1
00:00:02,760 --> 00:00:06,960
The practice of science has
shaped the modern era,

2
00:00:06,960 --> 00:00:09,800
but how are discoveries made?

3
00:00:09,800 --> 00:00:12,680
And how does science progress?

4
00:00:12,680 --> 00:00:16,760
Three British scientists,
world leaders in their fields,

5
00:00:16,760 --> 00:00:22,040
have changed our understanding
of our universe, our planet
and ourselves.

6
00:00:22,040 --> 00:00:27,880
A physicist whose mysterious
radio signals from space
re-wrote astronomy.

7
00:00:27,880 --> 00:00:30,920
She actually recognised that
there was something happening.

8
00:00:30,920 --> 00:00:36,520
I suspect that perhaps only 1 in 100
people would have spotted it.

9
00:00:36,520 --> 00:00:42,560
A chemist whose radical theory
about our planet
divides the scientific world.

10
00:00:42,560 --> 00:00:48,240
He's one of the greatest
thinkers of the current age
and destined to go down in history.

11
00:00:48,240 --> 00:00:53,880
And a biologist who discovered
the secret of life in a sea urchin.

12
00:00:53,880 --> 00:00:57,960
Your fundamental discoveries
have profoundly increased

13
00:00:57,960 --> 00:01:02,440
our understanding
of how the cell cycle is controlled.

14
00:01:02,440 --> 00:01:07,000
Their stories tell us about
the nature of scientific enquiry
in the modern world.

15
00:01:07,000 --> 00:01:11,600
About how scientific breakthroughs
are made,

16
00:01:11,600 --> 00:01:15,200
and about the workings
of the scientific brain.

17
00:01:34,520 --> 00:01:37,400
Scientists are very keen to...
to get at the truth,

18
00:01:37,400 --> 00:01:41,000
to get to the bottom of things,
but there is no such thing
as ultimate truth.

19
00:01:41,000 --> 00:01:44,480
Every time you turn over
one stone and you find something

20
00:01:44,480 --> 00:01:47,720
interesting underneath and that just
leads you to another stone.

21
00:01:47,720 --> 00:01:51,280
And there are layers, it's sort of
real onion skin, and go down and down

22
00:01:51,280 --> 00:01:55,600
and down and down and down, and there
always wrinkles to be figured out.

23
00:01:55,600 --> 00:01:58,280
And what's curious, I've found,
is that some things

24
00:01:58,280 --> 00:02:01,320
are very easy to find out
once you know how to find them out.

25
00:02:01,320 --> 00:02:05,240
Some things, very simple questions,
turn out to be amazingly difficult.

26
00:02:05,240 --> 00:02:10,480
It's utterly unpredictable
which ones sort of fall out
and which ones don't.

27
00:02:15,200 --> 00:02:19,000
Tim Hunt's remarkable career
has led to the understanding

28
00:02:19,000 --> 00:02:21,840
of one of the greatest
scientific mysteries of all.

29
00:02:21,840 --> 00:02:23,360
Cell division.

30
00:02:23,360 --> 00:02:27,800
The complex process
in all plants and all animals

31
00:02:27,800 --> 00:02:30,800
that underpins life itself.

32
00:02:31,840 --> 00:02:37,320
That it happens and even why it
happens are straightforward
propositions,

33
00:02:37,320 --> 00:02:43,960
but until Tim Hunt,
nobody knew exactly how one
cell divided to become two.

34
00:02:52,320 --> 00:02:55,400
The unravelling of that
key mechanism was so fundamental

35
00:02:55,400 --> 00:03:01,840
to the understanding of life
that in 2001 Hunt was awarded
the Nobel Prize.

36
00:03:05,040 --> 00:03:11,200
It was the crowning glory of a life
devoted to scientific research
at the very highest level.

37
00:03:11,200 --> 00:03:17,280
Recognition of a discovery that
owed its existence to Tim Hunt's
singular approach to science.

38
00:03:19,360 --> 00:03:24,720
One moment you're ignorant,
and the next moment you sort of get
that little tiny, tiny clue

39
00:03:24,720 --> 00:03:30,840
that sort of sheds an enormous
amount of light on the whole thing.

40
00:03:32,440 --> 00:03:37,160
That's a sort of mysterious
thing about science.
It's different from engineering.

41
00:03:37,160 --> 00:03:42,640
I mean, you've been able
to build a bridge over a river
for thousands of years.

42
00:03:42,640 --> 00:03:45,760
The basic principles are understood.

43
00:03:45,760 --> 00:03:50,640
But in science you're never
quite sure where you are actually,
most of the time.

44
00:03:50,640 --> 00:03:54,440
You know, you've got to enjoy
swimming in this sea

45
00:03:54,440 --> 00:03:57,320
of unknowingness.
Otherwise what's the point?

46
00:04:01,400 --> 00:04:04,400
There's a famous quote from a
physicist named Leon Lederman,

47
00:04:04,400 --> 00:04:08,800
which says, "Those who never
stop asking silly questions
grow up to be scientists".

48
00:04:08,800 --> 00:04:12,840
And Tim, to me, is the exemplar of
that sort of person because there is

49
00:04:12,840 --> 00:04:16,080
nothing that Tim doesn't
want to know the answer to.

50
00:04:16,080 --> 00:04:21,000
One of the things he thinks
about is why the sky is blue.

51
00:04:21,000 --> 00:04:22,720
Questions like that.

52
00:04:22,720 --> 00:04:26,760
And what I think we're seeing
is a very curious mind,

53
00:04:26,760 --> 00:04:30,840
the sort of mind that a child has,
which always asks questions.

54
00:04:30,840 --> 00:04:35,600
And most people lose that curiosity,
but Tim has it in spades.

55
00:04:35,600 --> 00:04:40,120
I like to tell the story of having
learned that I'm a Nobel Laureate,

56
00:04:40,120 --> 00:04:43,680
of my daughter,
who was then seven, Celia,

57
00:04:45,240 --> 00:04:48,760
saying,
"Daddy, why is the ceiling opaque?"

58
00:04:48,760 --> 00:04:53,800
And I looked up at the ceiling,
oh, light doesn't get through
the ceiling. And then...

59
00:04:53,800 --> 00:04:59,560
then I looked out of her window and
I thought, "Oh, goodness, how does
light get through the window?"

60
00:04:59,560 --> 00:05:03,120
And I realised we'd done all the
sort of measuring refractive indices

61
00:05:03,120 --> 00:05:08,160
for A level, but nobody had ever told
us why light gets through the glass

62
00:05:08,160 --> 00:05:10,680
but doesn't get through the wall.

63
00:05:10,680 --> 00:05:15,560
And this seems like a really
rather fundamental thing,
so I then started asking people,

64
00:05:15,560 --> 00:05:17,400
how does it work? How does it work?

65
00:05:17,400 --> 00:05:22,080
And physicist friends, biologist
friends and absolutely everybody
I ran into, you know?

66
00:05:22,080 --> 00:05:24,760
Why does light get through glass?

67
00:05:24,760 --> 00:05:28,960
I mean it was so interesting,
different people
use different approaches.

68
00:05:28,960 --> 00:05:32,200
This is a good example of how
a biologist thinks about things.

69
00:05:32,200 --> 00:05:37,280
So when I sort of... I knew
that glass was a frozen liquid.

70
00:05:37,280 --> 00:05:39,680
So I thought, well,
what other liquids?

71
00:05:39,680 --> 00:05:42,160
Maybe it's because it's a liquid
that light...

72
00:05:42,160 --> 00:05:47,520
Then I suddenly realised
that mercury was a liquid
and light is reflected off mercury.

73
00:05:47,520 --> 00:05:52,280
It doesn't go through mercury at all.
So that hypothesis
was out the window.

74
00:05:52,280 --> 00:05:56,720
And then I thought about carbon, and
carbon comes in the blackest black

75
00:05:56,720 --> 00:06:00,240
that absorbs light better
than absolutely anything on Earth.

76
00:06:00,240 --> 00:06:06,720
But also in diamond, which is the
sort of sparkliest, most translucent
stuff you could possibly imagine.

77
00:06:06,720 --> 00:06:10,960
And that then tells you that
it's to do with the electrons,

78
00:06:10,960 --> 00:06:15,000
how the electronic configurations
of the actual material.

79
00:06:15,000 --> 00:06:18,480
And then you realise that it's to do
with the theories of how photons

80
00:06:18,480 --> 00:06:23,760
interact with electrons and then
you know you're lost, basically!

81
00:06:23,760 --> 00:06:27,400
He writes a problems book with his
friend, John Wilson, and they once

82
00:06:27,400 --> 00:06:32,120
worked out how far up an Alp
one Mars bar would take you.

83
00:06:32,120 --> 00:06:34,840
It's that sort of thing.
How many calories are there?

84
00:06:34,840 --> 00:06:39,400
What do calories translate to
in terms of vertical motion
for a human?

85
00:06:39,400 --> 00:06:42,440
So he's doing that, I think,
in his head most of the time.

86
00:06:42,440 --> 00:06:47,320
Except when he's looking vacant,
when he really is vacant.
He must have some of those moments.

87
00:06:47,320 --> 00:06:49,680
But I think he is
continuously thinking about

88
00:06:49,680 --> 00:06:53,480
most of the situations he's in
and wondering what's happening.

89
00:06:56,520 --> 00:07:01,720
Tim Hunt's passion
for scientific enquiry
started when he was a small boy.

90
00:07:03,200 --> 00:07:06,640
I just loved old radio sets
and there were a lot around.

