Beautiful Minds (3/3)

The practice of science has shaped the modern era,
but how are discoveries made?
And how does science progress?
Three British scientists, world leaders in their fields,
have changed our understanding of our universe, our planet and ourselves.
A physicist whose mysterious radio signals from space re-wrote astronomy.
She actually recognised that there was something happening.
I suspect that perhaps only 1 in 100 people would have spotted it.
A chemist whose radical theory about our planet divides the scientific world.
He's one of the greatest thinkers of the current age and destined to go down in history.
And a biologist who discovered the secret of life in a sea urchin.
Your fundamental discoveries have profoundly increased
our understanding of how the cell cycle is controlled.
Their stories tell us about the nature of scientific enquiry in the modern world.
About how scientific breakthroughs are made,
and about the workings of the scientific brain.
Scientists are very keen to... to get at the truth,
to get to the bottom of things, but there is no such thing as ultimate truth.
Every time you turn over one stone and you find something
interesting underneath and that just leads you to another stone.
And there are layers, it's sort of real onion skin, and go down and down
and down and down and down, and there always wrinkles to be figured out.
And what's curious, I've found, is that some things
are very easy to find out once you know how to find them out.
Some things, very simple questions, turn out to be amazingly difficult.
It's utterly unpredictable which ones sort of fall out and which ones don't.
Tim Hunt's remarkable career has led to the understanding
of one of the greatest scientific mysteries of all.
Cell division.
The complex process in all plants and all animals
that underpins life itself.
That it happens and even why it happens are straightforward propositions,
but until Tim Hunt, nobody knew exactly how one cell divided to become two.
The unravelling of that key mechanism was so fundamental
to the understanding of life that in 2001 Hunt was awarded the Nobel Prize.
It was the crowning glory of a life devoted to scientific research at the very highest level.
Recognition of a discovery that owed its existence to Tim Hunt's singular approach to science.
One moment you're ignorant, and the next moment you sort of get that little tiny, tiny clue
that sort of sheds an enormous amount of light on the whole thing.
That's a sort of mysterious thing about science. It's different from engineering.
I mean, you've been able to build a bridge over a river for thousands of years.
The basic principles are understood.
But in science you're never quite sure where you are actually, most of the time.
You know, you've got to enjoy swimming in this sea
of unknowingness. Otherwise what's the point?
There's a famous quote from a physicist named Leon Lederman,
which says, "Those who never stop asking silly questions grow up to be scientists".
And Tim, to me, is the exemplar of that sort of person because there is
nothing that Tim doesn't want to know the answer to.
One of the things he thinks about is why the sky is blue.
Questions like that.
And what I think we're seeing is a very curious mind,
the sort of mind that a child has, which always asks questions.
And most people lose that curiosity, but Tim has it in spades.
I like to tell the story of having learned that I'm a Nobel Laureate,
of my daughter, who was then seven, Celia,
saying, "Daddy, why is the ceiling opaque?"
And I looked up at the ceiling, oh, light doesn't get through the ceiling. And then...
then I looked out of her window and I thought, "Oh, goodness, how does light get through the window?"
And I realised we'd done all the sort of measuring refractive indices
for A level, but nobody had ever told us why light gets through the glass
but doesn't get through the wall.
And this seems like a really rather fundamental thing, so I then started asking people,
how does it work? How does it work?
And physicist friends, biologist friends and absolutely everybody I ran into, you know?
Why does light get through glass?
I mean it was so interesting, different people use different approaches.
This is a good example of how a biologist thinks about things.
So when I sort of... I knew that glass was a frozen liquid.
So I thought, well, what other liquids?
Maybe it's because it's a liquid that light...
Then I suddenly realised that mercury was a liquid and light is reflected off mercury.
It doesn't go through mercury at all. So that hypothesis was out the window.
And then I thought about carbon, and carbon comes in the blackest black
that absorbs light better than absolutely anything on Earth.
But also in diamond, which is the sort of sparkliest, most translucent stuff you could possibly imagine.
And that then tells you that it's to do with the electrons,
how the electronic configurations of the actual material.
And then you realise that it's to do with the theories of how photons
interact with electrons and then you know you're lost, basically!
He writes a problems book with his friend, John Wilson, and they once
worked out how far up an Alp one Mars bar would take you.
It's that sort of thing. How many calories are there?
What do calories translate to in terms of vertical motion for a human?
So he's doing that, I think, in his head most of the time.
Except when he's looking vacant, when he really is vacant. He must have some of those moments.
But I think he is continuously thinking about
most of the situations he's in and wondering what's happening.
Tim Hunt's passion for scientific enquiry started when he was a small boy.
