EDGE 8 — March 4, 1997


A Talk with John Maddox

"My guess is that if the question of human extinction is ever posed clearly, people will say that it's all very well to say we've been a part of nature up to now, but at that turning point in the human race's history, it is surely essential that we do something about it; that we fix the genome, to get rid of the disease that's causing the instability, if necessary we clone people known to be free from the risk, because that's the only way in which we can keep the human race alive. A still, small voice may at that stage ask, but what right does the human race have to claim precedence for itself. To which my guess is the full-throated answer would be, sorry, the human race has taken a decision, and that decision is to survive. And, if you like, the hell with the rest of the ecosystem."


Ian Stewart on Reuben Hersh

I was told that when Jung invented the idea of the collective subconscious, a quirk of the German language left it ambiguous whether he meant a single pool of knowledge into which all humans dip, or a collections of separate — but very similar — pools. When we use a single word 'mathematics' we seem to be thinking of a single collective pool — but, like all human knowledge and thought, it is really a collection of separate pools.

Daniel Goleman on Joseph LeDoux

All this means that to model the mind in a significant way, you need the cyber equivalent of an amygdala. All else is a shallow version of the mind at work.

Steven Pinker on Joseph LeDoux

Put these bits of evidence together and one begins to consider a developmental theory opposite to the stimulus-response-linkage account — kids don't start off fearless and gradually acquire fears through conditioning; they start out fearful (not necessarily at birth, but in the first few years) and gradually master them, with adult phobias being childhood fears that never went away.

Joesph Ledoux Responds to Daniel Goleman, Douglas Rushkoff, William Calvin, Paolo Pignatelli, and Steven Pinker

Coming Events

Jared Diamond, Murray Gell-Mann, J. Doyne Farmer, Stewart Kauffman, Seth Lloyd, Lee Smolin, and Charles Simonyi

(10,359 words)

John Brockman, Editor and Publisher | Kip Parent, Webmaster


Ian Stewart on Reuben Hersh

From: Ian Stewart
Submitted: 2/28/97
Re: Reuben Hersh

One point that did occur to me concerns the argument that because there were nine planets around before humans came on the scene, that means that the number 'nine' in effect existed already.

I don't agree. The problem is that the universe has no concept of 'planet', and in a sense would not know what to count. It is humans who classify the billions of objects floating around in the solar system according to size and shape, and decide that some are planets and others not. Without this classificatory step, there is nothing to count. In short, until something selects a set of things, there is no preexisting concept of number.

This is not to say that I agree with Reuben that maths is purely some kind of human activity. (I'm not sure that's what he meant anyway.) I imagine, for instance, that other intelligent beings — if they exist, which I think likely — could develop a similar kind of system. However, I don't see why it has to be similar to ours, except in 'style'. For instance, aliens that take the physical form of plasma vortices in the atmosphere of a star might know far more magnetohydrodynamics than we do, but have no concept of 'triangle'. I think their maths would be in the same philosophical area as ours, but might not mesh terribly consistently.

I was told that when Jung invented the idea of the collective subconscious, a quirk of the German language left it ambiguous whether he meant a single pool of knowledge into which all humans dip, or a collections of separate — but very similar — pools. When we use a single word 'mathematics' we seem to be thinking of a single collective pool — but, like all human knowledge and thought, it is really a collection of separate pools. Because maths is very precisely determined, the education system can ensure that all those pools overlap in a very consistent manner, giving the illusion of a shared common pool. I think this is the sense in which maths is basically contained in human minds. BUT there is a more abstract sense in which it is the common pool — leading a virtual existence but feeling just as real to each of us as we dip into our part of it as a physical experience does — and that's a more interesting kind of existence. It's why many mathematicians think platonistically. Medicine, say — and definitely music — is not as tightly constrained o be consistent, so is NOT really the same kind of thing.

IAN STEWART is the 1995 recipient of the Royal Society's Michael Faraday medal for outstanding contributions to the public understanding of science. He is author of Does God Play Dice?, The Problems of Mathematics, Another Fine Math You've Got Me Into, and Nature's Numbers. He writes the "Mathematical Recreations" column of Scientific American and is mathematics consultant to New Scientist and to Encyclopedia Britannica. He has written articles for such magazines as Discover, New Scientist and The Sciences. He lives in LondonDaniel Goleman on Joseph LeDoux

Daniel Goleman and Steven Pinker on Joseph LeDoux

From: Daniel Goleman
Submitted: 2/26/97

Re: Joseph Ledoux


LeDoux's groundbreaking work has, understandably, been embraced by neuroscientists, even psychoanalysts, as the best insight so far into the workings of the emotional brain and the role of unconscious processing of emotions in mental life. But the field that should be standing up and paying attention is artificial intelligence. LeDoux has shown the neural circuitry that accounts for the fact—established in separate research by cognitive/social psychology—that the act of cognition entails emotion. That is, as we comprehend that this or that is an 'X', we already have an opinion about—as we realize what it is, we like it or we don't. And this affective processing occurs in the very first phase of the act of cognition—we actually have the emotional reaction many milliseconds before we know exactly what it is we're reacting to.

