A conversation with the molecular biologist who co-discovered DNA.
James Watson: I’m James Watson, the co-discoverer of the double helical structure of DNA in 1953.
Question: What was the key breakthrough that led to the discovery of DNA?
James Watson: Well, there were two. A methodological one, where we borrowed from Linus Pauling, that the most direct route to the structure was building molecular models as opposed to trying to deduce the structure entirely from x-ray defraction data. There was a decision that Crick and I made in October, 1951.
The second was the realization that the data of Erwin Chargaff showing similar amounts of adenine and thymine and timing and of guanine and cytosine indicated that they must be paired to each other in the DNA structure. Once you had that, in fact the structure followed within several weeks.
Question: Did your inability to find a date at Cambridge contribute to your discovery of DNA?
James Watson: The best thing that ever happened to me was I didn’t find a date because that would have... you know, the right girl I would have found more interesting than the, you know. If I had a girl to play tennis or something, I would have preferred doing that than just, you know, thinking about DNA. Whereas my great advantage was, I was at the time the only person truly obsessive about DNA. And you know, so many people were just obsessive about some unrealized you know, emotional problem. So at Cambridge University, I mean, today Cambridge University is filled with, you know, well-dressed, attractive, intelligent girls. The two Cambridge colleges when I was there, the girls were out of town, we virtually never saw them and you know. It was just lucky it was for a later time in my life.
Question: Have you been happy with the progress in molecular biology since you discovered DNA?
James Watson: Well, initially I wanted to you know, move on from the structure of DNA to RNA and that didn’t seem to fall out, so that was a disappointment. But on the whole, it was that everything occurred faster than we thought it would. That you know, we had the genetic code, the first details in '61, and its completion by '66. That was only 13 years. And I never thought it would go so fast.
And then, I never even dreamed, you know, that we would be able to sequence long stretches of DNA. You would actually see the structure of specific genes. Then we were likely thinking in terms of small viruses because we knew they contained only several genes. And so maybe the ultimate would be to some day work out the structure of a sequence of a virus containing several thousand letters. But once it started it just has moved, you know, with always... You know, we had the method before we almost had the questions to ask about what we were seeing.
Question: You were the second person, after Craig Venter, to have your genome sequenced; what did you learn?
James Watson: Not much. I learned that I had a polymorphism, which meant that I metabolized some important drugs more slowly and therefore they would pose greater risk to me if I took too much of them. So that was a very useful fact. And so, if I was you know, suddenly to go psychotic and they gave me an anti-psychotic, unless they were careful they could kill me with it. And you know, you’d just think it was an overdose, but no, it was my genes.
Then I sort of confirmed my hunch that I digested milk poorly, that... if I had a large consumption of ice cream. And I had noticed something was strange when I was working out the DNA structure, I was having constant stomach pains which other people were saying, “Well you’re just nervous about racing or with Linus Pauling.” But it was in fact, I’m still trying to be like an American and drinking a quart a day. And by that time I had lost the... was losing the ability to digest lactose.
Question: What did you choose not to learn about your genome?
James Watson: I chose not to find out whether I had a serious risk for Alzheimer’s. And at the time, you know, it was a little murky. It’s getting much clearer now. So Craig Venter, who put his entire sequence on, it came out that he’s at risk. But he could probably define the risk better by looking at the sequence today as opposed to a few years ago.
Question: How much does it cost to sequence a genome today?
James Watson: Well, I think it’s still, to be honest, about $20,000. There’s always a question about how you do the accounting and so on, but the cost of the reagents that you put into the machine and how often do you use the machine. So, but there’s a lot who believe it’s going to fall by another factor of 10, certainly within 10 years and maybe a soon as three or four. At which point then, the cost of you know, sequence scanning will be essentially trivial and the whole cost will then go toward interpreting it.
Question: Is Craig Venter a great biologist or a great marketer?
James Watson: Well, he’s certainly a great marketer. He’s highly intelligent and he certainly pushed us toward completing the human genome project sooner than we would have otherwise, and it was a very good thing he existed. Though, at the time, I feared his winning because then the human genome project would belong to... the data belong to his company. And I thought that was just going to slow things down.
So normally I’d like, you know, data to be obtained as fast as possible, but not if it went into private hands. You know, some DNA sequences have been patented and monopoly situations which have basically slowed down research and have made medical testing more expensive.
Question: Is Venter’s creation of synthetic life as game-changing as he has painted it to be?
