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DNA and the Brain: In Search of Mental Disorder Genes

James Dewey Watson
3 July 2008, Moscow House of Scientists

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Текст лекции в переводе Петра Петрова
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G. Georgiev. Я академик Георгий Георгиев, мне поручено открыть сегодняшнее заседание. Несколько слов по-русски, потом по-английски. Мы с Джимом Уотсоном знакомы в течение многих лет. В конце шестидесятых я впервые посетил его лабораторию в Гарварде, где Джим как раз объяснял мне новые интересные достижения своей лаборатории в области регуляции экспрессии генов. Потом Джим — он и до этого бывал, и потом неоднократно бывал у нас в институте, бывал дома у многих из наших ученых. Мы тоже бывали у него дома, в Колд-Спринг-Харборе, где он проработал сорок лет и где он создал очень мощную научную школу. Ну вот, это, так сказать, два слова по-русски, а теперьEnglish 1 — let me introduce Professor Jim Watson.


It is a great, great pleasure for me, and great honor for me to introduce him to you. And, of course, everybody in this audience knows quite well that Jim discovered the structure of DNA, the famous double helix. And he and Francis Crick were awarded their Nobel Prize for this discovery. However, many of you maybe don't realize that this was not just a discovery: this was the beginning of the new, modern biology, the biology that exists today. So all modern biology came from double helix. And, moreover, not only modern biology, but also the future medicine also depends on this discovery.

So, after the discovery of double helix Jim moved to Harvard, United States, — the double helix was in Cambridge, England, — and there he had a very active department with many brilliant scientists, like Mark Ptashne and Wally Gilbert, and there, there was a series of very important researches developed under supervision of Jim, mostly devoted to the control of realization of genetic information in cells.

Then Jim moved to Cold Spring Harbor, as director of Cold Spring Harbor Laboratory. And under him this laboratory very soon converts to one of the major, the most important centers of molecular biology throughout the whole world. The Cold Spring Harbor Symposia, which I visited pretty often, were one of the central events in the molecular biology in those days, and also now. In Cold Spring Harbor, Jim was mostly interested by the cancer problem. And the collective which he combined there made a lot of very important works in understanding how the normal cell is converted into the cancer cell. And Jim was actually one of the activators of all this big program.

I wish to say that Jim is characterized by great scientific provision. He was an initiator of the program, so-called Human Genome Project. Actually, it was the determination of the base sequence of the whole genome of humans. And many scientists of that time, many very important scientists, did not believe this project's realistic, they believed that it's a completely non-realistic project. But Jim was, as always, right, and the sequence of human genome was solved even sooner than it was planned at the beginning. So it was again a very important achievement of science in general.

And now, as I understand, the main interest of Jim is concentrated in brain and different kind of brain diseases, and I hope that today we'll learn a lot about this very important question.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

J. D. Watson. I want to thank my hosts in Moscow for giving me a really very interesting and rewarding week in Moscow. It's much better than even I hoped. And now I want to particularly thank this House of Scientists for giving me the opportunity of such a large audience. And those who are running the House, I want to thank them.

I'll speak a little, to start with, about my philosophy of how to get science done.

I am just 80 years old. And for 20 years, once I got to school, for 20 years I was a student. And then for 20 years I was an active scientist: first doing DNA, and then, at Harvard University, having students working on protein synthesis. And then, at the age of 40, I changed the course of my life as I became the director of a scientific institute, interested in genetics. There were several reasons: the laboratory had no money, and we'd fail, but probably the chief reason was that I wanted to start a rather big effort to understand how viruses cause cancer. I could see that it's a project much bigger than I could do in the university, and so my interest would be best served by being the boss and hiring other people to do science.

So, after the age of almost 40, I didn't have any more students, I didn't have a laboratory. Becoming the director of the institute, I had no laboratory. My chief function was just to hire people, to get the right people. If you have a scientific institute, I think they are perfect devices for working on a problem, whereas universities are not very good places to, say, understand cancer. You can do it, but you have also a psychology of competing interests, and it is hard to really focus in the university. If you want to focus, a scientific institute is the way, and I wanted to focus.

From the start I wanted to have the institute populated by young people, people who just — the worst was people who had been postdocs before I hired them. So there was no thing trying to hire big people. I tried to hire people that no one had heard of, but who, for some reason I thought, would be good. And, of course, the chief reason that you want to hire them is they want to work on cancer, because they want the job. They wanted to understand cancer. And my job was to find the money. So, if I could find the money, and then once they were hired, I really didn't ever tell them what to do. My rule, for best running it, is to delegate as much power to other people. Trying to have all decisions made by other people, if you can. So I had an assistant director. He'd made a lot of decisions that saved me a lot of work. And I tried to make myself so unnecessary that I could go to Europe for a year, and it wouldn't make any difference. Because I wasn't really telling people what science to do, I hired other people, for them to decide what science was to be done.