91
00:07:06,640 --> 00:07:11,520
I mean they were just so amazing
and so beautifully made
and they were the tuning device.

92
00:07:11,520 --> 00:07:14,720
I guess I longed to be an
electrical engineer and be able to

93
00:07:14,720 --> 00:07:18,960
design the circuits.
Although I was completely hopeless,
I couldn't do it.

94
00:07:18,960 --> 00:07:24,720
I loved it, I loved it.
I loved making motors and microphones
and loudspeakers.

95
00:07:24,720 --> 00:07:27,160
Always wanted to understand
how things worked.

96
00:07:27,160 --> 00:07:31,960
I mean, here, you stick this
Bakelite box on the table and you

97
00:07:31,960 --> 00:07:36,600
tune the dial and voices come
from the universe towards you.

98
00:07:36,600 --> 00:07:40,560
And you look inside,
"What's doing this?"
It's just these glowing valves.

99
00:07:42,200 --> 00:07:47,920
I remember making fuses too,
that was good fun. So you soak a
piece of string in sodium chlorate.

100
00:07:47,920 --> 00:07:51,600
And then I remember one time,
we tried to accelerate its drying out

101
00:07:51,600 --> 00:07:55,560
so we put it under the grill,
which was a big mistake
cos the thing went kaboom!

102
00:07:57,360 --> 00:08:02,280
He was older than I was, so he was
the leader and I was the follower...

103
00:08:02,280 --> 00:08:05,360
behind,
if I'm to be absolutely honest.

104
00:08:05,360 --> 00:08:09,800
Which was good. He was good, he
was imaginative about it, you know?

105
00:08:09,800 --> 00:08:12,160
We did interesting and fun things.

106
00:08:12,160 --> 00:08:15,440
I suppose we were quite
scientific about it really.

107
00:08:15,440 --> 00:08:21,160
Now I come to think of it, I think
he's very, sort of inquisitive.
He likes to try everything out.

108
00:08:21,160 --> 00:08:25,080
I just wanted to know how things
work, all the time. How do things...

109
00:08:25,080 --> 00:08:27,200
What's behind this, you know?

110
00:08:27,200 --> 00:08:30,920
And I loved the idea that you could,
you know, there was...

111
00:08:30,920 --> 00:08:35,360
a sort of simple explanation
behind everything you could see.

112
00:08:36,400 --> 00:08:41,080
This passion to really understand
how things worked, persisted

113
00:08:41,080 --> 00:08:44,040
and shaped his entire
scientific career.

114
00:08:44,040 --> 00:08:47,800
It led him to the challenge
of understanding life itself

115
00:08:47,800 --> 00:08:51,000
and to the fundamental process
that drives it.

116
00:08:51,000 --> 00:08:55,080
Our lives start with a single cell.

117
00:08:55,080 --> 00:08:58,320
That first cell splits to become two,

118
00:08:58,320 --> 00:09:03,800
and then they in turn divide into two
to become four, and so on.

119
00:09:03,800 --> 00:09:08,480
So, after just 48 doublings, you have
a hundred thousand billion cells

120
00:09:08,480 --> 00:09:13,040
in your body, and you're ready
to spring forth as a human being.

121
00:09:14,640 --> 00:09:18,880
The miracle of cell division is,
at its most dramatic,

122
00:09:18,880 --> 00:09:21,600
a process that creates new life.

123
00:09:21,600 --> 00:09:24,960
But it's also
fundamental to maintaining life,

124
00:09:24,960 --> 00:09:28,600
and it's this that reveals
the complexity at its core.

125
00:09:30,440 --> 00:09:34,520
Everything is being replaced
all of the time.

126
00:09:34,520 --> 00:09:37,760
There are new molecules
being put in place of old ones.

127
00:09:37,760 --> 00:09:39,880
The old ones are sort
of recycled and...

128
00:09:39,880 --> 00:09:44,320
I always remember
when I went as a junior proctor,

129
00:09:44,320 --> 00:09:50,560
we went and visited this air-force
base, and I was very thrilled
because we saw a Canberra bomber.

130
00:09:54,720 --> 00:09:57,160
So I asked,
"Gosh, is this really an original?"

131
00:09:57,160 --> 00:10:00,680
They said, "The pilot's seat
might be, but everything else...

132
00:10:00,680 --> 00:10:02,760
"it's got new wings,
it's got new fuselage,

133
00:10:02,760 --> 00:10:07,240
"it's got new this..."
The thing had been totally replaced

134
00:10:07,240 --> 00:10:10,600
and yet it was still a Canberra
bomber and not some other kind.

135
00:10:10,600 --> 00:10:13,480
It wasn't a Spitfire, it wasn't
anything. We're like that.

136
00:10:16,760 --> 00:10:20,800
Life and cells have the ability to
patch themselves all of the time.

137
00:10:20,800 --> 00:10:23,880
Damage is being done all of the time.

138
00:10:23,880 --> 00:10:27,720
You have a new nose basically,
certainly every seven years.

139
00:10:27,720 --> 00:10:31,200
I mean there isn't a single thing,
component, in your nose left.

140
00:10:31,200 --> 00:10:36,080
But the amazing thing is
it's still your nose, you know?
It doesn't...it hasn't grown,

141
00:10:36,080 --> 00:10:40,440
it hasn't shrunk,
it's still got the same shape
that you were born with, so to speak.

142
00:10:40,440 --> 00:10:42,320
Absolutely remarkable, you know?

143
00:10:42,320 --> 00:10:44,240
So how these cells know...

144
00:10:44,240 --> 00:10:48,840
I mean there's a cell here,
in the tip of my nose, that knows
it's a cell in the tip of my nose

145
00:10:48,840 --> 00:10:52,720
and if something happens and that
cell dies then, it's neighbours say,

146
00:10:52,720 --> 00:10:54,960
"Oh, dear.
Tim's lost the tip of his nose.

147
00:10:54,960 --> 00:10:57,560
"We'd better put in a new
cell there cos it's gone."

148
00:10:57,560 --> 00:10:59,800
And that's replaced by cell division.

149
00:11:02,440 --> 00:11:05,680
For Hunt,
understanding this great mystery

150
00:11:05,680 --> 00:11:09,120
means breaking it down
to its smallest components.

151
00:11:09,120 --> 00:11:14,440
Life, all life, can be understood
as a series of complex mechanisms,

152
00:11:14,440 --> 00:11:19,840
a myriad of individual processes
happening within the cell.

153
00:11:19,840 --> 00:11:23,280
The way that I think of it is that,
you imagine yourself shrunk down

154
00:11:23,280 --> 00:11:27,440
to the size of a molecule,
and you're standing
by this amazing molecular machine

155
00:11:27,440 --> 00:11:29,880
and watching how all the things,

156
00:11:29,880 --> 00:11:33,160
come in and out and pull
each other and push each other.

157
00:11:33,160 --> 00:11:36,000
Those are the terms in which
you want to understand it.

158
00:11:36,000 --> 00:11:39,240
There are different philosophies
of how you should do science

159
00:11:39,240 --> 00:11:41,880
or can do science,
and one philosophy

160
00:11:41,880 --> 00:11:48,800
is reductionism. The idea that you
can explain everything in terms
of the smallest bits inside it.

161
00:11:48,800 --> 00:11:54,840
Like explaining the whole of nature
in terms of atoms, or quarks,
or sub-atomic particles,

162
00:11:54,840 --> 00:11:58,200
and that way of thinking
has led to molecular biology.

163
00:11:58,200 --> 00:12:01,560
The way to understand life
is to understand the smallest things

164
00:12:01,560 --> 00:12:05,640
in living organisms, molecules,
DNA, proteins and so forth.

165
00:12:05,640 --> 00:12:11,520
And that somehow, out of
understanding all the details,
the big picture will emerge.

166
00:12:11,520 --> 00:12:14,520
Tim is definitely working
within that tradition.

167
00:12:14,520 --> 00:12:19,240
This approach had started when he
was a teenager, when he came across

168
00:12:19,240 --> 00:12:23,840
a problem that would take him
more than 20 years to solve.

169
00:12:23,840 --> 00:12:29,120
When I was doing A level biology,
I remember seeing an amazing movie
of biochemical pathways

170
00:12:29,120 --> 00:12:32,480
with compounds flowing down
and cycles going round

171
00:12:32,480 --> 00:12:35,120
and things spinning off
and all that kind of stuff.

172
00:12:35,120 --> 00:12:38,400
I remember thinking at the time
it was all very well these pathways,

173
00:12:38,400 --> 00:12:40,720
but there didn't seem to be
any control.

174
00:12:40,720 --> 00:12:44,200
How could you have all those
reactions going on simultaneously?

175
00:12:44,200 --> 00:12:46,240
There's got to be
something controlling it.

176
00:12:46,240 --> 00:12:48,320
This was very thrilling.
A kind of revelation.

177
00:12:50,160 --> 00:12:56,240
So, what I suddenly realised
was that control was
the fundamental issue of all life.

178
00:12:56,240 --> 00:13:00,680
From then on, I knew that being a
biologist was what I was cut out for.

179
00:13:08,400 --> 00:13:12,240
Tim Hunt was brought up in Oxford,
where the disciplines

180
00:13:12,240 --> 00:13:17,000
of the academic life
and a passion for detail,
were part of his heritage.

181
00:13:19,800 --> 00:13:25,640
Dad was something called a
Keeper of the Western Manuscript
at the Bodleian Library.

