Avi Solomon: Were there any formative experiences in your childhood that shaped your career?

Dan Everett: Well, by far the most important experience in my childhood was the death of my mother when I was eleven. She was twenty-nine. That changed my life, and it taught me that life is extremely fragile. And I knew from that point on that I was going to die and never feared dying. Because I felt that if my mother had died, I certainly didn't have any fear of dying.

Another important thing was music. I found the guitar, and played music, and wanted to be a famous musician. I had insecurities and issues that were the result of the fact that my mother had died so young, and music really helped me through all of that. And also it turned out I was pretty good at music, that if I stuck with something long enough, I could get really good at it. That encouraged me when I went to college, even though I had not been a very good student in high school, to believe that if I worked hard, I could be a good student.

So these things encouraged me and changed me, and gave me different perspectives on my life. Those were two of the most important things of my childhood.

Avi: You describe your uncle in World War II recounting how his Marine platoon got shot on the beaches, and what their last words were.

Dan: They said "Momma". He was in the Marines that were the first on the beaches, and he was eighteen years old. Most of these men were eighteen. He said the last thought everybody had was for their mother. It's a really sobering thing. I know that I'm sixty years old, and my mother has been dead for forty-nine years, but there's not a day that goes by that I don't think about her, and when things happen. I think every young man is close to their mother ñ that's the normal. I realize that there are dysfunctional relationships, but it is a surprisingly powerful force in male lives.

Avi Solomon: How did you come to live with the Pirahã?

Dan: I met a young woman in high school and she had been raised in Brazil, her parents were missionaries. We decided after we got engaged that we would be missionaries ourselves, so took all the training, and went off to Brazil to translate the bible and we were asked to work with the Pirahã because their language wasn't related to any other known language. I had done well in linguistic training, and so the mission thought that we might be the people to take up the challenge, because no one else had been able to figure out the language.

Avi: You went to convert them, but they kind of ended up converting you.

Dan: That's right. I went to tell them about God, and the need to be saved so that they could go to heaven and not go to hell, but what I found was a people for whom most of the things that were important to me seemed irrelevant. They couldn't understand why I thought that I had any right to tell them how to live, although they tried very hard to understand me because they treated me with respect. And they couldn't understand why I could think that someone whom I had never seen, never met, whom no one I knew had ever seen or ever met, could be the basis for teaching them how they ought to live.

Also, the quality of their lives was better in most respects than most people I knew who were religious. Just the way that they coped with the difficulties of life around them, and related to one another. This is not to say that they're a perfect people. Nobody is. But I found them extremely inspiring and challenging. And I certainly couldn't, after a while, justify to myself the idea that I knew more about how to live than they did.

Avi: During the course of your fieldwork you underwent a triple crisis, a personal, intellectual, and religious crisis.

Dan: On the personal level, it was a very hard time for me. Before I met my current wife I was all alone. There were some days of dark depression in there. And it was the end of my thirty-plus year marriage. But that wasn't by design. That happened as a result of my religious change. I would have loved to have avoided those things. Obviously the hardest thing by far for me, was to have my children not talk to me for quite some time. It's still hard on my daughters. You know, they go back and forth between talking to me and not talking to me. But I really believed and still believe that I had to tell the truth as I understood it, and take the consequences.

As far as religion, I felt that I had been a hypocrite for a long time because I didn't believe in things that I said I believed in, and I had to be honest. Professionally, I realized that to contradict the major theory that I had been working with, to say that I thought it was wrong was going to create a lot of opposition. I didn't really anticipate how much, but I knew it would cause some. But that's what I felt and that's what I had to say.

Avi: What gave you the resilience to pull through?

Dan: I feel like it was being able to look at myself in the mirror and know that I was saying what I believed, and no longer pretending things that I didn't believe. And it was meeting my current wife. She has been the greatest source of encouragement and support that I've ever had.

Avi: What is your definition of language?

Dan: My concept of language is broader than many theoreticians. To me language is far more than grammar. Grammar is simply the way that we take, for example, words and put them together in sentences. That's a simple component. But language to me includes all the things that we talk about, and the ways that we talk about them. So it includes poetry, and conversation as well as sentences, phrases and words. And each individual item, whether it's a sentence or whether it's a word, is a sign in the sense of the Swiss linguist Saussure. It has meaning, and it has form. And the meanings and the forms are largely ñ not exclusively, but largely shaped by the values of the culture that produces them. So just like some cultures have words that aren't found in other cultures. One example is Haggis, which is a food in Scotland, but a lot of cultures don't eat that food, so they don't have the name for it. By the same token, different cultures have different constraints on the shape and the meaning that's conveyed by sentences so that the very grammar is shaped by the culture.

Let me just say what I mean by culture. I mean knowledge, and ways of interacting, and I mean a set of values ranked in a certain way so that each culture not only has a set of values, but it knows which values are ranked higher than other values and have higher priority or more importance. Culture is one of the largest, most important shapers of the form and meaning of our language. And that has been overlooked and denied, in fact, by many modern theories of grammar.

Avi: How did you learn the Pirahã language?

Dan: By working daily and starting off with simple objects. I would point to an object, and say it's name in English. Like a stick, or a leaf, an animal, a part of my body. Saying the name in English, and then writing down whatever they responded, and trying to figure out whether that was the noun I was after. Then I would do things with the objects. Throw the stick. Drop the leaf. Hit myself. And try to get verbs. And by working very slowly, setting a goal of ten words a day for myself, I worked all day every day for the better part of a year. After about six or seven months I could say a lot of things. But it took me about a year of hard work before I felt like I could say pretty much what I needed.

Avi: The Pirahã language has rules of empirical evidence built into it.

Dan: That's right. Every verb ends with a suffix that tells you whether what you're saying was directly observed, or inferred, or just overheard by hearsay. So they don't talk about things that they haven't witnessed themselves, or that somebody they know hasn't witnessed. They don't have stories of the ancient past because that doesn't make any sense to them. You were never there. And they don't have stories about what's going to happen to them in the future. They speculate a little bit, but it's not an important part for them. They don't make plans for the distant future because again, you haven't seen that. You haven't been there. So they live one day at a time. It's not like they don't know that there is a past, or they don't know there is a future. They just don't talk about it because it doesn't make any sense to them to talk about it.

The interesting thing about the Pirahã language is that it's like the Basque of the Amazon. It's not related to any other known Amazonian language. That means that if it ever did come from any other Amazonian language, it's been more than 6,000 years. We can tell, for example, that German and English, and French were the same language 6,000 years ago because we can see similarities between them today. But we can't find any similarity between Pirahã and other Amazonian languages, which indicates that it's probable that it has been distinct for more than 6,000 years. The descriptions of Pirahã culture that we have from about 1784, indicate a culture very similar to the way that it is today, although more numerous. So you know, it's possible that if we went back several thousand years, it's not only possible, it's probably likely the Pirahã culture was different. Maybe the language was different. Probably it was. But we know that for the last several hundred years at least their culture has been relatively stable, and the way that they live today was the way that they were living in the 1700s.

Avi: So what is the secret of their happiness?

