830
ten or more fail and that's it you pull
the plug at that first stage

716
00:57:10,830 --> 00:57:17,430
i ran that clinical trial at that time
it was amazing

717
00:57:17,430 --> 00:57:21,350
because three out of the 12 patients was
a very small clinical trial three out of

718
00:57:21,350 --> 00:57:24,010
the 12 patients showed that all of the
tumor went away

719
00:57:24,720 --> 00:57:29,400
We never see this in a phase one trial.
It's so rare that it's sort of like, you

720
00:57:29,400 --> 00:57:33,800
know, finding the pot at the end of the
rainbow. You know, you feel like, am I

721
00:57:33,800 --> 00:57:37,240
really seeing this or am I imagining it,
right? It's just unbelievable.

722
00:57:38,900 --> 00:57:45,460
I became aware that CTLA-4 was the focus
of an early set of clinical trials that

723
00:57:45,460 --> 00:57:52,100
was through the clinical trial grapevine
producing a little bit of activity in

724
00:57:52,100 --> 00:57:53,540
patients with advanced melanoma

725
00:57:54,640 --> 00:57:56,480
Obviously, I wanted to be part of that.

726
00:58:08,840 --> 00:58:14,220
I remember going Christmas shopping in a
wheelchair in the mall where we grew up.

727
00:58:17,520 --> 00:58:19,580
That was probably the worst Christmas
ever.

728
00:58:23,440 --> 00:58:26,460
I remember sitting underneath the
Christmas tree with Rob, and I was a

729
00:58:26,460 --> 00:58:28,360
huddling mess on the floor.

730
00:58:29,220 --> 00:58:31,840
And he just held me and told me to work
it out.

731
00:58:33,160 --> 00:58:36,220
That Christmas was hard because I didn't
think I was going to see the next one.

732
00:58:46,860 --> 00:58:51,220
She comes to clinic and I say, I think
that we're really at the point where the

733
00:58:51,220 --> 00:58:55,000
readily available standard options are
not working for you.

734
00:58:56,280 --> 00:59:00,620
There is a clinical trial that you could
consider participating in.

735
00:59:02,160 --> 00:59:07,200
I remember Dr. Walchuk explaining it to
me in very, very simple terms, that

736
00:59:07,200 --> 00:59:11,040
instead of an outside agent like
chemotherapy, your body then uses its

737
00:59:11,040 --> 00:59:12,800
own immune system to fight off cancer.

738
00:59:13,420 --> 00:59:16,780
It allows it to turn on the immune
system and recognize cancer in a way

739
00:59:16,780 --> 00:59:17,780
that it previously couldn't.

740
00:59:21,880 --> 00:59:24,700
Sharon got four doses of ipilimumab.

741
00:59:25,980 --> 00:59:27,720
The treatments were not like
chemotherapy.

742
00:59:29,160 --> 00:59:33,140
Chemotherapy, you go back three or four
days in that week. You live at that

743
00:59:33,140 --> 00:59:34,140
oncologist's office.

744
00:59:34,840 --> 00:59:35,840
It's your home.

745
00:59:36,100 --> 00:59:37,360
This was different.

746
00:59:37,640 --> 00:59:39,920
I had a shot in my leg.

747
00:59:40,510 --> 00:59:44,110
And then I had a 90-minute IV infusion.
That was it.

748
00:59:45,790 --> 00:59:51,890
Because I wasn't in chemotherapy either,
I didn't feel nauseous. I didn't feel

749
00:59:51,890 --> 00:59:55,170
the incredible fatigue that came along
with it.

750
00:59:55,430 --> 00:59:59,570
I noticed a difference in myself just
from changing treatments.

751
01:00:01,410 --> 01:00:07,150
Once a drug is proven safe in Phase I
trials, it moves into Phase II and Phase

752
01:00:07,150 --> 01:00:08,150
III.

753
01:00:08,640 --> 01:00:13,320
These trials include far more patients
studied over much longer time periods.

754
01:00:13,640 --> 01:00:16,280
They can cost hundreds of millions of
dollars.

755
01:00:17,320 --> 01:00:21,660
We never could have developed ipilimumab
as a small company, even a publicly

756
01:00:21,660 --> 01:00:23,760
traded company, we never could have
raised that much money.

757
01:00:24,960 --> 01:00:29,760
Mederex has defined a partner with deep
pockets, but the big pharma companies

758
01:00:29,760 --> 01:00:30,920
are wary of the risk.

759
01:00:32,360 --> 01:00:37,140
For any hope of success, ipilimumab
needs a champion inside the

760
01:00:37,140 --> 01:00:38,300
pharmaceutical industry.

761
01:00:40,120 --> 01:00:44,860
When I left the NIH to go to industry, I
went to Bayer that was building an

762
01:00:44,860 --> 01:00:45,940
oncology program.

