DNA & the Brain | James Watson | Talks at Google

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, which is obvious to everyone in this room, but I'm going to do it slightly indirectly. I want to introduce first Bruce Stillman, who is the president of Cold Springs, I believe that's 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 and research, and also there's a cancer institute there. And as you know, we've been looking hard at cancer and sort of some of the things we could do there. And I want to introduce Bruce and then let Bruce introduce Dr. James D. Watson.

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. 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 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. I hope some of you actually used it at college. Then he, 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 with you today, the Double Helix. It was a New York Times bestseller 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're 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 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.

Thank you. R. So I'm told I got 40 minutes, and so I'll try and rush through several things. I was told people wanted to hear about DNA in the brain, but I also know that wherever I go, people are always asking me, you know, how did we find the structure of DNA? So I'll spend about 10 minutes just talking about those days together with sort of some rules. Why I think it was Francis Crick and I found the double helix. So this shows me my first ambition as a young scientist. I wanted to be an ornithologist. I was a keen bird watcher. 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 physicist Erwin Schrodinger. And Schrodinger said the essence of life was information. And said, well, it had to be stable information. And so it must be on a molecule. It couldn't be a gas, it was a 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 had never really, you know, thought of genetics and molecules in that sort of solid way. And so I, that fall, I, instead of applying to Cornell to be an ornithologist, I applied to Caltech, to 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. And 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 the. 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 the test tube. They Weren't they were making nucleosides, 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 it was talk was given by a young or 30 year old, 35 year old English physicist Morris Wilkins, who said it was crystalline. So that meant DNA had a three dimensional structure and despite all DNA molecules probably being different because they were carrying different pieces of information, they could still fold up into a common structure. Wilkins didn't seem to show any interest in me. So luckily my PhD supervisor at Indiana Luria arranged for me to go to Cambridge University and there are for sure. My first day I met Francis Crick who was then working on proteins and I was in a lab whose objective was to find a 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 the alpha helix. The way polypeptides folded up had been proposal by Linus Pauling about six months before. And Max Perutz at Cambridge actually proved the alpha helix was right. He tilted a synthetic polypeptide and got the 1.5 Angstrom 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 planar and it just made everything fourfold. They were very embarrassed. So I mean sort of, you know, a 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, you know, solve it rigorously or could you sort of guess it using clues such as the repeated longer fiber axis was 3.4 angstroms or something like that? That is, was there enough information now by the time I arrived, the covalent structure was worked out. It was a regular 3, 5 phosphodiester structure. We 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 divinodion, 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 any more model building because we, Crick had a LOUD VOICE and he sort of offended 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 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. And he had written the people Wilkins who had heard about the X ray photograph saying could he have a copy? And Wilkinson 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. There was, this is me in about a year after I arrived in Cambridge. I spent a year letting my hair grow long because I arrived as an American with a crew cut. In those days, she had short hair. And Odile Crick said I looked like, you know, I'd be confused as American Air Force. And so, you know, and I arrived without 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 said, I asked me whether, you know, they thought I was Irish, which afterwards I realized is, you know, maybe a little better than an Englishman. And. 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 with pH1 and cells are 7. So the structure was preposterous. And we rushed over to the chemical laboratory and they said, yeah, Pauling had made a mistake. And so then the people in Cambridge let us go ahead. You know, it wasn't a two person, you couldn't be gentlemen, you know, polling wasn't not working on it because London was working on it. And so I took the polling paper 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 which just had a helix. And Rosalind was very intelligent and never really had looked at the picture before. She wanted to solve the crystalline structure. And this was para crystalline. So within a month we had the structure on 28-2-53. And so I'll give you a couple reasons why we became famous, why we found it. Not that. The first is 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. In part, 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'd get an answer soon, maybe the next day. So you shouldn't sort of, you know, work on a problem when you think It'll 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. Okay? You know, people sort of trust you for put up with you for three years. And 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 was then redeviling 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. Okay? Now, Rosalind Franklin had met Francis and disliked him and didn't want to talk to him. Now, she didn't, though 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'd analyzed that there are two chains, one going up and down. So she didn't really. She wanted to do it herself. Okay? So it really pays, particularly when everyone else thinks you're 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, you know, it's helpful. And the last thing which was important, and never be the brightest person in any room you're in, you know, particularly if it's this big, because if you're the brightest person, you know, in a place no one can help you. So 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 Donahue was out of Caltech. He said, you got the hydrogen atoms in guanine and thymine in the wrong place. Now I just copied them out of the textbooks and assumed that the textbook figure was right, but it wasn't. So if Donahue 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. So now it could have been solved in kings. They just had to talk to each other. So I think those sort of reasons, you know, 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 had taken care of that, 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, main things to get there. But too many people are concerned with their pride and all that. It was very useful for me never to have been brought up thinking I was bright because I, you know, it's very easy to ask for help. And if you're going to need help, ask for it quick. You know, don't wait a week. If you don't know something quick, find someone who does. Okay. That was the sort of went out at the. When we knew it was a big thing, we put in this little sentence that has not escaped our notice. It was a little letter to nature. And of course, now the interesting you may think was surprising, no one asked us to give a talk in Cambridge. We never gave a public talk on double hicks, no seminar. And so the first public talk was given across the Atlantic when at a meeting in Coast Point Harbor. And for five years, you know, except for one case, there was just no one wrote articles about how public are articles, how important DNA was. And it really took the great experiment at Caltech by Meselson and saw what showed the strands separated and then work out of Kornberg's lab at Stanford here, which Showed the strands ran in opposite directions, not crystallographic, but another way. So five years after the double hit, 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 genes, the DNA sequence determined the