Initially, our institution was very poor, and so there were no permanent scientists. In fact, that was a very good thing, because I didn't want anyone to stay on very long. I just wanted them to do good science, and, knowing they had no security, and would never get tenure, they'd move on to a good university. So I could keep the age of people under 40 — by not offering security. Because when I had got into science at the age of 20, I came to know Max Delbrück, the German physicist, and Max was always constantly telling me that beyond 25 you begin to go downhill. So by 40 you're there. That was the policy: no security, people work hard, do science, they do the science of their own ideas, and then they find a job some other place. I was effectively the boss for about 25 years.

We ran that way, and we became successful, essentially because I was never bored by the science done at the laboratory. Everything people were doing, I was interested in — that's why I hired them.

And second, my job was not to bore the people who would give us money. So I had to actually be excited by what we were doing, and the laboratory luckily was located in a region of some very rich people, and through these very rich people we could move much faster than we could if we were totally dependant on the government. Good science is sort of essentially elitist. We were trying to move faster than other people. And to be different from other people, you have to pace. And at least in the United States it helps to have some private money to let you move faster. So I really never worried about money for 25 years. Because the science was good, the neighbors liked this. And we kept getting bigger and bigger.

And another thing, besides reserving the power of who we hired, I had all the power of what buildings would look like, and what trees we would plant. It's been my feeling that scientists are not on the average very interested in aesthetics. They don't care what things look like as long as they can do their experiment. But if there's an institution, you have a long future, you probably wanted to have some grandeur. And if it looks slightly grand, people are more secure giving you money, because it doesn't look like you're going to fail. So my job was I got a lot of pleasure from trying to design handsome buildings that looked like they would stay permanent. And planting trees. Now I see some trees that I planted 40 years ago, and they're getting big.

My successor has enough power, the way I did it. He has let people get old. And sometimes that makes sense. Actually, after I'd been there, in Cold Spring Harbor, 15 years, I gave security to someone. So he got tenure, and it's about basically his work I'm talking to you now. He is 57, and he still acts young. So, you can have rules, and then you should break them. But it's hard for universities to break rules. Because it seems unfair to someone. It's tricky to just improvise.

And the other thing which is I think why I was successful as a sort of boss is that I wanted things to happen as fast as possible. So I would always make a decision as soon as I could. Someone would come into my office, and I would give him an answer, not saying I will wait a week and think about it. Just say yes. I found it was a very good policy to say yes every time someone came into the office. Because it showed your faith in them. And if you should say no, you should fire them. You want people you can say yes to. So I never really had appointments, and my door was always open, and I tried to move fast.

One way to move fast is to have no committees. No committees, just make decisions. So we never had committees to hire people. We just hired people. Now we have committees! It slows you down, because you are trying to be fair to everyone. Whereas I've found, in science it doesn't pay to be fair to everyone. Because it just slows you down, and if you don't do something, someone else will do it before you.

And then the other is I thought, if we do something, we should try and be at least as good as anyone else in the world. Never do something unless you have a chance of being at the very top. Never go in and say, well, I will be number ten. Either you go and think you will be one, and of course you are happy if you're three. But at least so.

Initially, our competitors were people in London. And they grew old, so we didn't think about them. And then for a long time just basically I tried to be as good as MIT. With much less money and with superficially much less distinguished people. MIT can afford people who everyone else says is good, whereas I had to hire people before anybody else said they were good.

If you think about it, having my own lab, doing my own science would have kept me from thinking about my competitors. I always think that we want to be first. That's all. And sometimes you are, and sometimes you aren't, but at least you have the objective.

Now I'll give a talk and go through the work of Michael Wigler, who developed technology for finding genetic differences in cancer cells before you could sequence them.

I will explain the moment that Wigler is an unusual person. He would make a terrible boss, because he really only thinks by himself, and by himself about his own science. And Michael always needs someone like me who supports him. But before I hired him he had been a very successful PhD student at Columbia University, in Medical School. And he had worked out a method for getting DNA into cells. The thing was to make a normal cell a cancer cell by adding DNA. And this way you could isolate a cancer gene. So it was a technology which he developed, and then it turned out to be very useful commercially, in getting genes into animal cells to make biotechnology drugs, proteins.

Wigler's work let Columbia University get a patent which made Columbia University 600 million dollars. Wiggler himself collected about a hundred million dollars. So Mike is a rich scientist. But after becoming rich, his science has gone on at the same high level. He never wanted to be a scientist to become rich. Being rich just let him have more freedom. So he lives in a big house across the water from me, which was the summer house of John Foster Dulles. Which, when you think of it, makes me laugh, that a scientist can be as successful as Wall Street lawyers.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

These are some of the rules. And a sort of rule, that is, a really difficult rule, let's go back to that, an institution is either getting bigger or smaller. And so if it's successful, it will get bigger. But you can't get bigger forever, so that's a problem. But if you don't build new buildings, your good people will go some other place. Success demands growth. And it's sort of true for all companies. Companies have to get bigger, and sometimes they collapse. You get too big. So, just to conclude, what was the solution to Cold Spring Harbor getting too big. I wanted to turn it into a university. More or less to keep it alive. If we don't become a university, then we will collapse. And that means giving people tenure. And my rule is, I really wanted to give tenure only to people over 50. Not at 35, because if you can go through to 50, you probably won't burn out.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