763
01:00:47,120 --> 01:00:52,060
I really wanted to supervise the
development of ipi. When Bayer declined,

764
01:00:52,580 --> 01:00:58,580
I left Bayer after seven years
specifically to bring ipilimumab

765
01:00:58,580 --> 01:00:59,580
forward.

766
01:01:02,240 --> 01:01:05,760
BMS was not sure they were going to take
it at all. So I came at just the right

767
01:01:05,760 --> 01:01:06,760
time.

768
01:01:06,920 --> 01:01:10,940
And I was ready to advocate for it. I
went to BMS.

769
01:01:11,180 --> 01:01:13,800
I said, let me walk you through why this
is important.

770
01:01:15,400 --> 01:01:17,080
I must admit, I was apprehensive.

771
01:01:17,880 --> 01:01:21,600
The fact that BMS had another antibody
would have been one of the reasons that

772
01:01:21,600 --> 01:01:24,700
a lot of companies had given for not
working with us.

773
01:01:25,300 --> 01:01:26,680
You know, BMS can kill you.

774
01:01:26,980 --> 01:01:30,500
Stocks to watch today. A big one will be
Bristol-Myers Squibb.

775
01:01:30,830 --> 01:01:34,610
There were other reasons to be
apprehensive of Bristol Myers Squibb.

776
01:01:35,470 --> 01:01:38,410
Bristol Myers had a pretty good
reputation.

777
01:01:39,170 --> 01:01:40,990
Then that started to fade.

778
01:01:42,660 --> 01:01:47,780
They did a deal for a drug from a small
company called Imclone.

779
01:01:48,020 --> 01:01:52,300
The drug sparked an insider trading
scandal that led to a seven-year prison

780
01:01:52,300 --> 01:01:55,700
sentence. Pessimism propelled by news
that yet another corporate giant may

781
01:01:55,700 --> 01:01:56,780
have accounting problems.

782
01:01:57,040 --> 01:02:01,160
Today, it's Bristol-Myers Squibb in the
government's crosshairs. So they went

783
01:02:01,160 --> 01:02:06,060
through in the early to mid-2000s a very
hard...

784
01:02:06,590 --> 01:02:10,030
period bristol meyer squibb one of the
leaders in the industry forecast

785
01:02:10,030 --> 01:02:13,930
disappointing earnings growth for its
second quarter so what we were asking

786
01:02:13,930 --> 01:02:20,710
bms to do is invest a healthy amount of
money into the belief that

787
01:02:20,710 --> 01:02:26,330
these drugs were going to work it was
against the grain a lot of our external

788
01:02:26,330 --> 01:02:31,170
advisors said we were probably investing
too much in immunotherapy because

789
01:02:31,170 --> 01:02:32,390
nothing had worked before

790
01:02:35,500 --> 01:02:40,300
My presentation focused not on the
response rate, which was very low at the

791
01:02:40,300 --> 01:02:46,720
time, but one patient who had received,
I think it was a single dose at the

792
01:02:46,720 --> 01:02:50,760
time, that now two and three years out
was still in remission.

793
01:02:52,220 --> 01:02:57,400
The very first public meeting, Rachel
made it a point for me to come and sit

794
01:02:57,400 --> 01:02:58,400
next to her.

795
01:02:59,040 --> 01:03:01,560
And I'll never forget because I was
sitting there and there were some

796
01:03:01,560 --> 01:03:05,230
people. I had very little understanding
of immunology. They were making comments

797
01:03:05,230 --> 01:03:10,130
about what they thought this meant or
that meant. I was just sitting there

798
01:03:10,130 --> 01:03:11,130
going, oh, bullshit.

799
01:03:11,670 --> 01:03:16,230
And I was just sort of under my breath,
you know, going, oh, my God.

800
01:03:17,010 --> 01:03:19,310
And obviously getting agitated.

801
01:03:19,610 --> 01:03:22,810
And Rachel, you know, kept looking at
me.

802
01:03:23,530 --> 01:03:24,530
And afterwards...

803
01:03:24,940 --> 01:03:28,880
She says, OK, well, I wrote down every
time you started snorting and stuff. And

804
01:03:28,880 --> 01:03:29,879
so what about this?

805
01:03:29,880 --> 01:03:30,880
What's wrong with that?

806
01:03:30,980 --> 01:03:34,100
What's wrong with this from her notes?
And so we went over the notes for a

807
01:03:34,100 --> 01:03:36,040
while. It was really a lot of fun.

808
01:03:36,720 --> 01:03:40,640
I was part of the group of people who
was following, let's call it the

809
01:03:40,640 --> 01:03:42,640
conventional path of cancer research.

810
01:03:43,000 --> 01:03:47,640
Jim Allison and the immunology crowd was
thinking about it differently.

811
01:03:48,060 --> 01:03:50,640
And the mainstream was more or less
ignoring that.

812
01:03:52,620 --> 01:03:54,100
Innovation is extremely difficult.

813
01:03:54,890 --> 01:03:58,850
There was somebody, a regulatory person
on my team, who yelled at me, screamed

814
01:03:58,850 --> 01:03:59,850
at me.