sequence of amino acids and proteins. Okay, so that's the story. And I wrote it up in the double helix. And it was fun writing because it was a good story. And I tried to write it like it was a novel. And I wanted it to be as good as the great cats be. So, you know, I've been a voracious reader when I was a child and, you know, was still in Cambridge, so, you know, I really didn't know people, but I knew people through books. And so then they finally did make a movie or a docudrama. And I was played by Jeff Goldblum, which I first thought was a bad choice. I would have preferred John McEnroe, but we got to. But he was orthogonal to everyone, and I probably was at that time. It did catch, sort of the arrogance of it. But Francis Crick wasn't played well. And so now they're going to make movies. Bob. Rosalind Franklin. I'm going to be the villain. So someone had suggested that in order, so that. And I can't always forget his name, but it's something like Ashton Kushner, that he could play me. And then, despite my being the villain, you know, 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 high 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 there was. It was, you know, at the time, one thought, well, she came from a wealthy family. We didn't know that she was just a snob. I don't think she was a snob. She just probably didn't see faces very well. I'll come back to the other now. I want to go on. Then the next, go fast on DNA in the brain. So I think this century will see the 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 to mouse a whole related, trying to get enough information, comparative information, begin to see really where the essential parts of the DNA molecules are. And so it's sort of, you know, 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 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 from the first. And, you know, 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't 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 monogozygotic 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. And so. In order to study cancer at Coastal Marine harbor, we worked out a technique which is called roma. It's basically taking tiny representations, little oligo, little bits of DNA, and we're now up to a chip which has 380,000 representations. So you're sampling our genome at 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 think, well, you just changed the letter from A to T 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 base, 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 will be possible probably to sequence everyone's DNA at reasonable cost or 10. 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, 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 stereotype 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 100,000. But if you sort of broaden the definition to say you're not, you know, you can't. Some autistics don't speak, but you can speak and your social interactions are. Are bad, then it can go up to about 1 in 100. So awkward kids, and most awkward kids are boys. Boys are more awkward than girls. Why? We don't know. It could be because we only have one X chromosome or we have a Y chromosome. Okay, all right, so there's this. Now, girls do get autism. And I think Rosalind Franklin was of this type of high intelligence, but really she 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 ease. Okay, now here, then I'll just go through this very fast. These copy number of polymorphisms, all of us carry about 10 of them. And just, you know, for people who count, one of these scans costs about $1,000. If you don't go 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 us about $10 million to do this study. Okay, so you can do that. And we're trying to look at autism, and you can look at it in two ways. You can look at families where you have more than one Autistic child. Okay. So you have two. And in other cases you can. 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. Okay. And in rare cases, you can see chromosomal defects. And 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 a sort of unambiguous way. And this was an interesting case where we saw a change on 15. And I say that. 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 any confirmation. Right now there are big 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 just. I'll go fast here. Anyways, it's a gene which is expressed in the central nervous system. So you can see you just got one case. Well, how do you know it's the cause of it? But the answer is in most, when you get a deletion, 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 would like to do is find a large number, just repeat. And here's another one. This is a protein again, expressed in parts of the brain. And this one, and I should. Autism in the 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. Okay? It's creepy in the following sense, that 50 years ago there was a psychiatrist at the University of Chicago, Bruno Bethelheim, 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 children, 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 they were the cause of it. Now, that was given up about 20 years ago, and then it Was sort of generally believed that the parents 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 to 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. Okay, now it turns out that when he looks at the parents of autistic children, that the mothers are more systematizers than on the average and the fathers are. So that. Yeah. And then, okay, so 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, you know, beauty, not friends. Okay, so you know, they. I know everyone laughs, but when you get down to it, it's nasty, okay, because you know, there's sort of rumors, you know, that more autistic children are born to MIT graduates, there's more autism here in Silicon Valley. Okay, probably true. Okay, 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 had high testosterone and then when he does the measurements that basically it leads to the male mind. Okay, 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, you know, the parents? What genes really predispose you to that? So knowing, you know, friends with autistic children where the women are very highly intelligent, I think if you'd ask them, well, would they have you know, taken a test to not have such a child, they'd probably say yes. So I think it's, you know, that autism may be to intellectuals what HIV was to the homosexual community, something which 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, you know, 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 you know, there are probably some in this room, so many can become functional. But in many cases it's a very hard burden to bear, both, particularly for the people who have the disease. So sort of to conclude autism is just one of many other things. We're now trying to, you know, be serious in 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 this sense that we'll understand when people sort of 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 to people who seem to be awkward, realizing that they were born awkward. It wasn't just that, you know, they didn't want to be with their bigger brother or little sister or something like that, that they didn't really have the choice and that the 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 understood autism. Those of us who work with it, you know, using this framework of younger people, you better do something in three years. So we're sort of operating under the three year rule. You know, we got to accomplish an awful lot fast and I think we will. So the Human Genome Project, which, you know, when people first started it, there was lots of opposition, I think. Well, my last thing is that sort of, you know, at the time I was a young teacher and so on, when political correctness came in, it was sort of everyone sort of thought it would be nice to believe that all humans weren't that different from each other as we could only change the environment, that is to nurture everything would be. We could do away with a lot of the inequality in the world. Now we're witnessing, particularly as now we're placing greater sort of intellectual demands on people, a widening of inequality despite all our, you know, in terms of wages. And some of this probably has some genetic component, something which, you know, you're supposed not to say, but I suspect it's true. And therefore, you know, I think the. 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, you know, positive effort on our part to keep this divide between those who have and those who have not getting greater in society. So thank you.