Here's Wigler on the left, and the group. His group is about 15 people. So it's not 40 people or something, it's about 15. And about half of them are trained in mathematics, because when you work at the lab of the human genome, you have to be trained in mathematics to analyze the data. And Wigler, when he was a student, he was a math major. So Wigler likes math. And the tree behind you can see is about 120 years old, that beautiful tree.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

Wigler's method was that with a human genome, you have the possibility of isolating regions where a gene normally present in two copies suddenly would go to three copies. Or you might lose one gene, and instead of having two, have one.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

They published a paper, and it was now four years ago. The first paper saying that if you look for the gene not at the level of chromosomes, but use DNA chips, copy number polymorphisms, every person contained about 10 big ones. Because the first technology only picked up big ones. And then the work was confirmed by someone else. Until this work, everyone studied simple mutations, changing one base to another, but this was focusing on these.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

And this is out of date, but I think the interesting thing is that about half the genetic variation in humans is caused by these changes in gene number. And the other half of changes in human is due to A turning T, or adding a base, or losing a base. But some of these changes can be a million bases, they can be quite big, and contain many genes.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

This is a simplification of human genome, this is really what all human genomes look like. In all the chromosomes, you find regions where the copy number is either increased or decreased. And the reason these occur — and I speak now to experts — is, because of repetitive DNA, you get done crossing over, illegitimate crossing over. So the regions, the enzymes which are trying to do crossing over, think two regions are the same. They are the same, but they are located on different parts of the chromosome, and then you get this crossing over. So, one can say, given the human genome, copy number variations always occur. In fact they occur pretty commonly.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

What Wigler first essentially tried to do was to see whether you had a case of this in studying autism, the disease when children cannot speak and in some cases have extreme learning problems, their IQ is low, and their behavior is often repetitive, they are extremely frustrated. It's not surprising that their behavior is repetitive. As the human diseases go, the worst thing that can happen to parents is to have an autistic child. I mean it is very-very difficult to raise the child. What Wigler did was to look at DNA from when both parents seem normal and the child was autistic. And what they found was that about 10% of the autistic children lost rather big sections of DNA. So autism was caused by losing DNA, having one copy instead of two, but it could often be a region that would contain 20 genes.

Autism, before Wigler, was thought of as possibly only happening when several different genes made the child grow autistic. But it's a funny disease, because you get a deletion, and if the deleted chromosome becomes part of a boy, he becomes autistic. If the chromosome is in a girl, the girl will not be autistic. For some reason the ratio's about 5 : 1. So, some girls get autism, but many fewer than boys. If you get a girl, and she inherits an autistic chromosome, she can talk and all that. But half her sons will be autistic, because you have the bad chromosome, and if it goes to a boy, so. Essentially the chromosome will be lost in a couple of generations. It will appear in boys, and then will be gone.

So, autism, as we've just seen, is not due to pre-existing genes, but the creation of new genes. There was a theory which was proposed by a psychologist at the University of Chicago just after World War II. We had a school for autistic children, because parents couldn't handle them, and he observed that the mothers of autistic children, he said, had very little interest in their children. And he called them «iceberg mothers». So the cause of autism under that theory was that the child became autistic because there was no affection shown by the parent. And then people didn't like that. It sounds terrible. But probably the observation, which has been repeated by the English psychologist Simon Baron-Cohen, first in London and now in Cambridge, is that the women who are carriers of an autistic chromosome are slightly autistic and have no interest in children, or very little interest in children.

It looks like half of autism occurs just out of the blue, mothers have affection for children, and they aren't different from anyone else, but if they've inherited an autistic chromosome, that leads to lack of affection toward children.

So, why women are protected? Being protected, it slightly occurs, because of their children. Nothing nice about this result. What people are now trying to do is to make mouse models of autism, take the genes.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

The trouble is that most of autism will probably be due to a mutation which is just new and isn't the same as a pre-existing change.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

There is a second complication, a real complication about autism. There was a condition called Asperger's syndrome, where the children have normal intelligence, but very poor social interactions. Now it's called a type of autism. And it's more common than conventional autism. And so the frequency of autism, which, it was used to be said, was one in a thousand children, gets close to one in a hundred, if you include Asperger's. These are people who are obsessive, don't interact well with other people, but can be sometimes extremely bright. And ratio of boys to girls is 10 : 1.

People have written that Bill Gates is Asperger's. He enjoyed computers as opposed to people. Whether it's true, and whether it's right or wrong. Some now are writing that Einstein was possibly a little autistic. And it may be true that half of the really talented mathematicians are somewhat Asperger's. So there is a connection between Asperger's syndrome and mathematics, which will be very interesting to work out, because some mathematicians are very good with people, but even when I was a boy I was told that mathematicians were strange. So I think there's probably some truth to it. The most extreme are the idiot savants, who can do these fantastic calculations and who virtually are hopeless by themselves. They are idiotic, that's how you'd call them.