815
01:03:59,890 --> 01:04:02,050
We don't get it. We're wasting our time.

816
01:04:05,390 --> 01:04:10,270
And it was not just the members of the
team, because back in the day, most of

817
01:04:10,270 --> 01:04:12,570
the doctors were not immuno-oncology
believers.

818
01:04:13,690 --> 01:04:15,890
That's why it was hard to get patients
on the study initially.

819
01:04:16,130 --> 01:04:17,170
That's why it took so long.

820
01:04:17,810 --> 01:04:21,070
There was like a year where that
clinical study could not be enrolled. It

821
01:04:21,070 --> 01:04:23,250
was very, very slow.

822
01:04:23,610 --> 01:04:27,250
No one wanted to hear about another
cancer immunotherapy agent. It was, you

823
01:04:27,250 --> 01:04:28,950
know, forget it. We don't want to talk
to you.

824
01:04:29,710 --> 01:04:32,670
And you can imagine a lot of doors
slammed in his face.

825
01:04:35,850 --> 01:04:41,110
You might argue that there is a defense
mechanism against new ideas. They are

826
01:04:41,110 --> 01:04:45,450
seen as mutations, as cancerous to a
body of thought.

827
01:04:48,090 --> 01:04:52,490
You don't know whether the new idea is
something potent or deadly.

828
01:04:54,190 --> 01:04:57,910
And that's why they're often viewed with
skepticism, and that's why it takes a

829
01:04:57,910 --> 01:05:03,430
really powerful idea combined with
someone willing to push it forward to

830
01:05:03,430 --> 01:05:04,430
make it happen.

831
01:05:05,190 --> 01:05:07,650
I inherited predisposition for cancer.

832
01:05:08,750 --> 01:05:14,630
My mother had melanoma, my grandfather
had pancreatic cancer, and my beloved

833
01:05:14,630 --> 01:05:18,290
uncle got glioma when he was 58.

834
01:05:18,730 --> 01:05:21,670
So I know that cancer is coming for me.

835
01:05:22,570 --> 01:05:24,930
I know it's coming from my family.

836
01:05:27,030 --> 01:05:30,250
I'm just about the age my uncle was when
he got his brain tumor.

837
01:05:31,150 --> 01:05:33,110
The stakes are so high.

838
01:05:34,130 --> 01:05:41,130
The opportunity is so great that somehow
it just

839
01:05:41,130 --> 01:05:47,770
didn't matter when people yelled at me
or created barriers.

840
01:05:52,110 --> 01:05:53,350
Because we're going to make it work.

841
01:05:54,070 --> 01:05:55,350
We're going to make it happen.

842
01:06:01,870 --> 01:06:02,970
I'm still in Berkeley.

843
01:06:04,410 --> 01:06:09,010
But the action had moved to New York,
where the companies are and a lot of the

844
01:06:09,010 --> 01:06:10,770
studies were going on at Sloan
Kettering.

845
01:06:13,430 --> 01:06:18,530
I thought, well, there's some
not-so-good stuff happening to my baby

846
01:06:18,530 --> 01:06:19,530
over there.

847
01:06:20,070 --> 01:06:21,530
And I better move again.

848
01:06:27,620 --> 01:06:32,480
Jim decides he needs to be in New York
where the major trials are going on.

849
01:06:32,720 --> 01:06:37,080
When I asked Jim why he needed to be
there, he said, I went there to be a

850
01:06:37,080 --> 01:06:38,080
nuisance.

851
01:06:39,380 --> 01:06:42,500
He wanted to stay on the scientists. He
wanted to stay on the FDA. He wanted to

852
01:06:42,500 --> 01:06:43,640
stay on Bristol-Myers Squibb.

853
01:06:48,120 --> 01:06:50,740
Anytime a lab moves, it's always a tough
decision.

854
01:06:51,640 --> 01:06:55,960
especially if you're moving across the
country. People have roots in a given

855
01:06:55,960 --> 01:07:00,300
area. I'd been in the Bay Area for
almost a dozen years at that point.

856
01:07:01,520 --> 01:07:05,080
So when Jim decided to move from
Berkeley to Sloan-Kettering, I think

857
01:07:05,080 --> 01:07:09,240
it's a testament to how dedicated all of
us were to this work and the promise we

858
01:07:09,240 --> 01:07:16,120
saw in it that I would say at least 90%
of the people at Jim's lab picked up and

859
01:07:16,120 --> 01:07:17,120
moved cross-country.

860
01:07:23,180 --> 01:07:26,200
It was a tough move in that, you know,
you're moving all your stuff, you're

861
01:07:26,200 --> 01:07:28,040
moving a lab. Things in the labs are
delicate.

862
01:07:30,480 --> 01:07:37,060
We actually lost an entire freezer full
of sort of critical, unreplaceable

863
01:07:37,060 --> 01:07:38,060
reagents.

