I've got an article in today's New York Times about one of my perennial fascinations—musical hallucinations. One of the reasons that I find this condition so interesting is that it gives us a look under the neurological hood. Our brains do not simply take in objective impressions of the world. They are continually coming up with theories, and they test them against perceptions every moment of our waking lives. It would be impossible to test them against a complete picture of reality, because the world is simply too complex and ever-changing. Instead, the brain makes quick judgments on scraps of information, revising bad theories that don't make good predictions or using good theories as the basis for actions. Some scientists argue that musical hallucinations are evidence that our brains even make theories about music. When we hear stray sounds, we match them to tunes in our memory, in a sort of internal game of Name That Tune. Unfortunately, some people can't test their theories well enough, it seems, and so they wind up thinking a church choir is singing in the next room, when in fact there is only silence.

There's one line of evidence that supports this explanation of musical hallucinations that I didn't have room in the article to explore. It turns out that some people have an analogous problem with their vision. They suffer from a condition known as Charles Bonnet syndrome, in which they have visual hallucinations. In some cases, the hallucinations are nothing but textures or wallpaper-like patterns. In other cases, people may see a row of people floating in front of them. Reginald King, the elderly gentleman who described his musical hallucinations to me, also suffers from Charles Bonnet syndrome. He told me about how he would see patterns on the ceiling, or sometimes a cat or a dog running across his bed.

Victor Aziz, one of the scientists I interviewed for this story, has noticed that some other people also experience both visual and musical hallucinations, and doesn't think it's a coincidence. It's possible that regions of the brain that handle processing complex structures of both sound and sight can short-circuit in a similar way, producing similar hallucinations. And interestingly, brain scans of people with visual hallucinations are strikingly similar to those of people with musical hallucinations. In each case, the higher information-processing centers become active even when the regions that normally relay information from the senses are quiet. If we accept a theory of what we see, it's as real as the theories of what we hear.

How long can an idea stay tantalizing?

Back in 2003, I blogged about an experiment that suggested, incredibly enough, that our long-term memories are encoded by prions— the misfolded proteins that are generally accepted to be the cause of mad cow disease. The evidence came from studies of a protein (known as CPEB) that plays a key role in laying down memories in neurons. Scientists found that it had a structure much like prions. When a normal protein misfolds and becomes a prion, it acquires the ability to lock onto other proteins and force them to misfold in the same way. The misfolding can spread until it has devastating results—as in the case of mad cow disease, in which prions from cow brains get into our own brains. But the discovery of prion-like memory proteins hinted that maybe they could play a beneficial role as well.

Not long after I blogged on this research, I ran into a neuroscientist I know (and who shall remain nameless). He sneered at the prion paper, pointing out that the authors of the paper didn't show that the protein acts like a prion in neurons. Instead, they had only shown that it acts like a prion when it is inserted into yeast. They took this peculiar step because yeast have prions, and they had the tools to study prion behavior in yeast. It is far harder to experiment with prions in neurons. But this neuroscientist I spoke to thought they shouldn't have gone public until they had taken this last, hard step.

I've been waiting ever since. And in the June issue of Nature Review Genetics I came across a paper entitled "Prions as adaptive conduits of memory and inheritance." One of the co-authors is Susan Lindquist of MIT, one of the scientists who made the memory-prion connection back in 2003. Eager for an update, I read on. And what do I find? There's a lot of new research on the role of prions in yeast, where they may play an important role in evolution. But as for prions and memory, there's nothing beyond what Lindquist had to offer in 2003.

My patience has probably been irreparably damaged by today's minute-by-minute news cycle, but I have to wonder why we're still in prion-memory limbo. Is the next experiment too hard to do? Does it take years to finish? Or is the link between memories and prions just not there?

Just as I'm tempted to give up hope, out comes another paper. It may not seal the deal, but at least keeps me eager for more. Psychiatrists in Switzerland were inspired by the original prion-memory experiments to look for evidence in people's genes. Some studies have suggested that the strength of people's memories is at least partly the result of genetic variation. But no one knew which genes were involved. So the psychiatrists took a look at the prion protein gene (PRNP), which causes mad-cow disease when it misfolds. (No one is sure what it does for us in its normal shape.) People have different versions of PRNP, some of which are more prone to misfolding than others. The scientists genotyped 354 subjects to see which version they carried and then gave them a memory test.

In a paper in press at Human Molecular Genetics, they report that people with one or two copies of the misfolding version recalled 17% more information than those without a copy. It's a puzzling result for many reasons, not the least of which is the fact that the link originally proposed between prions and memory did not involve PRNP but CBEP. But it's enough to keep me wanting more.

Blogging will be light for a few days because my hard drive devoured itself last night. I just wanted to mention a couple brain-related items. First off, I've got a profile in today's New York Times of Michael Gazzaniga, one of the most fascinating people involved in science today. His research on the split minds of people with split brains would be fascinating enough, but now he's trying to use these insights to make sense of the confusing choices that bioethics now forces us to make. (Gazzaniga's a feisty member of the President's Council on Bioethics.) For another take on the brain and our sense of who we are, let me also direct your attention to the paperback edition of Soul Made Flesh, which is due in bookstores in June and is already available on Amazon. It looks at the birth of neurology in the 1600s. If you think these are strange times, neurologically speaking, imagine an era when people thought the brain was no more capable of thought than a bowl of curds.

Evolutionary psychologists argue that we can understand the workings of the human mind by investigating how it evolved. Much of their research focuses on the past two million years of hominid evolution, during which our ancestors lived in small bands, eating meat they either scavenged or hunted as well as tubers and other plants they gathered. Living for so long in this arrangement, certain ways of thinking may have been favored by natural selection. Evolutionary psychologists believe that a lot of puzzling features of the human mind make sense if we keep our heritage in mind.

The classic example of these puzzles is known as the Wason Selection Task. People tend to do well on this task if it is presented in one way, and terribly if it is presented another way. You can try it out for yourself.

Version 1:

You are given four cards. Each card has a number on one side and a letter on the other. Indicate only the card or cards you need to turn over to see whether any of these cards violate the following rule: if a card has a D on one side, it has a 3 on the other side.

Version 2:

Now you're a bouncer at a bar. You must enforce the rule that if a person is drinking beer, then he must be over 21 years old. The four cards below each represent one customer in your bar. One side shows what the person is drinking, and the other side shows the drinker's age. Pick only the cards you definitely need to turn over to see if any of these people are breaking the law and need to be thrown out.

The answer to version one is D and 5. The answer to version two is beer and 17.

If you took these tests, chances are you bombed on version one and got version two right. Studies consistently show that in tests of the first sort, about 25% of people choose the right answer. But 65% of people get test number two right.

This is actually a very weird result. Both tests involve precisely the same logic: If P, then Q. Yet putting this statement in terms of social rules makes it far easier for people to solve than if it is purely descriptive.

Leda Cosmides and John Tooby of the University of California at Santa Barbara have argued that the difference reveals some of our evolutionary history. Small bands of hominids could only hold together if their members obeyed social rules. If people started cheating on one another--taking other people's gifts of food, for example, without giving gifts of their own--the band might well fall apart. Under these conditions, natural selection produced a cheating detection system in the brain. On the other hand, our hominid ancestors did not live or die based on their performance on abstract logic tests. Rather than being a general-purpose problem-solver, the human brain became adapted to solving the problems that our ancestors regularly faced in life.