182
00:13:29,480 --> 00:13:34,320
He had a sort of encyclopaedic feel
for what was where,

183
00:13:34,320 --> 00:13:37,920
and you could
use these manuscripts,

184
00:13:37,920 --> 00:13:44,960
which were actually bound into books,
to trace who knew what, when.

185
00:13:47,160 --> 00:13:52,680
Manuscripts were copied by monks.
There was no printing in those days.

186
00:13:52,680 --> 00:13:55,840
Everything had to be copied, and
the monk would make the odd mistake.

187
00:13:55,840 --> 00:14:02,160
But those mistakes then tended
to be copied faithfully
by the next copyist.

188
00:14:02,160 --> 00:14:06,920
Then that book would be taken to
the next monastery,
and so you could actually

189
00:14:06,920 --> 00:14:12,840
trace a genealogical tree
of the spread of knowledge
across Europe by this technique.

190
00:14:16,000 --> 00:14:18,920
His office
at the Bodleian was quite remarkable.

191
00:14:18,920 --> 00:14:23,560
There was a huge table.
It was quite a big room, and in
the middle of the table, the papers,

192
00:14:23,560 --> 00:14:26,200
the letters were about a foot deep,
or something.

193
00:14:26,200 --> 00:14:29,200
And then towards the edge they sort
of thinned out rather,

194
00:14:29,200 --> 00:14:31,680
cos otherwise
they'd have spilled onto the floor.

195
00:14:31,680 --> 00:14:35,920
So I don't know how he managed
his correspondence,
but I'm exactly the same.

196
00:14:37,280 --> 00:14:41,880
It's a sort of classification system
whereby the less important things

197
00:14:41,880 --> 00:14:47,320
fractionate to the bottom of the pile
and the important things either
stay on the top or rise to the top.

198
00:14:49,360 --> 00:14:53,680
Tim and my Dad are very
alike in many, many ways.

199
00:14:53,680 --> 00:14:57,680
They are both very scholarly.

200
00:14:57,680 --> 00:15:04,760
Tim is a stickler for science
and the way that it is carried out

201
00:15:04,760 --> 00:15:10,240
and for all the principles
of keeping science honest.

202
00:15:10,240 --> 00:15:15,600
My father was an
absolute stickler for scholarship.

203
00:15:17,480 --> 00:15:23,400
Dad was very keen on the right
way of doing things, and I've
always felt that too, in science.

204
00:15:23,400 --> 00:15:29,760
And that's served me well
because it's the details in
biology that unlocks the secrets.

205
00:15:32,400 --> 00:15:38,520
Hunt's academic career began in
earnest when he went to Cambridge
to read natural sciences.

206
00:15:38,520 --> 00:15:45,240
He found himself thrown
into a world of scientific optimism
and mild eccentricity.

207
00:15:45,240 --> 00:15:49,240
Tim and I were very close friends.
We used to do a lot of things
together.

208
00:15:49,240 --> 00:15:52,720
We were often called the
Terrible Two. I'm not quite sure why

209
00:15:52,720 --> 00:15:55,760
I don't think we were
particularly terrible, but...

210
00:15:55,760 --> 00:15:57,280
they were...

211
00:15:59,160 --> 00:16:03,680
..I think people found us
a sort of unusual pair of people
to have around.

212
00:16:07,320 --> 00:16:12,240
Most people had just ordinary white
lab coats, but Tim and I dyed ours

213
00:16:12,440 --> 00:16:15,280
and his most characteristic clothing
at the time

214
00:16:15,280 --> 00:16:21,840
was a pink boiler suit
that he used to wear at the lab, and
indeed, walking around Cambridge.

215
00:16:21,840 --> 00:16:26,320
And in the winter this was...
Wasn't warm enough,

216
00:16:26,320 --> 00:16:31,160
so he needed something warmer. Then
he had sort of third-hand fur coats.

217
00:16:31,160 --> 00:16:35,600
So he wore these rather eccentric,
long fur coats over his
pink boiler suit.

218
00:16:36,920 --> 00:16:40,560
You never felt that it was
an affectation in his case.

219
00:16:40,560 --> 00:16:43,280
He made eccentricity seem normal.

220
00:16:47,720 --> 00:16:50,880
We found rooms in The Eagle pub

221
00:16:50,880 --> 00:16:55,480
and we lived there for three years,
while we were doing our PhDs.

222
00:16:55,480 --> 00:17:00,160
We were nocturnal, so we used to go
back into the lab and start work

223
00:17:00,160 --> 00:17:04,880
about ten, and usually work through
till three or four in the morning.

224
00:17:04,880 --> 00:17:10,560
And we had loudspeakers in both
our labs and we draped wires
over the outside of the building.

225
00:17:10,560 --> 00:17:16,440
And so at night
we had the whole laboratory
resounding to this wonderful music.

226
00:17:16,440 --> 00:17:23,000
Sort of Monteverdi operas,
symphonies, going on all night in
the lab and the whole lab echoed.

227
00:17:25,520 --> 00:17:29,600
So we had
a very nice way of working there.

228
00:17:33,560 --> 00:17:38,760
Hunt had arrived at Cambridge
at precisely the right time
for a young scientist

229
00:17:38,760 --> 00:17:43,080
who was passionate about
the emerging science
of molecular biology.

230
00:17:46,480 --> 00:17:48,480
I think Cambridge was...

231
00:17:50,120 --> 00:17:53,640
..a good place for high objectives.

232
00:17:54,800 --> 00:17:56,440
It was a site of great science

233
00:17:56,440 --> 00:18:01,160
and you were supposed to do it
in a sort of understated way.

234
00:18:01,160 --> 00:18:07,840
And when I think back at it,
it was probably then...in biology,

235
00:18:07,840 --> 00:18:12,080
the leading university in the world.
If you just put
what people were trying to do.

236
00:18:12,080 --> 00:18:17,120
There was no other place which had
the focus on important things.

237
00:18:17,120 --> 00:18:23,240
'Dr James Watson, aged only 34,
an American biologist who worked
for two years at Cambridge.

238
00:18:23,240 --> 00:18:27,640
'Francis Crick, aged 46, worked in
the Admiralty on mine detection

239
00:18:27,640 --> 00:18:29,960
'during the war,
then switched to biology.

240
00:18:29,960 --> 00:18:36,000
'They puzzled about the mechanism
of inheritance that makes you
so much like your parents.

241
00:18:36,000 --> 00:18:39,160
'Between them, they shared
the Nobel Prize for medicine'.

242
00:18:39,160 --> 00:18:42,840
I think Tim was very impressed
by the molecular approach

243
00:18:42,840 --> 00:18:47,000
that Crick was advocating, and
indeed most people were advocating.

244
00:18:47,000 --> 00:18:50,760
And that was the sort of
high noon of molecular biology,

245
00:18:50,760 --> 00:18:54,720
the genetic code
had just been cracked,

246
00:18:54,720 --> 00:18:59,000
the mechanism of protein synthesis
had just been worked out.

247
00:18:59,000 --> 00:19:02,680
Tim was working out
some of the details of all this.

248
00:19:02,680 --> 00:19:04,800
It was a period of enormous optimism

249
00:19:04,800 --> 00:19:08,840
and people thought that this was
the way forward to understand life.

250
00:19:10,400 --> 00:19:17,160
When Watson and Crick lounged around,
chatting about things about
which they knew nothing,

251
00:19:17,160 --> 00:19:21,520
but as a result of this,
they discovered the structure of DNA,
the most important...

252
00:19:22,120 --> 00:19:27,080
arguably the most important
scientific, biological discovery
of the 20th century.

253
00:19:27,080 --> 00:19:32,480
There's more than one way
of doing good science,
and that's extremely true, you know?

254
00:19:32,480 --> 00:19:34,920
I mean you just have to take...
it's so hard.

255
00:19:34,920 --> 00:19:38,560
I think that's what a lot of people
don't understand, it's so hard,

256
00:19:38,560 --> 00:19:42,440
and so slow that you have to take
little clues

257
00:19:42,440 --> 00:19:44,680
from wherever they come from.

258
00:19:45,680 --> 00:19:50,360
Jim Watson was a fellow of my college
and don't quite know

259
00:19:50,360 --> 00:19:53,960
how I first met him, but I mean
he would just drop by.

260
00:19:53,960 --> 00:19:56,280
Jim has an amazing property.

261
00:19:56,280 --> 00:20:01,440
He sort of drops by, he sort of pops
out in your life at crucial moments.

262
00:20:03,760 --> 00:20:06,760
Very interesting man,
very interesting man.

263
00:20:06,760 --> 00:20:10,800
You could actually see that he also
really, really cared about

264
00:20:10,800 --> 00:20:15,240
getting to the bottom of things,
and that's what's finally important.

265
00:20:15,240 --> 00:20:21,000
I mean, those people who are actually
trying to get to the bottom of
things, not for their own glory,

266
00:20:21,000 --> 00:20:26,320
but just because they really,
really want to understand.
I think that's terribly important.

267
00:20:26,320 --> 00:20:29,560
Cambridge was always rather
amusing in those days because

268
00:20:29,560 --> 00:20:33,760
Francis would have about
one idea I think every two weeks

269
00:20:33,760 --> 00:20:37,200
and it'd take a couple of days for
him to be convinced it was no good.

270
00:20:37,200 --> 00:20:39,720
And in those couple of days we'd...

271
00:20:39,720 --> 00:20:43,800
he'd never stop talking,
and if we were in sort of

272
00:20:43,800 --> 00:20:48,040
good spirits we could, you know,
really ask him difficult questions.