864
01:07:39,380 --> 01:07:44,080
Somewhere in the desert, halfway across,
the refrigerated truck that it was

865
01:07:44,080 --> 01:07:45,300
plugged into blew a fuse.

866
01:07:47,160 --> 01:07:49,500
So there was some pain to go with that
move.

867
01:08:09,610 --> 01:08:12,970
Jim being in New York was truly a fish
out of water.

868
01:08:14,950 --> 01:08:19,689
I'm not sure Jim walked more than three
blocks from his apartment on the Upper

869
01:08:19,689 --> 01:08:20,689
East Side.

870
01:08:22,229 --> 01:08:25,529
But, you know, he didn't move to New
York to take advantage of what New York

871
01:08:25,529 --> 01:08:26,509
has to offer.

872
01:08:26,510 --> 01:08:29,410
He moved to take advantage of what Sloan
Kettering had to offer.

873
01:08:33,029 --> 01:08:37,450
Putting pressure on Jim is Pfizer, the
world's largest drug company.

874
01:08:40,330 --> 01:08:45,029
Seeing the progress of IPI, Pfizer has
launched a competitive cancer drug,

875
01:08:45,229 --> 01:08:47,970
drawing from Jeffrey Bluestone's work.

876
01:08:49,189 --> 01:08:53,950
I went to Pfizer, and they got excited
about it. We were on track. I was

877
01:08:53,950 --> 01:08:57,010
working on them to make the drug, and
things looked really good.

878
01:08:59,729 --> 01:09:05,630
Tremilimumab was being developed by
Pfizer, and the early signals for both

879
01:09:05,630 --> 01:09:07,790
of the medicines were remarkably
similar.

880
01:09:08,939 --> 01:09:11,460
Pfizer came in late when they saw
Reasons to Believe.

881
01:09:11,720 --> 01:09:12,819
Very classic.

882
01:09:13,300 --> 01:09:16,920
We think maybe you have something here.
We have one just like it.

883
01:09:17,460 --> 01:09:19,660
We're going to beat you.

884
01:09:23,740 --> 01:09:30,439
The race is on, and watching it closely
is the FDA, the U.S. government agency

885
01:09:30,439 --> 01:09:34,380
that determines whether a drug is safe
and effective enough for patients.

886
01:09:37,640 --> 01:09:42,300
The FDA is judging the clinical trials
by standards developed for evaluating

887
01:09:42,300 --> 01:09:43,300
chemotherapy.

888
01:09:45,660 --> 01:09:51,460
The rules said if a patient hadn't had
their tumor shrink by 30% within 12

889
01:09:51,460 --> 01:09:52,979
weeks, they failed.

890
01:09:54,940 --> 01:09:59,120
In Pfizer's trial, the tumors don't
shrink after 12 weeks.

891
01:09:59,340 --> 01:10:00,340
They grow.

892
01:10:01,640 --> 01:10:06,300
Failing to meet FDA standards, Pfizer
decides to cut its losses.

893
01:10:08,340 --> 01:10:12,020
Pfizer did this giant trial, and just
everybody was watching.

894
01:10:12,500 --> 01:10:13,500
It failed.

895
01:10:14,000 --> 01:10:15,280
You know, a big blow.

896
01:10:15,520 --> 01:10:18,580
You know, the biggest drug company in
the world just abandons the whole field.

897
01:10:18,680 --> 01:10:22,100
I mean, everybody, when we started out,
one of the main criticisms we had is,

898
01:10:22,140 --> 01:10:26,320
immunotherapy's never worked, it'll
never work, it's a bunch of voodoo, and

899
01:10:26,320 --> 01:10:28,440
you shouldn't even try it.

900
01:10:29,960 --> 01:10:32,280
Now here's this big failure.

901
01:10:33,660 --> 01:10:36,480
BMS thought there's only one other in
the class.

902
01:10:36,680 --> 01:10:37,780
It just failed.

903
01:10:38,240 --> 01:10:42,400
We don't want to put more money in. In
fact, should we be closing the studies

904
01:10:42,400 --> 01:10:43,400
you're doing now?

905
01:10:43,800 --> 01:10:47,460
Many of my colleagues said, this will
never work.

906
01:10:47,680 --> 01:10:49,100
This is a dry well.

907
01:10:50,300 --> 01:10:55,380
Jim struggles to make it clear that
ipilimumab is not a chemotherapy drug

908
01:10:55,380 --> 01:10:57,700
and doesn't behave like one.

909
01:10:58,900 --> 01:11:00,340
People go back to their community.

910
01:11:00,940 --> 01:11:04,340
As soon as they got back, they'd put
them on some chemotherapy drugs that had

911
01:11:04,340 --> 01:11:07,280
been shown never to work. But now
they're responding to such and such. I

912
01:11:07,280 --> 01:11:08,280
said, yeah, right.

913
01:11:08,500 --> 01:11:10,200
You know, it's another de-explanation.

914
01:11:11,600 --> 01:11:15,480
They're just responding late, which is
what I showed you in the mice.