So I'm pleased to say we have about 10 or 15 minutes to take questions. So if people could ask questions by signing up and going to the mics, that would be great. Go ahead. 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. Simon Baron Cohen. Who's Simon Baron Baron Cohen? It's a hyphenated name. He's in Cambridge, England. He had an op ed piece in the New York Times last September when, you know, in reference to Larry Summers, not well received remarks that Harvard.

Thank you very much.

On the right.

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.

No, I don't. I think there's the sort of. No, I don't want to make any prediction because a given family, and that's part of the complexity, you can have two children, same parents, and one will be sort of high intelligent autism and the other will be low intelligent 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, 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 the difficulties in working memory.

My next question actually is sort of, it so happens follows on from that. When I read A Beautiful Mind, the biography of John Nash. It seemed, 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 his biography and what you have to say about that.

I met John Nash a couple years ago at Coastal Spring Harbor. He was a very nice man. You know, he has a schizophrenic son. Early on, I think it's very hard to distinguish sort of this autism from schizophrenia.

I see.

I mean, the psychiatrists have problems.

My third question.

Okay, the last.

All right, okay. So I have to pick. Okay, 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 of a. Because you had dismissed his whole genome shotgun sequencing idea. And I was wondering how you would characterize the interaction.

I think that's slightly a misstatement of what happened. He'd done. Shotgunning of bacteria was successful. The human people who were running the public program didn't think shotgun could then handle the repetitive sequences DNA and wanted to go by using clones of defined location. Venture took a big gamble and partially won. I think those of us who connected to the public program think we proceeded in the right way. That is a really high resolution. 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're going to do is resequence. You have one which you know to very high accuracy and you compare everything to this one. And that's where we are now. I see.

Thank you.

Yes.

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?

Well, we'll later. What is needed is a. 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 it, sequences from Australia, Ireland, so on. So there's going to be just an enormous database necessary to contain all this DNA. And right now there are 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 resequencing and the costs go down, then there'll 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. Thank you, sir. Okay.

Hi. I was just noticing.

I.

First of all, I'm a great fan. I read the double helix when I was knee high to whatever and. But as I was. As you were talking, I noticed the sort of a tendency you have to sort of put things along a single axis. It's, 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 whatever it is, it's enormously complex and multidimensional and to collapse it onto these single things, I'm just not sure how meaningful it is.

Oh, 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, you know, 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 a very overlapping. But it's useful in trying to possibly. There was a sample. We just had a meeting on genetics of autism. The average IQ of the parents of autistic children in Seattle is 112. That means something. Okay.

Okay, thank you.