Couple this intrinsic role of feeling in cognition with Antonio Damasio's work, showing that sound decision-making and information-processing in life depends on intact circuitry to the amygdala, and the conclusion is that need to know our feelings about our thoughts, or we have no preferences. The only realm where feelings don't matter is the purely abstract and cognitive—mathematics, for example, But only mathematics for technicians—not for theoretical work or creative insight: we're back to the need for feelings—for intuition, for the "feel" of what's "right".

All this means that to model the mind in a significant way, you need the cyber equivalent of an amygdala. All else is a shallow version of the mind at work.

Dan Goleman

DANIEL GOLEMAN is a psychologist and award-winning writer who covers the behavioral and brain sciences for The New York Times, and is the author of numerous books including Vital Lies, Simple Truths, The Meditative Mind, the international bestseller Emotional Intelligence, and coauthor of The Consumer's Guide to Psychotherapy. He has taught at Harvard University and was previously senior editor of Psychology Today.

From: Steven Pinker
Submitted: 2/28/97
Re: Joseph Ledoux

I like Joseph Ledoux's approach, in which he studies a single system at many levels of analysis, from psychology to molecules. Decades ago, Tinbergen suggested that anything in psychology has to be understood at four levels — mechanism, development, function, and phylogeny. Ledoux's intensive analysis of one psychological faculty may present a special opportunity to realize Tinbergen's ideal. I'd like to throw out a couple of questions that speak to the integration of the four levels; they come from my own approach to fear in How the Mind Works.

1. LeDoux says, "We aren't born with phobia. Somehow they are acquired through experience and stored in the brain as links between stimuli (like snakes or heights) and fear responses." It's true that we aren't born with phobias, but it doesn't follow that we necessarily acquire them, or that if we do, that it's by forming links between stimuli and responses, as "Little Albert" allegedly did in Watson's experiment. The alternative is that fearful responses emerge as a product of the postnatal maturation of the brain. A number of psychologists, anthropologists, and ethologists have presented evidence for this possibility (Seligman, Rachman, Marks, Nesse, and others).

First, children spontaneously become fearful of a standard list of stimuli in the preschool years (strangers, separation, loud noises, spiders, deep water, the dark, carnivorous animals, etc.). Second, according to cross-cultural surveys, most typical phobic objects (such as snakes) are feared in all cultures — and it is often the cultures that have the *least* exposure to the objects that fear them the most (e.g., snake phobia in American cities). Third, many phobics have had no encounters with the object of the phobia. Fourth, fear responses to objects such as snakes appear in several laboratory-raised primates — D. O. Hebb reported that his Yerkes chimps freaked out the first time they saw a snake, and Marc Hauser tells me his tamarins gave alarm calls to a piece of rubber tubing on the floor! Even primates that seem to acquire a fear of snakes, such as rhesus macacques, acquire it by observing others, not by Pavlovian conditioning, and acquire it only for standard scary things like snakes, not, say, for rabbits.

Put these bits of evidence together and one begins to consider a developmental theory opposite to the stimulus-response-linkage account — kids don't start off fearless and gradually acquire fears through conditioning; they start out fearful (not necessarily at birth, but in the first few years) and gradually master them, with adult phobias being childhood fears that never went away. It strikes me that this theory fits the rest of LeDoux's account fairly well. I wonder whether he has a preference for one of the two developmental theories, and what the evidence is on the prenatal and postnatal maturation of the amygdala and its connections to the rest of the brain, in monkeys and in humans.

2. Ledoux mentions that "the amygdala projects back to the neo-cortex in a much stronger sense than the neo-cortex projects to the amygdala. The implication is that the ability of the amygdala to control the cortex is greater than the ability of the cortex to control the amygdala. And this may explain why it's so hard for us to will away anxiety; emotions, once they're set into play, are very difficult to turn off." Well, it explains it at a mechanistic or proximate level, though it doesn't explain it a an ultimate or functional level, since it raises the question of *why* the connections evolved to be so asymmetrical, at least in humans (assuming the primate asymmetry were conserved in our evolution). I've suggested an ultimate or functional explanation — that a lack of cognitive control of the emotions can be an asset in strategic conflict between partial adversaries (in the case of fear, between conspecific threateners and targets), because they make threats and promises (including a "promise" of surrender in an aggressive encounter) more credible.

Of course, there are alternative explanations — conceivably there's some kind of evolutionary inertia or developmental constraint making it impossible to grow symmetrical connections between amygdala and cortex. It strikes me that Ledoux's project offers the promise of allowing us to decide between the accounts someday. Perhaps one could look at the development of the connections, and see if the growth factors (or other molecular guides) and the genes controlling them are the kinds of things that can easily be modulated in development, with different parts of the brain, or the brains of different species or even different individuals, showing fine-tuned control of the degree of symmetry or asymmetry of that kind of connection. We know that fearfulness shows variation across life stages, species, breeds (e.g., of dogs), and individuals; perhaps one could compare the size of their amygdalas or the strength or asymmetry of their connections to the rest of the brain. One could even selectively breed animals for different kinds of fear response and look at their brains. If there was fine-tuned, systematic variation in the neuroanatomy across these comparisons, it would suggest that there is no inviolable neurodevelopmental constraint but that natural selection had considerable freedom in selecting the genes that wire up animals' brains, presumably in the service of the survival demands of their niche and social system.-

Steven Pinker

STEVEN PINKER is professor in the Department of Brain and Cognitive Sciences at MIT; director of the McDonnell-Pew Center for Cognitive Neuroscience at MIT; author of Language Learnability and Language Development, Learnability and Cognition, The Language Instinct, and the forthcoming How the Mind Works (Norton).