The Wason Selection Task has become the center of the debate over evolutionary psychology. Some critics, such as the French psychologist Dan Sperber, claim that Cosmides and Tooby can't make such strong statements about human reasoning from the Wason Selection Task. Others claim that the brain can't be sliced up into modules so nicely.

The controversy has taken a very interesting turn now, thanks to brain imaging. A team of Italian psychologists had people lie in an MRI scanner and work their way through a set of puzzles that followed the same line of logic as the ones I presented above. They then compared how the brain responded to the challenges to see if indeed the brain works differently when it is solving problems in terms of social exchange than when the problem is more abstract.

The psychologists didn't use a conventional Wason Selection Task like the ones above, because they wanted to make the problems as similar as possible, except that one dealt with social exchanges. Brain imaging requires this sort of strict experimental design, because it's very easy to see differences in brain activity that aren't actually relevant to the question a scientist wants to answer. For example, if one puzzle just so happens to involve picturing an object, some of the brain's visual processing may become active. So the researchers told their subjects that the puzzles would involve a hypothetical tribe. A purely descriptive puzzle might require subjects to consider the rule, "If a person cracks walnut shells, then he drinks pond water." The subjects might then see a set of cards that read, "He didn't drink pond water," "He didn't crack walnut shells," He cracked walnut shells," and "He drank pond water." The researchers also had their subjects solve puzzles that involved social exchanges. The rule in these cases might be, "If you give me sunflower-seeds, then I give you poppy petals."

The psychologists report the results of the test in a paper in press at the journal Human Brain Mapping (click the html link to get the whole paper for free). The results are fascinating--although the researchers don't claim to have settled the debate over the cheater module. Both the social exchange and descriptive version of the puzzle activated the same network of regions on the left side of the brain. One region (the angular gyrus) is considered important for semantic tasks. A second region is located near the left temple (the dorsolateral prefrontal cortex). It's essential for considering many different pieces of information at once. The third region, the medial prefrontal cortex, becomes active when people need to bear in mind a larger goal while they solve the many small problems it poses. Previous studies have shown that the left side of the brain plays a much more important role than the right in reasoning and coming up with explanations for how the world works in general.

Now here's the kicker: the social exchange version of the problem doesn't just activate this left-brain network. It also activates the same regions in the right side of the brain. Many studies in which people have thought about social situations have tended to turn on the right side of the brain more than the left, and so in one sense this result isn't too surprising. But it is surprising when you consider that the descriptive version of the puzzle that only switch on parts of the left side of the brain involved thinking about other people and their actions. You might think that that would be social enough to engage any parts of the brain specializing in social thinking. Apparently not. Only when the puzzle involved rules for social exchanges did the right-brain network come on line.

Is this the cheater module? It's conceivable that the Italian psychologists tapped into some social brain circuit that isn't specifically adapted for enforcing social rules, but for some somewhat broader group of social problems. It would be interesting if a test other than the Wason Selection Task could trigger the same left versus left-right patterns. The precise evolutionary forces that shaped this feature of the mind may not be clear yet. But this experiment is an important step towards working out the biology between the strange results of the Wason test. Clearly, our brains throw a lot more neurons at logic problems when they concern our social lives instead of abstractions. Analytic philosophers are made, you could say, but political philosophers are born.

Update: 7:15 pm-- I decided to change the first version of the test to avoid ambiguity.

Update: Tuesday, 8:15 am-- Some commenters have argued that people do better with the bar version of the puzzle because people have more experience with it than with abstract logic. Actually, many variations of the puzzle have been tested out, and the same results emerge. Notice, for example, that the Italian scientists who did the most recent study put the puzzles in terms of a hypothetical tribe, with which the subjects had no experience at all. Despite this different format, almost precisely the same fraction of the subjects got the different versions write as in more familiar versions of the test, such as the bartending example.

Thanks also to the sharp readers who pointed out that the puzzles need to be If-Then propositions.

I've got an article in tomorrow's New York Times about a startling new way to control the nervous system of animals. Scientists at Yale have genetically engineered flies with neurons that grow light-sensitive triggers. Shine a UV laser at the flies, and the neurons switch on. In one experiment, the scientists were able to make decapitated flies leap into the air by triggering escape-response neurons. In another, they put the trigger in dopamine-producing neurons, and the flash sent healthy flies walking madly around their dish. (You can read the paper for free at Cell's web site.)

In working on this story, I was reminded of the research being done now with implanted electrodes, which I wrote about last year in Popular Science. Much of this research focuses on listening in on neurons to control robots or computers. But the electrodes have also been used to send electricity into the brain to control an animal. In one case, scientists steered a rat by sending jolts into its brain.

But those who feel anxious about the genetic engineering I write about tomorrow should bear a couple things in mind. First off all, this method only lets scientists turn on an entire type of neurons. All the escape-response neurons became active in the first experiment. All the dopamine-producing neurons became active in the second. That's a far cry from a complex set of signals that might make an animal carry out a complex behavior. But that's not what the scientists who designed this new method had in mind, anyway. They want to develop new ways to do experiments on the nervous system.

Still, science fiction writers should pay heed. It's conceivable, for example, that a completely unethical scientist could engineer similar triggers into a human brain (although it could also fail completely). And another thing that inspires the sci-fi imagination is the experiment on dopamine-producing neurons. Dopamine is a neurotransmitter that give the brain a sense of expectation and anticipation, priming it to learn how to gain rewards. It's also what cocaine exploits to produce its addictive pleasure. In other words, when the scientists switched on their laser, the flies got the biggest high of their lives.

Scientists studying people in minimally conscious states have published the results of brain scans showing that these people can retain a surprising amount of brain activity. The New York Times and MSNBC, among others, have written up accounts.

I profiled these scientists for a 2003 article in the New York Times Magazine, when they were at an earlier stage in their research. Things certainly have changed since then. When my article came out, hardly anyone had heard of Terri Schiavo, the Florida woman in a permanent vegetative state who is at the center of a battle between her parents, who want to keep her feeding tube in, and her husband, who wants it taken out. Since then, her case has made national headlines, and a law has been passed in her name. I for one will be keeping close attention to how this new paper is received (and used) in the debate over Terri Schiavo, because I had the displeasure of watching my article get pulled into the debate and distorted for political ends.

The key point to bear in mind about this new research is that there's a difference between people in a permanent vegetative state and people in a minimally conscious state. Neurologists have developed bedside tests to determine which state a given patient is in. People in minimally conscious states show fleeting, but authentic, awareness of their surroundings, for example. People in vegetative states do not. Neurologists cannot make this diagnosis from the reports of family members, because it is easy to see awareness in a loved one when there is, in fact, none. That doesn't mean that family members are necessarily wrong if they say a loved one is aware. It's just that a doctor needs to test a patient objectively, using methods that don't rely on his or her own interpretation.

Some people have argued that this test is circular: people are simply defined minimally conscious if they pass a test for minimal consciousness. But the designers of the test have shown that it does have predictive power. For one thing, people who rise to a minimally conscious state have a small but real chance of recovering consciousness (although they may never return to their former selves). People who stay in a permanent vegetative state for many years, by contrast, almost never recover.