I just loved old radio sets and there were a lot around.
I mean they were just so amazing and so beautifully made and they were the tuning device.
I guess I longed to be an electrical engineer and be able to
design the circuits. Although I was completely hopeless, I couldn't do it.
I loved it, I loved it. I loved making motors and microphones and loudspeakers.
Always wanted to understand how things worked.
I mean, here, you stick this Bakelite box on the table and you
tune the dial and voices come from the universe towards you.
And you look inside, "What's doing this?" It's just these glowing valves.
I remember making fuses too, that was good fun. So you soak a piece of string in sodium chlorate.
And then I remember one time, we tried to accelerate its drying out
so we put it under the grill, which was a big mistake cos the thing went kaboom!
He was older than I was, so he was the leader and I was the follower...
behind, if I'm to be absolutely honest.
Which was good. He was good, he was imaginative about it, you know?
We did interesting and fun things.
I suppose we were quite scientific about it really.
Now I come to think of it, I think he's very, sort of inquisitive. He likes to try everything out.
I just wanted to know how things work, all the time. How do things...
What's behind this, you know?
And I loved the idea that you could, you know, there was...
a sort of simple explanation behind everything you could see.
This passion to really understand how things worked, persisted
and shaped his entire scientific career.
It led him to the challenge of understanding life itself
and to the fundamental process that drives it.
Our lives start with a single cell.
That first cell splits to become two,
and then they in turn divide into two to become four, and so on.
So, after just 48 doublings, you have a hundred thousand billion cells
in your body, and you're ready to spring forth as a human being.
The miracle of cell division is, at its most dramatic,
a process that creates new life.
But it's also fundamental to maintaining life,
and it's this that reveals the complexity at its core.
Everything is being replaced all of the time.
There are new molecules being put in place of old ones.
The old ones are sort of recycled and...
I always remember when I went as a junior proctor,
we went and visited this air-force base, and I was very thrilled because we saw a Canberra bomber.
So I asked, "Gosh, is this really an original?"
They said, "The pilot's seat might be, but everything else...
"it's got new wings, it's got new fuselage,
"it's got new this... " The thing had been totally replaced
and yet it was still a Canberra bomber and not some other kind.
It wasn't a Spitfire, it wasn't anything. We're like that.
Life and cells have the ability to patch themselves all of the time.
Damage is being done all of the time.
You have a new nose basically, certainly every seven years.
I mean there isn't a single thing, component, in your nose left.
But the amazing thing is it's still your nose, you know? It doesn't... it hasn't grown,
it hasn't shrunk, it's still got the same shape that you were born with, so to speak.
Absolutely remarkable, you know?
So how these cells know...
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
and if something happens and that cell dies then, it's neighbours say,
"Oh, dear. Tim's lost the tip of his nose.
"We'd better put in a new cell there cos it's gone. "
And that's replaced by cell division.
For Hunt, understanding this great mystery
means breaking it down to its smallest components.
Life, all life, can be understood as a series of complex mechanisms,
a myriad of individual processes happening within the cell.
The way that I think of it is that, you imagine yourself shrunk down
to the size of a molecule, and you're standing by this amazing molecular machine
and watching how all the things,
come in and out and pull each other and push each other.
Those are the terms in which you want to understand it.
There are different philosophies of how you should do science
or can do science, and one philosophy
is reductionism. The idea that you can explain everything in terms of the smallest bits inside it.
Like explaining the whole of nature in terms of atoms, or quarks, or sub-atomic particles,
and that way of thinking has led to molecular biology.
The way to understand life is to understand the smallest things
in living organisms, molecules, DNA, proteins and so forth.
And that somehow, out of understanding all the details, the big picture will emerge.
Tim is definitely working within that tradition.
This approach had started when he was a teenager, when he came across
a problem that would take him more than 20 years to solve.
When I was doing A level biology, I remember seeing an amazing movie of biochemical pathways
with compounds flowing down and cycles going round
and things spinning off and all that kind of stuff.
I remember thinking at the time it was all very well these pathways,
but there didn't seem to be any control.
How could you have all those reactions going on simultaneously?
There's got to be something controlling it.
This was very thrilling. A kind of revelation.
So, what I suddenly realised was that control was the fundamental issue of all life.
From then on, I knew that being a biologist was what I was cut out for.
Tim Hunt was brought up in Oxford, where the disciplines
of the academic life and a passion for detail, were part of his heritage.
Dad was something called a Keeper of the Western Manuscript at the Bodleian Library.
He had a sort of encyclopaedic feel for what was where,
and you could use these manuscripts,
which were actually bound into books, to trace who knew what, when.
