Wednesday, January 31, 2007

Apologies to any Pynchon readers for the delay...

I have to apologize for the fact that I haven't posted any new Pynchon material recently. I still am working on the essay/science primer for Against the Day, however the task has turned out to be more formidable than I first anticipated. The problem is this: there is so much material that could be included in a primer on vectors, quaternions, space-time, etc., much more than I have the time or, in some cases, expertise to cover. In order to keep things focused on the truly relevant science, I must finish a second reading of the book.

I'm well on my way through that second reading, furiously taking notes, and I'm working on various portions of the essay, but it will probably be at least a month before I finish and can post my results.

In the meantime, I highly recommend this book, which I'd bet was one of Pynchon's sources on quaterions and vector analysis (as you can imagine, there just aren't that many books out there on the history of vector analysis): A History of Vector Analysis. It looks like it's hard to find - I picked up a copy from my local university library. I'll leave you with a few choice excerpts from the book that relate to what Hamilton was trying to accomplish with quaternions, and how his efforts were viewed:

p. 37, from an 1857 review of Hamilton's work on quaternions:

"It is confidently predicted, by those best qualified to judge, that in the coming centuries Hamilton's Quaternions will stand out as the great discovery of our nineteenth century."

[In reality, quaternions were eclipsed by vector analysis only a few decades later.]

p. 23-24: From an essay published by Hamilton in 1837, a section called "On Algebra as the Science of Pure Time" (to understand this passage, recall that imaginary numbers are multiples of the square root of -1):

"The thing aimed at, is to improve the Science, not the Art nor the Language of Algebra. The imperfections sought to be removed, are confusions of thought, and obscurities or errors of reasoning; not difficulties of application of an instrument nor failures of symmetry in expression...

"For it has not fared with the principles of Algebra as with the principles of Geometry. No candid and intelligent person can doubt the truth of the chief properties of Parallel Lines, as set forth by EUCLID in his Elements, two thousand years ago... The doctrine involves no obscurity nor confusion of thought, and leaves in the mind no reasonable ground for doubt, although ingenuity may usefully be exercised in improving the plan of argument.

"But it requires no peculiar scepticism to doubt, or even to disbelieve, the doctrine of Negatives and Imaginaries, when set forth (as it has commonly been) with principles like these: that a greater magnitude may be subtracted from a less, and that the remainder is less than nothing; that two negative numbers, or numbers each denoting magnitudes less than nothing, may be multiplied the one by the other, and that the product will be a positive number, or a number denoting a magnitude greater than nothing; and that although the square of a number, or the product obtained by multiplying that number by itself, is therefore always positive, whether the number be positive or negative, yet that numbers, called imaginary, can be found or conceived or determined, and operated on by all the rules of positive and negative numbers, as if they were subject to those rules, although they have negative squares, and must therefore be supposed to be themselves neither positive or negative, nor yet null numers, so that the magnitudes which they are supposed to denote can neither be greater than nothing, nor less than nothing, nor even equal to nothing. It must be hard to found a SCIENCE on grounds such as these..."

[Note in this upcoming section that Hamilton speculates that with geometry as the science of space, perhaps algebra could become the science of time:]

Hamilton asks "whether existing Algebra, in the state to which it has been already unfolded by the masters of its rules and of its language, offers indeed no rudiment which may encourage a hope of developing a SCIENCE of Algebra: a Science properly so called; strict, pure, and independent; deduced by valid reasonings from its own intuitive principles; and thus not less an object of priori contemplation than Geometry, nor less distinct, in its own essence, from the Rules which it may teach or use, and from the Signs by which it may express its meaning..."

He suggests that "the Intuition of TIME is such a rudiment... The argument for the conclusion that the notion of time may be unfolded into and independent Pure Science, or that a Science of Pure Time is possible, rests chiefly on the existence of certain priori intuitions, connected with that notion of time, and fitted to become the sources of a pure Science; and on the actual deduction of such a Science from those principles, which the author conceives that he has begun."