915
01:11:16,760 --> 01:11:21,320
You go back to Jim's early experiments
in mice with CTLA-4.

916
01:11:22,200 --> 01:11:25,700
Jim observed that the T cells were
entering.

917
01:11:26,240 --> 01:11:30,640
into the tumors and they were expanding
in size before the t cells then were

918
01:11:30,640 --> 01:11:33,600
able to destroy the tumors and then they
would shrink in size

919
01:11:33,600 --> 01:11:41,260
so

920
01:11:41,260 --> 01:11:46,060
jim had to convince bristol myers-quibb
to do a much more expensive much more

921
01:11:46,060 --> 01:11:52,860
lengthy trial unlike jim who to

922
01:11:52,860 --> 01:11:53,860
his credit

923
01:11:54,420 --> 01:11:59,200
persevered and did whatever it took i
felt i had done exactly what i normally

924
01:11:59,200 --> 01:12:04,180
would do which is to just let the other
folks make the drug little did i know at

925
01:12:04,180 --> 01:12:07,760
the time that they would give up on it
so quickly

926
01:12:07,760 --> 01:12:14,740
jim was visibly angry he'd just go into

927
01:12:14,740 --> 01:12:20,260
a tirade i've got to make this happen
because the easiest you'll never get

928
01:12:20,260 --> 01:12:25,960
fired for saying no if you're you know
responsible for spending a lot of money

929
01:12:25,960 --> 01:12:30,520
the skepticism was widespread and
frankly jim experienced it probably

930
01:12:30,520 --> 01:12:31,020
every day

931
01:12:31,020 --> 01:12:38,080
every

932
01:12:38,080 --> 01:12:43,520
time i'd see him he would just you could
see his blood pressure going up that was

933
01:12:43,520 --> 01:12:49,240
hard on him during those years and hard
on people around him that was a trying

934
01:12:49,240 --> 01:12:52,160
time jim became rather obsessed

935
01:12:53,230 --> 01:12:58,410
The science and the project just
consumed him, and I really couldn't be a

936
01:12:58,410 --> 01:12:59,410
part of that.

937
01:13:02,450 --> 01:13:09,050
With no science background of my own,
our son off in college, we

938
01:13:09,050 --> 01:13:10,770
had less and less in common.

939
01:13:11,030 --> 01:13:15,070
That didn't mean that we didn't admire
each other and care greatly for each

940
01:13:15,070 --> 01:13:18,390
other, but we just decided to go our
separate ways.

941
01:13:29,260 --> 01:13:31,160
I was afraid the drug was going to go
down.

942
01:13:32,300 --> 01:13:39,180
And I invested not just myself, but my
family, you know.

943
01:13:40,260 --> 01:13:42,140
It was a tough time.

944
01:13:44,940 --> 01:13:50,560
I think any great, big, disruptive
change that you're pushing for is going

945
01:13:50,560 --> 01:13:52,100
to take some single-mindedness.

946
01:13:53,440 --> 01:13:57,080
Whether it has to be sacrifice, I don't
know. I suppose maybe it does.

947
01:14:09,160 --> 01:14:14,100
At Memorial Sloan Kettering Cancer
Center, doctors are seeing in patients

948
01:14:14,100 --> 01:14:16,340
exactly what Jim has predicted.

949
01:14:17,520 --> 01:14:20,780
Patients were coming in and telling us
that they felt well.

950
01:14:21,160 --> 01:14:24,200
Even though the CAT scans are showing
that the tumors are growing, these

951
01:14:24,200 --> 01:14:26,740
patients said, I'm feeling really great
on this treatment.

952
01:14:27,020 --> 01:14:32,080
Some people, after they came off of the
clinical trials of ipilimumab, began to

953
01:14:32,080 --> 01:14:34,920
get better with no further therapy.

954
01:14:35,720 --> 01:14:38,260
And this was quite striking.

955
01:14:39,370 --> 01:14:43,530
And so at that point, clinicians like
Jed Walchuk asked these kind of

956
01:14:43,530 --> 01:14:48,950
immovable, implacable forces, Big Pharma
and the United States government, the

957
01:14:48,950 --> 01:14:51,850
FDA, to change the trial.

958
01:14:52,410 --> 01:14:58,430
The risk BMS was taking at the time was
we were committing to years more

959
01:14:58,430 --> 01:15:01,890
of clinical study before we'd ever get
approval.

960
01:15:02,910 --> 01:15:06,850
In an environment where there was
tremendous uncertainty about whether

961
01:15:06,850 --> 01:15:08,010
this thing was going to work or not.

962
01:15:08,460 --> 01:15:14,400
We were asked to do another five years
of expensive, long, tedious trials.

963
01:15:15,280 --> 01:15:19,180
There were investors that didn't think
this was going to work.

964
01:15:19,560 --> 01:15:23,380
We hadn't had a long track record of
recent success.

965
01:15:24,360 --> 01:15:25,460
This takes a toll.