Manuscripts were copied by monks. There was no printing in those days.
Everything had to be copied, and the monk would make the odd mistake.
But those mistakes then tended to be copied faithfully by the next copyist.
Then that book would be taken to the next monastery, and so you could actually
trace a genealogical tree of the spread of knowledge across Europe by this technique.
His office at the Bodleian was quite remarkable.
There was a huge table. It was quite a big room, and in the middle of the table, the papers,
the letters were about a foot deep, or something.
And then towards the edge they sort of thinned out rather,
cos otherwise they'd have spilled onto the floor.
So I don't know how he managed his correspondence, but I'm exactly the same.
It's a sort of classification system whereby the less important things
fractionate to the bottom of the pile and the important things either stay on the top or rise to the top.
Tim and my Dad are very alike in many, many ways.
They are both very scholarly.
Tim is a stickler for science and the way that it is carried out
and for all the principles of keeping science honest.
My father was an absolute stickler for scholarship.
Dad was very keen on the right way of doing things, and I've always felt that too, in science.
And that's served me well because it's the details in biology that unlocks the secrets.
Hunt's academic career began in earnest when he went to Cambridge to read natural sciences.
He found himself thrown into a world of scientific optimism and mild eccentricity.
Tim and I were very close friends. We used to do a lot of things together.
We were often called the Terrible Two. I'm not quite sure why
I don't think we were particularly terrible, but...
they were...
.. I think people found us a sort of unusual pair of people to have around.
Most people had just ordinary white lab coats, but Tim and I dyed ours
and his most characteristic clothing at the time
was a pink boiler suit that he used to wear at the lab, and indeed, walking around Cambridge.
And in the winter this was... Wasn't warm enough,
so he needed something warmer. Then he had sort of third-hand fur coats.
So he wore these rather eccentric, long fur coats over his pink boiler suit.
You never felt that it was an affectation in his case.
He made eccentricity seem normal.
We found rooms in The Eagle pub
and we lived there for three years, while we were doing our PhDs.
We were nocturnal, so we used to go back into the lab and start work
about ten, and usually work through till three or four in the morning.
And we had loudspeakers in both our labs and we draped wires over the outside of the building.
And so at night we had the whole laboratory resounding to this wonderful music.
Sort of Monteverdi operas, symphonies, going on all night in the lab and the whole lab echoed.
So we had a very nice way of working there.
Hunt had arrived at Cambridge at precisely the right time for a young scientist
who was passionate about the emerging science of molecular biology.
I think Cambridge was...
.. a good place for high objectives.
It was a site of great science
and you were supposed to do it in a sort of understated way.
And when I think back at it, it was probably then... in biology,
the leading university in the world. If you just put what people were trying to do.
There was no other place which had the focus on important things.
'Dr James Watson, aged only 34, an American biologist who worked for two years at Cambridge.
'Francis Crick, aged 46, worked in the Admiralty on mine detection
'during the war, then switched to biology.
'They puzzled about the mechanism of inheritance that makes you so much like your parents.
'Between them, they shared the Nobel Prize for medicine'.
I think Tim was very impressed by the molecular approach
that Crick was advocating, and indeed most people were advocating.
And that was the sort of high noon of molecular biology,
the genetic code had just been cracked,
the mechanism of protein synthesis had just been worked out.
Tim was working out some of the details of all this.
It was a period of enormous optimism
and people thought that this was the way forward to understand life.
When Watson and Crick lounged around, chatting about things about which they knew nothing,
but as a result of this, they discovered the structure of DNA, the most important...
arguably the most important scientific, biological discovery of the 20th century.
There's more than one way of doing good science, and that's extremely true, you know?
I mean you just have to take... it's so hard.
I think that's what a lot of people don't understand, it's so hard,
and so slow that you have to take little clues
from wherever they come from.
Jim Watson was a fellow of my college and don't quite know
how I first met him, but I mean he would just drop by.
Jim has an amazing property.
He sort of drops by, he sort of pops out in your life at crucial moments.
Very interesting man, very interesting man.
You could actually see that he also really, really cared about
getting to the bottom of things, and that's what's finally important.
I mean, those people who are actually trying to get to the bottom of things, not for their own glory,
but just because they really, really want to understand. I think that's terribly important.
Cambridge was always rather amusing in those days because
Francis would have about one idea I think every two weeks
and it'd take a couple of days for him to be convinced it was no good.
And in those couple of days we'd...
he'd never stop talking, and if we were in sort of
good spirits we could, you know, really ask him difficult questions.
I'm very much a hero worshipper.
Francis Crick was really our hero, you know? Omnipresent figure at seminars.
