THINKING ALLOWED
Conversations On The Leading Edge
Of Knowledge and Discovery
With Dr. Jeffrey Mishlove

JEFFREY MISHLOVE, Ph.D.: Hello and welcome. I'm Jeffrey Mishlove. This is Part 2 of a two-part series on "The Scientific Search for the Soul." With me is one of the world's great scientists of the twentieth century, Dr. Francis Crick, who received the Nobel Prize in 1962 for his discovery of DNA. Dr. Crick is the author of Life Itself, What Mad Pursuit?, and The Astonishing Hypothesis, and he is a faculty member at the Salk Institute in San Diego, California. Welcome again, Francis.

FRANCIS CRICK, Ph.D.: Thank you.

MISHLOVE: In Part 1 of this program we explored many different ideas related to your "astonishing hypothesis" that the neuron and the neural system, billions of neurons interacting together, form the basis of consciousness. We've talked about reverberating circuits in the brain and many of the different nuances of the science of neurology. I'd like to begin now by looking at the process of attention. Back in the last century, neurologists, and of course the great American psychologist William James, wrote about attention as being fundamental to the idea of human consciousness.

CRICK: Well, of course we're mainly interested in the visual system, and you can say roughly there are two forms of attention. One is the very obvious one, like you move your eyes, because you only see very clearly in the very center of your visual field, as you can easily tell by looking here and then trying to see what there is out here. So when you're interested in something, then you move your eyes. But psychologists have shown that even when your eyes are stationary, between the eye movements, there appears to be a mechanism which is moving around in some way. They're not totally agreed exactly how it should be described. Some things, when you look at them, pop out, no matter how many what are called distractors there are around the field, and so on. Other things, you have to search; that's the impression it gives. The more distractors there are, the longer it takes to look.

MISHLOVE: Now, what is a distractor?

CRICK: Well, suppose you're looking for a letter T among a whole lot of other letters. The other letters are the distractors. They're something similar but different, essentially.

MISHLOVE: As I recall from my undergraduate days in psychology, one of the basic effects of the visual system is retinal fatigue. If you didn't move your eyes around all the time, the images would fatigue. You'd lose sight of them altogether.

CRICK: That's absolutely right. But those are only very small movements.

MISHLOVE: Micromovements.

CRICK: And it's difficult in fact to keep your eyes so still that you can do that. By instruments or by wearing something on your eyes, you can show that that's the case. So that I don't think is what is involved. What is involved, as William James said, is concentrating on one thing at the expense of other things which you pay less attention to. It's not the same as just being alert, for example; it's a selective process -- this rather than that, rather than just going to sleep.

MISHLOVE: It would seem as if the notion of attention is fundamental to consciousness, in the sense that the brain is capable of processing a great deal of information at one time -- sensory information, motor information, cognitive, visual information. And yet only a small part of that is really conscious.

CRICK: Yes. We don't know that there isn't a very fleeting form of consciousness which doesn't need attention. James talked about this. He called it the fringe, for example. We don't know that, and it's plausible. But the one of course we're more focused on is this one which, as the jargon is now, is enriched by attention. In other words, if you attend to it, then you can remember it longer, you see more details, you see it with more precision, and so on. And so this is a subject which is studied by psychologists, and they are broadly agreed about the mechanism, but not sufficiently well about the details that we can immediately map it onto the brain. But of course you can ask the neuroscientists, can they see the effects of attention? And yes -- this is usually done on a monkey -- you can tell it alters the firing of the neuron, depending what it's attending to, even though it is not moving its eyes, so what's coming in is constant. And if you inactivate certain parts of the brain the attentional mechanism doesn't seem to work as well. But all this is in a very preliminary stage. We can't really say what is the proper basis of it, and it needs a lot more experimental work.

MISHLOVE: Well, it strikes me that even a reptile is capable of evidencing attention from one thing to another.

CRICK: Well, certainly reptiles -- I was going to say can move their eyes, because of course some birds don't move their eyes. Owls, you know, don't move their eyes; they move their heads, like this, you see.