Joesph Ledoux Responds to Daniel Goleman, Douglas Rushkoff, William Calvin, Paolo Pignatelli, and Steven Pinker

From: Joseph Ledoux
Submitted: 3/3/1997

Response to: Daniel Goleman, Douglas Rushkoff, William Calvin, Paolo Pignatelli, and Steven Pinker

Computation and Emotion

There are lots of good reasons why cognitive science ignored emotion at the beginning. Emotion just wasn't what this approach was about. When cognitive science started claiming to be the new science of the mind, instead of a science of cognition, though, emotion and related topics should no longer have been ignored. But they were, and, for the most part, still are. As Dan Goleman points out, this leads to a shallow view of how the mind works.

To be fair, though, many of the leading researchers in AI and cognitive science have from time to time recognized this. The problem is that this recognition hasn't led the rank and file of cognitive science to embrace emotions with open arms. For the most part, emotion is still one of those messy things you need to control in a good cognitive experiment, rather than something you should study.

It's worth noting, though, that there's a growing interest in emotions in AI. There is, however, some work in AI that has tried to bridge the cognition- emotion gap. For example, there are models of emotional face perception and emotional language recognition, and an expert system that simulates stimulus evaluation processes. Also, there's an internet "Cognition-Affect Group" that functions as a clearinghouse for announcing and describing new findings or just plain asking questions of people who have an interest in the subject. Good starts, but more is needed.

My own efforts in this area have involved the development of a connectionist model of the fear conditioning network. Rather than starting with a psychological theory of emotion (a tough task to accomplish) I start with an understanding of the neural system that underlies one kind of emotion - fear (as modeled by fear conditioning). This work, but the way, is done in collaboration with connectionist modelers. The model is anatomically constrained. These constraints allow the model to discover many aspects of the behavior and physiology of fear conditioning that we've identified through animal studies. The model has even made novel, non-intuitive predictions about the effects of brain lesions. We've then gone back and tested the predictions in the rat, and the model was right.

Another point about the model is that it is modular. This means that we can pick one structure, like the amygdala, and fill it with simulated neurons that have real physiological and biochemical properties, while leaving the rest of the model to function at the systems level (linked structures with generic neuron-like unit). These kinds of hybrid models that include both neural network and detailed neuronal compartmental components are potentially very powerful. The modular nature of the model means that we can also take other brain regions that have been simulated with some success, like the hippocampus or areas of neocortex, and integrate those with our model. We're doing this to try to understand how cognitive functions such as attention and contextual processing influence and are influenced by fear arousal.

Have we explained all of emotion through animal studies?

Douglas Rushkoff has the feeling that my ideas about emotion might work for survival mechanisms like fear, but not for other more complex emotions. I would be the first to admit this. One of my main points is that we need to study each emotion on its own terms, and I make no claim that I've got anything to say about emotion in general. I'm happy if I can contribute something to our understanding of fear. Fear is, after all, the emotion that most often goes wrong and accounts for most so-called emotional disorders. Remember, Freud's whole theory was based on anxiety.

Memory and Stress

Hippocampal functions (including explicit, declarative memory) can be impaired by high levels of steroid hormones (stress hormones) floating around in the blood. This is a well-documented finding supported by studies of hippocampal physiology in animals and by studies of hippocampal-dependent memory in stressed animals and in humans with high levels of steroids (such as in Cushing's disease and in people with severe depression). These facts are documented in The Emotional Brain (http://www.cns.nyu.edu/home/ledoux/book.html).

William Calvin calls this a teaching example. He's of course right when he says that there's no way to know whether a stress-induced impairment in hippocampal function might account for "false memories" in traumatized people. I didn't mean to imply that stress effects on hippocampus could account for false memories. I only meant that this phenomenon might help explain why there is sometimes an amnesia for traumatic experiences. False memory is something else that comes later to fill in the gaps left by the amnesia.

This brings us to Paolo Pignatelli's question about why the amygdala can't make up for the hippocampal impairment in cases of stress-induced amnesia. I argued that in stressful situations the amygdala and hippocampus each form their own memories. The amygdala forms unconscious emotional memories, and the hippocampus conscious memories about emotional situations. The amygdala memories lead to bodily responses, while the hippocampal memories just lead to thoughts. When the hippocampus is "shut down" by stress the amygdala continues to form its unconscious memories, and may form even stronger ones.

Pignatelli asks, why can't the hippocampus later get the information from the amygdala, converting the amygdala's unconscious memory into a conscious one? Actually, he's not the first to want to know this. Many proponents of "recovered memory" have tried to make this case. Pignatelli comes at it from a perfectly good theoretical position. If the amygdala and hippocampus are both computing machines, by which he means Universal Turing Machines, then shouldn't there be a way for one to read the output of the other?