273
00:20:48,040 --> 00:20:51,080
I'm very much a hero worshipper.

274
00:20:51,080 --> 00:20:57,040
Francis Crick was really our hero,
you know? Omnipresent figure
at seminars.

275
00:20:57,040 --> 00:21:02,920
He'd often be sort of sat at the back
of a seminar and he would
almost always ask questions.

276
00:21:02,920 --> 00:21:07,400
Sometimes in the...if it was OK,
within the body of the talk.

277
00:21:07,400 --> 00:21:12,200
And these questions were
always trying to clarify things.
To get to the bottom of things.

278
00:21:12,200 --> 00:21:17,080
And unlike some people who ask,
in Cambridge, who ask questions
to show how clever THEY were,

279
00:21:17,080 --> 00:21:20,960
actually, they were often questions,
which revealed how ignorant he was.

280
00:21:20,960 --> 00:21:24,800
But he still had the confidence to
ask, because if you didn't understand

281
00:21:24,800 --> 00:21:28,560
that particular point, the whole
thing just would be incomprehensible.

282
00:21:28,560 --> 00:21:32,360
Certain things I think
can be thought to be alive.

283
00:21:32,360 --> 00:21:34,880
I think we would agree
that you and I are alive.

284
00:21:34,880 --> 00:21:38,520
The difficulty comes with the
borderline cases, like the viruses,

285
00:21:38,520 --> 00:21:41,880
and I think really what it comes to
is you're really arguing about

286
00:21:41,880 --> 00:21:43,720
a word when you ask the question.

287
00:21:43,720 --> 00:21:46,640
Is a virus... is the polio
virus alive, for example?

288
00:21:46,640 --> 00:21:51,840
Tim, because he started
working on how proteins are made,
the process called translation,

289
00:21:51,840 --> 00:21:54,280
he was very connected
to those people because

290
00:21:54,280 --> 00:21:58,040
that was part of the central dogma.
DNA makes RNA, makes protein.

291
00:21:58,040 --> 00:22:00,520
And the question is
how do you make protein?

292
00:22:00,520 --> 00:22:04,600
What are the nuts and bolts
of those steps
and how do you control that process?

293
00:22:04,600 --> 00:22:07,080
That's really where
Tim started as a scientist.

294
00:22:08,880 --> 00:22:12,760
It was the beginning of a journey
that would lead to Hunt unravelling

295
00:22:12,760 --> 00:22:15,360
the fundamental mystery
of cell division.

296
00:22:15,360 --> 00:22:19,840
A journey that began with
understanding the biochemistry
of proteins.

297
00:22:25,160 --> 00:22:29,240
Proteins do absolutely everything.
I used to enjoy telling students,

298
00:22:29,240 --> 00:22:34,760
when we sort of started out
on a journey through cell biology
and biochemistry that,

299
00:22:34,760 --> 00:22:38,800
I look at your face and I'm
looking at proteins, you know?

300
00:22:38,800 --> 00:22:43,680
That's your skin and I can see
that your blood is red
because your lips are pink,

301
00:22:43,680 --> 00:22:50,520
and the eyes are clear but
that's protein specially arranged
so that the light can go through it.

302
00:22:50,520 --> 00:22:53,880
So, the hair
is a different kind of protein

303
00:22:53,880 --> 00:22:57,240
from the skin
and related but different.

304
00:22:57,240 --> 00:22:59,920
And so on. So that's all...
that's all protein.

305
00:22:59,920 --> 00:23:02,880
Everything you're made of,
stuff you can really feel,

306
00:23:02,880 --> 00:23:07,600
it's tough stuff, you know?
If you've ever eaten a piece of
gristle you know how ghastly

307
00:23:07,600 --> 00:23:12,680
and tough protein can be. But they
can also catalyse chemical reactions

308
00:23:12,680 --> 00:23:16,960
to make sure that what you eat
then becomes you,

309
00:23:16,960 --> 00:23:21,200
and you alone
because you break down all
the proteins into their components,

310
00:23:21,200 --> 00:23:25,800
and then build them up again
to your own cells' components.

311
00:23:25,800 --> 00:23:30,520
At Cambridge, Tim Hunt began working
on the problem of how individual

312
00:23:30,520 --> 00:23:37,040
proteins were made, and specifically
how this process was controlled.

313
00:23:37,040 --> 00:23:39,520
What became clear

314
00:23:39,520 --> 00:23:43,560
and what was nice about all of
this stuff is that you could...

315
00:23:43,560 --> 00:23:47,240
you could turn protein synthesis
on and off.

316
00:23:47,240 --> 00:23:51,320
And it was the fact that you could
turn it on and off

317
00:23:51,320 --> 00:23:57,680
meant that you were really studying
the control of protein synthesis
in a test tube.

318
00:23:57,680 --> 00:24:02,640
And finding out what the molecular
mechanism behind that switch was,

319
00:24:02,640 --> 00:24:05,880
became a sort of all-consuming goal.

320
00:24:11,760 --> 00:24:17,240
In 1968,
Tim Hunt received an invitation
that would change his life.

321
00:24:19,280 --> 00:24:22,400
I'd come to New York to work
with a man called Irving London,

322
00:24:22,400 --> 00:24:28,200
who was actually the Head of the
Department of Medicine at the
Albert Einstein College of Medicine.

323
00:24:28,200 --> 00:24:32,720
But he was very keen on research
and he was interested in exactly

324
00:24:32,720 --> 00:24:36,960
the same problem as I was, which was
the control of protein synthesis.

325
00:24:39,440 --> 00:24:44,200
I lived on the Upper West Side,
not far Columbia University really,

326
00:24:44,200 --> 00:24:47,920
but had to travel
to the Far East Bronx.

327
00:24:47,920 --> 00:24:51,400
I mean probably about
a 40-minute subway ride...

328
00:24:53,720 --> 00:24:57,280
through some of the roughest,
crime-ridden districts in the world.

329
00:24:57,280 --> 00:24:59,720
There was no question
of looking respectable.

330
00:25:02,760 --> 00:25:05,800
I used to read The New York Times
from cover to cover going out,

331
00:25:05,800 --> 00:25:12,280
and the Journal of Molecular Biology
coming home, quite often,
usually pretty late at night.

332
00:25:12,280 --> 00:25:16,840
It was a cultural, as well as a
scientific opportunity for Hunt,

333
00:25:16,840 --> 00:25:21,240
who went about documenting his time
in the us by taking photographs.

334
00:25:26,040 --> 00:25:29,200
I saved up enough money
to buy a Pentax camera

335
00:25:29,200 --> 00:25:32,680
that had a little meter built
into it, and this was the beginnings

336
00:25:32,680 --> 00:25:37,520
of the real revolution.
So you didn't have to worry about
exposures and all that kind of stuff.

337
00:25:40,040 --> 00:25:44,280
Very obsessed with these sort of
great French photographers

338
00:25:44,280 --> 00:25:47,880
who sort of somehow sort of capture
the minute of the passing scene.

339
00:25:50,520 --> 00:25:52,120
I absolutely loved that.

340
00:25:56,920 --> 00:26:04,320
In the lab, Hunt and Irving London
were trying to capture significant
moments in protein synthesis.

341
00:26:04,320 --> 00:26:10,200
They separated the individual
proteins manufactured in cells
using chromatography.

342
00:26:10,200 --> 00:26:13,840
Each horizontal line represents
an individual protein

343
00:26:13,840 --> 00:26:17,120
and each column,
a different point in time.

344
00:26:21,880 --> 00:26:26,200
You have to keep on taking time
points and, I don't know,

345
00:26:26,200 --> 00:26:30,920
half a dozen, maybe ten samples
per time course would be enough.

346
00:26:32,520 --> 00:26:38,440
The technique made it possible to
see the ebb and flow of proteins
as they were produced in the cell,

347
00:26:38,440 --> 00:26:42,520
in a way that taking
a single measurement could not.

348
00:26:42,520 --> 00:26:44,760
I learned a great
deal about technique.

349
00:26:44,760 --> 00:26:50,000
Watching, measuring the rates
of protein synthesis and
being precise about controls.

350
00:26:50,000 --> 00:26:52,840
And making sure that you saw the
big picture and not...

351
00:26:52,840 --> 00:26:56,320
sort of like making a movie
rather than just taking snapshots.

352
00:26:59,160 --> 00:27:02,440
In New York,
Hunt had equipped himself

353
00:27:02,440 --> 00:27:06,480
with the tools he'd later need
to make his greatest breakthrough.

354
00:27:08,360 --> 00:27:11,000
But as is so often the way
in science,

355
00:27:11,000 --> 00:27:15,640
serendipity and chance encounters
also played their part.

356
00:27:15,640 --> 00:27:19,720
About this time I went to a talk
by a guy called John Gerhart,
and very soon

357
00:27:19,720 --> 00:27:23,200
I was right on the edge of my seat
because he was explaining his studies

358
00:27:23,200 --> 00:27:29,520
on MPF, maturation promoting factor,
the magical missing link which seemed
to be the trigger for cell division.

359
00:27:32,120 --> 00:27:38,000
For years, biologists had known
that theoretically,
something must make a cell divide.

360
00:27:38,000 --> 00:27:41,640
But try as they might,
they couldn't find it.

361
00:27:41,640 --> 00:27:44,440
They had, however, given it a name.