That's all I'm trying to say. And so we're trying to come to grips with. And certainly fetal testosterone, which is, you know, levels vary between males and females. Those are good boys and girls. Does seem to affect whether you're going to have this empathetic mind or the systematizing knowing that. It's a great oversimplification. But, you know, you know, my life just goes toward babies. I go away from them.

Yes, I understand.

Okay. I mean, very young babies, you know.

But I love infants. And I'm also mathematical.

Yes. There are some people who are good in both. There are some of us who are just awkward.

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.

Yeah, but I think, you know, Larry Summers statement was probably correct and his big mistake was apologizing.

Oh, no, not at all.

Oh, no.

Okay, but I think enough said here. I don't want to say take up too many.

No, no, no, no.

But being an empathetic person.

Yeah, no, no, no, I think you would. You know what, we don't know if you would do these tests that the people who are very, you know, good at mathematics, highly empathetic, whether if you, a father and a 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. Okay, I understand and I think it's very important that we answer it because. It's a bit creepy now if you're, you know, MIT doesn't want to study this. You know, Simon has tried to get them to, you know, have a formal study and we had at our meeting someone who's MIT graduate, married to an MIT graduate and you know, seemingly have normal children, but he would just like that study done, that's all. As to whether they, 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.

Yes, thank you very much.

Yes.

As a female who has Asperger's syndrome and has the male mind of the Baron Cohen. I also have an Asperger 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 as 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 children to function better with others in society and if there are any advantages that you've seen for those with that particular variation.

Did that make sense?

I think you would be better qualified to ask that, you know, if this was behind Rosalind Franklin's inability really to become, you know, close to either men or women, then I don't see any advantage. She got out of it, but, you know, made her suspicious and unable to interact with her 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, you know, use what she had. So I. Think the tragedy, you know, 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, you know, it's not, you know.

It'S not a cut and dried situation.

You know, when you see it close up, and I see it very close up, it's very tragic.

It can be, yes.

If we can take three more questions.

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 lots going on besides genetics. 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 autism autistic. And so parents are wanting to have their child declared autistic so they can put them in the schools. We had a talk about this and as far back as 1978, if they used to work wider definition of autism, it was coming close to 1 in 150. That's 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 they socially, they're mixed. So to the extent that that would increase the probability of autistic children, we may be seeing that. But whether, you know, that could double the total autistic burden, no one knows yet. We really have to find the genes. That's what we're, you know, that's what we're trying to do. Yes.

Hi, Dr. Watson, thank you for being here. As a mother of a child with ADD and petty 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 about the third of autumn.

Autistic children have epileptic events.

So they are connected, but not necessarily epileptic children.

Are destined epileptic children. Many epileptic children have not a trace of autism. But behind some cases of autism are defects in the nervous system which also manifest itself as epilepsy.

Thank you very much.

Dr. Watson. Thank you for sharing your thoughts today. You 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 its phenotype, I'm wondering whether you think that refining or understanding with new tools for 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.

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, you know, milk nature for as much as we can, then back to nurture.

Is the doing correlating with poorly defined phenotypic characteristics or is the doing the refinement of the.

No, we have to refine the phenotype. But the phenotype certainly and the psychotic diseases, you know, can vary over the course of a lifetime. They can go from one behavior to another. So our sort of feeling is if we the genes are said sort of solid, so we want to find the genes and then once we know that, then begin to see how environmental influences go. I think 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 in another person. So a parent can, you know, have a gene and have some phenotype. The child can have that because others of his genes are different and they're all interacting. And it's very complicated. So, You know, you can either just, hey, it's so complicated, you're going to do something else, or, you know, you 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. You know, it may put to rest that people believe, you know, that it's vaccines or, you know, the other potential causes of autism. But is there. That is, you know, this is our. This. It's awful to say autism is the disease of the entire, of the male mind. You know, I mean, that's. I'm paraphrasing Simon Baron Cohen on that, but I think he's right.

One last question.

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. Change the future in genetics research and specifically the focus of molecular evolution of certain important proteins and genes.

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 time people are going to be geneticists and half molecular biologists. I mean, half will be molecular biologists, half will be, you know, 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, you know, have a little department of Applied Math because we, you know, our people need help.

Do you think 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?

I bet a given person is going to the other for the most part, and there will be a few people who straddle both, but both are just increasingly complicated and it will be hard, you know, to master both, you know, better have the computational person next to you in the sense that I had Francis Crick next to me, you know, it went faster. So you don't want to, you know, say you got to do all these things and have a 10 year PhD program. You know, I think we're. You want to get people out really doing real science in their early 20s. Not. Yeah.

Thank you.

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 who 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.