Dan: I believe that they're happy because they don't worry about the past, and they don't worry about the future. They feel that they're able to take care of their needs today. They don't want things that they can't provide for themselves. At least they never have in my experience. In other words, I take in things and they will ask for a few little things that I have that they don't make, such as pots and pans or matches. And if I give it to them, fine, and if I don't give it to them, fine. They're not materialistic. They value being able to travel quickly and lightly. I've never met another group, not even another Amazonian group, that is so little concerned with material objects.

Avi: The Pirahã use various ways to express themselves, especially whistling and humming.

Dan: They're not the only group in the world that does this, but it's especially important to them. They hum and whistle, and they use other kinds of speech much more than many other groups. So anything they can say using consonants and vowels and what we would consider to be normal speech, they can also say by whistling or humming. Because they use the tones of their language and they use the rhythm of their language to communicate, and that's rich enough. It's much richer in some respects than languages like English, so that they actually have enough information in the tones and rhythm of their humming and whistling to talk about anything. Women do not whistle. Men can hum like the women, but only men can whistle, and they use it almost always when they're hunting. It's a good way of communicating and sounding like birds.

Daniel Everett

Avi: They also have a special language for communicating with spirits.

Dan: Actually "spirits" is a bad translation. I started calling them "spirits" when I was a Christian missionary. And what they are to the Pirahã are jungle entities that are not humans, but look like humans. And they all talk in a falsetto voice. But they're tangible. You know, I mean if you saw them or I saw them, which I have many times, to us in our way of thinking, they're just Pirahã talking in a high falsetto voice. But to the Pirahã they are really different creatures. They'll say there's one of those "fast mouths". And I'll say "Well, that looks just like so-and-so from the village". And they'll say "Yes, they look just like Pirahã. But you can tell they're not because they talk in those high voices". I suppose that the closest thing we have to it is saying that someone is possessed. But it's not quite the same to the Pirahã. They would say that that is not a Pirahã. In fact if you find a Pirahã man that claims to be one of these jungle entities—it's always men that do this—these fast mouths, and you talk to him later, he will deny any knowledge of it. He will say "That wasn't me, I wasn't there".

It's a different concept of what's objective or subjective. It doesn't neatly fall in our dichotomy of fact versus fiction. And so for example, even when they dream, they'll tell you about dreaming and while they know that it's not the same as being awake, they consider it just as valid an experience. So the fact that I dreamed I was walking on the moon means that in some sense I did walk on the moon.

Avi: The Pirahã have an intimate knowledge of their environment.

Dan: The Pirahã can tell you what the name of every different species of tree according to the way that they classify them. They can tell you what animals live in those trees. They can tell you what kind of food those trees produce. They can tell you about the animals. They can tell you which ones can be tamed, which ones can't be tamed. Which ones are good for eating. Where they live. If you're going along the river and you see bubbles coming to the top of the water, they can tell you whether that's a fish or whether it's the rock underneath. And every Pirahã child that I've ever asked is able to give me the same information. So everyone learns about nature and their environment very early on in their lives. Each individual Pirahã is fully capable of providing for themselves. Any Pirahã child, a boy, can provide for himself from the time he's nine or ten years old.

Avi: Did your children also pick up stuff from the Pirahã children?

Dan: Yes. My daughters, when they were young, would take off with Pirahã girls during the day in a canoe, and disappear, and be gone until evening. And come back singing with them, and they would walk with them through the jungle and pick up things with them, and learn the names for those things. My son from the time he was three years old had a Pirahã bow and arrow, and would run with the Pirahã boys all around the village and sometimes into the jungle. And they would tell me all sorts of things about animals they had seen, and often come back with animals and lots of different things like berries and nuts that they'd collected in the jungle.

Avi: How can we try and emulate some of this in our own lives?

Dan: I think the main thing is being observant. You know, our children can't begin to take care of themselves when they're nine or ten years old, because they're not forced to observe and to learn about you know, the world around them. There are certainly many members of our culture who are extremely observant and knowledgeable about nature, but it's not general in our culture. The Pirahã have to survive. They don't have the concept of going to a supermarket to get their food. When I tell them about it, they find it very boring. They have to feed themselves every day. They don't store food. So each day when they wake up they're hungry. Each day they have to find food. They have to find food for their children, for themselves, for their family. And that means knowing where to find the food.

One night a Pirahã man came in to the village and told me that a bushmaster, one of the most poisonous snakes of the jungle, tried to bite him. And that he was tired, but tomorrow morning he was going to go out and kill the snake. So he left early the next morning, and he came back about 11:00 am or noon with this enormous poisonous snake with an arrow through its head, and he stuck it into a tree, and it was just hanging from the tree. He said to me "He thought he would bite me, but I bit it!". I can't imagine knowing enough about my environment to go back and find the same snake that tried to bite me the day before in the thick jungle.

Avi: So the Pirahã have made a cultural choice to live in the present and it shapes their language?

Dan: That's right. They've made a choice. So for example, everything that Pirahã say has to come with a marker for where they got the evidence. And that is why their grammar is radically different from the grammars of many other languages. Because the taboos on talking about things for which you don't have evidence for have profound impact on the actual structure of the language.

Avi: Are individuals in the Pirahã culture conscious that they're choosing to live in the present?

Dan: I wouldn't say so. If you think about some of the things that we do on a regular basis, we make decisions in our lives every day, and there are things that we don't do, but it's not conscious. It's just something that we do. To take one extreme example - my anthropology professor, the first one I ever had, asked the class to spit in their hands. And some people didn't want to do it, but others did. He said, okay, now lick it back up. Nobody wanted to do that. He said "But why? What is the problem? It just was in your mouth a couple of seconds ago, and now you don't want to lick it back up". Who knows that we don't want to do that? Do Americans tell themselves that if they expel something from their body they don't want to take it back in their bodies?

The Pirahã are not like that in some ways. I mean, a lot of things that they consider repugnant we don't, and things we consider repugnant they don't. But nobody goes around and teaches anyone that it's wrong to do this, and it's wrong to do that. These are just values that we absorb, and we internalize them through imitation. And by cultural constraints on talking in a similar way.

Say for example, in the marriage ceremony in English when you put the ring on the spouse, you say "With this ring I thee wed". Nobody talks like that today. But you do it in that ceremony, and nobody is conscious of why they do it that way. So there's all kinds of ritualistic language. So it's that cultural form that affects the language that we use, but it's not conscious to people. They can say "Oh yes, that's right, that's the way I say it". But they wouldn't be able to tell you why.

Avi: Another expression of culture shaping language is their relationship to numbers or quantities.

Dan: They don't need numbers, and they don't need quantities except in very relative amounts. So they can say a small pile of things, or a big pile of things. But they don't need any more than that, and they don't have words for any more than that. A number of people have claimed that numbers are innate and that the concept of counting is innate. It's difficult to reconcile claims like that with the fact that the Pirahã have no numbers and don't count. That's a very controversial claim, but it has now been tested and corroborated by three separate studies in major scientific journals by people who've actually been there. So factually it's quite sound and well tested to say that Pirahã don't have numbers. And the reason they don't have numbers is because they don't need numbers. There's no task in their culture for which numbers are important.