So to me it seems possible that there has been a selection against mathematical ability in many societies. Because it makes you worse with people.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

We are just at the beginning of studying it. Initially we thought this copy number was about 10% of autism. But now, with the DNA chip technology that lets you look at smaller and smaller copy number variations, it certainly can be at least 30%. And maybe 50% — small ones are harder to study.

Half of human genetic diseases may be due to these sorts of changes, and the other half are more conventional type of when one base changes into another. But if you want to work at the genomic level, DNA sequencing has been, until recently, too expensive. The big change is that soon, through copy number variation, we will discover regions of DNA which were removed or too much of and lead to autism. Then we will sequence large numbers of autistic people to see how much of autism is caused by conventional mutations. So that 10% will go down to 50% as the technology gets better. And maybe snips that haven't been discovered. We will see.

So, autism is inheritable once the gene is first inserted into a woman. Then it can be inherited.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

Then I want to say a little about schizophrenia. Conventional genetics was pretty disappointing. There were initial hopes that schizophrenia might be caused by only a few changes. But if I can keep the conclusion, we think schizophrenia will be much like autism, and a very large number of different changes in different genes upset the functioning of the nervous system. So you either end up with autism or schizophrenia. But I should emphasize: we are just at the very-very beginning. So almost everything I say could be wrong — except I don't think so.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

This is essentially what we do.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

We're beginning to see copy number variation in schizophrenia, but in a large number of different cases, different genes.

This is the sum of MIT and our own lab. Even though we were in a sense competing with them, my team was talking to them all the time, so we shared the information. The probability values are too low. I mean they're not good enough yet. So it's our impression we'll probably have to look at 30,000 people with schizophrenia before we get an idea of the universal changes. It costs right now about a thousand dollars per person to look, if the DNA has been collected for some other reason, just under our work. And so 30,000 demands 30 million dollars. So the sums of money are large.

I should say, where did we get the money to spend millions of dollars? It didn't come from the government, it came from parents who had autistic or mentally ill children. All the work in autism is supported by a foundation set up by the mathematician Jim Simons, who gave up being head of the math department at Stony Brook to become a financial investor. And last year he himself made three billion dollars — through mathematics. But he has an autistic daughter. He supports that work, and there is another family called Stanley, who have a bipolar son, and they already have pledged about 200 million dollars to study schizophrenia and bipolar disease.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

One thing we're discovering now is that we are finding genetic regions where if you get changes, sometimes it leads to autism, sometimes to schizophrenia. And we don't understand why.

This child was called normal. But he had attention-deficit disorder. It really looks like it's a dominant gene, whatever the effect is. So it's going to be complicated in that you get a change to the nervous system which, depending on your other exact genetic composition, could lead to any depression or so on.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

This is just evidence, for those who are experts, what the changes look like. Region of 22 has been long known to be unstable.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

This is a new regulant.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

To finally summarize, we've only looked at about 200 cases, and in people with schizophrenia we are observing copy number changes which we've never seen before, that you don't see in normal people.

Презентация лекции Джеймса Уотсона «ДНК и мозг: в поисках генов психических заболеваний». Дом ученых. 3 июля 2008 года

They largely occur in genes which control the functioning of the nervous system. The frequency of schizophrenia is generally said to be the same world around, 1%. And it's been debated, are the changes dominant or recessive. I won't go into the reasons, but it increasingly looks like they are at least semidominant. So that if one of the parents has schizophrenia, half the children will have some abnormality, though in many cases it will not be schizophrenia. But the child will be not quite normal.

Schizophrenia is a real horror of a disease: in opposition to bipolar disease, it's accompanied by the lowering IQ by about 15 points. This IQ difference goes back to early childhood. So from early childhood the nervous system is not working well. And it's not just conventional learning. Children who are going to be schizophrenic walk four months later. Walking you have to learn.

It won't be true of everyone. Since so many genes are involved, I must oversimplify. But schizophrenia can cause, since some first days, a weakening of cognition in learning, which in later life — generally after adolescence or during adolescence — can lead to psychosis.

The drugs which are used to treat schizophrenia control the psychosis and have no effect on cognition. There are many exceptions, but having a low IQ increases the probability of having schizophrenia. Whereas bipolar disease seems to be, if anything, the mania. If it's not accompanied by depressive psychosis, it can make you more productive.

So, the message, I guess, — I'll just conclude — is that the genomic techniques have proven without a doubt that schizophrenia has a genetic component; it's going to be very complex; and probably we'll be lucky if we really have the main picture clear in five years, but simply in 10. Once the genes can be isolated, then we will put these mutant genes in mice and see if you could cure mice. Mice don't get schizophrenia, but when you put the gene in, he behaves slightly, you know, — their social interactions decrease. So there is something in common.

I think it's going to be very exciting. Then you can say, well, why am I so focused on schizophrenia? It's very simple. About the time we were thinking of starting the Human Genome Project, we began to worry that my elder son was schizophrenic. And yes. So it was the realization that we were unlikely ever to understand the disease until we really got the human genome. And then, until we got the technologies to reduce the cost, we would never be able to do it. I have hopes that within five years we will know enough, so I could look at my son and find out what's wrong. It doesn't mean I'll be able to cure him, but at least we will know what's wrong.

