"DNA and the Brain" - Dr. James Watson speaks at Google


Uploaded by Google on 16.07.2007

Transcript:

MALE SPEAKER: Good morning.
Testing.
Testing.
Morning, everybody.

Well, when I started this job at Google, I didn't know that
I would have the pleasure of doing what I get to do today,
how much is obvious to everyone in this room.
But I'm going to do this slightly indirectly.
I want to introduce first Bruce Stillman, who is the
president of Cold Spring--
I believe that's the title.
He joined as a postdoc in '79 thinking he'd stay three
years, and has been there ever since.
Bruce both is the president of Cold Spring Harbor Research,
and also there's a cancer institute there.
And as you know, we've been looking hard at cancer and
some of the things we could do there.
And I want to introduce Bruce and then let Bruce introduce
Dr. James D. Watson.

[APPLAUSE]
BRUCE STILLMAN: Thank you.
We're here for two purposes.
One is Jim is going to give a talk, but we're going to talk
to people at Google later because Cold Spring Harbor
Laboratory is one of the leading genetics research
centers in the country-- in fact, in the world.
And I think a lot of the things that we do at Cold
Spring Harbor and what you do here can mesh together.
It's a great pleasure to introduce Jim.
As you know from the picture behind me, he and Francis
Crick in 1953 discovered the double helix structure of DNA.
Jim was 23 at the time, and then had to figure out what he
was going to do for the rest of his life.
Which is a tough problem.
And quite remarkably, Jim has really topped everything that
he's done previously.
He went to from Cambridge in England, where he and Francis
worked, to Caltech, and then to Harvard.
At Harvard University, he wrote one of the--
well, the first textbook in the new field of molecular
biology, which revolutionized not only the field of
molecular biology, but the way textbooks were written.
And that textbook, now in its fifth edition, has been really
the mainstay of the field of molecular biology.
And I hope some of you actually used it at college.
Then in between then he won the Nobel Prize with Francis
Crick and Maurice Wilkins in 1962.
In 1968 wrote the famous book, which some of you I see have
with you today, The Double Helix.
It was a New York Times best seller book and really changed
the way people perceive science and
scientists, I think.
Then just a year after that, Jim came down to Cold Spring
Harbor Laboratory from Harvard.
Cold Spring Harbor Laboratory is on the north shore of Long
Island, about 30 miles from midtown Manhattan.
And took over an institution that was running out of steam.
We were founded in 1890, and we were the first institution
in the United States to do genetics.
But Jim really transformed Cold Spring Harbor and became
one of the leading scientific administrators and leaders in
the country, and has been at Cold Spring Harbor ever since.
He was director from '68 to 1993, and then became
president until 2003.
I succeeded him as director and president in 2003.
Jim is now our chancellor, and he's still writing books.
And his talk about today, which is something that's very
much on his mind, is DNA and The Brain.
So it's a pleasure to introduce Jim Watson.
DR. JAMES D. WATSON: Thank you, Rich.
[APPLAUSE]
DR. JAMES D. WATSON: So I'm told I've got 40 minutes, and
so I'll try and rush through several things.
I was told people wanted to hear about DNA and the brain,
but I also know that wherever I go, people are always asking
me, how did we find the structure of DNA?
So I'll spend about 10 minutes just talking about those days.
[UNINTELLIGIBLE]
sort of some rules why I think it was Francis Crick and I
found the double helix.

This shows me in my first ambition as a young scientist.
I want to be an ornithologist. I was a keen bird watcher, and
my father was one. this shows me when I was 18 at the
University of Michigan Biological Station taking a
course in advanced ornithology.

By then, I suspected I was going to give up bird watching
because I had, the previous winter, read the book What Is
Life? by the famed Austrian physicists Erwin Schrodinger.
And Schroeder said the essence of life was information.
And said, well, it had to be stable information, so it must
be in a molecule.
Couldn't be a gas--
it was the molecule.
And this molecule must have unique properties such that
the information could be exactly copied.
And I had been sort of raised on Darwin, but I never really
thought of genetics and molecules in that
sort of solid way.
So that fall, instead of applying the Cornell to be an
ornithologist, I applied to Caltech for genetics.
They turned me down.
And fortunately, I had applied to Indiana, which I was told
was second best. It was actually better than Caltech
because it had basketball.

So the main message I got out of my three years
at Indiana was that--
go on to study DNA.