Hamilton here draws a comparison between Euclidean geometry as a pure science of space, and his efforts to make algebra a pure science of time. Historically, and in light of Against the Day, it is interesting to note that Hamilton wrote this before Non-Euclidean geometry became widely known (after 1860, according to Crowe), and long before experiments suggested there was anything wrong with our intuitive notions of time which Hamilton wanted to rely on. In essence, Hamilton's quaternions and Euclidean geometry are part of a classical world that came to an end during the time frame of Pynchon's book. (In the long run, vector analysis and quaternions themselves, instead of being a science of time, became an algebra dealing with space.)

Monday, January 22, 2007

Introducing Indy Science Blogs Part 2

I didn't get a chance earlier to introduce all of the fascinating blogs on the newly launched Indy Science blogs. So here are the rest of the introductions:

If you like robots, astronomy and rocketry, check out Ed at Robot Guy.

Barry Leiba is a researcher at IBM, and he writes about life, politics, and technology issues at Staring at Emtpy Pages.

Emily DeVoto is an epidemiologist who writes about health care and its relationship to the media at The Antidote - check out her recent post on evidence based medicine.

And The Rational Fool writes, a whole lot of things - India, bioethics, economice, science, and Richard Dawkins - go check it out.

It's a diverse group, so you're guaranteed to find something you're interested in. Subscribe to the RSS feed and keep up with what's going on in the world of health and science.

Sunday, January 21, 2007

John Tierney's Science Blog at the NY Times

John Tierney, a conservative/libertarian/who knows? columnist at the NY Times has started a science blog. I'm usually not very optimistic about pundits commenting on science - the results are rarely good, with one of the worst cases being Gregg Easterbrook. The pundits usually have a muddled grasp of the technical issues and view scientific debate through a deep partisan tint.

However, the NY Times science section has much higher standards than opinion magazines like Slate and The New Republic, and so far Tierney's blog looks interesting. I recommend checking it out.

Is Systems Biology Teaching Us Anything New?

What I find most exciting about basic molecular biology today is the prospect of building a quantitative understanding of how a cell works. Many other scientists are excited about this as well, leading to the current popularity of what's being called 'systems biology.' The idea is that maybe we can understand the design principles behind a cellular process - how the behavior of a cell emerges from all of those detailed physical interactions among proteins, nucleic acids and other components of the cell. If that sounds vague to you, well, that's because it is vague. It's a nice sentiment, but I think biologists still have a hard time defining just what it is we want to learn.

Think of this problem from a historical perspective: biology has several profound organizing theories that have been fantastically useful as explanations for what happens in biological systems. As the geneticist Dobzhansky famously put it, nothing in biology makes sense except in the light of evolution. The same thing holds true for genetics (you don't have adaptive evolution if you don't have genes encoding traits that are passed on from one generation to the next), biochemistry (all organisms are made of molecules that obey the laws of physics and chemistry - not some mysterious substance that transcends physical laws), and molecular biology (DNA makes RNA makes Protein). Each of these theories has been successful by those criteria that define a good scientific theory; for example, they have explained previously mysterious phenomena, they have predicted completely new phenomena that have since been verified, and they have opened up huge new avenues of research. Each one of these theories has changed the way the entire community of biologists operates.

Will systems biology do that? I hope so, but I don't know. It hasn't yet. Let's take the cell division cycle, for example, since it's a process that's near and dear to my heart. It's also a process that is crucial for understanding human disease, notably cancer. How can systems biology help us understand the cell cycle? How can it help us understand and cure cancer?

A recent paper in Nature, from Michael Laub's lab, reports the identification of an "integrated genetic circuit." This is a very nice paper, with a clear set of experiments, that identifies certain interactions among key cell cycle proteins that control division in the bacterium Caulobacter crescentus. The interactions identified in this research explain how it is that a key cell cycle regulator protein, called CtrA, is cyclically switched on and off during the various stages of the cell cycle.