966
01:15:26,660 --> 01:15:27,740
This takes a toll.

967
01:15:52,720 --> 01:15:56,600
It was in the final throes of metastatic
prostate cancer.

968
01:15:57,020 --> 01:15:59,300
And the drug was in trials by then.

969
01:15:59,580 --> 01:16:02,560
And there were really good results
coming back.

970
01:16:03,460 --> 01:16:05,960
But it was just not possible.

971
01:16:06,220 --> 01:16:10,980
And that was, you know, it was
frustrating.

972
01:16:11,320 --> 01:16:16,100
But, you know, at the time, I just
wasn't so sure about whether it would

973
01:16:16,100 --> 01:16:19,680
really, at the end of the day, do my
brother any good because he was so sick

974
01:16:19,680 --> 01:16:20,680
by then.

975
01:16:29,520 --> 01:16:33,320
I remember him calling me from Dallas
when, you know, Mike was dying.

976
01:16:33,520 --> 01:16:38,420
And he was in his arms at the time. And
you can imagine, you know, what that

977
01:16:38,420 --> 01:16:39,420
would do to you.

978
01:16:45,940 --> 01:16:51,680
When I was first told I had prostate
cancer, I was terrified because it was a

979
01:16:51,680 --> 01:16:52,980
week after my brother had died.

980
01:16:56,200 --> 01:16:59,120
I had been working with the prostate
group at Sloan Kettering.

981
01:16:59,520 --> 01:17:03,600
So I went over to the oncologist's
office. The secretary said, he's with

982
01:17:03,600 --> 01:17:04,800
somebody. I said, I don't care.

983
01:17:05,080 --> 01:17:06,600
I didn't read on his story.

984
01:17:07,080 --> 01:17:11,020
And I said, can I talk with you? He
said, let me. I said, no, now.

985
01:17:11,680 --> 01:17:13,500
I need to talk to you right now.

986
01:17:19,580 --> 01:17:24,480
My oncologist said, in your case,
because of family history, I think we'd

987
01:17:24,480 --> 01:17:25,480
better take it out.

988
01:17:26,700 --> 01:17:28,140
Anyway, they caught it very early.

989
01:17:40,670 --> 01:17:43,530
Sharon came back for her first set of
imaging.

990
01:17:44,450 --> 01:17:48,150
I got a phone call from the radiologist.
Now, usually, you should know,

991
01:17:48,190 --> 01:17:50,110
radiologists don't call with good news.

992
01:17:50,650 --> 01:17:55,850
They call to make you aware of some
awfulness that they have seen on a scan.

993
01:17:56,250 --> 01:18:01,210
And this was a very serious radiologist,
very well respected.

994
01:18:01,790 --> 01:18:06,690
And he called and he said, Jed, I'm
reading your patient Sharon's CAT scans.

995
01:18:06,850 --> 01:18:09,570
He goes, I have to ask you something. He
goes...

996
01:18:10,060 --> 01:18:13,400
What happened to her? I'm like, what do
you mean what happened? He goes, what

997
01:18:13,400 --> 01:18:15,440
did she get? All the cancer went away.

998
01:18:16,580 --> 01:18:20,580
And so that was an important moment for
many of us.

999
01:18:27,460 --> 01:18:33,040
With enough patients showing improved
health, BMS decides to commit to the

1000
01:18:33,040 --> 01:18:37,560
full five-year study and accept the
enormous financial risk.

1001
01:18:39,800 --> 01:18:43,440
Bristol-Myers Square made the decision
with everybody in the room then to use

1002
01:18:43,440 --> 01:18:48,540
overall survival as the endpoint and not
to use the typical sort of tumor

1003
01:18:48,540 --> 01:18:51,900
shrinkage immediately endpoint, but look
to see how patients did over a long

1004
01:18:51,900 --> 01:18:52,900
period of time.

1005
01:18:54,200 --> 01:18:58,900
I give the team at Bristol-Myers, and
Rachel was the lead of that team, credit

1006
01:18:58,900 --> 01:19:04,740
for... listening to us and for being
open to the observations that we were

1007
01:19:04,740 --> 01:19:10,420
really making on the front lines and to
working with us to find a way to capture

1008
01:19:10,420 --> 01:19:11,920
this new biology.

1009
01:19:14,100 --> 01:19:19,120
Most companies and most people in those
companies at that time would wash their

1010
01:19:19,120 --> 01:19:20,980
hands and walk away.

1011
01:19:21,340 --> 01:19:24,240
And so I give great credit to BMS.

1012
01:19:24,460 --> 01:19:28,820
They went with the science. They
believed the scientist and they believed

1013
01:19:28,820 --> 01:19:29,820
the data.

1014
01:19:35,170 --> 01:19:39,630
Dr. Walchuk, in his ever-so-calm voice,
said, So, Sharon, the man that invented

1015
01:19:39,630 --> 01:19:41,290
this is here today.