The brain scan findings now being reported also strengthen the notion of a minimally conscious state. The researchers scanned the brains of patients diagnosed as minimally conscious, playing the voice of loved ones through headphones, scratching their skin, and doing other tests to check for the function of their brain. They found that the patients responded in important ways. Some patients responded to the recordings with strong activity in regions of the brain involved in language and memory, for example. But in the absence of stimuli, the brains of the patients used less energy than a person would under anesthesia.

On the other hand, earlier scans of people diagnosed as being in a permanently vegetative state showed at most only isolated islands of activity in the cortex, where higher brain functions take place. So the difference detected by bedside tests is mirrored by a difference detected in the brain scanner.

It's crucial neither to overplay or underplay the importance of this work. People who are coping with the staggering burden of a loved one in a truly permanent vegetative state should not see this as evidence that their loved one is conscious and simply "locked in" to an unresponsive body. Nor should pundits raise false hopes by claiming that this is the case.

But it is also true that people with impaired consciousness are not getting the attention they deserve, starting with a good diagnosis. Thirty percent of people in a permanent vegetative state may actually be minimally conscious. It would be fantastic if some day doctors could make a precise diagnosis of brain-damaged patients simply by running them through some tests in a scanner. For now, though, only a handful of people with impaired consciousness in the entire world have been scanned at all. Eventually, it might be possible to use the knowledge gained from these tests to start finding ways to help people recover more of their consciousness, perhaps through brain stimulation. Today there's nothing a doctor can do but wait and watch.

Unfortunately, people with impaired consciousness are more likely to be simply warehoused, getting hardly any attention from a neurologist. Are we, as a society, ready to give these voiceless people the care they deserve?

Soul Made Flesh made Amazon.com's Editor's Pick list of the ten best science books of 2004. It's an honor, although it seems a little premature to call 2004 over!

I am sure that in 50 years, we are going to know a lot more about how the mind works. The fusion of psychology and genetics will tell us about how our personality is influenced by our genes, and they'll also show exactly how the environment plays a hand as well. The preliminary evidence is just too impressive to seriously doubt it. Likewise, I am sure that we will have a deeper understanding how our minds have evolved, pinpointing the changes in DNA over the past six million years have given us brains that work very differently than apes. Again, the first results can't help but inspire a lot of hope.

Given where I stand on all this, I would have thought that I'd enjoy Dean Hamer's new book, The God Gene: How Faith is Hard-Wired In Our DNA. The time is ripe, judging from the string of books that have been published in the past few years on the link between religion and biology. I thought that Hamer, a geneticist, might be able to throw some interesting information into the mix, thanks to his expertise in behavioral genetics. The book turned out to be elegant and provocative, and, as I write in my review in the new issue of Scientific American, disappointingly thin on the evidence. From a single study that Hamer hasn't even published yet, he weaves an incredibly elaborate scenario in which faith is an adaptive trait. I wouldn't be surprised if it is the product in some way of natural selection, but now is hardly the time to be writing a book claiming to have figured out its origins--not to mention making appearances on talk shows and the like. Too many links between behavior and genes have already crashed and burned (including some Hamer himself has made).

Update, 9/27: Scientific American has posted the review on their site

The soft spot on a baby's head may be able to tell us when our ancestors first began to speak.

We have tremendously huge brains--six times bigger than the typical brain of a mammal our size. Obviously, that big size brings some fabulous benefits--consciousness, reasoning, and so on. But it has forced a drastic reorganization of the way we grow up. Most primates are born with a brain fairly close to its adult size. A macaque brain, for example, is 70% of adult size at birth. Apes, on the other hand, have bigger brains, and more of their brain growth takes place after birth. A chimpanzee is born with a brain 40% of its adult size, and by the end of its first year it has reached 80% of adult size. Humans have taken this trend to an almost absurd extreme. We are born with brains that are only 25% the size of an adult brain. By the end of our first year, our brains have reached only 50%. Even at age 10, our brains are not done growing, having reached 95% of adult size. For over a decade, in other words, we have newborn brains.

It's likely that this growth pattern evolved as a solution to a paradox of pregnancy. Brains demand huge amounts of energy. If mothers were to give birth to babies with adult-sized brains, they would have to supply their unborn children with a lot more calories in utero. Moreover, childbirth is already a tight fit that can put a mother's life in jeopardy. Expand the baby's head more, and you raise the risks even higher.

Extending the growth of the brain obviously gave us big brains, but it may have endowed us with another gift. All that growth now happened not in the dark confines of the womb, but over the course of years of childhood. Instead of floating in an aminotic sac, children run around, fall off chairs, bang on pots, and see how loud they can scream. (At least mine do.) In other words, they are experiencing what it's like to control their body in the outside world. And because their brains are still developing, they can easily make new connections to learn from these experiences. Some researchers even argue that only after the brains of our ancestors became plastic was it possible for them to begin to use language. After all, language is one of the most important things that children learn, and they do a far better job of learning it than adults do. If scientists could somehow find a marker in hominid fossils that shows how their brains grew, it might be possible to put a date on the origin of language.

That's where the soft spot comes in.

The oldest hominids that look anything like humans first emerged in Africa about 2 million years ago. They were about as tall as us, with long legs and arms, narrow rib cages, flat faces, and small teeth. The earliest of these human-like hominids are known as Homo ergaster, but they rapidly gave rise to a long-lived species called Homo erectus. H. erectus probably originated in Africa, but then burst out of the home continent and spread across Asia to Indonesia and China. The Homo erectus people who stayed behind in Africa are probably our own ancestors. The Asian H. erectus thrived until less than 100,000 years ago. They could make simple stone axes and choppers, and had brains about two-thirds the size of ours.

Paleoanthropologists have found only a single braincase of a baby Homo erectus. It was discovered in Indonesia in 1936, and has since been dated to 1.8 million years old--close to the origin of the species. While scientists have had a long time to study it, they haven't made a lot of progress. One problem is that the fossil lacks jaws or teeth, which can offer clues to the age of a hominid skull. The other problem is that the interior of the braincase was filled with rock, making it hard to chart its anatomy.

In the new issue of Nature, a team of researchers rectified this problem with the help of a CT scanner. They were able to calculate the volume of the child's brain, and then they were able to map the bones of the skull more accurately. As babies grow, the soft spot on their skull closes up and other bones are also rearranged in a predictable sequence. Chimpanzees, our closest living relatives, also close up their skulls in the same pattern, with some small differences in timing. The H. erectus baby, its skull shows, was somewhere between six and eighteen months old. Despite its tender age, the Homo erectus baby had a big brain--84% the size of adult Homo erectus brains as measured in fossil skulls.

A single battered braincase still leaves plenty of room for uncertainty, but it's still a pretty astonishing result. At a year old, this Homo erectus baby was almost finished growing its brain. It spent very little time developing its brain outside the womb, suggesting that it didn't have enough opportunity to develop the sophisticated sort of thinking that modern human children do. If that's true, then it's unlikely it could ever learn to speak. If these researchers are right, then future CT scans of younger hominid skulls should be able to track the rise of our long childhood.

"A world without memory is a world of the present," Alan Lightman wrote in Einstein's Dreams. "The past exists only in books, in documents. In order to know himself, each person carries his own Book of Life, which is filled with the history of his life...Without his Book of Life, a person is a snapshot, a two-dimensional image, a ghost."

Most people would probably agree with Lightman. Most people think that our self -knowledge exists only through the memories we have amassed of our selves. Am I a kind person? Am I gloomy? To answer these sorts of questions, most people would think you have to open up some internal Book of Life. And most people, according to new research, are wrong.