But they didn't teach too much about DNA at the time because
actually, the covalent structure of DNA wasn't worked
out when I was in graduate school.
It was only completed in 1951 in Cambridge, England.
So I went off to Europe to supposedly--
in Copenhagen, the lab which was going to try and make DNA
in a test tube.
They weren't-- they were making nucleusides, which is a
big difference.
And so I was totally bored and didn't do any of it.
But my life was changed by going to a meeting in the
spring of 1951 in Naples, where I saw this x-ray
photograph of DNA.
And the talk was given by a young--
or 30 year old, 35 year old--
English physicist, Maurice Wilkins, who said it was
crystalline.
So that meant DNA had a three dimensional structure.
And despite all DNA molecules probably be different- because
they were carrying different pieces of information--
they could still fold up into a common structure.
And Wilkins didn't seem to show any interest in me.
So luckily my PhD supervisor in Indiana, Luria, arranged
for me to go to Cambridge University.
And there, actually my first day, I met Francis Crick, who
was then working on proteins.
And I was in a lab whose objective was to find the
three dimensional structure of proteins.
And they were working on hemoglobin and myoglobin.
And I was supposed to join a myoglobin group.
But I met Francis.
And at that time, all the talk in Cambridge was on the alpha
helix, the way polypeptides folded up.
It had been proposed by Linus Pauling about six months four.
And Max [? Fruchs ?]
at Cambridge actually proved the alpha helix was right.
He tilted a synthetic polypeptide and got the 1.5
engstrom repeat of the alpha helix.
So Cambridge was both excited that they proved Pauling, but
humiliated because they had proposed models before and had
not made the peptide bond plainer.
And had just made everything four-fold--
they were very embarrassed.

So [UNINTELLIGIBLE]
the question I asked Francis, well, if Pauling had solved
the structure of the polypeptide chain by just
building models using sort of chemical principles, could you
do the same thing to DNA?
Did you really have to solve it rigorously, or could you
sort of guess in using clues such as the [UNINTELLIGIBLE]
fiber axis was 3.4 engstroms or something like that.
That this was, is there enough information?
Now, by the time I arrived the covalent
structure was worked out.
It was a regular 3.5 [UNINTELLIGIBLE]
structure.
We had made a go at it.
Wilkins had told us he thought there were three chains, and
we didn't know how to pack the chains together.
I was trying to use [UNINTELLIGIBLE], so it was
pretty awful.
And then it sort of turned out that DNA was supposedly to be
worked on in London and proteins in Cambridge.
So we were told not to do anymore model building because
Crick had a loud voice and he sort of offended the Sir
Lawrence Bragg.
And Bragg's sole ambition was to get Crick out of the place
by getting him a PhD, and then he wouldn't have to hear
Francis's very loud voice.
But at that time, we thought, well, if DNA is a gene it's
actually more important than protein, and Linus Pauling
will try and come up with a structure.
So we told the [UNINTELLIGIBLE], he had
written the [UNINTELLIGIBLE]
Wilkins, who had heard about the x-ray photographs saying
could he have a copy, and Wilkins sent him one--
didn't want to send him one.
But then a year later we heard that Linus had a three
dimensional model of the DNA.
And so I was very worried.
And we thought, well, maybe--
could he really solve it without seeing any data?
And the answer was, he could have, but he didn't.

This is me and--
about a year after I arrived in Cambridge.
I spent the year letting my hair grow long.
Because I arrived as an American with a crew cut.
In those days, you had short hair.
And [UNINTELLIGIBLE]
Crick said I looked like I would be confused as
American Air Force.
And I arrived without a tie or anything like that.
By that time, I was trying to look like an Englishman.
I only partially succeeded at that time.
Both my dentist and the tutor downstairs
from me asked me whether--
you know, they thought I was Irish.

Which afterwards I realized is maybe a little better than an
Englishman.

But anyways, Pauling came up and proposed a three chain
structure, and it was just--
it was wrong.
Because he held together the three
chains by hydrogen bonds.
He used hydrogens linking phosphate groups.
Well, that you can only do if you're down a PH 1,
and cells are seven.
So the structure was preposterous.
And we rushed over to the chemical laboratory and they
said, yeah, Pauling had made a mistake.
So then the people in Cambridge let us go ahead.
It wasn't a two person--
you couldn't be gentlemen.
You know, Pauling wasn't not working out because London
wasn't working out.

So I took the Pauling into London and
saw Rosalind Franklin.
And my book tells the whole story--
I won't say.
But Raymond Gosling in her lab had taken an extraordinary
picture, [UNINTELLIGIBLE]
helix.
And Rosalind very intelligent and never really had looked at
the picture before.
She wanted to solve the crystalline structure, in this
was a paracrystalline.
So within a month, we had the structure.
On the 20 of February of '53.
So I'll give you a couple reasons why we became famous.
Why we found it and not them.
The first as we worked on something before
its time had come.

That is, except for Pauling and except for the people in
London, Francis and I were the only people trying to do the
three dimensional structure of it DNA.
And part of that was because the two dimensional had just
been worked out, but people thought, you know, it's going
to be complicated.
And they would work on simpler things.
Now, the second is, we actually thought we could get
an answer soon, maybe the next day.
So you shouldn't work on a problem when you think it will
take you 10 years to get the answer, particularly when
you're young.
Because if it takes you 10 years, you'll be out of your
job long before then if you don't get the answer.
So I think a good rule is, think you can do something in
three years.
You know, people sort of trust you, put up with
you for three years.
So it actually took us only 18 months.
And we thought we could do it by building models, and that
didn't require solving the phase problem or any of the
things which would then be doubling x-ray
crystallography.
So we had a way to do it.
The third thing was that you should talk to your
competitors.
Instead of viewing them as enemies, have them as friends.
So you tell them what you think, and they tell
you what you think.
And that happens, and you can do that until you get very
close to the answer.