James Watson: I don’t think about it at all. To me it’s not. But I’m not a chemist, and I’ve been so focused on getting enough knowledge so we can cure cancer that I’ll just stay focused on that and let other people... I don’t think we’re going to, you know, this idea of creating a new form of life, we’re just making a very close mimic to what already exists. So I wouldn’t say it’s a new form of life at all. It’s just a very... but always a question is, could there be a life form, you know, basically in some inaccessible place. You know, like deep in the oceans where a form of life which is totally dependent on RNA exits. That would be, you know, a bombshell of unbelievable proportions.
And so if someone said they found that, I would just say: "Wonderful." But I don’t expect them to find it. And so, and then you’d know if you could be in another solar system there might be other forms of life, but again, I only like to think about things which I know we’ll have a chance of knowing whether we’re right or wrong. I never could read science fiction. I was just uninterested in it. And you know, I don’t like to read novels where the hero just goes beyond what I think could exist. And it doesn’t interest me because I’m not learning anything about something I’ll actually have to deal with. So, where you would put Frankenstein, I don’t know, but he never intrigued me, I must confess. You know, in a movie you can make up those sort of things, but... well a lot Steven Spielberg just turns me... and the whole Harry Potter thing, I just don’t want to watch it because to me it’s not reality.
Question: Do you spend much time reading scientific journals?
James Watson: Well I think I have to... if I want to... I’d like to say three hours per day, but that you know, probably in a day when I’m on my desk and not in New York City or something. But I think I would read more than most people, even those younger than me who are so busy doing things. So I have the leisure time actually to read. And I think that’s what we’ve lost now in sort of science today is leisure.
Now Crick and I had plenty of leisure because nothing was happening when we were trying to find the DNA structure. There was, you know, there weren’t hundreds of new facts appearing almost every week that we might learn about. And now people lead, defensively, want to be sure that they’re... you know, people will think they are experts, so they’ve become more and more narrow experts and not very broad. And I still can’t get over when I was at a pharmaceutical company, they half-jokingly but I’m sure the reality was true. They had 1000 PhD technicians. As you got your PhD, you were just a technician. No one was... you were hiring you for a very narrow thing and not to show any big thoughts at all. So, with so many facts, what I miss now are thinkers. The [...] were smart.
Now when I was a boy, you know, smart people were respected, now it’s, you know, people do things, who do it. And also you find that there hasn’t been one person doing it; there are 50 names on the paper. And our famous paper for instance, mine, could have included Morris Wilkins’ name on it because he was really part of it. He didn’t make the discovery, but he was you know, part of the stuff just before it. So we asked him to put his name on the paper, and he said, no. That would have been a three-person paper.
But, the... I worry about people really thinking big. I don’t find many people who do so now. When I was a student at the University of Chicago, Robert Hutchens in his speech, said “The function of the College of the University of the Chicago was to prepare you for greatness.” He used those words because our education was largely reading the great books. And you were reading the great books, not to be a teacher, but to let you go beyond the great books and produce another great book. So, that was how he saw it. Of course, he would know that that would happen very often, but it was still there that...
And it’s certainly in dreams of people, you know, that they do something big. Most of the time they keep it secret because you know, it’s more realistic and often then you get braggarts who tell you, you know, they’re doing something great and you don’t believe them. But nonetheless, you know, in some sort of quiet way, you should have big dreams.
Question: How can we encourage this in our education system?
James Watson: I think stop having 50 names on a paper. Just you know, accept the fact that the rest really didn’t think at all about it. And you should really, you know, were just technicians, you know, in a real sense—and reserve authorship for people who put together the sentences. I mean, now, you know, put together the answer. Whereas, I feel it very unsatisfactory to be the mother of a scientist now. And after son handed in a paper where there were 20 other people on the paper. And she’d wonder, "Is he going anywhere?"
So, and another problem may be, though it is against everything we now say, we may be training too many scientists. That is, we’re training people who really don’t want to think, they just want to have jobs. And they consume money. And so you’d lose some, you know, if you cut out people who didn’t have real dreams. But if you go into science, I think you better go in with a dream that maybe you too will get a Nobel Prize. It’s not that I went in and I thought I was very bright and I was going to get one, but I’ll confess, you know, I knew what it was. And Crick’s thinking was otherwise, but the moment I saw that structure I thought: “We’re gonna get a Nobel Prize.” I knew it in five minutes, it was so obvious.
Question: What was Rosalind Franklin’s role in the discovery of DNA?
