How I discovered DNA James Watson
so I thought it’d be a podium so I’m a
bit scared Chris asked me to tell again
how we found the structure of DNA and
since you know I follow his orders I’ll
do it but it slightly bores me and yeah
I wrote a book so I’ll say something
I’ll say a little about you know how the
discovery was made in life Francis and I
found it and then I hope maybe I have at
least five minutes to say what makes me
tick now back of me is a picture me when
I was 17 I was at the University of
Chicago in my third year and I was my
third year because the University of
Chicago let you in after two years of
high school so you it was fun to get
away from high school and because I very
small not so good in sports or anything
like that but I should say that my
background my father has you know raised
to be an Episcopalian and Republican but
after one year of college he became an
atheist and a Democrat and my mother was
Irish Catholic and what she didn’t take
to religion too seriously and by the age
of 11 I was no longer going to Sunday
Mass and going on bird-watching walks
with my father so early on I heard of
Charles Darwin I guess you know he was a
big hero and you know you understand
life as it now exists through evolution
and at the University of Chicago I was
the ology major and thought I would end
up you know if I was bright enough maybe
getting a PhD from Cornell in
ornithology then and the Chicago paper
that was a review of a book
who called what is life by the great
physicist Schrodinger and that of course
is another question I want to know you
know Darwin explained life after it got
started but what was the essence of life
and shortener said the essence was
information present on our chromosomes
and it had to be present on a molecule I
never really thought of molecules before
you know chromosome four this was
molecule and somehow were the
information was probably present in some
digital form and there was a big
question how do you copy the information
so that was the bookend so from that
moment on I wanted to be a geneticist
understand the gene and through that
understand life so I had you know a hero
at a distance wasn’t a baseball player
was Linus Pauling and so I applied to
Caltech and they turned me down so I
went to Indiana which was actually as
good as Caltech in genetics and sight
they had fared with a good basketball
team so I had a really quite happy life
at Indiana and it was in Indiana I got
the impression that you know the gene
was likely to be DNA and so when I got
my PhD I should go in search for DNA so
I first went to Copenhagen because I
thought well maybe I could become a
biochemist but I discovered my chemistry
was very boring it wasn’t going anywhere
toward you know saying what the gene was
it was just nucleotides and oh that’s
the book little book you can read it
about two hours and but then I went to a
meeting in Italy and there was an
unexpected speaker was another program
he talked about being a this was Moore’s
Wilkins he was trained as a physicist
and after the war he wanted to do
biophysics and he picked DNA because DNA
had been shown at the Rockefeller
Institute to possibly be the genetic
molecules on the chromosomes most people
believed was proteins
but woke of the surf you know I thought
DNA was the best bet and he showed this
x-ray photograph and his sort of
crystalline so DNA had a structure even
though it would probably different
molecules carry different set of
instructions so there was something
Universal about the DNA molecule so I
wanted to work with him but he didn’t
want to form a birdwatcher and I ended
up in Cambridge England so I went to
Cambridge because up it was really the
best place in the world then for x-ray
crystallography an x-ray crystallography
is now subjective you know chemistry
department in those days it was in the
domain of the physicists so the best
place for x-ray crystallography was at
the Cavendish laboratory at Cambridge
and there I met Francis Crick I went
there without knowing him he was 35 I
was 23 and within the day we decided
that maybe one could take a shortcut to
finding the structured and not salvaged
by a rigorous fashion but build a model
molecular model using some coordinates
of you know lengths all that sort of
stuff from x-ray photographs but just
that’s what the mouse house should have
fold up and the reason for doing so
instead of the photograph is Linus point
about six months before he proposed the
alpha helical structure for proteins and
in doing so he banished the man on the
right sir Lawrence Wright who was the
Cavendish professor this is photograph
several years later when Bragg had
caused a smile he certainly wasn’t
smiling when I got there because he was
solid humiliated by Pauling getting the
Alpha helix and the Cambridge people
failing because they weren’t chemists
and certainly neither quick or I were
chemists so we tried to build a model
and he Frances the locus of local said
he thought okay he likes x-ray diagram
he thought
was compatible with a here so we built a
three stranded models the people from
London came up welcome said this
collaborator or possible collaborator
Rosen Franklin came up and sort of
laughed at our model they said it was
lousy and it was so we were told to
build no more models we were incompetent