Now, Rosalind Franklin had met Francis and disliked him and
didn't want to talk him.
She didn't--
the story is she was a crystallographer.
She actually didn't know much
crystallography and needed help.
She didn't know anything about space groups.
And there was a space group which would have told her, if
she ad analyzed it, that there are two chains-- one
going up, one down.
So she didn't really--
she wanted to do it herself.
So it really pays, particularly when everyone
else thinks your crazy, to have one person who thinks
you're sane.
So I had Francis and he had me.
So maybe you should never do something far out if everyone
thinks you're crazy.
Because it's as little reassurance as possible.
I mean, it's helpful.
And the last thing which was important--
never be the brightest person in any room you're in.
Particularly if it's this big.
Because if you're the brightest person in a place,
no one can help you.
Now, it turned out neither Crick or I knew any chemistry,
and we were trying to do chemistry.
So at a crucial point I was getting nowhere, and someone
said, Jerry Donohue, who was out of Caltech, he said,
you've got the hydrogen atoms and guanine and thymine in the
wrong place.
Now, I just copied them out the textbooks and assumed that
the textbook figure was right, but it wasn't.
So if Donohue hadn't been a quantum chemist, we wouldn't
have done it.
Also, Francis wasn't the best crystallographer.
Cambridge was then probably the best
university in the world.
So that's sort of the reason you go to a good university.
You know, there are people who can help you.

Now, it could have been solved in case-- they just had to
talk to each other.
So I think those sorts of reasons--
have an important problem, know how to get there, work in
a pair if you can, and seek a lot of help.
Don't be afraid you don't know anything.
Just find the person who does.
Then you don't have to--
I thought I was going to actually have to learn math,
You know, I'd taken [UNINTELLIGIBLE], but it
turned out that as long as I was in a room with Francis, I
didn't have to know any math.
Because he knew.
So the important thing is to get the answer, not really
have it all in your own brain.
So go for the answer, not for how you get there.
The main thing is to get there.
But too many people are concerned with, you know,
their pride and all that.
It was very useful for me never to have been brought up
thinking I was bright.
Because it was very easy to ask for help.
And if you're going to need help, ask for it quick.
Don't wait a week.
If you don't know something, quick, find someone who does.
OK.
That was
[AUDIO BREAK]
DR. JAMES D. WATSON: When we knew it was a big thing, we
put in this little sentence, this is not
[UNINTELLIGIBLE PHRASE].
It was a little letter to nature.
And of course--
Now, the interesting thing you may think was surprising, no
one asked us to give a talk in Cambridge.
We never gave a public talk on the double helix.
No seminar.

So the first public talk was given across the Atlantic at a
meeting in Cold Spring Harbor.
And for five years, except for one case, there was just no
one who wrote articles about how--
public articles-- on how important DNA was.
And it really took the great experiment at Caltech by
[UNINTELLIGIBLE]
and [UNINTELLIGIBLE], which showed the strands separate,
and then work out of Kornberg's lab at Stanford
here, which showed the strands ran in opposite directions.
Not crystallographic, but in another way.
So five years after the double helix, then it was accepted.

But you know, about 20 people got interested in it, and that
was sufficient to keep the next five years going.

When it was obvious--
you wanted to find out how the DNA sequence determined the
sequence of amino acids and proteins.
OK, so that's the story.
And I wrote it up in The Double Helix, and it was fun
writing because it was good story.
And I tried to write it like it was a novel, and I wanted
it to be as good as The Great Gatsby.
You know, I'd been a voracious reader when I was a child.
You know, was still in Cambridge.
So I really didn't know people, but I knew people
through books.

And then they finally did make a movie, or docudrama, and I
was played by Jeff Goldblum.
Which I first thought was a bad choice.
I would have preferred John McEnroe.
But they got Goldblum.
But he was [UNINTELLIGIBLE]
to everyone, and I probably was at that time.
So it did catch sort of the arrogance of it.
But Francis Crick wasn't played well.
So now they're going to make movies about Rosalind
Franklin, and I'm going to be the villain.
So someone suggested [UNINTELLIGIBLE]
and I always forget his name, but it's
something like Ashton Kushner.

That he could play me.
And that despite my being the villain, I'd
come out all right.
But you know, Rosalind tragically got ovarian cancer
even before we got the Nobel Prize and died a very--
it was very sad.
She became close to Francis Crick afterwards, liked him.
I think she was highly intelligent autism.
Her awkwardness with people I think--

she liked mathematics and really just couldn't face
people very easily.
She misread their social clues, and I think
[UNINTELLIGIBLE].
She came from a wealthy family.
We did know that-- she was just a snob.
I don't think she as a snob.
She just probably didn't see faces very well.
Now, I'll come back to the--
Now, I want to go on to the next--
I've got to go fast--
on DNA and the brain.
So I think this century will see that coming together of
psychology and biology in the way that the last century was
the coming together of chemistry and biology.
So our main object of attention
is going to be humans.
Not fruit flies, not mice, but humans.
And it will all be possible because we can read the DNA
messages in our chromosomes.
So the tool for understanding humans will be DNA.
And so as a precursor to that was the big Human Genome
Project, which was finished three years ago.
And since doing, that they've done the chimp, the mouse, a
whole related--
trying to get enough information, comparative
information.
Begin to see really where the essential parts of the DNA
molecules are.