The authors aren't claiming that they are producing a quantitative model, but they use the language of systems biology, notably by calling their set of novel interactions an "integrated genetic circuit." So what then is a non-integrated genetic circuit? How does a biological integrated circuit relate to the integrated circuit used in electronics?

Ultimately, this study, and many others like it, are largely filling in the molecular details of a specific process, something molecular biologists have been doing for decades. Feedback loops and regulatory interactions are valuable, but not new. In some cases, we are getting enough detailed data to build some primitive computer models, but these models are largely descriptive - reproducing what extensive experimental work has already shown.

So is systems biology ever going to amount to something like the paradigm-shifting initiation of molecular biology in the 50's and 60's? Are there any Really Big Questions left in biology, or are we now just finding better, faster ways to fill in the details? I think there are big questions left, but they're still poorly defined and often lost in the flood of genomic research. One telling gap in our knowledge is the origin of living cells from nonliving systems - we can't build a cell from scratch. We don't have the theoretical tools to understand, rigorously, how the first cells could have arisen from available components on the early earth, for example. This suggests that there is more we need to understand about how physical systems can cohere together to produce something that can adapt to its environment and reproduce. Not just molecular details, but new concepts of how physical systems organize themselves.

For now I'm just raising questions, but in future posts I'll discuss how we might go about finding some answers.

Introducing Indy Science Blogs

This blog is part of the newly launched Indy Science Blogs - a group of science bloggers that coalesced in the wake of a mass rejection email from Science Blogs. Science Blogs didn't have the courtesy to blind cc the addresses of all the recipients, exposing our email addresses to dozens of strangers. Some of us strangers got together and formed the brand new Indy Science Blogs.

There are some great blogs at Indy Science Blogs. Visit the site, or check out some of my links to the right to see all the blogs. I'm just going to highlight a few:

The Beauty Brains has fascinating articles on the science of beauty products - if, like me, you like the intersection health and chemistry, or if, unlike me, you use many beauty products, check out this great blog.

Susan, a science writer over at Hug the Monkey writes about how "a single hormone called oxytocin is responsible for life's most fulfilling emotions: love, trust and commitment." Amazingly enough, it is possible to write a blog about a single hormone. Susan has some fascinating material on how the biology of the brain shapes who we are.

Trisha at Women's Health Research News writes about research relating to birth control, pregnancy, osteoporosis, and just about any other health issue that concerns women.

And Sibin at Context Switch is a PhD student in computer science who writes about whatever strikes his fancy, and happens to like Thomas Pynchon as well.

There are more blogs I haven't mentioned - head on over to Indy Science Blogs to see the rest.

And for you newcomers here - what's this blog about? You should know two things about me:

- I am almost completely HTML illiterate, which is why this blog doesn't have any fancy bells and whistles.

- Infant twins + seven-year old = not enough time left for blogging. It's been a hectic year, but now that sleep is more available in our house as the twins get older, I will pick up the pace here at Adaptive Complexity.

Here I write about my interests in the hope that some of those interests overlap with your interests:

- the future of basic research in biology - what do we want to learn now? Is systems biology any good?
- conveying the latest research in genomics to the public who should know about the exciting things that are being done with their tax money.
- science in the media
- science in literature - not science fiction necessarily, but usually the kind of stuff you find in books by Thomas Pynchon or Richard Powers
- book reviews of popular science books
- defending science against absurd claims by anti-evolutionists and other cranks.

So have a look around, and come back for more if you like what you see. And go check out Indy Science Blogs!

Monday, January 15, 2007

The Science of Light, Space-Time, and Vectors in Thomas Pynchon's Against the Day

OK, Pynchon fans, this is the first draft of my first installment on the science in Against the Day. I have to preface this with two cautionary notes:

1. This is an early and still very rough draft.
2. There are many more connections to be drawn with the book. I'm on my second reading, taking notes as I go, so by the time I finish I'll be able to flesh this out much more.