Neuroscientists would call Lightman's Book of Life episodic memory. The human brain has a widespread system of neurons that store away explicit memories of events, which we can recall and describe to others. Some forms of amnesia destroy episodic memories, and sometimes even destroy the capacity to form new ones. In 2002, Stan B. Klein of the University of California at Santa Barbara and his colleagues reported a study they made of an amnesiac known as D.B. D.B. was 75 years old when he had a heart attack and lost his pulse. His heart began to beat after a few minutes, and he left the hospital after a few weeks. But he had suffered brain damage that left him unable to bring to mind anything had done or experienced before the heart attack. Klein then tested D.B.'s self-knowledge. He gave D.B. a list of 60 traits and asked him whether they applied to him not at all, somewhat, quite a bit, or definitely. Then he gave the same questionnaire to D.B.'s daughter, and asked her to use it to describe her fater. D.B.'s choices significantly correlated with his daughter's. D.B.'s Book of Life was locked shut, and yet he still knew himself.

A few other amnesiacs have shown a similar level of self-knowledge, but it's hard to draw too many lessons from them about how normal brains work. So recently Matthew Lieberman of UCLA and his colleagues carried out a brain-scanning study. They wanted to see if they could find different networks in the brain that make self-knowledge possible. They also wanted to see if these networks functioned under different circumstances--for example, when thinking about ourselves in very familiar contexts and unfamiliar ones.

They picked two groups of people to test: soccer players and improv actors. They then came up with a list of words that would apply to each group. (Soccer players: athletic, strong, swift; actors: performer, dramatic, etc.) They also came up with a longer list of words that applied specifically to neither (messy, reliable, etc.). Then they had all the subjects get into an fMRI scanner, look at each word, and decide whether it applied to themselves or not.

The volunteers' brains worked differently in response to different words. Soccer-related words tended to activate a distinctive network in the brains of soccer players, the same one that actor-related words switched on in actors. When they were shown words related to the other group, a different network became active. And, as Lieberman and his colleagues report in an upcoming issue of the Journal of Personality and Social Psychology, it just so happens that they had predicted precisely which two networks would show up in their scans. (Here's the full pdf on Lieberman's web site.)

When people were presented with unfamiliar words, they activated a network Lieberman calls the Reflective system (or C system for short). The Reflective system taps into parts of the brain already known to retrieve episodic memories. It also includes regions that can consciously hold pieces of information in mind. When we are in new circumstances, our sense of our self depends on thinking explicitly about our experiences.

But Lieberman argues that over time, another system takes over. He calls this one the Reflexive system (or X system). This circuit does not include regions involved in episodic memories, such as the hippocampus. Instead, it is an intuition network, tapping into regions that produce quick emotional responses based not on explicit reasoning but on statistical associations. (The picture I show here is a figure from the paper, with the X and C systems mapped out.)

The Reflexive system is slow to form its self-knowledge, because it needs a lot of experiences to form these associations. But it becomes very powerful once it takes shape. A soccer player knows whether he is athletic, strong, or swift without having to open up the Book of Life. He just feels it in his bones. He doesn't feel in his bones whether he is a performer, or dramatic, and so on. Instead, he has to think explicity about his experiences. Now D.B.'s accurate self-knowledge makes sense. His brain damage wiped out his Reflective system, but not his Reflexive system.

This research is fascinating on its own, and even more so when you think about the evolution of the self. Judging from the behavior of humans and apes, I'd guess that the Reflective system seems to be far more developed in us, while apes may share a pretty well developed Reflexive system. Does that mean that a Reflexive self existed before a Reflected one? Is the self we see in the Book of Life a recent innovation sitting an ancient self that we can't put into words? And does that mean that chimpanzees have a Reflexive self? Is that enough of a self to warrant the sort of rights we give to humans because they are aware of themselves?

Our brains are huge, particularly if you take into consideration the relative size of our bodies. Generally, the proportion of brain to body is pretty tight among mammals. But the human brain is seven times bigger than what you'd predict from the size of our body. Six million years ago, hominid brains were about a third the size they are today, comparable to a chimp's. So what accounts for the big boom? It would be flattering ourselves to say that the cause was something we are proud of--our ability to talk, or our gifts with tools. Certainly, our brains show signs of being adapted for these sorts of things (consider the language gene FOXP2). But those adaptations probably were little more than tinkerings with a brain that was already expanding thanks to other factors. And one of those factors may have been tricking our fellow hominid.

In the 1980s, some primatologists noticed that monkeys and apes--unlike other mammals--sometimes deceived members of their own species, in order to trick them out of food or sneak off for some furtive courtships. The primatologists got to thinking that deception involved some pretty sophisticated brain power. A primate needed to understand something about the mental state of other primates and have the ability to predict how a change in that mental state might change the way other primates behaved.

The primatologists then considered the fact that humans aren't the only primates with oversized brains. In fact, monkeys and apes, on average, have brains twice the size you'd predict for mammals of their body size. Chimpanzees and other great apes have particularly big brains, and they seemed to be particularly adept at tricking each other. What's more, primates don't simply have magnified brains. Instead, certain regions of the brain have expanded, such as the neocortex, the outer husk of the brain which handles abstract associations. Activity in the neocortex is exactly the sort of thinking necessary for tricking your fellow ape.

Taking all this into consideration, the primatologists made a pretty gutsy hypothesis: that the challenges of social life--including deception--actually drive the expansion of the primate brain. Sometimes called the Machiavellian Intelligence hypothesis, it has now been put to its most rigorous test so far, and passed quite well. Richard Byrne and Nadia Corp of the University of St. Andrews in Scotland published a study today in the Proceedings of the Royal Society of London. (The link's not up yet, but here's a New Scientist piece.) They found that in 18 species from all the major branches of primates, the size of the neocortex predicts how much deception the species practices. Bigger brains mean more trickery. They were able to statistically rule out a number of other factors that might have created a link where none existed. And they were able to show that deception is not just a side-effect of having a big brain or something that opportunistically emerges more often in big groups. Deception is probably just a good indicator of something bigger going on here--something psychologists sometimes call "social intelligence." Primates don't just deceive one another; they also cooperate and form alliances and bonds, which they can keep track of for years.

While deception isn't just an opportunistic result of being in big groups, big groups may well be the ultimate source of deception (and by extension big brains). That's the hypothesis of Robin Dunbar of Liverpool, as he detailed last fall in the Annual Review of Anthropology. Deception and other sorts of social intelligence can give a primate a reproductive edge in many different ways. It can trick its way to getting more food, for example; a female chimp can ward off an infanticidal male from her kids with the help of alliances. Certain factors make this social intelligence more demanding. If primates live under threat of a lot of predators, for example, they may get huddled up into big groups. Bigger groups mean more individuals to keep track of, which means more demands on the brain. Which, in turn, may lead to a bigger brain.