Also, having numbers requires generalization, and those generalizations go beyond the Pirahã principle that you talk about the present, and you avoid generalizations whenever possible. I mean, if the Pirahã has a word for dog ñ and they of course, do ñ any noun is a generalization. So if a Pirahã says parrot, they don't just mean one parrot. They mean all parrots. So clearly they generalize. And they generalize to the degree that all languages have to generalize. You can't have a language without being able to talk about a noun or things, and the events that they participate in. You know, so there's a thing and it does something. Or a thing and something happens to it. So they can do that. But they avoid unnecessary generalizations that go beyond the needs of their culture. And numbers are such a generalization, so they don't have them. They don't have words for colors. They can clearly see colors and describe them but don't have words for them. They don't have words that some philosophers and linguists have considered to be essential to all human languages, such as quantifiers like the word "all", or "each", or "every". They don't have words like that.

Avi: They might not have that, but there's a tradeoff with happiness.

Dan: When you talk about how complex a language is, it can be very simple in some respects and very complicated in others. The Pirahã word structure is very complicated. And a lot of things we do with complicated sentences, the Pirahã do with simple sentences, but very complicated words. However, this refusal of theirs to generalize beyond the present and their refusal to worry about the past or the future is, I believe, crucial to their happiness.

And what's the evidence for their happiness? On the one hand every visitor that I take down to the Pirahã comments that they've never seen people smile and laugh so much. That's one superficial evidence of happiness. But you also don't find Pirahã sitting around depressed and crying. You don't find chronic fatigue syndrome. You don't find suicide. The concept of suicide is foreign to them. I've never seen evidence for any of the mental disorders that we associate with depression, sadness and lack of happiness among the Pirahã. They just work, they come home, and they talk. They're happy. They sing at night. And they get up and do it again. It's just an amazing degree of satisfaction without the need for consciousness-altering drugs or states.

>Daniel Everett performs "Colors in my Life"

Avi: You described a day where the whole tribe was at the beach having a huge party.

Dan: Yes. In the rainy season there are no beaches because the river comes up more than seventy feet. Since food becomes harder to get in the rainy season because you have the same amount of fish, but in much greater volume of water, the Pirahã tend to spread out, and you find very small villages of maybe one or two families. But in the dry season when the river goes down and the beaches come out and the fish are easy to catch, they get together on the beaches in large groups. And you'll find beaches with over 100 Pirahã for a couple of months during the dry season. And in that case, they're singing and dancing every night. They could go on dancing for forty-eight hours, sometimes even for seventy-two hours. But that doesn't mean that everyone's awake for that entire period of time. It just means that you dance and dance and dance, and then when you get tired, you might step out and take a nap, and then get back up and start dancing again. But the noise and the happiness and all this stuff going on with it continues on. And if you're like me, and not able to do that all the time, and trying to sleep, it gets frustrating! They're just happy the whole time!

Avi: They also do not express recursion in their language.

Dan: That's correct. That's a cultural choice. Here's how it works. In the Pirahã language, every verb has a meaning, and that meaning includes the participants in the action. So take the verb "hit". That is ñ whatever hit means, plus the person doing the hitting, and the thing being hit. So I hit you. You're the thing being hit. I'm the person doing the hitting. Every part of that basic verb's meaning has to be warranted by a suffix on the verb that tells you where the evidence came from.

Now if I start to make it more complicated, so instead of ñ so let's say that I say John hits Bill. That's fine. John and Bill and hit are all warranted. We know whether the evidence was observed, whether it was overheard, or whether it was inferred. But the minute I say John said that Peter hit Bill, all I can tell is the evidence for John said. I can't tell about the evidence where Peter hit Bill. Each verb has to be separate, and have its own evidence expressed for it. That's a simplified explanation. And the fact that each verb and its participants have to be evidenced, warranted by these suffixes that gives the source of evidence means that there can't be any recursion in the language.

Here's another way of thinking about it. This isn't the technically correct way of thinking about it, but it does get the idea across. When we utter a simple sentence, every part of it is new information. John hit Bill. I'm telling you that something happened. If I say on the other hand the man who you saw yesterday hit Bill. The "who you saw yesterday" is old information. That's why we put it in there so we can keep track of things. And that's a recursive structure, but it violates the fact that it's not an assertion, it's not new information, there's a part of that that's old information. So as long as you say that each sentence has to carry only new information, and we have to know the source of the evidence, there can be no recursion in the language.

And that follows from the principle of immediacy of experience that I've talked about. Because that immediate experience tells us that it has to have been experienced by the person speaking, or by someone who told the person speaking. And that is reflected in the grammar by these suffixes that tell us where the evidence comes from. And those suffixes, by their very nature, prohibit recursion.

Avi: That kind of reminds me of a Yoga Sutra which talks about these three kinds of knowledge!

Dan: I've often seen a strong correlation and compatibility between the Pirahã worldview and Zen Buddhism.

Avi: Your recursion claim has aroused intense controversy.

Dan: Many claims I've made have been controversial. And every single one of them has been independently tested. Thirty years ago, I made claims about the way the rhythm of the language worked. And UCLA sent down a phonetics specialist, Peter Ladefoged, who was probably the greatest in the world at that time. Then he went with me to the tribe and tested these claims. And only after he said we had verified them did people begin to accept that. And it's the same thing. People have tested the number claim. They've tested the color claim. And they've tested the recursion claim.

At the last Linguistic Society of America meeting in Portland, Oregon a paper was presented by MIT cognitive scientists who had gone through all of the Pirahã data very carefully , and they made sure to go through data that was not collected by me, but by the previous missionary. Because the feeling was if they went through data collected by me, somebody could say well, he just made up that data, or he doctored it up. But they went through stories and text collected by another missionary who was there before me, and their conclusion after going through all of these examples very carefully was that they didn't see any clear evidence for recursion in the language. In fact, they saw evidence for the contrary. That there wasn't recursion in the language. And that was a very well attended talk, and some of my critics were there as well as a lot of neutral observers. And this wasn't my research. This was somebody else's research testing my research. So I believe that the absence of recursion is far more accepted today among people who think of Pirahã than it was just a few months ago, since the studies have come in.

Avi: How hopeful are you that the Pirahã will survive their encounter with modernity?

Dan: I have to say that overall I'm not really optimistic. I don't want to underestimate them. They're a very strong and resilient people, but the history of these kinds of contexts is not good. But I do have a lot of faith in the Pirahã inner strength and if any culture can stand up to this kind of pressure, it's theirs.

Avi: And hopefully, we the colonized can learn from them.

Dan: There's tremendous amounts we can learn from them, and in fact, from all other groups and peoples who are not like ourselves. I am currently working on a book idea called "Wisdom From Strangers" about how we can learn very important valuable lessons from people who are unlike ourselves. In fact, the more unlike us they are, the more we can learn. You cannot learn what you need to learn just by staying in the library. You have to have these experiences to take you beyond the boundaries of what you know, and make you live in ways that you never knew before. ]]> http://boingboing.net/2012/03/26/the-grammar-of-happiness-an-i.html/feed 25 http://boingboing.net/2012/01/03/what-its-like-for-a-mathemat.html http://boingboing.net/2012/01/03/what-its-like-for-a-mathemat.html#comments Tue, 03 Jan 2012 22:33:52 +0000 Maggie Koerth-Baker http://boingboing.net/?p=137134 It's hard to explain the experience of expertise. That's why one of the first things they teach you in journalism school is to avoid questions like, "What's it like to be a mathematician?" It's hard for your interview subject to know how to respond and you seldom get a useful answer.