This essay will come in 4 installments, one every week or so - if you like this, keep checking back.

Here we go:

Thomas Pynchon is well known for the dense and obscure references to history, pop-culture, and especially science in his novels. His recent novel Against the Day is set during the turn of the 19th Century, a time when our understanding of space, time, and light, rooted in classical physics, was completely overturned and replaced by a revolutionary new perspective based on the theories of special and general relativity. Pynchon takes the science of this period and incorporates it deeply into the language and structure of Against the Day, more so perhaps than in any of his other novels. Against the Day is suffused with meditations on light, space, and time, and often plays with the tension between different perspectives in math and physics - classical physics versus relativity, or Maxwell's laws of electromagnetism described with the imaginary numbers of quaternions versus the real numbers of vector analysis. This material is not just filler - it's critical to the core of Against the Day, a fact which has been underappreciated in early reviews of the novel. One reviewer claimed that a new generation of writers has a "grasp of the systems that fascinate Pynchon -- science, capitalism, religion, politics, technology -- [that] is surer, more nuanced, more adult and inevitably yields more insight into how those systems work than Pynchon offers here." When it comes to science at least, this claim is not true - Pynchon's achievement in Against the Day proves that he is peerless as a poet who can mine the most abstract realms of very real science for gems of insight, and set them beautifully into the context of the humanity that is the ultimate concern of his novels.

My goal here is twofold: first, to illustrate how Pynchon goes beyond using science as simply a backdrop, or a way to show off his amazing erudition - he weaves scientific concepts into the language and structure of his book; and second, to lay out a primer on the basic scientific ideas so that readers of Against the Day can make their own discoveries about the novel. There are four main topics that I cover here: the Michelson-Morley experiment and the breakdown of classical physics, space-time and special relativity, the development of vector analysis and the eclipse of quaternions (I have a good guess at the identity of the 'Baedeker' that Pynchon 'looted' for his material on quaternions and vectors), and finally, Riemann surfaces. These four topics cover most of the scientific references in Against the Day. Pynchon, being a sucker for historical trivia, is mindful of the chronological development of these subjects, so I'll cover most of them from a historical perspective, including some famous, now-rejected explanations proposed for the negative result of the Michelson-Morley experiment. It is also important to note the science Pynchon did not include in the novel - other important advances were being made at the time, by some of the same characters, advances that Pynchon hardly mentions such as those in statistical mechanics (and yes, entropy) made by J.W. Gibbs. In this book, Pynchon has chosen to focus on space, time, and light.

The Michelson-Morley Experiment and the Failure of Classical Physics
The Michelson-Morley experiment (actually, a series of experiments performed over several years) was one of the definitive experiments providing physical evidence of the inadequacy of classical notions of space and time. The attempts to deal with the negative results of this experiment eventually led to Einstein's theories of special and general relativity, which are based on a completely different and very strange new way of viewing space and time. This new outlook has since been proven beyond any doubt by decades of experiments.

Early on in the book, Pynchon drops clues that the Michelson-Morley experiment is important for many of the themes that we'll find throughout Against the Day, and he even hints that the technical setup of the experiment itself is incorporates into the structure of Against the Day. A major character, Merle Rideout reads about the upcoming experiment and heads to Cleveland to learn more. He is encouraged by his friend, Yale professor Heino Vanderjuice, who tells him:

"Mr. Rideout, we wander at the present moment through a sort of vorticalist twighlight, holding up the lantern of the Maxwell Field Equations and squinting to find our way. Michelson's done this experiment before, in Berlin, but never so carefully. This one could be the giant arc-lamp we need to light our way into the coming century." (p. 58)

At the time this conversation takes place, in 1887, Michelson had improved on the design of his interferometer (the device used to carry out the experiment), so that it was easily sensitive enough to definitively answer the question he was posing. The negative outcome of this experiment was a major stepping-stone towards the development of a new understanding of light, space, and time. To see how this new understanding arose, we have to first understand the questions in classical physics that led to the Michelson-Morley experiment.