If that's true, then the human brain may have begun to emerge as our ancestors huddled in bigger groups. It's possible, for example, that early hominids living as bipeds in patchy forests became easier targets for leopards and other predators. Brain size increased modestly until about two million years ago. It may not have been able to grow any faster because of the diet of early hominids. They probably dined on nuts, fruits, and the occasional bit of meat, like chimpanzees do today. That may not have been enough fuel to support a really big brain; brain tissue is incredibly hungry, demanding 16 times more energy than muscle, pound for pound. It was only after hominids began making butchering tools out of stones and got a steady supply of meat from carcasses that the brain began to expand. And it was probably around this time (between 2 and 1.5 million years ago) that hominids began evolving the extraordinary powers of deception (and other sorts of social intelligence) that humans have. We don't just learn how other people act--we develop a powerful instinct about what's going on in their minds. (I wrote about the neuroscience behind this "mentalizing" last year in an article for Science.)

So next time you get played, temper your anger with a little evolutionary perspective. You've just come face to face with a force at work in our evolution for over 50 million years.

UPDATE 7/3/04: A skeptical reader doubted some of my statements about the brain and the energy it requires. Those who crave more information should check out Northwestern University anthropologist William Leonard's article "Food for Thought" in Scientific American.

In the New York Times this morning, the poet Diane Ackerman has written an essay about the brain, in which she waxes eloquent about its ability to discern patterns in the world. The essay is distilled from her new book, An Alchemy of the Mind, which I've just reviewed for the Washington Post. I didn't much like the book, although it took me a while to figure out what was bothering me about it. If you read the essay, you can get the flavor of the book, not to mention Ackerman's general style in her previous books (which have taken on subjects such as endangered species and the senses). Ackerman has a fondness for sipping tea, tie-dye dresses, and hummingbird feeders, and an even greater fondness for writing about them. I know people who have been put off by her aesthetics, and I find them cloying as well. But that wasn't really at the heart of my dislike of the book. (And besides, my own aesthetics leans towards shark tapeworms and dissected sheep brains, so I'm hardly one to complain about other people.) It took me a few days to realize that the problem with the book was embedded in a deeper problem: how we talk about nature (which includes our own minds).

By we, I don't mean cognitive neuropsychologists or planetologists or molecular ecologists. I mean the rest of us, or the collective us, the ones who consciously or unconsciously create the language, metaphors, and stories that serve as our shared understanding of the world. The words we use, even in passing, to describe genes or brains or evolution can lock us into a view of nature that may be meaningful or misleading. When people say, "Being dull is just written into his DNA," they may only intend a light joke, but the metaphor conjures a false image of how personality emerges from genetics and environment and experience. This figure of speech may seem like nothing more than a figure of speech until people step into the office of a genetics counselor to find out about their unborn child.

The brain suffers from plenty of bad language. In some cases, the language is bad because it's unimaginative. In Alchemy of the Mind, Ackerman points out that calling neurotransmitters and receptors keys and locks does a disservice to their soft, floppy nature. In other cases, though, the language is bad because it's based on gross simplifications of outmoded ideas. Yet it survives, taking on a life of its own separate from the science. My favorite example, which I wrote about last year, is the bogus story you always hear about how we only use ten percent of your brain.

Ackerman indulges in this sort of bad language a lot. One example: she loves referring to our "reptile brain," as if there was a nub of unaltered neurons sitting at the core of our heads driving our basic instincts. The reality of the brain--and of evolution--is far more complex. The brain of reptilian forerunners of mammals was the scaffolding for a new mammal brain; the old components have been integrated so intimately with our "higher" brain regions that there's no way to distinguish between the two in any fundamental way. Dopamine is an ancient neurotransmitter that provides a sense of anticipation and reward to other animals, including reptiles. But our most sophisticated abilities for learning abstract rules, carried out in our elaborate prefrontal cortex, depend on rewards of dopamine to lay down the proper connections between neurons. There isn't a new brain and an old brain working here--just one system. Yet, despite all this, it remains seductive to use a phrase like "reptile brain." It conjures up lots of meanings. Ackerman floods her book with such language, which I grouse about other bad language in my review.

Which makes me wonder, as a science writer myself: is all poetry is ultimately dangerous? Does scientific understanding inevitably get abandoned as we turn to the juicy figure of speech?

Update: 6/14/04 11 AM: NY Times linked fixed

I always like book reviews that combine books that might not at first seem to have that much in common. In the new issue of Natural History, the neuroscientist Williams Calvin reviews Soul Made Flesh along with The Birth of the Mind, a fascinating book by Gary Marcus of NYU. If you haven't heard of Marcus's new book--which explores how genes produce minds--definitely check it out.

It's strange enough hearing yourself talking on the radio. It's stranger still to see a transcript someone makes of you talking on the radio. Recently I was interviewed about Soul Made Flesh on Australian Broadcasting Corporation's show "All in the Mind." Instead of an audio archive, ABC has posted a transcript of the show. While I can't claim I spoke in perfect paragraphs, we had an interesting talk about how the brain became the center of our existence.

I was asked a couple weeks ago to contribute a piece to a special series of articles in Newsweek about the future of Wi-Fi. I must admit that a fair amount of the stuff that's on the Wi-Fi horizon seems a little banal to me. It's nice to know that I will be able to swallow a camera-pill that will wirelessly send pictures of my bowels to my doctor, but it hardly cries out paradigm shift. On the other hand, I've been deeply intrigued and a little disturbed by the possibility that the next digital device to go Wi-Fi is the human brain. Here's my short essay on the subject.

My book Soul Made Flesh looks at the roots of neuroscience in the 1600s. The first neurologists saw their work as a religious mission; they recognized that it was with the brain that we made moral judgments. In order to finish the book, I looked for living neuroscientists who carry on those early traditions today. I was soon fascinated by the work of Joshua Greene, a philosopher turned neuroscientist at Princeton. Greene is dissecting the ways in which people decide what is right and wrong. To do so, he poses moral dilemmas to them while he scans their brains. I mentioned Greene briefly in Soul Made Flesh and then went into more detail in a profile I wrote recently. Greene and I will join forces tomorrow on the show “New York and Company” on WNYC tomorrow around 12:30 pm. You can listen to us on the radio or on the web.

This week I am in England to give some talks about Soul Made Flesh, which has just been published here. In addition to talking on the BBC, I'll be talking at Blackwell's in Bristol on Tuesday, and at the Museum of the History of Science at Oxford University on Wednesday. I've posted details and links to even more details on the talks page of my web site.

It's a bit daunting coming here, the very place where much of my book is set. But the response has been kind so far. This morning the eminent historian Lisa Jardine wrote a generally good review in the Sunday Times. Meanwhile, stateside, another Brit (Adam Zeman) wrote a positive review in The New York Times Book Review.

While I'm here, I hope to have a little spare time to blog a bit on some interesting new research (and fisk the latest creationist shenanigans). If logistics get the better of me, I'll definitely get back on track next week when I get home.

In February I wrote an article in Popular Science about a project to implant electrodes in a monkey's brain allowing the monkey to control a robot arm with its mind. The goal of this work is to let paralyzed people operate prosthetic limbs by thought alone. Now the research team has announced another big step in that direction: their first work on humans.

They implanted their electrodes into the brains of people undergoing surgery for Parkinson's disease and tremor disorders, and then had the patients play a video game with a joystick. (In brain surgery, patients don't get general anasthesia.) After a little gaming, the researchers removed the electrodes and the surgery resumed. The signals the electrodes captured from the brains of patients as they produced action commands proved to be so clear that a computer was able to use them to predict which way the patients had moved the joystick. Now the researchers are applying to the government to do long-term research on electrodes implanted in quadriplegics.