You may not agree all those ways your tax dollars are spent, but they are all, at least, fairly tangible. When it's time for re-election, your senator can point to a roads project, a school, a saintly grandmother, or a missile silo. Through these projects, Americans are being educated, cared for, and protected.

But it's hard to make that clear cost/benefit analysis for basic scientific research. At least, not on a timetable that matches up with election cycles.

Basic research is often weird, and it's often boring. It's the years spent mapping the neurons of zebra fish, so that future scientists can have a more detailed biological model to work with. It's the chemical analysis that has to happen, so that two decades from now somebody else can discover a new cancer-fighting drug. Basic research is about curiosity, and knowledge for knowledge's sake. By it's very nature, basic research relies on public funding. But by it's very nature, it's hard to explain how the public benefits from the basic research we fund.

Attila Kovacs is one of the scientists who put your tax dollars to work. An astrophysicist at the University of Minnesota, he specializes in the study of space dust. That is, yes, dust. In space. It's the sort of thing that would be very easy to mock. (Imagine Bill O'Reilly making a joke about lemon-scent space Pledge.) But Kovacs says space dust matters more than you think. And he makes a good case for why it's important to spend tax dollars on funny-sounding science.

Maggie Koerth-Baker: You study space dust, but what does that really mean? Is this the same thing as dust on Earth, just in space? Or is space dust something a little different than the stuff that builds up on our bookshelves and end tables?

Attila Kovacs: In some ways it is similar. I like to think of Earth as a giant dust ball. Earth was made of space dust, but it went through a lot of evolution so dust that’s on Earth now isn't exactly the same. We don't actually know the structure of space dust, but we can guess. It probably has metallic core surrounded by a carbon or silicate shell and an ice mantel. They may be shaped like snow-flakes or a crumpled piece of paper. And we know that a typical speck of space dust is about 0.1 microns, about 1 thousandth of the width of your hair. It's hard to get your hands on space dust. We can only get indirect evidence through observation, by looking at the light that goes through the dust.

For instance, we know the size of space dust because light that has a wavelength larger than the particles of dust has come through the dust. We can see how different wavelengths of light either get blocked or go through the dust layers and we can put a size on that.

But what really makes dust interesting to me is its intricate connection to star formation. Dust is produced by stars in their dying phase, and it's also an essential ingredient for making new stars and planets. Interstellar dust is mostly heated by massive young stars less than a million years old. In fact, most of the light from stars is absorbed and re-emitted as heat by dust. So, by measuring the heat contained in dust we can get an accurate picture of the current level of star-formation in galaxies at all ages of the Universe. Through the dust, we can directly measure the complete star-formation history of the universe and get a glimpse at when and how the galaxies and stars came into being. This is what I research.

Yet another interesting aspect of space dust is its role in the chemistry of space. Most molecules, including molecular hydrogen, water, CO, and even some organic compounds that we see in space, have formed on the surfaces of dust grains, which act as catalytic surfaces enabling chemical reactions at the low temperatures and densities of space. There is no other way to make such molecules. All the precursor organic molecules of life on Earth probably formed on dust grains around a dying star, before our Sun and solar system were even born.

A scanning electron microscope image of an interplanetary dust particle. CC licensed, via Wikipedia.

MKB: When did you decide to dedicate your life to studying space dust?

AK: I was drawn to astronomy from a very young age. Soon after I learned to read, my grandmother took me to a bookstore, and told the clerk to get me whatever book I wanted. I told him I wanted a book about astronomy. The clerk got me something appropriate for a child of age 6, with pretty drawings of a smiling Sun and all, but I was very upset. I told him I wanted something much more serious. In the end, we settled on a book that would be your college-level intro astronomy. I loved it. I did not understand it all, but I still loved it. Later my interests turned to physics. But physics was a pretty dry landscape. A lot of the really crazy discoveries go back to the beginning of 20th century. Astronomy is always new and exciting. Every time you turn on a new telescope, there's always something new you’ll discover. That's what drew me back to astronomy.

As for dust, dust is the most prominent thing that you will see in space, even more than stars and star-light. More than half of all the light from galaxies in the universe is radiated as heat from dust grains. It’s also the most critical ingredient in the chemistry of the interstellar medium.

MKB: I’m assuming you’re not the only person studying this stuff. What makes your approach different? What aspects of space dust are you looking at that your colleagues aren’t?

AK: To some degree all of us are doing somewhat different work, but that doesn't mean there's not overlap. But I think it's important to have that overlap. That's where you get the credibility of science. Without that there’s no way to check whether somebody is right or wrong. Redundancy is a cross check.

What I personally do different: We do the same sort of observations. When I get observing time to look at a few galaxies on a telescope, there are people doing similar observations. But what's unique about what I do is the models that I use for analyzing the data and the tools I develop. Most astronomers who observe similar subjects are really users of technology. They use what's there. I, on the other hand, try to think about what will be the next gadget we can bring to the telescope that will enable us to do this research even better. I don't know a lot of people in the “dust” community that do that.

For example, I’ve worked to develop the equivalent of digital cameras for this long wavelength light, that lies between the infrared and radio bands. Essentially, they’re very sensitive thermometers. When you put them on telescopes then the light from the distant galaxy heats up the detector and you notice this very small temperature change. The instruments I helped to build are used on telescopes in Hawaii, Chile and Spain. And more recently I had an interesting idea on how to build an instrument that would split that light into 1000 different colors for each pixel, and then you can take pictures of both the dust and the dominant chemistry in galaxies. You can get a vast amount of information from that because you will be able to detect and map dozens of molecular lines in distant galaxies all at once. I’m hoping to build such an instrument and get it and on a telescope in a few years.

MKB: That sounds expensive. How do you fund this research? Who funds it, and how does that process work for you?

AK: We're relying a lot on government agencies, particularly the NSF (National Science Foundation) or NASA. And there are two ways to get funding. First is through regular grant projects, which are 3-year cycles where you apply for a grant to do specific research. And NASA also provides funding to use their space telescopes. So you can propose to do a specific bit of science with them and if you get observing time then they'll give you some money to help you with that.

The process starts with a proposal. You tell them what you want to do, why it's important, and what you hope to learn. You really have to justify your work. They don't just give you money because it's nifty. The grants are peer reviewed. And your peers decide whether it merits funding or not. They look at what you've done before with funding. They look at the potential impact, and what you'll do to communicate your science to the public. This is how they select who gets the funding. Typically it's for a 3 year cycle. Every 3 years your whole life hangs in the air. And it's far from guaranteed. Most things I apply for, 1 out of 20 or 1 out of 100 proposals are successful. It's far from easy.

Pig at the Minnesota Tax Cut Rally 2011, a Creative Commons Attribution (2.0) image from fibonacciblue's photostream.

MKB: How expensive is your work? When you do win these grants, what does the money go toward?

AK: At the bottom level it's the salary. I get around $40,000 and when you add overheads and whatnot that the university pays, it’s maybe $70,000. To do the science we have to build the instruments. We can't just use our eyes on the telescope, and those tools typically cost a few million to develop.

Then there’s the telescopes themselves. A 10 meter radio telescope up on some high mountain, that’s maybe $10 to $15 million to build, and a few millions a year to run. Private donors often pay for the construction of telescopes that will bear their name — like the famous Keck telescopes in Hawaii, paid for by W. M. Keck. A space telescope can be upwards of $1 billion.