So it's our instruction books.
And for 100 years or more, there's a question of nature
versus nurture.
You know, to what extent are we determined by our genes,
and to what extent are you determined by your
environment?
And there's generally a crucial stage in people's
lives when they give up nurture and think it's nature,
and that's when their second child is born.
And they see the second child is completely different than
the first. And they have to ask why.
But it's at about this stage.
And I'm pretty long past that, so I'm a nature guy.
And nurture is important, but it's hard to quantitate it.
Whereas you can actually quantitate DNA in some sense.
So we'll study what we can study knowing that it's not
the complete answer. and that when you have monozygotic
twins, sometimes the monozygotic twins are very
similar, and sometimes one will have full blown
schizophrenia and the other won't.
And you have to ask, why?
So there's something besides just the genes, but I guess my
answer is, let's start with genes now that we have them.
So until now, these you couldn't do real--
you know, were you bright because you had a good
teacher, or because you had good genes?
Now you can probably answer, and the answer is probably
more your genes than your teachers.

In to study cancer at Cold Spring Harbor, we worked out a
technique which is called ROMA.
It's basically taking tiny representations, little bits
of DNA, and we're now up to a chip, which has 380,000
representations.
So you're sampling our genome with 3,080 spots.
And we're looking for cases where part of the gene is
present or is present in two copies.
So probably most of you say, well, you just change the
letter from A to G or G to C. But there are a lot of small
rearrangements when DNA is copied.
Lots of mistakes come in by which a gene goes from one to
two copies, or it's just completely deleted.
Now, these are things that are easier to detect than the
single base changes.
So this will be the technique which we'll use for the next
five years.
In about five years from now, it'll be possible probably to
sequence everyone's DNA at a reasonable cost
[UNINTELLIGIBLE].
So right now, this is-- we're just in a hurry.
So we're using an imperfect thing, and it's been very
effectively used in studying breast cancer.
And now we're looking at it in autism.
Now autism, in the most extreme form, is people have
essentially no social interaction.
They just don't react to other people.
They have low IQ.
They often have very
repetitive, stereotyped behaviors.
They can't sleep well.
And it's a terrible burden on any family which has an
autistic child.
And it was generally believed that the number
was about 1 in 1,000.
But if you sort of broaden the definition to say you can't--
some autistic don't speak-- but you can speak and your
social interactions are bad.

Then it can go up to about 1 in 100.
Sort of awkward kids.
And most awkward kids are boys.
Boys are more awkward than girls.

Why, we don't know.
Could be because we only have one X chromosome, or we have a
Y chromosome.
[LAUGHTER]
DR. JAMES D. WATSON: Now, girls do get autism.
And I think Rosalind Franklin was of this type of high
intelligence, but really, she just didn't see faces.
Now, you can sort of do brain scans and have them exposed to
faces, and autistic people really don't
see faces very much.
That part of the brain doesn't light up.
So it's a real defect.
It's not, you know, they see the face-- they probably don't
even see it.
Or they don't see it to the [UNINTELLIGIBLE].

Now, here-- and I'll just go through this very fast--
[UNINTELLIGIBLE]
number of polymorphisms always carry about 10 of them.
And just for people who count, one of these scans costs about
$1,000 if you don't call into effect indirect costs.
We're trying to lower it.
Probably a year from now we'll get the cost down.
But we've been limited by money, and the only way we
were able to do it is that a mathematician who's been very
successful investing other people's money has an autistic
daughter, and he's given to us about $10
million to do this study.
OK.
So you can do that.
And we're trying to--
and you can look in two ways.
You can look at families where you have more than one
autistic child.

So you have two.
And in other cases, you couldn't--
and where you think that the parents probably are carrying
some genes which predispose the children to autism.
You can also do it when two seemingly absolutely normal
people have an autistic child.

And in rare cases, you can see chromosomal defects.

Here's just a map, and you can see that particularly on
chromosome 15 there are duplications of DNA which
frequently lead to autism.
And these are the two methods we're sort of doing.
And so we can begin to really see these changes in an
unambiguous way.
And this was an interesting case where we
saw a change on 15.
And then we had read that someone else had found a
change on 15.
We thought we've confirmed him, but then turned out that
we had used the same DNA as he.
So it wasn't a confirmation.
Right now, they're being samples of DNA from children
with autism, and particularly from families where there's
more than one child.