He'd often be sort of sat at the back of a seminar and he would almost always ask questions.
Sometimes in the... if it was OK, within the body of the talk.
And these questions were always trying to clarify things. To get to the bottom of things.
And unlike some people who ask, in Cambridge, who ask questions to show how clever THEY were,
actually, they were often questions, which revealed how ignorant he was.
But he still had the confidence to ask, because if you didn't understand
that particular point, the whole thing just would be incomprehensible.
Certain things I think can be thought to be alive.
I think we would agree that you and I are alive.
The difficulty comes with the borderline cases, like the viruses,
and I think really what it comes to is you're really arguing about
a word when you ask the question.
Is a virus... is the polio virus alive, for example?
Tim, because he started working on how proteins are made, the process called translation,
he was very connected to those people because
that was part of the central dogma. DNA makes RNA, makes protein.
And the question is how do you make protein?
What are the nuts and bolts of those steps and how do you control that process?
That's really where Tim started as a scientist.
It was the beginning of a journey that would lead to Hunt unravelling
the fundamental mystery of cell division.
A journey that began with understanding the biochemistry of proteins.
Proteins do absolutely everything. I used to enjoy telling students,
when we sort of started out on a journey through cell biology and biochemistry that,
I look at your face and I'm looking at proteins, you know?
That's your skin and I can see that your blood is red because your lips are pink,
and the eyes are clear but that's protein specially arranged so that the light can go through it.
So, the hair is a different kind of protein
from the skin and related but different.
And so on. So that's all... that's all protein.
Everything you're made of, stuff you can really feel,
it's tough stuff, you know? If you've ever eaten a piece of gristle you know how ghastly
and tough protein can be. But they can also catalyse chemical reactions
to make sure that what you eat then becomes you,
and you alone because you break down all the proteins into their components,
and then build them up again to your own cells' components.
At Cambridge, Tim Hunt began working on the problem of how individual
proteins were made, and specifically how this process was controlled.
What became clear
and what was nice about all of this stuff is that you could...
you could turn protein synthesis on and off.
And it was the fact that you could turn it on and off
meant that you were really studying the control of protein synthesis in a test tube.
And finding out what the molecular mechanism behind that switch was,
became a sort of all-consuming goal.
In 1968, Tim Hunt received an invitation that would change his life.
I'd come to New York to work with a man called Irving London,
who was actually the Head of the Department of Medicine at the Albert Einstein College of Medicine.
But he was very keen on research and he was interested in exactly
the same problem as I was, which was the control of protein synthesis.
I lived on the Upper West Side, not far Columbia University really,
but had to travel to the Far East Bronx.
I mean probably about a 40-minute subway ride...
through some of the roughest, crime-ridden districts in the world.
There was no question of looking respectable.
I used to read The New York Times from cover to cover going out,
and the Journal of Molecular Biology coming home, quite often, usually pretty late at night.
It was a cultural, as well as a scientific opportunity for Hunt,
who went about documenting his time in the us by taking photographs.
I saved up enough money to buy a Pentax camera
that had a little meter built into it, and this was the beginnings
of the real revolution. So you didn't have to worry about exposures and all that kind of stuff.
Very obsessed with these sort of great French photographers
who sort of somehow sort of capture the minute of the passing scene.
I absolutely loved that.
In the lab, Hunt and Irving London were trying to capture significant moments in protein synthesis.
They separated the individual proteins manufactured in cells using chromatography.
Each horizontal line represents an individual protein
and each column, a different point in time.
You have to keep on taking time points and, I don't know,
half a dozen, maybe ten samples per time course would be enough.
The technique made it possible to see the ebb and flow of proteins as they were produced in the cell,
in a way that taking a single measurement could not.
I learned a great deal about technique.
Watching, measuring the rates of protein synthesis and being precise about controls.
And making sure that you saw the big picture and not...
sort of like making a movie rather than just taking snapshots.
In New York, Hunt had equipped himself
with the tools he'd later need to make his greatest breakthrough.
But as is so often the way in science,
serendipity and chance encounters also played their part.
About this time I went to a talk by a guy called John Gerhart, and very soon
I was right on the edge of my seat because he was explaining his studies
on MPF, maturation promoting factor, the magical missing link which seemed to be the trigger for cell division.
For years, biologists had known that theoretically, something must make a cell divide.
But try as they might, they couldn't find it.
They had, however, given it a name.
I think there's an interesting lesson to be learnt from MPF because
when it was originally conceived
it had a rather abstract nature. It was just factor...
a factor that was present in cells that made other cells divide.
But one had no idea quite what it was.