MISHLOVE: But it's still an attention mechanism.

CRICK: Yes, that's right.

MISHLOVE: And I understand from your writing and from others that the mechanism of attention is at the older parts of the brain.

CRICK: Well, we believe again it's something to do with the thalamus, which is the gateway to the cortex. So it's not the really old part of the brain, which is concerned with sort of eating and drinking and sex and that sort of thing. But it is a satellite, you might say -- that's not quite the right word. It's something which is associated with these two big cortical sheets.

MISHLOVE: The thalamus is crucial to your understanding. That would be considered part of the mammalian brain, wouldn't it?

CRICK: Yes. In birds you do get something which is a bit like what we have, but by and large this cortical system and the thalamus is most obvious and better developed in mammals.

MISHLOVE: Well, one way to look at the nature of human consciousness would be to compare our brain with those of other animals and notice the difference. Another way to understand consciousness is to look at people whose brains have been damaged in various places or ways, and notice how that affects their behavior.

CRICK: Well, there are of course some very dramatic cases when you look at how it affects how they see things. One sort of damage you can have is such that you see more or less perfectly well. You can see shapes, you can see movements, and so on, but you only see in black and white. You've lost color. This happened to a New York painter; Oliver Sacks gave a description of it. And he not only lost the ability to see colors, but he couldn't imagine colors, and his dreams, which before that were full of color, also were now in black and white. And moreover -- people said, "Well, it's really not so bad. It's just like looking at an old movie." But then he said, "Ah, but it's real." And it was particularly distressing in relation to his wife, because his wife appeared to have the complexion of a rat, and he couldn't easily make love to her because of this, even if he closed his eyes, because it still was the same in his imagination. Perhaps the most dramatic one is a lady in Germany who again can see pretty well -- she can see color and shape and so on -- but she can't see movement. And that resulted -- if she pours out the tea, what she sees is a gleaming column of liquid. She doesn't see it move, and she can see there's tea in the cup, but she doesn't see it rise up. If she goes out into the street she feels very threatened, because she sees an automobile, and then the next moment it's somewhere else, and it's quite threatening. Now, the easiest way to grasp that is to think about you looking at the hour hand of a clock. It is moving very slowly, but you can't see it move, but if you look again you can see that it has moved. So that's in her case. Now, some people find this very counter-intuitive, because they say if she can see it, and if it's moving, why can't she see it move? And the answer is that you have to have a bit of your brain which shows movement, and that's the bit she's lost. And this is the sort of way you have to learn to think about the brain.

MISHLOVE: In other words, particular nerves, or groups of neurons, are responsible for very specific kinds of sensory function.

CRICK: Yes, responding to different things. And moreover that's the essence of the thing. See, people think when they look at something it's so effortless they can't see what the problem is when you study it. But in actual fact, psychologists can show that it's a very difficult process, that you have to construct a representation in your head corresponding to the visual aspects of the world outside. Well, just to give a simple example, what comes into your eyes -- and after all, you can see even with one eye -- is a two-dimensional picture. But your brain has to give the best three-dimensional interpretation on that. And the net result is that there are a lot of different areas which specialize in different things -- not totally, and they're all talking to each other, and trying to work out, in the light of past experience, what's the best interpretation of what's coming into the eyes, and what is out there. But it all happens so fast, and with so little effort, that you don't realize that process is going on.

MISHLOVE: Now isn't it the case that if brain damage occurs to a young child, even an infant, that they can very often recover their mental functioning?

CRICK: That depends on the nature of the damage. It's particularly true of language, because for right-handed people language is on the left part of the brain. So if a small child gets damaged there, the right half can take over. And it is also true to some extent, if you just have damage in a patch, as it were, the neurons just outside the patch will be able to take over a little bit. But it won't necessarily take it over entirely. So it depends on the exact nature of the damage, and of course, as you implied, the age of the person.

MISHLOVE: As we get older our brains, our neurons, our nervous system, is less flexible or plastic?