I think Pignatelli has raised an interesting point. I don't really know enough about the theory of computation to say whether the amygdala and hippocampus, or any other two brain regions, satisfy the requirements of Universal Turing Machines. However, it seems to me that they are best thought of as special purpose rather than universal computers. I don't know of any evidence that would support the idea that the memories of these two systems are shared, but there is some evidence that they are not. The evidence comes from a study Jeff Muller did in my lab last year. The study wasn't done with Pignatelli's question in mind, so it doesn't completely answer his question, but it goes pretty far.

We temporarily put the amygdala to sleep in rats. This is done by injecting a drug directly into the amygdala that shuts down neural activity, but only for a short while. While the amygdala was out, the rats, which were otherwise fully awake, underwent a standard fear conditioning procedure. The next day, after the drug wore off, we tested the rats. They showed no sign of having learned. Presumably the hippocampus was awake and storing information. But the amygdala couldn't later use that information to express learned fear responses. We know that the amygdala injection didn't affect the hippocampus since even permanent amygdala lesions don't interfere with hippocampal-dependent memory in rats or humans. This is pretty good evidence that the amygdala can't convert a hippocampal memory into something it can use to do its work. It doesn't answer the specific question (whether the hippocampus can read amygdala memories) but it does answer negatively the reverse question, and seems to suggest that brain areas are specific rather than universal computers.

Maturation vs. Learning

I think many of the issues raised by Steve Pinker about the evolutionary and maturational basis of fears and phobias are addressed in The Emotional Brain. The evolutionary and developmental researchers that Pinker cites are covered and endorsed there. I tend to emphasize learning because I want to see how far the fear conditioning model can go rather than because I think it can explain everything. Pinker asks whether my account can easily include the idea that some adult fears and phobias are developmentally programmed childhood fears that never went away. I think this kind of idea can fit right in. I view fear learning as something that a fear detection network does. This network can detect dangers that are programmed in by evolution, as well as those we've learned about. Many of the things that make otherwise normal people afraid are things we've learned about, whereas many phobias seem to involve things that were dangerous to our ancestors. In either case the stimulus goes to the amygdala, which unleashes the responses. The only difference between a learned and an innate releaser of fear responses is how the amygdala was programmed to detect the stimulus.

While I thus agree with Pinker's point that evolutionary and maturational factors are important, I'd like to add a couple of additional points of support for the role of learning. First, there are some instances of phobia where there is a triggering event, even if this isn't always the case. Second, certain evolutionarily programmed fears have to be massaged by experience, as when baby monkeys need to observe snake fear in others once in order to express it themselves. Third, not all learning is associative in nature. Jake Jacobs and Lynn Nadel have in fact raised the possibility that non-associative processes might be important in getting phobias going in some cases. A related notion comes from Jay Schulkin and Jeff Rosen, who are proposing that amygdala kindling might be a kind of non-associative neural trigger of phobias. Finally, some phobias involve non-biologically relevant stimuli, like cars and elevators. Here experience (associative or non-associative) would seem to be key.

Pinker also asks about the maturation of the amygdala. There's not a lot of work on this. Just as emotion has been ignored by cognitive science, the amygdala has been ignored by neurobiology. The neocortex and hippocampus, the king and queen of cognition, have been preferred targets of study. However, here's what the data available suggest. The amygdala matures relatively early after birth, whereas the hippocampus comes in much later. Jacobs and Nadel have suggested that the late development of the hippocampus accounts for infantile amnesia, that inability to consciously remember what happened to you in early childhood. However, because the amygdala is up and running, it can form its memories. A child that's abused will then have unconscious (fear conditioned) memories throughout life, but will never be able to verbalize why he reacts the way he does. That the amygdala never forgets is suggested by lots of evidence, again documented in The Emotional Brain. The amygdala's memories can be inhibited (by extinction or therapy processes) but these extinguished responses (unconscious implicit memories) can usually be brought back. They return as implicit not as conscious memories.

Pinker's final point is about why the cortex and amygdala are asymmetrically connected — the connections from the amygdala to the cortex are stronger than the other way around. He suggests that this may have a purpose — lack of cognitive control over emotion can be an asset in strategic conflict, since it makes threats more credible. His alternative is that there's some kind of evolutionary inertia that prevents the development of symmetrical connections. I prefer the second choice over the first, mainly because it's grounded in "brain" rather than "mind" evolution. In any event, as Pinker points out, now that we've pinpointed the kinds of circuits that are involved in fear, we can begin to ask the really interesting questions about how that system relates to the rest of the brain, and that's going to help us understand the cognitive/emotional mind, or, in other words, the real mind, as opposed to the one that much of cognitive science has been stuck on.

JOSEPH LEDOUX is the Henry and Lucy Moses Professor of Science at the Center for Neural Science, New York University, and author of the recently published The Emotional Brain: The Mysterious Underpinnings of Emotional Life. LeDoux's home page contains additional information about his lab's research.


A Talk with John Maddox

John Maddox, who recently stepped down as editor of Nature, occupies a unique place in today's culture. During the past 23 years he managed to build Nature into the premier publication of its kind, while still retaining the respect of the international science community for his intellect and writing.