As is the case with many neuroscientific breakthroughs (memory-boosting drugs for the elderly, sleep-suppressing drugs for narcoleptics), the thorny question arises: should healthy people be allowed (or required for their job) to get an implant? After all, wouldn't you want to run your computer, your car, or your military killer-robot with your mind?

Attention Virginian readers of the Loom: I'll be heading to warmer climes later this week to speak in Charlottesville at the Virginia Festival of the Book. On Thursday at 4 I'll be speaking on a panel about science and society. On Friday at 4 I'll be speaking again on scientific discoveries and how they change us. I'm looking forward to listening to my fellow panelists, who include Robin Marantz Henig and James Shreeve. See you there.

I've posted a new batch of reviews for Soul Made Flesh on my web site. The newest is from Ross King, the author of Brunelleschi's Dome and Michelangelo and the Pope's Ceiling. His review in yesterday's Los Angeles Times is a rare sort--he likes the book (which he calls "thrilling") for what the book really is, rather than as a projection of some phantom in his own mind.

A review of a different sort comes from Simon Conway Morris of the University of Cambridge. Conway Morris is a first-rate paleontologist who has shed a lot of light on how the major groups of animals alive today emerged in the Cambrian Period. In recent years he's also started to nudge some more spiritual notions into public view, suggesting for instance that the evolution of life has displayed a built-in direction towards us, or at least something like us. Conway Morris reviews Soul Made Flesh in the March issue of Bioscience, which is published by the American Institute of Biological Sciences. I can't complain about a review that calls my book "a wonderful read," but on the other hand, I found it odd that Conway Morris criticizes me for concluding that we know something more about how the brain works now than people did in 1600. He seems to think I'm attacking his personal notion of the human soul, when in fact I'm actually talking about how the seventeenth century notion of the soul was transformed--in part--into an understanding of the brain. As peculiar as it may be, it's well-written, though.

Three weeks ago, I gave a talk at Stanford University about my new book Soul Made Flesh. A wonderful crowd turned out and peppered me with excellent questions afterwards, each of which could have become new talks of their own. CSPAN was there to film it, and they'll be broadcasting the talk this Saturday, March 20, at 9 am EST on BookTV.

You may want to check out this little RSS a commenter forwarded to me that converts the BookTV schedule to any time zone. Also, if you miss the talk, it will probably repeated on another weekend, so check back to their site.

Here's an added incentive to watch: you don't have to look at the nervous, quavering face of an author, interspersed only by slow pans across a silent, expressionless audience. I brought along a Powerpoint file loaded with gorgeous, bizarre seventeenth century artwork to go along with the story of the search for the soul and the dawn of neurology. Straight from my laptop to your eyes.

When George Bush quietly dismissed two members of his Council on Bioethics on the last Friday in February, he probably assumed the news would get buried under the weekend’s distractions. But ten days later, it’s still hot—see, for example, two articles in Slate, and an editorial in the Washington Post, as well as Chris Mooney's ongoing coverage at his blog. Bush failed to appreciate just how obvious the politics were behind the move. The two dismissed members (bioethicist William May and biochemist Elizabeth Blackburn) have been critical of the Administration. Their replacements (two political scientists and a surgeon) have spoken out before about abortion and stem cell research, in perfect alignment with the Administration. Bush also failed to appreciate just how exasperated scientists and non-scientists alike are becoming at the way his administration distorts science in the service of politics (see this report from the Union of Concerned Scientists, which came out shortly before the bioethics flap). And finally, Bush failed to appreciate that Blackburn would not discreetly slink away. Instead, she fired off a fierce attack on the council, accusing them of misrepresenting the science behind stem cell research and other hot-button issues in order to hype non-existent dangers.

The chairman of the council, Leon Kass, failed as well when he tried to calm things down last Wednesday. He claimed that the shuffling had nothing to do with politics, and that he knew nothing about the personal of his new council members. Reporters have pointed out the many opportunities when Kass almost certainly did learn about those views.

But Kass stumbled on another count, one that I think speaks to a profound problem with the council and one that I haven’t read much comment on. Kass claimed that Blackburn had to be replaced because the council will now be focusing on neuroscience, rather than reproduction and genetics, Blackburn's areas of expertise. If that’s true, then the council is not ready for a shift to the brain. If the Bush administration wanted to beef up the council's neuroscience credentials, surely they would have replaced Blackburn and May with neuroscientists. They did not. In fact, the council as it's now constituted has only one member who does research on neuroscience.

Even more troubling, though, is the indifference the council has shown to what neuroscience tells us about bioethics itself.

Kass has written in the past about how we should base our moral judgments in part on what he calls "the wisdom of repugnance." In other words, the feeling you get in your bones that something is wrong is a reliable guide to what really is wrong. The Council on Bioethics embraces Kass's philosophy. They have declared that happiness exists to let us recognize what is good in life, while real anger and sadness reveal to us what is evil and unjust. "Emotional flourishing of human beings in this world requires that feelings jibe with the truth of things, both as effect and as cause," they write. By extension, repugnance is a good guide for making decisions about bioethics. If cloning gives you the creeps, it’s wrong.

But what exactly produces those creeps? In recent years neuroscientists and psychologists have made huge strides in understanding both emotions and moral judgments. They've scanned people's brains as they decide whether things are right or wrong; they've looked at the brain's neurochemistry, and they've gotten insights from the brains of animals and the fossils of ancient hominids as well. And their conclusions seriously undermine the philosophy of the council.

In the April issue of Discover, I have an article about one of the leaders in this new field of "neuro-morality," a philospher-neuroscientist named Joshua Greene at Princeton University. Greene argues that feeling that something is right or wrong isn't the same as recognizing that two and two make four, or that the sky is blue. It feels the same only because our brains respond to certain situations with emotional reactions that happen so fast we aren't aware of them. We are wired to get angry at deception and cruelty; even the thought of harming another person can trigger intense emotional reactions. These "moral intuitions" are ancient evolutionary adaptations, which exist in simpler versions in our primate relatives.

When our ancestors stood upright and got big brains, Greene argues, these moral intuitions became more elaborate. They probably helped hominids survive, by preventing violence and deception from destroying small bands of hunter-gatherers who depended on each other to find food and raise children. But evolution is not a reliable guide for figuring out how to lead our lives today. Just because moral intuitions may be the product of natural selection doesn't mean they are right or wrong, any more than feathers or tails are right or wrong.

Jonathan Cohen, Greene’s coauthor (and boss and at Princeton), was invited to speak to the council at a public meeting in January. He suggested that we need to understand that moral intuitions are not automatically moral truths--particularly when they're applied to complicated ethical quandaries about science and technology that our ancestors never had to confront. It was good of the council to invite Cohen, but judging from their comments after Cohen's talk, the message didn't really take. The wisdom of repugnance seems to be still in charge.

That's too bad, because understanding our moral intuitions is crucial to making sound decisions about cloning, stem cells, giving psychiatric drugs to children, and all the other issues the council is charged to consider. The neurobiology of moral judgments promises to reveal why these issues are such political flashpoints, by showing how each side in these debates becomes utterly convinced that the right choice is as obvious as the color of the sky. There’s a biology to bioethics, and the President’s council needs to understand it.