And what you needed to do was to turn that abstraction into a physical reality and you do that by
determining what molecules make it up. And science quite often inhabits that territory.
You have an idea, an abstract thought about what's going on,
but you have to turn it into something more concrete.
It was nowhere near what I was working on at the time,
but it struck me as a really delicious problem.
You could almost taste it, within grasp.
You could begin to think about what it was and how it might work.
Hunt's interest in the stubbornly elusive MPF stayed with him.
A decade later he was dividing his time between Cambridge and the US,
looking at protein synthesis in cell division.
Woods Hole is a famous marine biological laboratory
at the seaside, near Boston. And that was in the summer of 1982.
Alongside a friend, Eric Rosenthal, who was doing some experiments on clam eggs, and what we were
doing was to try to compare the kinds of proteins made in clam eggs, before and after fertilisation.
With Tim's help, Eric showed that the proteins that
you make before you fertilise a clam egg and afterwards, are different.
And there are three proteins that you make much more of after you've
fertilised the egg, and they got the imaginative names A, B and C.
And so when Eric would do experiments, in each experiment he always saw a lot of C.
And in some experiments he saw a lot of A and B, and some experiments he saw almost none.
So my friend had been taking snapshots, comparing the patterns of protein synthesis,
and he noticed that sometimes the proteins were there and sometimes that they weren't.
And it was just a complete mystery to me.
Why would the proteins sometimes be there and sometimes not be?
Normally, proteins would synthesise and stay there.
They didn't just go away. I'd never seen anything like it.
It was an intriguing problem.
A problem whose solution might provide another piece of the MPF jigsaw,
and one that Hunt was ideally placed to investigate.
What you really needed was a movie to understand what was going on,
very much the same kind of approach that I'd developed in New York.
Eric never had the time or the inclination or,
the desire to overcome the experimental difficulties, to take that leap and pursue that.
And Tim saw something that he didn't expect to see,
and then, in that situation, scientists have to make a decision.
Do I stay narrowly focused on what I thought I was doing
and just ignore this thing as being a will-o'- the-wisp, or do I realise
that I've seen something that is much more important and pursue that?
I started my own research on sea-urchin eggs to see if the same kind of things were happening.
I just wanted to get to the bottom of it.
The experiment was very, very simple. That's the important thing.
So one day, and it turns out the experiment started at eight o'clock
at night, and the others had all gone out dancing or drinking or something,
so I was left all alone in the lab, it was just me and some sea-urchin eggs.
And I checked they were fertilised, added the label, and then took out samples roughly every ten minutes.
We just analysed the samples on something called
an SDS polyacrylamide gel, which was very standard,
and we knew exactly how to do and do it very beautifully, though I say so myself.
I saw this protein which was actually the very first one whose synthesis you could just detect.
And it got stronger and stronger and stronger, and then it faded away.
All the other ones just went on getting stronger and stronger.
I looked at it and thought, "Extraordinary!" The way the experiment was done
there was no question that this protein going away must mean that it was being degraded
and being degraded specifically.
There was just this one protein went away.
All the others behaved as you could have expected.
Looking at the full picture in this way, taking samples over time,
let me see that the protein wasn't coming and going randomly.
It was coming and going in a very distinct cycle.
I looked at this and...
"Gosh!" you know? That's absolutely amazing.
There it was, on this gel in black and white.
Hunt called the protein cyclin
because it came and went with the cell's cycle.
He knew that what he was witnessing was significant,
but he had no idea what it could mean.
As it happened, I think I must have got the result on a Friday morning.
On Friday evening I ran into John Gerhart
at the wine and cheese party, after the Friday evening lecture.
John was the man whose talk about MPF, the magical missing link,
had excited me so much all those years ago.
So suddenly, everything was coming full circle.
This was the most exciting conversation,
scientific conversation, of my entire life, I mean bar none.
Extraordinary. I remember somebody came and tried to talk to me, I just brushed them off
because this conversation I was having was so important
to get it right. And it was absolutely the key.
And so from that moment on, this is very unusual,
the other things I've told you about, it often took weeks or months to figure out what was going on.
But basically I'd seen this protein go away and I knew in my heart of hearts that somehow this was
really important, and somehow deeply connected, intimately connected with the cell division control machinery.
And it was something that nobody had ever, ever in their wildest
imaginings thought of, that the protein might actually just go away.
At the time that Tim discovered cyclin, it was sort of like the Northwest Passage.
It's like knowing that the Northwest Passage exists
but I can't point to it on a map and tell you exactly where it is.
And so the search, if you like, is for that discovery of what is the molecule that is MPF?
And so when Tim discovered cyclin there's immediately this congruence
between, here's cyclin, a protein we have to make to get cells to divide.