CRICK: Well, we don't pick up, we don't learn things quite as easily, you know. When young people learn language, they sort of just soak it up. It's harder as you get older. But it's still plastic, or you couldn't remember what you had for breakfast.

MISHLOVE: Of course memory is still one of the great mysteries in neurological science, isn't it?

CRICK: Yes, but I think we know more about memory than we do about consciousness. For example, of course we know there are short forms of memory and intermediate forms and longer forms. And the longer forms of memory -- the classic one is to say, "your memory of the Statue of Liberty." Now until I said that you weren't thinking of the Statue of Liberty.

MISHLOVE: That's right.

CRICK: But there were connections in your brain such that when the nerves' ends were cued, they brought up this image of the Statue of Liberty in your brain. Now that's a sort of passive memory. But the short-term memory is probably much more active, and only lasts for a short time. Then in addition there are different sorts of memory -- what's called categorical memory, the meaning of a word, the meaning of the word broadcast, or something like that. Then there's episodic memory, of what has happened recently. You can have people have brain damage who can remember what's happened in the last half minute or so, but not beyond that, so that if they were introduced they'd say, "How nice to meet you," and so on. If you went out of the room and came back two minutes later, they'd deny ever having seen you. And there's a third type of memory which is a memory of skills -- how you swim, how you drive a motorcar. And one way of saying that is that the people who have this damage, for example, they remember the meaning of the word breakfast, they still remember how to eat their breakfast, but they have no idea what they had for breakfast. And more than that, we know now some of the molecular machinery that's involved in memory, and without going into all the details, if we make those molecules act less well, then a rat won't be able to remember where it's been in the maze, for example. But you're quite right that the study is really only beginning, but it has made a good beginning.

MISHLOVE: When you talk about molecular machinery of memory, can you elaborate on that? How is that thought to operate?

CRICK: Well, you have to really ask, how do you send signals from one nerve cell to another? What a nerve cell is, or most of them is, it has what's called an axon, an output cable, and it sends an electrical pulse, which is regenerative so it doesn't decay as it goes down, and as it reaches a certain point it branches and branches again. So it sends its signal to a thousand or ten thousand different contacts with other nerve cells. Those are called synapses. Now, what happens there is this electrical, or electrochemical, signal comes along, and that produces an electrochemical signal in the next neuron, but not directly. What it actually does is to release a little packet of chemical, and that chemical then goes and sits on molecules in the second one, and when it sits there it opens the gate --

MISHLOVE: Crosses the synapse.

CRICK: Yes, that's right. It opens the gate, and lets charged atoms -- ions, that is -- go in and out, and therefore make some electrical alteration.

MISHLOVE: On the membrane of the next cell.

CRICK: Yes, and those are the molecules we're talking about. Now to have a memory, what you have to do, it has to be associative. You don't just strengthen that contact because it's being used. You want to strengthen it because it's associated with something else. And what happens is, if you have a lot of other signals coming into that part of the nerve cell, then when this signal comes in it makes a difference. In other words, it alters that receptor, sends a different chemical signal, and then that one is strengthened or weakened. So we understand all that. We understand the molecules involved. We have the genes for them; we know their sequences. What we don't know is what happens when -- it's actually calcium ions -- get in. There's a lot of complicated process following it we don't understand.

MISHLOVE: If I can just summarize what you've said, it seems to me that you're suggesting that on the membrane of the neurons, and the chemicals that cross the synapse, in that region there are ways that will enable the neuron itself to remember a particular kind of signal so that it might be more likely to fire when that particular signal comes again.

CRICK: Yes, well that's just for the one synapse. Of course if it has to make much effect on the neuron it has to be multiple synapses.

MISHLOVE: Because every neuron is connected to perhaps thousands of other neurons. It's constantly sending and receiving signals to thousands of other neurons.