UPDATE: Welcome to readers clicking through from the National Review Online link. Rameh Ponnuru's objections to this post are rather scatter-shot--he suggests that the "wisdom of repugnance" is not the philosophy of the council--or it is in the case of a couple people who don't agree with the Administration on a couple points--or it's not. In the interest of clarity, please note the quotations I offered above on the nature of emotions. These come from "Beyond Therapy," the book-length report published by the council. In these passages and elsewhere, "moral realism" as it's known, is an underlying assumption. This is of course, a consensus statement and not the opinion of a monolithic entity, but it's the document that people will look at as the council's stance. (It was Blackburn's objections to "Beyond Therapy" that appear to have gotten her in big trouble, judging from her post-dismissal comments.) And if you look over the transcripts of Cohen's presentation, the comments of several members are consistent with a desire to see in Cohen's work that idea that moral intuitions are faithful guides to moral truths.

Over on my web site I've posted an article I've just written for the Sunday Telegraph Magazine in England about an eerie brain disorder called musical hallucinosis. You've probably had a tune stuck in your head for an hour at least once in your life. Now imagine that the tune played all day and night--and imagine that it sounded as real as if a marching band was standing by your window.

Here's how it starts:

Janet Dilbeck clearly remembers the moment the music started. Two years ago she was lying in bed on the California ranch where she and her husband were caretakers. A mild earthquake woke her up. To Californians, a mild earthquake is about as unusual as a hailstorm, so Dilbeck tried to go back to sleep once it ended. But just then she heard a melody playing on an organ, "very loud, but not deafening," as she recalls. Dilbeck recognized the tune, a sad old song called When You and I Were Young, Maggie.

Maggie was her mother's name, and when Dilbeck (now 70) was a girl her father would jokingly play the song on their home organ. Dilbeck is no believer in ghosts, but as she sat up in bed listening to the song, she couldn't help but ask, "Is that you, Daddy?"

She got no answer, but the song went on, clear and loud. It began again from the beginning, and continued to repeat itself for hours. "I thought, this is too strange," Dilbeck says. She tried to get back to sleep, but thanks to the music she could only doze off and on. When she got up at dawn, the song continued. In the months to come, Dilbeck would hear other songs. She heard merry-go-round calliopes and Silent Night. For a few weeks, it was The Star-Spangled Banner.

Go here to read the rest.

Brain disorders always grab our attention because they have the power to warp the fabric of reality, or at least our experience of it. But they can tell us even deeper things about ourselves--specifically, how the human mind was assembled over the course of evolution. Autistic people, for example, lack what psychologists call a theory of mind--an intuition of what other people are thinking. In an article I wrote last year for Science, I detailed research that shows how the evolution of a theory of mind was key to the rise of social intelligence in humans, perhaps even making language possible.

Musical hallucinations may offer some clues to another important feature of human evolution: our capacity for music. Like language, music in humans has no real counterpart elsewhere in the animal kingdom. Birds and whales sing, but their songs have little of the flexibility and creativity that marks human music. And music, researchers are finding, is processed by a complicated network of regions in the brain. Musical hallucinations may emerge when that network is cut off from the outside world by deafness, and it seizes on stray impulses in the brain, cranking them up into the perception of real tunes. But how did this special faculty for music evolve? Scientists I've spoken to don't think there's a good explanation out there yet. When a good explanation does come along, it will have to account for music either as an adaptation in itself or as a byproduct of other adaptations--or some combination of both. The building blocks of music seem to be nested within our ability to understand language and other complex noises--detecting pitch, tempo, and so on. One could argue that proto-music gave our ancestors some reproductive advantage. Perhaps songs gave bands of hominids a powerful sense of solidarity. Or perhaps it is nothing but a fortunate fluke, its pleasure deriving from reward networks that evolved for other functions long before anyone hummed a tune.

Update: 3/9/04 1:20 Theory of mind link fixed

If you want to hear about brain science at its birth and today, check out the public radio show Tech Nation, this week. In the first half of the show, I'll be talking about Soul Made Flesh. In the second half, Steven Johnson will be talking about his excellent new book, Mind Wide Open. You can find out where and when you can listen to the show at the program's web site, or listen to it on their site archive.

(A note to subscribers: sorry for the mysterious email address that appeared on your notification. I have yet to fully master the mysteries of Movable Type.)

If you live in the Bay Area, please join me noon on Monday, February 23, at Stanford University for a talk about Soul Made Flesh. (Here are all the details.)

The talk is sponsored by the Stanford University Center for Biomedical Ethics and the Stanford Brain Research Institute. It's gratifying that such great organizations that are dedicated to twenty-first century neuroscience are interested in the adventures of a motley crew of seventeenth century alchemists and natural philosophers.

The talk is free and open to the public. And if that's not incentive enough, CSPAN will be there to film the talk for BookTV. If you ever wanted to be on television asking a question about the soul with a boom mike dangling over your head, now's your chance. (When BookTV decides on the broadcast date, I'll post it here and on my events page.)

I'll be on Fresh Air with Terry Gross today, talking about Soul Made Flesh. If you miss it today, it will be archived at the show's web site.

If you're in New York, you've got two chances on Tuesday January 27 to hear me talk about Soul Made Flesh. At 5:30 I'll be giving a talk in the "Mind Over Body" lecture series at New York Public Library's Science and Industry Branch at 188 Madison Ave. I'll then be heading to the East Villiage to talk in the more intimate setting of KGB (85 E. 4th St.) at 7:30. Both events are free.

At noon today in New York I'll be at the Makor Center of the 92nd St. Y at 35 W. 67 St. to talk about Soul Made Flesh.

Today I'll be talking for an hour about Soul Made Flesh on Minnesota public radio. You can listen to the broadcast live online at 11 am EST (the show will be archived). At 2 pm EST, you can listen online again when I talk on the Glen Mitchell show on Dallas public radio.

Some thoughts on the intersection of evolution and global warming coming this afternoon. In the meantime, check out Pharyngula's check-box comparison of the similarities between Soul Made Flesh and Quicksilver. Damn, why did I leave out those pirate neurologists...?

Oliver Sacks muses on how we construct our perceptions of reality. (Via ALDaily.)

By sheer coincidence (or some journalistic twist of fate) two magazine articles of mine are coming out this week, and they just so happen to make a nice neurological pairing.

In Science, I've written an essay about what seventeenth-century natural philosophers have to teach twenty-first century neuroscientists about the brain. In the February issue of Popular Science, my cover story looks at the latest work on brain-machine interfaces that will let people control machines with thought alone. Inevitably, the Pop Sci piece can only focus on a time scale of a few years. But the latest brain-machine interfaces seem to me to be the ultimate incarnation of the dreams of the scientific revolution.

Before the 1600s, the world was filled with souls and soul-like forces. In addition to the immortal human soul, there were souls in our organs, in plants, in stars. Water rose in a straw because it abhorred a vaccuum and sought to fill it. In the 1600s, natural philosophers began to dismantle these souls. Galileo busted up the old Aristotelian physics. Descartes offered up the body as an earthen machine. Robert Boyle saw matter as corpuscles--what we call molecules and atoms--colliding and reacting without any purpose driving them from within. Many of these natural philosophers believed that it was essential to take the soul out of nature in order to save Christianity from pagan alternatives. But they also believed that doing so would let mankind master nature. If nature was made up of blind matter that was obedient to God's laws, then unlocking those laws through observation and experiment would turn the world into a scientific paradise of riches and health.