And here's MPF, something which pushes cells into the stage where they're just about to divide.
Why did I have this sense
that the going away of cyclin was intimately related to the control
of the cell's cycle, and why did that explain so much,
that I internally felt intuitively that it was probably the right answer?
Although it had to be, you know... you had to nail it. You couldn't just take it for granted.
And I'm not sure that I can give a very coherent, you know...
Because it was more of a gut feeling.
The truth of the matter is that I didn't dare hope that my cyclin,
which was going up and down like a yo-yo, was part of MPF.
That would have just been way too good to be true.
That would have been like an instant Nobel Prize, and, you don't get instant Nobel Prizes
just by doing one dumb-ass experiment on a Saturday morning, so to speak, you know?
The excitement felt in Tim's circle at Woods Hole was not matched in the
wider scientific community and Hunt was brought abruptly down to earth.
People looked at me as though I was slightly deranged.
I had quite a hard time.
Indeed, when I sent off our first paper about this work to the journal Cell, the editor wrote back to me,
"Dear Tim, the good news is we will publish your paper, but the bad news is in nothing like its present form. "
And one of the reviewers said, "It was wild speculation based on faulty logic".
I can remember him ringing up and saying that he was...
I can't remember what phrase he used,
but he was essentially saying that he was
tired of science and of research.
Most people didn't have a problem with it seeming to have something to do with the cell cycle,
but showing that it controlled the cell cycle was a much trickier thing to actually establish.
He is a stickler for the world of people...
.. peer recognition and all the rest of it.
Well, his peers didn't recognise him, did they?
They were just sceptical, and rightly so in a way, that, you know, I wasn't... I...
Let's reserve judgment, put it that way, right?
I think that's a perfectly legitimate thing to do.
We had a lot of work to do and...
I mean this was one of the funniest periods of my life.
Little bit scary... good, because...
because people were so sceptical nobody... nobody was still prepared to make that plunge themselves.
Right? And that was...
That was kind of... so it gave us a lot of space actually.
Tim is not one of those arrogant scientists.
He actually suffers a lot from self doubt.
Often people are black and white, you know? This is right, this is wrong. Tim understands greyness.
He understands that sometimes problems are not very clear and the best thing to do is talk about them.
And these are features that mark out, in my view at least, a very good scientist.
Hunt was faced with the daunting task of explaining exactly why
the mercurial cyclin was in fact MPF, the stuff of life.
His first instinct was to collaborate.
Once you've got an idea, it's very good to bounce it off other people.
You've got a result and you think it means this
and you find your peers, your competition, the people who are actually working on this,
and trying to sort of tease out as much as you possibly can
to suck the data absolutely dry, right down to the bone, so that you can...
So very interesting, the sort of the relationships with competitors.
And... you know? I always found the best thing was to tell everybody everything.
It was Hunt's spirit of openness that led to his fruitful collaboration
with the man who would be instrumental in helping him complete the cyclin story.
I'd been working on sort of genetic approaches to how the cell division cycle is regulated.
I'd been doing that since the early to mid 1970s,
and my work was abstract and I didn't have any idea about how
the biochemistry, the chemical molecules that were involved, but I was very interested in that.
And in the early '80s I was gradually getting
towards getting towards looking at what molecules might be involved, using genetic approaches.
And so I started to get very interested in other people's work, which might illuminate that.
And I also was going to conferences and meetings where Tim was talking,
and he was talking about this protein that was appearing and disappearing.
So I obviously thought this could be, if luck was in the right place,
this could be an element of the same sort of problem that I was interested in.
If cyclin was to unlock the mystery of the magical MPF,
it would be necessary to explain its precise role in cell division.
What's more, it would need to be present in the dividing cells
of all living things, not just a single species.
Tim Hunt, Paul Nurse and their colleagues, set to work in earnest.
We all knew each other and we all worked on different things.
She worked on clams, he worked on yeast,
I worked on frogs and sea urchins, and it was great and there was so much to be found out.
The first thing, you see this in sea-urchin eggs, and you say,
"OK, that's interesting. That's how sea urchins do it. "
Then you see it in clams, and that's pretty significant because
clams and sea urchins, if you look at the tree of life, they're pretty far apart.
So that suggests that it's at least in all sea creatures, molluscs and echinoderms.
Now we're descended form echinoderms, so if echinoderms do it probably we do too.
To go then from frogs and to try and make the MPF connection was really important.
So once we knew it was there in frogs we could be utterly confident that it was going to be there in humans.
And then it was clear that it was absolutely universal.
This time there could be no doubting the veracity or the importance of their discovery.