362
00:27:46,720 --> 00:27:51,160
I think there's an interesting
lesson to be learnt from MPF because

363
00:27:51,160 --> 00:27:53,200
when it was originally conceived

364
00:27:53,200 --> 00:27:56,640
it had a rather abstract nature.
It was just factor...

365
00:27:56,640 --> 00:28:01,560
a factor that was present in cells
that made other cells divide.

366
00:28:01,560 --> 00:28:04,280
But one had no idea
quite what it was.

367
00:28:04,280 --> 00:28:10,920
And what you needed to do was
to turn that abstraction into a
physical reality and you do that by

368
00:28:10,920 --> 00:28:15,720
determining what molecules make
it up. And science quite often
inhabits that territory.

369
00:28:15,720 --> 00:28:18,920
You have an idea, an abstract
thought about what's going on,

370
00:28:18,920 --> 00:28:21,560
but you have to turn it
into something more concrete.

371
00:28:21,560 --> 00:28:24,440
It was nowhere near what I was
working on at the time,

372
00:28:24,440 --> 00:28:27,040
but it struck me
as a really delicious problem.

373
00:28:27,040 --> 00:28:29,120
You could almost taste it,
within grasp.

374
00:28:29,120 --> 00:28:33,200
You could begin to think about
what it was and how it might work.

375
00:28:40,120 --> 00:28:45,200
Hunt's interest in the stubbornly
elusive MPF stayed with him.

376
00:28:45,200 --> 00:28:49,840
A decade later he was dividing his
time between Cambridge and the US,

377
00:28:49,840 --> 00:28:52,720
looking at protein synthesis
in cell division.

378
00:28:54,280 --> 00:28:56,880
Woods Hole is a famous
marine biological laboratory

379
00:28:56,880 --> 00:29:00,560
at the seaside, near Boston.
And that was in the summer of 1982.

380
00:29:00,560 --> 00:29:07,080
Alongside a friend, Eric Rosenthal,
who was doing some experiments
on clam eggs, and what we were

381
00:29:07,080 --> 00:29:13,240
doing was to try to compare
the kinds of proteins made in clam
eggs, before and after fertilisation.

382
00:29:13,240 --> 00:29:17,880
With Tim's help,
Eric showed that the proteins that

383
00:29:17,880 --> 00:29:22,440
you make before you fertilise a clam
egg and afterwards, are different.

384
00:29:22,440 --> 00:29:25,960
And there are three proteins that
you make much more of after you've

385
00:29:25,960 --> 00:29:30,360
fertilised the egg, and they got
the imaginative names A, B and C.

386
00:29:30,360 --> 00:29:37,240
And so when Eric would do
experiments, in each experiment
he always saw a lot of C.

387
00:29:37,240 --> 00:29:43,080
And in some experiments he saw
a lot of A and B, and some
experiments he saw almost none.

388
00:29:44,120 --> 00:29:49,160
So my friend had been taking
snapshots, comparing the patterns
of protein synthesis,

389
00:29:49,160 --> 00:29:54,440
and he noticed that
sometimes the proteins were there
and sometimes that they weren't.

390
00:29:58,760 --> 00:30:01,160
And it was just
a complete mystery to me.

391
00:30:01,160 --> 00:30:04,400
Why would the proteins sometimes
be there and sometimes not be?

392
00:30:06,040 --> 00:30:08,560
Normally, proteins would synthesise
and stay there.

393
00:30:08,560 --> 00:30:11,560
They didn't just go away.
I'd never seen anything like it.

394
00:30:11,560 --> 00:30:14,800
It was an intriguing problem.

395
00:30:14,800 --> 00:30:19,040
A problem whose solution might
provide another piece
of the MPF jigsaw,

396
00:30:19,040 --> 00:30:23,400
and one that Hunt was
ideally placed to investigate.

397
00:30:23,400 --> 00:30:26,960
What you really needed was a movie
to understand what was going on,

398
00:30:26,960 --> 00:30:30,400
very much the same kind of approach
that I'd developed in New York.

399
00:30:32,680 --> 00:30:37,800
Eric never had the time
or the inclination or,

400
00:30:37,800 --> 00:30:43,880
the desire to overcome
the experimental difficulties,
to take that leap and pursue that.

401
00:30:48,280 --> 00:30:51,760
And Tim saw something
that he didn't expect to see,

402
00:30:51,760 --> 00:30:55,400
and then, in that situation,
scientists have to make a decision.

403
00:30:55,400 --> 00:30:59,880
Do I stay narrowly focused
on what I thought I was doing

404
00:30:59,880 --> 00:31:04,320
and just ignore this thing as being
a will-o'-the-wisp, or do I realise

405
00:31:04,320 --> 00:31:08,200
that I've seen something that is
much more important and pursue that?

406
00:31:14,440 --> 00:31:19,480
I started my own research on
sea-urchin eggs to see if the same
kind of things were happening.

407
00:31:19,480 --> 00:31:23,000
I just wanted to get
to the bottom of it.

408
00:31:23,000 --> 00:31:26,720
The experiment was very, very simple.
That's the important thing.

409
00:31:26,720 --> 00:31:30,280
So one day, and it turns out the
experiment started at eight o'clock

410
00:31:30,280 --> 00:31:34,120
at night, and the others had all gone
out dancing or drinking or something,

411
00:31:34,120 --> 00:31:38,440
so I was left all alone in the lab,
it was just me
and some sea-urchin eggs.

412
00:31:39,960 --> 00:31:45,360
And I checked they were fertilised,
added the label, and then took out
samples roughly every ten minutes.

413
00:31:49,720 --> 00:31:52,400
We just analysed the samples
on something called

414
00:31:52,400 --> 00:31:56,800
an SDS polyacrylamide gel,
which was very standard,

415
00:31:56,800 --> 00:32:00,880
and we knew exactly how to do
and do it very beautifully,
though I say so myself.

416
00:32:08,160 --> 00:32:13,000
I saw this protein which was
actually the very first one whose
synthesis you could just detect.

417
00:32:13,000 --> 00:32:17,760
And it got stronger and stronger and
stronger, and then it faded away.

418
00:32:17,760 --> 00:32:21,840
All the other ones just went on
getting stronger and stronger.

419
00:32:21,840 --> 00:32:25,800
I looked at it and thought,
"Extraordinary!"
The way the experiment was done

420
00:32:25,800 --> 00:32:30,040
there was no question that this
protein going away
must mean that it was being degraded

421
00:32:30,040 --> 00:32:31,880
and being degraded specifically.

422
00:32:31,880 --> 00:32:34,320
There was just this
one protein went away.

423
00:32:34,320 --> 00:32:37,160
All the others
behaved as you could have expected.

424
00:32:38,760 --> 00:32:44,400
Looking at the full picture in
this way, taking samples over time,

425
00:32:44,400 --> 00:32:47,520
let me see that the protein
wasn't coming and going randomly.

426
00:32:47,520 --> 00:32:51,560
It was coming and going
in a very distinct cycle.

427
00:32:53,800 --> 00:32:55,840
I looked at this and...

428
00:32:55,840 --> 00:32:59,080
"Gosh!" you know?
That's absolutely amazing.

429
00:33:01,280 --> 00:33:05,200
There it was, on this gel
in black and white.

430
00:33:05,200 --> 00:33:07,440
Hunt called the protein cyclin

431
00:33:07,440 --> 00:33:10,200
because it came and went
with the cell's cycle.

432
00:33:10,200 --> 00:33:13,320
He knew that what he was witnessing
was significant,

433
00:33:13,320 --> 00:33:15,960
but he had no idea
what it could mean.

434
00:33:19,240 --> 00:33:22,840
As it happened, I think
I must have got the result
on a Friday morning.

435
00:33:22,840 --> 00:33:25,320
On Friday evening
I ran into John Gerhart

436
00:33:25,320 --> 00:33:29,280
at the wine and cheese party,
after the Friday evening lecture.

437
00:33:29,280 --> 00:33:32,920
John was the man whose talk about
MPF, the magical missing link,

438
00:33:32,920 --> 00:33:35,200
had excited me so much
all those years ago.

439
00:33:35,200 --> 00:33:37,720
So suddenly,
everything was coming full circle.

440
00:33:37,720 --> 00:33:40,120
This was the most
exciting conversation,

441
00:33:40,120 --> 00:33:43,800
scientific conversation,
of my entire life, I mean bar none.

442
00:33:43,800 --> 00:33:48,720
Extraordinary. I remember somebody
came and tried to talk to me,
I just brushed them off

443
00:33:48,720 --> 00:33:51,720
because this conversation
I was having was so important

444
00:33:51,720 --> 00:33:55,040
to get it right.
And it was absolutely the key.

445
00:33:55,040 --> 00:33:57,840
And so from that moment on,
this is very unusual,

446
00:33:57,840 --> 00:34:02,920
the other things I've told you about,
it often took weeks or months
to figure out what was going on.

447
00:34:02,920 --> 00:34:09,480
But basically I'd seen this protein
go away and I knew in my heart
of hearts that somehow this was

448
00:34:09,480 --> 00:34:16,480
really important, and somehow deeply
connected, intimately connected with
the cell division control machinery.

449
00:34:16,480 --> 00:34:19,920
And it was something that nobody
had ever, ever in their wildest

450
00:34:19,920 --> 00:34:24,840
imaginings thought of, that the
protein might actually just go away.

451
00:34:24,840 --> 00:34:30,520
At the time that
Tim discovered cyclin, it was sort
of like the Northwest Passage.