I. Classical Relativity
Albert Michelson began his famous series of experiments because the laws of classical physics, which in general were spectacularly successful, were running into trouble in one critical area: moving reference frames. Although we not may use the term 'reference frame' very often, we deal with moving reference frames in our everyday experience. As we have all experienced, Newton's laws of motion don't depend on whether we're on the ground or in a vehicle moving at a constant speed (constant here is an important qualifier). For example, you can play tennis on a steadily moving (that is, non-accelerating) cruise ship just as easily (or not so easily, in my case) as you play tennis on land - you handle yourself and the tennis ball the same way. Or, if you're on a steadily moving (again, non-accelerating) train, you can bounce a ball against the floor, and it behaves just as if you were bouncing it on the floor of your kitchen back home. The ball bounces straight up and down, keeping up with the train as you bounce it, as long as the train does not suddenly accelerate. From your perspective, or reference frame on the train, Newton's laws of motion, which govern the movement of the ball you are bouncing, are exactly the same as they would be if you were standing outside on the ground. Newton's laws apply equally well to moving and stationary reference frames (as the moving frame is not accelerating).

To someone standing on the ground outside of our hypothetical train, watching you bounce the ball as you go by, the situation looks a little different, but still completely in accordance with Newton's laws. This outside observer sees that the ball isn't going straight up and down; it's also moving forward with you and the train, nevertheless, the ball is also obeying Newton's laws from this outside perspective. All of this is common sense and intuitively obvious to us, but one can also show that it works out mathematically as well.

While this phenomenon is true of Newton's laws of motion, the classical laws of electricity and magnetism do not hold in different moving reference frames. To see what this means, we can use one key example: light. Maxwell's classical laws of electromagnetism imply that the speed of light is constant (in a given medium like a vacuum - light moves at different speeds in different media like water or air). If we simply treat light the way we treated Newton's laws in our above examples of the cruise ship or the train, the speed of light would not be constant for observers in different moving reference frames. If I'm standing on the ground watching a pulse of light go by, I would see that it's going at 300,000,000 meters per second (m/s). Someone on a train moving at 50 m/s, watching that same pulse of light go by, would perceive the light to be moving at 299,999,950 m/s. (This difference is of course, too small to be perceptible to unaided human senses). In this case, the speed of light, unlike Newton's laws, is not constant for observers in different reference frames, and thus the laws of electromagnetism would be different, depending on your frame of reference. So, while Newton's laws are the same whether you're playing tennis on the ground or on a cruise ship, this appears to not be true for Maxwell's laws of electromagnetism. Maxwell's laws would thus not be the correct laws to describe the behavior of light in moving reference frame. (At this point, we should be careful to remember that these are just theoretical considerations - we haven't discussed any actual experiments to really determine what happens with Maxwell's laws on a moving train or a cruise ship.)

Physicists in the late 19th century were well aware of this conundrum. They believed that there had to be one universal frame of reference where the speed of light was constant in any direction, in which Maxwell's laws of electromagnetism were perfectly valid; all other objects in the universe moved relative to the absolute space of this universal reference frame. This was called the aether frame of reference - aether was the stuff (although what kind of stuff, nobody knew) through which light supposedly propagated, much like sound must propagate through air or some other medium. The earth therefore moved relative to the stationary aether, much like a train moves relative to the 'stationary' earth. If this was in fact true, that the earth moves relative to the aether, then this movement should be detectable by experiment. And here is where Michelson and Morley come in.