This philosophy had one particularly troubling aspect: how did the human mind fit into the world? Was it also just matter in motion? Thomas Hobbes was happy to say it was. Others didn't want to be mistaken for atheists.Boyle's friend Thomas Willis used the priniciples of the scientific revolution to get the first good understanding of the brain, which he envisioned as a chemical engine of memory, perception, and emotions.

Today this approach to nature has given rise to, among other things, brain-machine interfaces. If, as promised, they someday give paralyzed people some measure of control, they will be yet another example of promoting health through the mastery of nature. But the remarkable thing is what is being mastered here. As one of the bioengineers I spoke to pointed out, he and his colleagues don't see the brain as some mysterious organ, but as a very complicated digital device that is sending out a series of 1s and 0s. By reading the code, they can do something with it. The brain itself--complete with its intentions and plans--has become yet another natural thing to be harnessed. In my opinion, this is both thrilling and terrifying.

I've posted the text and the pdf version of my Science essay on my web site. The table of contents for the February issue of Popular Science is online, but they haven't posted the articles yet. When I get some time, I'll put the text on my site and update this post with the link.

Number seven

I can already see the grim look many Americans will have as they chew on their Christmas roast tomorrow. They'll be thinking about yesterday's report that a cow in Washington state tested positive for mad cow disease. There's some comfort in knowing that so far it's just a single cow, and that American cattle are regularly screened for bovine spongiform encephalitis. The grimmest look this Christmas may be on the faces of McDonald's shareholders and cattle ranchers. A single Canadian cow that test positive wreaked havoc on the entire beef industry up north. But this Christmas also brings a fascinating discovery about the bizarre agents that cause disorders such as mad cow disease: they may actually record our memories.

The work comes from the lab of Eric Kandel, the Columbia University neuroscientist who won the 2000 Nobel Prize for medicine. Kandel got the prize for figuring out some of the molecular underpinnings of memories. Each neuron has one set of branches that send outgoing signals and another set that receives incoming ones. These signals can only jump from one neuron to the next if an outgoing branch nuzzles up to an incoming one, creating a junction called a synapse. Kandel studied how the neurons in a sea slug change as memories are laid down. (These are obviously not memories of the Proustian sort--just simple associations, such as the memory of a shock coming after the flash of a light.) He showed that new synapses are created and other ones grow stronger as memories form. Kandel also identified a number of the molecules that seem to be responsible for strengthening these connection. (His Nobel prize lecture makes for good reading.)

Kandel did not rest on his laurels, but immediately tackled some of the big questions about memory that he and other neuroscientists had yet to figure out. A neuron may have tens of thousands of synapses, but only a few of them may change as a memory forms. Yet the instructions to make proteins that cause this change come from a neuron's single bundle of DNA. If the nucleus gets a signal to form new synapse-strengthening proteins, how do the proteins go only to the right synapses. And, even more importantly, how do those synapses stay strong for decades, when proteins themselves live only a short period of time?

Kandel and his coworkers reasoned that a memory-forming synapse must get some sort of "synaptic mark" that tagged it for synapse-strengthening proteins. They then looked for molecules that might be responsible for the mark. As they report in the December 26 issue of Cell, they have discovered what may well be the synaptic mark in a compound called cytoplasmic polyadenylation element binding protein (CPEB for short). CPEB can be found in cells throughout the body, but they found a special form of it in the neurons of sea slugs, and then later found it in fruit flies and mammals. They found that CPEB is synthesized during the earliest stages of memory formation, and probably drives the production of molecules that physically lay down new synapses and tells them where to grow. Evidence suggests that the protein can do this by "waking up" dormant RNA molecules in the synapse. (RNA is the messenger molecule that carries copies of genetic information to the protein-building factories of the gene.)

To understand how CPEB could do all this, the researchers looked closely at its structure. That's when they had a shock: CPEB has much the same structure as the agent that causes mad cow disease.

Mad cow disease is infectious, but it's caused not by a virus or a bacterium. Instead, it's caused by a rogue protein called a prion. The normal version of the protein (called PrP) may do a number of jobs in the body, and seems particularly important in the brain. But sometimes a PrP gets a funny kink in it and folds into a new shape. This new prion then bumps into a normal PrP and forces the normal copy to take on its own strange shape. The prions clump together and force others to join them in Borg-like fashion. Mad cow disease can spread if cows eat feed that has been supplemented with other cows--in particular, if the feed contains prions. Humans eating those sick cows can take in the prions as well and get a fatal brain disease of their own called Creutzfeld-Jacob disease.

Prions were the object of scorn and skepticism for years, in part because they were so different as pathogens from viruses or bacteria. Prions had no genetic material, and yet they spread like genetically-based pathogens. Eventually the evidence became too much to ignore (and also won Stanely Prusiner of the University of California at San Francisco a Nobel of his own). But prions were revolutionary in another way that most people don't know about: they enjoy a unique kind of evolution.

In the early 1990s scientists realized that yeast contain prions. These aren't mutant PrPs, however, but two completely different proteins that just so happen to have the ability to change shape and force other proteins to clump with them. Unlike mad cow prions, yeast prions don't necessarily harm their hosts--in fact, they actually make yeasts thrive better than without them. And since yeasts are single-celled, they can pass down their prions to their offspring. (A prion in your brain won't get down to your sperm or eggs, so you can't infect your kids.)

In other words, a yeast can inherit prions from its parents, despite the fact that it has inherited no prion gene. This non-DNA based inheritance is a lot more like what Lamarck was talking about than Darwin.

Kandel and his Columbia team joined forces with an expert on prions in yeast, Susan Lindquist of MIT. Together, they inserted copies of the gene for the synaptic mark CPEB into yeast so that they could experiment on them and see whether they were in fact prions. They found that indeed, CPEB can exist in two different states. In one, the protein roams the cell alone. In the other, it forces other CPEB to change shape and form clumps with it. They also found that only when it takes on its prion form can CPEB bind to RNA.

The researchers propose a simple but elegant hypothesis for how prions can build memories. They suggest that certain signals entering a synapse can trigger CPEB to become a prion. As a prion, it can wake up sleeping RNA in the synapse, creating proteins for strengthening it. It also keeps grabbing other CPEB molecules and turning them into prions as well, so that even after the original prion has fallen apart, others continue to do the job. The neverending power of prions, in other words, is what keeps our memories alive.

In a commentary in the same issue of Cell, Robert Darnell of Rockefeller University says that if this work holds up to scrutiny (if it's replicated in neurons rather than yeast, for one thing), it will prove "nothing less than extraordinary." It would be extraordinary enough if memory proved to be based on prions, but the finding--along with the earlier work on yeast--raises the possibility that prions actually do a lot of important things in our bodies, and that we cannot understand them unless we are willing to let go of our vision of life as nothing but genes creating proteins. That may not make this Christmas's roast any tastier, but it should help revive the low reputation of prions.

I will never figure out the publishing world. My new book, Soul Made Flesh officially publishes on January 6, 2004. But Amazon and Powell's both say they've got it now and can get it to customers in 1-2 days. I guess time isn't what it used to be.

I have put some early reviews on my web site. Booklist: "Remarkable." Kirkus Reviews: "Absorbing and thought-provoking." Publisher's Weekly: "Illuminating."

Reminder: seven days left till Christmas.

Here's a new development in the search I described last week for the genes that make us uniquely human. Science's Michael B