452
00:34:30,520 --> 00:34:33,440
It's like knowing that the
Northwest Passage exists

453
00:34:33,440 --> 00:34:37,160
but I can't point to it on a map
and tell you exactly where it is.

454
00:34:37,160 --> 00:34:42,960
And so the search, if you like,
is for that discovery of what
is the molecule that is MPF?

455
00:34:42,960 --> 00:34:48,040
And so when Tim discovered cyclin
there's immediately this congruence

456
00:34:48,040 --> 00:34:53,040
between, here's cyclin, a protein we
have to make to get cells to divide.

457
00:34:53,040 --> 00:34:59,360
And here's MPF, something which
pushes cells into the stage where
they're just about to divide.

458
00:35:08,960 --> 00:35:11,920
Why did I have this sense

459
00:35:11,920 --> 00:35:16,880
that the going away of cyclin was
intimately related to the control

460
00:35:16,880 --> 00:35:20,920
of the cell's cycle, and why
did that explain so much,

461
00:35:20,920 --> 00:35:27,320
that I internally felt intuitively
that it was probably
the right answer?

462
00:35:27,320 --> 00:35:33,720
Although it had to be, you know...
you had to nail it. You couldn't just
take it for granted.

463
00:35:33,720 --> 00:35:38,960
And I'm not sure that I can give
a very coherent, you know...

464
00:35:38,960 --> 00:35:41,360
Because it was more of a gut feeling.

465
00:35:45,480 --> 00:35:49,160
The truth of the matter is that I
didn't dare hope that my cyclin,

466
00:35:49,160 --> 00:35:52,160
which was going up and down
like a yo-yo, was part of MPF.

467
00:35:52,160 --> 00:35:54,640
That would have just been
way too good to be true.

468
00:35:54,640 --> 00:35:59,920
That would have been like an instant
Nobel Prize, and, you don't get
instant Nobel Prizes

469
00:35:59,920 --> 00:36:05,120
just by doing one
dumb-ass experiment on a Saturday
morning, so to speak, you know?

470
00:36:06,560 --> 00:36:11,040
The excitement felt in Tim's circle
at Woods Hole was not matched in the

471
00:36:11,040 --> 00:36:16,000
wider scientific community and Hunt
was brought abruptly down to earth.

472
00:36:17,960 --> 00:36:20,880
People looked at me as
though I was slightly deranged.

473
00:36:20,880 --> 00:36:22,680
I had quite a hard time.

474
00:36:22,680 --> 00:36:28,000
Indeed, when I sent off our first
paper about this work to the journal
Cell, the editor wrote back to me,

475
00:36:28,000 --> 00:36:34,640
"Dear Tim, the good news is we will
publish your paper, but the bad news
is in nothing like its present form."

476
00:36:34,640 --> 00:36:41,600
And one of the reviewers said,
"It was wild speculation
based on faulty logic".

477
00:36:41,600 --> 00:36:45,560
I can remember him ringing up
and saying that he was...

478
00:36:45,560 --> 00:36:47,600
I can't remember what phrase
he used,

479
00:36:47,600 --> 00:36:51,040
but he was
essentially saying that he was

480
00:36:51,040 --> 00:36:54,760
tired of science and of research.

481
00:36:54,760 --> 00:36:59,600
Most people didn't have a problem
with it seeming to have something to
do with the cell cycle,

482
00:36:59,600 --> 00:37:06,160
but showing that it controlled the
cell cycle was a much trickier thing
to actually establish.

483
00:37:06,160 --> 00:37:12,160
He is a stickler for
the world of people...

484
00:37:13,440 --> 00:37:15,760
..peer recognition
and all the rest of it.

485
00:37:15,760 --> 00:37:19,120
Well, his peers
didn't recognise him, did they?

486
00:37:19,120 --> 00:37:23,560
They were just sceptical,
and rightly so in a way, that,
you know, I wasn't...I...

487
00:37:23,560 --> 00:37:27,240
Let's reserve judgment,
put it that way, right?

488
00:37:27,240 --> 00:37:29,840
I think that's a perfectly
legitimate thing to do.

489
00:37:29,840 --> 00:37:31,680
We had a lot of work to do and...

490
00:37:31,680 --> 00:37:34,600
I mean this was one of the
funniest periods of my life.

491
00:37:34,600 --> 00:37:37,200
Little bit scary...good, because...

492
00:37:37,200 --> 00:37:43,480
because people were so sceptical
nobody...nobody was still prepared
to make that plunge themselves.

493
00:37:43,480 --> 00:37:45,920
Right? And that was...

494
00:37:45,920 --> 00:37:49,280
That was kind of... so it gave
us a lot of space actually.

495
00:37:49,280 --> 00:37:52,000
Tim is not one of those
arrogant scientists.

496
00:37:52,000 --> 00:37:54,280
He actually suffers a lot
from self doubt.

497
00:37:54,280 --> 00:38:01,160
Often people are black and white,
you know? This is right, this is
wrong. Tim understands greyness.

498
00:38:01,160 --> 00:38:06,440
He understands that sometimes
problems are not very clear and the
best thing to do is talk about them.

499
00:38:06,440 --> 00:38:12,120
And these are features that
mark out, in my view at least,
a very good scientist.

500
00:38:16,360 --> 00:38:20,680
Hunt was faced with the daunting
task of explaining exactly why

501
00:38:20,680 --> 00:38:25,920
the mercurial cyclin
was in fact MPF, the stuff of life.

502
00:38:25,920 --> 00:38:28,720
His first instinct
was to collaborate.

503
00:38:31,440 --> 00:38:37,080
Once you've got an idea, it's very
good to bounce it off other people.

504
00:38:38,920 --> 00:38:41,800
You've got a result
and you think it means this

505
00:38:41,800 --> 00:38:46,440
and you find your peers,
your competition, the people
who are actually working on this,

506
00:38:46,440 --> 00:38:49,720
and trying to sort of tease out
as much as you possibly can

507
00:38:49,720 --> 00:38:55,560
to suck the data absolutely dry,
right down to the bone,
so that you can...

508
00:38:55,560 --> 00:39:01,120
So very interesting, the sort of
the relationships with competitors.

509
00:39:01,120 --> 00:39:05,800
And...you know?
I always found the best thing
was to tell everybody everything.

510
00:39:09,240 --> 00:39:13,480
It was Hunt's spirit of openness
that led to his fruitful
collaboration

511
00:39:13,480 --> 00:39:19,200
with the man who would be
instrumental in helping him
complete the cyclin story.

512
00:39:19,200 --> 00:39:25,200
I'd been working on sort of
genetic approaches to how the
cell division cycle is regulated.

513
00:39:25,200 --> 00:39:29,520
I'd been doing that since
the early to mid 1970s,

514
00:39:29,520 --> 00:39:34,920
and my work was abstract
and I didn't have any idea about how

515
00:39:34,920 --> 00:39:39,840
the biochemistry, the chemical
molecules that were involved,
but I was very interested in that.

516
00:39:39,840 --> 00:39:43,160
And in the early '80s
I was gradually getting

517
00:39:43,160 --> 00:39:47,800
towards getting towards looking at
what molecules might be involved,
using genetic approaches.

518
00:39:47,800 --> 00:39:53,000
And so I started to get very
interested in other people's work,
which might illuminate that.

519
00:39:53,000 --> 00:39:58,600
And I also was going to
conferences and meetings
where Tim was talking,

520
00:39:58,600 --> 00:40:02,800
and he was talking about
this protein that was appearing
and disappearing.

521
00:40:02,800 --> 00:40:08,000
So I obviously thought this could
be, if luck was in the right place,

522
00:40:08,000 --> 00:40:13,360
this could be an element
of the same sort of problem
that I was interested in.

523
00:40:17,440 --> 00:40:21,720
If cyclin was to unlock the mystery
of the magical MPF,

524
00:40:21,720 --> 00:40:25,760
it would be necessary to explain
its precise role in cell division.

525
00:40:25,760 --> 00:40:29,280
What's more, it would need to be
present in the dividing cells

526
00:40:29,280 --> 00:40:33,280
of all living things,
not just a single species.

527
00:40:33,280 --> 00:40:38,160
Tim Hunt, Paul Nurse and their
colleagues, set to work in earnest.

528
00:40:39,160 --> 00:40:42,600
We all knew each other and we all
worked on different things.

529
00:40:42,600 --> 00:40:45,480
She worked on clams,
he worked on yeast,

530
00:40:45,480 --> 00:40:51,440
I worked on frogs and sea urchins,
and it was great and there was
so much to be found out.

531
00:40:56,400 --> 00:40:59,720
The first thing, you see this
in sea-urchin eggs, and you say,

532
00:40:59,720 --> 00:41:02,720
"OK, that's interesting.
That's how sea urchins do it."

533
00:41:02,720 --> 00:41:06,080
Then you see it in clams,
and that's pretty significant because

534
00:41:06,080 --> 00:41:10,280
clams and sea urchins,
if you look at the tree of life,
they're pretty far apart.

535
00:41:10,280 --> 00:41:16,520
So that suggests that it's
at least in all sea creatures,
molluscs and echinoderms.

536
00:41:16,520 --> 00:41:21,840
Now we're descended form
echinoderms, so if echinoderms do it
probably we do too.

537
00:41:25,520 --> 00:41:31,880
To go then from frogs and to try
and make the MPF connection
was really important.

538
00:41:34,440 --> 00:41:41,280
So once we knew it was there in frogs
we could be utterly confident that
it was going to be there in humans.

539
00:41:41,280 --> 00:41:44,480
And then it was clear that
it was absolutely universal.