II. Michelson and Morely Attempt to Measure the Absolute Speed of the Earth
Albert Michelson (who, like many characters in Against the Day, grew up in mining towns) and Edward Morley developed an extremely sensitive instrument to measure the speed of the earth relative to the hypothesized aether. The reasoning behind the experiment goes something like this: if light propagates at a constant speed through the aether (at 300,000,000 m/s), and if the earth moves at a certain speed relative to the aether (at, say, 30,000 m/s), then light moving in the same direction as the earth should appear to move more slowly to an observer on the earth - the speed of light in the aether, minus the speed of the earth. It's like driving on the highway - if you are going 60 mph and driving behind a car going 90 mph, then from your perspective the car in front is moving away from you at 30 mph. Michelson and Morley measured the speed of the earth relative to the aether and came up with a disturbing result - relative to the aether, the earth was not moving at all.

I'm won't describe exactly how the Michelson-Morley experiment worked - good explanations can be found in a physics textbook or a Google search. However, the basic setup of the experiment has a connection to some of the plot structure in Against the Day, as well as to the themes of double refraction and bilocation.

In the experiment, a light beam is split into two separate beams, which travel away from each other at a 90˚ angle, are reflected by mirrors, and then travel back and meet up, at which point they are either in phase or out of phase with each other (see the diagram below). If the earth is moving relative to the aether, the different light beams will travel different distances, and come back out of phase with each other.

Pynchon hints that there is a connection here with bilocation and double refraction, as well as human Michelson-Morley experiments (such as, possibly, when characters split up, go on long journeys and meet up again in or out of phase with each other in some way). There are some critical passages beginning on p. 61, where Merle "got the idea in his head that the Michelson-Morley experiment and the Blinky Morgan manhunt were connected." Blinky is referred to as a "human interferometer" or "A double-refractor, for that matter." (p. 62) In one of the earliest examples of bilocation in the book, Merle suspects that Morgan and Morely are the same person:

"... suppose when they split that light beam, that one half of it is Michelson's and the other is his partner Morley's, which turns out to be the half that comes back with the phases perfectly matched up - but under slightly different conditions, alternative axioms, there could be another pair that don't match up, see, in fact millions of pairs, that sometimes you could blame it on the Aether, sure, but other cases maybe the light goes someplace else, takes a detour and that's why it shows up late and out of phase, because it went where Blinky went when we was invisible, and-" (p. 62)

The connection between Iceland spar and the Michelson-Morley experiment is made more explicit later in the book, where the Cohen explains to Lew Basnight that his goal is to eventually be able to pass through Iceland spar, "which is an expression in crystal form of Earth's velocity as it rushes through the Aether, altering dimensions, and creating double refraction...." (p. 688)

Pynchon plays with this idea at multiple places throughout the book. He also includes elements of an aether culture - worshippers who show up for the Michelson-Morley experiment (p. 59-60), as well as hints of a whole science of aether weather, with which the Chums of Chance seem to be involved - a network of ships and balloons to monitor the ether is hinted at on p. 60. (Historically, people did in fact come up with elaborate ideas using putative aether behavior, such as vortices, to explain physical phenomena.)

Returning to Michelson and Morley - the results of their experiment were negative. They could detect no movement of the earth relative to the aether. Over the next several decades, scientists came up with various explanations for the negative result. One explanation, mentioned in Against the Day, is that the earth drags some of the aether along with it (and thus the earth isn't moving relative to the dragging layer of aether, so you don't detect a change in the speed of light). One of Pynchon's characters draws an analogy between this explanation and the dimples on a golf ball, and the lift of the golf ball through the air and the lift of the earth through the aether. [I'm sure Pynchon includes more, but I'll have to pick that up on a second reading.]