That’s expensive. But you have to think of what it costs to the typical taxpayer. With just a single dollar of tax you pay every year, how much can you buy when it’s combined with the $1 everyone else pays? For $1 per person every year, you’re going to pay for 2000 post-doc researchers. That’s 2000 people like me. Or you could buy up to 100 instruments to put on the telescopes. Or your $1 can also buy you a few telescopes a year or one space telescope every few years.

MKB: You do basic research, stuff that’s really driven by curiosity, not by short-term practical goals. In a time of tight budgets, why is that important? In a recession, is space dust really something we can afford to spend money on?

AK: These are difficult times and when the money is tight we have a tendency to ask whether this is practical, and do we really need it. The answer to that is that it's not the need that drives discovery. It's the other way around: discovery drives our needs. You can only need things that you already know about. What basic science does is look for new knowledge. What it will be made of in the future, we don't know. But often it brings us new things that will be very practical.

My favorite example is electricity. Electricity, when it was discovered, wasn't anything useful. But once it's discovered, then you can start thinking about how you'll use it. What you have to think about is this: What is practical is something very short term. Basic science is much more forward looking. Some of it will produce useful things 10 to 30 years from now.

If you’re tight on your own budget how do you trade off on everyday necessities versus saving for retirement? You can't pay for rent and food at the cost of not saving at all for retirement. So when the budget is tight you have to cut back on both ends, rather than eliminating one. And we should do that in science. You can’t sacrifice the future because times are bad now.

MKB: Okay, but is there something you can look at and say, "This is what people will get if they fund me?" Is there anything tangible?

AK: For my work specifically? Well, you never know where it will take you. There are some things you can foresee a little bit. But I’m hesitant to guess. You do get benefits from astrophysics, though. There’s the selfish curiosity of knowing, but in that process we create technologies to detect the light we're analyzing. And a lot of those will be practical in the future.

When you're using your digital camera today, you’re using technology that optical astronomy developed 30 years ago. Today it's in your camera. Lots of technologies from radio astronomy are in your cellphone today. You wouldn't have that without basic science trying to detect light at different wavelengths. You really have no idea where the technologies we develop today will take you in another 10, 20 or 30 years.

MKB: But why government funding? Why not find a private organization or corporation that wants to help you research space dust?

AK: I think there's many sides to this. Right now, private funding tends to be product based. It has to lead to a product within a few years for a private company to be interested. So it may be practical and possible for things with immediate applications, but it's hard for me to see why a corporation would be interested in something long term and uncertain.

Basic research used to be privately funded in the past, like with Bell Labs. That used to be THE place where basic research was happening. But somehow that model has disappeared and I think it's because corporations are looking for more short term goals. There's really no corporation doing basic research in the same way Bell Labs did.

But there are also reasons why you might not want it, even if they were interested. Corporations are interested in proprietary technologies and getting out ahead of another company. They won't share what you discovery and they'll use it exclusively to their advantage. They'll file patents and protect their turf. And that’s fine. But the reason we want public funding is that we want to generate public knowledge. We want to share this with the world. We want it to be immediately available to everyone around us. Science doesn’t have trade secrets. I think public funding is essential to keep it that way.

Main Image: Cosmic dust of the Andromeda Galaxy as revealed in infrared light by the Spitzer Space Telescope. Public domain, via Wikipedia.

The genius in her latest novel, Lightning Rods, is DeWitt herself, who cooks up one of the funniest stories I’ve read in recent memory. It’s a highbrow version of the movie Office Space with a Jonathan Ames-esque plot. Read my exclusive, in-depth interview below with DeWitt about the new novel, as well as her writing habits and her tips to would-be novelists.

David K. Israel: As I understand it, you actually finished this manuscript for Lightning Rods before completing and publishing The Last Samurai. Sounds like an interesting story for aspiring novelists. What happened there?


Helen DeWitt: Not quite. I finished it after completing but before publishing The Last Samurai.

I wrote a lot of The Last Samurai between September 1995 and June 1996, but there were structural problems. I needed a clear block of time to think about it, was working freelance as a legal secretary. The wife of one of the lawyers was an indie producer, saw 2 chapters, LOVED them, wanted to option for a film – I thought I might get £1000 and a clear month in 1996 to finish the book.

She introduced me to an agent, Stephanie Cabot, of the London office of William Morris. Stephanie LOVED the chapters. Said she could get an advance on 6. In July 1996 an editor expressed interest in a preemptive bid and Stephanie told him it was too early. It took 9 months for the agency to finalize the option contract. In the end work on the book was disrupted for 18 months by unsolicited advice from editors, who thought the book “needed work” but were not willing to provide the money which would enable me to do it.

There was a complete manuscript by this point, but I had so many other voices in my head they had driven out the voices of the characters, couldn’t tell whether the book was what it ought to be or not. Couldn’t look at it. No idea what to do. Thought I would never write again. Nowhere to turn. Suddenly, out of nowhere, came this funny voice, this guy who was down and out, working out his frustrations with sexual fantasies he was trying to set up to his own satisfaction. Well, I LOVE Mel Brooks’ The Producers; I LOVE “Springtime for Hitler;” the guy made me laugh hysterically the way “Springtime for Hitler” made me laugh.

I thought: OK, Samurai is too much, I can’t publish this book now. I’ll write a book with a single voice, with NO Greek, NO Japanese, NO Old Norse!!!!! I’ll go away and write 10 books in a year! Each doing ONE THING! And SOME day I’ll be in a position to publish this crazy book with Greek and Japanese and Old Norse . . .

So I saved up some money and quit my job and moved to Chesterfield, and I did nothing but write for a year. I worked on a lot of different books; by July 1999 Lightning Rods was finished and others were coming up for completion . . . . and in August a friend showed LR and Samurai to Jonathan Burnham at Talk Miramax Books. Who LOOOOOOOVED Samurai and did not want LR. And took Samurai to the Frankfurt Bookfair! And caused a sensation! But many of the people who LOOOOOOOOOVED Samurai were shocked and appalled by LR. One book was inspired by Seven Samurai, the other by The Producers, people didn’t get it.

In 2001 Jonathan decided he wanted LR after all and offered what Publishers Marketplace calls a good deal. But I wanted an editor who was genuinely enthusiastic about the book; I was nervous of giving him the world rights he wanted (first time round it had been hard to get paid); and I desperately wanted someone capable of looking after my other books, which (like Samurai, unlike LR) were technically challenging. Translations of Samurai kept trickling back in which the Greek was gibberish.

I talked to an agent in New York who said: “If you sign with me I will introduce you to at least 3 and at most 5 new editors.” That seemed unambiguous. Jonathan, meanwhile, upped his mere paltry good deal to a MAJOR deal for two books, LR + 1. $500K+ is a tidy sum, but there was the Greek-into-gibberish concern, and he still wanted the world rights. And amid all the excitement I got a royalties statement in which Miramax made a $150,000 accounting error in its own favor; it was not getting noticeably easier to get paid. So I signed with the agent, thinking she could handle the royalties snafu and introduce me to new editors as promised, and she went straight into negotiations with Miramax. No new editors, deal fell apart . . .

