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[MUSIC PLAYING]
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OLIVIA JUDSON: In the
early 20th century,
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physicists and chemists unlocked
secrets of the atom that
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changed the world forever.
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[EXPLOSION]
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But life remained
a profound mystery.
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Among life's deepest
secrets was inheritance.
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Everyone knew that traits
like the shape of a peapod
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or the color of eyes and hair
were passed on from generation
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to generation.
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But no one knew how
such information
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was stored or transmitted.
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Scientists were
convinced that there
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had to be a biological molecule
at the heart of the process,
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and that molecule had to have
some pretty special qualities.
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SEAN CARROLL: The
three-dimensional arrangement
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of atoms in those
molecules had to explain
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the stability of life, so that
traits were passed faithfully
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from generation to
generation, and also
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the mutability of life.
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You have to have change in
order for evolution to happen.
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OLIVIA JUDSON: The
challenge of solving
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this mysterious arrangement of
atoms, this fundamental secret
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of life, was taken up in 1951
by two unknown scientists.
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Less than 18 months
later, they would
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make one of the
great discoveries
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of the 20th century.
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They met and joined forces
of the Cavendish Laboratory
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in Cambridge, England.
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One was a 23-year-old
American named James Watson.
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ROBERT OLBY: He had a
crew cut when he first
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came to Cambridge.
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And that was very rare in
Cambridge in those days.
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He liked to wear
what I call gym shoes
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and leave the laces untied
and things like that.
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He was quite an enfant
terrible, I would say.
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But behind that, of course,
was his extreme, intense love
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of science, right from his early
years, and his determination.
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OLIVIA JUDSON: The other was an
Englishman named Francis Crick.
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Trained as a physicist,
his academic career
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had been interrupted by the
outbreak of the Second World
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War.
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It wasn't until 1949 that he
got back into academic science.
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He was anxious to
make up for lost time,
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and, now, interested in biology.
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Crick and Watson
connected instantly
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when they met in 1951.
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They both loved to talk science.
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JAMES WATSON: Francis
and I both liked ideas.
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And as long as I could
talk to Francis, you know,
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I felt every day was worthwhile.
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OLIVIA JUDSON: Crick was always
ready to share his thoughts,
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though he rarely did so quietly.
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JAMES WATSON: Any
room he was in, he
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was going to make more
noise than anyone else.
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KAROLIN LUGER: They
would constantly
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throw crazy idea at each
other, dismiss them,
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have another idea, follow that
a little further, dismiss that.
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But then something
comes out of left field.
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So it's kind of
this give and take.
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FRANCIS CRICK: We did have
different backgrounds,
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but we had the same interests.
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We both thought that finding
the structure of the gene
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was the key problem.
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OLIVIA JUDSON: The
idea of the gene
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dates back to Gregor
Mendel's experiments
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with peapods in the 1860s.
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By the 1920s, genes had
been convincingly located
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inside the nucleus of cells,
and associated with structures
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called chromosomes.
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It was also known
the chromosomes
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are made of proteins
and the nucleic acid--
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deoxyribonucleic acid, or DNA.
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That meant the genes had to be
made of either DNA or protein.
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But which was it?
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Protein seemed the better bet.
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There are lots of
different kinds of them,
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and they do lots of different
stuff inside the cell.
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In contrast, DNA didn't
seem very interesting.
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It's just repeated
units of a sugar
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linked to a phosphate
and any of four bases.
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The readiness to dismiss
DNA was so entrenched
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that it persisted even after
Oswald Avery showed that it
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can carry genetic information.
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SEAN CARROLL: Avery had
isolated a substance
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that conveyed a trait from
one bacterium to another.
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And this transforming
principle, as he called it,
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he showed that it
was not destroyed
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by a protein-digesting
enzyme, but was destroyed
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by a DNA-digesting enzyme.
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OLIVIA JUDSON: Watson and
Crick were among the few who
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found Avery's work persuasive.
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They thought genes
were made of DNA.
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They also thought that solving
the molecular structure
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of the molecule would reveal
how genetic information is
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stored and passed on.
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At the time, a
powerful technique
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for solving molecular
structure was being perfected--
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X-ray crystallography.
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KAROLIN LUGER: At its
best, X-ray crystallography
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can determine the position
of every single atom
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in the molecule that you're
analyzing with respect
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to every other single atom.
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OLIVIA JUDSON: Not
that it's easy.
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The picture you end up with
is a diffraction pattern.
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And to make sense of it, to
work out where the atoms are,
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involves interpreting
lengthy calculations.
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And in the 1950s,
the equipment was
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primitive and
difficult to maintain.
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The X-ray sources
weren't very bright.
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And on top of that, DNA is not
an easy molecule to work with.
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KAROLIN LUGER:
Basically, picture snot.
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It's kind of hard to pick
it up and do stuff with it
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and analyze it.
