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