If you know David Mamet’s State and Main, this gives something of the flavor of the behind-the-scenes machinations, the backstabbing, the chicanery -- but we probably don’t want to spend a whole interview on a decade of S&M, S&M II, S&M III, S&M IV . . . S&M MCMDXLIX . . . Suffice it to say, if Lightning Rods had not been inspired by the tasteless genius of “Springtime for Hitler,” it would have been easy to find a new publisher. I blame Mel Brooks.


DI: Your protagonist in Lightning Rods is a man. As a woman, is it harder to write from the male POV?


HDW: Funnily enough, I now find it easier to come up with male characters. When I was a child I drew incessantly, but could only draw girls – I would draw up lists of girls’ names, every name I could think of, on yellow legal pads, and then draw long sagas with this cast of hundreds of girls. And I couldn’t draw boys at all. But at some point, I’m not sure how this happened, I started to notice the way men are obsessives: creating a male character doesn’t feel like writing from a ‘male’ POV, what you do is you get inside the head of someone with a particular kind of obsession, and understanding the obsession makes the character plausible, and this turns out to feel like a male character because women are often more inhibited (I feel) about giving free reign to their obsessions.

There’s also – bearing in mind the fact that LR is partly about sex – that men are more confident about generalizing from their own sexual preferences to those of other men. If you (I) talk to a man, the man will often say something like “Most men are interested in breasts.” I think: WOW. How do you know? I assume YOU know your sexual preferences; how can you be so confident that most other men share them? Did you do a survey? Because I certainly think I know my own sexual preferences, but I would never feel confident of generalizing from them to say Most women are interested in X. So it’s possible to be much more confident, creating a male character with certain sexual preferences, that the character will be plausible. (And then, you know, I’d show the book to men and laugh because it actually worked.)







DI: Without any spoilers, talk a little bit about how you got the idea for this fascinating novel. Where did the seed come from and how did you develop it?


HDW: Two things. One source of the book went a long way back. When I did my doctorate at Oxford I met my ex-husband David, an Orthodox Jew who loved Mel Brooks’ The Producers. If “Springtime for Hitler” came up in the conversation David would be unable to resist launching into a word-perfect rendition, with all the business. David doesn’t much like what I would describe as the arthouse response to the Holocaust, but he loved The Producers and “Springtime for Hitler.” So I thought that was interesting. In The Producers, you have a couple of Jews who, you might think, epitomize the Nazi view of the inferior race: one fat, sexually perverse, the other a diffident accountant, both incorrigibly materialistic – and yet we love these characters, their imperfections are part of their humanity. I liked the idea of a likable sleazeball as a character.

The other was the response I’ve sketched in above to The Last Samurai when it was first sent out to editors. My ex was the most brilliant student his tutor at Oxford had ever had; we had both done a special subject in Aristophanes; he had introduced me not only to Mel Brooks but to the whole tradition of British satire (Blackadder; Yes, Minister; Dennis Potter’s Pennies from Heaven and The Singing Detective). To go from this kind of intellectual engagement to unsolicited advice from persons of no demonstrable competence was profoundly humiliating; at the risk of spoilers, it felt like being fucked from behind through a hole in the wall. So it’s not that I sat down to write a satire on publishing, but whatever it is that writes the books came up with this, this was the voice that came into the head. 


DI: What’s your writing process like? Do you have set hours? Are you looking for a certain number of words or pages per day?


HDW: That’s hard to answer. The thing that works best for me is to clear time and admit NO INTERRUPTIONS. WITHOUT EXCEPTION. I don’t necessarily work on a single book. I have a rough word count that would probably amount to a finished book. For each book I can say that if I wrote 2000 words a day it would be finished on Day X. I have a workbook in Excel with the number of words written in each book, and the date each book would be finished if I wrote 2000 words a day. Needless to say, I’m unlikely to write 2000 words a day on each book. I write down however many words I’ve written on each book in a day, and I then change the finish date according to how many words have been written. So if 4000 words are written on one book, the completion date of all the others goes back a day . . .

It’s not always possible to work that way. What happens is, I’m dealing with some long-drawn-out publishing problem. If I let the voices in a book take over, if there is no social self, I will offend people with whom I’m doing business. What is to be done?

Well, there are all sorts of technical problems to address. So I go into Illustrator and spend hours grappling with the pen tool. Or I open up the statistical graphics package R and start setting up plots. Or (purists will be appalled) I start playing around with charts in Excel.

I mooch around online filled with shame and self-loathing. I experiment with a series of ads on Project Wonderful. (It doesn’t feel like work, but maybe it IS work.) I discover a webcomic, Penny and Aggie, and read many many episodes, filled with shame and self-loathing. And suddenly I discover a brilliant graphic solution to a problem I’ve been grappling with for years!!!!! How to display poker hands graphically in a way that sets a series of strong hands next to the slightly better hands that win. 


DI: Do you rewrite as you go or do you like to get a draft done first and then go back?

HDW: I think I mainly write episodes and leave them alone for a while until I know how they will fit in the larger framework. There’s something, though, that this somehow doesn’t capture. I once read an interview of Michael Caine in which he talked of working with Sir Laurence Olivier on Sleuth. Olivier turned up the first day and was lackluster, disengaged. The next day he turned up wearing a small moustache and was suddenly electrifying. He explained to Caine that he always needed a prop, a bit of business, the right sort of costume, to inhabit the character.

Something like this seems to work for me. I may have a vague idea about a character – he is learning Japanese at an early age, say. But I don’t know how to make this work formally, I don’t know what to do with the narrative. I then buy some software that lets me input Japanese within my wordprocessing program. I start playing around, I come up with bits of Japanese. And suddenly I see that I can make visible the development of the character just by using a succession of kanji! I don’t cut out text – I have eliminated the need for 20 pages of text just by using this software!!!! So a lot of what I do, it seems to me, is look around for the moustache, the bit of business. (This obviously militates against word count as a measure of progress. 


DI: Your work is always very character-driven. I’m curious if you start with a protagonist and then develop the plot as you write or if you have the beginning, middle and end all set in your mind before you start writing.





HDW: When I wrote The Last Samurai I had a very clear structure in mind. Thank God. I knew how it would end. So I was confident that it WOULD end, could be finished. In the case of Lightning Rods, though, I didn’t know how it would end up; I started writing, and new episodes occurred to me as I went along. It seemed possible to write that way, I think, because it was written in a single voice, with a straightforward linear narrative; if there are different voices and many different stories one needs a clear picture of the structure.






DI: You protagonist, Joe, is a salesman and an ideas man, or so he claims to be. What kind of research, if any, did you do to get into his mind?


HDW: Ha! None. But when I was 19 I met a guy in Provincetown who was trying to make ends meet selling Electrolux. He was studying Russian and Chinese at Yale, very smart guy, but somewhat unmanned by the reality of demonstrating the virtues of Electrolux. (One demo: you used the vacuum cleaner with attachment on a bed, then dumped the resultant dust in a disgusting pile on the floor.) Years later I rented a room in a house in East London; one of the tenants sold sofas, then a mobile phone service. His room was crammed with books on salesmanship. So I realized there was this whole rhetoric of self-improvement and persuasion and seat-of-the-pants sociology in which would-be salesmen immersed themselves. 


DI: What are you working on now? What can we expect soon?