Now it's the time to study the genetics of psychiatric diseases, and the real way is getting family history and all that, plus DNA.

And, just to say something about the cost of doing a complete genome. My genome was done for a cost of a million dollars. That was 18 months ago. Recently two people have been sequenced using a different technology, cheaper one, for a hundred thousand dollars. And probably within five years, for the cost of a cheap American or Russian car, you could get your whole DNA sequence. I don't advise people getting sequenced as opposed to buying a car, but if your son or daughter isn't behaving normally, maybe then you should look at the DNA. I don't think you will look at the DNA and predict if someone will be schizophrenic, I think that we're so far from that level of knowledge, but it's very satisfying to me to think that if I can live another 10 years and then we will understand schizophrenia.

To end it, people who are working on schizophrenia over the next few years will not be bored. They will be doing something and should be excited.

So, that's my message.

And again I say how happy I am to be back again seeing my friends in Moscow.

*  *  *

A. Piotrovskaya, executive director of Dynasty Foundation. Добрый вечер. Позвольте мне, собственно, от лица фонда «Династия» и от вас от всех поблагодарить господина Уотсона за столь интересную лекцию.


У нас есть время для вопросов, и в помощь нам в этом процессе я хочу пригласить на сцену Николая Казимировича Янковского, члена-корреспондента РАН и директора Института общей генетики РАН. Спасибо большое.

В зале находятся девушки с микрофонами. Пожалуйста, желающие задать вопросы, поднимайте руки, девушки к вам подойдут.English 2

N. Yankovsky. Так, ну, наверное, сначала молодым, и особенно сначала девушкам. Прошу вас.English 3

Question. А какие еще болезни вы хотите изучать, кроме шизофрении и аутизма?English 4

J. D. Watson. I think we will just go through, to start with, all forms of mental disorder: serious depression, we will just go through everything. Then, finally, you can do things which sound silly: you could find out why some people are happy when they should be unhappy. You know, people who are too happy. This century will see the coming together of psychology and biology.

Question. Здравствуйте. Считается, что вы самый выдающийся ученый XX века, из ныне живущих. Многие ученые становятся жертвами науки, и уделяют больше времени науке, чем семье. Если это не так в вашем случае, то как вам это удалось?English 5

J. D. Watson. I think it was so, in my case: I got married when I was 40. So I didn't have children when I was really running a lab. So I could really be more effective. On the other hand, there were no women in my life. So I was rather lonely.

Question. Несколько лет назад я прочла статью о трехцепочечной ДНК. Скажите, пожалуйста, возможна ли такая структура?English 6

J. D. Watson. I really don't know enough to answer your question. I made three-stranded DNA structures about 50 years ago, and so, you know — I can't answer.

Question. Господин Уотсон! Как известно, около двухсот тысяч белков, открытых ныне, определяют взаимодействие организмов с окружающим миром и все внутренние процессы. И примерно полтора или два процента наследственного аппарата кодируют эти двести тысяч белков. Как на ваш взгляд, для чего природа заложила в геном, в наследственный аппарат человека такой огромный ресурс, который пока не реализуется? Спасибо.English 7

J. D. Watson. The question is, why do we have more proteins than we have genes, and the answer is the phenomenon of RNA splicing, where the original RNA molecules are processed in slightly different ways, using different numbers of proteins. In some cases, there is the potential for an extraordinary number of different proteins. How important this will be, I do not know, but some mutations are going to affect splicing, and protein defects will be the cause of the disease. I can't be more specific.

Question. I think I will ask in English, because it would be just faster. I want to ask not about science, but about funding of science. What do you think, is it OK, the situation, the current situation with science, that most scientists, after they have their PhD, they have to go to technology companies, because the salaries are incomparable. And in fact the Genome Project was finished only with the help of Celera Genomics, and other biotechnology companies. And is it OK? What do you think about the current way of science? Should it be changed or not?

J. D. Watson. The way of science was very different when I was young, because there were very few scientists, and the amount of money per scientist was much greater, because they were fewer in numbers. But at that time, the only jobs were academic jobs. I think we probably would expect that many people trained with PhDs will go to work in industry, or become journalists, or become the government. And I think that will be a very good thing, because, at least in the United States, we don't have enough technical competence in our government. So I think we really have to expect that we're training people to show them the scientific method, how you do it, but then you will go out, and your career will not necessarily have any connection to what your PhD thesis was about. That's both good and bad. But I think, at least in the United States, we have a shortage of well-trained people to run our country. And the general thing, the salaries of scientists are far too low. And I am sure, right now, people in Russia who would have become scientists now want to become businessmen, because they can buy a better car, or have a car at all. On the other hand, that is not necessarily a bad thing for Russia right now, because you have to get your business going to generate the money to pay for the science. So, having bright people going to business, it is not a bad idea.