And here you can just sort of see there's a deletion.
That's something occurring on chromosome 20.
And I'll go fast here.
Anyways, it's a gene which is expressed in the central
nervous system.
So you can see they've just got one case.
Well, how do you know it's the cause of it?
But the answer is in mostly--
if you just take the average person, he has not got a
deletion or a change which isn't present in the parent.
So if you see something appearing,
maybe it's due to autism.
What you'd like to do is find a large number.
Just repeat.
Here's another one.
This is a protein, again, expressed in
parts of the brain.
And this one--
and I shouldn't--
autism children are generally highly mentally retarded.
Or, the classical autism ones.
And just sort of a summary.
And then I'll go to familiar autism.
And this is rather creepy.
It's creepy in the following sense: that 50 years ago there
was a psychiatrist at the University of Chicago,
[UNINTELLIGIBLE]
who studied autistic children.
And he said the cause of autism was that the mothers
were emotionally cold and didn't give the warmth, and so
the cause of autism was just bad behavior by the mothers.
And this was accepted.
And so women with autistic children bore the burden not
only of a child that couldn't return their affection, but
that they were the cause of it.
Now, that was a sentiment given up about 20 years ago.
And then it was sort of generally believed that the
parent's behavior had nothing to do with it.
Now, there's a psychologist at Cambridge University, Simon
Baron-Cohen, who some of you may have heard.
He writes of the male mind and the female mind--
a politically incorrect statement.
But that the male mind, which is found in many women, is
people who like the systematize, who like
mathematics.
Whereas the female mind is people who like social
interactions, are empathizing with other people.
Caring people.
So systematizing and caring people.
And there are many more males who are systematizers than
women are systematizers.
So he identifies these things by giving you a
self-assessment test. You answer 20 questions about
yourself, and then you can be put into these two categories.
And it's more accurate than you would think.
Now it turns out that when he looks at the parents of
autistic children, the mothers are more systematizers than on
the average.
And the fathers are.
So that the sort of nasty conclusion from this is that
too much mathematical ability is bad for your children.

So if you're really bright in math, you know, a man, marry
for beauty, not brains.
OK.
So I know everyone laughs, but when you get
down to it, it's nasty.

Because there's sort of rumors that more autistic children
are born to MIT graduates.
There's more autism here in Silicon Valley.
OK?
Probably true.

Now, how does the male mind arise?
Simon Baron Cohen has pretty good data that it's the fetal
testosterone.
That if you get too much--
a certain high level of testosterone in sort of the
third month of development, that leads to the male mind.

And he hasn't shown that that leads to autism, but he's been
following--
he takes amniotic fluid and then he follows the women
afterwards and sees that those which have high testosterone--
and then when he does the measurements, that basically
it leads to the male mind.
So really what we're trying to do-- and I will
stop in a few minutes--
is that autism, because the brain is so complicated, and
what we've shown is due to a lot of changes in a lot of
different genes, not just one.
But there's something strange, which we haven't yet found--
why it's in males more than in females.
And really, what is it that's transmitted from the parents?
What genes really predispose you to that?
So knowing friends with autistic children, where the
women are really highly intelligent, I think he would
ask them, well, would they have taken a test to not have
such a child, they'd probably say, yes.

So I think it's that autism may be to intellectuals what
HIV was to the homosexual community.
Something which it really pays to take a big interest in and
get the answers as fast as possible, and hopefully
decrease the incidence of autism.
Now, on the good side, if you can identify sort of high
intelligent autistic children early on and give them special
schooling, you can help them, and many go to college.
And there are probably some in this room.
So many can become functional, But there in many cases, it's
a very hard burden to bear both particularly for the
people who have the disease or not.
So to conclude, autism is just one of the many other things.
We're now trying to be serious on understanding
schizophrenia, and a whole variety of things.
So I think we'll begin to really understand sort of the
mental differences between people and personality
differences, and we'll begin to understand it.
I think what we will end up by doing that is we'll probably
be a better world in the sense that we'll understand when
people sort of go to another part of the room and don't
want to socialize, that maybe they don't have any choice.
And so we'll be much more compassionate to people who
seem to be awkward, realizing that they were born awkward,
it wasn't just that they didn't want to be with their
bigger brother or sister or something like that, that they
didn't really have the choice.
And that their brains weren't working properly, and that
they need help.
So I think 50 years from now--
I'm sure by then--
we'll sort of completely understand autism.
Those of us who work with it using this framework of
younger people, you better do something in three years.
So we're sort of operating on a three year rule.
You know, we've got to accomplish an awful lot fast.
And I think we will.
So the Human Genome Project, which, when people first
started it, there was lots of opposition I think--

well, my last thing is that at the time
I was a young teacher.
And when political correctness came in, everyone sort of
thought it would be nice to believe that all humans
weren't that different from each other, that if we could
only change the environment, that is, to nurture, we could
do away with a lot of the inequality of the world.

Now we're witnessing, particularly now we're placing
greater certain intellectual demands on people, a widening
of inequality, despite all our-- in terms of wages.