HDW: Er, interviews, mainly, at the moment. In a somewhat hit-and-miss way. When things went wrong with Miramax back in 2004 I ended up in a psychiatric ward with the press besieging the hospital; there were thousands of hits on Google, journalists clamoring for interviews – but my publishers were reluctant to exploit this windfall. I pointed out to one agent, a few years later, that if I should crack up again and attempt suicide to press furore it would help if he could organize a press conference; he said firmly that if a client attempted suicide no responsible agent would set up a press conference, because there is more to life than sales. No unscrupulous agents have come forward offering representation – Edward Orloff, who has been looking after LR, is a man of unimpeachable integrity – so here we are.

That said, before I got this offer of publication from New Directions I was concentrating on three books. Stolen Luck is a book about poker using Tuftean information design to give readers a feel for both the game and the mathematics. Sexual Codes of the Europeans starts with a blog describing sexual codes of five European cities – that is, ways of signaling different sets of sexual preferences. The codes are fictional, but travelers to the cities start deploying the codes so they become real; this has all sorts of unanticipated consequences. (One man works out that if you knew the next city whose code was to be published you could buy up property. Manipulate developers. To the public at large, meanwhile, it’s just another form of diversity in our networked age.) Recovery is a book about addiction – there’s a draft of a couple of hundred pages. I hope to get back to these some time in November and finish them in 2012, but of course they can’t all be published at once; I’d hope to bring them out in 2013, 2014, and 2015.

DI: Lastly, do you have any advice for aspiring novelists?

HDW: Advice is probably the wrong word.

There are things I didn’t understand when I started out.

I live in Berlin, which once, famously, had a Wall. On one side was the West; there was KaDeWe, a famous department store, a monument to materialism; there were also all kinds of people experimenting with different kinds of art, social structures, lives. On the other side was the East: command economy, paucity of consumer goods, society of surveillance, secrecy, patronage – and with all this the compulsory rhetoric of ideological enthusiasm. (I read a chilling interview the other day of Angela Merkel’s husband, Joachim Sauer: “Die Kunst war, morgens noch in die Spiegel schauen zu können …” – “The art was, still be to able to look at yourself in the mirror in the morning, but not to be expelled from secondary school or lose your university place or jeopardise your scientific career opportunities.” To have any kind of career it was necessary to make certain decisions.)

So look. Of course there are things you can do to make yourself a stronger writer – they will not be the same for every writer.

You can think of that lunatic Pound: if there is good poetry written in a language, learn enough of the language to read the poetry. If you read something in translation and are blown away, find the text in the original language, get a dictionary, get a grammar, keep your translation to hand, read at least one paragraph of the sentences the author actually wrote.

You can read a wide range of genres. You can engage with a wide range of disciplines – philosophy, history, sociology, economics, cryptography, mathematics, yes, but not only disciplines learned by reading, perhaps you learn rock climbing, or lockpicking, or glassblowing, or tae kwon do. Perhaps you learn computer programming, perhaps you learn a lot of these artificial languages.

Perhaps you live somewhere cheap, so the time you spend earning money buys as much time as possible. Perhaps you find a way of earning money that will let you go anywhere. Perhaps you travel – perhaps you immerse yourself in different cultures, you go to Japan, Finland, Turkey, Peru.

Any of these things could help you write better texts, and the list is no doubt much longer.

If the aspiration is to be published, though, to be a professional writer – if it’s not enough to publish online, produce your own books, show work to people you know and respect – you will need a completely different – I was going to say, set of skills, and then I was going to say, it’s a question of character. (Fast Eddie Felson had talent; Minnesota Fats had talent and character . . . ) Then I was going to say, it’s a question of luck.

So the challenge is not to write well; the challenge is not to find ways to deal with this system; the challenge is to deal with the system without damaging the work.

Time will say nothing but I told you so.

If I could tell you I would let you know.

Helen DeWitt's homepage
Paper Pools]]> http://boingboing.net/2011/10/03/an-interview-with-novelist-helen-dewitt.html/feed 1 http://boingboing.net/2011/10/01/science-saturday-allergies-symbiotic-bacteria-and-scientific-literacy.html http://boingboing.net/2011/10/01/science-saturday-allergies-symbiotic-bacteria-and-scientific-literacy.html#comments Sat, 01 Oct 2011 14:48:33 +0000 Maggie Koerth-Baker http://boingboing.net/?p=121319

I had a great conversation with Christina Agapakis, a science blogger at Scientific American and a scientist studying synthetic biology. In this episode of Bloggingheads.tv's Science Saturday, you'll find out what Christina learned when she traced her allergies on a phylogenetic tree, why she's currently obsessed with symbiotic bacteria, why I think adults need more opportunities for informal science education after they've left school, and how scientists and educators are trying to address clashes between science and culture.

I had a great conversation with Christina Agapakis, a science blogger at Scientific American and a scientist studying synthetic biology. In this episode of Bloggingheads.tv's Science Saturday, you'll find out what Christina learned when she traced her allergies on a phylogenetic tree, why she's currently obsessed with symbiotic bacteria, why I think adults need more opportunities for informal science education after they've left school, and how scientists and educators are trying to address clashes between science and culture.

In the video, I talked about my experience at the 6th Science Center World Congress. For a little more on that, check out the story I wrote about why adults need science museums to pay more attention to them. ]]> http://boingboing.net/2011/10/01/science-saturday-allergies-symbiotic-bacteria-and-scientific-literacy.html/feed 4 http://boingboing.net/2011/08/24/going-under-what-we-dont-know-about-anesthetics.html http://boingboing.net/2011/08/24/going-under-what-we-dont-know-about-anesthetics.html#comments Wed, 24 Aug 2011 16:16:48 +0000 Maggie Koerth-Baker http://boingboing.net/?p=115264

The majority of people reading this sentence will, at some point in their lives, undergo a medical treatment that requires general anesthesia. Doctors will inject them with a drug, or have them breathe it in. For several hours, they will be unconscious.

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The majority of people reading this sentence will, at some point in their lives, undergo a medical treatment that requires general anesthesia. Doctors will inject them with a drug, or have them breathe it in. For several hours, they will be unconscious. And almost all of them will wake up happy and healthy.

We know that the general anesthetics we use today are safe. But we know that because they've proven themselves to be safe, not because we understand the mechanisms behind how they work. The truth is, at that level, anesthetics are a big, fat question mark. And that leaves room for a lot of unknowns. What if, in the long term, our anesthetics aren't as safe for everyone as we think they are?

The only way to know for sure is to figure why anesthetics cause unconsciousness, and how one drug differs from another. Roderic G. Eckenhoff, MD, is a professor at the University of Pennsylvania's Perelman School of Medicine. He's one of the people trying to figure out what general anesthetics really do inside the human body, and how we can use that information to discover even safer drugs than the ones we already rely on today. How does he study that? By drugging tadpoles.

This week, Chemical and Engineering News published a profile of Eckenhoff and his work, written by journalist Carmen Drahl. That piece inspired me to call up Eckenhoff and find out more about what we think we know about anesthetics, why it's taking medical scientists so long to understand such a commonly used class of drugs, and why tadpoles make an ideal model animal.

Maggie Koerth-Baker: Describe for me, in your own words, the current basic theory of how anesthetics work. We're talking about chemicals binding to protein receptors, correct? But what does that mean? Why do proteins matter?