540
00:41:46,080 --> 00:41:52,920
This time there could be no doubting
the veracity or the importance
of their discovery.

541
00:41:52,920 --> 00:41:57,160
Every single animal, every single
plant uses exactly the same

542
00:41:57,160 --> 00:42:01,640
fundamental mechanism
to catalyse cell division.

543
00:42:01,640 --> 00:42:06,320
And by the time we knew all this,
it became pretty much irrefutable.

544
00:42:21,560 --> 00:42:24,640
Suddenly, people...the scales fell
from everybody's eyes

545
00:42:24,640 --> 00:42:29,240
and everybody realised that this
was the secret and this was the basis
of cell division.

546
00:42:35,160 --> 00:42:39,640
One of the greatest mysteries
in biology had been solved.

547
00:42:39,640 --> 00:42:44,120
The continued existence of all life
on earth could now be explained.

548
00:42:44,120 --> 00:42:47,400
Cell division was no longer
governed by theoretical construct,

549
00:42:47,400 --> 00:42:50,800
but by real chemicals
on a real protein

550
00:42:50,800 --> 00:42:55,680
called cyclin, discovered
in a sea urchin by Tim Hunt.

551
00:42:55,680 --> 00:42:59,920
Now, the scientific establishment
beat a path to his door.

552
00:43:10,160 --> 00:43:13,040
The Nobel Prize is the only
scientific prize

553
00:43:13,040 --> 00:43:16,000
that the public generally
know about, so it is iconic.

554
00:43:16,000 --> 00:43:21,280
I mean there are quite a few
other prizes which
sort of lead up to it and...

555
00:43:21,280 --> 00:43:23,720
But it's the Nobel Prize
that really matters.

556
00:43:23,720 --> 00:43:27,280
Tim phoned me and he had to come
down to London from his lab

557
00:43:27,280 --> 00:43:29,760
for a press conference
with Paul Nurse.

558
00:43:29,760 --> 00:43:33,040
So he'd dropped by my office and
he looked like he'd been in

559
00:43:33,040 --> 00:43:36,760
a road accident, he was in shock
I would say, very pale, very shaky.

560
00:43:36,760 --> 00:43:42,760
And we went to tell Celia at that
point, who was at primary school and
sort of old enough to understand.

561
00:43:42,760 --> 00:43:47,680
The head teacher said when we got
to the door we looked like
we'd been in an accident, basically.

562
00:43:47,680 --> 00:43:50,400
We're going, "Won the Nobel Prize,
what shall we do?"

563
00:43:50,400 --> 00:43:52,400
And Tim really didn't believe it.

564
00:43:52,400 --> 00:43:57,000
He almost thought that somebody...
that it was a spoof,
although I think he had talked

565
00:43:57,000 --> 00:43:59,480
directly to the Swedes,
whereas I had not.

566
00:43:59,480 --> 00:44:02,920
I said,
"People wouldn't be so cruel, Tim,
certainly not to you."

567
00:44:02,920 --> 00:44:08,400
Until the King had actually given me
this bloody medal, I really thought
that somebody might come in and...

568
00:44:08,400 --> 00:44:11,040
"No, sorry, made a ghastly mistake."

569
00:44:12,800 --> 00:44:14,280
Dr Hartwell,

570
00:44:14,280 --> 00:44:18,440
Dr Hunt and Dr Nurse.

571
00:44:18,440 --> 00:44:21,960
Your fundamental discoveries
have profoundly increased

572
00:44:21,960 --> 00:44:26,080
our understanding
of how the cell cycle is controlled.

573
00:44:26,080 --> 00:44:30,400
This new knowledge
has a huge impact on cell biology

574
00:44:30,400 --> 00:44:35,600
with broad applications in many
fields of biology and medicine.

575
00:44:35,600 --> 00:44:39,920
It's very moving because
you know this is the pinnacle
of your scientific career.

576
00:44:39,920 --> 00:44:46,680
And I now ask you to step forward
to receive the Nobel Prize from
the hands of his majesty, the King.

577
00:44:52,000 --> 00:44:56,040
APPLAUSE

578
00:45:06,120 --> 00:45:09,080
Oh, yeah,
I still feel enormously proud.

579
00:45:09,080 --> 00:45:10,640
Hugely so.

580
00:45:19,960 --> 00:45:25,160
I think the Nobel Prize rewards
significant achievements in science,

581
00:45:25,160 --> 00:45:29,160
which are of importance
for science as a whole.

582
00:45:29,160 --> 00:45:34,320
And the Nobel Prize is really about
rewarding things which become

583
00:45:34,320 --> 00:45:37,920
foundational parts of
conventional science.

584
00:45:37,920 --> 00:45:43,440
The key discoveries that are the
foundations of established science,

585
00:45:43,440 --> 00:45:47,320
and discovering the way that cell
division works

586
00:45:47,320 --> 00:45:51,400
is a key discovery in history,
in the history of biology,

587
00:45:51,400 --> 00:45:55,600
and I think that's why
Tim's Nobel Prize was a Nobel Prize.

588
00:45:57,280 --> 00:46:02,720
There are always these pioneers
who work things out
and who had the idea first,

589
00:46:02,720 --> 00:46:07,240
and I think it's absolutely fine
to honour those people actually.

590
00:46:07,240 --> 00:46:12,520
I mean if you look at the list of
biological Nobel Prize winners,

591
00:46:12,520 --> 00:46:18,680
it really is a sort of,
a role call of major discoveries
down the last hundred odd years.

592
00:46:19,680 --> 00:46:23,480
The question that I always ask when
I'm trying to understand science,

593
00:46:23,480 --> 00:46:26,000
"Why did they know that
and they don't know this?"

594
00:46:26,000 --> 00:46:29,920
If you go back to the history
you say, "We know this because we
were working on that.

595
00:46:29,920 --> 00:46:33,040
"And we accidentally found that
and then that led to..."

596
00:46:33,040 --> 00:46:38,880
There is a sort of thread
running through it,
kind of continuity of ideas.

597
00:46:38,880 --> 00:46:42,000
If you like,
it's all just this gradual

598
00:46:42,000 --> 00:46:48,160
opening of a flower, an intellectual
flower that takes you from the
golden age of molecular biology,

599
00:46:48,160 --> 00:46:53,720
through worrying about how you
make proteins, to discovering the
protein that controls cell division.

600
00:46:53,720 --> 00:46:57,240
I think one of the things that's so
fantastic about all the fame and,

601
00:46:57,240 --> 00:47:02,160
publicity that accompanies things
like getting the Nobel Prize

602
00:47:02,160 --> 00:47:07,160
is that lots of the people
who go there, nice or not,

603
00:47:07,160 --> 00:47:11,520
are people who are just
unbelievably ambitious.

604
00:47:11,520 --> 00:47:15,240
And Tim certainly, like most
scientists, is competitive.

605
00:47:15,240 --> 00:47:18,360
He wants to do things
that are important.

606
00:47:18,360 --> 00:47:24,040
But he's really a scientists'
scientist in a way that I think
we've a little bit lost a sort of

607
00:47:24,040 --> 00:47:30,680
almost 19th-century tradition of
the independently wealthy gentlemen
who does things just cos it's fun.

608
00:47:30,680 --> 00:47:36,400
And I think Tim's spirit
of fun and generosity
and excitement about science

609
00:47:36,400 --> 00:47:43,080
as little contaminated by
personal ambition as it is in him,
makes him such a remarkable person.

610
00:47:45,520 --> 00:47:50,240
I have here his Nobel medal,
which he kindly gave to the College

611
00:47:50,240 --> 00:47:53,040
because he thought it
would be locked up in a bank,

612
00:47:53,040 --> 00:47:56,280
but if it's in Clare College
at least it would be seen.

613
00:47:56,280 --> 00:47:58,640
He's that sort of man.
Very generous.

614
00:47:58,640 --> 00:48:03,080
And we miss him here because
when he moved onto greater things,

615
00:48:03,080 --> 00:48:07,760
of course we lost him, but he was
always the life and soul of
the party,

616
00:48:07,760 --> 00:48:11,240
always good for a laugh,
cheered us all up.

617
00:48:11,240 --> 00:48:12,760
In fact, still miss him.

618
00:48:12,760 --> 00:48:15,400
I love to see him
when he comes here.

619
00:48:15,400 --> 00:48:18,680
He still comes on a regular
basis, but not enough for me.

620
00:48:24,720 --> 00:48:28,800
Today, Tim Hunt works
for Cancer Research UK.

621
00:48:30,400 --> 00:48:33,600
It was a move that had a
special poignancy for him.

622
00:48:33,600 --> 00:48:39,160
Before he was awarded his Nobel
Prize, his mother had been
diagnosed with the disease.

623
00:48:46,560 --> 00:48:50,560
I got this postcard from her
and it said,

624
00:48:50,560 --> 00:48:55,360
"Had lovely holiday in Scotland,
but ate poisonous mushroom."

625
00:48:55,360 --> 00:49:00,920
It wasn't the poisonous mushroom,
it was the fact that her liver was
already just one horrible mass

626
00:49:00,920 --> 00:49:06,160
and had stopped working, basically.
That's what was upsetting her.
It took a little while before...

627
00:49:06,160 --> 00:49:07,760
She was very funny about it.

628
00:49:07,760 --> 00:49:11,960
They took her down to some
X-ray machine and the young intern

629
00:49:11,960 --> 00:49:16,320
took one look at her X-ray
and said, "Oh, my God!"