III. Revising Our Notions of Space and Time
One possible solution to handle the negative result of the experiment was to try to modify the laws of electromagnetism. Maxwell's equations were quite young compared to Newton's laws, so it seemed obvious that the problem was with Maxwell and not Newton. However, it became clear that Maxwell's laws were in fact correct, and eventually (as Einstein's theory of special relativity became accepted), that light traveled at a constant speed in any non-accelerating reference frame - not just in one universal aether reference frame. This means that whether you are standing on the ground or traveling at 100,000,000 m/s in a (currently fictitious) space ship, a light pulse will always appear to be traveling at 300,000,000 m/s. To go back to our highway analogy - you're going 60 mph behind a car going 90 mph, and instead of appearing to move away from you at 30 mph, the car appears to be going 90 mph away from you. The implication of this very weird phenomenon is that our everyday ideas about space and time are not correct.

Maxwell's equations weren't the problem - Newton's laws were. The physicist Henri Lorentz, between 1895 and 1905 proposed that objects in motion experience length contraction and time dilation, a proposal (in mathematical form) which could account for the results of the Michelson-Morley experiment. In other words, as you move faster and faster, space (from your frame of reference) shrinks in certain directions, and time slows down. If you go through Lorentz's math (known as the Lorentz tranformation), you see that space and time components, in one reference frame, get mixed together when you move to a different reference frame - space and time are not separate, they depend on how one is moving.

We can think about this by drawing an analogy with the video game Frogger In the game, you get a frog across the road by moving it left, right, up, or down. Now, imagine it this way - instead of having the frog face directly across the road, it's rotated at a 45˚ angle to the right, facing diagonally across the road - the frog's reference frame has rotated. 'Up' now (in this reference frame) is the equivalent of some 'up' and some 'right' in the original reference frame. 'Up' in one reference frame is a mixture of 'up' and 'right' in another.

The analogy isn't perfect (going over the math is the best way to look at it), but that's roughly what's going on with space-time. Instead of 'up' and 'left' in Frogger, we have three space dimensions and one time dimension, and how you perceive the combination of those dimensions depends on your frame of reference. (Unlike in our hypothetical game of Frogger, where we just changed the reference frame by rotating the frog, changing space-time reference frames depend on motion - the faster you move, the more slowly time passes, etc.)

So how we perceive space and time depends on how we are moving. (Does the eternal youth of the Chums of Chance somehow depend on their motion?) But no matter how we move, no matter what our reference frame, light moves at the same speed for all of us.

Pynchon makes a lot of this material, playing with both the language and the concepts. Stay tuned for a future draft, with much more complete references to the book.

In Part 2, I'll discuss special relativity and space-time, the new outlook that replaced the old worldview of classical physics.

For further reading:
Feynman Lectures on Physics, Vol. 1 chapter 15
Modern Physics for Scientists and Engineers, by John Taylor and Christopher Zafiratos.
The Fabric of the Cosmos, Brian Greene.

Thursday, January 11, 2007

How the microorganisms in your gut can make you fat...

Blogging around here has been slow lately - now that the crazy holiday season is over, I'm immersed in an essay I'm writing on the remarkable use of science in Thomas Pynchon's latest novel Against the Day. I think what Pynchon did in this novel has been severely underappreciated in the reviews that have been published, because you have to have enough awareness of the science to pick up on Pynchon's references and see what he's doing with them. One example: at one point in the novel a character (who is a math student studying Riemann manifolds) walks through a brick wall; Pynchon is playing around here with the notion of 'cuts' on a Riemann surface.

There's a whole lot more, and I'm putting something together that will hopefully be fun for Pynchon fans with little science background, induce scientists who haven't read a Pynchon novel to pick one up, and not make people who are both Pynchon fans and scientists cringe.

In the mean time, I have to highlight some recent papers that have come out of Jeff Gordon's lab here at the Center for Genome Sciences. The Gordon lab studies the interaction between the genes of mice and the microorganisms that live in their guts. We all have many, many different types of microorganisms living inside our intestinal tract, and the Gordon lab has been studying how that population of microorganisms impacts how we process food for energy. This is how the Gordon lab puts it in their most recent paper:

"The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus."

This paper reports that mice without these gut microorganisms don't become obese when fed a high-fat, high-sugar diet, and identifies several enzymes that may be related to this resistance to obesity.