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Polymers are not fun to work
with from that point of view.
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OLIVIA JUDSON: The Cavendish
was famous for X-ray
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crystallography.
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But the director of the lab
didn't want his stuff X-raying
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DNA.
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He knew that a group at
King's College in London
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was already doing
that, and he didn't
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want to be seen as competing.
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JAMES WATSON: It just
wasn't good manners.
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OLIVIA JUDSON: The
King's College scientist
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who had initiated the work
on DNA was Maurice Wilkins.
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Like Crick, he was
trained as a physicist,
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and had only recently
become interested
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in biological questions.
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Though he was drawn to
the problem of the gene,
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Wilkins lacked Watson and
Crick's burning urgency
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to find a solution.
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Complicating things for
Wilkins was his relationship
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with his colleague,
Rosalind Franklin.
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She was a talented
crystallographer.
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But when she joined
the team at King's, she
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believed that she would be
leading its DNA research.
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KAROLIN LUGER:
She had the notion
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that this was her project.
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He had the notion it was his
project, and, if anything,
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she should help him in his
effort to solve the structure.
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And so this is a
recipe for disaster.
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OLIVIA JUDSON: The times
and their personalities
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worked against an
effective partnership.
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KAROLIN LUGER: This
was a time when
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it was very, very hard
for women in science
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to be taken seriously.
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And so I would imagine that
Rosalind Franklin had to be,
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perhaps, quite assertive.
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OLIVIA JUDSON: She certainly
asserted her independence.
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Wilkins, by all
accounts a shy man,
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reluctantly agreed that
they would work separately.
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London is only 75
miles from Cambridge.
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That means that Watson and
Crick could easily keep tabs
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on the work being
done at King's.
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But another potential
competitor was thousands
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of miles away in California.
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Linus Pauling was renowned as
the greatest physical chemist
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of his generation.
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He was widely admired
for his ability
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to build accurate models
of complex molecules.
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Watson and Crick were
convinced that it was just
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a matter of time before
Pauling used this technique
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to solve DNA.
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Biological molecules come
in a variety of shapes.
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Pauling and Watson
and Crick suspected
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DNA might be a
helix of some kind.
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But if so, how were the sugar,
the phosphate, and the bases
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arranged?
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Early in his
collaboration with Watson,
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Crick had worked
out mathematically
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what the X-ray diffraction
pattern of a helical molecule
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should look like.
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Shortly afterwards,
Watson went to London
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to hear Franklin report on
some of her recent work.
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When he got back, he told Crick
what he remembered of her talk,
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and they decided
to build a model.
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In a few days, they had one.
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It was a helix with three sugar
phosphate chains on the inside
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and the bases sticking out.
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KAROLIN LUGER: At that time,
the only interesting thing
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about the DNA
molecule is the bases.
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And so it made perfect sense.
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I mean, only an idiot
would put them inside.
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Because then they're hidden.
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OLIVIA JUDSON: They invited
Wilkins and Franklin
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to come and take a look.
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Unfortunately, Watson
had misremembered
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some of her key measurements.
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Franklin saw this immediately,
and quickly and derisively
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dismissed their effort.
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She went on to craft a mocking
announcement for the death
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of DNA as a helix.
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It was an embarrassment
that did not sit well
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with the Cavendish leadership.
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JAMES WATSON: We were forbidden,
in a sense, to work on DNA.
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OLIVIA JUDSON: The failure of
the first model was painful.
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But it can also be seen as just
part of the scientific process.
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KAROLIN LUGER: I would
actually maintain
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that, in order to arrive
at the right solution,
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you have to put out a
couple of wrong ones.
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And that's just the
nature of discovery.
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And if you're afraid
of making a mistake,
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you're going to fail
in this business.
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OLIVIA JUDSON: Through
1952, Watson and Crick
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read and talked over
anything and everything that
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could prove relevant for their
ongoing, but now underground,
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quest to discover
the structure of DNA.
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JAMES WATSON: To me, there was
only one way I could be happy--
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or two ways-- solve DNA
or get a girlfriend.
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[LAUGHS]
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And I didn't get a girlfriend,
so it was solve DNA.
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OLIVIA JUDSON: The year
ended with Watson and Crick
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thinking about DNA, Franklin
taking pictures of DNA, Wilkins
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avoiding Franklin, and Pauling
a distant, but worrisome,
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presence.
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Then, in January 1953,
everything changed.
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News came that Pauling was
indeed preparing a paper
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on the structure of DNA.
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Watson secured a copy
of the manuscript
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and found, to his great
relief, the Pauling
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was proposing a triple helix.
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It was very similar to
the one that he and Crick
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had been shamed into
abandoning the previous year.
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Relieved, he headed to
London to share the news
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that the race for
DNA wasn't over,
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only to find that Rosalind
Franklin wasn't particularly
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interested in what
he had to say.