630
00:49:16,320 --> 00:49:19,160
And she'd trained as a
physiotherapist, and she knew

631
00:49:19,160 --> 00:49:24,160
what hospital life was like,
and it amused her very much
that he behaved so badly.

632
00:49:24,160 --> 00:49:27,600
I mean this is absolutely not
what you do in front of a patient.

633
00:49:27,600 --> 00:49:31,560
But she was funny like that about...
very funny about herself.

634
00:49:32,600 --> 00:49:35,880
The cancer had, by this time, turned
into something called ascites,

635
00:49:35,880 --> 00:49:38,240
free-living cancer cells
in her belly.

636
00:49:38,240 --> 00:49:41,560
I tried to read... I knew nothing
about cancer at that point.

637
00:49:41,560 --> 00:49:46,680
How can it be that these cancer cells
are actually sucking the goodness
out of her good tissues?

638
00:49:46,680 --> 00:49:53,280
And why is it the muscles
waste away and her brain was as sharp
as anything, right to the end?

639
00:49:53,280 --> 00:49:59,400
I mean, there was no sign of mental
deterioration whatsoever,
it's just her body was failing.

640
00:49:59,400 --> 00:50:03,240
I mean, as a scientist,
that really fascinated me

641
00:50:03,240 --> 00:50:07,720
and I longed, and I have ever since
that day, longed to work on that.

642
00:50:11,000 --> 00:50:17,360
It was announced in October,
or something like that, and she
was dead just before Christmas.

643
00:50:17,360 --> 00:50:21,720
One time, she came into
the room and said, "I want you to
know, I'm not afraid of dying."

644
00:50:36,240 --> 00:50:42,240
After I'd heard that I won the Nobel
Prize it was a very...
you know...you sort of...

645
00:50:42,240 --> 00:50:45,440
It's hard to describe the emotions
that go through your mind.

646
00:50:45,440 --> 00:50:50,960
But one of them was
I was just driving out along...
you know, just coming in...

647
00:50:50,960 --> 00:50:53,440
Oh, God, what's it called?

648
00:50:53,440 --> 00:50:55,880
Along the Finchley Road
basically, the A41,

649
00:50:55,880 --> 00:51:02,000
and suddenly tears welled up
in my eyes because I thought how
proud my parents would have been.

650
00:51:02,000 --> 00:51:06,800
And it was, it was really sort of
awful actually, weird,
I mean just weird.

651
00:51:15,120 --> 00:51:19,040
I was very thrilled when
the opportunity came
to work in a cancer institute.

652
00:51:19,040 --> 00:51:23,680
Because of my mum
and partly because I think it's just
a very, very interesting problem,

653
00:51:23,680 --> 00:51:28,520
and partly because an awful lot
of people die of it.

654
00:51:28,520 --> 00:51:34,080
I mean understanding how the cell
cycle works does kind of inform
aspects of cancer research, but it...

655
00:51:34,080 --> 00:51:41,880
As I often say, if I did discover a
cure for even one cancer, nobody
would be more thrilled than me.

656
00:51:41,880 --> 00:51:47,240
But it's not what motivates me,
for one. I mean, you know...

657
00:51:47,240 --> 00:51:50,480
I just want to try and understand
what the hell is going on.

658
00:51:51,760 --> 00:51:57,600
Cancer is characterised by
cells dividing out of control,
but understanding why they do

659
00:51:57,600 --> 00:52:01,080
is a problem that has resisted
solution for over 50 years.

660
00:52:01,080 --> 00:52:06,720
The time has come in America
to turn toward conquering
this dread disease.

661
00:52:09,800 --> 00:52:15,560
It is perhaps the last great battle
that modern medicine has to wage.

662
00:52:15,560 --> 00:52:20,560
The time has come in America
when the same kind of

663
00:52:20,560 --> 00:52:24,840
concentrated effort that split the
atom and took man to the moon

664
00:52:24,840 --> 00:52:28,280
should be turned toward
conquering this dread disease.

665
00:52:30,400 --> 00:52:34,960
But it's not just an issue of
funding and political will.

666
00:52:36,200 --> 00:52:41,280
I think
that we are still remarkably poor

667
00:52:41,280 --> 00:52:45,600
at dealing with cancer, and so
when I teach students about it

668
00:52:45,600 --> 00:52:50,600
I draw the analogy
between John Kennedy

669
00:52:50,600 --> 00:52:53,560
declaring that Americans
will put people on the moon.

670
00:52:53,560 --> 00:52:58,880
And I say exactly how long it took
and how much money it cost,
which was a lot.

671
00:52:58,880 --> 00:53:02,800
And then Richard Nixon,
declaring war on cancer.

672
00:53:02,800 --> 00:53:08,880
And so he set out, as a public aim,
defeating cancer

673
00:53:08,880 --> 00:53:13,560
and we've had more than 30, probably
approaching 40 years, since then.

674
00:53:16,240 --> 00:53:21,680
And when I talk about that I say,
putting people on the moon
required 19th century,

675
00:53:21,680 --> 00:53:25,560
or actually even earlier physics,
right? Basically, Newtonian physics.

676
00:53:25,560 --> 00:53:28,200
An engineering challenge,
not a scientific challenge.

677
00:53:28,200 --> 00:53:31,640
The problem with cancer is it's
a scientific challenge, right?

678
00:53:31,640 --> 00:53:34,680
We don't understand
exactly what cancer is.

679
00:53:34,680 --> 00:53:39,360
Knowing the molecules that control
cell division helps us a little.

680
00:53:41,200 --> 00:53:46,000
If anyone can make headway in the
defeat of cancer, it's Tim Hunt.

681
00:53:46,000 --> 00:53:50,240
Not because he is better funded
or has a superior work ethic than

682
00:53:50,240 --> 00:53:57,480
his fellow scientists, but simply
because of his undiminished thirst
for discovering how things work.

683
00:53:57,480 --> 00:54:02,160
Quite often it happens that
problems get solved out of left-field
by people just coming at it

684
00:54:02,160 --> 00:54:07,520
a different way. Very rarely happens
that biological problems are solved
by a direct, frontal attack.

685
00:54:10,480 --> 00:54:16,160
Tim Hunt's career
is, in many ways, typical of
the 21st century scientist.

686
00:54:16,160 --> 00:54:18,800
A rarefied world of
research institutes

687
00:54:18,800 --> 00:54:25,440
and searching peer reviews,
of academic conferences and sparking
ideas off fellow scientists.

688
00:54:27,760 --> 00:54:34,080
But there is a particular cast
of mind that can go beyond
even the most cutting-edge science.

689
00:54:37,120 --> 00:54:40,320
There are two sorts of scientists.

690
00:54:40,320 --> 00:54:43,520
There are people who
are really interested in big ideas

691
00:54:43,520 --> 00:54:47,800
and experiments, to them,
are simply a means to big ideas.

692
00:54:47,800 --> 00:54:50,440
The big thinkers, the speculators,

693
00:54:50,440 --> 00:54:55,360
you know, experiments,
unpleasant means to an end, often.

694
00:54:55,360 --> 00:54:59,360
And then there's another class of
scientist who just like to fiddle,

695
00:54:59,360 --> 00:55:05,080
to tinker. And to many of those
people, speculation is anathema.

696
00:55:05,080 --> 00:55:09,440
It means going beyond your data in a
sense, going somewhere where almost

697
00:55:09,440 --> 00:55:11,600
emotionally you're
not supposed to go.

698
00:55:11,600 --> 00:55:17,000
And what, to me, is unique about Tim
is he's both of those people.

699
00:55:27,440 --> 00:55:29,880
I think that my main talent
is sort of spotting

700
00:55:29,880 --> 00:55:33,200
funny little things that don't
quite make sense and that,

701
00:55:33,200 --> 00:55:35,920
you know...

702
00:55:35,920 --> 00:55:40,400
Isaac Newton talked about
shiny pebbles on the beach,
like a little boy

703
00:55:40,400 --> 00:55:44,320
wandering around seeing shiny...
looking for shiny pebbles
on the beach.

704
00:55:44,320 --> 00:55:49,880
I'm quite good at looking for
shiny pebbles and seeing things which
aren't actually on the mainstream

705
00:55:49,880 --> 00:55:55,440
but which lead you off
in a new direction and are incredibly
illuminating about what's going on.

706
00:55:55,440 --> 00:55:58,560
I mean, in other words,
I'm a good discoverer of things.

707
00:56:08,200 --> 00:56:10,720
Discovering things
is the most fun, I think.

708
00:56:10,720 --> 00:56:17,280
Because they tend to, sort of
illuminate whole fields in a way that
you couldn't believe.

709
00:56:17,280 --> 00:56:21,280
One moment you're ignorant
and the next moment
you get that little tiny,

710
00:56:21,280 --> 00:56:28,560
tiny clue that sort of
sheds an enormous amount of light
on the whole thing.

711
00:56:35,840 --> 00:56:43,000
It's not up to me, I don't think,
to decide whether my mind
is beautiful or not.

712
00:56:43,000 --> 00:56:46,760
But it's my mind and it's taken
me to some exciting places

713
00:56:46,760 --> 00:56:49,280
and answered
some very interesting questions

714
00:56:49,280 --> 00:56:52,640
and it's given me a lot of fun,
and for that, I'm very grateful.

715
00:57:16,800 --> 00:57:19,880
Subtitles by Red Bee Media Ltd

716
00:57:19,880 --> 00:57:22,840
E-mail subtitling@bbc.co.uk