CRICK: That's right. And of course because it's like that, that explains why very tiny amounts of chemicals can alter people's behavior, because they go and sit on some of these molecules, different types of them, and that alters -- for example, you can have one the signal which is to calm down the neuron. And if you therefore put a chemical which increases that, that will calm you down or send you to sleep, if that's what sleeping pills are. And we've seen that, of course, recently in things like Prozac. So that's why tiny amounts of chemicals will do that. In the case of LSD, for example, you only need 150 micrograms to have all these funny experiences, you see. It's minute. And that's because they fit into special places, these little molecules, these drugs which you take. They fit into special places in these other molecules. They've been tailored to do that.

MISHLOVE: Do you have a sense of the process by which hallucinogenic drugs such as LSD, or psychedelic drugs, actually affect the brain? What is going on there?

CRICK: Well, I don't have a detailed knowledge, no, I don't, and I'm not sure that anybody else really knows. They have a rough idea.

MISHLOVE: We know that obviously there's a chemical influence.

CRICK: Well, typically, different ones act in different ways. But a common thing is to see colors more vividly, for example, and often to see things move in a way when they're not actually moving, and things of that sort. So they boost up in some way the activities of what you might call the color parts of the brain and the moving parts of the brain and so on. But the government isn't very keen on giving money for research on that sort of thing.

MISHLOVE: Not at all. Well, I suppose many neuroscientists would feel that the study of the chemical interactions at the synapses of the brain is a very fruitful area for research.

CRICK: Absolutely, but most of it's done in the context of mental illness or conditions like depression and things of that sort.

MISHLOVE: Your agenda is to look at the nervous system more intensely in order to understand consciousness, whereas other neuroscientists, I think, are looking at smaller problems than the problem of consciousness. What are some of the experiments or approaches that you would like to see done to further elucidate the mystery of consciousness?

CRICK: Well, of course our main interest is in the visual system, because we think that's the easiest way to approach it. So let me address that. The basic paradigm you want to use is you have a person or an animal, a monkey, looking at something which can be perceived in two different ways. You probably remember those drawings of Escher, for example, and you can draw a simple outline of a cube.

MISHLOVE: Figure-ground reversal. Our Thinking Allowed logo is an example of that.

CRICK: That's right. Now then you can ask the question, well, which nerve cells in the visual system are staying the same, because they're, as it were, really dealing with the input? And which ones are following the percept? That's what you see.

MISHLOVE: The percept.

CRICK: We use that for a fancy word. It just means what you see. Now, it's difficult to do it for the two cases we've mentioned, but you can do it with something called binocular rivalry, and you can see an example of this, a demonstration of this, at the Exploratorium in San Francisco. Binocular rivalry means essentially that if you put a visual signal coming into one eye which is fairly different from that coming into the other eye, but they're as it were on top of each other, the brain doesn't see a mixture. It prefers to see first one and then the other. So what you do, Jeffrey, if you were there, you'd have a white screen behind you, and I would be sitting here with a mirror, like this. And my left eye would be looking at you, and I would hold up my hand -- it helps if there's a white screen behind there. So I put my hand so it is roughly covering your face. And then if I go like this, wave my hand, your face disappears. You should try it -- you know, just get a lady's mirror and try it.

MISHLOVE: OK.

CRICK: So you can do that on an animal, but you don't do faces. What you do is you give the animal what's call fringes, so the line's going up in one eye and down in the other, and you train the animal to say which way they're going.

MISHLOVE: But why is the wagging of the hand involved?

CRICK: Because it's more salient. It attracts attention, you see, and so on. And if you move your eyes the face comes back again. It's alleged -- I'm not sure I can always do this -- but if I were to get you to smile, and I concentrate on the smile and wave my hand, your face would go but your smile would remain. This is called the Cheshire cat phenomenon. But anyhow, we don't do that particular thing on monkeys, but Nikos Logothetis has done experiments in which you put things going up and down, and of course then again you see them first going up and then you see them down, and so on, in a special sort of way. It's not regular and not quite irregular. And then you find the monkey does the same. So then you put electrodes into the monkey's visual system, in the part concerned with movement, and you ask which neurons are constant and following the input, and which ones are changing with the percept? And he does find one that changed with the percept. Now it so happens that we had for very flimsy reasons suggested they should be in the lower layers of the cortical sheet. It's a sheet and it's got layers of a sort. And indeed, although it isn't published yet, he is showing that.