In this discussion he talks about what we need to be concerned about: the increasing accumulation of data on a huge scale, lack of quantitative progress in biology, infection, impact, cloning, and the stability of the human genome.-


SIR JOHN MADDOX, who recently retired having served 23 years as the editor of Nature, is a trained physicist, who has served on a number of Royal Commissions on environmental pollution and genetic manipulation. His books include Revolution in Biology, The Doomsday Syndrome, Beyond the Energy Crisis, and the forthcoming What Remains to be Discovered: The Agenda for Science in the Next Century (The Free Press,US; Macmillan, UK)


JB: Let's talk about the questions you're asking yourself.

MADDOX: There's an extremely interesting question that seems to me to be very urgent: how on earth is science going to cope with the accumulation of data, on a huge scale, of recent years. This relates to another question that hasn't been given enough attention in recent years: when on earth is biology going to become a quantitative science, like physics and chemistry - when there's good evidence to believe that it can't make progress in some fields without becoming much more quantitative.

Let me give an illustration of what I mean. In a field like cell biology, everyone now has a clear picture of how the cell cycle is driven. You have proteins called cyclins, which are meant to interact with another protein called Cdk. Cdk plus cyclin activates two successive steps essential to the cell cycle. One of them is the replication of the cell's DNA; the other is the actual fission of the cell into two daughter cells. It seems to me high time that people recognize that the complexity of this system is so great that it can't really be dealt with in the simple way in which textbooks ordinarily deal with description, i.e. the explanation of events.

If, for example, you have an ordinary bacterial cell going through the process of cell division, it may be prompted to do that by some external signal in the environment; it may be prompted to do it simply because time has passed - twenty minutes is the length of time it takes the E. Coli to divide into two, and maybe just twenty minutes is up. There are several different molecular influences acting on this complex of cyclin and Cdk which is what actually triggers off the cell division. The complexity of the problem is so great that you can't comprehend it in the language I've been using; you can't comprehend it in the language of the textbooks, because it has become a mathematical problem. Nevertheless, very few people take this seriously.

There's more to it than that. I'm advocating that in the case of the cell cycle this is a specific biological problem. How do we understand the cell cycle? What makes a cell divide? What can we say about the competing influences on a cell - the external environment, the internal need of the cell, the need of some other cell in the same organism. How do these competing influences conspire to decide that the cell is now going to divide into two. What we need are mathematical models for saying what actually goes on.

There are other fields like that. Take the way in which the muscles in our arms work. Any molecular biologist will now tell you this understanding is one of the big triumphs of the past ten or fifteen years, that muscle fibers are made of actin and myosin, two proteins - and the idea is that the myosin molecule which is smaller than the actin molecule, acts as a kind of enzyme at the head of the actin fiber, that can ratchet itself along a parallel actin fiber.

Molecular biologists say, ah, we now understand how muscles contract. But nobody has done the thermodynamics of this problem. It's obviously a matter of great interest to the world at large to know how much energy is used. The molecular biologist will tell you it comes from ATP. ATP, adenosine triphosphate, is actually the universal source of energy in living cells, and everyone says that's fine, but actually what are the thermodynamic aspects? This question is not considered, and it's a crucial question, because that's the kind of consideration that would tell us when it is that muscles become tired, when they no longer function, or when they become rigid, and go into spasm. There are all kinds of important abnormalities in muscle behavior that would be explained by thermodynamics, if people put their minds to the task. The molecular biologists may have answered the "how ? question, but they will not be able to answer the "why?" question until somebody has done the thermodynamics.

What I'm saying underneath all this is that perhaps molecular biology got itself into the condition in which it's far too easy to get data, and therefore there is no incentive to sit down and think about the data and what they mean. But I'm sure that as the years go by, and not many years, people are going to have to be thinking much harder about how they get accurate quantitative data about the behavior of cells, muscles - all these things in living creatures.

JB: What is the relation of the acquisition of such data to the development of technological tools that allow you to formulate models and execute on those models. Are your perceptions related to the development in increased computational power?

MADDOX: The case I'm making actually doesn't depend on the improvement of computer technology, but what you say is absolutely right; that to solve some of these problems is going to require unprecedented computer technology. But let me illustrate it this way: suppose you want to understand how a cloud functions, a cloud in the sky. Sometimes you get rain out of a cloud, but not always - you see clouds up there but no rain coming out of them. Why is that? The reason is that in a cloud you have a constant upward and downward flow of drops of water, particles of ice and so on, and it's in a dynamic situation. For every cloud the bottom is at some temperature and the top is at another temperature - a lower temperature, of course. Sometimes this dynamic stability of the cloud becomes unstable, perhaps because there's a shift of the temperature, perhaps because something goes through it like a projectile, an aircraft perhaps which may leave a trail of condensation behind it if it's travelling through the humid atmosphere, But you can only understand cloud behavior and answer the question when will this cloud produce rain, if you have a model which can be in that case quite a simple model.

In the case of the cell, and the cell cycle, it's a much more complicated model I'm looking for, and there in reality one would need supercomputers to handle the model The models people have built so far - I'm thinking of John Tyson at the Virginia Polytechnic and Albert Goldbeter at the Free University in Brussels -have been handled on ordinary desktops, but everyone agrees they're not sufficiently refined. Once you start refining them you get into real problems. But there's some parts of science that can only be understood when you make a model. The cell cycle is one, the muscle is another, and each of them, being biological problems, are very complicated.