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ROBERT OLBY: Following
his departure
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from Rosalind Franklin's
room, he encountered Wilkins.
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And Wilkins took
him into his room,
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and then took out of
the drawer a picture
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which had been taken
by Rosalind Franklin.
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OLIVIA JUDSON:
That picture would
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become one of the
most famous images
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in all biology,
Franklin's Photo 51.
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Jim Watson recognized
the diffraction pattern
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immediately.
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It was a helix.
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And based on this,
Watson thought
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it might have just two chains--
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a double helix.
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About the same
time, Francis Crick
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was shown a report
on Franklin's work
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that included an observation
on the symmetry of DNA.
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This led Crick to
a crucial insight
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that Franklin had missed.
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The two backbones had to
run in opposite directions.
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That led him to the conclusion
that the sugar phosphate
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backbones had to be on the
outside with the bases inside.
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So Watson started to
build models again.
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He experimented with
pairing like with like--
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adenine with adenine, thymine
with thymine, and so on.
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That would make each
chain identical.
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Watson thought that
could explain how
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genetic information is stored.
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He thought he had the solution.
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But then a Cambridge
colleague told him
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that the bases could not pair
with themselves in that way.
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And Crick pointed
out that the model
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didn't take account of something
else that was known about DNA.
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A few years earlier, another
chemist interested in DNA,
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Erwin Chargaff, had
reported a puzzling fact
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about the molecule.
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KAROLIN LUGER: He analyzed the
chemical composition of DNA
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in different species.
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And what he found
is that the amount
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of As-- the base adenine--
and the amount of base Ts
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was always the same.
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And Gs and Cs were
always the same.
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OLIVIA JUDSON: But no
one, including Chargaff,
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had figured out what
those base ratios meant.
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With Chargaff's data
in mind, Jim Watson
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went alone to the lab
one Saturday morning
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and started playing
with cardboard cutouts.
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JAMES WATSON: I began
moving them around.
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And I wanted an
arrangement where I
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had a big and a small molecule.
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So how did you do it?
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Somehow, you had to
formed linked bonds.
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So here's A and
here's T. And I wanted
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this hydrogen to point
directly at this nitrogen.
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So I had something like this.
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[ZAPPING]
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Oh.
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So then I went to link the pair.
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I wanted this nitrogen
to point to this one.
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And it looked like this.
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[ZAPPING]
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Whoa.
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They look the same.
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And you can push one
right on top of the other.
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[ZAPPING]
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We knew, even if we
go up to the ceiling,
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we were building a tiny
fraction of a molecule.
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Hundreds of millions
of these base
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pairs in one
molecule, all fitting
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into this wonderful
symmetry, which
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we saw the morning
of February 28, 1953.
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OLIVIA JUDSON: The model
fit the measurements,
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both from the X-ray
diffraction pictures
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and from Chargaff's data.
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But most important of all,
the arrangement of the bases
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immediately revealed
how DNA works.
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FRANCIS CRICK: The key
aspects of the structure
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was the complementary
nature of the bases.
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If you had a big
one on this side,
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you had to have a particularly
small one on this side,
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or vice versa, and so
on, all the way up.
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So it meant that, by
separating the two chins,
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you could then easily make
a new complementary copy
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by just obeying these
pairing rules of which one
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went with what.
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And that solved in one
blow the whole idea
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of how you replicate a gene.
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OLIVIA JUDSON: The structure
immediately revealed
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two things--
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how genetic
information is stored
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and how changes or
mutations happen.
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The information is stored by
the sequence of the bases.
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Mutations occur when
the sequence is changed.
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JAMES WATSON: It's a
simpler and better answer
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than we ever dared hope for.
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FRANCIS CRICK: And I remember an
occasion when Jim gave a talk.
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It's true, they gave him one
or two drinks before dinner.
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It was rather a short
talk, because all
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he could say at the end was,
well, you see, he's so pretty.
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He's so pretty.
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JAMES WATSON: I think
everyone just took joy in it,
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because the field needed us.
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But on the other hand, the
biochemistry department
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didn't invite us to
give a seminar on it.
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SEAN CARROLL: When the
structure of the double helix
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was revealed, most biologists
instantly recognized the power
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of the explanation before them.
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Here was this
beautiful molecule that
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could explain both
the stability of life
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over huge amounts of time and
its mutability in evolution.
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OLIVIA JUDSON: That triumph was
reported in the journal Nature.
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It made headlines
around the world,
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and was celebrated nine years
later with a Nobel Prize.
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KAROLIN LUGER: That's kind of
what every scientist dreams
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about, to make a discovery
that has this kind of impact.
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SEAN CARROLL: For
biologists, the discovery
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of the double helix opened
up a whole new world.
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It was a passport to all
the mysteries of life--
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mysteries that biologists
have been decoding ever since.
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[MUSIC PLAYING]
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