James Watson: She provided the... some crucial pieces of information. Her great handicap, which I would now say we would use the term Asperger’s, she didn’t know how to deal with other people; didn’t know how to ask for help. And, if anything, probably paranoid about people stealing her data. And if she’d come out to Cambridge and shown her data to Crick, she... Crick would have told her how to solve her problem. She had a clue, but she didn’t know how to interpret it, and Francis would have immediately have told her what it was because his own work in Cambridge, just by accident, had let him deal with that problem. So he could have told her, and she had gone back to London and he would have said, "You know, there are two chains and she said the phosphoruses were on the outside then they would have to be held together by the bases. And once you say that, you are very close to the structure.
So... I don’t think her name deserved to be on the paper, I mean, she really fought bitterly saying it was the helix, and didn’t collaborate. And because of her... her failure to interact effectively, it was hard to know how bright she was, and why she was so strongly against it being a helix. I don’t know. You know, afterwards, I would never ask her those questions, we were not... afterwards we weren’t at all unpleasant to each other, we liked to talk to each other. I mean we could you know, talk to each other. But I never asked her if she wanted to spontaneously say something, but she never did.
Question: How successful is cancer treatment now?
James Watson: Oh, we are now highly successful with about 20% of cancer. In fact, initially, you know, we can do something. The problem is, that cancers tend to get more dangerous and resistant to chemotherapy. And today we postpone a lot of deaths from cancer, but we don’t finally prevent enough of them. So that if there was no cancer research, 700,000 Americans would die of cancer every year, today 600,000. A lot of them live longer now, and that’s good. I’d like to move to a situation where you know we only lose 100,000 each year—that is, we've prolonged it enough. And I think there’s a real chance we can move to such a situation over the next decade.
Question: What are the most exciting avenues of cancer research?
James Watson: Well, now we’ve been focusing on sort of the organized cell, what we call the epithelial cell. Most human cancers are of tissues lining glands and they’re likely touching each other so liquids don’t pass through the membranes, et cetera. But then there are other cells in our body which are not tightly organized and mobile. We call them mesenchymal. And most cancers progress toward a mesenchymal form, which up to now we’ve not very successfully treated.
But I think we... I think there’s the hope, or it’s my hope, that whereas we know there are many different forms of cancer to start with, they all progress toward something similar, in a sense, similar to a stem cell, a differentiated stem cell. So that if you’re killed by prostate cancer, it may be not that different than being, you know, dying from lung cancer or a melanoma. That is, the bad cells have roughly the same biochemistry, underlying biochemistry. And so if we can kill one of the sort of terminal-stage cancer, we might be able to do all of it. At least, that’s my hope. I know there are few other people who think my way, but the slogan you get now is: "They’re all going to be genetically different. And we’ll have to use personalized therapy.”
Well, before I was treated I would like my DNA to be looked at. But the best way to finally cure me would be not to focus on the unique features, but the features common to all cancer cells.
Question: What is the state of mental illness research?
James Watson: In the case of the brain, you know, you have disorganized thinking. But we don’t know what thinking is. So, you can’t look at... and say it’s not thinking right. So we didn’t come to, you know, a real chance to fight back against cancer until we do the basic, say laws in which DNA operated. And then finding how chromosomes divide, et cetera, and all those details.
Once we had that, then we could ask what... I guess why does the cancer cell behave differently? The case of the brain is clearly so complicated that in reality, about the only people that think about the brain are outsiders who are not capable of understanding it. That is the people who are sort of bright enough, or you know, trained enough know how inherently complex it is. And Francis Crick spent 20 years trying to think about it. In the end, nothing came out of it.
So, you know, in a perverse way, I think the only people that really know should think about how the brain operates are those people who deal with schizophrenia or bipolar disease where you know the brain just doesn’t work. So because for the most part the people who study it, who only got into the field because they have a child or they have a sister or a brother or, you know, you’re in it because you want to cure someone.
So we can take away delusions from people with schizophrenia, but they’re very cognitively impaired and we don’t know how to repair the cognition defects. And that’s why the become homeless if there’s no one taking care of them; they just really can’t look after themselves. So the thought that you can teach the homeless to take care of themselves. No, we have to take care of them.
Question: You have a personal interest in this?
James Watson: Yes. I have a son, who is a... not an ordinary form of schizophrenia, but clearly, cannot take care of himself. And the great fear of then, of all parents is, when the parents die, who takes care of your child? And the answer is: they become homeless. You know, unless there is sufficient money in the family or something, but, given the structure of society today... The mentally ill are treated very cruelly. We sort of deny their existence. Congress has virtually no interest in them. A great interest in cancer, but no interest... no one wants to hold a hearing on it.