And some of this stuff probably has some genetic
component, something which we are supposed not to say.
But I suspect it's true.
And therefore, I think to have a society which is
satisfactory, those of us in this room somehow have to see
that the people who aren't in this room don't belong to a
totally different world.
So we really have to maybe accept the fact that all
humans really have quite different potentials, and
those with potentials which don't allow them to be in this
room nonetheless have to be part of our society.
And it will take probably some real positive effort on our
part to keep this divide between those who have and
those who have not getting greater in society.
Thank you.

[APPLAUSE]
MALE SPEAKER: So I'm pleased to say we have about 10 or 15
minutes to take questions.
So if people could ask questions by standing up and
going to the mics, that would be great.

Go ahead.
AUDIENCE: My ears aren't working
perfectly this morning.
I'm going to ask you if you would please to pronounce
again the name of the psychologist who has the
theory of the male mind and female mind.
DR. JAMES D. WATSON: Simon Baron-Cohen.
[INTERPOSING VOICES]

DR. JAMES D. WATSON: It's a hyphenated name.
He in Cambridge, England.
He had an op-ed piece in the New York Times last September
in reference to Larry Summers' not
well-received remarks at Harvard.
AUDIENCE: Thank you very much.
MALE SPEAKER: On the right.
AUDIENCE: I actually have a few questions.
So one is, since we're venturing into the realm of
political incorrectness, all the autistic people that I've
ever heard of were white.
I was wondering if-- but, of course, that doesn't mean
anything, that's purely anecdotal--
I was wondering if you know anything
about the racial incidence.
DR. JAMES D. WATSON: No, I don't.

I think there's probably--

no, I really don't.
I don't want to make any prediction.
Because a given family-- and that's part of thr--
you can have two children, same parents, and one will be
sort of high intelligent autism, and the other will be
low intelligence autism.
So that's in the same family.
So that's the only fact I can give you.
The other fact is that sometimes high intelligent
autism is very hard to distinguish from sort of
juvenile schizophrenia.
But it doesn't progress into the delusional form.
But people with the Asperger's syndrome have an impaired,
slightly impaired IQ and
difficulties in working memory.
AUDIENCE: My next question actually is--
it so happens, follows on from that.
When I read A Beautiful Mind, the biography of John Nash, I
felt strongly that even before he went into schizophrenia,
when he was a young man, it seemed to
me like he was autistic.
I was wondering if you were familiar with this biography
and what you have to say about that.
DR. JAMES D. WATSON: I met John Nash a couple years ago
at Cold Spring Harbor.

Was a very nice man.
He has schizophrenic son.

Early on, I think it's very hard to distinguish this
autism from schizophrenia.
AUDIENCE: I see.
DR. JAMES D. WATSON: I mean, the psychiatrists have
problems.
AUDIENCE: My third question--
DR. JAMES D. WATSON: OK, the last one.
AUDIENCE: All right.
OK, so I have to pick.
OK, so my third question was I had read that Craig Venter
decided to leave the public Human Genome Project and start
his private company because you had dismissed his whole
genome shotgun sequencing idea.
And I was wondering how you would characterize the
interaction.
DR. JAMES D. WATSON: I think that's slightly a misstatement
of what happened.
He [UNINTELLIGIBLE]
shotgunning of bacteria was successful.
The Human people who were running the public program
didn't think shotgun could then handle the repetitive
sequences of DNA and wanted to go by using
clones of defined location.

Venter took a big gamble, and [UNINTELLIGIBLE].
I think those of us who are connected to the public
program think we've proceeded in the right way.
There is a really high res--
since then, the computing power has increased
enormously.
You can do things that you couldn't do back five
or six years ago.
so you can now shotgun a human.
You probably won't put it perfectly together just by
shotgunning.
Right now, everything we've got to do is re-sequence.
You have one which you know to very high accuracy, and you
compare everything to this one.
And that's where we are now.
AUDIENCE: I see.
Thank you.
DR. JAMES D. WATSON: Yes.
AUDIENCE: So I don't think there's a nerd in this room
that doesn't think this is cool in some way or another.
The question is, what can we do for you?
It was mentioned that we might be able to help you out.
Could you elaborate a little more on that, please?
DR. JAMES D. WATSON: Well, we'll--
what is needed is--

in a simple way, if you Google DNA and you wanted to look at
the DNA sequences of one given gene in a million people,
that's sort of what we want to do.
And then you want people to have analyzed it and spotted
sequences from Australia, Ireland, you know, so on.
So there's going to be just an enormous database necessary to
contain all this DNA.
And right now, people are dealing with this sort of
perfect human genome sequence and analyzing it.
And that's what our database is.
Because of privacy and a lot of issues, no one has yet sort
of said, we'll go for the big database.
But once we begin to do all this re-sequencing and the
costs go down, then there will be the big database.
And I think we want to get it started soon, because already
there's data and you don't know how to get it.
AUDIENCE: Thank you, sir.
AUDIENCE: Hi.
I was just noticing--
first of all, I'm a great fan.
I read The Double Helix when I was knee-high to whatever.
But as you were talking, I noticed a sort of a tendency
you have to sort of put things up along a single axis.
In other words, people, how bright are they?
What is their exact IQ?
Is it a male mind, or is it a female mind?
But to me, it seems as if the lesson of DNA is that this
whatever it is, it's enormously complex and
multi-dimensional.
And to collapse it onto these single things, I'm just not
sure how meaningful it is.
DR. JAMES D. WATSON: Well, it may be very meaningful if
you're trying to figure out why your child is autistic.
That's all.
It's a way of-- you know, everything is very complex.