Every single animal, every single plant uses exactly the same
fundamental mechanism to catalyse cell division.
And by the time we knew all this, it became pretty much irrefutable.
Suddenly, people... the scales fell from everybody's eyes
and everybody realised that this was the secret and this was the basis of cell division.
One of the greatest mysteries in biology had been solved.
The continued existence of all life on earth could now be explained.
Cell division was no longer governed by theoretical construct,
but by real chemicals on a real protein
called cyclin, discovered in a sea urchin by Tim Hunt.
Now, the scientific establishment beat a path to his door.
The Nobel Prize is the only scientific prize
that the public generally know about, so it is iconic.
I mean there are quite a few other prizes which sort of lead up to it and...
But it's the Nobel Prize that really matters.
Tim phoned me and he had to come down to London from his lab
for a press conference with Paul Nurse.
So he'd dropped by my office and he looked like he'd been in
a road accident, he was in shock I would say, very pale, very shaky.
And we went to tell Celia at that point, who was at primary school and sort of old enough to understand.
The head teacher said when we got to the door we looked like we'd been in an accident, basically.
We're going, "Won the Nobel Prize, what shall we do?"
And Tim really didn't believe it.
He almost thought that somebody... that it was a spoof, although I think he had talked
directly to the Swedes, whereas I had not.
I said, "People wouldn't be so cruel, Tim, certainly not to you. "
Until the King had actually given me this bloody medal, I really thought that somebody might come in and...
"No, sorry, made a ghastly mistake. "
Dr Hartwell,
Dr Hunt and Dr Nurse.
Your fundamental discoveries have profoundly increased
our understanding of how the cell cycle is controlled.
This new knowledge has a huge impact on cell biology
with broad applications in many fields of biology and medicine.
It's very moving because you know this is the pinnacle of your scientific career.
And I now ask you to step forward to receive the Nobel Prize from the hands of his majesty, the King.
APPLAUSE
Oh, yeah, I still feel enormously proud.
Hugely so.
I think the Nobel Prize rewards significant achievements in science,
which are of importance for science as a whole.
And the Nobel Prize is really about rewarding things which become
foundational parts of conventional science.
The key discoveries that are the foundations of established science,
and discovering the way that cell division works
is a key discovery in history, in the history of biology,
and I think that's why Tim's Nobel Prize was a Nobel Prize.
There are always these pioneers who work things out and who had the idea first,
and I think it's absolutely fine to honour those people actually.
I mean if you look at the list of biological Nobel Prize winners,
it really is a sort of, a role call of major discoveries down the last hundred odd years.
The question that I always ask when I'm trying to understand science,
"Why did they know that and they don't know this?"
If you go back to the history you say, "We know this because we were working on that.
"And we accidentally found that and then that led to... "
There is a sort of thread running through it, kind of continuity of ideas.
If you like, it's all just this gradual
opening of a flower, an intellectual flower that takes you from the golden age of molecular biology,
through worrying about how you make proteins, to discovering the protein that controls cell division.
I think one of the things that's so fantastic about all the fame and,
publicity that accompanies things like getting the Nobel Prize
is that lots of the people who go there, nice or not,
are people who are just unbelievably ambitious.
And Tim certainly, like most scientists, is competitive.
He wants to do things that are important.
But he's really a scientists' scientist in a way that I think we've a little bit lost a sort of
almost 19th-century tradition of the independently wealthy gentlemen who does things just cos it's fun.
And I think Tim's spirit of fun and generosity and excitement about science
as little contaminated by personal ambition as it is in him, makes him such a remarkable person.
I have here his Nobel medal, which he kindly gave to the College
because he thought it would be locked up in a bank,
but if it's in Clare College at least it would be seen.
He's that sort of man. Very generous.
And we miss him here because when he moved onto greater things,
of course we lost him, but he was always the life and soul of the party,
always good for a laugh, cheered us all up.
In fact, still miss him.
I love to see him when he comes here.
He still comes on a regular basis, but not enough for me.
Today, Tim Hunt works for Cancer Research UK.
It was a move that had a special poignancy for him.
Before he was awarded his Nobel Prize, his mother had been diagnosed with the disease.
I got this postcard from her and it said,
"Had lovely holiday in Scotland, but ate poisonous mushroom. "
It wasn't the poisonous mushroom, it was the fact that her liver was already just one horrible mass
and had stopped working, basically. That's what was upsetting her. It took a little while before...
She was very funny about it.
They took her down to some X- ray machine and the young intern
took one look at her X-ray and said, "Oh, my God!"
And she'd trained as a physiotherapist, and she knew
what hospital life was like, and it amused her very much that he behaved so badly.