Question: Do you think mental disorders like schizophrenia are strongly genetic?
James Watson: I would say, predisposition 100%. Whether it progresses to full-blown schizophrenia, probably some environmental influences, such as... It’s clear that if you’re pre-disposed to schizophrenia, smoking marijuana will tip you over. But marijuana won’t tip over someone into schizophrenia that is probably not predisposed to it. So, you know, most people smoke it and, you know, do not end up in mental hospitals. But some do.
Question: How will science pinpoint the genetic components of mental disorders?
James Watson: We’ve sort or proposed, you know, sequencing 100,000 in mental ill people because it’s not going to be just one gene that’s... you know, you can stop a car from functioning by, you know, destroying a large number of different parts. And the same way you can sort of put the brain and make it dysfunctional by just destroying one small part of a whole operating system. So, we’re pretty sure there’s at least hundreds of genes. But we think they will be put together where there will be some pathway to this schizophrenia, by which we can intervene in some cases.
And it’s too complicated now for me to say, but it may be even though many genes are involved, the way the brain works may nonetheless enable us to cure some. Some cases of autism, which look as hopeless as anything is that when people have abnormally high temperature and fever their symptoms diminish.
Now, so you think, well just raise their temperature a couple of degrees and they won’t be so sick. We’re in fact going to have a meeting about this. So, I’m dominated you know, I want to... we have to get the genetic information, but as a parent, I want something good to happen, you know, over the next five to 10 years.
Question: How much do we know about the genetic components of behavior?
James Watson: We know in animals there’s sort of forms that are called instinctive. And I think you know, I tell everyone, I think this century which you know, has another 90 years to run, will be the century you know, when psychology becomes a science. You know, that when our chief focus will move—hopefully after we’ve got on top of most cancer—toward understanding healthy aspects. You know, why we behave differently and, you know, very practical things; trying to get better ways to stop depression and so on.
Most psychology departments, when we get near them, are not science departments. And so, you know, people say well you have to have something called cognitive science. I’d like to believe, you know, that people would actually like to know the truth about themselves. But certainly some people would not want you to study whether in anyway men and women are any different. You know, seeing if you discover differences, it would just perpetuate wrong behavior. Likewise, they really don’t want to really measure intelligence because they don’t want intelligence to be something you are born with as opposed to having it been largely determined by how you grow up.
So psychology departments now are just not as bad as anthropology, but almost as bad. Just totally dominated by political correctness. Which to me, you know... in the past, political correctness has never been a way to more toward the truth. It’s like, you know, saying something is religiously correct. You start from that.
Question: So there are genetic differences in intelligence?
James Watson: Yes. You know. How much they are we know very little. But because we don’t want to pinpoint some people as unable to learn—unless it’s so bad that you have to. We’re sort of avoiding maybe learning some how and some day to make our brains work better. I worry now that human life in day-by-day life has got more difficult because it’s just so complex and that more and more people aren’t really equal to the complexities of current life. And I think that may underlie this, you know, awful phenomena of the rich people getting so rich because they’re just using their, you know, innate intelligence to think faster and to seize opportunities faster. And you know, there could be other reasons. You know, there are other reasons. Last night my wife and I saw "Wall Street," you know, far from a perfect movie, but, to say the least, thought-provoking.
Question: Are men genetically smarter than women?
James Watson: On the intelligence tests, men do worse in verbal things and they’re able to do spatial things better. And this has been related, whether correctly or wrongly, to our past evolutionary role as hunter/gatherers where we really had to strike out and be able to find home again. So we had to really look at visual clues and think constantly about where we are. Whereas women were, you know, staying in a fixed place. Whether that’s right or wrong, but the truth is that we only have IQ tests which makes the sexes essentially the same because we adjust the tests so that they contain some questions which girls would do better on and some which would be a boy. And you can bias the tests and then one sex or the other would be called the brightest.
There is a fact that at the ends of these curves of intelligence, there are more boys. Many more mentally retarded boys than girls, and at the extreme highest level, but not really very important. There seem to be more boy, you know... true math geniuses... but true math genius is so often accompanied by you know, strange behavior or anti-social behavior. It’s not clear that people really want to give birth to boys at those ends of the curves, either end.
Recorded on September 28, 2010
Interviewed by Paul Hoffman