JB: Speaking of cells, let's jump off this track for a minute and talk about the cloning experiment in Scotland. People are having a hard time getting their heads around it.

MADDOX: I look at the scientific importance of that experiment in the following way: it seems to me is that it is a demonstration that you can take an ordinary cell from a person's body, a somatic cell as it's called, and recreate the genome from that. The reason that's interesting and important is that up until now people haven't been sure whether the DNA in every cell of our body retains the power of making an embryo. This experiment shows that that happens. You can in principle take a cell from your skin or anywhere and make it into an embryo which then grows up into a person. That rules out a number of possibilities for the ways in which different tissues of our body have their different characteristics. Now a liver cell and a kidney cell are outwardly very different; a skin cell and a nerve cell are very different to look at, in their properties, and their behavior. But in practice, the difference could be because their genes have been changed in some way. This experiment in Scotland shows their genes have not been changed radically. They've been silenced, perhaps, but only temporarily. That's very important.

Now as to the practical importance, it seems to me that the immediate value of it is in animal husbandry, and that is in those fields where people have been trying to use sheep, or pigs, or cows, to generate biochemicals - to make medicines in sheep. There's a lot of interest in this. The procedure is quite simple: you introduce the human gene responsible shall we say for making insulin, into sheep, and then you collect the insulin from the sheep, and you find it's human insulin, not sheep insulin. Thus you have natural human medicine generated on a farm.

This kind of work is very difficult, because it's very much a matter of chance to where the human insulin gene will go. If you can take a successful chance, a case where the gene has gone in the right place and it's producing in the sheep a lot of insulin, then you can clone that sheep and get many many other sheep. You don't have to rely on chance any more. So that's going to be the immediate practical value.

The dangerous question is what happens when people start doing it to themselves - to people. For what it's worth, in Britain and many other countries, it's against the law to do this; it's a criminal offense to manipulate the human embryo beyond 14 days of life, and it's in fact a criminal offense to do so without the approval of a licensing authority. How effective that interdiction would be in other countries is anybody's guess. My guess is that countries like Morocco, which has been in the vanguard of sex change operations for many, many years will be in the vanguard of people cloning. So in that spirit, it's a question of waiting to see how the technology works out, and trying to get some kind of international understanding on the circumstances where it would make a lot of sense.

Are there any circumstances in which it would make a lot of sense? I can think of one. Coming back to one of the other questions I mentioned at the beginning, suppose we got into a situation where we had reason to believe that there was something wrong, something inherently wrong, with a set of genes that people have inherited, which have been evolved, of course, over the past four and a half million years, since we separated from the great apes. Suppose that we had reason to believe that one of those genes was going to cause trouble as time went on. For example, there is a case which one shouldn't make too much of, but's it's an illustrative case, of Huntington's disease, where there's a normal gene in every one of us, which makes a protein called huntington - nobody knows what its function is. This gene - this gene at cell division, when people procreate, produces a bit of nonsense at the end, and if the bit of nonsense is longer than a certain amount, it actually gives a person Huntington's disease - and he or she dies. That's bad news. There are half a dozen other diseases like that, same unbalanced mechanism. If there were a lot of those incidences, you could pretty well say that the time will come in the evolution of people when we'll all be dying of Huntington's. One way of avoiding it would be to clone people who didn't have this propensity. That's about the only circumstance in which I can see people cloning, as the last resort for the human race to avoid a calamity that would be brought about by gross instability of the human genome. I'm not saying that this is a real prospect now, but maybe in a hundred generations it could be.

JB: What other areas are causes of concern to you?

MADDOX: I've got a very simple view about the environmental problem that we all know about which is that a great deal of the excitement there's been in the past 25 years about the environment can be boiled down to this: one can say look, you can get whatever environment you wish, provided you are prepared to pay for it. You can get air as clean as you like, water as clean as you like provided that taxes, and the regulation of the private sector is tight enough to meet the standards laid down. This does mean, of course, that the countries that can afford a clean environment are the rich countries, and the environment they purchase is a big purchase - sometimes out of public funds, sometimes out of private funds. Poor countries can't afford a decent environment, but as they get rich they will enjoy the wealth necessary to make them see that a clean environment is good for them.

The real environment problems now, it seems to me, are things like infection. We've had AIDS pop up since the early 1980's; it's been a big shock to people that there could be such a completely novel disease doing such terrible damage and apparently untreatable by existing remedies. It's my belief that there must be many other diseases like this waiting for us as the centuries tick by. Suppose, for example, that there were a really infectious cancer virus, something which could just give you lung cancer if you took it in as if it were flu. There's only one known human cancer virus at present, but there are many in the cases of domestic animals like cats, such as the leukemia virus that's well known. The only human cancer known is papilloma virus which causes cervical cancer. And we all know that quite apart from these bizarre novel viruses, there are ordinary bacteria, like E. Coli, that from time to time acquire mutations that make them more virulent. The new E. Coli strain 170, for example, has caused a lot of damage in the United States, in Japan, and now in Britain. Dozens of people have died of food poisoning, in effect.