Roderic G. Eckenhoff, MD: The real simple answer is that we don't know. We don't even know what class of macromolecule, for certain, underlies the effects of general anesthetics. And anesthetics don't just do one thing. They produce a myriad of effects ranging from hypnosis, to amnesia, to pain relief and a range of other effects that are much less desirable, like hypothermia, nausea, and vomiting.

But most of us think about the primary effect, which would be unconsciousness, and the answer is still we don't know for sure. But there has been a gradual shift in the field to thinking that protein targets are the likely candidates for this interaction. The main reason is selectivity. Even though "unconsciousness is unconsciousness" the whole spectrum of what the unconsciousness looks like aren't always the same from drug to drug. Some patients are more dysphoric afterwards, for instance. There are components of the electroencephalogram that look different from one drug to the next. That leads us to believe that there's some selectivity.

That's a bit of a surprise, actually, that the drugs aren't all working the same. In the last 5 years or so that's come more to the forefront. A very, very small molecule like halothane, which isn’t used in the United States anymore, might act differently than a drug that's more popular today called isoflurane. There's surprising selectivity to these drugs and we're only now starting to appreciate. And when you talk about selectivity, you're talking about proteins because they have the most diversity in terms of structure.

Ion channels [A type of protein—MKB] are also important because they transduce most communication and signaling in the central nervous system. If we think the drugs affect synaptic transmission, for example, then there's a host of ion channels that could be candidates. They are prime targets simply because of what they do. The evidence to date looking at ion channels in vitro strongly supports that notion.

MKB: In the Chemical and Engineering News article, writer Carmen Drahl talks about some of the major discoveries behind how anesthetics work, and we find out that these discoveries happened in the 1980s. What took so long?

RE: That gives you some insight into how difficult the problem will be. A large group of people has been working on this for a long time and we barely know what class of macromolecule underlies the effects. That's remarkable at this stage, given the millions of dollars that have been poured into the problem. It’s taken so long because we've been searching for the single target or just a few ... but it's probably a bigger problem than that.

My bias, which is somewhat speculative, but evidence supported, is that we're talking about interactions with as many as 10, 20, or even 50 different protein targets. That constellation of small effects disrupts the extraordinarily well-timed signaling in the central nervous system to produce the final common pathway of unconsciousness.

What we’ve seen is that people have their favorite targets that they work on in vitro and when they work their way back up to an intact animal they find that this target has only a very small contribution to the overall effect, in contrast to in vitro work. That's been reproduced time and time again. The model that seems to work best is a small-effects-at-multiple-targets model. How does one achieve selectivity then? What you’re probably seeing is each drug affecting different but overlapping mix of targets.

MKB: We've been using anesthetics for more than a century without really understanding how they work. What does that mean for safety? Are there cases where we know, in retrospect, that an anesthetic was being used improperly because we thought it worked differently than it really did?

RE: The first question is about safety. We started with two principle drugs in 1850, chloroform and diethylether. Those two grew up together and the latter is a very safe anesthetic, but it’s explosive and flammable. So it doesn't mix well with today's electronics. Chloroform is unsafe, in the sense that it's metabolized into reactive products in the liver and causes liver toxicity. It also has bad cardiovascular effects. So both drugs have gone by the wayside and the safety profile of the drugs we do use has continuously improved. But it’s not because of us knowing how they work. It's all been empirical, trial and error stuff.

Today, we have drugs that are safe in the short term, but we’re worried about long lasting effects, especially cognitive effects in the vulnerable brain, for example the elderly and children. Effects could last well beyond duration of administration. That's gotten people worried. That's why we're trying to come up with other chemotypes that don't do these things.

MKB: I think this is one of those things that would sound quite scary to a lot of people — that their anesthesiologist doesn't really know exactly how anesthetics work. But we use these things every day, so it must be safer than it sounds. Why is that not actually as big of a problem as people might think?

RE: Because we get away with it. Worldwide, it's estimated that over 200 million general anesthetics are given each year. In this country alone it’s something like 40 or 50 million per year. Really, only 30-40% of people make it through life without experiencing a general anesthetic. Based on the safety profiles, the bad things that happen and are directly attributable to anesthetic are very rare. But that's just the tip of the iceberg. We don't know what else we're doing long term. We're just not set up to know that yet.

MKB: Besides the fluorescence which makes it easier to track through a tadpole's body, what makes 1-aminoanthracene, the anesthetic you're working with, a better drug? What could it do for humans that existing anesthetics don't already do?

RE: I wouldn't give that to any human. Aminoanthracene is strictly a lab anesthetic that helps us to understand what the microscopic and molecular targets might be. It's only advantage is that it’s fluorescent. If you do reading on 1-aminoanthracene you know they aren't good molecules to have in you for any length of time. Probably carcinogenic.

We have two arms to our research, finding the targets and trying out new drugs. Aminoanthracene has helped in both arms. One arm of the project is discovering new drugs — we've done a large screen of half a million compounds and are now sorting through the hits to find a new class of general anesthetic. The other arm tries to identify what the molecular targets might be. Finding the targets helps us to direct drug development a bit more.

MKB: How is this different from localized anesthetics? Do we understand those better?

RE: The mechanism of local anesthetics for things like epidurals, spinals, local anesthesia, we think we understand that a lot better. They're bigger molecules and there’s a good relationship between selectivity of the molecule and its size — local anesthetics are more selective about what they affect. And part of the safety also comes from the fact that we only give a little bit in a very selective place, to begin with. By the time it disseminates into the rest of the body the concentrations are so low that it does nothing. Dose matters. For example, if you give enough local anesthetic intravenously, they can cause seizures and cardiovascular collapse. But in small doses it’s safe.

MKB: I think a lot of people will be interested in the fact that you work with tadpoles, and not a model that's more familiar to the general public, like mice. Carmen Drahl writes that this is because tadpoles are cheap, and that they are an excellent mimic for human responses to anesthetic. When we say "excellent mimic" what are we really talking about? How does a tadpole on anesthesia resemble a human?

RE: Basically, this sounds kind of primitive, but the basic endpoint used in anesthesia is that when a surgeon cuts the patient, they don't move. I'm serious. It's very, very crude, but it's the coin of the realm. The bottom line is that when you do something that ought to hurt the animal, it doesn't respond. In a tadpole that means trying to elicit a startle reflex by tapping their dish, or tapping the tadpole itself. If it doesn’t do anything, it’s considered anesthetized.

That behavior, loss of movement, we see in animals going all the way down to the fruit fly or the nematode. Any animal that can move can be an anesthetic model. But what I really mean by “mimic” is that concentrations required to produce that endpoint are almost the same, within 10 or 20% or so, of those required to achieve the endpoint in humans. And that’s right across a large number of common anesthetics.

The ability to be anesthetized is a very conserved response. I wrote a paper a few years back on “Why can all of biology be anesthetized?” The response even extends to plants!

MKB: So why can all of biology be anesthetized?

RE: I have a theoretical, protein-based argument — that proteins have small hydrophobic cavities that are essential to their movements and function. If you fill those holes with a small hydrophobic molecule, like anesthetics, you're going to inhibit or change the function of the protein in some way. It may be such a small change that it doesn't matter, or it can matter a lot. But all proteins have these cavities, so all of biology should be affected.

Thanks to Aaron Rowe!

Image: P1110844CrvHC, a Creative Commons Attribution Share-Alike (2.0) image from thirteenofclubs's photostream

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