But you could do these tests, and on the whole, there's a
difference between the way men and women answer.
Some women answer exactly the same way men do.
And so it's very overlapping.
But it's useful in trying to possibly--
There was a sample.
We just had a meeting on the genetics of autism.
The average IQ of the parents of autistic children in
Seattle is 112.
That means something.
OK?
AUDIENCE: OK, thank you.
DR. JAMES D. WATSON: That's all I'm trying to say.
And so we're trying to come to grips with it.
And certainly, fetal testosterone, which levels
vary in between males and females--
[UNINTELLIGIBLE]
boys and girls--
does seem to affect whether you're going to have this
empathetic mind or this systematizing.
Knowing that it's a great over simplification.
But you know, my wife just goes toward babies.
I go away from them.
AUDIENCE: Yes, I understand.
DR. JAMES D. WATSON: I mean, very young babies.
AUDIENCE: But I love infants, and I'm also mathematical.
DR. JAMES D. WATSON: Yes.
There are some people who are good in both.
There are some of us who are just awkward.
AUDIENCE: But I'm awkward, too--
I just like babies.
But I just wanted to add one thing, which is that I know
that you tend to say, oh, and then there are these
politically correct people.
Well, it's not just political correctness.
I think that there are arguments that those of us who
are pretty much on the other side of the ideological divide
do make and that they're credible arguments.
DR. JAMES D. WATSON: Yeah, but I think that Larry Summers'
statement was probably correct, and his big mistake
was apologizing.
AUDIENCE: Oh no, not at all.
DR. JAMES D. WATSON: Oh no-- yeah, OK.
AUDIENCE: But I think enough said here.
I don't want to take up too many other people's time.
Being an empathetic person.

DR. JAMES D. WATSON: No, I think you would--
you know, what we don't know if you would do these tests
that the people who are very good at mathematics, highly
empathetic, whether a father and mother with both those
qualities, whether they have as high a probability of
having an autistic child as if both parents are sort of
missing in empathy.
I think that's really the question we're trying to ask.
AUDIENCE: OK, I understand.
DR. JAMES D. WATSON: And I think it's very important that
we answer it.
Because it's a bit creepy now.
You know, MIT doesn't want to study this.
Simon has tried to get them to have a formal study.
And we had at our meeting someone who was an MIT
graduate and married to an MIT graduate, and they seemingly
have normal children.
But he would just like that study done.
That's all.
As to whether the--
and I think it's worth really getting data here in Silicon
Valley whether the incidence of autism is higher.
Because the definition can be broad.
It's not a simple thing to answer.
But knowing parents of autistic children, it's a very
important thing to answer.
AUDIENCE: Yes.
Thank you very much.
AUDIENCE: As a female who has Asperger's syndrome, and has
the male mind of the Baron-Cohen, I also have an
Asperger's son.
So this was exceptionally interesting to me.
I'm wondering if--
I know that people with severely autistic children are
very concerned about their children, and it's important
to study that.
I'm wondering if there is any look at this is more of a
natural variation among human brains, and if the new
technologies which allow us to interact with each other in
more technological ways-- without the facial, body
language, and things like that--
are developing--
to me, they seem to be very helpful for those with
Asperger's and other high functioning autism.
I'm wondering if you're looking at that as ways to
help Asperger's children to function better
with others in society.
And if there any advantages that you've seen for those
with that particular variation.
DR. JAMES D. WATSON: I think you would be
better qualified to--
you know, if this was behind Rosalind Franklin's inability
really to become close to either men or women, then I
don't see any advantage she got out of it.
But you know, it made her suspicious, unable to interact
with their colleagues.
In a way--
you know, she had that picture.
She should have got the structure.
We didn't steal it from her, she just didn't
use what she had.
So I think the tragedy was that she did have this
inability to interact with people, and I
think that hurts you.
In the world that we're in today, where computers--
you seem to interact with computers through computers,
then that's clearly better for someone who doesn't have to
look at a face.
But I have a son who finds it difficult to look at faces.
So it's not--

AUDIENCE: It's not a cut and dried situation.
DR. JAMES D. WATSON: You know, when you see it close up-- and
I see it very close up-- it's very tragic.
AUDIENCE: It can be, yes.
MALE SPEAKER: If we can take three more questions.

AUDIENCE: I appreciate that there may be a strong genetic
component to autism, but it's also the case that you can get
autism by taking certain chemicals at
certain points of gestation.
And the incidence of autism seems to be rising rather
dramatically.
That would seem to suggest that there's a lot going on
besides genetics.