These bacteria are going to become more and more common as the years go by because we are putting the bacteria under such enormous pressure with the intelligent use of antibiotics in hospitals, curing the sick, and so on, the bacteria really have nowhere to go unless they become more virulent.

So we must expect that however good the defenses are - by defenses I mean the drugs, the hygiene - the bacteria are going to keep on getting more virulent unless they can be really hit hard. We have the prospect ahead of us of increasing threats from viruses and bacteria, and the organisms that cause diseases like malaria. It's actually part of the price we pay for living longer, for being healthier. It's just one of those things, something that one ought to reckon with, not wring one's hands about.

There's another worry, one which perhaps sounds unreasonable. I believe that it's only a matter of time before the world will have to plan to avoid catastrophe by the impact of asteroids. It's now known that 64 million years ago the Cretaceous Period and the dinosaurs were brought to an end because there was a big impact of an asteroid ten kilometers across - about six miles across - the impact site has been found on the Caribbean coast of Mexico, and the crater it left in the ground is 180 kilometers - about 110 miles across. It put up dust into the atmosphere, and the dust stayed there for so long that the vegetation died off, and the dinosaurs that ate grass died off with it, and lots of other species as well. That kind of event is likely to recur every few tens of millions of years.

Luckily, the techniques are good enough to be able to pick up about 90% of the objects that size in the neighborhood of the earth. They're called asteroids, or they may be comets. The biggest difficulty is that of a cometary impact because comets travel at a faster speed than asteroids and the warning would be less. But if you think that the whole world was put to an end 64 million years ago pretty well, by one impact, is it not sensible that the human race should do something to protect its own stake in the future? I believe we should be planning to do something about events like that that might happen in the future. Of course smaller impacts can do a lot of damage too. I think it's only a matter of time before people will be setting out to track those things, and to destroy them.

JB: How will this be implemented?

MADDOX: There are lots of very interesting problems that people haven't really thought about; for example, the best way of avoiding an impact is to explode a nuclear weapon near the projectile. If you can catch it early enough, shall we say several days before it's going to hit the earth, then a quite small nuclear weapon, shall we say 100 megatons, would be enough to nudge it in one direction or the other, but the most efficient way is actually to slow it down; to explode the thing in front of the asteroid. There are a number of associated hazards - if the explosion were not absolutely accurately timed, it might blow the asteroid up, and that might seem good news except there would then be several fragments, and one of those would certainly hit the earth, and it might still be quite big. So the best thing is a carefully controlled explosion to nudge the thing away.

The trouble with that is that the Russians and the United States are now against the deployment of nuclear weapons in space; the Chinese are probably against the development of other people's nuclear weapons in space; nobody has talked about the question anyway. So the idea that it might be announced there's going to be an impact a year from now wouldn't actually leave enough time for people to get around the table and decide what best to do about it. My own opinion is that there's going to have to be rather formal negotiation quite soon on what would happen if there were an impending impact. There would have to be arrangements that would make sure that no nuclear weapon authorized for use under this program could be used to divert an asteroid onto some sensitive part of the world, like China or Russia - and so on. All kinds of problems.

JB: How much time would we have?

MADDOX: It depends. In the worst case there would be hardly any warning at all - a couple of days. A couple of days is too little time to do anything. And the chance that a large object, ten-kilometer object, would arrive with only two or three days' warning is probably about ten percent. No program that one can think of devising is going to avoid the worst case - you can't get absolute security - but you could at least hope to get rid of ninety percent of the big impacts.

In the case of asteroids, the warning probably would be quite long, possibly even two or three years, because these asteroids make circuits about the sun just like the planets do, but they go in eccentric orbits, which is why they can hit the earth. This means that if you pick one up on a particular orbit, you might be able to figure out that on its next orbit, or its next but one, it's going to hit the earth. You've got quite some time to plan what to do in that case. And the feasibility of doing something will of course improve as time passes, so in that case one could begin by hoping to avoid half the large objects, quite soon, and, maybe in a hundred years, to avoid ninety percent of the large objects. However, we'll still be stuck with the problem of the ten percent.

JB: How do these ten percent sneak in?

MADDOX: They begin as comets and the thing about comets is that nobody is entirely clear how they find their way into the inner solar system. The theory - and there's no confirmation of this at all - is that right at the edge of the solar system, roughly at the place where the sun's gravitation field is comparable with the gravitational field due to external objects, like molecular clouds, other stars, and so on - there's a cloud of cometary material called the Oort Cloud, named after the Dutch astronomer Van Oort. What's said to happen is that these objects are either deflected into the solar system by a passing star, or attracted in by some conjunction of one of the outer planets with Jupiter, so that they start drifting into the solar system.

They spend some time with Neptune, and some time with Saturn, some time with Jupiter, and either they become asteroids, in which case there's relatively little problems, or in some extreme cases they start heading in from the outer region of the solar system, and they just make one pass at the sun. That's the most dangerous case, because these hyperbolic comets, as they are called, are traveling very fast, and they haven't been seen before, and they will only make one pass at the sun anyway. In that case it would really be quite hard to be sure that one could spot them many days in advance of an impact. That would be curtains.

JB: Ok, we've talked about data handling, infection, cloning, and impact. Going beyond cloning, let's talk about the stability of the human genome.