1016
01:19:41,610 --> 01:19:42,910
Would you like to meet him?

1017
01:19:44,030 --> 01:19:47,550
Yes! He calls me up, says, Come down.

1018
01:19:47,950 --> 01:19:52,550
He didn't tell me that. You know, I
found out why I was there only when I

1019
01:19:52,550 --> 01:19:53,550
walked into the room.

1020
01:19:54,230 --> 01:19:59,030
Dr. Allison walked in, and I pretty much
almost lifted him up off the floor, gave

1021
01:19:59,030 --> 01:20:01,030
him a giant bear hug.

1022
01:20:01,790 --> 01:20:02,910
I just couldn't talk.

1023
01:20:03,370 --> 01:20:06,670
I couldn't talk. How in the world are
you supposed to adequately thank

1024
01:20:06,670 --> 01:20:10,790
somebody standing across from you that
you are 100% positive that without them,

1025
01:20:10,790 --> 01:20:12,110
you wouldn't be here?

1026
01:20:13,730 --> 01:20:15,450
There is no thank you for that.

1027
01:20:17,890 --> 01:20:23,030
Oh, meeting her was amazing because
until then, you know, it was just

1028
01:20:23,030 --> 01:20:24,610
numbers. You know, it was a concept.

1029
01:20:25,730 --> 01:20:27,950
She was the first patient I'd ever met.

1030
01:20:29,530 --> 01:20:32,410
And all we could think about at the end
of that was we got to get a picture.

1031
01:20:32,990 --> 01:20:35,570
We look around the room, and nobody has
a camera.

1032
01:20:36,630 --> 01:20:40,190
The only camera that we could find was
one that they took pictures of a

1033
01:20:40,190 --> 01:20:43,350
melanoma with to send out and get
studied.

1034
01:20:43,650 --> 01:20:47,710
It's not the best quality in the world,
but it definitely memorializes one of

1035
01:20:47,710 --> 01:20:48,710
the best days ever.

1036
01:20:51,070 --> 01:20:52,950
Every single scan since.

1037
01:20:53,390 --> 01:20:56,650
I have another MRI coming up here in
about two weeks, so say a little prayer.

1038
01:20:59,170 --> 01:21:00,370
No evidence of disease.

1039
01:21:01,480 --> 01:21:03,220
In every one sense.

1040
01:21:16,040 --> 01:21:20,180
Now she has her family, two kids, two
beautiful kids.

1041
01:21:21,740 --> 01:21:26,580
I still choke up when I think about
that.

1042
01:21:41,870 --> 01:21:48,630
In 2011, 15 years after Jim Allison made
his initial discovery, the

1043
01:21:48,630 --> 01:21:50,910
clinical trials are finally complete.

1044
01:21:53,450 --> 01:21:57,190
I remember the moment when we saw the
data.

1045
01:21:57,730 --> 01:22:04,390
I can see the people around me. It is
imprinted like a picture because we knew

1046
01:22:04,390 --> 01:22:05,390
we were changing the world.

1047
01:22:06,510 --> 01:22:09,570
Rachel Humphrey came running up.

1048
01:22:09,960 --> 01:22:15,380
the stairs, breathless, to show me the
survival curves, one for the control and

1049
01:22:15,380 --> 01:22:17,440
one for the patients that received Ippy.

1050
01:22:18,480 --> 01:22:21,600
One curve stayed different for as long
as we studied.

1051
01:22:22,480 --> 01:22:27,100
After years, you start to think that
maybe you've cured these patients.

1052
01:22:31,680 --> 01:22:34,840
I happened to be at a melanoma meeting
at Cold Spring Harbor.

1053
01:22:36,200 --> 01:22:40,180
I was sitting next to Harold Varmus, and
I had my iPad on and kept checking it.

1054
01:22:40,240 --> 01:22:41,700
And he said, you know, what are you
doing?

1055
01:22:41,920 --> 01:22:45,620
And I said, well, the FDA is supposed to
announce its decision on the MP today.

1056
01:22:47,160 --> 01:22:49,340
All of a sudden, I got this email.

1057
01:22:50,080 --> 01:22:56,360
It was about 11 on the East Coast, which
meant it was 8 in California. And

1058
01:22:56,360 --> 01:22:59,440
there's Alan in the Metarex crowd
holding glasses and whiskey.

1059
01:23:01,080 --> 01:23:04,280
And I looked at Harold. I said, I guess,
he said, I guess that's good news. I

1060
01:23:04,280 --> 01:23:07,600
said, I think that's good news, yes. And
he said, either that or they just like

1061
01:23:07,600 --> 01:23:08,600
to drink in the morning.

1062
01:23:42,120 --> 01:23:47,980
Allison and others like him have only
begun the thing. Each generation will

1063
01:23:47,980 --> 01:23:48,980
build on the next.

1064
01:23:49,140 --> 01:23:55,100
We're not nearly at the end of this
story. I mean, we're somewhere in the

1065
01:23:55,100 --> 01:23:56,580
very first few chapters.