Question. Здравствуйте. Скажите, пожалуйста, а если исследовать не только болезни, какие еще перспективы может дать изучение работы генов, отвечающих за функции головного мозга?English 8

J. D. Watson. Yes, it's whether the genome is only useful for disease. I think it will eventually tell us a great deal about human personality, our emotions. And so it won't just be disease, but just what makes us human in an interesting way. You know, I've always viewed human beings as products of evolution. And so, through studying human DNA you better understand what human beings are. And what motivates people. Then there is, you know, biotechnology. Which Russia has, like other European countries, not given enough emphasis to. It's been America and China now. I think there is an enormous use of genomic DNA methods in producing useful commercial products. And, hopefully, we will get new sources of energy through getting better enzymes. Just trying to improve human life. So I think people who've really become experts at DNA should — you know, if they also have common sense — will succeed at life.

Question. Professor Watson, could you please comment on the work of the well-known psychologist Arthur Jensen, who claimed that the human intelligence has an inheritable genetic component, and about how this is related probably to the recent scandal in which you were involved personally?

J. D. Watson. Well, I never would intentionally have made that statement, which greatly embarrassed me, and I apologized for it. The general statement of Jensen, that human intelligence has a genetic component, is a total fact. There is no doubt about that. It's really the variation between different people, the origin of nature versus nurture, but it's not at all surprising that our abilities are a function of genes. You know, if our brain works very well, we'll be more successful. And, unfortunately, you know, there seems to be a difference of abilities that is at least shown by tests. What those tests mean deeply, I don't want to say. But I don't think you — it's unfair to say that Arthur Jensen was an evil man. He was treated as an evil person, but he was not. He was a very good psychologist.

Question. Доктор Уотсон, при изучении таких умственных расстройств, о которых вы говорили, возникает масса этических проблем. И у меня вопрос следующий. Каков ваш прогноз, по какому пути пойдет общество, когда будут уже изучены все гены, влияющие на развитие шизофрении и аутизма, — по пути абортов тех плодов, которые могут в последующем развить эти заболевания, или по пути все-таки лечения их?English 9

J. D. Watson. I want just to articulate it, that geneticists did not create the ethical problems, we have life today without genetics filled with ethical things. Some people succeed, some don't succeed. How do you prevent the growing inequality in society? I think we will — through the knowledge of the genome — we will at least know what's the true nature of the problems that society faces. And I think we will treat each other better. You know, as an example, we sort of blame mathematicians because they are not more social. But maybe they can't be, so we shouldn't blame them, we should just be very lucky that they are good mathematicians, instead of saying, you know, they are not going to be good on a television program.

Question. У меня вопрос касательно прошлой лекции. Господин Уотсон, как вы можете объяснить нестабильность генома раковых клеток? Не только от ткани к ткани, но и от поколения к поколению?English 10

J. D. Watson. I think that question is too technical for me, with that to try and answer it here.

Question. Доктор Уотсон, у меня вопрос следующий. Я хотел спросить, исследовались ли эти дупликации, о которых вы говорили в своем докладе, у других приматов. И, в связи с этим, следующий вопрос: могут ли эти дупликации играть роль в видообразовании — скажем, в появлении человека как вида?English 11

J. D. Watson. Well, if you look at chromosomes of different species, they are often quite different. And that shows there's a lot of evolution at the level of these chromosomal changes. So, the changes I've been talking about are very important — will probably turn out to be very important factors in evolution. Even though most are harmful, some will be beneficial.

Question. Скажите, пожалуйста, как вы считаете, могут ли через 10 лет, или через 50, допустим, в школах по генетическому анализу определять способность детей, допустим, к математике, или к музыке, или к занятиям литературой, или к занятиям биологией, или это невозможно технически? Или, может быть, это и не врожденные способности, а всё зависит от воспитания? Спасибо.English 12

J. D. Watson. It's a very difficult question you asked — to what extent you should send children with different abilities to different schools? It certainly works for music. And so you want to let children to work at their abilities, and some children have many more abilities and should be allowed to move faster. So I don't think you'd want to put everyone in the same school. I was very lucky that I was taken and put into, you could say, a very elitist school, which trained me much better. It was sort of compatible with my own desire for learning.

Question. Скажите, пожалуйста... Известно, что психопатология, бывает, проявляется при разных метаболических расстройствах. С одной стороны. А с другой стороны, есть очень много генов, которые приписывают к шизофрении, и они все очень с маленьким эффектом. Может ли быть так, что каждому гену соответствует какое-то метаболическое расстройство, и это объединяется в шизофрению по формальному признаку? Что такой отдельной болезни нет? Может быть так?English 13

J. D. Watson. Well, I think our personalities are largely dictated by our genes, not by the way we've been raised. You're sort of born with your personality. What genes will — you know, it would be fun to study people who are exceptionally happy. We would probably learn something. So, I am for basically allowing — I think people should be allowed to satisfy their curiosity, by trying to find the genetic origin to human characteristics. Forbidding the search for finding these things, I think, would be, you know, a remarkable fascistic-type government that really doesn't want you to be free.