MADDOX: I dealt with that in the case of the sheep but let me add this to it, because I think it's important. Up until now it's been the assumption of most generations living on the surface of the earth, that the ideal condition of human beings is that in which we recognize that we're a part of the natural world, and our goal is harmony with the natural world. If you think of it, what natural selection, Darwinian natural selection, does, is precisely to make the successful species, those that survive, fit for the environment at the time. It's a device for making sure that everything is in harmony with the natural world. We have accepted, I think, as the human race, that this is indeed the case, that we must accept our dependence on the natural world and our need to be in harmony with it.

What happens, then, if we learn that we are one of those many species destined to become extinct because for some reason or another our genome hasn't worked out to be quite as stable as it might have been. In those circumstances we would have a nasty choice. We would have to decide, would we not, whether or not we let ourselves become extinct, as part of our dependence on nature, part of our being a part of nature, or whether we actually struggle against it; do something about it.

My guess is that if the question of human extinction is ever posed clearly, people will say that it's all very well to say we've been a part of nature up to now, but at this turning point in the human race's history, it is surely essential that we do something about it; that we fix the genome, to get rid of the disease that's causing the instability, if necessary we clone people known to be free from the risk, because that's the only way in which we can keep the human race alive. A still, small voice may at that stage ask, but what right does the human race have to claim precedence for itself. To which my guess is the full-throated answer would be, sorry, the human race has taken a decision, and that decision is to survive. And, if you like, the hell with the rest of the ecosystem.

JB: What are the scientific issues bothering people today that don't worry you?

MADDOX: It's interesting that more than a quarter of a century has passed since the publication of The Limits to Growth, the Club of Rome document, which seemed to me to produce a far too simpleminded view of the global problem. The global problem is not the shortage of resources. It's true that we are using up petroleum at quite a rapid rate, two billion tons a year, and the amount of petroleum in the surface of the earth is not by any means infinite. But there's a natural balancing mechanism in those simple scenarios of shortage. The balancing mechanism is price. What we're pretty sure of is that we've now used up one dollar a barrel oil; it's all gone. There's some two dollar a barrel oil left in Saudi Arabia, but the Saudi Arabians are very careful about the degree to which they let their stuff be exploited, and that appears on the market at fifteen dollars a barrel like everybody else's oil. So price is really a regulator of scarcity.

Even when petroleum becomes so expensive that it's used only for the production of chemicals - some of the few chemicals that can be produced exclusively from petroleum - the world will not stop. There are plenty of other ways of generating energy which at present are more expensive than petroleum - like nuclear power, even solar power, in small quantities, like hydrogen, which can be made by electrolyzing water, and used as a fuel - so there are all kinds of ways. The future is going to be dependent upon on other sources of energy than the ones we at present use.

The argument that we're using scarce, irreplaceable sources of energy is an argument not worth its salt; not worth listening to seriously. We're using up cheap resources, and in due course we're going to have to use more expensive ones, which is an argument of course for wealth creation, economic growth. So my view of the Club of Rome's argument on the Limits of Growth is just that. It's an economic question, always has been, and it will be in the future and it will be dealt with in economic terms.

But the other environmental problems that seem to me to be much more important, are those concerning the safety of people's lives. After all, the avoidance of pollution is primarily a problem of how do you keep people healthy. That's what the end purpose is supposed to be, keeping people alive and healthy. The big threat there has been, and remains, infection, which we've talked about. It seems to me another is global warming. Global warming is the scenario that's supposed to happen when, because of the accumulation of carbon dioxide in the atmosphere, the temperature on the surface of the earth is increasing. I'm in a very odd position on this. I accept that global warming, because of carbon dioxide, is going to be a reality at some stage in the future. I disagree with the way in which the forecasts have been made by the organization called the Intergovernmental Panel on Climate Change, which is under the UN umbrella, although it's really a child of the United Nations Environmental Agency and the World Meteorological Organization.

These people have produced so far two assessments of the seriousness of global warming, and they predict that during the next century the temperature will increase by between two and three degrees centigrade - which doesn't sound much but actually would be a lot. This is the average temperature, and that would mean that in places like the southern Sahara it would become even more like a desert, and it might even mean that in some parts of the United States, like Texas, it would become a bit like the Sahara.

But the real problem is that all this is based on computer modeling, and while I'm fully enthusiastic about computer modeling as a way of understanding scientific problems, and comprehending large amounts of data, I think it's dangerous to rely on computer modeling when you are trying to make predictions about the real world. In fact the satellites that have been used to measure the temperature show that the temperature is increasing less rapidly than the computer models predict, by a factor of three. So I think that the scenario is less gloomy than the Intergovernmental Panel of Climate Change says.

On the other hand, it's going to happen sometime, and we have to do something about it. It raises the whole question about how do you get an equitable relationship between the rich and the poor countries. The rich countries have to acknowledge that they can't unilaterally deny developing countries the right to follow in the same kind of path as they themselves have followed in their own economic development. On the other hand, the poor countries have to accept that they can't let their demands on the global system increase as rapidly as their populations increase. They have to accept some kind of restraint on population as a tradeoff. That's going to be such a terribly difficult negotiation and it's very hard to see how it could be completed in the next century.


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