MISHLOVE: We're going so fast and covering so much, I'd like to just step back and kind of recap what we're talking about. First of all, I guess the idea is that the stimulus, the image that you're looking at -- let me make it simple, something like this, the figure-ground reversal. It stays the same.

CRICK: Yes.

MISHLOVE: But sometimes if you look at this image, you might see a vase; sometimes you would look at it and you might see two heads.

CRICK: Yes.

MISHLOVE: So something is changing in the brain.

CRICK: That's right.

MISHLOVE: And of course there are many more sophisticated types of stimulus. So you can measure when that change takes place in the brain, what's going on.

CRICK: But it's very difficult to do it in human brains, because the neurons which are responding always in the same way are very close to the ones which are responding to the different ways, and therefore it's much easier to put in an electrode which can pick up individual nerve cells, and that we can really, for ethical reasons, only do in the monkey.

MISHLOVE: I see. But now you seem to have a way of knowing when the monkey changes its percept.

CRICK: You train the monkey, by essentially rewarding it, to say whether it's seeing something going -- well, it would be difficult with this, you see, but in the actual case whether it's seeing something going up or whether it's going down. You have to take a lot of precautions to make sure the monkey isn't cheating. You can tell in a way because of the rhythm in which it does it, which follows a certain particular pattern called the gamma distribution, which we know is what happens in humans. And you see the same pattern in the monkey. You have to be very careful the monkey doesn't latch onto something else.

MISHLOVE: These experiments sound ultimately quite subtle. When you're dealing with a monkey there must be many variables.

CRICK: Well, there are a lot of precautions to make sure that the monkey -- see, you don't know exactly what the monkey is seeing. You have to assume that it's seeing in the same way as you. Eventually we shall have to be able to do things like this on humans. But it's so much easier to find out what to look for by doing it on the monkey, and see if there are techniques which we can conceivably use on humans.

MISHLOVE: I suppose in the distant future they'll train the monkeys in sign language so the monkeys can just tell you.

CRICK: Well, that's more complicated. Remember, monkeys, even chimps, have a great difficulty in doing any grammar. Certainly you can tell them -- they can signal whether it's red or green, or whether it's left or right, or up or down, or something. It may take you weeks to train that. It takes quite a time.

MISHLOVE: The other thing you mentioned were the layers of the cortex.

CRICK: Yes. Well, it so happened that -- the cortex of course has got --

MISHLOVE: That's the outside of our brain.

CRICK: Yes, that's right. A folded sheet. We have one on each side of the head. And it's there that much of what you see takes place, not necessarily exclusively there, but largely there. And there are a lot of different visual cortical areas, as we said earlier -- some which are more interested in movement, some which are more interested in color. But it is layered, and they have the curious thing that apart from the top layer, which doesn't have any nerve cells, the major inputs usually go into the middle layers, called layer 4, and then it goes to these upper layers, and they just talk to other neurons here or in other parts of the cortex. But some of the neurons in the lower layers send their information out of the cortex. So it's a reasonable guess that the result of what you see, the result of the computation, happens in the lower layers. That's just a guess. But two very able research workers some time ago showed -- in a cat it was in this case -- that when they were in slow-wave sleep, essentially, some of the neurons there were less active. And so probably the ones that you see with may be in those lower layers.

MISHLOVE: The lower layers of the cortex, or of the brain?

CRICK: The lower layers of the cortex. Still very preliminary.

MISHLOVE: Well, I know you've mentioned your hypothesis that there is some kind of a reverberating circuit between layer 4 of the cortex, as I recall, one of the lower layers, and the thalamus itself.

CRICK: Six and 4, yes. That's a separate speculation.

MISHLOVE: A very interesting idea about consciousness. Dr. Francis Crick, what a pleasure to be with you again.

CRICK: So nice.

MISHLOVE: Thank you very much.

CRICK: Thank you, Jeffrey.

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