The December 21/28 issue of Nature featured the Gordon lab's research on the cover and contained this paper and this paper connecting obesity with gut microbiota.

The studies look at the types of microorganisms present in the guts of obese mice and humans, compared with lean mice and humans. The group also has studied how these microorganisms "harvest energy from the diet."

These studies rely on mice with defined populations of gut microorganisms and genome sequencing. To look at what's living in a particular mouse's gut, you isolate some fecal samples from mice with various mutant genes, and then sequence the DNA to find out what's in there. The Gordon lab has germ-free mice - mice born without any microorganisms in their guts and kept sterile until the researchers add a defined population microorganisms. So you can take the microbiota from an obese mouse, put it in the gut of a germ-free lean mouse, and see if that lean mouse becomes obese.

Of course I'm really simplifying a lot here; I suggest checking out the abstracts I've linked to. This is an interesting, innovative way to use sequencing to study genes and health.

Sunday, January 07, 2007

Carl Zimmer on the Two (Biology) Cultures

C.P. Snow lamented the divide between the Two Cultures - the Humanities and the Sciences, since he felt that they each had so much to offer the other. There is a similar divide in biology - two cultures, representing those biolgists whose work is rooted in natural history, and those whose work is rooted in molecular biology. Biologists who attach cameras to deep-diving sperm whales, who trudge through the rain forest collecting plant species, who hunt whale fossils, work deeply in natural history. They know a lot about ecology, anatomy (plant or animal), cladistics, and the difference between the Devonian and the Permian eras - stuff that someone like me, a biochemist, hasn't studied since college biology. Molecular biologists, on the other hand - live almost completely within the realm of molecules or model organisms. Their expertise is in using very sophisticated experimental and computational tools to understand what goes on at the cellular and molecular level, and they deal with processes and analystical techniques that most natural history biologists haven't studied since their college molecular biology class.

Carl Zimmer, a superb science writer, tackles these two cultures in PLoS Computationl Biology, highlighting how the advent of genome sequencing has driven these two fields closer together - at least in terms of subject matter. Molecular biologists have used their recently developed tools in genomics to venture into territory that has traditionally belonged to natural history - phylogeny, the genealogical relationships among groups of organisms. As a result, there has occasionally been conflict between these two cultures, but Zimmer points out that there is great potential for fruitful cooperation.

My father, a geologist, told me about a seminar he attended recently. The speaker, who might have been a paleontologist, was lamenting the fact that the genomes that have been sequenced exclude key organisms that could shed light on unrseolved issues in natural history. I don't know of any specific examples, because as I mentioned before, my knowledge of natural history is limited to what I learned as a sophomore in college. Most 'biomedical' researchers, including those who run and fund the big genome sequencing centers, are in the same boat. I don't know if they ever seriously consult their colleagues in natural history about which genomes to sequence next. What a great chance for collaboration - those who work in natural history could come up with a list of 15-20 organisms they would like to see sequenced, and the two cultures could work together to produce some real progess on these open questions in natural history. To answer such questions would almost definitely not require complete, thorough (and expensive) coverage of entire genomes - just well-chosen regions. This extensive amount of data, combined with the fossil record, could produce advances in our understanding of key evolutionary events, like the Cambrian Explosion.

One specific advantage of well-chosen genomes suggested by the seminar speaker my father told me about, was the proper calibration of the molecular clock. Biologists who try to put a timeline on evolutionary history are usually not that successful, in some cases producing results that are geologically completely unreasonable. This seminar speaker suggested that we could calibrate this molecular clock much better than we can now, by choosing to sequence certain groups of animals whose fossil record is very well documented. And, importantly, we shouldn't have the molecular biologists try to figure out on their own which groups those are - we should get those who really know the fossil record involved. A well-calibrated molecular clock would be a valuable tool - even outside of studies focused purely on evolution. This is just one potential advantage of greater interaction between these two cultures.