Question. Профессор Уотсон, у меня вопрос, я прошу прощения, не совсем по мозгу, скорее по структуре непосредственно ДНК. Вот открытая двухспиральная структура, она очень хорошо описана сейчас, посчитаны углы между разными группами атомов, и в принципе это преподается и подается как неотъемлемое свойство самой молекулы, такая конформация. Однако я недавно услышал, что сейчас теория разрабатывается о том, что такая структура — это не есть химическое свойство, а наоборот, поддерживается ферментами. И что ДНК, вполне устойчиво — возможно, чуть менее устойчиво, но всё равно вполне жизнеспособно, — может существовать в очень многих других конформациях.English 14

J. D. Watson. You are talking about other changes, other than the changes in the four letters? So, the epigenetics, chemically modifying the DNA by modifying the proteins around it. That could be — that's a very hot topic in biology, and I can't give you an answer of how important it be. We know that some of these changes seem to be involved in cancer, but it's not clear whether the majority, or even just a tiny minority. We don't know. That genes are not the total answer is shown by the fact that identical twins are not completely identical.

Question. Профессор Уотсон, известно, что вы, в ваших широчайших исследованиях, занимались и проблемой расовых отличий ДНК, что вызвало ажиотаж в кругах расистов. К сожалению, такие люди есть и в России, и ваше слово в этом отношении — это слово авторитета высочайшего значения. Можете ли вы сказать вот людям такого рода, что все расы все-таки равноправны и человечество едино?English 15

J. D. Watson. You know, I think, are there genetic differences between people in different parts of the world? Yes. All I want to say is when you have evolved in separate places and under separate environment, you should not expect the genes to be the same. Whether you, say, call it equal or unequal, but, you know, my skin is too light, so I get a lot of skin cancer. Other people have darker skin. So, to say that everyone in the world is essentially the same, that's not true. My son isn't the same. And mutations can be very devastating. And the belief that evolution has stopped, say, ten thousand years ago — that's probably just nonsense. It's just going on. And if you separate populations, they are going to go in different directions. I think the future will give the answer. I never wanted to be quoted in the newspaper about IQ, because I'm not an authority and I couldn't defend any statement I made, so I was very embarrassed that I seemingly insulted people that I did not wish to insult.

Question. Профессор Уотсон, ваш коллега Крик в 1972 году вместе с химиком Оргелом выпустил статью, посвященную панспермии. Не могли бы вы высказать свои взгляды на эту тему?English 16

J. D. Watson. I don't want to say anything about the origin of life. It occurred so far back, under conditions with which we really don't know what the Earth was like, three billion years ago. So I don't think we will ever know how life arose. But it doesn't bother me. I mean, there are just some things we can't find out. The main thing is to understand life as it now exists. It would be a big bonus if we could say this is how life came about, but I'm afraid we won't be able to. On the other hand, you should speculate about it. It's rather fun, if you're a chemist, to think how did life start.

N. Yankovsky. Нам осталось совсем чуть-чуть, и пройдет полтора часа, и мы сделаем перерыв — на несколько лет. И поэтому последние два вопроса.English 17

Question. Mr. Watson, did you know something new or something interesting about yourself from the sequence and annotation of your individual genome?

J. D. Watson. My own sequence, you know, is three billion letters, so I never looked at it. I'm relying on other people to tell me. Until you sequence a thousand of people — The only thing my sequence has told me is why my stomach aches when I eat ice-cream. Because I only have one copy of the good lactase gene. So milk is bad for me. That my genome told me. Otherwise, it has not changed my life at all. And I never expected it would probably change. But I thought that maybe I would get some information which would benefit my children. That they may be carriers of some genetic — you know, have one copy of some recessive disease gene. But we haven't found that. So I have no advice for my children. For a brief while, they told me I had a breast cancer gene. Which would then have a probability of being present in my nieces. But it turned out that the change which I had, they said you shouldn't call it breast cancer. So, you know, I haven't lost anything. I told people I did not want to know the structure of the gene for the protein apolipoprotein E, which is prognostic, slightly prognostic for Alzheimer's. I did not want to know whether I was at risk to get Alzheimer's, because I can't do anything about it. But I reached 80 without Alzheimer's, so I sort of figured out I'll reach 82. But you know, you can't really say. I have a grandmother who died of Alzheimer's, so I have one in four probability of inheriting the gene that made her sick. But, you know — I don't think people should — Craig Venter, he released his own genome, and he has one bad copy of the Alzheimer's promoting allele. So, unless we can cure Alzheimer's, Venter may be at risk, and ten years from now he may regret knowing that. But, you know, time will tell.

Question. Профессор Уотсон, скажите, пожалуйста, в какой степени ваши исследования подтверждают или опровергают философски-эволюционные обобщения Ричарда Докинза.English 18

J. D. Watson. You know, about Richard Dawkins, he is a very clever and intelligent person. And his book "The Selfish Gene" was a very provocative and I think correct book. Dawkins has written many books, and his latest is about religion, which I think it's best that I say nothing about.

Question. Профессор Уотсон, вы ничего не говорили о роли метилирования ДНК, в частности о метилировании X-хромосомы в аутизме. Что вы об этом думаете?English 19

J. D. Watson. Methylation of DNA. That methylation of X is an important current topic, and you could learn more by looking into your textbooks than I can tell you. It's not a field that I follow as closely now. OK.