and so we didn’t build any models and
Francis sort of continued to work on
proteins and basically I did nothing and
except we’d you know basically reading
is a good thing you get facts and we
kept telling the people in London the
Linus Pauling’s going to move on to DNA
if DNA is that important Linus will know
do you build a model and everyone will
be scooped in fact he’d written the
people in London could he see their
x-ray photograph and they had the wisdom
to say no so he didn’t have but there
was ones in the literature actually
Linus didn’t look after that Jeffrey but
about a fifteen months after I got to
Cambridge or ruiers began to appear from
Linus Pauling son who’s in
Cambridgeshire his father was now
working on DNA and so one day Peter came
in is Peter polling and gave me a copy
of his father’s manuscript and boy I was
scared because I thought you know we may
be scooped I have nothing to do no
qualifications for anything and so there
was the paper and he proposed its
free-standing structure and I’m here it
was just it was crap
so this was you know unexpected from the
world and so it was held together by
hydrogen bonds between phosphate groups
well if the peach pH cells have around
seven those hydrogen bonds couldn’t
exist we rushed over to the chemistry
department and said could Pauling be
right and Alex had said no so we were
happy and yeah we were still in the game
but we were frightened that someone in
the Caltech would tell Laurie and I said
he was wrong
and so regs had build models and the
month after we got the polling
manuscript I should say I took the
manuscript in London the show the people
you tell said Linus was wrong and they
were still in the game and it should
immediately start building models but
here Wilkins said no hey rosalind
Franklin was leaving in about two months
and after she left he would start
building models and so I came back with
that news the Cambridge and Bragg said
build models all right of course I
wanted to build models and there was
picture of Rosalind and she really you
know in one sense she was a camera so
really she would been trained that she
didn’t know any organic chemistry or
quantum chemistry she was a
crystallographer and I think part of the
reason she didn’t want to build models
and she wasn’t a chemist whereas Pauling
was the chemist and so quick and I you
know started building models and I
learned a little chemistry but not
enough well we got the answer on 28th of
February 53 and it was because of a rule
which to me is a very good rule never be
the brightest person in the room and we
weren’t I mean we went to best chemists
in the room I went in and showed them a
pairing I’d done and Jerry Donahue he
was a chemist he says wrong you’ve got
the hydrogen
so in the wrong place I just put them
down like they were in their books said
they were wrong so the next day you know
after hi so while he might be right so I
changed locations and then we found the
base pairing and Frances Amelie said the
change run in episode directions and we
knew we were right so it was a pretty
you know all happened about two hours
you know from nothing to thing and we
knew it was big because you know if you
just put a next to T and gtex to see you
have a copying mechanism so we saw how
genetic information is carried it’s the
order of the four bases so in the
sensitiveness or digital type
information and you copy it by going
from strand separating so is it you know
if it didn’t work this way you know you
know you might as well believe it
because you didn’t have any other scheme
but that’s not the way most scientists
think well scientists are really rather
Dell they said we won’t think about it
until we know it’s right but you know we
thought was at least 95 percent right or
99 percent right so think about it the
next five years there were essentially
something like five references to our
work in nature
none and so we were left by ourselves
and trying to do the last part of the
trio how do you how what does the
genetic information do and it was pretty
obvious that it provided the information
down RNA molecule and then how do you go
from RNA protein for about three years
we just I tried to solve the structure
RNA it didn’t yield didn’t give good
x-ray photographs I was largely I’m
happy a girl didn’t marry me and we
really you know sort of shitty time
so there’s a picture of Francis snide
before I met the girl so I’m still
looking happy but there is what we did
when we didn’t know where to go forward
we formed a club and called it the RNA
tie club George gamma office a great
physicist he designed the tie he was one
of the members and the question was how
do you go from a four-letter code to the
20-letter code' of proteins Feynman was
a member and Teller and friends of gamma
that’s the only foot no we’re only
photograph twice and in both occasions
you know one of us was missing the tie
there’s princess up on the upper right
and that works rich the MD turned
crystallographers next to me this was
taken in Cambridge in the September of
1955 and I’m smiling okay so first I
think because the head of the girl his
boy she is gone and and so I didn’t
really get happy until 1960 because then
we found out basically you know there
are three forms of RNA and we knew