I mean this is absolutely not what you do in front of a patient.
But she was funny like that about... very funny about herself.
The cancer had, by this time, turned into something called ascites,
free-living cancer cells in her belly.
I tried to read... I knew nothing about cancer at that point.
How can it be that these cancer cells are actually sucking the goodness out of her good tissues?
And why is it the muscles waste away and her brain was as sharp as anything, right to the end?
I mean, there was no sign of mental deterioration whatsoever, it's just her body was failing.
I mean, as a scientist, that really fascinated me
and I longed, and I have ever since that day, longed to work on that.
It was announced in October, or something like that, and she was dead just before Christmas.
One time, she came into the room and said, "I want you to know, I'm not afraid of dying. "
After I'd heard that I won the Nobel Prize it was a very... you know... you sort of...
It's hard to describe the emotions that go through your mind.
But one of them was I was just driving out along... you know, just coming in...
Oh, God, what's it called?
Along the Finchley Road basically, the A41,
and suddenly tears welled up in my eyes because I thought how proud my parents would have been.
And it was, it was really sort of awful actually, weird, I mean just weird.
I was very thrilled when the opportunity came to work in a cancer institute.
Because of my mum and partly because I think it's just a very, very interesting problem,
and partly because an awful lot of people die of it.
I mean understanding how the cell cycle works does kind of inform aspects of cancer research, but it...
As I often say, if I did discover a cure for even one cancer, nobody would be more thrilled than me.
But it's not what motivates me, for one. I mean, you know...
I just want to try and understand what the hell is going on.
Cancer is characterised by cells dividing out of control, but understanding why they do
is a problem that has resisted solution for over 50 years.
The time has come in America to turn toward conquering this dread disease.
It is perhaps the last great battle that modern medicine has to wage.
The time has come in America when the same kind of
concentrated effort that split the atom and took man to the moon
should be turned toward conquering this dread disease.
But it's not just an issue of funding and political will.
I think that we are still remarkably poor
at dealing with cancer, and so when I teach students about it
I draw the analogy between John Kennedy
declaring that Americans will put people on the moon.
And I say exactly how long it took and how much money it cost, which was a lot.
And then Richard Nixon, declaring war on cancer.
And so he set out, as a public aim, defeating cancer
and we've had more than 30, probably approaching 40 years, since then.
And when I talk about that I say, putting people on the moon required 19th century,
or actually even earlier physics, right? Basically, Newtonian physics.
An engineering challenge, not a scientific challenge.
The problem with cancer is it's a scientific challenge, right?
We don't understand exactly what cancer is.
Knowing the molecules that control cell division helps us a little.
If anyone can make headway in the defeat of cancer, it's Tim Hunt.
Not because he is better funded or has a superior work ethic than
his fellow scientists, but simply because of his undiminished thirst for discovering how things work.
Quite often it happens that problems get solved out of left-field by people just coming at it
a different way. Very rarely happens that biological problems are solved by a direct, frontal attack.
Tim Hunt's career is, in many ways, typical of the 21st century scientist.
A rarefied world of research institutes
and searching peer reviews, of academic conferences and sparking ideas off fellow scientists.
But there is a particular cast of mind that can go beyond even the most cutting-edge science.
There are two sorts of scientists.
There are people who are really interested in big ideas
and experiments, to them, are simply a means to big ideas.
The big thinkers, the speculators,
you know, experiments, unpleasant means to an end, often.
And then there's another class of scientist who just like to fiddle,
to tinker. And to many of those people, speculation is anathema.
It means going beyond your data in a sense, going somewhere where almost
emotionally you're not supposed to go.
And what, to me, is unique about Tim is he's both of those people.
I think that my main talent is sort of spotting
funny little things that don't quite make sense and that,
you know...
Isaac Newton talked about shiny pebbles on the beach, like a little boy
wandering around seeing shiny... looking for shiny pebbles on the beach.
I'm quite good at looking for shiny pebbles and seeing things which aren't actually on the mainstream
but which lead you off in a new direction and are incredibly illuminating about what's going on.
I mean, in other words, I'm a good discoverer of things.
Discovering things is the most fun, I think.
Because they tend to, sort of illuminate whole fields in a way that you couldn't believe.
One moment you're ignorant and the next moment you get that little tiny,
tiny clue that sort of sheds an enormous amount of light on the whole thing.
It's not up to me, I don't think, to decide whether my mind is beautiful or not.
But it's my mind and it's taken me to some exciting places
and answered some very interesting questions
and it's given me a lot of fun, and for that, I'm very grateful.
Subtitles by Red Bee Media Ltd
E- mail subtitling@bbc. co. uk