N. Yankovsky. Thank you very much, Dr. Watson. Я предполагаю, что кто-то из организаторов дальше знает, что делать. Или мы просто скажем спасибо и всё? Тогда на этом закончена официальная часть. Спасибо, нам всем тоже, и спасибо вам!English 20


1 I am Academician Georgy Georgiev, and I open today’s session. A few words in Russian, and then English. Jim Watson and I have known each other for quite some time. In late sixties I for the first time visited his laboratory in Harvard, where Jim was just explaining to me the new interesting achievements of his lab in the regulation of gene expression. Then Jim, who had already been here, many times visited our institute, and was a guest of many of our scientists at home. We also were his guests in his home, in Cold Spring Harbor, where he worked for forty years and where he founded a very strong scientific school. Well, this is, so to speak, a couple of words in Russian, and now —...

2 Good evening. I would like to thank Dr. Watson, that is, from Dynasty Foundation, and from all of you, for this interesting talk. We have some time for questions, and I’d like to call onstage Nikolay Kazimirovich Yankovsky, corresponding member of the Russian Academy of Sciences and director of the Institute of General Genetics of RAS. Thank you. There are girls with microphones in this room. Who wants to ask questions, please raise your hand, and the girls will come to you.

3 So, well, probably let’s first have questions from the younger persons, and especially ladies first.

4 And what other disorders you plan to study, besides schizophrenia and autism?

5 You are considered the most prominent living scientist of the 20th century. Many scientists eventually become victims of science, and spend more time on science than on family. If this is not so in your case, how did you manage to avoid this?

6 A few years ago, I read an article about three-stranded DNA. Could you please say whether such a structure is possible?

7 Mr. Watson, it is known that around two hundred thousand proteins discovered by now determine the interactions of the organism with the environment and all the internal functions. And around one and a half or two per cent of the hereditary apparatus encode these two hundred thousand proteins. What do you think is the reason for nature to have provided the genome, the hereditary apparatus of humans, with such a large resource, which is not being realized so far?

8 Could you please say, if we do something besides research on diseases, what perspectives can the study of genes responsible for brain functions can give us?

9 Dr. Watson, when such mental disorders as those you discussed are studied, a great many ethical problems arise. And I have the following question. What’s your prediction, what way shall society take, when all the genes that influence the development of schizophrenia and autism will be already known, the way of terminating pregnancies with fetuses that may in the future develop these diseases, or the way of, after all, treating them?

10 I have a question related to your previous lecture. Mr. Watson, how could you explain the instability of cancer cell genome? Not only from tissue to tissue, but also from generation to generation?

11 Dr. Watson, I have the following question. I would like to ask you, were these duplications, which you discussed in your talk, studied in other primates? And another question, related to this one: can these duplications play some part in specification — say, in the emergence of our species?

12 Could you tell, do you think that in 10 years, or maybe in 50, they will determine the abilities of kids at school in such fields as maths, or music, or literature, or biology, by genetic analysis, or is it techinically impossible? Or maybe these abilities are not inherited, but everything depends on the upbringing? Thank you.

13 Could you please say... It is known that psychopathy sometimes emerges under different metabolic disorders. On the one hand. And, on the other hand, there are many genes that are attributed to schizophrenia, and all of them have very little effect. Could it be that each gene is related to some particular metabolic disorder, and all these cases are considered schizophrenia formally? That there is no such single disease? Could that be? (The interpreter evidently mistranslated this question, so the answer of Dr. Watson is, in fact, to a different question. — Translator’s note.)

14 Professor Watson, I have a question, I’m sorry, not exactly about the brain, but rather on the structure of DNA itself. The double-helical structure that was discovered, it is very well described today, all the angles between different groups of atoms have been calculated. And they teach it and present it as an inherent property of the molecule, this confirmation. But I have heard not long ago that they now develop this theory, that such a structure is not a chemical property, it is, on the contrary, supported by enzymes. And that DNA can be quite stable — maybe not as stable, but still quite viable — can exist in very many other conformations.

15 Professor Watson, it is known that you, in your wide scope of research, studied also the question of racial differences in DNA, which caused some excitement among racists. Unfortunately, we have such people in Russia as well, and your word in this field has very much authority. Could you tell them, people of this sort, that all the races have equal rights after all, and that humanity is united?

16 Professor Watson, your colleague Crick, together with the chemist Orgel, published a paper on panspermia in 1972. Could you express your opinion on this subject?

17 We have but very little time now, and an hour and a half will be over, and we’ll make a break — for a few years. So, the last two questions, please.

18 Professor Watson, could you please tell to what degree your studies prove or disprove the philosophical evolutionary generalizations of Richard Dawkins?

19 Professor Watson, you did not say anything about the role of DNA methylation, in particular, X chromosome methylation in autism. What do you think about it

20 I think some of those who organized the talk now knows what to do next. Or shall we just say thank you and that’s all? Then let’s finish the official part. Thanks, to us all too, and thanks to you!

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