basically DNA provides him for RNA RNA
price information protein and that led
Marshall nirenberg you know take RNA
synthetic RNA put it in a system making
protein you made poly phenylalanine
oh you mean tell me so that’s first eat
first cracking of the genetic code and
was all over by 1966 so that’s what
Chris wanted me to do it was a so what
happens in soon well at that time I
should go back when we found the
structure of DNA in my first talk at
Cold Spring Harbor the physicist Leo’s
liar he looked and he said are you going
to patent it and but he knew patent law
and we couldn’t happen because she no
use for it and so then I didn’t become a
useful molecule and the lawyers didn’t
enter into the equation until 1973 20
years later when Boyer and Cohen with in
San Francisco and Stanford came up with
their method in recombinant DNA and
Stanford patented made a lot of money
and as they patent something which you
know could you do useful things and then
they learned how to read the letters of
the code and boom we’ve know how to buy
tech industry and but we’re still a long
ways from you know ask the answering a
question which sort of dominated my
childhood which is how do you nature
nurture and so I’ll go on I’m hard have
a time but this is Michael wiggler a
very very clever mathematician turned
physicist and he developed a technique
which essentially will let us look at
sample DNA eventually a million spots
along if there’s a chip there a
conventional one then there’s one made
by photolithography by a company in
Madison called nimble Chen which is way
ahead of Affymetrix and we use their
technique and what you can do is sort of
compare DNA of normal say versus cancer
and you can see on the top that chances
which are bad show insertions or
deletions
so the DNA is really badly mucked up
whereas if you have a chance of
surviving the DNA isn’t so marked up so
we think that this will eventually lead
to what we call DNA biopsies before you
get treated for cancer you should really
look at this technique and get a feeling
of the face of the enemy it’s not a it’s
only a partial log but it’s a I think
it’s going to be very very
so we started with breast cancer because
there’s lots of money for it no
government money and now I have a sort
of vested interest I want to do it for
prostate cancer so you know you aren’t
treated if you know it’s not dangerous
and so well but we there was either
looking at cancer cells looked at normal
cells and made a really sort of
surprising observation which is all of
us have about ten places in our genome
where we’ve lost the gene or gained
another one so we’re we’re sort of all
imperfect and the question is well if
we’re round here you know these losses
or gains might not be too bad but if
they see deletions or complications
occurred in the wrong day maybe you were
they are sick so the first disease he
looked at was autism and has reasonably
we looked at autism as we had the money
to do it to look at it individuals about
$3,000 and the parent of a child with
Aspergers disease the high intelligence
autism had sent a thing to a
conventional company didn’t do it
couldn’t do it by conventional genetics
we’re just scanning it we began to find
genes for autism and you can see here
there are a lot of them so a lot of
autistic kids are autistic because they
just lost a big piece of DNA I mean big
piece at the molecular level we saw one
autistic kid five million bases just
missing from one of his grown self we
haven’t yet looked at the parents but
the parents probably don’t have that
loss or they wouldn’t be parents now so
our autism study is just beginning we
got three million dollars I think it’ll
costs at least 10 to 20 before you’d be
in a position to help parents who have
had an autistic child or think they may
have an autistic child and can we
spot the difference so this same
technique should probably look at all
it’s a wonderful way to find genes and
so I’ll conclude by saying we’ve looked
at twenty people with schizophrenia and
we thought would probably had to look at
several hundred before we got a picture
but as you can see that 7 out of 20 had
a change which was very high any of the
controls over three so what’s the
meaning of the controls were they crazy
also and we didn’t know it or you know
where they normal
I would guess they’re normal and what we
think in schizophrenia is their genes
that predispose you and whether this is
one predisposes and then there’s only a
sub segment of the population that’s
capable being schizophrenic now we don’t
have really any evidence allergy what
I’ve seen to give a hypothesis the best
guess is that if you’re left-handed
you’re programmed with schizophrenia 30
percent of schizophrenic people are
left-handed and schizophrenia has a very
funny genetics which means 60 percent of
the people are genetically left-handed
were only half of it short I don’t have
the time to say it now some people will
think they’re right-handed are
genetically left-handed okay I’m just
saying that if you think oh I don’t
carry a left-handed gene so therefore I
you know children will be a risk of
schizophrenia you might okay
so it’s me an extraordinary exciting
time we ought to be able to find the
gene for bipolar there’s relationship
and if I had enough money we’d find them
all this year I think