1066
01:24:01,340 --> 01:24:06,620
This happens fairly regularly. I get
emails, but many times a handwritten

1067
01:24:06,620 --> 01:24:07,620
note.

1068
01:24:08,060 --> 01:24:10,640
This is from somebody I've never met.

1069
01:24:12,010 --> 01:24:18,990
Dear Dr. Allison, two years ago today,
my 63-year-young husband Richard was

1070
01:24:18,990 --> 01:24:23,650
diagnosed with metastatic melanoma to
the brain and everywhere else.

1071
01:24:23,950 --> 01:24:30,590
Thanks to you, your fortitude and
determination

1072
01:24:30,590 --> 01:24:34,910
to prove that immunotherapy had promise,
Richard is alive and well, healthy and

1073
01:24:34,910 --> 01:24:38,050
happy, and has been treatment-free for
over a year.

1074
01:24:41,740 --> 01:24:47,180
And he says, the words thank you do

1075
01:24:47,180 --> 01:24:53,980
not begin to cover the gratitude we have
for you and your persistence

1076
01:24:53,980 --> 01:24:58,940
through all this to see that
immunotherapy be brought to people

1077
01:24:58,940 --> 01:24:59,940
worldwide.

1078
01:25:00,120 --> 01:25:05,420
Our family is eternally grateful for the
extra years we've given us with Richard,

1079
01:25:05,580 --> 01:25:09,300
a wonderful father, husband, sincerely.

1080
01:25:10,220 --> 01:25:11,220
And it's from his wife.

1081
01:25:15,980 --> 01:25:21,240
For sure, it's knowing that we've done
something like this that makes it all

1082
01:25:21,240 --> 01:25:22,240
worthwhile.

1083
01:25:24,860 --> 01:25:29,480
So... I need a drink.

1084
01:25:38,470 --> 01:25:39,950
Look, I'm in the eye.

1085
01:25:41,070 --> 01:25:46,570
I didn't come here and I ain't leaving.
So don't sit around and cry. Just roll

1086
01:25:46,570 --> 01:25:48,510
me up and smoke me one eye.

1087
01:25:50,150 --> 01:25:53,010
Now you won't see no sad and teary eye.

1088
01:25:54,470 --> 01:25:57,350
When I get my wings and it's my time to
fly.

1089
01:25:59,130 --> 01:26:04,650
Call my friends and tell them there's a
party. Come on by and just roll me up

1090
01:26:04,650 --> 01:26:05,970
and smoke me one eye.

1091
01:26:08,290 --> 01:26:12,970
When I played with Willie Nelson at the
Austin City Limits Festival, I was

1092
01:26:12,970 --> 01:26:13,970
scared.

1093
01:26:15,770 --> 01:26:20,410
It was hard to relax, you know, when I'm
playing with my buddies, you know, it's

1094
01:26:20,410 --> 01:26:21,410
like fun.

1095
01:26:22,030 --> 01:26:25,130
But if you're playing with Willie,
you're like, I gotta get this, I gotta

1096
01:26:25,130 --> 01:26:26,130
get this.

1097
01:26:56,970 --> 01:27:01,210
Thank you. Thank you so much. I'm so
honored. You know, of course, it's a

1098
01:27:01,210 --> 01:27:04,010
scientist's dream.

1099
01:27:04,910 --> 01:27:11,630
We think that the discoveries that you
have made have enabled an entirely new

1100
01:27:11,630 --> 01:27:15,690
principle for cancer therapy. I mean, we
think it's absolutely fantastic.

1101
01:27:16,410 --> 01:27:18,730
Be out and build a roaring fire.

1102
01:27:20,510 --> 01:27:23,430
Roll me in the flames for about an hour.

1103
01:27:24,940 --> 01:27:28,780
Take me out and twist me up and point me
toward the sky.

1104
01:27:29,020 --> 01:27:32,100
And just roll me up and smoke me when I
die.

1105
01:27:33,640 --> 01:27:36,480
Roll me up and smoke me when I die.

1106
01:27:37,820 --> 01:27:41,940
And if anyone don't like it, look, I'm
in the eye.

1107
01:27:43,120 --> 01:27:48,540
I didn't come here and I ain't leaving,
so don't sit around and cry. Just roll

1108
01:27:48,540 --> 01:27:50,580
me up and smoke me when I die.

1109
01:28:09,089 --> 01:28:12,170
Pam Sharma was tenured at MD Anderson.

1110
01:28:12,770 --> 01:28:15,930
She was a big name in the cancer world
in her own right.

1111
01:28:18,710 --> 01:28:23,710
It was talking professionally for...
quite a few years, and then eventually

1112
01:28:23,710 --> 01:28:24,990
there was a romance.

1113
01:28:26,810 --> 01:28:31,450
Jim said to her one day, there's no one
who can stand either of us.

1114
01:28:32,230 --> 01:28:36,330
Who else is going to talk about T-cells
all day? We should get married.