DR. JAMES D. WATSON: It's not increasing very rapidly--
the definition of autism is changing.
And special schools are coming into existence which, to be
admitted to, you have to be declared autistic.
And so parents are wanting to have their child declared
autistic so they can put them in the schools.
We had to talk about this.
And as far back as 1978, if they had used a wider
definition of autism, it was coming close to 1 in 150.
That's the way back then.
So I think it's more ascertainment.
Now, the marriage pattern is changing.
Intelligent women are much more likely to marry
intelligent men than they were in the past because they're in
the same schools with them and socially they're mixing.
So to the extent that that would increase the probability
of autistic children, we may be seeing that.
But whether that could double the total autistic burden, no
one knows yet.
We really have to find the genes.

That's what we're trying to do.
AUDIENCE: Hi, Dr. Watson.
Thank you for being here.
As a mother as a child with ADD and petit mal epileptic
seizures, which she has thankfully outgrown, in my
studies and learnings about her, that seems to be on the
tree of life, kind of on the same branch as autism.
Autism kind of branches off as the
diagram that I was reviewing.
DR. JAMES D. WATSON: About 1/3 of autistic children have
epileptic events.
AUDIENCE: So they are connected, but not necessarily
epileptic children are destined--
DR. JAMES D. WATSON: Many epileptic children have not a
trace of autism, but behind some cases of autism are
defects in the nervous system which also
manifests itself as epilepsy.
AUDIENCE: Thank you very much.

AUDIENCE: Dr. Watson, thank you for sharing
your thoughts today.
He said you were excited about studying nature because
nurture seems so difficult to quantify.
And while the tools of molecular biology are
wonderful, it seems most of the questions here have
suggested that measuring human
phenotype is the real frontier.
And here in this place full of databases of human behavior
and it's phenotype, I'm wondering whether you think
that refining or understanding with new tools for the
description of childhood behavior, and the effects of
debilitating illness during childhood, and congenital
environment, and how that shows up in phenotype is the
real frontier, and that the tools for molecular biology
are sort of ahead of our description of behavior.
DR. JAMES D. WATSON: I think it's just this decade is the
decade when we suddenly have the tools to do this.
So we might as well just do it.
And then after we've milked nature for as much as we can,
then back to nurture.
AUDIENCE: Is the doing correlating with poorly
defined phenotypic characteristics, or is the
doing the refinement of the phenotype?
DR. JAMES D. WATSON: No, we have to refine the phenotype.
But phenotype is certainly in the psychotic diseases.
You know, it can vary over the course of a lifetime.
They can go from one behavior to another.
So my sort of feeling is that if we--

the genes are solid, so we want to find the genes and
then once we know that, then we'll begin to see how
environmental influences go.
And it's going to be--

the real complexity to it is that there's just an enormous
amount of human variation.
And the same particular mutant gene in one person will bring
about a different effect than it does is another person.
So a parent can have a gene and have some phenotype, the
child can have that, but because others of his genes
are different, and they're all interacting, then it's very
complicated.

You know, you could either, hey, it's so complicated I'm
going to do something else.
Or just say, autism is an awful thing, and we're going
to find out what causes it.
I think that's just our attitude.
And 10 years ago we couldn't have done anything-- now we
can, so we should do it.

And you know, it may put to rest that people believe that
it's vaccines or the other potential causes of autism.

You know, this is awful to say: autism is a disease of
the male mind.

I mean, I'm paraphrasing Simon Baron-Cohen on that, but I
think he's right.
MALE SPEAKER: One last question.
AUDIENCE: My question has a slightly different focus.
And I was wondering how you think the recent advances in
computational biology, bioinformatics, and proteomics
is going to change the future in genetics research, and
specifically, the focus of molecular evolution of certain
important proteins and genes.
DR. JAMES D. WATSON: Well, I think you can't handle all the
data without these computational tools.

Probably in a few years, if you go to a genetics
department, half the people are going to be geneticists
and half molecular biologists--
I mean, half will be molecular biologists, half will be
mathematically trained.
So you just can't look at the data and get out the data you
want without mathematics.
And at Cold Spring Harbor, we want to have a little
department of applied math.
Because our people need help in looking into that.
AUDIENCE: Do you feel that the two fields will come together,
or do you think you will continue to have bench
scientists and computational scientists on either side
working together?

DR. JAMES D. WATSON: I bet a given person is going to
[UNINTELLIGIBLE] the other for the most part, and there will
be a few people who straddle both.
But that both are just increasingly complicated, and
it'd be hard to master both.
Better have the computational person next to you.
In the sense that I had Francis Crick next to me--
it went faster.
So you don't want to say you've got to do all these
things and have a tenure PhD program.
I think you want to get people out really doing real science
in their early 20s.
AUDIENCE: Thank you.

[APPLAUSE]
MALE SPEAKER: So I want to thank everyone for coming.
I have to say, the talk was more germane to me than I
expected, being the uncle of a nephew
with Asperger's syndrome.
For those of you got the book, and you know who you are, if
you'd like to get the book signed Dr. Watson has very
kindly agreed to sign the books back in
that area over there.
And one more I think round of applause, and then thank you.